Breast cancer research and treatment 2014-11
Impact of estrogen receptor (ER) and human epidermal growth factor receptor-2 (HER2) co-expression on breast cancer disease characteristics: implications for tumor biology and research.
Abstract
ER and HER2 are critical drivers of breast cancer biology and can interact when co-expressed, but less data describe the impact of ER/HER2 co-expression on clinical disease characteristics. We studied the impact of ER and HER2 (co)-expression in a cohort of 1,187 patients with invasive breast cancer and compared disease characteristics among different groups according to ER and HER2 status. Age, tumor size, grade, nodal status, TNM stage, and metastatic sites were compared and significance determined using the appropriate t tests. All p values were two-tailed. Compared to ER-negative/HER2-negative disease as the control group, ER expression was associated with older age, smaller tumors, lower grade, earlier TNM stage, and increased bone involvement in de novo metastasis, while HER2 had no significant impact on these characteristics. ER and HER2 co-expression was associated with lower grade and higher bone involvement in de novo metastasis, reflecting a retained impact for ER. HER2 impact on ER-positive disease was reflected by younger age, higher grade and TNM stage, and increased frequency of visceral involvement in de novo metastasis. Within the ER-positive/HER2-positive group, triple positive breast cancer (ER+/PgR+/HER2+) was associated with younger age compared to ER+/PgR-/HER2+ disease (mean age of 50.8 vs. 56 years, p = 0.0226). PgR was also associated with younger age in ER+/HER2- disease with a mean age of 57.6 years in ER+/PgR+/HER2- disease vs. 63.4 years in ER+/PgR-/HER2- disease (p < 0.0001). In conclusion, ER has a profound impact on breast cancer characteristics, including a retained impact when co-expressed with HER2. Similarly, HER2 dramatically modulates ER-positive breast cancer making it more aggressive. PgR association with young age may be related to hormonal levels of the premenopausal state, with HER2 providing an earlier growth advantage in triple positive disease, suggesting a specific dependence for this subset on high estrogen levels.
Related Questions
For a patient with well differentiated de novo triple positive metastatic breast cancer who did not respond to THP, do you sequence all available HER2 targeted options before endocrine therapy?
Endocrine combinations for triple positive breast cancer are honestly a bit understudied. We are starting to get more data in this space, SUMMIT, for example, neratinib + fulvestrant + trastuzumab. I think endocrine based combinations are very interesting and there are likely some tumors that are mo...
For a patient with isolated CNS recurrence of HR+HER2+ breast cancer after completion of adjuvant therapy, what, if any, systemic therapy would you start after completion of local therapy?
It is important to maintain curative intent in this situation. Most typically, patients with ER+/HER2+ (or triple positive breast cancer) are the youngest of all patients with ER+ breast cancer (Alqaisi et al BCRT 2014), and while anti-HER2 therapy is key, it is also critical to emphasize the role o...