Impact of tamoxifen therapy on fertility in breast cancer survivors

Abstract

Objective: To determine whether tamoxifen use is associated with decreased ovarian reserve and decreased likelihood of having a child after a breast cancer diagnosis, using data from the Furthering Understanding of Cancer, Health, and Survivorship in Adult (FUCHSIA) Women Study.

Design: Population-based cohort study.

Setting: Not applicable.

Patient(s): Three hundred ninety-seven female breast cancer survivors aged 22-45 years whose cancer was diagnosed between ages 20 and 35 years and who were at least 2 years after diagnosis; 108 survivors also participated in a clinic visit.

Intervention(s): None.

Main outcome measure(s): Time to first child after cancer diagnosis, clinical measures of ovarian reserve (antimüllerian hormone [AMH] and antral follicle count [AFC]) after cancer.

Result(s): Women who had ever used tamoxifen were substantially less likely to have a child after the breast cancer diagnosis (hazard ratio [HR] 0.29; 95% confidence interval [CI], 0.16, 0.54) than women who had never used tamoxifen. After adjusting for age at diagnosis, exposure to an alkylating agent, and race, the HR was 0.25 (95% CI, 0.14, 0.47). However, after adjusting for potential confounders, women who had used tamoxifen had an estimated geometric mean AMH level 2.47 times higher (95% CI, 1.08, 5.65) than women who had never taken tamoxifen. Antral follicle count was also higher in the tamoxifen group compared with the tamoxifen nonusers when adjusted for the same variables (risk ratio 1.21; 95% CI, 0.84, 1.73).

Conclusion(s): Breast cancer survivors who had used tamoxifen were less likely to have a child after breast cancer diagnosis compared with survivors who never used tamoxifen. However, tamoxifen users did not have decreased ovarian reserve compared with the tamoxifen nonusers.

Keywords: Breast cancer; cancer survivorship; infertility; ovarian reserve; tamoxifen.

Figure 1

Unadjusted Kaplan-Meier curves of time to first child following breast cancer diagnosis by tamoxifen status (A, includes all breast cancer survivors; B, restricted to women who were childless at diagnosis; C, restricted to women who had not yet met their reproductive goals at the time of diagnosis; D, restricted to women who were estrogen/progesterone receptor positive^a; E, tamoxifen group versus women who were hormone-receptor (ER/PR) negative^b) in a cohort of young breast cancer survivors, censored at time of hysterectomy, bilateral oophorectomy, tubal ligation, or study interview; F, excludes women who reported their period stopping during cancer treatment and never returning. ^aWomen who took tamoxifen and women with documented hormone receptor status in medical records were considered to be hormone-receptor positive. ^bBreast cancer survivors who are estrogen/progesterone receptor negative are generally not candidates for adjuvant tamoxifen.

Figure 1

Unadjusted Kaplan-Meier curves of time to first child following breast cancer diagnosis by tamoxifen status (A, includes all breast cancer survivors; B, restricted to women who were childless at diagnosis; C, restricted to women who had not yet met their reproductive goals at the time of diagnosis; D, restricted to women who were estrogen/progesterone receptor positive^a; E, tamoxifen group versus women who were hormone-receptor (ER/PR) negative^b) in a cohort of young breast cancer survivors, censored at time of hysterectomy, bilateral oophorectomy, tubal ligation, or study interview; F, excludes women who reported their period stopping during cancer treatment and never returning. ^aWomen who took tamoxifen and women with documented hormone receptor status in medical records were considered to be hormone-receptor positive. ^bBreast cancer survivors who are estrogen/progesterone receptor negative are generally not candidates for adjuvant tamoxifen.

Figure 1

Unadjusted Kaplan-Meier curves of time to first child following breast cancer diagnosis by tamoxifen status (A, includes all breast cancer survivors; B, restricted to women who were childless at diagnosis; C, restricted to women who had not yet met their reproductive goals at the time of diagnosis; D, restricted to women who were estrogen/progesterone receptor positive^a; E, tamoxifen group versus women who were hormone-receptor (ER/PR) negative^b) in a cohort of young breast cancer survivors, censored at time of hysterectomy, bilateral oophorectomy, tubal ligation, or study interview; F, excludes women who reported their period stopping during cancer treatment and never returning. ^aWomen who took tamoxifen and women with documented hormone receptor status in medical records were considered to be hormone-receptor positive. ^bBreast cancer survivors who are estrogen/progesterone receptor negative are generally not candidates for adjuvant tamoxifen.