The Prognosis and Predictive Value of Estrogen Negative/Progesterone Positive (ER−/PR+) Phenotype: Experience of 1159 Primary Breast Cancer from a Single Institute

Abstract

Breast cancer is a serious worldwide public health problem and is currently the most common cancer overall. Its endocrine therapy is related to the expression of the steroid hormones, estrogen receptor (ER), and progesterone receptor (PR). Breast cancers can be presented under multiple profiles of steroid hormones: ER(−)/PR(+), ER(+)/PR(−), double-positive/negative ER, and PR. 2–8% of all breast cancers express only PR (ER−/PR+) which is an abnormal phenotype, with less known about their behaviors and outcomes. Our study was performed on a large and well-characterized database of primary breast cancer from 2012 to 2019, up to 1159 cases. These cases were divided according to ER and PR expression, as we put all of our focus on ER-negative/PR-positive group, more specifically ER−/PR+/HER2+ and ER−/PR+/HER2− gene expressions, to highlight their features and find a pattern that links HR (hormone receptors) profiles and breast cancer subtypes. Out of the informative cases, 94 patients (8%) had ER−/PR+ breast cancers, while 676 (58.4%) had ER+/PR+, 88 (7.6%) had ER+/PR−, and 164 (14.2%) had ER−/PR− tumors. The ER−/PR+ group was statistically correlated with a high risk of recurrence and death in midway between the double-negative and double-positive HR. According to HER2 status, a low DFS was observed in patients ER−/PR+/HER2−, which is closer to the DFS of TNBC cases but worse than ER+/PR any. On the other side, the ER−/PR+/HER2+ showed also a poorer DFS closer to the HER2+ subgroup in between TNBC and ER+/PR any. The clinicopathological features of the ER−/PR+/HER2− and ER−/PR+ HER2+ have distinguished the patients into two groups with a difference in some clinicopathological characteristics: both groups had closer OS estimation, which was worse than ER−/PR any and better than TNBC and HER2. The ER−/PR+/HER2− seems to increase the risk of recurrence than ER−/PR+/HER2+ when compared to ER+/PR any. On the other hand, the ER−/PR+/HER2+ seems to increase the risk of death more than ER−/PR+/HER2− in comparison with ER+/PR any. Our results support that ER−/PR+ tumors really exist and are rare and clinically and biologically distinct subtypes of breast cancer. In addition, our analysis, which was based on dividing the groups according to HER2 expression, has revealed the existence of two distinct groups; this gave the ER−/PR+ subgroup a heterogeneity characterization. Moreover, this breast cancer subtype should not be treated as a luminal tumor but rather according to the HER2 expression status.

The role of modern parameters and their relationship with recurrence risk as assessed by Oncotype DX: real-world evidence

“…Hormone receptors (HRs) are prognostic and predictive factors for invasive breast cancer outcomes [ 16 ]. Regarding the accuracy of the HR percentage in correlating with prognosis, there is evidence from cohorts where it was observed that in luminal tumours, the absence of PR expression was associated with worse survival, with survival rates comparable to triple-negative tumours [ 17 , 18 ]. This situation is infrequent and is observed in 2%–8% of cases.…”

“…For high-risk patients, chemotherapy was found to provide additional invasive disease-free survival benefits. Finally, for patients in the intermediate-risk group (RS [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25], it was suggested to consider other clinical factors, such as menopausal status and clinical risk, when recommending adjuvant chemotherapy along with endocrine therapy [8]. Subsequently, the RXponder trial, conducted by Kalinsky et al [9] reported on the results of 5,083 patients with axillary involvement of one to three lymph nodes.…”