Change search
Refine search result
1 - 42 of 42
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 1. Aaltonen, Kirsimari
    et al.
    Ahlin, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Amini, Rose-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Salonen, Laura
    Fjällskog, Marie Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Heikkilä, Pävi
    Nevanlinna, Heli
    Blomqvist, Carl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Reliability of cyclin A assessment on tissue microarrays in breast cancer compared to conventional histological slides2006In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 94, no 11, p. 1697-1702Article in journal (Refereed)
    Abstract [en]

    Cyclin A has in some studies been associated with poor breast cancer survival, although all studies have not confirmed this. Its prognostic significance in breast cancer needs evaluation in larger studies. Tissue microarray (TMA) technique allows a simultaneous analysis of large amount of tumours on a single microscopic slide. This makes a rapid screening of molecular markers in large amount of tumours possible. Because only a small tissue sample of each tumour is punched on an array, the question has arisen about the representativeness of TMA when studying markers that are expressed in only a small proportion of cells. For this reason, we wanted to compare cyclin A expression on TMA and on traditional large sections. Two breast cancer TMAs were constructed of 200 breast tumours diagnosed between 1997-1998. TMA slides and traditional large section slides of these 200 tumours were stained with cyclin A antibody and analysed by two independent readers. The reproducibility of the two readers' results was good or even very good, with kappa values 0.71-0.87. The agreement of TMA and large section results was good with kappa value 0.62-0.75. Cyclin A overexpression was significantly (P<0.001) associated with oestrogen receptor and progesterone receptor negativity and high grade both on TMA and large sections. Cyclin A overexpression was significantly associated with poor metastasis-free survival both on TMA and large sections. The relative risks for metastasis were similar on TMA and large sections. This study suggests that TMA technique could be useful to study histological correlations and prognostic significance of cyclin A on breast cancer on a large scale.

  • 2.
    Ahlin, Cecilia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Aaltonen, Kirsimari
    Amini, Rose-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Nevanlinna, Heli
    Fjällskog, Marie-Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Blomqvist, Carl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Ki67 and cyclin A as prognostic factors in early breast cancer: What are the optimal cut-off values?2007In: Histopathology, ISSN 0309-0167, E-ISSN 1365-2559, Vol. 51, no 4, p. 491-498Article in journal (Refereed)
    Abstract [en]

    AIMS: To find the optimal cut-off values for cyclin A and Ki67 in early breast cancer tumours and to evaluate their prognostic values. METHODS AND RESULTS: Tissue microarray (TMA) slides were constructed from 570 T1-4 N0-1 M0 breast cancer tumours. The TMA slides were stained for cyclin A and Ki67 using immunohistochemistry with commercial antibodies. To investigate the optimal cut-off values for cyclin A, Ki67 average and maximum values the material was split into two parts at cut-offs defined by dividing it into deciles. For each cut-off value the relative risk (RR) for metastasis-free survival (MFS) and overall survival (OS) was calculated comparing patients with high versus low cyclin A or Ki67 expression. When using a cut-off value around the seventh decile, cyclin A and Ki67 score correlated with the highest RR ratio for MFS in the chemotherapy-naïve subgroup. Among patients having received adjuvant chemotherapy, no statistically significant differences in MFS or OS were found. CONCLUSIONS: The optimal cut-off value for cyclin A average is 8% and for cyclin A maximum value 11%; for Ki67 the corresponding values are 15% and 22%. Additional studies are needed to verify these results.

  • 3. Ahlin, Cecilia
    et al.
    Fernö, Mårten
    Amini, Rose-Marie
    Karolinska universitetssjukhuset, Stockholm.
    Tolockiene, Egle
    Blomqvist, Carl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Bergh, Jonas
    Fjällskog, Marie-Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Ki-67 och cyklin A – prognostiska faktorer vid bröstcancer: Dags att införa proliferationsmarkörer i klinisk rutin2010In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 107, no 10, p. 672-675Article in journal (Refereed)
  • 4.
    Ahlin, Cecilia
    et al.
    Orebro Univ, Dept Oncol, Orebro, Sweden..
    Lundgren, Claudia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Embretsen-Varro, Elin
    Orebro Univ, Dept Oncol, Orebro, Sweden..
    Jirstrom, Karin
    Lund Univ, Dept Pathol & Oncol, Lund, Sweden..
    Blomqvist, Carl
    Orebro Univ, Dept Oncol, Orebro, Sweden.;Univ Helsinki, Dept Oncol, Helsinki, Finland..
    Fjällskog, Marie-Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    High expression of cyclin D1 is associated to high proliferation rate and increased risk of mortality in women with ER-positive but not in ER-negative breast cancers2017In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 164, no 3, p. 667-678Article in journal (Refereed)
    Abstract [en]

    Cyclin D1 has a central role in cell cycle control and is an important component of estrogen regulation of cell cycle progression. We have previously shown that high cyclin D expression is related to aggressive features of ER-positive but not ER-negative breast cancer. The aims of the present study were to validate this differential ER-related effect and furthermore explore the relationship between cyclin D overexpression and CCND1 gene amplification status in a node-negative breast cancer case-control study. Immunohistochemical nuclear expression of cyclin D1 (n = 364) and amplification of the gene CCND1 by fluorescent in situ hybridization (n = 255) was performed on tissue microarray sections from patients with T1-2N0M0 breast cancer. Patients given adjuvant chemotherapy were excluded. The primary event was defined as breast cancer death. Breast cancer-specific survival was analyzed in univariate and multivariable models using conditional logistic regression. Expression of cyclin D1 above the median (61.7%) in ER breast cancer was associated with an increased risk for breast cancer death (OR 3.2 95% CI 1.5-6.8) also when adjusted for tumor size and grade (OR 3.1). No significant prognostic impact of cyclin D1 expression was found among ER-negative cases. Cyclin D1 overexpression was significantly associated to high expression of the proliferation markers cyclins A (rho 0.19, p = 0.006) and B (rho 0.18, p = 0.003) in ER-positive tumors, but not in ER-negative cases. There was a significant association between CCND1 amplification and cyclin D1 expression (p = 0.003), but CCND1 amplification was not statistically significantly prognostic (HR 1.4, 95% CI 0.4-4.4). We confirmed our previous observation that high cyclin D1 expression is associated to high proliferation and a threefold higher risk of death from breast cancer in ER-positive breast cancer.

  • 5.
    Borjesson, Susanne
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Lifestyle and rehabilitation in long term illness.
    Nordin, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Centre for Research Ethics and Bioethics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Lifestyle and rehabilitation in long term illness.
    Fjällskog, Marie-Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    Peterson, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Arving, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Lifestyle and rehabilitation in long term illness. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Nurses’ experiences of taxane-induced pain in people treated for breast cancerIn: Article in journal (Other academic)
  • 6.
    Börjesson, Susanne
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Lifestyle and rehabilitation in long term illness. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Center for Clinical Research Dalarna.
    Nordin, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Lifestyle and rehabilitation in long term illness.
    Fjällskog, Marie-Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    Rissanen, Ritva
    Karolinska Inst, Dept Publ Hlth Sci, Stockholm, Sweden.
    Peterson, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Arving, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Lifestyle and rehabilitation in long term illness.
    Colored body images reveal the perceived intensity anddistribution of pain in women with breast cancer treated with adjuvant taxanes:: a prospective multi-method study of pain experience2018In: Scandinavian Journal of Pain, ISSN 1877-8860, E-ISSN 1877-8879, p. 581-591Article, review/survey (Refereed)
    Abstract [en]

    Background and aims:

    Breast cancer is the most prevalent adult cancer worldwide. A broader use of screening for early detection and adjuvant systemic therapy with chemotherapy has resulted in improved survival rates. Taxane-containing chemotherapy is one of the cornerstones of the treatment. However, taxane-containing chemotherapy may result in acute chemotherapy-induced nociceptive and neuropathic pain. Since this pain may be an additional burden for the patient both during and after taxane chemotherapy, it is important to rapidly discover and treat it. There is yet no gold standard for assessing taxane-induced pain. In the clinic, applying multiple methods for collecting information on pain may better describe the patients’ pain experiences. The aim was to document the pain during and after taxane through the contribution of different methods for collecting information on taxane-induced pain. Fifty-three women scheduled for adjuvant sequential chemotherapy at doses of ≥75 mg/m2 of docetaxel and epirubicin were enrolled in the study.

    Methods:

    Prospective pain assessments were done on a visual analog scale (VAS) before and during each cycle of treatment for about 5 months, and using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire’s (EORTC-QLQ-C30) two pain questions at baseline, 3 months, and 12 months. Participants scoring pain on the VAS >30 and undergoing an interview also colored their pain on a body image during treatment and at 12 months.

    Results:

    Surprisingly widespread, intense pain was detected using a multi-method approach. The colored body image showed pain being perceived on 51% of the body surface area during treatment, and on 18% 12 months after inclusion. In general, the pain started and peaked in intensity after the first cycle of taxane. After Cycle 3, most women reported an increase in pain on the VAS. Some women continued to report some pain even during the epirubicin cycles. The VAS scores dropped after the last chemotherapy cycle, but not to the baseline level. At baseline, 3 months and 12 months after inclusion, the women who estimated VAS >30 reported higher levels of pain on the pain questions of the EORTC-QLQ-C30.

