Nonsurgical Prevention Strategies in BRCA1 and BRCA2 Mutation Carriers - PubMed (original) (raw)

Review

. 2021 Apr;16(2):144-148.

doi: 10.1159/000507503. Epub 2020 May 11.

Affiliations

Review

Nonsurgical Prevention Strategies in BRCA1 and BRCA2 Mutation Carriers

Christian F Singer. Breast Care (Basel). 2021 Apr.

Abstract

Background: Female carriers of a BRCA1 or 2 germline mutation face a high lifetime risk to develop breast and ovarian cancer. Risk-reducing surgery, such as prophylactic bilateral mastectomy and prophylactic bilateral salpingo-oophorectomy, are proven strategies to prevent breast and ovarian cancer. These procedures are, however, associated with considerable side effects, and the uptake of these highly effective interventions is therefore low in many countries. This highlights the need for alternative and noninvasive strategies for risk reduction in mutation carriers.

Summary: While endocrine treatments with tamoxifen and aromatase inhibitors (AI) have been shown to be effective in secondary prevention, their benefit in primary prevention has never been prospectively evaluated. Moreover, their side effect profile makes them inappropriate candidates for chemoprevention in healthy premenopausal women. Recently, denosumab, a well-tolerated osteoprotective drug, has been shown to have an antitumoral effect on RANK+, _BRCA1_-deficient luminal progenitor cells in vitro, and has been demonstrated to abrogate tumors in _BRCA1_-deficient mouse models.

Key message: The prospectively randomized, double-blind BRCA-P trial is currently investigating the preventative effect of denosumab in healthy BRCA1 germline mutation carriers.

Keywords: BRCA1 mutation; Breast cancer; Denosumab; Primary prevention.

Copyright © 2021 by S. Karger GmbH, Freiburg.

PubMed Disclaimer

Conflict of interest statement

C.F. Singer has received research support, travel fees, and honoraria from Amgen and AstraZeneca, which is relevant to the topic reviewed in this paper. The BRCA-P Trial is funded by Amgen, Department of Defence, and by the German Ministry of Research and Education.

Similar articles

Cited by

References

    1. Kuchenbaecker KB, Hopper JL, Barnes DR, Phillips KA, Mooij TM, Roos-Blom MJ, et al. BRCA1 and BRCA2 Cohort Consortium Risks of Breast, Ovarian, and Contralateral Breast Cancer for BRCA1 and BRCA2 Mutation Carriers. JAMA. 2017 Jun;317((23)):2402–16. - PubMed
    1. Heemskerk-Gerritsen BA, Jager A, Koppert LB, Obdeijn AI, Collée M, Meijers-Heijboer HE, et al. Survival after bilateral risk-reducing mastectomy in healthy BRCA1 and BRCA2 mutation carriers. Breast Cancer Res Treat. 2019 Oct;177((3)):723–33. Epub ahead of print. - PMC - PubMed
    1. Kotsopoulos J, Huzarski T, Gronwald J, Singer CF, Moller P, Lynch HT, et al. Hereditary Breast Cancer Clinical Study Group Bilateral Oophorectomy and Breast Cancer Risk in BRCA1 and BRCA2 Mutation Carriers. J Natl Cancer Inst. 2016 Sep;109((1)) - PMC - PubMed
    1. Galimberti V, Vicini E, Corso G, Morigi C, Fontana S, Sacchini V, et al. Nipple-sparing and skin-sparing mastectomy: review of aims, oncological safety and contraindications. Breast. 2017 Aug;34(Suppl 1):S82–4. - PMC - PubMed
    1. Visvanathan K, Chlebowski RT, Hurley P, Col NF, Ropka M, Collyar D, et al. American Society of Clinical Oncology American society of clinical oncology clinical practice guideline update on the use of pharmacologic interventions including tamoxifen, raloxifene, and aromatase inhibition for breast cancer risk reduction. J Clin Oncol. 2009 Jul;27((19)):3235–58. - PMC - PubMed

Publication types

LinkOut - more resources