Breast Cancer Research and Treatment

, Volume 123, Issue 2, pp 491–498

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

  • Kerryn W. Reding
  • Jonine L. Bernstein
  • Bryan M. Langholz
  • Leslie Bernstein
  • Robert W. Haile
  • Colin B. Begg
  • Charles F. Lynch
  • Patrick Concannon
  • Ake Borg
  • Sharon N. Teraoka
  • Therese Törngren
  • Anh Diep
  • Shanyan Xue
  • Lisbeth Bertelsen
  • Xiaolin Liang
  • Anne S. Reiner
  • Marinela Capanu
  • Kathleen E. Malone
  • The WECARE Collaborative Study Group
Epidemiology

DOI: 10.1007/s10549-010-0769-3

Cite this article as:
Reding, K.W., Bernstein, J.L., Langholz, B.M. et al. Breast Cancer Res Treat (2010) 123: 491. doi:10.1007/s10549-010-0769-3

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.

Keywords

Adjuvant therapy BRCA1 BRCA2 Breast cancer Chemotherapy Contralateral Counter-matching Tamoxifen 

Abbreviations

BRCA1

Breast cancer susceptibility gene 1

BRCA2

Breast cancer susceptibility gene 2

CAF/CEF

Cyclophosphamide epirubicin/adriamycin, 5-fluorouracil

CBC

Contralateral breast cancer

CMF

Cyclophosphamide, methotrexate, 5-fluorouracil

DHPLC

Denaturing high-performance liquid chromatography

ER

Estrogen receptor

UBC

Unilateral breast cancer

Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • Kerryn W. Reding
    • 1
    • 2
  • Jonine L. Bernstein
    • 3
  • Bryan M. Langholz
    • 4
  • Leslie Bernstein
    • 5
  • Robert W. Haile
    • 4
  • Colin B. Begg
    • 3
  • Charles F. Lynch
    • 6
  • Patrick Concannon
    • 7
  • Ake Borg
    • 8
  • Sharon N. Teraoka
    • 7
  • Therese Törngren
    • 8
  • Anh Diep
    • 4
  • Shanyan Xue
    • 4
  • Lisbeth Bertelsen
    • 9
  • Xiaolin Liang
    • 3
  • Anne S. Reiner
    • 3
  • Marinela Capanu
    • 3
  • Kathleen E. Malone
    • 1
    • 2
  • The WECARE Collaborative Study Group
  1. 1.Division of Public Health SciencesFred Hutchinson Cancer Research CenterSeattleUSA
  2. 2.Department of EpidemiologyUniversity of Washington School of Public HealthSeattleUSA
  3. 3.Department of Epidemiology and BiostatisticsMemorial Sloan-Kettering Cancer CenterNew YorkUSA
  4. 4.Department of Preventive MedicineUniversity of Southern CaliforniaLos AngelesUSA
  5. 5.Division of Cancer Etiology, Department of Population SciencesCity of Hope National Medical Center/Beckman Research InstituteDuarteUSA
  6. 6.Department of EpidemiologyUniversity of IowaIowa CityUSA
  7. 7.Department of Biochemistry and Molecular Genetics and Center for Public Health GenomicsUniversity of VirginiaCharlottesvilleUSA
  8. 8.Department of OncologyLund UniversityLundSweden
  9. 9.Institute of Cancer EpidemiologyDanish Cancer SocietyCopenhagenDenmark