Abstract

Abstract Background: Triple negative breast cancer (TNBC) is a subtype of breast cancer which lacks hormone receptor (HR) expression and HER2 gene amplification, and is the most aggressive subtype with a heterogeneous genetic profile. Menopausal status is an important factor when considering endocrine therapy for patients with HR-positive tumors. Breast cancer in younger women can be more aggressive than in older women. Moreover, the menopausal status has limited predictive power for distant recurrence and overall survival (OS) in HR-positive cases. The aim of this retrospective study is to evaluate the clinical significance of menopausal status in breast cancer subtypes, especially TNBC. Methods: Primary breast cancer patients who underwent curative surgery from January 2002 to March 2021 were enrolled in this study. A total of 5153 invasive breast cancer cases with Stage I-III were analyzed. The distribution of cases according to the menopausal status was investigated according to each subtype, and the clinicopathological characteristics and prognosis were compared between pre- and postmenopausal TNBC patients. The factors investigated included nodal status, tumor size, nuclear grade, ER/PgR and HER2 status, p53 overexpression, and the Ki-67 index value. Breast cancer subtypes were categorized based on the immunohistochemistry (IHC) data derived from ER/PgR, HER2 and Ki-67 (cutoff: 20%) in invasive tumors. The disease-free survival (DFS) was compared between menopausal status in each subtype using the Kaplan-Meier and the log-rank test. Cox's proportional hazard model was used to perform univariate and multivariate analyses of the factors related to DFS. The median follow-up period was 95 months. Results:. 1. There were significant differences in menopausal status among the subtypes. TNBC was frequently seen in postmenopausal patients, and Luminal B and Luminal/HER2 subtypes were more common in premenopausal patients. 2. There was no difference in DFS in Luminal A/B and HER2 subtypes, but a significant difference was seen in the TNBC patients (premenopausal patients had a poorer DFS than the postmenopausal patients). 3. There was no significant correlation between menopausal status, tumor size and nodal status in TNBC. On the other hand, premenopausal patients significantly correlated with a higher Ki-67 index value, p53 overexpression and a higher nuclear grade. 4. Moreover, premenopausal patients often received (neo)adjuvant chemotherapy, but there was no significant difference in the pCR rate between the pre- and postmenopausal status. 5. A multivariate analysis revealed that menopausal status, nodal status and tumor size were significant factors for DFS in TNBC. Conclusion: Menopausal status significantly correlates with breast cancer subtypes. TNBC was often seen in postmenopausal patients, and these patients tend to have more favorable factors and a better DFS than premenopausal patients. These findings suggest that menopausal status is an important factor for evaluating the biology and prognosis in TNBC cases. Citation Format: Nobuyuki Arima, Reiki Nishimura, Tomofumi Osako, Yasuhiro Okumura, Masahiro Nakano, Mamiko Fujisue, Hiroko Otsuka. Triple negative breast cancer: An analysis of the subtypes and the effects of menopausal status on invasive breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-07-09.

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