HER2 Testing of Multifocal Invasive Breast Carcinoma: How Many Blocks Are Enough?
Gillian C Bethune, Martin C Chang. Mount Sinai Hospital, Toronto, ON, Canada; University of Toronto, Toronto, ON, Canada
Background: The human epidermal growth factor receptor 2 (ERBB2) oncogene/oncoprotein, commonly known as HER2, is routinely evaluated in invasive breast carcinoma because of its predictive and prognostic value. When multiple ipsilateral invasive foci are present, the current CAP breast cancer protocol recommends evaluating HER2 in 1 block of the largest tumor focus, and testing additional smaller foci if a higher grade or different histologic type is seen. The evidence supporting this recommendation is unclear. The objective of this study is to determine the diagnostic yield of testing multiple blocks in cases of multifocal breast carcinoma.
Design: In accordance the protocol approved by the institutional research ethics board, we identified 246 consecutive cases of primary multifocal (ipsilateral) invasive breast carcinoma in which more than one tumor block were tested for HER2 between 2006 and 2011. We performed an audit of HER2 results in all cases. For foci considered equivocal by both immunohistochemistry (2+) and FISH (ratio between 1.8 and 2.2), the HER2 status was considered “negative” for a ratio of 2.0 or less, and “positive” if the ratio was > 2.0. For all cases in which ipsilateral tumor foci showed differences in HER2 status, the tumor size, grade, and histologic features of each focus were recorded.
Results: Of 246 cases, 198 (80%) had 2 foci and 48 (20%) had 3 to 6 foci. In cases with 2 foci, both foci were tested. In cases with >2 foci, selected foci were tested (up to 5 blocks). Only 16/246 (6.5%) demonstrated a difference in HER2 status between tumor foci. The largest tumor focus was HER2-positive in 12/16 (75%) of these cases; 7/12 (58%) of these largest tumor foci were also the highest-grade foci. Overall, testing of the largest focus resulted in the most-positive result in 242/246 (98%) of cases. Of the remaining 4 discordant cases, 1/4 (25%) had 2 foci of the same size and 3/4 (75%) were in smaller foci that also had higher grade or different histology. Not a single focus (0%) that was smaller and similar histologically yielded a more-positive HER2 result.
Conclusions: The large majority of multifocal breast carcinomas are not discordant with respect to HER2 status. Testing of a single largest focus yielded the most-positive result in >98% of cases. Including equal-sized or smaller foci with a higher grade or different histology would yield the most-positive result in 100% of cases. Tumour size, grade, and histologic type should therefore be examined if HER2 testing of more than 1 focus is under consideration.
Tuesday, March 5, 2013 1:00 PM
Poster Session IV # 45, Tuesday Afternoon