    Conclusions:

    This study contributes information on how different pain assessment tools offer different information in the assessment of pain. The colored body image brings another dimension to pain diagnostics, providing additional information on the involved body areas and the pain intensities as experienced by the women. A multi-method approach to assessing pain offers many advantages. The timing of the assessment is important to properly assess pain.

    Implications:

    Pain relief needs to be included in the chemotherapy treatment, with individual assessment and treatment of pain, in the same way as is done in chemotherapy-triggered nausea. There is a time window whereby the risk of pain development is at its highest within 24–48 h after receiving taxane chemotherapy. Proper attention to pain evaluation and treatment should be in focus during this time window.

  • 7. Deb, Siddhartha
    et al.
    Johansson, Ida
    Byrne, David
    Nilsson, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Constable, Leonie
    Fjällskog, Marie-Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Dobrovic, Alexander
    Hedenfalk, Ingrid
    Fox, Stephen B.
    Nuclear HIF1A expression is strongly prognostic in sporadic but not familial male breast cancer2014In: Modern Pathology, ISSN 0893-3952, E-ISSN 1530-0285, Vol. 27, no 9, p. 1223-1230Article in journal (Refereed)
    Abstract [en]

    Male breast cancer is poorly understood with a large proportion arising in the familial context particularly with the BRCA2 germline mutation. As phenotypic and genotypic differences between sporadic and familial male breast cancers have been noted, we investigated the importance of a hypoxic drive in these cancers as this pathway has been shown to be of importance in familial female breast cancer. Expression of two major hypoxia-induced proteins, the hypoxia-inducible factor-1 alpha (HIF1A) and the carbonic anhydrase IX (CA9), examined within a large cohort including 61 familial (3 BRCA1, 28 BRCA2, 30 BRCAX) and 225 sporadic male breast cancers showed that 31% of all male breast cancers expressed either HIF1A (25%) and/or CA9 (8%) in the combined cohort. Expression of HIF1A correlated with an increased incidence of a second-major malignancy (P=0.04), histological tumor type (P=0.005) and basal phenotype (P=0.02). Expression of CA9 correlated with age (P=0.004) in sporadic cases and an increased tumor size (P=0.003). Expression of HIF1A was prognostic for disease-specific survival in sporadic male breast cancers (HR: 3.8, 95% CI: 1.5-9.8, P=0.006) but not within familial male breast cancer, whereas CA9 was only prognostic in familial male breast cancers (HR: 358.0, 95% CI: 9.3-13781.7, P=0.002) and not in sporadic male breast cancer. This study found that hypoxic drive is less prevalent in male breast cancer compared with female breast cancer, possibly due to a different breast microenvironment. The prognostic impact of HIF1A is greatest in sporadic male breast cancers with an alternate dominant mechanism for the oncogenic drivers suggested in high risk familial male breast cancers.

  • 8.
    Fjällskog, M L
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Onkologi.
    Frii, L
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Bergh, J
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Is Cremophor EL, solvent for paclitaxel, cytotoxic?1993In: Lancet, ISSN 0140-6736, Vol. 342, no 8875, p. 873-Article in journal (Other scientific)
  • 9.
    Fjällskog, M L
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Onkologi.
    Frii, L
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Bergh, J
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Paclitaxel-induced cytotoxicity--the effects of cremophor EL (castor oil) on two human breast cancer cell lines with acquired multidrug resistant phenotype and induced expression of the permeability glycoprotein.1994In: Eur J Cancer, ISSN 0959-8049, Vol. 30A, no 5, p. 687-90Article in journal (Other scientific)
  • 10.
    Fjällskog, M L
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Department of Oncology, Radiology and Clinical Immunology.
    Sundin, A
    Department of Oncology, Radiology and Clinical Immunology.
    Westlin, J E
    Department of Oncology, Radiology and Clinical Immunology.
    Öberg, K
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Onkologisk endokrinologi.
    Tiensuu Janson, E
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Eriksson, B
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Treatment of malignant endocrine pancreatic tumors with a combination of alpha-interferon and somatostatin analogs.2002In: Med Oncol, ISSN 1357-0560, Vol. 19, no 1, p. 35-42Article in journal (Refereed)
  • 11.
    Fjällskog, Marie-Louise
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Granberg, Dan
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Welin, Staffan
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Eriksson, Christoffer
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Oberg, Kjell
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Eriksson, Barbro
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Treatment with Cisplatin and Etoposide in Patients with Neuroendocrine Tumors2001In: Cancer, Vol. 92, no 5, p. 1101-1107Article in journal (Refereed)
  • 12.
    Fjällskog, Marie-Louise
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Hessman, Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Eriksson, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Janson, Eva Tiensuu
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Upregulated expression of PDGF receptor beta in endocrine pancreatic tumors and metastases compared to normal endocrine pancreas2007In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 46, no 6, p. 741-746Article in journal (Refereed)
    Abstract [en]

    Platelet-derived growth factor receptor (PDGFR) beta signaling is involved in autocrine growth stimulation of tumor cells, tumor angiogenesis and regulation of tumor interstitial fluid pressure. Development of PDGFR antagonists has further increased the interest for PDGFR as targets for anticancer treatments. Malignant endocrine pancreatic tumors (EPTs) express PDGFR beta both in stroma and on tumor cells. To investigate the role of PDGFR beta signaling in EPTs we compared PDGFR beta expression in normal endocrine pancreas to malignant EPTs and metastases. PDGFR beta expression was examined by immunohistochemistry using specific polyclonal antibodies in ten tissue samples from normal endocrine pancreas, 21 from primary EPTs and 19 from metastases. In eight patients we compared the expression in normal endocrine pancreas to the corresponding primary tumor and metastases, in two patients normal tissue to the primary tumor and in 11 patients primary tumors to the corresponding metastases. Six of ten tissues containing normal pancreas stained negative for PDGFR beta on endocrine cells, while seven of ten stained positive in the stroma. Eighteen of 21 (86%) primary tumors stained positive for PDGFR beta on tumor cells and all had positive stroma stainings. All 19 metastases stained positive for PDGFR beta on tumor cells and in evaluable stroma (n=16). We have found that PDGFR beta is more frequently expressed in primary EPTs and metastases as compared to normal endocrine pancreatic tissue. This is also true for PDGFR beta expression in the corresponding stroma. We suggest that new therapeutic options to inhibit the growth and spread of EPTs could include targeting of PDGFR beta.

  • 13.
    Fjällskog, Marie-Louise
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. onkologi.
    Janson, Eva Tiensuu
    Department of Medical Sciences.
    Tratamento dos tumores endócrinos do pâncreas.2004In: Câncer Hoje- A Oncologia baseada em Evidência., Vol. 2, no 5, p. 17-25Article, review/survey (Other (popular scientific, debate etc.))
  • 14.
    Fjällskog, Marie-Louise
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Ludvigsen, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Eriksson, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Janson, Eva T
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Expression of somatostatin receptor subtypes 1 to 5 in tumor tissue and intratumoral vessels in malignant endocrine pancreatic tumors2003In: Medical Oncology, ISSN 1357-0560, E-ISSN 1559-131X, Vol. 20, no 1, p. 59-67Article in journal (Refereed)
    Abstract [en]

    Somatostatin analogs are well established in the treatment of malignant endocrine pancreatic tumors (EPTs). Our goal is to individualize their treatment using receptor-subtype-specific analogs and, therefore, exploring the receptor expression is highly important. We have examined the expression of somatostatin receptor (sst) subtypes 1–5 on tumor cells and in intratumoral vessels in 28 tumor tissues from malignant EPTs with immunohistochemistry using sst-subtype-specific polyclonal antibodies. We found that sst2 and sst4 stained positive in 90% and sst1 in 70% of the tumor tissues, whereas sst3 and sst5 stained positive in only 50% of the tumor tissues. Sst expression in intratumoral vessels was high for sst2 and sst4 (80%), moderate for sst1 (40%), and low for sst3 and sst5 (10%). The ssts were evenly distributed among the different tumor subtypes. However, tumors belonging to the same subgroup of EPTs showed a variable expression of receptor subtypes. No differences in receptor-subtype expression could be seen between poorly and well-differentiated tumors, nor between primary tumors and metastases. Prior medical treatment did not influence sst expression pattern. In conclusion, sst2 and sst4 were expressed in most tumor tissues and intratumoral vessels from EPTs. However, sst3 and sst5 were lacking in half of the tumor tissues and in most of the intratumoral vessels. These differences indicate the importance of determining each tumor’s subset of receptors before treatment with receptor-subtype-specific analogs is initiated. The importance of sst expression in intratumoral vessels is not yet known.

  • 15.
    Fjällskog, Marie-Louise
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Tiensuu Janson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Treatment of endocrine pancreatic tumors2005In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 44, no 4, p. 329-338Article in journal (Refereed)
    Abstract [en]

    Endocrine pancreatic tumors are rare with an incidence of 4 per million inhabitants. Most tumors are malignant except for insulinomas that usually are benign. They are slowly growing in the majority of cases but there are exceptions with rapidly progressing malignant carcinomas. Because of the rarity of these tumors large randomized trials are difficult to accomplish. However, most physicians treating these patients agree that surgery should be considered in all cases and that medical treatment with chemotherapy and biotherapy is well established for this group of patients.

