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BMC Cancer. 2016 May 27;16:337. doi: 10.1186/s12885-016-2373-3.

SLCO1B1*5 polymorphism (rs4149056) is associated with chemotherapy-induced amenorrhea in premenopausal women with breast cancer: a prospective cohort study.

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Department of Obstetrics and Gynecology, University of Rostock, Klinikum Suedstadt, Suedring 81, Rostock, 18059, Germany.
Department of Obstetrics and Gynecology, University of Rostock, Klinikum Suedstadt, Suedring 81, Rostock, 18059, Germany.
Institute of Immunology, University of Rostock, P.O.B. 100888, Rostock, 18055, Germany.



Because inheritance is recognized as playing a role in age at menarche and natural menopause, the development of chemotherapy-induced amenorrhea (CIA) might depend on inherited genetic factors; however, studies that explore such a correlation are few and have received scant attention. Given the importance of this topic we conducted a comprehensive genotype study in young women (≤45 years) with early-stage breast cancer.


Our approach tested the effect of variant polymorphisms in drug metabolism enzymes (DMEs) using a predesigned pharmacogenomics panel (TaqMan® OpenArray®, Life Technologies GmbH, Darmstadt, Germany) in premenopausal women (n = 50). Patients received contemporary chemotherapy; in all cases a cyclophosphamide-based regimen with a dose of at least 500 mg/m(2) for six cycles. CIA was considered to be present in women with no resumption of menstrual bleeding within 12 months after completion of chemotherapy or goserelin.


Twenty-six patients (52 %) showed CIA during follow-up whereas 24 women (48 %) remained premenopausal. Of all the DMEs studied, only the SLCO1B1*5 (rs4149056) genotype was associated with the development of CIA (P = 0.017). Of the 26 patients who were homozygous for the T/T allele SLCO1B1*5, 18 (69.2 %) developed CIA compared with 8 (30.8 %) of the 22 patients who were heterozygous (C/T allele). The association of heterozygous SLCO1B1*5 allele (OR 0.038; 95%CI: 0.05-0.92) with a lower risk of developing CIA remained significant in a binary logistic regression analysis that include age, SLCO1B1*5 allele variants, and goserelin therapy.


Patient age and SLCO1B1*5 allele variants predict the likelihood of young women with breast cancer developing CIA.


Breast cancer; Chemotherapy-induced amenorrhea; OpenArray genotyping; SLCO1B1; Single nucleotide polymorphism

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