Change search
CiteExportLink to record
Permanent link

Direct 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
Long-term effects of adjuvant tamoxifen treatment on cardiovascular disease and cancer
Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The aims of this thesis were to investigate the long-term effects of adjuvant tamoxifen treatment on breast cancer recurrence and mortality, cardiovascular disease, and the incidence of secondary cancer.

Between 1982 and 1992, postmenopausal patients with early stage breast cancer were included in a randomized clinical study of 2 or 5 years of postoperative tamoxifen therapy. The trial was planned by the Swedish Breast Cancer Group, and it included 4610 patients. Follow-up on causes of death, hospitalizations and secondary cancers were obtained from national population-based registries. 

All-cause mortality, breast cancer-specific mortality and mortality from coronary heart disease were decreased in the 5-year group, but the incidence of endometrial cancer was increased (Paper I). The incidence and mortality of cerebrovascular diseases were increased during the active treatment phase, and reduced after the active treatment (Paper II). Similar results were seen for subgroups of cerebrovascular diseases such as stroke and ischemic stroke. In the 5-year group, the morbidity from coronary heart disease was reduced during treatment but not after treatment was stopped (Paper III). This was the case also for heart failure and for atrial fibrillation/flutter. For secondary cancers the lung cancer risk was reduced, as well as the lung cancer mortality (Paper IV). An increased risk was observed for endometrial cancer, but appeared to decrease over time. The risk of contralateral breast cancer was reduced, with most of the reduction after treatment was stopped. For distance recurrences the risk was reduced both during treatment and a few years after treatment was stopped. The breast cancer mortality was also reduced, especially during the post-treatment phase.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2014. , 45 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1430
Keyword [en]
Adjuvant, adverse events, breast cancer, cerebrovascular disease, coronary heart disease, heart failure, lung cancer, second primary cancer, tamoxifen
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:liu:diva-112085DOI: 10.3384/diss.diva-112085ISBN: 978-91-7519-182-9 (print)OAI: oai:DiVA.org:liu-112085DiVA: diva2:763072
Public defence
2014-12-19, Eken, ingång 65, Campus US, Linköpings universitet, Linköping, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2014-11-21 Created: 2014-11-13 Last updated: 2014-11-21Bibliographically approved
List of papers
1. Coronary heart disease mortality after 5 years of adjuvant tamoxifen therapy: Results from a randomized trial
Open this publication in new window or tab >>Coronary heart disease mortality after 5 years of adjuvant tamoxifen therapy: Results from a randomized trial
Show others...
2005 (English)In: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 97, no 21, 1609-1610 p.Article in journal (Refereed) Published
Abstract [en]