  • 16.
    Granberg, Dan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Eriksson, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Wilander, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Grimfjärd, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Fjällskog, Marie-Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Skogseid, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Experience in treatment of metastatic pulmonary carcinoid tumors2001In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 12, no 10, p. 1383-1391Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    The only cure for patients with pulmonary carcinoids is surgery. In the present paper, we report the results of medical treatment of patients with metastatic tumors, their circulating hormone markers, and immunohistochemical profile of the tumors. PATIENTS AND

    METHODS/RESULTS:

    The response to systemic antitumoral treatment was studied in 31 patients with metastatic pulmonary carcinoids. Median survival from treatment start was 25 months. Alpha-interferon treatment has resulted in stable disease in 4 of 27 patients (median duration 15 months), while 23 patients showed progressive disease. Somatostatin analogues given as single drug treatment resulted in progressive disease. Streptozotocin and 5-fluorouracil resulted in progressive disease in seven of seven patients. Stable disease was obtained for 8 and 10 months respectively in two of two patients treated with streptozotocin + doxorubicin. Two of eight patients treated with cisplatinum + etoposide showed a significant decrease in tumor size lasting six and eight months respectively, and one displayed stable disease for seven months. Elevation of plasma chromogranin A was seen in 93%.

    CONCLUSIONS:

    The results of systemic antitumoral treatment of pulmonary carcinoids with distant metastases are generally discouraging. Chemotherapy with cisplatinum + etoposide, or doxorubicin combined with streptozotocin or paclitaxel may be of value. Alpha-interferon and octreotide offer efficient symptomatic relief, but stabilizes tumor growth in merely 15% of the cases. Plasma chromogranin A is the most frequently elevated tumor marker.

  • 17.
    Grönberg, Malin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    Ahlin, Cecilia
    Orebro Univ, Fac Med & Hlth, Dept Oncol, Orebro, Sweden..
    Naeser, Ylva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    Tiensuu Janson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. Kings Coll London, Fac Life Sci & Med, London, England..
    Fjällskog, Marie-Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    Ghrelin is a prognostic marker and a potential therapeutic target in breast cancer2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 4, article id e0176059Article in journal (Refereed)
    Abstract [en]

    Ghrelin and obestatin are gastrointestinal peptides, encoded by the same preproghrelin gene. Both are expressed in breast cancer tissue and ghrelin has been implicated in breast cancer tumorigenesis. Despite recent advances in breast cancer management the need for new prognostic markers and potential therapeutic targets in breast cancer remains high. We studied the prognostic impact of ghrelin and obestatin in women with node negative breast cancer. Within a cohort of women with breast cancer with tumor size <= 50 mm, no lymph node metastases and no initiation of adjuvant chemotherapy, 190 women were identified who died from breast cancer and randomly selected 190 women alive at the corresponding time as controls. Tumor tissues were immunostained with antibodies versus the peptides. Ghrelin expression was associated with better breast cancer specific survival in univariate analyses (OR 0.55, 95% CI 0.36-0.84) and in multivariate models, adjusted for endocrine treatment and age (OR 0.57, 95% CI 0.36-0.89). Obestatin expression was non-informative (OR 1.2, 95% CI 0.60-2.46). Ghrelin expression is independent prognostic factor for breast cancer death in node negative patients-halving the risk for dying of breast cancer. Our data implies that ghrelin could be a potential therapeutic target in breast cancer treatment.

  • 18.
    Grönberg, Malin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Fjällskog, Marie-Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Jirström, Karin
    Tiensuu Janson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Expression of ghrelin is correlated to a favorable outcome in invasive breast cancer2012In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 51, no 3, p. 386-393Article in journal (Refereed)
    Abstract [en]

    Background. Expression of the peptide hormones ghrelin and obestatin has previously been demonstrated in human mammary glands. However, the clinical implications of the expression of these peptides in breast cancer are unclear. The aim of this study was to investigate the potential clinical value of ghrelin and obestatin as breast cancer biomarkers. Methods. A tissue microarray containing breast cancer specimens from 144 patients was immunostained with antibodies directed towards ghrelin and obestatin. Using varying cut-offs, the expression of the two peptides was evaluated and correlated to previously known prognostic factors in breast cancer and to the outcome. Cox regression analysis was used to assess whether these markers may predict survival of breast cancer patients. Results. Moderate to strong immunoreactivity for ghrelin and obestatin was observed in 71.5% and 77.1% of the cases, respectively. Ghrelin and obestatin expression was significantly but weakly correlated to low histological grade, estrogen receptor positivity, small tumor size and low proliferation. Only ghrelin expression was significantly correlated to better recurrence-free and breast cancer-specific survival (HR = 0.3-0.4, p = 0.02-0.05) in both uni- and multivariate analyses. The optimal cut-off was any ghrelin expression versus none. Reproducibility between the two readers was very good for both stainings with kappa values of 0.94-1.00. Conclusions. Patients with tumors expressing ghrelin had 2.5-3 times lower risk for recurrence or breast cancer death than those lacking ghrelin expression. Ghrelin expression is easily assessable with high reproducibility using immunohistochemistry. Further investigations are needed to establish the clinical significance of ghrelin as a biomarker in breast cancer.

  • 19.
    Grönberg, Malin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    Nilsson, Cecilia
    Vastmanland Cty Hosp, Ctr Clin Res, Vasteras, Sweden.
    Markholm, Ida
    Lund Univ, Dept Clin Sci, Div Oncol & Pathol, Lund, Sweden;Lund Univ, CREATE Hlth Strateg Ctr Translat Canc Res, Lund, Sweden.
    Hedenfalk, Ingrid
    Lund Univ, Dept Clin Sci, Div Oncol & Pathol, Lund, Sweden;Lund Univ, CREATE Hlth Strateg Ctr Translat Canc Res, Lund, Sweden.
    Blomqvist, Carl
    Univ Helsinki, Dept Oncol, Helsinki, Finland;Orebro Univ Hosp, Dept Oncol, Orebro, Sweden.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. Kings Coll London, Fac Life Sci & Med, London, England.
    Tiensuu Janson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    Fjällskog, Marie-Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    Ghrelin expression is associated with a favorable outcome in male breast cancer2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 13586Article in journal (Refereed)
    Abstract [en]

    Ghrelin and obestatin are two gastrointestinal peptides, derived from a common precursor. Expression of both peptides have been found in breast cancer tissue and ghrelin has been associated with breast cancer development. Ghrelin expression is associated with longer survival in women diagnosed with invasive and node negative breast cancer. The clinical implications of the peptide expression in male breast cancer are unclear. The aim of this study was to investigate the role and potential clinical value of ghrelin and obestatin in male breast cancer. A tissue microarray of invasive male breast cancer specimens from 197 patients was immunostained with antibodies versus the two peptides. The expression of the peptides was correlated to previously known prognostic factors in breast cancer and to the outcome. No strong correlations were found between ghrelin or obestatin expression and other known prognostic factors. Only ghrelin expression was statistically significantly correlated to breast cancer-specific survival (HR 0.39, 95% CI 0.18-0.83) in univariate analyses and in multivariate models, adjusted for tumor size and node status (HR 0.38, 95% CI 0.17-0.87). HR for obestatin was 0.38 (95% CI 0.11-1.24). Ghrelin is a potential prognostic factor for breast cancer death in male breast cancer. Patients with tumors expressing ghrelin have a 2.5-fold lower risk for breast cancer death than those lacking ghrelin expression. Drugs targeting ghrelin are currently being investigated in clinical studies treating metabolic or nutritional disorders. Ghrelin should be further evaluated in forthcoming studies as a prognostic marker with the aim to be included in decision algorithms.

  • 20.
    Hellerstedt-Börjesson, Susanne
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences.
    Arving, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences.
    Nordin, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences.
    Fjällskog, Marie-Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Holmström-Knutsson, Iinger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Health Services Research. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Women with breast cancer: Experiences and impact of chemotherapy-induced pain on daily life2014In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 50, no S2, p. S108-S108Article in journal (Other academic)
  • 21.
    Hellerstedt-Börjesson, Susanne
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Lifestyle and rehabilitation in long term illness.
    Nordin, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Lifestyle and rehabilitation in long term illness.
    Fjällskog, Marie-Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine oncology.
    Holmström, Inger K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Health Services Research. Malardalen Univ, Sch Hlth Care & Social Welf, Vasteras, Sweden.
    Arving, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Lifestyle and rehabilitation in long term illness.
    Women Treated for Breast Cancer, Experiences of Chemotherapy-Induced Pain:: Memories, Any Present Pain and Future reflections2016In: Cancer Nursing, ISSN 0162-220X, E-ISSN 1538-9804, Vol. 39, no 6, p. 464-472Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Breast cancer survivors make up a growing population facing treatment that poses long-standing adverse effects including chemotherapy-related body function changes and/or pain. There is limited knowledge of patients' lived experiences of chemotherapy-induced pain (CHIP).

    OBJECTIVE: The aim of this study was to explore CHIP and any long-standing pain experiences in the lifeworld of breast cancer survivors.

    METHODS: Fifteen women participated in a follow-up interview a year after having experienced CHIP. They were interviewed from a lifeworld perspective; the interviews were analyzed through guided phenomenology reflection.

