Low-progesterone receptor expression predicts nodal pathological complete response after neoadjuvant chemotherapy in premenopausal patients with ER-positive/HER2-negative breast cancer.

BACKGROUND: Estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer (BC) shows heterogeneous response to neoadjuvant chemotherapy (NAC). Although low progesterone receptor (PgR) has been associated with greater chemosensitivity, it is unclear whether its predictive value differs according to menopausal status. METHODS: We retrospectively analyzed 213 patients with node-positive, ER-positive/HER2-negative BC who underwent surgery and axillary lymph node dissection (ALND) after NAC between January 2010 and April 2025. All patients received anthracycline- and taxane-based regimens. Multivariable logistic regression was performed to identify predictors of achieving pathological complete response in the axillary lymph node (ypN0), and interaction terms were included to evaluate whether the effect of PgR differed according to menopausal status. RESULTS: Among 213 patients, 47 (22%) achieved ypN0. Clinical complete response (OR 5.29; 95% CI 1.44–19.40; p = 0.01) and high Ki-67 (≥ 30%) (OR 3.62; 95% CI 1.14–11.50; p = 0.03) independently predicted ypN0. Low PgR expression (≤ 5%) and premenopausal status were not independently associated with ypN0. In the final multivariable interaction model, the interaction between low PgR (≤ 5%) and premenopausal status remained significant (OR 9.52; 95% CI 1.22–74.50; p = 0.03). CONCLUSIONS: The association between low PgR status (≤ 5% vs. > 5%) and ypN0 after NAC may differ according to menopausal status and appeared to be more pronounced in premenopausal patients with ER-positive/HER2-negative BC. PgR assessment may help identify patients more likely to achieve ypN0 and may provide additional information for future studies evaluating axillary de-escalation.