# Impact of Age and Menopausal Status on T-DM1 (Ado-Trastuzumab Emtansine) Treatment Outcomes in HER2-Positive Breast Cancer

## TL;DR

This study examines how age and menopausal status affect treatment outcomes for HER2-positive breast cancer patients using T-DM1, finding that age is a more significant factor than menopause.

## Contribution

The study provides new insights into the independent impact of menopausal status on T-DM1 outcomes when controlling for age in HER2-positive breast cancer.

## Key findings

- Postmenopausal patients had higher lung metastasis and mortality rates compared to premenopausal patients.
- Menopausal status did not independently affect T-DM1 response or toxicity after adjusting for age.
- Age was the dominant factor influencing performance status, metastatic burden, and mortality risk.

## Abstract

Background/Objectives: HER2-positive breast cancer is an aggressive subtype with an established responsiveness to HER2-targeted therapies like ado-trastuzumab emtansine (T-DM1). However, inter-patient variability in treatment response and toxicity remains a challenge. Hormonal status, particularly menopausal state, may influence breast cancer behavior, therapeutic tolerance, and outcomes, yet data on its effect in patients treated with T-DM1 are scarce. This study aimed to evaluate whether menopausal status independently affects treatment response, side effects, and survival outcomes in HER2-positive breast cancer patients receiving T-DM1, accounting for the confounding role of age. Methods: This retrospective cohort study included 98 female patients with HER2-positive breast cancer treated with T-DM1: 53 premenopausal and 45 postmenopausal. The clinical characteristics, metastatic patterns, treatment history, T-DM1 outcomes, and toxicities were recorded. The statistical analysis included chi-square, t-tests, Mann–Whitney U tests, and Spearman’s correlations. Partial correlation analyses were conducted to isolate the effect of menopausal status by controlling for age. Results: The postmenopausal patients showed higher rates of lung metastasis (42.2% vs. 20.8%) and mortality (60.0% vs. 39.6%) than premenopausal patients. However, no significant differences were found in the T-DM1 response or toxicity profiles. After adjusting for age, menopausal status had no independent association with the treatment outcomes or side effects. Age was the dominant factor influencing performance status, metastatic burden, and mortality risk. Conclusions: Menopausal status affects disease presentation but not T-DM1 efficacy or toxicity when age is accounted for. Treatment decisions should consider age and clinical profile rather than menopausal classification alone when managing HER2-positive breast cancer with T-DM1.