    RESULTS: A past perspective: CHIP is often described in metaphors, leads to changes in a patient's lifeworld, and impacts lived time. The women become entirely dependent on others but at the same time feel isolated and alone. Existential pain was experienced as increased vulnerability. Present perspective: Pain engages same parts of the body, but at a lower intensity than during CHIP. The pain creates time awareness. Expected normality in relationships/daily life has not yet been achieved, and a painful existence emerges in-between health and illness. Future perspective: There are expectations of pain continuing, and there is insecurity regarding whom to turn to in such cases. A painful awareness emerges about one's own and others' fragile existence.

    CONCLUSIONS: Experiencing CHIP can impact the lifeworld of women with a history of breast cancer. After CHIP, there are continued experiences of pain that trigger insecurity about whether one is healthy.

    IMPLICATIONS FOR PRACTICE: Cancer survivors would likely benefit from communication and information about and evaluation of CHIP.

  • 22.
    Hellerstedt-Börjesson, Susanne
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Lifestyle and rehabilitation in long term illness.
    Nordin, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Lifestyle and rehabilitation in long term illness.
    Fjällskog, Marie-Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Holmström, Inger K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Health Services Research.
    Arving, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Lifestyle and rehabilitation in long term illness.
    Women With Breast Cancer: Experience of Chemotherapy-Induced Pain: Triangulation of Methods2015In: Cancer Nursing, ISSN 0162-220X, E-ISSN 1538-9804, Vol. 38, no 1, p. 31-39Article in journal (Refereed)
    Abstract [en]

    BACKGROUND

    Chemotherapy treatment for cancer diseases can cause body pain during adjuvant therapy.

    OBJECTIVE

    The aim was to describe the perceived impact of adjuvant chemotherapy-induced pain (CHIP) on the daily lives of women with newly diagnosed breast cancer, using triangulation.

    METHOD

    Fifty-seven women scheduled for chemotherapy in doses of 75 mg/m2 or greater of epirubicin and/or docetaxel participated. Twenty-two of these women registered pain with values of 4 or more on the visual analog scale on day 10 following chemotherapy. Of these 22, 16 participated in an interview and colored a printed body image. A qualitative thematic stepwise analysis of the interviews was performed.

    RESULTS

    Chemotherapy-induced pain had a profound impact on daily life. Ten women reported the worst possible pain, with visual analog scale scores of 8 to 10. Three different categories crystallized: perception (A) of manageable pain, which allowed the women to maintain their daily lives; perception (B) of pain beyond imagination, whereby the impact of pain had become more complex; and perception (C) of crippling pain, challenging the women's confidence in survival.

    CONCLUSIONS

    The findings highlight the inability to capture CHIP with 1 method only; it is thus necessary to use complimentary methods to capture pain. We found that pain had a considerable impact on daily life, with surprisingly high scores of perceived pain, findings that to date have been poorly investigated qualitatively.

    IMPLICATIONS FOR PRACTICE

    Nurses need to (1) better identify, understand and treat CHIP, using instruments and protocols; and (2) provide improved communication about pain and pain management.

  • 23.
    Humphries, Matthew P.
    et al.
    Univ Leeds, Leeds Inst Canc & Pathol, Leeds, W Yorkshire, England..
    Rajan, Sreekumar Sundara
    Univ Leeds, Leeds Inst Canc & Pathol, Leeds, W Yorkshire, England..
    Droop, Alastair
    Univ Leeds, Leeds Inst Canc & Pathol, Leeds, W Yorkshire, England.;Univ Leeds, MRC Med Bioinformat Ctr, Leeds, W Yorkshire, England..
    Suleman, Charlotte A. B.
    St James Univ Hosp, Dept Histopathol, Leeds, W Yorkshire, England..
    Carbone, Carmine
    Azienda Osped Univ Integrata, Ctr Comprehens Canc, Verona, Italy..
    Nilsson, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Honarpisheh, Hedieh
    Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA..
    Cserni, Gabor
    Bacs Kiskun Cty Teaching Hosp, Dept Pathol, Kecskemet, Hungary..
    Dent, Jo
    Calderdale Hosp, Halifax, England..
    Fulford, Laura
    Surrey & Sussex NHS Trust, Redhill, Surrey, England..
    Jordan, Lee B.
    Univ Dundee, NHS Tayside, Dundee, Scotland..
    Jones, J. Louise
    Barts Canc Inst, London, England..
    Kanthan, Rani
    Univ Saskatchewan, Dept Pathol & Lab Med, Saskatoon, SK, Canada..
    Litwiniuk, Maria
    Poznan Univ Med Sci, Greater Poland Canc Ctr, Poznan, Poland..
    Di Benedetto, Anna
    Regina Elena Inst Canc Res, Dept Pathol, Rome, Italy..
    Mottolese, Marcella
    Regina Elena Inst Canc Res, Dept Pathol, Rome, Italy..
    Provenzano, Elena
    Addenbrookes Hosp, Dept Histopathol, Cambridge, England..
    Shousha, Sami
    Imperial Coll Healthcare NHS Trust, Dept Histopathol, London, England.;Charing Cross Hosp, Imperial Coll, London, England..
    Stephens, Mark
    Univ Hosp North Staffordshire, Stoke On Trent, Staffs, England..
    Walker, Rosemary A.
    Univ Leicester, Canc Studies & Mol Med, Leicester, Leics, England..
    Kulka, Janina
    Semmelweis Univ, Dept Pathol 2, Budapest, Hungary..
    Ellis, Ian O.
    Nottingham City Hosp, Fac Med & Hlth Sci, Nottingham, England..
    Jeffery, Margaret
    Queen Alexandra Hosp, Pathol Ctr, Dept Histopathol, Portsmouth, Hants, England..
    Thygesen, Helene H.
    Univ Leeds, Leeds Inst Canc & Pathol, Leeds, W Yorkshire, England..
    Cappelletti, Vera
    Fdn IRCCS Ist Nazl Tumori, Dept Expt Oncol & Mol Med, Milan, Italy..
    Daidone, Maria G.
    Fdn IRCCS Ist Nazl Tumori, Dept Expt Oncol & Mol Med, Milan, Italy..
    Hedenfalk, Ingrid A.
    Lund Univ, Dept Oncol & Pathol, Clin Sci, Lund, Sweden.;Lund Univ, CREATE Hlth Strateg Ctr Translat Canc Res, Lund, Sweden..
    Fjällskog, Marie-Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    Melisi, Davide
    Azienda Osped Univ Integrata, Ctr Comprehens Canc, Verona, Italy.;Univ Verona, Dept Med, Digest Mol Clin Oncol Res Unit, Verona, Italy..
    Stead, Lucy F.
    Univ Leeds, Leeds Inst Canc & Pathol, Leeds, W Yorkshire, England..
    Shaaban, Abeer M.
    Queen Elizabeth Hosp Birmingham, Dept Cellular Pathol, Birmingham, W Midlands, England.;Univ Birmingham, Birmingham, W Midlands, England..
    Speirs, Valerie
    Univ Leeds, Leeds Inst Canc & Pathol, Leeds, W Yorkshire, England..
    A Case-Matched Gender Comparison Transcriptomic Screen Identifies eIF4E and eIF5 as Potential Prognostic Markers in Male Breast Cancer2017In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 23, no 10, p. 2575-2583Article in journal (Refereed)
    Abstract [en]

    Purpose: Breast cancer affects both genders, but is understudied in men. Although still rare, male breast cancer (MBC) is being diagnosed more frequently. Treatments are wholly informed by clinical studies conducted in women, based on assumptions that underlying biology is similar.

    Experimental Design: A transcriptomic investigation of male and female breast cancer was performed, confirming transcriptomic data in silico. Biomarkers were immunohistochemically assessed in 697 MBCs (n = 477, training; n = 220, validation set) and quantified in pre- and posttreatment samples from an MBC patient receiving everolimus and PI3K/mTOR inhibitor.

    Results: Gender-specific gene expression patterns were identified. eIF transcripts were upregulated in MBC. eIF4E and eIF5 were negatively prognostic for overall survival alone (log-rank P = 0.013; HR = 1.77, 1.12-2.8 and P = 0.035; HR = 1.68, 1.03-2.74, respectively), or when coexpressed (P = 0.01; HR = 2.66, 1.26-5.63), confirmed in the validation set. This remained upon multivariate Cox regression analysis [ eIF4E P = 0.016; HR = 2.38 (1.18-4.8), eIF5 P = 0.022; HR = 2.55 (1.14-5.7); coexpression P = 0.001; HR = 7.04 (2.22-22.26)]. Marked reduction in eIF4E and eIF5 expression was seen post BEZ235/everolimus, with extended survival.

    Conclusions: Translational initiation pathway inhibition could be of clinical utility in MBC patients overexpressing eIF4E and eIF5. With mTOR inhibitors that target this pathway now in the clinic, these biomarkers may represent new targets for therapeutic intervention, although further independent validation is required.

