Impact of 2013 ASCO/CAP guidelines on HER2 determination of invasive breast cancer: A single institution experience using frontline dual-color FISH

Breast. 2017 Aug:34:65-72. doi: 10.1016/j.breast.2017.05.001. Epub 2017 May 15.

Abstract

Purpose: The new ASCO/CAP guidelines published in 2013 (AC2013) significantly modified the scoring criteria for HER2-FISH, introducing the most controversial change to the HER2-equivocal category. We retrospectively evaluated the impact of AC2013 in a cohort of consecutive invasive breast cancers (IBCs) analyzed with frontline dual-color FISH.

Methods: 2788 consecutive IBCs were reclassified based on the AC2013 guidelines. Clinico-pathological features of equivocal IBCs were compared with HER2-negative and HER2-positive IBCs. FISH HER2-equivocal cases underwent reflex tests: HER2-IHC, RARA-FISH, and SMS-FISH. Overall and disease-free survivals were evaluated in AC2007 HER2-positive patients treated with trastuzumab and in patients that became eligible for target-therapy according to AC2013.

Results: Two-hundred HER2-negative cases (7.2%) were classified differently, following AC2013: 0.3% (8/2788) became HER2-positive and 6.9% (192/2788) HER2-equivocal. AC2013, compared with AC2007, significantly increased initial HER2-equivocal cases (6.9%vs1.6%, p < 0.001). AC2013 equivocal-IBCs affected older patients and showed pathological features between HER2-negative and HER2-positive IBCs. After reflex tests, 102 of the 190 equivocal cases (53.7%) were reclassified as HER2-positive, 51 (26.8%) as negative and 37 (19.5%) as equivocal. IHC tested negative in 44.7% of cases, whereas SMS-FISH showed the highest percentage of positive results (45.8%). Clinical outcomes showed no statistically significant differences.

Conclusion: Overall, 80.5% of FISH-equivocal cases were solved with at least one reflex test and 3.6% of patients became AC2013 HER2-positive, therefore eligible for target-therapy, but showed clinical outcomes similar to HER2-positive patients treated with trastuzumab. Our data belittle the clinical impact of AC2013 HER2-equivocal reclassification; further prospective randomized clinical studies are necessary to support these findings.

Keywords: ASCO-CAP; Breast cancer; Equivocal; FISH; HER2; Polysomy; Reflex tests.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Immunological / therapeutic use
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms, Male / genetics
  • Breast Neoplasms, Male / metabolism
  • Carcinoma, Ductal, Breast / drug therapy
  • Carcinoma, Ductal, Breast / genetics*
  • Carcinoma, Ductal, Breast / metabolism
  • Chromosome Aberrations
  • Chromosomes, Human, Pair 17
  • Disease-Free Survival
  • Female
  • Gene Dosage
  • Genetic Testing / standards
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence / methods
  • Male
  • Middle Aged
  • Practice Guidelines as Topic
  • Receptor, ErbB-2 / genetics*
  • Receptor, ErbB-2 / metabolism
  • Retinoic Acid Receptor alpha / genetics
  • Retrospective Studies
  • Smith-Magenis Syndrome / genetics
  • Survival Rate
  • Trastuzumab / therapeutic use
  • Young Adult

Substances

  • Antineoplastic Agents, Immunological
  • RARA protein, human
  • Retinoic Acid Receptor alpha
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Trastuzumab