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

  • Epidemiology
  • Published:
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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.

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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

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Acknowledgments

The authors would like to thank the study participants for their contribution to this research. This study was supported by NCI R01CA097397 and NCI U01CA083178. KWR was supported by the Cancer Epidemiology and Biostatistics Training Grant (2 T32 CA 09168), and the Department of Defense Breast Cancer Research Program Pre-doctoral Training Grant (06-1-0312).

Conflict of interest

The authors of this manuscript have no competing interests to declare.

Author information

Authors and Affiliations

  1. Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., Mail Stop M4-B874, Seattle, WA, 98109-1024, USA

    Kerryn W. Reding & Kathleen E. Malone

  2. Department of Epidemiology, University of Washington School of Public Health, Seattle, WA, USA

    Kerryn W. Reding & Kathleen E. Malone

  3. Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    Jonine L. Bernstein, Colin B. Begg, Xiaolin Liang, Anne S. Reiner & Marinela Capanu

  4. Department of Preventive Medicine, University of Southern California, Los Angeles, CA, USA

    Bryan M. Langholz, Robert W. Haile, Anh Diep & Shanyan Xue

  5. Division of Cancer Etiology, Department of Population Sciences, City of Hope National Medical Center/Beckman Research Institute, Duarte, CA, USA

    Leslie Bernstein

  6. Department of Epidemiology, University of Iowa, Iowa City, IA, USA

    Charles F. Lynch

  7. Department of Biochemistry and Molecular Genetics and Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA

    Patrick Concannon & Sharon N. Teraoka

  8. Department of Oncology, Lund University, Lund, Sweden

    Ake Borg & Therese Törngren

  9. Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark

    Lisbeth Bertelsen

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  1. Kerryn W. Reding
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  2. Jonine L. Bernstein
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  4. Leslie Bernstein
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Consortia

The WECARE Collaborative Study Group

Corresponding author

Correspondence to Kerryn W. Reding.

Additional information

Membership in the WECARE Study Collaborative Group is provided in the Appendix Section.

WECARE Study Collaborative Group

WECARE Study Collaborative Group

Memorial Sloan Kettering Cancer Center (New York, NY): Jonine L. Bernstein Ph.D. (WECARE Study P.I.); Colin B. Begg. Ph.D.; Marinela Capanu Ph.D.; Anne S. Reiner, M.P.H, Xiaolin Liang M.D.; Irene Orlow Ph.D, Tracy M. Layne, M.P.H

City of Hope (Duarte, CA): Leslie Bernstein Ph.D.; Laura Donnelly-Allen

Danish Cancer Society (Copenhagen, Denmark): Jørgen H. Olsen, M.D. MSc.; Michael Andersson M.D., D.M.Sc.; Lisbeth Bertelsen M.D., Ph.D.; Per Guldberg Ph.D.; Lene Mellemkjær Ph.D

Fred Hutchinson Cancer Research Center (Seattle, WA): Kathleen E. Malone Ph.D.; Noemi Epstein

International Epidemiology Institute (Rockville, MD) and Vanderbilt University (Nashville, TN): John D. Boice Jr. Sc.D.

Lund University (Lund, Sweden): Åke Borg Ph.D.; Therese Törngren M.Sc.,

New York University (New York, NY): Roy E. Shore Ph.D., Dr.P.H.

University of California at Irvine (Irvine, CA): Hoda Anton-Culver Ph.D.; Joan Largent Ph.D., M.P.H.

University of Iowa (Iowa City, IA): Charles F. Lynch M.D., Ph.D.; Jeanne DeWall M.A.

University of Southern California (Los Angeles, CA): Robert W. Haile Dr.P.H.; Bryan M. Langholz Ph.D.; Duncan C. Thomas Ph.D.; Anh T. Diep; Shanyan Xue M.D.; Nianmin Zhou, M.D; Evgenia Ter-Karapetova;

University of Southern Maine (Portland, ME): W. Douglas Thompson Ph.D.

University of Texas, M.D. Anderson Cancer Center (Houston, TX): Marilyn Stovall Ph.D.; Susan Smith M.P.H.

University of Virginia (Charlottesville, VA) and work performed at Benaroya Research Institute at Virginia Mason (Seattle, WA): Patrick Concannon, Ph.D.; Sharon Teraoka, Ph.D.; Eric R. Olson; Nirasha Ramchurren, Ph.D.

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Reding, K.W., Bernstein, J.L., Langholz, B.M. et al. Adjuvant systemic therapy for breast cancer in BRCA1/BRCA2 mutation carriers in a population-based study of risk of contralateral breast cancer. Breast Cancer Res Treat 123, 491–498 (2010). https://doi.org/10.1007/s10549-010-0769-3

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