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Cardiovascular Side Effects of Radiotherapy in Breast Cancer
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The aim of the thesis was to study cardiovascular side effects of radiotherapy (RT) in breast cancer (BC).

In a study base of 25,171 women with BC diagnosed 1970-2000, we found a statistically significant 12% increase of stroke, compared to the stroke incidence in the background population.

A case-control study of 282 cases with BC followed by a stroke and 1:1 matched controls with BC but not stroke was performed. In women irradiated to internal mammary chain (IMC) and supraclavicular lymph nodes (SCL) vs. a pooled group of women not irradiated or irradiated to targets other than IMC and SCL, a statistically significant increase of stroke with an odds ratio of 1.8 was observed. There were no associations between BC laterality, targets of RT, and hemisphere location of stroke. The radiation targets IMC and SCL, showed a statistically significant trend for an increased risk of stroke with daily fraction dose.

A study of 199 patients with BC, examined by coronary angiography, detected a four- to seven-fold increase of high grade coronary artery stenosis in mid and distal left anterior descending artery (LAD), including distal diagonal branch, when comparing women with irradiated left-sided BC to those with right-sided. An increase of clinically significant coronary artery stenosis was found in pre-specified hotspot areas for radiation among women irradiated to the left breast/chest wall or to the IMC. Thus, the coronary arteries should be regarded as organs at risk in RT of BC.

In a study of 15 BC patients treated with 3D conformal RT, a marked difference in dose distribution in mid and distal LAD between left- and right-sided BC was demonstrated. Irradiated right-sided BC mainly received low doses of scattered and transmitted radiation to the coronary arteries. On the contrary, tangential RT to the left breast without regional lymph node irradiation yielded coronary artery max doses of approximately 50 Gray to distal LAD, probably not safe concerning late radiation vascular effects.

To conclude, we found cardiovascular side effects in women irradiated for BC, resulting in stroke and coronary artery disease, and showed an association between the targets for RT and the anatomical location of these vascular events.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2012. , 77 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 800Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206
Keyword [en]
Breast Cancer, Radiotherapy, Cardiovascular, Stroke, Coronary artery stenosis, Coronary artery disease
National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
URN: urn:nbn:se:uu:diva-179811ISBN: 978-91-554-8446-0 (print)OAI: oai:DiVA.org:uu-179811DiVA: diva2:546414
Public defence
2012-10-05, Auditorium Minus, Gustavianum, Akademigatan 3, Uppsala, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2012-09-14 Created: 2012-08-23 Last updated: 2013-01-22Bibliographically approved
List of papers
1. Increased incidence of stroke in women with breast cancer
Open this publication in new window or tab >>Increased incidence of stroke in women with breast cancer
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2005 (English)In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 41, no 3, 423-429 p.Article in journal (Refereed) Published
Abstract [en]

Meta-analyses have shown an excess of vascular deaths in women with breast cancer given radiotherapy (RT). In women with breast cancer, RT to the supraclavicular lymph nodes gives a substantial radiation dose to the proximal carotid artery. RT is known to increase the risk of carotid stenosis and ischaemic stroke in head and neck cancer. A study base of 25,171 women with breast cancer was defined. A linkage between the study base and the Hospital Discharge Register yielded 1766 women who were diagnosed with a stroke after a breast cancer. The observed number of strokes was compared with the expected number in the background population. The Relative Risk (RR) of stroke in the study group with breast cancer was 1.12 (95% Confidence Interval (CI)=1.07-1.17). The increased risk was confined to the subtype cerebral infarction, RR=1.12 (95% CI=1.05-1.19). A statistically significant increase in the risk of stroke was seen among women with a history of breast cancer. Whether this risk is associated with the breast cancer disease per se or related to any treatment requires further study.

Keyword
Breast Neoplasms/complications/*epidemiology/mortality, Cause of Death, Cerebrovascular Accident/complications/*epidemiology/mortality, Female, Follow-Up Studies, Humans, Incidence, Middle Aged, Registries, Research Support; Non-U.S. Gov't, Risk Factors, Sweden/epidemiology
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-70414 (URN)10.1016/j.ejca.2004.11.013 (DOI)000227187400019 ()15691643 (PubMedID)
Available from: 2006-05-08 Created: 2006-05-08 Last updated: 2017-11-21Bibliographically approved
2. Radiation to supraclavicular and internal mammary lymph nodes in breast cancer increases the risk of stroke
Open this publication in new window or tab >>Radiation to supraclavicular and internal mammary lymph nodes in breast cancer increases the risk of stroke
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2009 (English)In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 100, no 5, 811-816 p.Article in journal (Refereed) Published
Abstract [en]

