Estrogen receptor-negative/progesterone receptor-positive breast cancer has distinct characteristics and pathologic complete response rate after neoadjuvant chemotherapy
Authors: Dou He , Li Fucheng , Wang Youyu , Chen Xingyan , Yu Pingyang , Jia Siyuan , Ba Yuling , Luo Danli , Gao Tian , Li Zhao ting , Xiao Min 
Published: October 2023

Abstract
Purpose The status of hormone receptors (HR) is an independent factor affecting survival and chemotherapy sensitivity in breast cancer (BC) patients, with estrogen receptor (ER) and progesterone receptor (PR) having the most significant effects. The ER-/PR+ phenotype has been controversial in BC, and experts will face many challenges in determining treatment strategies. Herein, we systematically analyzed the clinicopathological characteristics of the ER-/PR+ phenotype in BC patients and the response to chemotherapy.
Patients and methods We included two cohorts. The first cohort counted the clinical and pathological data and survival results of 72666 female patients in the Surveillance, Epidemiology, and End Results (SEER) database. The second cohort counted the clinical and pathological data and pCR rate of 879 patients in Harbin Medical University Cancer Hospital. The classification data were compared by the chi-square test and Fister's exact test of the Logistic regression model, and predictor variables with P<0.05 in the univariate analysis were included in the multivariate regression analysis. The Kaplan-Meier method evaluated breast cancer-specific survival (BCSS) and overall survival (OS) to investigate the relationship between different HR typing and survival and pCR.
Results In the two cohorts, 704 (0.9%) and 11 (1.3%) patients had the ER-/PR+ phenotype, respectively. The clinicopathological characteristics of patients with ER-/PR+ phenotype were between ER+/PR+ phenotype and ER-/PR- phenotype but preferred the latter. The ER-/PR+ phenotype is more common in young and premenopausal women, and most ER-/PR+ phenotypes are histologically III grade.
Survival analysis showed significant differences in OS and BCSS between different HR states and patients (P< 0.001). The survival results of patients with the ER+/PR+ phenotype were the best. The prognosis of the ER-/PR+ phenotype was similar to that of the ER-/PR- phenotype, and the ER+/PR- phenotype was between the three groups. On the other hand, we found that HR status was also an independent predictor of post-NAC pCR rate in BC patients. The ER+/PR- phenotype and ER-/PR- phenotype were more accessible to obtain pCR than the ER+/PR+ phenotype. Although there was no significant difference between the ER-/PR+ phenotype and ER+/PR+ phenotype, the effect of chemotherapy was better than other groups. In addition, similar results are obtained by subgroup analysis of the two queues according to the HER2 status.
Conclusion Our study found that the ER-/PR+ phenotype is objectively present. HR status is the main factor affecting BC's survival outcome and pCR rate. Patients with the ER-/PR+ phenotype disease earlier, higher clinical stage and histological grade, and a higher proportion of HER2 positive patients are the leading causes of poor prognosis. Patients with the ER-/PR+ phenotype can benefit significantly from chemotherapy and may require different therapeutic strategies. We need to pay more attention to this group and achieve individualized treatment, which will help us treat BC better and provide new targets and blueprints for our clinical treatment.