Background: While HER2+breast cancers demonstrate high rates of pathologic complete response (pCR) to neoadjuvant HER2-targeted therapy, there is a need to assess objective response in HER2 equivocal tumors. Methods: Retrospective chart review was conducted of patients diagnosed with invasive breast cancer who received neoadjuvant therapy (NAT) between 2010 and 2014 at our institution. Case inclusion required at least ER and HER2 status and pCR information. HER2 was measured by immunohistochemistry (IHC) with IHC 3+ and IHC 0/1+ cases considered positive and negative respectively. IHC 2+ cases were tested by FISH and classified using the 2013 ASCO HER2 guidelines ISH criteria for dual color probe. Cases were also classified by average HER2 copies/cell criteria. Results: 595 cases met criteria for inclusion. pCR rates according to HER2 status are reported below. Conclusions: Of the 46 patients with HER2 equivocal results, 31 (67%) received anti-HER2 NAT. 5 of 31 (16%) achieved pCR: 2 of 8 ER- (25%) and 3 of 23 ER+ (13%). The overall 16% pCR rate of HER2 equivocal tumors that received targeted therapy is similar to the 18% pCR rate of HER2- tumors (p = 1.0), but significantly lower than the 41% pCR rate of HER2+ tumors (p = 0.0087). In this small subset of HER2 equivocal cases treated with anti-HER2 NAT, pCR rates were similar to HER2- tumors. Further study is warranted to assess whether HER2 targeted therapy in HER2 equivocal tumors improves surgical outcomes, and survival.

*Statistically significant; **Results available on 588 of 595 cases Cases classified as equivocal based on HER2 gene copies per cell criteria