Chemotherapy-Induced Amenorrhea in Patients With Breast Cancer With a BRCA1 or BRCA2 Mutation

Abstract

A B S T R A C T PurposeTo determine the likelihood of long-term amenorrhea after treatment with chemotherapy in women with breast cancer who carry a BRCA1 or BRCA2 mutation. Patients and MethodsWe conducted a multicenter survey of 1,954 young women with a BRCA1 or BRCA2 mutation who were treated for breast cancer. We included premenopausal women who were diagnosed with invasive breast cancer between 26 and 47 years of age. We determined the age of onset of amenorrhea after breast cancer for women who were and were not treated with chemotherapy, alone or with tamoxifen. We considered chemotherapy-induced amenorrhea to have occurred when the patient experienced Ն 2 years of amenorrhea, commencing within 2 years of initiating chemotherapy, with no resumption of menses. ResultsOf the 1,426 women who received chemotherapy, 35% experienced long-term amenorrhea. Of the 528 women who did not receive chemotherapy, 5.3% developed long-term amenorrhea. The probabilities of chemotherapy-induced amenorrhea were 7.2% for women diagnosed before age 30 years, 33% for women age 31 to 44 years, and 79% for women diagnosed after age 45 years (P trend Ͻ .001). The probability of induced amenorrhea was higher for women who received tamoxifen than for those who did not (52% v 29%; P Ͻ .001). ConclusionAge at treatment and use of tamoxifen are important predictors of chemotherapy-induced amenorrhea in women who carry a BRCA1 or BRCA2 mutation. The risk of induced long-term amenorrhea does not seem to be greater among mutation carriers than among women who do not carry a mutation.

Fertility preservation in post-pubescent female cancer patients: A practical guideline for clinicians

“…For example, if a woman's age upon tamoxifen completion is 30, she may wish to postpone oocyte cryopreservation until then. However, if age upon completion is greater than 35, she may rather choose to harvest prior to initiation of tamoxifen (49). There is limited evidence to guide clinicians regarding the safety of temporary cessation of tamoxifen in order to attempt pregnancy.…”

Reproductive Issues in BRCA Mutation Carriers

“…Valentini et al examined the risk of long-term amenorrhoea after chemotherapy, defi ned as absent menses beginning within 2 years of starting treatment and continuing for at least 2 years [ 89 ]. They compared BRCA1 and BRCA2 mutation carriers with a small group of noncarriers, who underwent chemotherapy.…”

“…However, it has been hypothesized that BRCA mutations, in particular BRCA1, may be associated with reduced fertility. This is expressed by increased chemotherapy-induced amenorrhea [ 89 ], premature menopause [ 90 -93 ], primary occult ovarian insuffi ciency [ 94 ], reduced ovarian reserve [ 95 ], and infertility [ 96 -98 ]. The proposed link between BRCA mutation and fertility is suggested by several possible theories.…”

A Retrospective Study on the Onset of Menopause after Chemotherapy: Analysis of Data Extracted from the Jean Perrin Comprehensive Cancer Center Database Concerning 345 Young Breast Cancer Patients Diagnosed between 1994 and 2012

“…According to Valentini et al [30] , CIA occurs in 33% of patients between 31 and 44 years of age and in 79% of patients aged >45 years. According to the literature, the older women are, the greater the risk of CIA because the stock of follicles decreases with age.…”