[86] Breast Cancer HER2 Heterogeneity by FISH Pre and Post Neoadjuvant Chemotherapy: A Pilot Study

Kathi H Adamson, Suzanne M Dintzis, Rodney A Schmidt, David Mankoff, Kimberly H Allison. University of Washington, Seattle, WA

Background: In 2009 a College of American Pathologist expert panel (CAP-EP) published recommendations for reporting HER2 "heterogeneous" cases in which 5-50% of individual cells are amplified for HER2 by fluorescence in situ hybridization (FISH). As a pilot study to examine the potential implications of HER2 heterogeneity by these criteria, we examined a series of cases before and after neoadjuvant chemotherapy to see if minor populations of amplified cells changed with therapy.
Design: HER2 FISH was performed on 34 cases of locally advanced breast cancer, including 17 biopsies and their matched surgical excision specimens after treatment with neoadjuvant chemotherapy. The percentage of cells with HER2 amplification by HER2:CEP17 individual cell ratio (ICR) and HER2 individual signals per cell (ICS) were analyzed and compared between the pre-neoadjuvant and post-neoadjuvant specimens.
Results: Based on the 2009 CAP-EP guidelines for HER2:CEP17 ICR, 47% (8/17) of patients had HER2 heterogeneity either pre or post chemotherapy (see below table). The percent amplified cells in these cases increased post-treatment in 63% (5/8) of these cases and decreased in 38% (3/8). Interestingly, 50% (4/8) of cases that had <5% amplified cells by ICR became heterogeneous in the post treatment specimen and one case became amplified (case 3 below). Using ICS criteria, heterogeneity was less common: 0% (0/17) of pre-neoadjuvant and 12% (2/17) of post-neoadjuvant cases had HER2 heterogeneity. Both ICS heterogeneous cases had increased HER2 heterogeneity in the post-neoadjuvant cases (2.5%→8% and 0%→37.5%).

Heterogeneity by HER2:CEP17 ratio (ICR)

	Pre-Neoadjuvant (N=17)	Post-Neoadjuvant (N=17)
Heterogeneous Cases:	% Individual Cells With Ratio >2.2
1	25	4
2	11	0
3	8	63*
4	0	27.5
5	37.5	4
6	0	11.4
7	0	5
8	0	8
Cases With Heterogeneity:	24% (4)	24% (4)

*Amplified >50%; does not meet criteria for heterogeneity


Conclusions: The clinical significance of HER2 heterogeneity by FISH using the CAP-EP recommended criteria is still unclear. Minor populations of amplified cells can both increase and decrease post-chemotherapy and would be reported differently if ICR or ICS criteria are used. We plan to expand these studies to determine if there are more clinically and biologically relevant thresholds that should be used to report HER2 heterogeneity.
Category: Breast

Monday, March 19, 2012 9:30 AM

Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 26, Monday Morning