  • 24.
    Johansson, Ida
    et al.
    Lund Univ, Dept Oncol & Pathol, Clin Sci, Lund, Sweden.;Lund Univ, CREATE Hlth Strateg Ctr Translat Canc Res, Lund, Sweden..
    Lauss, Martin
    Lund Univ, Dept Oncol & Pathol, Clin Sci, Lund, Sweden.;Lund Univ, CREATE Hlth Strateg Ctr Translat Canc Res, Lund, Sweden..
    Holm, Karolina
    Lund Univ, Dept Oncol & Pathol, Clin Sci, Lund, Sweden.;Lund Univ, CREATE Hlth Strateg Ctr Translat Canc Res, Lund, Sweden..
    Staaf, Johan
    Lund Univ, Dept Oncol & Pathol, Clin Sci, Lund, Sweden.;Lund Univ, CREATE Hlth Strateg Ctr Translat Canc Res, Lund, Sweden..
    Nilsson, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Fjällskog, Marie-Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Ringner, Markus
    Lund Univ, Dept Oncol & Pathol, Clin Sci, Lund, Sweden.;Lund Univ, CREATE Hlth Strateg Ctr Translat Canc Res, Lund, Sweden..
    Hedenfalk, Ingrid
    Lund Univ, Dept Oncol & Pathol, Clin Sci, Lund, Sweden.;Lund Univ, CREATE Hlth Strateg Ctr Translat Canc Res, Lund, Sweden..
    Genome methylation patterns in male breast cancer - Identification of an epitype with hypermethylation of polycomb target genes2015In: Molecular Oncology, ISSN 1574-7891, E-ISSN 1878-0261, Vol. 9, no 8, p. 1565-1579Article in journal (Refereed)
    Abstract [en]

    Male breast cancer (hoc) is a rare disease that shares both similarities and differences with female breast cancer (FBC). The aim of this study was to assess genome-wide DNA methylation profiles in MBC and compare them with the previously identified transcriptional subgroups of MBC, luminal M1 and M2, as well as the intrinsic subtypes of FBC. Illumina's 450K Infinium arrays were applied to 47 MBC and 188 FBC tumors. Unsupervised clustering of the most variable CpGs among MBC tumors revealed two stable epitypes, designated ME1 and ME2. The methylation patterns differed significantly between the groups and were closely associated with the transcriptional subgroups luminal M1 and M2. Tumors in the ME1 group were more proliferative and aggressive than ME2 tumors, and showed a tendency toward inferior survival. ME1 tumors also displayed hypermethylation of PRC2 target genes and high expression of EZH2, one of the core components of PRC2. Upon combined analysis of MBC and FBC tumors, ME1 MBCs clustered among luminal B FBC tumors and ME2 MBCs clustered within the predominantly luminal A FBC cluster. The majority of the MBC tumors remained grouped together within the clusters rather than being interspersed among the FBC tumors. Differences in the genomic location of methylated CpGs, as well as in the regulation of central canonical pathways may explain the separation between MBC and FBC tumors in the respective clusters. These findings further suggest that MBC is not readily defined using conventional criteria applied to FBC.

  • 25.
    Johansson, Ida
    et al.
    Department of Oncology, Clinical Sciences and CREATE Health Strategic Center for Translational Cancer Research, Lund University, Lund.
    Nilsson, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Berglund, Pontus
    Department of Oncology, Clinical Sciences, Lund University, Lund, Sweden.
    Lauss, Martin
    Department of Oncology, Clinical Sciences and CREATE Health Strategic Center for Translational Cancer Research, Lund University, Lund.
    Ringner, Markus
    Department of Oncology, Clinical Sciences and CREATE Health Strategic Center for Translational Cancer Research, Lund University, Lund.
    Olsson, Håkan
    Department of Oncology, Clinical Sciences, Lund University, Lund, Sweden.
    Luts, Lena
    Department of pathology, Lund University Hospital, Lund, Sweden.
    Sim, Edith
    Department of Pharmacology, University of Oxford, UK.
    Thorstenson, Sten
    Department of Pathology, Linköping University Hospital, Linköping, Sweden.
    Fjällskog, Marie-Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Hedenfalk, Ingrid
    Department of Oncology, Clinical Sciences and CREATE Health Strategic Center for Translational Cancer Research, Lund University, Lund, Sweden.
    Gene expression profiling of primary male breast cancers reveals two unique subgroups and identifies N-acetyltransferase-1 (NAT1) as a novel prognostic biomarker2012In: Breast Cancer Research, ISSN 1465-5411, E-ISSN 1465-542X, Vol. 14, no 1, p. R31-Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION:

    Male breast cancer (MBC) is a rare and inadequately characterized disease. The aim of the present study was to characterize MBC tumors transcriptionally, to classify them into comprehensive subgroups, and to compare them with female breast cancer (FBC).

    METHODS:

    A total of 66 clinicopathologically well-annotated fresh frozen MBC tumors were analyzed using Illumina Human HT-12 bead arrays, and a tissue microarray with 220 MBC tumors was constructed for validation using immunohistochemistry. Two external gene expression datasets were used for comparison purposes: 37 MBCs and 359 FBCs.

    RESULTS:

    Using an unsupervised approach, we classified the MBC tumors into two subgroups, luminal M1 and luminal M2, respectively, with differences in tumor biological features and outcome, and which differed from the intrinsic subgroups described in FBC. The two subgroups were recapitulated in the external MBC dataset. Luminal M2 tumors were characterized by high expression of immune response genes and genes associated with estrogen receptor (ER) signaling. Luminal M1 tumors, on the other hand, despite being ER positive by immunohistochemistry showed a lower correlation to genes associated with ER signaling and displayed a more aggressive phenotype and worse prognosis. Validation of two of the most differentially expressed genes, class 1 human leukocyte antigen (HLA) and the metabolizing gene N-acetyltransferase-1 (NAT1), respectively, revealed significantly better survival associated with high expression of both markers (HLA, hazard ratio (HR) 3.6, P = 0.002; NAT1, HR 2.5, P = 0.033). Importantly, NAT1 remained significant in a multivariate analysis (HR 2.8, P = 0.040) and may thus be a novel prognostic marker in MBC.

    CONCLUSIONS:

    We have detected two unique and stable subgroups of MBC with differences in tumor biological features and outcome. They differ from the widely acknowledged intrinsic subgroups of FBC. As such, they may constitute two novel subgroups of breast cancer, occurring exclusively in men, and which may consequently require novel treatment approaches. Finally, we identified NAT1 as a possible prognostic biomarker for MBC, as suggested by NAT1 positivity corresponding to better outcome.

  • 26. Klintman, Marie
    et al.
    Strand, Carina
    Ahlin, Cecilia
    Beglerbegovic, Sanda
    Fjällskog, Marie-Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Grabau, Dorthe
    Gudlaugsson, Einar
    Janssen, Emiel A. M.
    Lovgren, Kristina
    Skaland, Ivar
    Bendahl, Par-Ola
    Malmstrom, Per
    Baak, Jan P. A.
    Ferno, Marten
    The Prognostic Value of Mitotic Activity Index (MAI), Phosphohistone H3 (PPH3), Cyclin B1, Cyclin A, and Ki67, Alone and in Combinations, in Node-Negative Premenopausal Breast Cancer2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 12Article in journal (Refereed)
    Abstract [en]

    Proliferation, either as the main common denominator in genetic profiles, or in the form of single factors such as Ki67, is recommended for clinical use especially in estrogen receptor-positive (ER) patients. However, due to high costs of genetic profiles and lack of reproducibility for Ki67, studies on other proliferation factors are warranted. The aim of the present study was to evaluate the prognostic value of the proliferation factors mitotic activity index (MAI), phosphohistone H3 (PPH3), cyclin B1, cyclin A and Ki67, alone and in combinations. In 222 consecutive premenopausal node-negative breast cancer patients (87% without adjuvant medical treatment), MAI was assessed on whole tissue sections (predefined cut-off >= 10 mitoses), and PPH3, cyclin B1, cyclin A, and Ki67 on tissue microarray (predefined cut-offs 7th decile). In univariable analysis (high versus low) the strongest prognostic proliferation factor for 10-year distant disease-free survival was MAI (Hazard Ratio (HR)=3.3, 95% Confidence Interval (CI): 1.8-6.1), followed by PPH3, cyclin A, Ki67, and cyclin B1. A combination variable, with patients with MAI and/or cyclin A high defined as high-risk, had even stronger prognostic value (HR=4.2, 95% CI: 2.2-7). When stratifying for ER-status, MAI was a significant prognostic factor in ER-positive patients only (HR=7.0, 95% CI: 3.1-16). Stratified for histological grade, MAI added prognostic value in grade 2 (HR=7.2, 95% CI: 3.1-38) and grade 1 patients. In multivariable analysis including HER2, age, adjuvant medical treatment, ER, and one proliferation factor at a time, only MAI (HR=2.7, 95% CI: 1.1-6.7), and cyclin A (HR=2.7, 95% CI: 1.2-6.0) remained independently prognostic. In conclusion this study confirms the strong prognostic value of all proliferation factors, especially MAI and cyclin A, in all patients, and more specifically in ER-positive patients, and patients with histological grade 2 and 1. Additionally, by combining two proliferation factors, an even stronger prognostic value may be found.

