In patients with breast cancer (BC), hormone receptor phenotype is an independent factor affecting outcomes. There is controversy surrounding the existence of estrogen receptor-negative/progesterone receptor-positive (ER-/PR+) BC, which some have attributed to technical reasons or different diagnostic thresholds rather than to biological factors. Nonetheless, it has been observed that survival outcomes vary based on PR status.
In patients with BC, hormone receptor phenotype is an independent factor affecting outcomes, such as prognosis and chemotherapeutic effect. There is controversy surrounding the existence of ER-/PR+ BC, which some have attributed to technical reasons or different diagnostic thresholds rather than to biological factors. However, it has been observed that survival outcomes vary based on PR status. It is estimated that <1.5% of BC cases are due to the ER-/PR+ phenotype.
Using data from two different cohorts, including the Surveillance, Epidemiology, and End Results (SEER) Program, which is the most extensive population-based cancer data set in the United States encompassing about 26% of the population (Cohort 1), and Harbin Medical University Cancer Hospital (HMUCH; Cohort 2), investigators determined the clinicopathological characteristics of patients with the ER-/PR+ phenotype. In Cohort 2, investigators also assessed for pathological complete response (pCR) following the administration of neoadjuvant chemotherapy (NAC) compared with patients with other BC phenotypes (i.e., ER+/PR+. RT+/PR-, ER-/PR-).
Data of female patients in Cohort 1 were included in the study if they were diagnosed with BC between January 1, 2010, and December 31, 2015, and data from female patients in Cohort 2 were included for those patients who were diagnosed with BC between January 1, 2012, and December 31, 2019. Additional inclusion criteria for Cohort 1 were that the cancer site and histologic type had to be indicated; pathology had to be invasive ductal carcinoma or invasive lobular carcinoma; tumors had to be T1-T4 and N0-N3; patients had to be aged between 20 and 80 years; and no distant metastases could be present. Additional inclusion criteria for Cohort 2 included pathological confirmation of BC before chemotherapy; completed NAC course; complete clinical and pathological data; T1-T3 tumors; and the performance of immunochemistry.
Of the 72,666 patients whose data were analyzed in the SEER database and 879 patients whose data were analyzed in the HMUCH database, only 704 patients (0.9%) and 11 patients (1.3%), respectively, had the ER-/PR+ phenotype. In Cohort 1, almost one-quarter of ER-/PR+ BC patients (24.0%) were aged 61 to 70 years. The majority of ER-/PR+ BC patients (95.3%) had invasive ductal carcinoma (IDC). Patients with ER-/PR+ had relatively higher histological grades compared with those with ER+/PR+ BC, with 80% being grade III versus 46.7% in patients with ER+/PR+ BC. The clinicopathological features of ER-/PR+ were similar to those of the ER-/PR- BC phenotype. Median follow-up was 75 months in this cohort and demonstrated a 5-year overall survival (OS) of 88.1% and 5-year BC-specific survival (BCSS) of 87.4%, both of which were lower than for the ER+/PR+ groups. OS and BCSS were similar between the ER-/PR+ and ER-/PR- phenotypes.
In Cohort 2, the median age was 52 years. Patients tended to be younger and had not undergone menopause. K167, P53, and HER2 were highly expressed in this group. In this cohort, 82% had IDC. Factors affecting pCR after NAC included T stage, ER expression, PR expression, HER-2 expression, K167 expression, histological grade, HR status, and clinical stage but not age, chemotherapeutic regimen, N stage, surgical method, menopausal status, BMI, or P53 protein expression.
The National Comprehensive Cancer Network (NCCN) guidelines advise that patients with ER-negative, PR-positive cancers may be considered for endocrine therapies, but the data for this group are limited. In a discussion that is under revision, NCCN states that benefits of chemotherapy appear to be significantly greater in patients with ER-negative disease than in ER+ patients.
Pharmacist should be familiar with this fairly uncommon form of BC and with the evolving recommendations for the management of this disease.
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