Predictive markers of chemotherapy-induced menopause in premenopausal women under the age of 40 with breast cancer.
Authors: Yu B , Lobo R , Crew KD , Ferin MJ , Douglas N , Nakhuda GS , Hershman DL 
Published: December 2010

Abstract #1118

Background: Premenopausal women undergoing adjuvant chemotherapy are at risk for chemotherapy induced menopause (CIM). To date, age &gt;40 has been the strongest predictor of ovarian failure. For women &lt;40, identifying patients early who are at greatest risk may alter treatment decisions, therefore early predictors of CIM are needed. Our objective was to assess a marker of ovarian reserve, Mullarian Inhibitory Substance (MIS), as well as estradiol (E2), Follicle Stimulating Hormone (FSH) and menstrual status, in young women undergoing adjuvant chemotherapy for breast cancer.&#x2028; Patients and Methods: We conducted a prospective cohort study in women aged less than 40 years undergoing chemotherapy for early stage breast cancer (n=26). Patients were treated with chemotherapy (adriamycin, cyclophosphamide and paclitaxel) following surgery. Serum MIS, FSH, and E2 were measured before chemotherapy, at weeks 6, 12 , 36 and 52. Controls were 134 age-matched women with known fertility. Hormone levels were compared in the 2 groups at baseline. Trends during chemotherapy were assessed based on age and correlated with menstrual status in the breast cancer patients only.&#x2028; Results: Compared with age-matched controls, patients with breast cancer had similar baseline MIS levels (median 0.94 vs. 0.86 ng/ml, p&gt;0.05). However, 29% of cancer patients had baseline MIS levels below the lower normal range (0.2 ng/ml). Serum MIS decreased significantly at 6 weeks and remained suppressed for 52 weeks (median 0.08 ng/ml at week 6, 0.05 ng/ml at week 12, 0.07 ng/ml at week 52, p&lt;0.05 compared to baseline). At 6 weeks after treatment, 96% of the patients had MIS levels below 0.2 ng/ml. E2 levels decreased during chemotherapy, however, at 52 weeks, the levels returned to baseline levels. The percentage of women with E2 &lt;30 pg/ml increased during chemotherapy and following chemotherapy. FSH levels increased 6 weeks after chemotherapy and returned to premenopausal levels by week 52, although only 33% of FSH levels were within premenopausal range (&lt;10 IU/L) at week 52. At 52 weeks, 11 of 26 cancer patients (42%) remained amenorrheic. In women &lt;35 years old, only 25% of women remained amenorrheic, whereas in women over 35 years, 50% were amenorrheic. Compared to women who regained menses, amenorrheic women had similar MIS values pre-chemotherapy and at 52 weeks post-chemotherapy.&#x2028; Conclusions: In women &lt;40, chemotherapy decreases MIS rapidly and dramatically, and therefore early changes in MIS can not be used as a predictor of CIM. Although E2 levels generally recover, with 58% of young women regaining some menstrual function by 52 weeks, MIS levels remain abnormal, with all values remaining below the normal range of age-matched fertile women. Age continues to be an important factor for the recovery of ovarian function, specifically endocrine function, after chemotherapy.

Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1118.