From January 1, 1983, through December 31, 1992, a total of 4610 patients entered a randomized trial that compared mortality among patients receiving 2 years of adjuvant tamoxifen therapy with that in patients receiving 5 years of adjuvant tamoxifen therapy, 4175 of whom were recurrence free after 2 years of tamoxifen therapy. Among the 2046 patients randomly assigned to the 5-year group all-cause mortality, breast cancer-specific mortality, and the incidence of contralateral breast cancer were reduced, compared with those among 2129 patients randomized in the 2-year group, but the incidence of endometrial cancer was increased. In addition, mortality from coronary heart disease was statistically significantly reduced in the 5-year group, compared with that in the 2-year group (hazard ratio = 0.67, 95% confidence interval = 0.47 to 0.94, P = .022 [two-sided Wald test]). Ten years after surgery, 2.1% of the patients in the 5-year group and 3.5% of those in the 2-year group had died from coronary heart disease. No statistically significant increases in mortality from other heart diseases, cerebrovascular diseases, or other vascular diseases were observed. © The Author 2005. Published by Oxford University Press. All rights reserved.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-31657 (URN)10.1093/jnci/dji342 (DOI)17468 (Local ID)17468 (Archive number)17468 (OAI)
Available from: 2009-10-09 Created: 2009-10-09 Last updated: 2017-12-13Bibliographically approved
2. Time dependent effects of adjuvant tamoxifen therapy on cerebrovascular disease: results from a randomised trial
Open this publication in new window or tab >>Time dependent effects of adjuvant tamoxifen therapy on cerebrovascular disease: results from a randomised trial
Show others...
2011 (English)In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 104, no 6, 899-902 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Tamoxifen has been associated with an increased risk of stroke. There is, however, little information on the effect in the post-treatment period. Using data from the Swedish Breast Cancer Group adjuvant trial of 5 vs 2 years of tamoxifen treatment, we now report both short-term and long-term effects on morbidity as well as mortality because of cerebrovascular disease. METHODS: Data from the Swedish National Hospital Discharge Registry combined with information from the Swedish Cause of Death Registry was used to define events of disease. Hazard ratios (HRs) were estimated using Cox regression. RESULTS: Comparing patients randomised to 5 years of tamoxifen with patients randomised to 2 years of tamoxifen, the incidence of cerebrovascular diseases was increased (HR 1.70, 95% CI 1.05-2.75) during the active treatment phase and reduced after the active treatment period (HR 0.78, 95% CI 0.63-0.96), and the difference in HR between the two time-periods was significant (P 0.0033). The mortality from cerebrovascular diseases was increased during the treatment period (HR 3.18, 95% CI 1.03-9.87) and decreased during the post-treatment period (HR 0.60, 95% CI 0.40-0.90) with a significant difference in HR between the two periods of follow-up (P=0.0066). Similar results were seen for subgroups of cerebrovascular diseases, such as stroke and ischaemic stroke. CONCLUSION: In an adjuvant setting, tamoxifen was associated with an increased risk of cerebrovascular disease during treatment, but a decreased risk in the post-treatment period.

Place, publisher, year, edition, pages
Nature Publishing Group, 2011
Keyword
breast cancer, tamoxifen, adjuvant treatment, adverse events, cerebrovascular disease
National Category
Social Sciences
Identifiers
urn:nbn:se:liu:diva-67321 (URN)10.1038/bjc.2011.45 (DOI)000288437500002 ()
Available from: 2011-04-08 Created: 2011-04-08 Last updated: 2017-12-11Bibliographically approved
3. Effects of adjuvant tamoxifen therapy on cardiac disease: results from a randomized trial with long-term follow-up
Open this publication in new window or tab >>Effects of adjuvant tamoxifen therapy on cardiac disease: results from a randomized trial with long-term follow-up
Show others...
2013 (English)In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 138, no 2, 467-473 p.Article in journal (Refereed) Published
Abstract [en]

Tamoxifen is associated with a reduced risk of coronary heart disease (CHD). However, there are few reports on long-term effects. Using data from a large Swedish randomized trial of 5 and 2 years of adjuvant tamoxifen in women with early breast cancer, we here present results on morbidity and mortality from cardiac diseases during treatment and long-term after treatment. A total of 4,150 patients were breast cancer recurrence-free after 2 years. Data from the Swedish National Hospital Discharge Registry combined with information from the Swedish Cause of Death Registry were used to define events of disease. Hazard ratios were estimated using Cox regression. Patients assigned to 5 years in comparison with 2 years of postoperative tamoxifen experienced a reduced incidence of CHD [hazard ratio (HR), 0.83; 95 % CI 0.70-1.00], especially apparent during the active treatment period (HR 0.65; 95 % CI 0.43-1.00). The mortality from CHD was significantly reduced (HR 0.72; 95 % CI 0.53-0.97). During the active treatment, the morbidity of other heart diseases was also significantly reduced (HR 0.40; 95 % CI 0.25-0.64) but not after treatment stopped (HR 1.06; 95 % CI 0.87-1.30). Similar results were seen for both heart failure and atrial fibrillation/flutter. As compared to 2 years of therapy, 5 years of postoperative tamoxifen therapy prevents CHD as well as other heart diseases. The risk reduction is most apparent during the active treatment period, and later tends to diminish.

