Hormonal therapies in young breast cancer patients: when, what and for how long?

Breast cancer in young women (<40 years) is a rare and complex clinical and psychosocial condition, which deserves multidisciplinary and personalized approaches. In young women with hormone-receptor positive disease, 5 years of adjuvant tamoxifen, with or without ovarian suppression/ablation, is considered the standard endocrine therapy. The definitive role of adjuvant aromatase inhibitors has still to be elucidated: the upcoming results of the Tamoxifen and EXemestane Trial (TEXT) and Suppression of Ovarian Function Trial (SOFT) trials will help understanding if we can widen our current endocrine therapeutic options. The optimal duration of adjuvant endocrine therapy in young women also remains an unresolved issue. The recently reported results of the ATLAS and aTToM trials represent the first evidence of a beneficial effect of extended endocrine therapy in premenopausal women and provide an important opportunity in high-risk young patients. In the metastatic setting, endocrine therapy should be the preferred choice for endocrine responsive disease, unless there is evidence of endocrine resistance or need for rapid disease and/or symptom control. Tamoxifen in combination with ovarian suppression/ablation remains the 1st-line endocrine therapy of choice. Aromatase inhibitors in combination with ovarian suppression/ablation can be considered after progression on tamoxifen and ovarian suppression/ablation. Fulvestrant has not yet been studied in pre-menopausal women. Specific age-related treatment side effects (i.e., menopausal symptoms, change in body image and weight gain, cognitive function impairment, fertility damage/preservation, long-term organ dysfunction, sexuality) and the social impact of diagnosis and treatment (i.e., job discrimination, family management) should be carefully addressed when planning long-lasting endocrine therapies in young women with hormone-receptor positive early and advanced breast cancer.