Risk of chemotherapy-related amenorrhoea (CRA) in premenopausal women undergoing chemotherapy for early stage breast cancer

PURPOSE: While chemotherapy has improved survival among younger women with breast cancer, it can induce temporary or permanent chemotherapy-related amenorrhoea (CRA), impacting survival benefit, quality of life and, importantly for younger patients, fertility. METHODS: This single institution retrospective study of 107 premenopausal women with early stage breast cancer who received neoadjuvant or adjuvant combined chemotherapy treatment investigates the association of clinicopathological factors (including age-related, gynaecological and tumour-related variables) with CRA and resumption of menses using generalised linear models for univariable and multivariate analyses. RESULTS: 76% of women developed CRA, of which only 40% resumed menses after treatment. Age at time of treatment and at menarche were significantly associated with CRA incidence, with higher rates linked to older age (≥ 40 years) and later menarche (at ≥ 13 years), in both univariable (P = 0.043 and P = 0.009, respectively) and multivariate (P = 0.010 and P = 0.012, respectively) analyses. Age at time of treatment, age at menarche and use of tamoxifen were significantly associated with resumption of menses (with greater resumption rates linked to younger age (< 40 years old), later menarche (≥ 13 years old) or no tamoxifen use status), in both univariable (P < 0.0001, P = 0.002 and P = 0.039, respectively) and multivariate (P = 0.001, P = 0.011 and P = 0.008, respectively) analyses. Menses resumption rates were also significantly higher (P = 0.015) in women with later cessation of menses (after 3–6 chemotherapy cycles rather than sooner). CONCLUSIONS: Age at menarche and, specially, at time of treatment are important risk factors for CRA. These variables could aid decision-making for treatment selection and fertility preservation among premenopausal women with early breast cancer.