Abstract P3-07-04: Impact of estrogen receptor (ER) and HER2 co-expression on breast cancer characteristics and disease presentation

Background: ER and HER2 expression can alter breast cancer biology and behavior. Rationalizing that ER-negative/HER2-negative breast cancer is the more undifferentiated form of the disease we evaluated the impact of ER expression, HER2 expression, and then their co-expression on biologic and clinical characteristics of breast cancer. Methods: We analyzed a prospectively collected data set for patients diagnosed with breast cancer at the Markey Cancer Center between January 2007 and December 2012. Out of 1257 patients with a new diagnosis of invasive breast cancer, 1187 had complete ER and HER2 biomarker data and were included in this study. Among the different phenotypic groups we compared traditional patient and disease characteristics including age, tumor size, stage, grade, nodal status, and sites of metastatic disease. Statistical significance was determined using the Chi-square test, Fisher's exact test, two-sample t-test, or log-rank test as appropriate. Results: The impact of ER expression was evaluated by comparing the ER-positive/HER2-negative group (n = 762) to the ER-negative/HER2-negative breast cancer group (n = 231). ER presence was significantly associated with older age (58 vs. 53 years, p<0.0001), smaller mean tumor size (1.8 vs. 2.3 cm, p = 0.0003), lower grade (p<0.0001), earlier stage at presentation (p = 0.0002), and higher frequency of bone involvement in stage 4 disease (56.3% vs. 34.1%, p = 0.0162. There was no significant difference detected in frequency of other sites of metastatic disease. In contrast to the striking impact of ER presence, HER2 had no significant impact on any of the above parameters tested in ER-negative disease when examined by comparing the ER-negative/HER2-positive group (n = 87) to the ER-negative/HER2-negative breast cancer group. To study the impact of both ER and HER2 co-expression, we compared the ER-positive/HER2-positive breast cancer group (n = 107) to the ER-negative/HER2-negative breast cancer group. Compared to ER-negative/HER2-negative breast cancer, ER-positive/HER2-positive disease was more likely to be lower in grade (p< 0.0001), had higher risk of node positive status (51.1% vs. 36.8%, p = 0.0215) and had higher frequency of bone involvement in stage IV disease (62.5% vs. 34.1%, p = 0.0484). There were no significant differences in any of the other parameters tested. Interestingly, within the subgroup of ER-positive/HER2-positive disease, the presence of progesterone receptor (PgR) positivity (n = 73), which is considered indicative of more ER dependence, was somewhat unexpectedly associated with a younger age at time of presentation (50.85 vs.56.06 years, P = 0.0226) compared to PgR-negative disease (n = 34), with no other significant impact noted for PgR presence. Conclusion: When compared to ER-negative/HER2-negative breast cancer as the control group, ER presence is associated with more profound changes in key breast cancer characteristics than HER2 positivity. In contrast, when both ER and Her2 are co-expressed, the influence of ER is markedly attenuated by HER2, with a more dominant aggressive disease phenotype, albeit with retention of some ER features as reflected by lower grade and higher frequency of bone involvement in stage IV disease. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-07-04.