Adverse effects of tamoxifen treatment on bone mineral density in premenopausal patients with breast cancer: a systematic review and meta-analysis.

BACKGROUND: It is well known that adjuvant tamoxifen treatment for breast cancer in postmenopausal women decreased bone loss. However, the effects of adjuvant tamoxifen therapy on bone mineral density (BMD) in premenopausal patients with breast cancer remains uncertain. Tamoxifen would have a potential impact of premenopausal BMD on health. The aim of this meta-analysis was to assess this in premenopausal women with primary breast cancer. METHODS: Through April 2020, studies reporting BMD changes of lumbar spine or hip in premenopausal women with primary breast cancer treated with adjuvant tamoxifen and tamoxifen plus chemotherapy or ovarian function suppression (OFS) were collected from EMBASE and PubMed. The meta-analysis was performed using random effects model of the standardized mean difference (SMD) of BMD in patients. RESULTS: A total of 1432 premenopausal patients were enrolled in eight studies, involving 198 patients treated with tamoxifen alone in three studies. After a 3-year median follow-up, adjuvant tamoxifen decreased the lumbar spinal and hip BMD by as much as an SMD of -1.17 [95% confidence interval (CI); -1.58 to -0.76)] and -0.66 (95% CI, -1.55 to 0.23), respectively. In subgroup analysis in patients treated adjuvant tamoxifen and tamoxifen plus chemotherapy or OFS according to follow-up duration, the bone change of < 3 years follow-up group was -0.03 SMD (95% CI, -0.47 to 0.41) and that of ≥ 3 years follow-up group was -1.06 SMD (95% CI, -1.48 to -0.64). Compared with patients who received tamoxifen alone, patients who received combination therapy with chemotherapy or OFS showed lesser bone loss at the lumbar spine. CONCLUSIONS: Our meta-analysis demonstrated that adjuvant tamoxifen therapy in premenopausal patients caused bone loss after 3 years of follow-up, especially at the lumbar spines. For a definite evaluation of the adverse effects of tamoxifen on bone, it is necessary to accumulate more relevant studies.

Prognostic Implication of YY1 and CP2c Expression in Patients with Primary Breast Cancer.

Yin Yang 1 (YY1) is a transcription factor that regulates epigenetic pathways and protein modifications. CP2c is a transcription factor that functions as an oncogene to regulate cell proliferation. YY1 is known to interact with CP2c to suppress CP2c's transcriptional activity. This study aimed to investigate YY1 and CP2c expression in breast cancer and prognostic implications. In this study, YY1 and CP2c expression was evaluated using immunohistochemical staining, Western blot and RT-PCR assays. Of 491 patients with primary breast cancer, 138 patients showed YY1 overexpression. Luminal subtype and early stage were associated with overexpression (p < 0.001). After a median follow-up of 68 months, YY1 overexpression was found to be associated with a better prognosis (disease-free survival rates of 92.0% vs. 79.2%, p = 0.014). In Cox proportional hazards model, YY1 overexpression functioned as an independent prognostic factor after adjustment of hormone receptor/HER2 status and tumor size (hazard ratio of 0.50, 95% CI 0.26-0.98, p = 0.042). Quantitative analysis of YY1 and CP2c protein expression in tumors revealed a negative correlation between them. In conclusion, YY1 overexpression is a favorable prognostic biomarker in patients with breast cancer, and it has a negative correlation with CP2c at the protein level.