Abstract P5-16-21: The association of higher tumor HER2 load with treatment response to neoadjuvant therapy in HER2 positive breast cancer patients
Authors: Lillemoe TJ , Susnik B , Grimm E , Kang S-HL , Swenson KK , Krueger JL , Finkelstein MJ , Tsai ML 
Published: March 2017

Background: Neoadjuvant therapy for HER2 positive invasive breast cancer is used to downstage tumor prior to surgery, objectively measure response, and evaluate novel therapies in clinical trials. Residual Cancer Burden (RCB) established by pathologic evaluation of post-treatment surgical specimens is a marker of tumor response to chemotherapy as well as predictor of recurrence-free survival in HER2 positive breast cancer. The relationship between the HER2 tumor load and the response to chemotherapy in not known.

Specific Aims: To evaluate RCB after neoadjuvant chemotherapy and HER2-targeted treatment for HER2-positive breast cancer, and to determine clinicopathologic factors associated with treatment response as represented by RCB.

Methods: This retrospective chart review included all HER2-positive breast cancer patients, stage I – III, receiving neoadjuvant chemotherapy and HER2-targeted therapy with post-treatment surgical resection at an Allina Health hospital from 2013-2016. Review of clinicopathologic variables included HER2/CEP17 ratio, HER2 absolute copies, ER/PgR status (using the H score calculation), patient age, baseline tumor size, and gross and microscopic pathology review of breast tissue specimens with RCB evaluation completed by breast pathologists. To compare factors related to response, chi-square with Monte-Carlo simulation was used to analyze dichotomous variables, and Mann Whitney U-tests were used for continuous variables.

Findings: The study included 97 patients. Upon surgical resection, complete pathologic response (RCB-0) was found in 47% (46/97 patients), and partial pathologic response (RCB-I) in 15% (15/97 patients). As compared to non-responders (RCB-2 and RCB-3) the complete and partial responders (RCB-0 and RCB-1) were associated with greater HER2/CEP17 ratios (10.2 vs. 6.5; p=0.003), and greater HER2 absolute copies (25 vs. 15.8; p &lt;0.001). Complete responders were associated with lower ER expression (H scores of 89.2 vs. 171.8; p=0.005) than non-responders, with RCB-1 responders associated with ER H-scores between RCB-0 and non-responders (H score=145.9). No significant differences were noted between responders and non-responders on age at diagnosis, pre-treatment tumor size, PgR expression, or the percentage of tumor infiltrating lymphocytes.

Conclusions: The majority of patients with HER2 positive tumors show considerable benefit with neoadjuvant chemotherapy and HER2-targeted treatment (63% in our study) based on RCB assessment. Predictors of response as measured by RCB include high HER2/CEP17 ratios, high absolute copies of HER2 signals by FISH, and lower ER expression.

Citation Format: Lillemoe TJ, Susnik B, Grimm E, Kang S-HL, Swenson KK, Krueger JL, Finkelstein MJ, Tsai ML. The association of higher tumor HER2 load with treatment response to neoadjuvant therapy in HER2 positive breast cancer patients [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-16-21.