[156] Semi-Quantitative Estrogen Receptor Expression Level Influences Response to Trastuzumab Containing Neo-Adjuvant Chemotherapy in HER2 Positive Tumors

R Bhargava, DJ Dabbs, S Beriwal, RR Johnson, AM Brufsky, B Lembersky, A Soran, GM Ahrendt. Magee-Womens Hospital of UPMC, Pittsburgh, PA

Background: Prior to 2006, use of trastuzumab in neoadjuvant chemotherapy (NACT) regimen was limited to clinical trials. Recently, trastuzumab is increasingly used pre-operatively in HER2+ breast carcinoma, often as TCH regimen (Taxotere, Carboplatinum, Herceptin). Pathologic complete response (pCR) to NACT without trastuzumab in hormone receptor negative/HER2+ tumors is seen in 27% to 45% cases. In contrast, estrogen receptor (ER)+/HER2+ tumors demonstrate pCR in ∼8% cases and is generally limited to weak to moderate ER+/HER2+ tumors (Cancer, in press). It is speculated that addition of trastuzumab to NACT regimen will increase the pCR rates in all HER2+ tumors.
Design: A list of HER2+ patients that received TCH NACT in the years 2006-2007 was obtained from our hospital tumor registry. The 34 HER2+ tumors were classified in 3 groups based on semi-quantitative hormone receptor and HER2 results as follows: ERBB2, Luminal A-HER2 Hybrid (LAHH), Luminal B-HER2 Hybrid (LBHH). The criteria for classification are shown in the table below. pCR was defined as absence of invasive carcinoma in the resection specimen and in the lymph nodes. Percentage tumor size reduction was also calculated based on pre-therapy size and detailed evaluation of the resection specimen.
Results:

pCR in various categories of HER2+ tumors

Tumor Class	Immunohistochemical Criteria	pCR	Average Tumor Size Reduction
ERBB2	ER/PR negative, HER2+	12/18 (67%)	88%
LAHH	Strong ER+, HER2+	2/11 (18%)	66%
LBHH	Weak/moderate ER+, HER2+	2/5 (40%)	90%

pCR: Pathologic Complete Response

The difference in pCR rates among 3 categories was borderline significant (p value: 0.059). Average tumor size reduction was significantly higher in ERBB2 and LBHH tumors compared to LAHH tumors (p value: 0.003).
Conclusions: Addition of trastuzumab to NACT regimen significantly increases the pCR rates in all HER2+ 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 NACT and the same principle could be applied in the adjuvant setting. Generally patient that achieve pCR have excellent prognosis compared to the one that fails to achieve pCR. Whether addition of trastuzumab in NACT regimen would have the same effect will be analyzed in the years to come.
Category: Breast

Tuesday, March 23, 2010 9:30 AM

Poster Session III # 59, Tuesday Morning