  • 27.
    Koliadi, Anthoula
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Nilsson, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Holmqvist, Marit
    Uppsala-Örebro Regional Oncologic Centre, Uppsala, Sweden.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    de la Torre, Manuel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Wärnberg, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Fjällskog, Marie-Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Cyclin B is an immunohistochemical proliferation marker which can predict for breast cancer death in low-risk node negative breast cancer2010In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 49, no 6, p. 816-820Article in journal (Refereed)
    Abstract [en]

    Patients with low-risk node negative breast cancer have an excellent prognosis with 5% breast cancer mortality at 10 years. However, prognostic factors are needed to identify poor prognostic patients who might benefit from adjuvant systemic therapy. Proliferation has been identified as the most important component of gene expression profiles. Cyclin B is a proliferative marker easily assessed by immunohistochemistry. We wanted to examine cyclin B as a prognostic factor in low-risk breast cancer patients. Patients and methods. Using an experimental study design, we compared women dying early from their breast cancer (n=17) with women free from relapse more than eight years after initial diagnosis (n=24). All women had stage I, node negative and hormone receptor positive disease. None had received adjuvant chemotherapy. Tumor samples were immunostained for cyclin B using commercial antibodies. Results. The mean percentage of cyclin B (12%) was significantly higher (p=0.001) in women dying from their breast cancer compared with women free from relapse ( 5%). High cyclin B (>= 9%) identified 11/17 patients dying from breast cancer and low cyclin B identified 22/24 patients free from relapse. The sensitivity and specificity of cyclin B was 65% and 92%, respectively. Discussion. We found that low-risk node negative patients with high expression of cylin B had a significantly worse outcome than patients with low expression of cyclin B. Cyclin B could separate patients with poor survival from those with good survival with 80% accuracy. We suggest that cyclin B might be a potent prognostic factor in this low-risk patient group.

  • 28.
    Lundgren, Claudia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Ahlin, Cecilia
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Amini, Rose-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Fjällskog, Marie-Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science.
    Blomqvist, Carl
    Cyclin E1 is a strong prognostic marker for death from lymph node negative breast cancer: A population-based case-control study2015In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 54, no 4, p. 538-544Article in journal (Refereed)
    Abstract [en]

    Background. A large proportion of women with lymph node negative breast cancer treated with systemic adjuvant treatment do not benefit from such therapy since the patient is already cured by local treatment. Several studies have suggested that proliferation markers are strong prognostic factors in early breast cancer. Cyclins are probably the most specific markers of cell proliferation. Previously high expression of cyclin E has been associated with breast cancer recurrence.

    Materials and methods. In this study we investigate the prognostic value of cyclin E1 in node negative breast cancer patients. In a population-based cohort 186 women who died from breast cancer were defined as cases and 186 women alive at the corresponding time as controls. Inclusion criteria were tumour size ≤ 50 mm, no lymph node metastases and no adjuvant chemotherapy. The study was designed to detect an odds ratio of 2.5 with a power of 90% and significance level of 0.05. Cyclin E1 was determined with immunohistochemistry (IHC) on tissue microarray (TMA).

    Results. High expression of cyclin E1 was significantly associated with breast cancer death, in both uni- and multivariate analyses with odds ratios (OR) 2.3 [univariate, 95% confidence interval (CI) 1.5-3.6] and 2.1 (multivariate, 95% CI 1.2-3.5).

    Discussion. Cyclin E1 is a strong prognostic factor for breast cancer death in a population-based and node negative patient cohort and can identify high-risk patients in this group.

  • 29.
    Lundgren, Claudia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Holmqvist, Marit
    Holmberg, Lars
    Blomqvist, Carl
    Fjällskog, Marie-Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    High Expression of Cyclin E Increases the Risk for Breast Cancer Death by 2-3 Fold in Node Negative Breast Cancer Patients2009Conference paper (Other academic)
  • 30. Löfdahl, Britta
    et al.
    Ahlin, Cecilia
    Holmqvist, Marit
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Zhou, Wenjing
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Fjällskog, Marie-Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Amini, Rose-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Inflammatory cells in node-negative breast cancer2012In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 51, no 5, p. 680-686Article in journal (Refereed)
    Abstract [en]

    Background.

    To study the impact of inflammatory cells in a clinically well-defined cohort of women with node-negative breast cancer in a nested case-control study design.

    Material and methods.

    The cohort was comprised of 190 women who died from breast cancer and 190 women still alive at the date of death for the corresponding breast cancer patients were used as controls. The inclusion criteria included; a tumour size ≤ 50 mm, no lymph node metastases and no initiation of adjuvant chemotherapy. Immunohistochemical stainings for CD3, CD4, CD8, FoxP3, CD20, tryptase and CD68 were performed on TMA blocks, evaluated and correlated to each other and to age, tumour size, histological grade, ER, PgR, Ki67 and cyclin A.

    Results.

    There was no difference regarding the amount or content of inflammatory cells in the cases compared to controls. T- and B-cells were highly correlated to each other but these cell types correlated to a lesser extent to macrophages and not at all to mast cells. A weak tendency of correlations between all the subsets of inflammatory cells and histological grade, Ki67 and cyclin A was observed, although a negative correlation was seen for mast cells.

    Conclusion.

    The amount or content of inflammatory cells in invasive breast cancer did not appear to influence death in node-negative breast cancer.

  • 31.
    Nilsson, Cecilia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Johansson, Ida
    Department of Oncology, Clinical Sciences and CREATE Health Strategic Center for Translational Cancer Research, Lund University, Lund.
    Ahlin, Cecilia
    Department of Oncology, Örebro University Hospital, Örebro, Sweden.
    Thorstenson, Sten
    Department of Pathology, Linköping University Hospital, Linköping, Sweden.
    Amini, Rose-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Holmqvist, Marit
    Uppsala-Örebro Regional Oncologic Center, Uppsala, Sweden .
    Bergkvist, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Hedenfalk, Ingrid
    Department of Oncology, Clinical Sciences and CREATE Health Strategic Center for Translational Cancer Research, Lund University, Lund, Sweden.
    Fjällskog, Marie-Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Molecular subtyping of male breast cancer using alternative definitions and its prognostic impact2013In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 52, no 1, p. 102-109Article in journal (Refereed)
    Abstract [en]

    Background.

    Male breast cancer (MBC) is an uncommon disease and there is limited information on the prognostic impact of routinely used clinicopathological parameters.

    Material and methods.

    In a retrospective setting, we reviewed 197 MBC patients with accessible paraffin-embedded tumor tissue and clinicopathological data. Immunohistochemical (IHC) stainings were performed on tissue microarrays and histological grading on conventional slides. Cox proportional regression models were applied for uni- and multivariate analyses using breast cancer death as the event.

    Results.

    Estrogen receptor (ER) and progesterone receptor positivity were demonstrated in 93% and 77% of patients, respectively. Nottingham histologic grade (NHG) III was seen in 41% and HER2 positivity in 11%. Classification into molecular subtypes using IHC markers according to three alternative definitions revealed luminal A and luminal B in 81% vs. 11%; 48% vs. 44% and 41% vs. 42% of cases. Two cases of basal-like were identified, but no cases of HER2-like. Factors associated with an increased risk of breast cancer death were node positivity (HR 4.5; 95% CI 1.8-11.1), tumor size > 20 mm (HR 3.3; 95% CI 1.4-7.9) and ER negativity (HR 10.9; 95% CI 3.2-37.9). No difference in breast cancer death between the luminal subgroups was demonstrated, regardless of definition.

    Conclusion.

    MBC tumors were more often of high grade, whereas HER2 overexpression was as frequent as in FBC. Lymph nodes, tumor size and ER status were independent predictors of breast cancer death. The prognostic impact of molecular subtyping in MBC seems to differ from that previously established in FBC.

  • 32.
    Nilsson, Cecilia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science.
    Koliadi, Anthoula
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Johansson, Ida
    Department of Oncology, Clinical Sciences and CREATE Health Strategic Center for Translational Cancer Research, Lund University, Lund.
    Ahlin, Cecilia
    Department of Oncology, Örebro University Hospital, Örebro, Sweden.
    Thorstenson, Sten
    Department of Pathology, Linköping University Hospital, Linköping, Sweden.
    Bergkvist, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Hedenfalk, Ingrid
    Department of Oncology, Clinical Sciences and CREATE Health Strategic Center for Translational Cancer Research, Lund University, Lund, Sweden.
    Fjällskog, Marie-Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    High proliferation is associated with inferior outcome in male breast cancer patients2013In: Modern Pathology, ISSN 0893-3952, E-ISSN 1530-0285, Vol. 26, no 1, p. 87-94Article in journal (Refereed)
    Abstract [en]

    Assessment of proliferation is important in female breast cancer and individual treatment decisions are based upon its results, especially in the lumina! subgroups. Gene expression analyses fail to group male breast cancer into the intrinsic subgroups previously established in female breast cancer. Even though proliferation has been shown to divide malebreast cancer into molecular subgroups with different prognoses, the clinical importance ofproliferation markers has not yet been elucidated. Previous studies in male breast cancer have demonstrated contradictory results regarding the prognostic impact of histological grade and Ki-67, parameters strongly associated with proliferation. The aim of the present project was to studyproliferation in male breast cancer by assessing other proliferation-related markers viz. cyclins A, B, D1 and mitotic count. A total of 197 male breast cancer cases with accessible paraffin-embedded material and outcome data were investigated. Immunohistochemical stainings were performed on tissue microarrays. Kaplan-Meier estimates and the Cox proportional regression models were used for survival analyses with breast cancer death as the event. The subset ofpatients with high expression of cyclin A (hazard ratio (HR) 3.7; P=0.001) and B (HR 2.7; P=0.02) demonstrated a poorer survival. Furthermore, high mitotic count was associated with an increased risk of breast cancer death (HR 2.5; P=0.01). In contrast, cyclin D1 overexpression was predictive of better breast cancer survival (HR 0.3; P=0.001). In conclusion, high levels of cyclin A and B expression and an elevated mitotic count result in a two to threefold higher risk forbreast cancer death, whereas cyclin D1 overexpression halves the risk. The clinical utility of these proliferation markers needs further elucidation. 