The aim of this study was to assess whether adjuvant treatment of breast cancer (BC) affects the risk of stroke, and to explore radiation targets and fraction doses regarding risk and location of stroke. In a Swedish BC cohort diagnosed during 1970-2003, we carried out a nested case-control study of stroke after BC, with relevant details extracted from medical records. The odds ratio (OR) for radiotherapy (RT) vs that of no RT did not differ between cases and controls (OR=0.85; confidence interval, CI=0.6-1.3). Radiotherapy to internal mammary chain (IMC) and supraclavicular (SCL) lymph nodes vs that of no RT was associated with a higher, although not statistically significant, risk of stroke (OR=1.3; CI=0.8-2.2). In a pooled analysis, RT to IMC and SCL vs the pooled group of no RT and RT to breast/chest wall/axilla (but not IMC and SCL), showed a significant increase of stroke (OR=1.8; CI=1.1-2.8). There were no associations between cancer laterality, targets of RT, and location of stroke. The radiation targets, IMC and SCL, showed a statistically significant trend for an increased risk of stroke with daily fraction dose. Our finding of a target-specific increased risk of stroke and a dose-response relationship for daily fraction dose, indicate that there may be a causal link between RT to the IMC and SCL and risk of stroke.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-103408 (URN)10.1038/sj.bjc.6604902 (DOI)000263905900022 ()19259096 (PubMedID)
Available from: 2009-05-19 Created: 2009-05-19 Last updated: 2017-12-13Bibliographically approved
3. Distribution of Coronary Artery Stenosis After Radiation for Breast Cancer
Open this publication in new window or tab >>Distribution of Coronary Artery Stenosis After Radiation for Breast Cancer
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2012 (English)In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 30, no 4, 380-386 p.Article in journal (Refereed) Published
Abstract [en]

PURPOSE

To study distribution of coronary artery stenosis among patients with breast cancer (BC) and to assess correlation between radiotherapy (RT) and location of stenosis.

PATIENTS AND METHODS

A Swedish BC cohort diagnosed from 1970 to 2003 was linked to registers of coronary angiography from 1990 to 2004, which yielded 199 patients. Stenoses of the coronary arteries were graded from 0 to 5, where 0 indicated a normal vessel and 5 indicated occlusion. Two hotspot areas for radiation were defined: proximal right coronary artery (prox RCA), mid and distal left anterior descending artery and distal diagonal (mdLAD + dD). RT regimens were categorized as high or low risk of irradiating the hotspot areas. Left breast/chest wall was considered high risk for mdLAD + dD; left internal mammary chain (IMC), high risk for prox RCA and mdLAD + dD from 1970 to 1995 and thereafter solely for mdLAD + dD; and right IMC, high risk for prox RCA. Other RT targets and no RT were considered low risk. Results were expressed in odds ratios (ORs) and 95% CIs.

RESULTS

For irradiated left- versus right-sided BC, the OR for grade 3 to 5 stenosis in mdLAD + dD was 4.38 (95% CI, 1.64 to 11.7), and for grade 4 to 5 stenosis, the OR was 7.22 (95% CI, 1.64 to 31.8). For high-risk RT versus low-risk or no RT, the OR for grade 3 to 5 stenosis in hotspot areas was 1.90 (95% CI, 1.11 to 3.24).

CONCLUSION

An increase of stenosis in mdLAD + dD in irradiated left-sided BC and an association between high-risk RT and stenosis in hotspot areas for radiation indicate a direct link between radiation and location of coronary stenoses.

National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-165741 (URN)10.1200/JCO.2011.34.5900 (DOI)000302620900016 ()22203772 (PubMedID)
Available from: 2012-01-09 Created: 2012-01-09 Last updated: 2017-12-08Bibliographically approved
4. Postoperative radiotherapy for breast cancer and coronary artery stenosis: A dosimetry study of 15 patients examined by coronary angiography after breast cancer treatment
Open this publication in new window or tab >>Postoperative radiotherapy for breast cancer and coronary artery stenosis: A dosimetry study of 15 patients examined by coronary angiography after breast cancer treatment
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(English)Manuscript (preprint) (Other academic)
National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
urn:nbn:se:uu:diva-179742 (URN)
Available from: 2012-08-22 Created: 2012-08-22 Last updated: 2013-01-22

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