A pilot study of predictive markers of chemotherapy-related amenorrhea among premenopausal women with early stage breast cancer

Abstract

Background: Premenopausal women treated for early stage breast cancer (ESBC) are at risk for chemotherapy-related amenorrhea (CRA). Prospectively-validated, predictive markers of CRA are needed.

Patients and methods: Premenopausal women with ESBC and planned chemotherapy (>/= 25% risk of amenorrhea) were evaluated. Follicle stimulating hormone (FSH), estradiol, Inhibin A and B, anti-Müllerian hormone (AMH), and quality of life (QOL) were prospectively evaluated pre-, post-, 6 months and 1 year post-chemotherapy and correlated with age and menstrual status. CRA was defined as absence of menses 1 year post-chemotherapy.

Results: Forty-four women were evaluated at the time of analysis. Median age at diagnosis and FSH 1 year post-chemotherapy were higher among women with CRA (44 yrs [33-51] vs. 40 yrs [31-43]; p = 0.03; 39.8 vs. 5.0 mLU/mL, p = 0.0058, respectively). Median estradiol 1 year post-chemotherapy was higher among women who resumed menses (108.3 vs. 41.3 pg/mL, p = 0.01). Pre-chemotherapy median Inhibin B and AMH were lower among women with CRA (33.2 vs. 108.8 pg/mL; p = 0.03; 0.16 vs. 1.09 ng/mL, p = 0.02, respectively). The risk of CRA was increased among women with lower pre-chemotherapy Inhibin B (RR = 1.67, p = 0.15) and AMH (RR = 1.83, p = 0.05). Amongst women whose pre-chemotherapy Inhibin B and AMH values were below the median, the incidence of CRA was 87.5%.

Conclusions: RESULTS indicate that pre-chemotherapy Inhibin B and AMH are lower among women experiencing CRA and may be predictive of CRA among premenopausal women facing chemotherapy for ESBC.

Figure 1

Median serum concentrations of follicle-stimulating hormone (FSH, 1a), estradiol (1b), Inhibin A (1c), Inhibin B (1d) and AMH (1e) based on age <35 years or ≥35 years. Red lines represent women aged <35 years. Green lines represent women aged ≥35 years.

Figure 1

Median serum concentrations of follicle-stimulating hormone (FSH, 1a), estradiol (1b), Inhibin A (1c), Inhibin B (1d) and AMH (1e) based on age <35 years or ≥35 years. Red lines represent women aged <35 years. Green lines represent women aged ≥35 years.

Figure 2

Median serum concentrations of FSH (2a), estradiol (2b), Inhibin A (2c), Inhibin B (2d), and AMH (2e) by chemotherapy-related amenorrhea (CRA) status. Red lines represent women who resumed menses at one year post-chemotherapy. Green lines represent women who experienced CRA.

Figure 2

Median serum concentrations of FSH (2a), estradiol (2b), Inhibin A (2c), Inhibin B (2d), and AMH (2e) by chemotherapy-related amenorrhea (CRA) status. Red lines represent women who resumed menses at one year post-chemotherapy. Green lines represent women who experienced CRA.

Figure 3

Median FACT-B normalized T scores by CRA status. Red lines represent women who resumed menses at one year post-chemotherapy. Green lines represent women who experienced CRA.

Figure 4

Median FACT-B normalized T scores by age. Red lines represent women who are aged <35 years. Green lines represent women who are aged ≥35 years of age.