  • 33. Nilsson-Ihrfelt, Elisabeth
    et al.
    Fjällskog, Marie-Louise
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Enheten för onkologi.
    Blomqvist, Carl
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Interfaculty Units, Centrum för klinisk forskning, Gävleborg. Enheten för onkologi.
    Ahlgren, Johan
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Edlund, Per
    Hansen, Jörgen
    Malmberg, Lena
    Villman, Kenneth
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Enheten för onkologi.
    Andersson, Gerhard
    Breast cancer on the Internet: the quality of Swedish breast cancer websites.2004In: Breast, ISSN 0960-9776, Vol. 13, no 5, p. 376-82Article in journal (Refereed)
  • 34. Nilsson-Ihrfelt, Elisabeth
    et al.
    Fjällskog, Marie-Louise
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Enh för onkologi.
    Liss, Anders
    Department of Surgical Sciences.
    Jakobsson, Olafur
    Blomqvist, Carl
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Enh för onkologi.
    Andersson, Gerhard
    Autobiographical memories in patients treated for breast cancer.2004In: J Psychosom Res, ISSN 0022-3999, Vol. 57, no 4, p. 363-6Article in journal (Other scientific)
  • 35. Niméus-Malmström, Emma
    et al.
    Koliadi, Anthoula
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Ahlin, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Holmqvist, Marit
    Uppsala-Örebro Regional Oncologic Centre.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Amini, Rose-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Jirström, K.
    Wärnberg, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Blomqvist, Carl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Fernö, M.
    Fjällskog, Marie-Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Cyclin B1 is a prognostic proliferation marker with a high reproducibility in a population-based lymph node negative breast cancer cohort2010In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 127, no 4, p. 961-967Article in journal (Refereed)
    Abstract [en]

    A large proportion of women with lymph node negative breast cancer treated with chemotherapy do not benefit from such treatment. Proliferation markers have been shown to recognize patients at high risk for recurrence. Ki67 has recently been included in the St Gallen guidelines. We investigated the prognostic importance of cyclin B1 in node negative breast cancer and included a study of reproducibility. In a population-based case-control study 190 women who died from breast cancer were defined as cases and 190 women alive at the time for the corresponding case's death as controls. Inclusion criteria were tumor size < 50 mm, no lymph node metastases, and no adjuvant chemotherapy. Tumor tissue was immunostained for cyclin B1. Two investigators evaluated the staining independently by counting approximately 100, 200, 500, and 1000 cells. Cyclin B1 was statistically significantly associated to breast cancer death, in both uni- and multivariate analyses (adjusted for tumor size, age, and endocrine therapy), with odds ratios 2-3 for both investigators. The agreement between the two investigators was good to very good, regardless of the number of counted cells (kappa values between 0.74 and 0.82).Cyclin B1 is a prognostic factor for breast cancer death in a population-based node negative patient cohort which can identify high-risk patients with a good to very good reproducibility. (c) 2009 UICC.

  • 36.
    Nordin, Karin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences.
    Rissanen, Ritva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences.
    Ahlgren, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Burell, Gunilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Fjällskog, Marie-Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Borjesson, Susanne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences.
    Arving, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences.
    How can health care help female breast cancer patients reduce their stress symptoms?: A randomized intervention study with stepped-care2012In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 12, p. 167-Article in journal (Refereed)
    Abstract [en]

    Background: A life threatening illness such as breast cancer can lead to a secondary diagnosis of PTSD (post traumatic stress disorder) with intrusive thoughts and avoidance as major symptoms. In a former study by the research group, 80% of the patients with breast cancer reported a high level of stress symptoms close to the diagnosis, such as intrusive thoughts and avoidance behavior. These symptoms remained high throughout the study. The present paper presents the design of a randomized study evaluating the effectiveness and cost-effectiveness of a stress management intervention using a stepped-care design.

    Method: Female patients over the age of 18, with a recent diagnosis of breast cancer and scheduled for adjuvant treatment in the form of chemotherapy, radiation therapy and/or hormonal therapy are eligible and will consecutively be included in the study. The study is a prospective longitudinal intervention study with a stepped-care approach, where patients will be randomised to one of two interventions in the final stage of treatment. The first step is a low intensity stress-management intervention that is given to all patients. Patients who do not respond to this level are thereafter given more intensive treatment at later steps in the program and will be randomized to more intensive stress-management intervention in a group setting or individually. The primary out-come is subjective distress (intrusion and avoidance) assessed by the Impact of Event Scale (IES). According to the power-analyses, 300 patients are planned to be included in the study and will be followed for one year. Other outcomes are anxiety, depression, quality of life, fatigue, stress in daily living and utilization of hospital services. This will be assessed with well-known psychometric tested questionnaires. Also, the cost-effectiveness of the intervention given in group or individually will be evaluated.

    Discussion: This randomized clinical trial will provide additional empirical evidence regarding the effectiveness of a stress-management program given in group or individually during adjuvant therapy in terms of decreased stress, minimizing fatigue, and maintaining or enhancing patients' quality of life and psychological well-being.

  • 37. Strand, Carina
    et al.
    Ahlin, Cecilia
    Bendahl, Pär-Ola
    Fjällskog, Marie-Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Hedenfalk, Ingrid
    Malmström, Per
    Ferno, Marten
    Combination of the proliferation marker cyclin A, histological grade, and estrogen receptor status in a new variable with high prognostic impact in breast cancer2012In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 131, no 1, p. 33-40Article in journal (Refereed)
    Abstract [en]

    Global gene expression profiles, consisting mainly of genes associated with proliferation, have been shown to subdivide histological grade 2 breast cancers into groups with different prognosis. We raised the question whether this subdivision could be done using a single proliferation marker, cyclin A. Furthermore, we combined cyclin A (CA), histological grade (G), and estrogen receptor-ER (E) into a new variable, CAGE. Our aim was to investigate not only the prognostic importance of cyclin A alone but also the value of the combination variable CAGE. In 219 premenopausal node-negative patients, cyclin A was assessed using immunohistochemistry on tissue microarrays. High cyclin A was defined as above the seventh decile of positive cells. Only 13% of the patients received adjuvant systemic therapy. Cox proportional hazards regression was used to model the impact of the factors on distant disease-free survival (DDFS). Cyclin A divided histological grade 2 tumors into two groups with significantly different DDFS (hazard ratio [HR]: 15, P < 0.001). When stratifying for ER status, cyclin A was a prognostic factor only in the ER positive subgroup. We found that CAGE was an independent prognostic factor for DDFS in multivariate analysis (HR: 4.1, P = 0.002), together with HER2. CAGE and HER2 identified 53% as low-risk patients with a 5-year DDFS of 95%. A new prognostic variable was created by combining cyclin A, histological grade, and ER (CAGE). CAGE together with HER2 identified a large low-risk group for whom adjuvant chemotherapy will have limited efficacy and may be avoided.

  • 38.
    Strand, Carina
    et al.
    Lund Univ, Skane Univ Hosp, Dept Clin Sci Lund, Div Oncol, SE-22185 Lund, Sweden..
    Bak, Martin
    Odense Univ Hosp, Dept Pathol, DK-5000 Odense, Denmark..
    Borgquist, Signe
    Lund Univ, Skane Univ Hosp, Dept Clin Sci Lund, Div Oncol, SE-22185 Lund, Sweden..
    Chebil, Gunilla
    Unilabs, Mammog, SE-25223 Helsingborg, Sweden..
    Falck, Anna-Karin
    Helsingborg Hosp, Dept Surg, SE-28185 Helsingborg, Sweden..
    Fjällskog, Marie-Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Grabau, Dorthe
    Lund Univ, Skane Univ Hosp, Dept Pathol, SE-22185 Lund, Sweden..
    Hedenfalk, Ingrid
    Lund Univ, Skane Univ Hosp, Dept Clin Sci Lund, Div Oncol, SE-22185 Lund, Sweden..
    Jirström, Karin
    Lund Univ, Dept Clin Sci Lund, Div Pathol, SE-22185 Lund, Sweden..
    Klintman, Marie
    Lund Univ, Skane Univ Hosp, Dept Clin Sci Lund, Div Oncol, SE-22185 Lund, Sweden..
    Malmström, Per
    Lund Univ, Skane Univ Hosp, Dept Clin Sci Lund, Div Oncol, SE-22185 Lund, Sweden.;Skane Univ Hosp, Skane Dept Oncol, SE-22185 Lund, Sweden..
    Olsson, Hans
    Linkoping Univ, Fac Hlth Sci, Cty Council Ostergotland,Mol & Immunol Pathol, Dept Clin Pathol & Clin Genet,Dept Clin & Expt Me, SE-58191 Linkoping, Sweden..
    Rydén, Lisa
    Lund Univ, Skane Univ Hosp, Dept Clin Sci Lund, Div Surg, SE-22185 Lund, Sweden..
    Stål, Olle
    Linkoping Univ, Fac Hlth Sci, Cty Council Ostergotland, Dept Clin & Expt Med,Div Oncol, SE-58185 Linkoping, Sweden..
    Bendahl, Pär-Ola
    Lund Univ, Skane Univ Hosp, Dept Clin Sci Lund, Div Oncol, SE-22185 Lund, Sweden..
    Fernö, Mårten
    Lund Univ, Skane Univ Hosp, Dept Clin Sci Lund, Div Oncol, SE-22185 Lund, Sweden..
    The combination of Ki67, histological grade and estrogen receptor status identifies a low-risk group among 1,854 chemo-naive women with N0/N1 primary breast cancer2013In: SpringerPlus, E-ISSN 2193-1801, Vol. 2, article id 111Article in journal (Refereed)
    Abstract [en]

