Abstract Background: Pathologic response to neoadjuvant therapy is the most important prognostic factor so new agents should aim to improve it. HER2 expression in breast cancer provides prognostic and predictive information of response to antiHER2 therapy. The quantification of HER2 expression by mRNA is one of the most potent markers of cellular dependence to HER2 pathway. Methods: From a series of 160 patients with early or locally advanced HER2 positive breast cancer who received neoadjuvant treatment with chemotherapy and antiHER2 drugs, mRNA expression of HER2 was analyzed in 69 specimens and it was correlated to pathologic complete response (pCR). Results: Median age was of 52.5 years (29-86), tumor size of 33mm (10-111), 39 (53%) patients had nodal involvement. Median ki67 expression was of 45% (17-80), 28 (38%) tumors were estrogen receptor (ER) positive and 46 (62%) negative. We also analyze the expression of tumor-infiltrating-lymphocytes (TILs) by immunohistochemistry in 43 samples because their expression is also a strong predictive of pathologic response. A total of 31/69 patients (45%) achieved a pCR with a median of mRNA expression of 7,55 (3,8 – 11) in comparison with 2.03 (1,2 -2,8) in patients without pCR (p: 0,002). In the univariable analysis, variables correlated to pCR were estrogen receptor=0 (OR 0,186 IC 95% 0,063-0,549, p: 0,002), mRNA (OR 5,689 IC 95% 1,854-17,452, p: 0,002) and TILs (OR 15,167 IC 95% 3,223-71,38, p: 0,001) and in the multivariable analysis, TILs and mRNA expression were found to be independent predictive factors for pCR. The quantification of HER2 by mRNA obtained an impressive response specially in ER negative patients with a rate of pCR of 100% in samples of mRNA expression upper of 3,6 and ER negative. However, patients with mRNA expression lower than 3,6 with a pCR rate of 32%, could reach to an 80% rate if they had high TILs expression. Conclusions: Quantification of HER2 expression by mRNA is a strong predictive factor of pCR (OR 5,689); achieving a 100% pCR in ER negative tumors. TILs are also a predictive factor for pCR (OR 15,167) and its combination with mRNA expression could improve pCR rates; thus, patients with mRNA expression lower than 3,6, if they had a higher TILs expression could reach to an 80% pCR. Citation Format: Gasol Cudós A, Morales Murillo S, Veas Rodriguez J, Velasco Sánchez A, Serrate López A, Melé Olivé J, Canosa Morales C. mRNA expression of HER2 by PCR as a strong predictor of pathologic response to neoadjuvant antiHER2 therapy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-10-17.