Impact of 2013 ASCO/CAP Guidelines on HER2 Determination of Invasive Breast Cancer: A Single Institution Experience Using Frontline Dual-Color FISH.

1028 Background: ASCO/CAP new guidelines published in 2013 (AC2013) significantly modified the scoring criteria for HER2-FISH. We retrospectively evaluated the impact of AC2013 in a five-year cohort of consecutive invasive breast cancers (IBCs) underwent frontline dual-color FISH. Furthermore, we applied three different reflex tests and investigated clinical outcomes of patients with HER2-equivocal IBC. Methods: 2788 consecutive IBCs that underwent frontline HER2/CEP17 determination in our institution from January 2009 to December 2013 were reclassified based on the AC2013 guidelines. FISH HER2-equivocal cases underwent reflex tests: HER2-IHC, RARA-FISH, and SMS-FISH. Clinico-pathological correlation was performed. Results: Two hundred HER2-negative cases (7.2%) were classified differently based on the AC2013: 0.3% (8/2788) became HER2-positive and 6.9% (192/2788) HER2-equivocal. AC2013 equivocal-IBCs represented a subgroup of grade 3, luminal-like subtype IBCs, in patients with a higher age. After reflex tests, among 190 equivocal cases 102 (53.7%) were reclassified as HER2-positive, 51 (26.8%) negative and 37 (19.5%) equivocal. IHC resulted negative in 44.7% (85), whereas SMS-FISH showed the highest percentage of positive results (45.8%). No statistically significant differences were identified in the disease-free and overall survival. Conclusions: AC2013 compared with AC2007 significantly increased initial HER2-equivocal cases (6.9%vs1.6%, p < 0.001). After reflex testing, 4.5% of patients not treated with anti-HER2 therapy (either HER2-positive or “ultimate equivocal”) resulted eligible to trastuzumab, but showed clinical outcome comparable with AC2007 HER2-positive patients, treated with trastuzumab. Our findings belittle the clinical impact of AC2013 HER2-equivocal reclassification; accordingly further studies are necessary to justify this category and the reclassification efforts by additional reflex tests.