    Background: The aim was to confirm a previously defined prognostic index, combining a proliferation marker, histological grade, and estrogen receptor (ER) in different subsets of primary N0/N1 chemo-naive breast cancer patients. Methods/design: In the present study, including 1,854 patients, Ki67 was used in the index (KiGE), since it is the generally accepted proliferation marker in clinical routine. The low KiGE-group was defined as histological grade 1 patients and grade 2 patients which were ER-positive and had low Ki67 expression. All other patients made up the high KiGE-group. The KiGE-index separated patients into two groups with different prognosis. In multivariate analysis, KiGE was significantly associated with disease-free survival, when adjusted for age at diagnosis, tumor size and adjuvant endocrine treatment (hazard ratio: 3.5, 95% confidence interval: 2.6-4.7, P<0.0001). Discussion: We have confirmed a prognostic index based on a proliferation marker (Ki67), histological grade, and ER for identification of a low-risk group of patients with N0/N1 primary breast cancer. For this low-risk group constituting 57% of the patients, with a five-year distant disease-free survival of 92%, adjuvant chemotherapy will have limited effect and may be avoided.

  • 39. Zduniak, K.
    et al.
    Ziolkowski, P.
    Ahlin, C.
    Agrawal, A.
    Agrawal, S.
    Blomqvist, Carl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Fjällskog, Marie-Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science.
    Weber, G. F.
    Nuclear osteopontin-c is a prognostic breast cancer marker2015In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 112, no 4, p. 729-738Article in journal (Refereed)
    Abstract [en]

    Background: Although Osteopontin has been known as a marker for cancer progression, the elevated production of this cytokine is not specific for cancer. We have identified the splice variant Osteopontin-c as being absent from healthy tissue but associated with about 75% of breast cancer cases. However, in previous studies of Osteopontin-c, follow-up information was not available. Methods: Here we have analysed 671 patients, comprising a cohort of 291 paraffin blocks plus a population-based case-control study of 380 arrayed breast tumor tissues. Results: We find that high staining intensity of nuclear Osteopontin-c is strongly associated with mortality in patients with early breast cancer. Cytosolic staining for exon 4, reflective of Osteopontin-a and -b also predicts poor outcome. By contrast, total Osteopontin does not correlate with prognosis. These diverse assessments of Osteopontin also do not correlate with each other, suggesting distinct expression patterns for the variant forms. Consistent with its role in tumor progression, not tumor initiation, Osteopontin-c is not correlated with proliferation markers (Ki-67, cyclin A, cyclin B, cyclin E and cyclin D), neither is it correlated with ER, PR or HER2. Conclusions: The addition of Osteopontin-c immunohistochemistry to standard pathology work-ups may have prognostic benefit in early breast cancer diagnosis.

  • 40.
    Zhou, Wenjing
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Jirström, Karin
    Amini, Rose-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Fjällskog, Marie-Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Sollie, Thomas
    Lindman, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Sørlie, Therese
    Blomqvist, Carl
    Wärnberg, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Molecular subtypes in ductal carcinoma in situ of the breast and their relation to prognosis: a population-based cohort study2013In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 13, p. 512-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Different molecular subtypes of breast cancer have been identified based on gene expression profiling. Treatment suggestions based on an approximation of these subtypes by immunohistochemical criteria have been published by the St Gallen international expert consensus panel. Ductal carcinoma in situ (DCIS) can be classified into the same molecular subtypes. Our aim was to study the relation between these newly defined subtypes and prognosis in DCIS.

    METHODS: TMA including 458 women from a population-based cohort with DCIS diagnosed 1986-2004 was used. Stainings for ER, PR, HER2 and Ki67 were used to classify the surrogate molecular subtypes according to the St Gallen criteria from 2011. The associations with prognosis were examined using Kaplan-Meier analyses and Cox proportional hazards regression models.

    RESULTS: Surrogate molecular subtyping could be done in 381 cases. Mean follow up was 164 months. Of the classified DCIS 186 were Luminal A (48.8%), 33 Luminal B/HER2- (8.7%), 74 Luminal B/HER2+ (17.4%), 61 HER2+/ER- (16.0%) and 27 Triple Negative (7.1%). One hundred and two women had a local recurrence of which 58 were invasive. Twenty-two women had generalised disease, 8 without a prior local recurrence. We could not find a prognostic significance of the molecular subtypes other than a higher risk of developing breast cancer after more than 10 years of follow-up among women with a Triple Negative DCIS (OR 3.2; 95% CI 1.1-9.8).

    CONCLUSIONS: The results from this large population-based cohort, with long-term follow up failed to demonstrate a prognostic value for the surrogate molecular subtyping of DCIS using the St Gallen criteria up to ten years after diagnosis. More than ten years after diagnosis Triple Negative DCIS had an elevated risk of recurrence.

  • 41.
    Zhou, Wenjing
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Johansson, Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Jirström, Karin
    Ringberg, Anita
    Blomqvist, Carl
    Amini, Rose-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Fjällskog, Marie-Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Wärnberg, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    A Comparison of Tumor Biology in Primary Ductal Carcinoma In Situ Recurring as Invasive Carcinoma versus a New In Situ2013In: International Journal of Breast Cancer, ISSN 2090-3170, E-ISSN 2090-3189, Vol. 2013, p. 582134-Article in journal (Refereed)
    Abstract [en]

    Introduction

    About half of all new ipsilateral events after a primary ductal carcinoma in situ (DCIS) are invasive carcinoma. We studied tumor markers in the primary DCIS in relation to type of event (invasive versus in situ).

    Methods

    Two hundred and sixty-six women with a primary DCIS from two source populations, all with a known ipsilateral event, were included. All new events were regarded as recurrences. Patient and primary tumor characteristics (estrogen receptor (ER), progesterone receptor (PR), HER2, EGFR, and Ki67) were evaluated. Logistic regression was used to calculate odd ratios and 95% confidence intervals in univariate and multivariate analyses.

    Results

    One hundred and thirty-six of the recurrences were invasive carcinoma and 130 were in situ. The recurrence was more often invasive if the primary DCIS was ER+ (OR 2.5, 95% CI 1.2-5.1). Primary DCIS being HER2+ (OR 0.5, 95% CI 0.3-0.9), EGFR+ (OR 0.4, 95% CI 0.2-0.9), and ER95-/HER2+ (OR 0.2, 95% CI 0.1-0.6) had a lower risk of a recurrence being invasive.

    Conclusions

    In this study, comparing type of recurrence after a DCIS showed that the ER-/HER2+ tumors were related to a recurrence being a new DCIS. And surprisingly, tumors being ER+, HER2-, and EGFR- were related to a recurrence being invasive cancer.

  • 42.
    Zhou, Wenjing
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Sollie, Thomas
    Tot, Tibor
    Pinder, Sarah E
    Amini, Rose-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Blomqvist, Carl
    Fjällskog, Marie-Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Christensson, Gunilla
    Abdsaleh, Shahin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Wärnberg, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Breast cancer with neoductgenesis: histopathological criteria and its correlation with mammographic and tumour features2014In: International Journal of Breast Cancer, ISSN 2090-3170, E-ISSN 2090-3189, Vol. 2014, article id 581706Article in journal (Refereed)
    Abstract [en]

    Introduction. Breast cancer with mammographic casting type calcifications, high grade DCIS with an abnormal number of ducts, periductal desmoplastic reaction, lymphocyte infiltration, and tenascin-C (TN-C) overexpression has been proposed to represent a more aggressive form of breast cancer and has been denominated as breast cancer with neoductgenesis. We developed histopathological criteria for neoductgenesis in order to study reproducibility and correlation with other tumour markers.

    Methods. 74 cases of grades 2 and 3 DCIS, with or without an invasive component, were selected. A combined score of the degree(s) of concentration of ducts, lymphocyte infiltration, and periductal fibrosis was used to classify cases as showing neoductgenesis, or not. Diagnostic reproducibility, correlation with tumour markers, and mammographic features were studied.

    Results. Twenty-three of 74 cases were diagnosed with neoductgenesis. The kappa value between pathologists showed moderate reproducibility (0.50) (95% CI; 0.41-0.60). Neoductgenesis correlated significantly with malignant type microcalcifications and TN-C expression (P = 0.008 and 0.04) and with ER, PR, and HER2 status (P < 0.00001 for all three markers).

    Conclusions. We developed histological criteria for breast cancer with neoductgenesis. Neoductgenesis, by our applied histopathological definition was related to more aggressive tumour biology and malignant mammographic calcifications.

1 - 42 of 42
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf