Pathologic complete response to neoadjuvant chemotherapy without trastuzumab in hormone receptornegative/HER2 Ć¾ tumors is seen in 27-45% of cases. In contrast, estrogen receptor (ER) Ć¾ /HER2 Ć¾ tumors demonstrate pathologic complete response in B8% of cases and is generally limited to weak-to-moderate ER Ć¾ /HER2 Ć¾ tumors. It is speculated that addition of trastuzumab to neoadjuvant chemotherapy regimen will increase the pathologic complete response rates in all HER2 Ć¾ tumors. A list of HER2 Ć¾ patients who received neoadjuvant chemotherapy (with trastuzumab) in the years 2007-2010 was obtained from our hospital database. The 104 HER2 Ć¾ tumors were classified into three groups based on semiquantitative hormone receptor and HER2 results as follows: ERBB2 (ER-/PR-[H-score r10]/HER2 Ć¾ ), Luminal B-HER2 Hybrid (LBHH; weak to moderate ER Ć¾ [H-score 11-199]/HER2 Ć¾ ), and Luminal A-HER2 Hybrid (LAHH; strong ER Ć¾ [H-score Z200]/ HER2 Ć¾ ). Pathologic complete response was defined as absence of invasive carcinoma in the resection specimen and in the lymph nodes. Percentage tumor volume reduction was also calculated based on pretherapy size and detailed evaluation of the resection specimen. In all, 52% (25 of 48 cases) of ERBB2 tumors showed pathologic complete response, which was significantly higher than the pathologic complete response rate in LBHH (33%; 10 of 30) and LAHH (8%; 2 of 26) tumors. Average percentage tumor volume reduction was also highest in ERBB2 tumors (86%), followed by LBHH (74%) and LAHH (64%) tumors. We conclude that addition of trastuzumab to neoadjuvant chemotherapy regimen significantly increases the pathologic complete response rates in all HER2 Ć¾ tumors. However, the benefit of trastuzumab is highest in ER-negative tumors and progressively decreases with increase in tumor ER expression. This information can be utilized to counsel patients considered for neoadjuvant chemotherapy and the same principle could be applied in the adjuvant setting.