Adjuvant systemic therapy for breast cancer in BRCA1/BRCA2 mutation carriers in a population-based study of risk of contralateral breast cancer Journal Article


Authors: Reding, K. W.; Bernstein, J. L.; Langholz, B. M.; Bernstein, L.; Haile, R. W.; Begg, C. B.; Lynch, C. F.; Concannon, P.; Borg, A.; Teraoka, S. N.; Törngren, T.; Diep, A.; Xue, S.; Bertelsen, L.; Liang, X.; Reiner, A. S.; Capanu, M.; Malone, K. E.
Article Title: Adjuvant systemic therapy for breast cancer in BRCA1/BRCA2 mutation carriers in a population-based study of risk of contralateral breast cancer
Abstract: Given the greatly elevated risks of contralateral breast cancer (CBC) observed in breast cancer patients who carry mutations in BRCA1 and BRCA2, it is critical to determine the effectiveness of standard adjuvant therapies in preventing CBC in mutation carriers. The WECARE study is a matched, case-control study of 708 women with CBC as cases and 1,399 women with unilateral breast cancer (UBC) as controls, including 181 BRCA1/BRCA2 mutation carriers. Interviews and medical record reviews provided detailed information on risk factors and breast cancer therapy. All study participants were screened for BRCA1 and BRCA2 mutations using denaturing high-performance liquid chromatography (DHPLC) to detect genetic variants in the coding and flanking regions of the genes. Conditional logistic regression was used to compare the risk of CBC associated with chemotherapy and tamoxifen in BRCA1/BRCA2 mutation carriers and non-carriers. Chemotherapy was associated with lower CBC risk both in non-carriers (RR = 0.6 [95% CI: 0.5-0.7]) and carriers (RR = 0.5 [95% CI: 0.2-1.0]; P value = 0.04). Tamoxifen was associated with a reduced CBC risk in non-carriers (RR = 0.7 [95% CI: 0.6-1.0]; P value = 0.03). We observed a similar but non-significant reduction associated with tamoxifen in mutation carriers (RR = 0.7 [95% CI: 0.3-1.8]). The tests of heterogeneity comparing carriers to non-carriers did not provide evidence for a difference in the associations with chemotherapy (P value = 0.51) nor with tamoxifen (P value = 0.15). Overall, we did not observe a difference in the relative risk reduction associated with adjuvant treatment between BRCA1/BRCA2 mutation carriers and non-carriers. However, given the higher absolute CBC risk in mutation carriers, the potentially greater impact of adjuvant therapy in reducing CBC risk among mutation carriers should be considered when developing treatment plans for these patients. © 2010 Springer Science+Business Media, LLC.
Keywords: adult; cancer chemotherapy; controlled study; treatment outcome; middle aged; young adult; gene mutation; major clinical study; case control study; mutation; case-control studies; doxorubicin; fluorouracil; cancer risk; united states; adjuvant therapy; cancer adjuvant therapy; chemotherapy, adjuvant; chemotherapy; methotrexate; neoplasm recurrence, local; breast cancer; antineoplastic combined chemotherapy protocols; logistic models; risk factors; cyclophosphamide; breast neoplasms; brca1 protein; brca2 protein; heterozygote; risk factor; risk assessment; population research; registries; medical record; tamoxifen; seer program; epirubicin; interview; dna mutational analysis; anthracycline derivative; genetic screening; genetic code; brca1; brca2; denmark; counter-matching; contralateral; likelihood functions; denaturing high performance liquid chromatography
Journal Title: Breast Cancer Research and Treatment
Volume: 123
Issue: 2
ISSN: 0167-6806
Publisher: Springer  
Date Published: 2010-09-01
Start Page: 491
End Page: 498
Language: English
DOI: 10.1007/s10549-010-0769-3
PUBMED: 20135344
PROVIDER: scopus
PMCID: PMC2903659
DOI/URL:
Notes: --- - "Export Date: 20 April 2011" - "CODEN: BCTRD" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Anne S Reiner
    126 Reiner
  2. Colin B Begg
    243 Begg
  3. Marinela Capanu
    221 Capanu
  4. Jonine L Bernstein
    105 Bernstein
  5. Xiaolin Liang
    41 Liang