Estrogen receptor-negative/progesterone receptor-positive breast cancer has distinct characteristics and pathologic complete response rate after neoadjuvant chemotherapy

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 relationship between clinicopathologic data and survival outcomes for 72,666 female patients in the Surveillance, Epidemiology, and End Results (SEER) database. The second cohort analyzed the relationship between clinicopathological data and pathologic complete response (pCR) rate in 879 patients at the 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 clinicopathologic features of patients with the ER-/PR + phenotype are more similar to those of the ER-/PR- phenotype. The ER-/PR + phenotype is more common in younger and premenopausal women, and most ER-/PR + phenotypes exhibit higher histological grades. Survival analysis showed that there were significant differences in OS and BCSS among patients with different HR states (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. 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- and ER-/PR- phenotypes were more sensitive to chemotherapy than the ER + /PR + phenotypes.

Conclusion: HR status is the main factor affecting BC's survival outcome and pCR rate. Patients with the ER-/PR + phenotype possess more aggressive biological factors and can benefit significantly from chemotherapy. 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.

Keywords: Breast cancer; Estrogen receptor; Neoadjuvant chemotherapy; Pathologic complete response; Progesterone receptor.

Fig. 1

Grouping flow chart of 72,666 BC patients collected in cohort 1

Fig. 2

Grouping flow chart od 879 BC patients collected in cohort 2

Fig. 3

Relationship of different HR combination subgroups and OS in the whole series (Kaplan–Meier method and log-rank test) Legend: The four different HR combinations were associated with significant differences in patient OS (log-rank, P < 0.001). The prognosis of patients with the ER-/PR + phenotype was similar to that of patients with the ER-/PR- phenotype (P = 0.978), and patients with the ER + /PR + and ER + /PR- phenotypes had a significantly better survival outcome than the other patients (P < 0.001), patients with ER-/PR + phenotype had a higher risk of death than other patients, and the mean survival time was 100.45 months. Abbreviation: ER, estrogen receptor; PR, progesterone receptor

Fig. 4

Relationship of different HR combination subgroups and BCSS in the whole series (Kaplan–Meier method and log-rank test) Legend: The four different HR combinations were significantly different from the BCSS of the patients (log-rank, P < 0.001). The prognosis of the patients with the ER-/PR + phenotype was similar to that of the patients with the ER-/PR- phenotype (P = 0.995), the best prognosis of the patients with the ER + /PR + phenotype, and the prognosis of the patients with the ER + /PR- phenotype was situated between the ER + /PR + phenotype (best outcome) and ER-/PR + phenotype (worst outcome) (P < 0.001). Patients with ER-/PR- phenotype had a higher risk of death than the other groups, with a mean survival time of 106.17 months. Abbreviation: ER, estrogen receptor; PR, progesterone receptor

Fig. 5

Relationship of different HR combination subgroups and OS in the HER-2 negative series (Kaplan–Meier method and log-rank test) Legend: The four different HR combinations were significantly different from the OS of the HER-2 negative patients (log-rank, P < 0.001). Among HER-2-negative patients, patients with ER-/PR + phenotype had the worst prognosis, but it was not significantly different from that of patients with ER-/PR- phenotype (P = 0.899), and patients with ER + /PR + phenotype had the best prognosis and the lowest risk. The prognosis of patients with ER + /PR- phenotype was located in the middle of the ER + /PR + phenotype (the best outcome) and ER-/PR + phenotype (the worst outcome) between them (P < 0.001). Abbreviation: ER, estrogen receptor; PR, progesterone receptor; HER-2, human epidermal growth factor receptor 2

Fig. 6

Relationship of different HR combination subgroups and BCSS in the HER-2 negative series (Kaplan–Meier method and log-rank test) Legend: The four different HR combinations were significantly different from the BCSS of the HER-2 negative patients (log-rank, P < 0.001). Among HER-2-negative patients, patients with ER-/PR + phenotype had the worst prognosis, but it was not significantly different from that of patients with ER-/PR- phenotype (P = 0.918), and patients with ER + /PR + phenotype had the best prognosis and the lowest risk. The prognosis of patients with ER + /PR- phenotype was located in the middle of the ER + /PR + phenotype (the best outcome) and ER-/PR + phenotype (the worst outcome) between them (P < 0.001). The overall results were similar to the whole group of patients. Abbreviation: ER, estrogen receptor; PR, progesterone receptor; HER-2, human epidermal growth factor receptor 2

Fig. 7

OS relationship between the ER-/PR + and ER + /PR any groups (Kaplan–Meier method and log-rank test) Legend: Regardless of how PR was expressed, when patients were positive for ER expression, their OS was significantly better than that of patients with ER-/PR + phenotypes (log-rank, P < 0.001). Abbreviation: ER, estrogen receptor; PR, progesterone receptor

Fig. 8

BCSS relationship between the ER-/PR + and ER + /PR any groups (Kaplan–Meier method and log-rank test) Legend: Regardless of how PR was expressed, when patients were positive for ER expression, their BCSS was significantly better than that of patients with ER-/PR + phenotypes (log-rank, P < 0.001). Abbreviation: ER, estrogen receptor; PR, progesterone receptor

Fig. 9

Group differences between the HR status using RECIST as the pathological criteria Abbreviation: ER, estrogen receptor; PR, progesterone receptor; PR, partial response; CR, complete response; PD, progressive disease, SD, stable disease