Spironolactone use does not increase the risk of female breast cancer recurrence: A retrospective analysis

      Background

      Spironolactone is used off-label for androgenic alopecia because of its ability to arrest hair loss progression and long-term safety profile. However, little is known about the safety of spironolactone in breast cancer (BC) survivors. Because spironolactone has estrogenic effects, there is a theoretical risk for BC recurrence. Given that spironolactone is an important tool in the treatment of alopecia, we investigated whether spironolactone increased risk for BC recurrence.

      Objective

      To determine whether spironolactone is associated with increased BC recurrence.

      Methods

      A retrospective analysis was conducted using the Humana Insurance database. Patients with a history of BC were identified using International Classification of Diseases codes, stratified by spironolactone prescription, and also matched 1:1 using propensity score analysis. Patient characteristics and cancer recurrence rates between both cohorts were compared and analyzed.

      Results

      BC recurrence developed in 123 patients (16.5%) who were prescribed spironolactone compared with 3649 patients (12.8%) who developed BC recurrence without spironolactone prescribed ( P = .004). After propensity matching, adjusted Cox regression analysis showed no association between spironolactone and increased BC recurrence (adjusted hazard ratio, 0.966; 95% confidence interval, 0.807-1.156; P = .953).

      Limitations

      Retrospective study.

      Conclusion

      Spironolactone was not independently associated with increased BC recurrence and may be considered for the treatment of alopecia in BC survivors.

      Key words

      Abbreviations used:

      BC ( breast cancer), CI ( confidence interval), FPHL ( female patterned hair loss), HR ( hazard ratio), ICD ( International Classification of Diseases)
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      References

        • Rathnayake D.
        • Sinclair R.
        Innovative use of spironolactone as an antiandrogen in the treatment of female pattern hair loss.
        Dermatol Clin. 2010; 28: 611-618
        • Levy L.L.
        • Emer J.J.
        Female pattern alopecia: current perspectives.
        Int J Womens Health. 2013; 5: 541-546
        • Mackenzie I.S.
        • Morant S.
        • Wei L.
        • et al.
        Spironolactone use and risk of incident cancers: a retrospective, matched cohort study.
        Br J Clin Pharmacol. 2016; 83: 653-663
        • Almukhtar R.
        Spironolactone use and the risk of breast cancer.
        J Am Acad Dermatol. 2016; 24: AB72
        • Biggar R.J.
        • Andersen E.W.
        • Wohlfahrt J.
        • et al.
        Spironolactone use and the risk of breast and gynecologic cancers.
        Cancer Epidemiol. 2013; 37: 870-875
        • World Health Organization
        International Agency for Research on Cancer Some thyrotropic agents. IARC Monographs on the Evaluation of Carcinogenic Risks to humans. Volume 79: Some Thyrotropic Agents.
        (2001. Available at:)
        http://monographs.iarc.fr/wp-content/uploads/2018/06/mono79.pdf
        Date: 2001
        Date accessed: February 20, 2020
        • Rozner R.N.
        • Freites-Martinez A.
        • Shapiro J.
        • et al.
        Safety of 5α-reductase inhibitors and spironolactone in breast cancer patients receiving endocrine therapies.
        Breast Cancer Res Treat. 2019; 174: 15-26
        • Mackenzie I.S.
        • Macdonald T.M.
        • Thompson A.
        • et al.
        Spironolactone and the risk of incident breast cancer in women older than 55 years: retrospective, matched cohort study.
        BMJ. 2012; 345: e4447
        • Colleoni M.
        • Sun Z.
        • Karen N.
        • et al.
        Annual hazard rates of recurrence for breast cancer during 24 years of follow-up: results from the International Breast Cancer Study Group Trials I to V.
        J Clin Oncol. 2016; 34: 927-935
        • Lupo M.
        • Dains J.E.
        • Madsen L.T.
        Hormone replacement therapy: an increased risk of recurrence and mortality for breast cancer patients?.
        J Adv Pract Oncol. 2015; 6: 322-330
        • BlueCross BlueShield of Alabama
        Coding Neoplasms.
        (Available at:)
        • Funder J.W.
        Spironolactone in cardiovascular disease: an expanding universe?.
        F1000Res. 2017; 6: 1738
        • Charny J.W.
        • Choi J.K.
        • James W.D.
        Spironolactone for the treatment of acne in women, a retrospective study of 110 patients.
        Int J Womens Dermatol. 2017; 3: 111-115
        • Quan H.
        • Sundarajan V.
        • Halfon P.
        • et al.
        Coding algorithms for defining comorbidities in ICD-9-CM and ICD-10 administrative data.
        Med Care. 2005; 43: 1130-1139
        • Faul F.
        • Erdfelder E.
        • Lang A.G.
        • Buchner A.
        G∗Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences.
        Behav Res Methods. 2007; 39: 175-191
        • Brufsky A.M.
        • Dickler M.N.
        Estrogen receptor-positive breast cancer: exploiting signaling pathways implicated in endocrine resistance.
        Oncologist. 2018; 23: 528-539
        • Kluger N.
        • Jacot W.
        • Frouin E.
        • et al.
        Permanent scalp alopecia related to breast cancer chemotherapy by sequential fluorouracil/epirubicin/cyclophosphamide (FEC) and docetaxel: a prospective study of 20 patients.
        Ann Oncol. 2012; 23: 2879-2884
        • McDonald J.
        • Goyal A.
        • Terry M.B.
        Alcohol intake and breast cancer risk: weighing the overall evidence.
        Curr Breast Cancer Rep. 2013; 5https://doi.org/10.1007/s12609-013-0114z
        • Kwan M.L.
        • Chen W.Y.
        • Flatt S.W.
        • et al.
        Postdiagnosis alcohol consumption and breast cancer prognosis in the after breast cancer pooling project.
        Cancer Epidemol Biomarkers Prev. 2013; 22: 32-41
        • Kowalksi A.
        • Striley C.W.
        • Varma D.S.
        • et al.
        Interactions between alcohol consumption and adjuvant hormone therapy in relation to breast cancer-free survival.
        J Breast Cancer. 2018; 21: 158-164
        • Abraha I.
        • Serraino D.
        • Giovannini G.
        • et al.
        Validity of ICD-9-CM codes for breast, lung, and colorectal cancers in three Italian administrative healthcare databases: a diagnostic accuracy study protocol.
        BMJ Open. 2016; 6: e010547