Place, publisher, year, edition, pages
SPRINGER, 233 SPRING ST, NEW YORK, NY 10013 USA, 2013
Keyword
Breast cancer, Tamoxifen, Adjuvant treatment, Adverse events, Heart failure, Coronary heart disease
National Category
Social Sciences
Identifiers
urn:nbn:se:liu:diva-91931 (URN)10.1007/s10549-013-2457-6 (DOI)000316821300012 ()
Available from: 2013-05-06 Created: 2013-05-06 Last updated: 2017-12-06
4. Effects of adjuvant tamoxifen therapy on the incidence of secondary cancer: results from a randomized trial with long term follow-up
Open this publication in new window or tab >>Effects of adjuvant tamoxifen therapy on the incidence of secondary cancer: results from a randomized trial with long term follow-up
Show others...
2014 (English)Manuscript (preprint) (Other academic)
Abstract [en]

BACKGROUND

Tamoxifen is a well-established endocrine treatment for breast cancer. We here present results with respect to second primary cancer from a large randomized trial of 5 and 2 years of adjuvant tamoxifen. Breast cancer distant recurrence and mortality are also reported.

METHODS

Our study included 4128 postmenopausal patients with early stage breast cancer who were alive and free of breast cancer recurrence after 2 years of tamoxifen therapy. They were randomized to receive three more years of therapy or stop tamoxifen. In the comparison of 5 years versus 2 years of postoperative tamoxifen treatment hazard ratios were estimated using Cox regression for different follow-up periods defined as: During treatment (2-5 years) and after treatment (5-10 years, 10-15 years, > 5 years, > 10 years and > 15 years).

RESULTS

In the five years group the incidence of lung cancer was halved (hazard ratio [HR], 0.45, 95% confidence interval [95% CI], 0.27-0.77 [P = .0038]), and lung cancer mortality was decreased. An increased risk was observed for endometrial cancer (HR, 1.83; 95% CI, 1.19-2.81 [P = .0059]), but this risk appeared to decrease over time. The risk of contralateral breast cancer was decreased (HR, 0.73; 95% CI, 0.56-0.96 [P = .022]), also in the period after treatment stopped. In the five years group, the risk of distant recurrence was decreased, and statistically significant reductions were observed both during treatment and in the five year period after treatment stopped. The breast cancer mortality was reduced, especially during the post-treatment phase.

CONCLUSIONS

In this randomized study, tamoxifen substantially reduces the risk of new cancer both in contralateral breast and in lung up to 10 years after treatment stopped.

Keyword
breast cancer, tamoxifen, adjuvant treatment, second primary cancer, lung cancer
National Category
Public Health, Global Health, Social Medicine and Epidemiology Cancer and Oncology
Identifiers
urn:nbn:se:liu:diva-112285 (URN)
Available from: 2014-11-21 Created: 2014-11-21 Last updated: 2015-03-31Bibliographically approved

Open Access in DiVA

Long-term effects of adjuvant tamoxifen treatment on cardiovascular disease and cancer(458 kB)967 downloads
File information
File name FULLTEXT02.pdfFile size 458 kBChecksum SHA-512
6016e362c615a3e0e55e30229560184d041e5a8aca67bc2f323f65e796e076e2fdac4b8630b99fa20b22cf9df38ed4739b27553da6ff371b50b8effd5bd16b3f
Type fulltextMimetype application/pdf
omslag(36 kB)38 downloads
File information
File name COVER01.pdfFile size 36 kBChecksum SHA-512
356bac26575415ec1024a4facb17bfdc699ec58a3b30a5111630e30ad05f67745cfee0a4ebc7b3aba2ac54837a554f060cdebd53cf57232e4a9405ac7c87e594
Type coverMimetype application/pdf

Other links

Publisher's full text

Search in DiVA

By author/editor
Rosell, Johan
By organisation
Division of Clinical SciencesFaculty of Health Sciences
Cancer and Oncology

Search outside of DiVA

GoogleGoogle Scholar
Total: 971 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
isbn
urn-nbn

Altmetric score

doi
isbn
urn-nbn
Total: 1927 hits
CiteExportLink to record
Permanent link

Direct 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