Progesterone receptor loss identifies luminal-type local advanced breast cancer with poor survival in patients who fail to achieve a pathological complete response to neoadjuvant chemotherapy

The aim of this study was to investigate the potential of progesterone receptor (PgR) as a biomarker for differentiating estrogen receptor (ER)-positive patients who fail to achieve a pathological complete response to neoadjuvant chemotherapy (NCT) with different prognoses. A total of 327 consecutive, locally advanced breast cancer patients with ER-positive disease were included in this study. According to their HER-2 and Ki-67 status, the patients were classified into the Luminal-A or Luminal-B subtype. We evaluated the clinical and pathological response to NCT and relapse or death occurring during follow-up according to PgR status in the different luminal subtypes. In the Luminal-B subtype, patients with PgR- tumors had a relatively higher pathological complete response (pCR) rate (29.5% vs. 4.7% pCR, P < 0.001) and Miller-Payne grades (45.5% vs. 23.5% of grade 4-5, P = 0033) compared to PgR+ tumors. In Luminal-B patients with residual tumor after NCT, PgR loss was also independently correlated with poor relapse-free survival (P = 0.017; HR = 0.430; PgR- as a reference) and overall survival (P = 0.013; HR = 0.355; PgR- as a reference). However, in the Luminal-A subtype, there were no statistically significant differences between PgR+ and PgR- disease in response to NCT or survival. Our findings have demonstrated the prognostic value of PgR loss in the neoadjuvant setting, indicating that ER+/PgR- Luminal-B tumors warrant further attention due to their high risk of relapse after primary treatment.