Estradiol is a key factor for tumorigenesis and prognosis of hormone receptor-positive breast cancer. Adipocytes are one source of estradiol in patients with breast cancer. Recent studies have shown that phosphorylated ribosomal protein S6 kinase-1 plays a critical role in adipogenesis. Therefore, estrogen depletion therapy might have beneficial effects in phosphorylated ribosomal protein S6 kinase-1-positive breast cancer. This study was conducted to evaluate the value of phosphorylated ribosomal protein S6 kinase-1 as a marker for gonadotropin-releasing hormone agonist treatment, a form of estrogen depletion therapy, for premenopausal patients with HR-positive, human epidermal growth factor receptor 2-negative breast cancer. We reviewed the medical records of 296 premenopausal patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative primary invasive breast cancer treated between 2008 and 2015. Phosphorylated ribosomal protein S6 kinase-1 positivity was defined by immunohistochemical staining scores of 1+, 2+ and 3+, whereas a score of 0 was considered negative. Phosphorylated ribosomal protein S6 kinase-1-positive tumors were found in 74.0% of the patients. In the phosphorylated ribosomal protein S6 kinase-1-positive group, disease-free survival of patients treated with a gonadotropin-releasing hormone agonist was significantly longer than that of patients treated without a gonadotropin-releasing hormone agonist (mean 106.7 months vs mean 91.1 months, P = 0.018). Phosphorylated ribosomal protein S6 kinase-1 is a potential biomarker for predicting the efficacy of gonadotropin-releasing hormone agonist therapy in premenopausal patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer.
Chan Sub Park, Jihye Choi, Min-Ki Seong, Sung-Eun Hong, Jae-Sung Kim, In-Chul Park, Hyesil Seol, Woo Chul Noh and Hyun-Ah Kim
Hyun-Ah Kim, Jihye Choi, Chan Sub Park, Min-Ki Seong, Sung-Eun Hong, Jae-Sung Kim, In-Chul Park, Jin Kyung Lee, Woo Chul Noh and the ASTRRA trial investigators
In the era of precision medicine, the prediction of ovarian function recovery from chemotherapy-induced amenorrhoea using feasible biological markers may be helpful to optimise the treatment strategy for young patients with hormone receptor-positive breast cancer. The purpose of this study was to investigate the accuracy of post-chemotherapy biological markers for predicting the recovery of ovarian function in breast cancer patients of the ASTRRA trial, with chemotherapy-induced amenorrhoea. Using data of 82 participants from a single institution in the ASTRRA trial, the post-chemotherapy serum levels of the anti-Müllerian hormone (AMH), oestradiol, inhibin B and other clinical factors associated with chemotherapy-induced amenorrhoea were evaluated. Recovery of ovarian function was defined by the resumption of menstruation manifested by vaginal bleeding. Fifty-two patients regained menstruation within 55 months after enrolment. In univariate analysis, <40 years of age (P = 0.009), oestradiol ≥37 pg/mL (P = 0.003) or AMH ≥800 pg/mL (P = 0.026) were associated with recovery of menstruation. On multivariate analysis, oestradiol (hazard ratio: 3.171, 95% CI: 1.306–7.699, P = 0.011) and AMH (hazard ratio: 2.853, 95% CI: 1.011–8.046, P = 0.048) remained as significant independent predictors for resumption of menstruation. The diagnostic accuracy of age, oestradiol and AMH in predicting the resumption of menstruation was 38.3, 23.3 and 86.7%, respectively. In conclusion, post-chemotherapy AMH level might be a relatively accurate predictor of the recovery of ovarian function, presented by resumption of menstruation in breast cancer patients with chemotherapy-induced amenorrhoea.