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Aromatase inhibitors and contralateral breast cancer in BRCA mutation carriers

  • Epidemiology
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Background

Deleterious BRCA mutations confer a significant lifetime risk of breast cancer (BC) as well as contralateral BC (CBC) in patients who do not undergo prophylactic mastectomy. Prior reports have suggested that tamoxifen reduces the risk of CBC in BRCA mutation carriers. Whether aromatase inhibitors (AI) have the same effect is unknown.

Methods

This is a retrospective review of patients diagnosed with non-metastatic ER+ BC between 2004 and 2014 with known BRCA mutation status. Patients were followed from primary diagnosis until CBC diagnosis or death. Median follow-up was 11.5 years. Risk of CBC was evaluated as time to event.

Results

935 subjects were included in this analysis, with 53 BRCA1 mutation carriers, and 94 BRCA2 mutation carriers. Median age at diagnosis was 42.7 years. Seventy-two percent (676) received tamoxifen and 43% (405) received AI. A total of 66 CBCs occurred, of which 10% (15/147) occurred in BRCA mutation carriers vs 6.5% (51/788) in BRCA wild type. Multivariate analyses indicated that BRCA status and AI use were significantly associated with CBC risk. AI use resulted in a significant reduction in risk of CBC (HR 0.44, p = 0.004) regardless of the BRCA mutation status. Tamoxifen use was not associated with reduced risk of CBC.

Conclusions

This is the first report showing that AIs reduce the risk of CBC in BRCA mutation carriers. The potential role of AIs as chemoprevention should be validated in larger independent cohorts.

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Data availability

The datasets generated during and/or analyzed during the current study are not publicly available as the database is actively updated and is the list of active and prior patients receiving care at MD Anderson Cancer Center.

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Funding

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript. The preliminary analysis that lead to this manuscript preparation was presented at ASCO in 2015, and the first author received an ASCO Merit award for the presentation.

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Authors and Affiliations

  1. Baylor College of Medicine, Houston, TX, USA

    Maryam Nemati Shafaee & Kristina Goutsouliak

  2. MD Anderson Cancer Center, Houston, USA

    Maryam Nemati Shafaee, Heather Lin, Therese B. Bevers, Angelica Gutierrez-Barrera & Banu Arun

  3. Stanford University, Stanford, USA

    Melissa Bondy

Authors
  1. Maryam Nemati Shafaee
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  2. Kristina Goutsouliak
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  3. Heather Lin
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  5. Angelica Gutierrez-Barrera
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  7. Banu Arun
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection were performed by [MNS and AG], analysis was performed by [HL, MNS, MB, and BA]. The first draft of the manuscript was written by [MNS] and all authors commented on the previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Maryam Nemati Shafaee.

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Conflict of interest

Therese Bevers, the 4th author, has received research grants from Toray International, Preferred Medicine and Namida Lab. All other authors have no conflict of interest to disclose.

Ethical approval

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of UT MD Anderson Cancer Center.

Consent to participate

Waiver of informed consent was obtained for this retrospective chart review.

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Nemati Shafaee, M., Goutsouliak, K., Lin, H. et al. Aromatase inhibitors and contralateral breast cancer in BRCA mutation carriers. Breast Cancer Res Treat 196, 143–152 (2022). https://doi.org/10.1007/s10549-022-06688-z

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  • DOI: https://doi.org/10.1007/s10549-022-06688-z

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