Impact of 2013 ASCO/CAP HER2 reporting guidelines in breast cancer: An assessment study from Indian oncology centre that primarily performs HER2 IHC testing with special emphasis on IHC equivocal category

Abstract

The ASCO/CAP guidelines for HER2 reporting in breast cancer published in 2007 and were updated in 2013 to assure that the right patient receives the targeted therapy. The updated guidelines have lowered the threshold for HER2 positivity criteria and altered the equivocal category for both IHC and FISH. This first study from India addresses the impact of these updated guidelines in the various reporting categories at a tertiary care centre. We compared the trend of HER2 IHC reporting 1 year before (Period A) and 1 year after (Period B) the implementation of updated 2013 ASCO/CAP guidelines. All HER2 equivocal IHC cases of post 2013 guidelines were reclassified as per 2007 guidelines to detect additional number of cases that have been put into equivocal category. Reflex FISH correlation was also assessed to detect any additional cases eligible for anti HER2 therapy with implementation of these updated guidelines. With implementation of updated 2013 guidelines, there was significant decrease in the number of cases scored as 1+ (from 30.7% to 20.6%; P value: .0001) while significant increase in number of 2+ cases (from 20.2% to 27.3%; P value: .004). Post 2013 guidelines, 39% (64 cases) of tumors were additionally put into the equivocal category which would have been considered as negative (score 1+) as per 2007 guidelines. The reflex FISH testing in these equivocal cases resulted in detection of only 1.5% of additional cases eligible for anti HER2 therapy. With implementation of updated 2013 guidelines, there is no significant increase in HER2 positivity trend. However, there is appreciable increase in IHC equivocal cases which subsequently led to increased reflex FISH testing without significantly contributing to the detection of additional eligible cases for anti HER2 therapy, but resulted in delaying of definite HER2 status along with financial implications.

Impact of 2013 ASCO/CAP guidelines on various HER2 reporting categories in breast cancer by fluorescent in-situ hybridization and Immunohistochemistry: A meta-analysis with systematic review

“…Total 16 studies [11,[13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] were reviewed; of these there were 20 estimates, which has been summarized in web Table 1. This table highlights frequency and percentage of various HER2 reporting categories by FISH and IHC method according to both 2007 and 2013 guidelines.…”

“…The results are shown in Table 3a and b. In IHC category, data of 3 studies [23][24][25] were pooled with effective total sample size was 3056 (cases reported by 2007 guidelines) and 1554 (cases reported by 2013 guidelines). The increase in the equivocal category was from 23.7 to 26.7 % (P value: 0.025) while the increase in the positive category was from 12.9 to 15.8 % (P value: 0.0088), [ Table 3a].…”

Morphological and molecular changes of oestrogen receptor‐positive breast cancer following bridging endocrine therapy: a United Kingdom multicentre study

“…HER2 positivity was defined as an immunohistochemical score of 3+ or a 2+ fluorescence in situ hybridization (FISH)-amplified as per the UK guidelines. 10 If the HER2 immunohistochemical score was 1+ or a 2+ score nonamplified on FISH, this was regarded as HER2-low breast cancer. 11 Detailed pathological review of the residual invasive carcinoma to assess for evidence of pathological response was undertaken.…”