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- Bernstein, Jonine L., et al.
(författare)
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Contralateral breast cancer after radiotherapy among BRCA1 and BRCA2 mutation carriers: A WECARE Study Report
- 2013
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Ingår i: European Journal of Cancer. - : Elsevier BV. - 1879-0852 .- 0959-8049. ; 49:14, s. 2979-2985
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Tidskriftsartikel (refereegranskat)abstract
- Background: Women with germline BRCA1 or BRCA2 (BRCA1/BRCA2) mutations are at very high risk of developing breast cancer, including asynchronous contralateral breast cancer (CBC). BRCA1/BRCA2 genes help maintain genome stability and assist in DNA repair. We examined whether the risk of CBC associated with radiation treatment was higher among women with germline BRCA1/BRCA2 mutations than among non-carriers. Methods: A population-based, nested case-control study was conducted within a cohort of 52,536 survivors of unilateral breast cancer (UBC). Cases were 603 women with CBC and controls were 1199 women with UBC individually matched on age at diagnosis, race, year of first diagnosis and cancer registry. All women were tested for BRCA1 and BRCA2 mutations. Radiation absorbed dose from the initial radiotherapy (RT) to the CBC location within the contralateral breast was reconstructed from measurements in a tissue-equivalent phantom and details available in the therapy records. Findings: Among women treated with radiation, the mean radiation dose was 1.1 Gy (range = 0.02-6.2 Gy). Risk of developing CBC was elevated among women who carried a deleterious BRCA1/BRCA2 mutation (rate ratio, RR = 4.5, confidence interval, CI = 3.0-6.8), and also among those treated with RT (RR = 1.2, CI = 1.0-1.6). However, among mutation carriers, an incremental increase in risk associated with radiation dose was not statistically significant. Interpretation: Multiplicative interaction of RT with mutation status would be reflected by a larger association of RT with CBC among carriers than among non-carriers, but this was not apparent. Accordingly, there was no clear indication that carriers of deleterious BRCA/BRCA2 mutations were more susceptible to the carcinogenic effects of radiation than non-carriers. These findings are reassuring and have important clinical implications for treatment decisions and the clinical management of patients harbouring deleterious BRCA1/BRCA2 mutations. Funding: All work associated with this study was supported by the U.S. National Cancer Institute [R01CA097397, U01CA083178]. (C) 2013 Elsevier Ltd. All rights reserved.
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| 2. |
- Poynter, Jenny N., et al.
(författare)
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Reproductive factors and risk of contralateral breast cancer by BRCA1 and BRCA2 mutation status: results from the WECARE study
- 2010
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Ingår i: Cancer Causes and Control. - : Springer Science and Business Media LLC. - 1573-7225 .- 0957-5243. ; 21:6, s. 839-846
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Tidskriftsartikel (refereegranskat)abstract
- Reproductive factors, such as early age at menarche, late age at menopause, and nulliparity are known risk factors for breast cancer. Previously, we reported these factors to be associated with risk of developing contralateral breast cancer (CBC). In this study, we evaluated the association between these factors and CBC risk among BRCA1 and BRCA2 (BRCA1/2) mutation carriers and non-carriers. The WECARE Study is a population-based multi-center case-control study of 705 women with CBC (cases) and 1,397 women with unilateral breast cancer (controls). All participants were screened for BRCA1/2 mutations and 181 carriers were identified. Conditional logistic regression models were used to evaluate associations between reproductive factors and CBC for mutation carriers and non-carriers. None of the associations between reproductive factors and CBC risk differed between mutation carriers and non-carriers. The increase in risk with younger age at menarche and decrease in risk in women with more than two full-term pregnancies seen in non-carriers were not significantly different in carriers (adjusted RRs = 1.31, 95% CI 0.65-2.65 and 0.53, 95% CI 0.19-1.51, respectively). No significant associations between the other reproductive factors and CBC risk were observed in mutation carriers or non-carriers. For two reproductive factors previously shown to be associated with CBC risk, we observed similar associations for BRCA1/2 carriers. This suggests that reproductive variables that affect CBC risk may have similar effects in mutation carriers and non-carriers.
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