Background: The current standard of treatment for locally advanced and early HER2+ breast cancer is the use of neoadjuvant chemotherapy (NAC) in combination with trastuzumab and pertuzumab. Mexican reports about its efficacy and predictive factors leading to pathological complete response (pCR) are scarce and few statistics are known. Methods: We performed a retrospective review of medical records of locally advanced and early HER2+ breast cancer patients who were treated with NAC in association with pertuzumab and trastuzumab. pCR was defined as the absence of residual invasive cancer cells in the breast and lymph nodes (ypT0/ypN0). Other histopathological features included Tumor type, estrogen, and progesterone receptor expression, HER2 status and Ki67. Clinical data included age, body mass index and number of metastatic nodes. Results: Thirty-five patients with early or locally advanced HER2+ breast cancer diagnosed and treated in a Comprehensive Cancer Center between January 2014 to June 2020 were included. The median age in the population was 47 years (range 28-79) with 20 patients under 50 years (57% of the total population). 40% of the patients were classified as overweight or obese at the time of diagnosis. The predominant histology was infiltrating ductal carcinoma (91%). The most frequent clinical stages were IIA, (34.2%) IIB (31.4%) and IIIA (22.8%). The population included patients with N0 (21.7%), N1 (56.5%), N2 (13%) and N3 (8.7%). Most tumors were larger than 2 centimeters at the time of diagnosis. T1 (17.4%), T2 (60.9%), T3 (17.4%) and T4 (4.3%). Most of the patients (77%) had a high proliferation index (Ki67 > 20). A total of 12 patients (34.3%) were hormone receptor (HR) negative and the rest (65.7%) were categorized as Triple Positive. The chemotherapy schemes used for NAC treatment were AC/THP (57.5%), THP (22.8%), TCHP (17.1%) and FEC/THP (2.7%) pCR was achieved in 60% of the patients. Patients with HR (-) achieved a pCR in 83% of the cases (10/12 patients) against 47.8% (11/23 patients) of the triple positive population. The Odds ratio (OR) for residual disease was 6.6 (95%CI 1.17-37.02) in the HR+ population. HR-/HER2+ tumors (p = 0.49) were independent predictors of pCR at multivariate logistic regression. No other variables including Ki67, BMI, age, tumor size, type of chemotherapy administered, and lymph node status were statistically significant. Conclusions: In this Mexican population there is a significant difference between the percentage of patients who achieve pCR in relation to the status of hormone receptors, favoring those patients with hormone receptor negative tumors. Nevertheless, most of the population achieves this benefit regardless of their hormone status, as HER2+ tumors showed sensitivity to chemotherapy and to the humanized anti-HER2 therapies. No other clinical or pathological variables were associated with pCR.