Pathological complete response rates in HER2 amplified breast cancers based on levels of HER2 amplification.

Abstract

e12632 Background: Untreated HER2 (Human Epidermal Growth Factor) amplified breast cancer has poorer prognosis, compared to those with HER2 negative status with shorter time to relapse and increased incidence of metastases and higher mortality. Both Trastuzumab and Pertuzumab (humanized monoclonal antibodies against HER2) have shown to improve PCR (Pathological Complete Response) rates when used in the neoadjuvant setting. However, whether the quantitative level of HER2 amplification affects PCR rates or disease-free survival/overall survival has not been well studied. If the level of HER2 amplification correlates with PCR rates, this could be a tool for clinicians to use as a predictive marker for response to therapy. Methods: This is a retrospective chart review of community oncology clinic patients with HER2 amplified breast cancer Stage I-III to evaluate the rates of PCR after HER2 targeted neo-adjuvant therapy categorized by HER2 CISH (Chromogenic in situ hybridization) amplification and stratified based on levels of amplification of < 3, 3 to 5, or > 5. Pathology reports were reviewed for report of PCR. Inclusion criteria was women age 19 to 90, HER2 positive biopsy proven breast cancer, Stage I-III, patients treated with neoadjuvant chemotherapy, adequate renal function, and left ventricular ejection fraction within normal range. Exclusion criteria was pregnancy, metastatic disease, history of other malignancies, and impaired renal or cardiac function. Results: The data consisted of 36 unique patients, 25% of whom had a HER2 below 3, 22.2% had a HER2 between 3 and 5, and 52.8% had a HER2 value > 5. There was found to be a statistically significant association between the level of HER2 amplification and PCR rates with increased amplification of HER2 relates with increased PCR rates (p value < 0.0176). Both three-year disease-free survival and three-year overall response rates were not statistically significantly associated with HER2 category (p value -0.2691 and 0.4692 respectively). Conclusions: The information from this study may introduce a future systematic approach to further risk stratify patients based upon their quantitative HER2 amplification level to help predict response to therapy. We have noted that a level of HER2 amplification > 5 led to significant association with PCR compared to < 3 and 3-5 values.