Clinical Outcomes and Intrinsic Subtypes of Breast Cancer Patients with Single Hormone Receptor-positive Receiving Neoadjuvant Chemotherapy

Background Extensive studies have highlighted the significance of estrogen receptor (ER) and progesterone receptor (PR) in breast cancer (BRCA). However, our understanding of patients with single hormone receptor (HR)-positive (sHR+) BRCA remains limited. This lack of understanding poses challenges in predicting prognosis and selecting appropriate treatments. Patients and Methods We collected data from a total of 825 human epidermal growth factor receptor 2 negative (HER2-) BRCA patients who underwent neoadjuvant chemotherapy (NAC) in two distinct cohorts. Four subgroups were created within each cohort based on their HR expression: ER+/PR+, ER+/PR-, ER-/PR+, and ER-/PR-. We conducted comparative analyses to assess clinicopathological characteristics, chemotherapy responsiveness, clinical outcomes, and intrinsic subtyping among these subgroups. Results ER+/PR- constituted 11.1% and 14.9% of samples in two cohorts, respectively, whereas ER-/PR+ comprised 8.3% and 3.7%. Higher histologic grades were more common in the ER-/PR+ group as compared to the ER+/PR+ subgroup (p=0.0075 in cohort 1; p=0.026 in cohort 2). Additionally, after multivariable analysis, ER-/PR+ were more likely to achieve pathological complete response (pCR) (cohort 1: OR =6.67; 95% CI, 2.63-16.94; p<0.001; cohort 2: OR =3.70; 95% CI, 1.08-11.84; p=0.030;). Between ER+/PR- and ER+/PR+, the distant recurrence-free survival (DRFS) was comparable. The survival outcomes in the ER-/PR+ subgroup present a partial inconsistency between the two cohorts. Furthermore, the ER-/PR+ subgroup exhibited a higher incidence of the basal-like subtype, while the ER+/PR- subgroup had a higher proportion of luminal-like subtypes. Conclusion This study highlighted the distinct clinical and genetic characteristics of sHR+ BRCA, emphasizing the potential need for optimized treatment strategies. MicroAbstract Limited studies compared the clinicopathological characteristics, chemotherapy responsiveness, clinical outcomes, and intrinsic subtyping between single hormone receptor-positive and other hormone receptor status breast cancer. We collected 825 breast cancer patients’ data who received neoadjuvant chemotherapy from two cohorts. Our research explored that patients diagnosed with single hormone receptor-positive breast cancer represent distinct clinical and genetic subgroups.