Long-term comparisons of the efficacy, safety, and pregnancy outcomes of adjuvant tamoxifen plus ovarian function suppression in premenopausal Han and Zhuang Chinese patients with hormone receptor-positive early breast cancer

Recent studies have shown that breast cancer is the most common malignancy in women and is associated with poor survival, particularly among premenopausal women.1 It is therefore important to investigate novel and effective therapeutic treatments for breast cancer.2 Comprehensive therapy currently consists of surgery, chemotherapy, radiotherapy, and hormone therapy as mainstream modalities.3 Although adjuvant oral tamoxifen is one of the most effective hormone therapies in hormone receptor-positive premenopausal breast cancer patients,4 fertility concerns remain an important factor affecting treatment strategies in young breast cancer patients.5 The American Society of Clinical Oncology (ASCO) 2014 guidelines suggested that tamoxifen alone should be used for an initial 5-year period in premenopausal patients with hormone receptor-positive breast cancer,6 and a meta-analysis of the Early Breast Cancer Trialists’ Collaborative Group demonstrated that 5 years of tamoxifen treatment was correlated with a significant reduction in breast cancer mortality.7 Loss of ovarian function and fertility constitute severe side effects of breast cancer treatment protocols, particularly chemotherapy.5 Ovarian function suppression (OFS) has been developed as a suitable strategy to protect ovarian function during chemotherapy, and accumulating evidence suggests that tamoxifen plus OFS results in better survival than tamoxifen alone.8–10 In 2003, the International Breast Cancer Study Group initiated the SOFT trial to determine the value of adding OFS to tamoxifen, and the role of the aromatase inhibitor exemestane plus OFS in hormone receptor-positive premenopausal breast cancer patients, compared with tamoxifen alone.11 The results of the SOFT trial suggested that the addition of OFS to tamoxifen was not beneficial in women with low-risk early-stage breast cancer, but did improve outcomes in women at higher risk of relapse who received adjuvant chemotherapy, but who had no treatment-induced amenorrhea.12 Similar results were observed in the E-3193, INT-0142 trials.13 The SOFT trial is currently the largest study of its kind to investigate the effects of tamoxifen plus OFS, and its results have been accepted worldwide.14 However, the SOFT trial did not investigate correlations between tamoxifen or OFS plus tamoxifen and pregnancy outcomes in patients. According to ASCO and European Society for Medical Oncology guidelines, cryopreservation of oocytes or embryos is a suitable procedure for fertility preservation in cancer patients.15,16 Lambertin17 and colleagues demonstrated that OFS exerted no effect on pregnancy in breast cancer patients; however, the effects of tamoxifen and OFS on pregnancy outcomes remain controversial. Most recent large and authoritative clinical trials have enrolled few Chinese women, particularly from minority populations, and the efficacy, safety, and pregnancy outcomes following OFS plus tamoxifen in premenopausal Han Chinese women with hormone receptor-positive early breast cancer compared with women from minority Chinese populations are thus unknown. In addition, there are presently no research reports comparing these indices between Han and Zhuang populations in southern China. We therefore designed the present clinical study to explore such issues.