Abstract P3-08-18: Association of tamoxifen use and ovarian aging in patients with invasive or pre-invasive breast cancer

Background: The use of tamoxifen has been shown to delay the recovery of chemotherapy-induced amenorrhea, however the independent impact of long-term endocrine therapy on ovarian aging is not known, and to our knowledge, has never been directly investigated. Understanding the effect of endocrine therapy on ovarian aging will help breast cancer patients of reproductive age make more informed and empowered decisions regarding their treatment. The aim of this study is to explore the relationship between tamoxifen therapy and age onset of menopause. Methods: We conducted a retrospective cohort study using patients identified through the UCSF Cancer Registry and UCSF SPORE database. Women who were diagnosed with Stage 1-3 invasive or in situ breast cancer between 1985 and 2011, who were premenopausal at the time of diagnosis and who did not receive systemic chemotherapy were included. Patients with recurrent disease and prior ovarian surgery were excluded. Eligibility was confirmed by telephone, and online or paper surveys were distributed to eligible subjects only. Age onset of menopause was the primary endpoint of the study and was defined as the age at which a woman had her last period and no menses for 12 months. Age onset of menopause was assessed through surveys. The primary analysis compared age onset of menopause between subjects who received tamoxifen for any duration and control subjects who never received tamoxifen. Secondary analyses were performed using a Cox proportional hazards model to determine whether duration of tamoxifen exposure and age of tamoxifen initiation impacted age onset of menopause in subjects treated with tamoxifen. Results: A total of 1137 potential subjects believed to meet eligibility criteria were identified and called, and 649 subjects were reached. Eligibility was confirmed by phone in 340 subjects. A total of 336 subjects consented to participate in the study, and 262 (78%) completed and returned the survey. 227 subjects were included in the primary analysis of which 110 subjects received prior tamoxifen, and 117 subjects received no prior tamoxifen. At the time of the survey, 16.3% vs. 20.2% of patients under age 50 that were exposed and not exposed to tamoxifen entered menopause, respectively. The median age onset of menopause was 50.94 and 51.34 for the tamoxifen and no tamoxifen groups, respectively. The hazard ratio between these groups was 1.077 which was not statistically significant (p = 0.6917). No association (p = 0.55) was found between the duration of tamoxifen use and the age onset of menopause. When controlling for tamoxifen duration, there was no significant difference (p = 0.93) in age onset of menopause between subjects who initiated tamoxifen prior to age 45 and those who initiated at age 45 or older. Conclusion: These data suggest that tamoxifen alone is not associated with an earlier age onset of menopause, and that tamoxifen use, in the absence of systemic chemotherapy, is unlikely to significantly accelerate ovarian aging. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-08-18.