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Safety of 5α-reductase inhibitors and spironolactone in breast cancer patients receiving endocrine therapies

  • Raquel N. Rozner
  • Azael Freites-Martinez
  • Jerry Shapiro
  • Eliza B. Geer
  • Shari Goldfarb
  • Mario E. LacoutureEmail author
Review

Abstract

Purpose

To provide dermatologists and oncologists with a foundation for practical understanding and uses of 5α-reductase inhibitors and spironolactone for breast cancer patients and survivors receiving endocrine therapies (ETs), including the effect of these treatments on sex hormone levels, any reported drug interactions, and any risk of malignancy.

Methods

All published studies from January 1978 through April 2018 were considered, using databases such as PubMed, Google Scholar, and Science Direct. Forty-seven studies were included in this review.

Results

There is no evidence of interactions between 5α-reductase inhibitors and spironolactone with ETs used in breast cancer. Sex hormone alteration with 5α-reductase inhibitor or spironolactone use is variable. Three randomized controlled trials, 1 case–control study, and 6 retrospective cohort studies, including 284 female patients, studied the effects of 5α-reductase inhibitors on serum estrogen levels. Levels were increased in 97 of 284 (34%) patients, decreased in 15 of 284 (5.3%) patients, and unchanged in 162 of 284 (57%) patients. Four retrospective cohort studies, 1 case study, and 1 double-blinded crossover study, including 95 female patients, assessed the effect of spironolactone on estrogen levels. Levels were increased in 25 of 95 (26%) patients, decreased in 6 of 95 (6.3%) patients, and unchanged in 64 of 95 (67%) patients. Ultimately, most patients did not have a significant alteration in the level of estrogen when using 5α-reductase inhibitors or spironolactone. No consistent evidence of increased risk of female breast cancer while on spironolactone was reported in 3 studies including 49,298 patients; the risk of breast cancer with the use of 5α-reductase inhibitors has not been studied.

Conclusions

Most patients did not show increased estrogen levels with spironolactone and there were no data suggesting increased risk of breast cancer. Based on hormonal and pharmacological activity, spironolactone may be considered for further research on alopecia and hirsutism in breast cancer patients.

Keywords

5α-Reductase inhibitors Spironolactone Female pattern hair loss Female breast cancer Endocrine therapy 

Notes

Funding

This study was supported in part by the NIH/NCI Cancer Center Support Grant P30 CA008748. This research was additionally funded in part by Beca Excelencia Fundación Piel Sana (Dr. Freites-Martinez) and the RJR Grant. The sponsors had no role in the design and conduct of the study; in the collection, analysis, and interpretation of data; in the preparation, review, or approval of the manuscript; or in the decision to submit the manuscript for publication.

Compliance with ethical standards

Conflict of interest

The authors declare no conflicts of interest with regard to the preparation of this manuscript.

Disclosures

Mario E. Lacouture has no relevant conflicts of interest with regard to preparation of this manuscript. He has served as consultant for Legacy, Adgero, Debiopharm,Galderma, Johnson and Johnson, Novocure Inc., Merck, Helsinn, Janssen, Menlo Ther, Novartis, Roche, Abbvie, Boehringer Ingelheim, Amgen, E.R. Squibb & Sons, EMD Serono, Genentech, Seattle Genetics, Bayer, Manner SAS,  Lutris, Paxman Coolers, Pfizer, Bristol-Myers Squibb, Silk Therapeutics, Foamix, and Medische Voet. He has received research funding from GSK, Novartis, Veloce, US Biotest, Berg, Bristol-Myers Squibb. Eliza B. Geer has no relevant conflicts of interest with regard to preparation of this manuscript. She has served as the principal investigator of research grants to MSKCC from Novartis, Strongbridge, Chiasma, and IONIS and has received occasional consulting honoraria from Novartis, Strongbridge, Corcept, and Pfizer. Jerry Shapiro has no relevant conflicts of interest with regard to preparation of this manuscript. He has served as a consultant for Aclaris, Samumed, Incyte, Replicel Life Sciences, and Shook, Hardy, Bacon LLP who represent Sanofi Aventis US LLC.

Ethical approval

This article does not contain any studies with human participants performed by any of the authors.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Raquel N. Rozner
    • 1
  • Azael Freites-Martinez
    • 1
  • Jerry Shapiro
    • 2
  • Eliza B. Geer
    • 3
  • Shari Goldfarb
    • 4
  • Mario E. Lacouture
    • 1
    Email author
  1. 1.Department of DermatologyMemorial Sloan-Kettering Cancer CenterNew YorkUSA
  2. 2.The Ronald O. Perelman Department of DermatologyNew York University School of MedicineNew YorkUSA
  3. 3.Multidisciplinary Pituitary and Skull Base Tumor CenterMemorial Sloan-Kettering Cancer CenterNew YorkUSA
  4. 4.Breast Medicine Service, Memorial Sloan Kettering Cancer Center, and Department of MedicineWeill Cornell Medical CollegeNew YorkUSA

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