M Ragazzi1, A Bisagni2, E Gasparini3, E Kuhn4, C Bassano2, I Tamagnini2, M Foroni2, M Bortesi2, G Falco5, G Ferrari5, L Braglia6, L Savoldi6, A Bologna7, R Di Cicilia7, G Bisagni7, G Gardini2. 1. Anatomic Pathology Unit, Arcispedale S. Maria Nuova-IRCCS, viale Risorgimento 80, 42123, Reggio Emilia, Italy. Electronic address: moira.ragazzi@asmn.re.it. 2. Anatomic Pathology Unit, Arcispedale S. Maria Nuova-IRCCS, viale Risorgimento 80, 42123, Reggio Emilia, Italy. 3. Department of Oncology, Scandiano Hospital, Via Martiri della Libertà 6, 42019, Scandiano, RE, Italy. 4. Department of Morphology, Surgery and Experimental Medicine and Laboratory of Technology for Advanced Therapies (LTTA), University of Ferrara, Via Fossato di Mortara 70, 44124, Ferrara, Italy. Electronic address: elisabettakuhn@hotmail.it. 5. Breast Surgery, Arcispedale S. Maria Nuova-IRCCS, viale Risorgimento 80, 42123, Reggio Emilia, Italy. 6. Scientific Directorate, Arcispedale S. Maria Nuova-IRCCS, viale Risorgimento 80, 42123, Reggio Emilia, Italy. 7. Department of Oncology, Arcispedale S. Maria Nuova-IRCCS, viale Risorgimento 80, 42123, Reggio Emilia, Italy.
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.
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.
Authors: Sally Agersborg; Christopher Mixon; Thanh Nguyen; Sramila Aithal; Sucha Sudarsanam; Forrest Blocker; Lawrence Weiss; Robert Gasparini; Shiping Jiang; Wayne Chen; Gregory Hess; Maher Albitar Journal: Breast Cancer Res Treat Date: 2018-03-22 Impact factor: 4.872
Authors: Caterina Marchiò; Patrizia Dell'Orto; Laura Annaratone; Felipe C Geyer; Tiziana Venesio; Enrico Berrino; Ludovica Verdun di Cantogno; Andrea Garofoli; Nelson Rangel; Laura Casorzo; Carmine dell'Aglio; Patrizia Gugliotta; Elena Trisolini; Alessandra Beano; Francesca Pietribiasi; Renzo Orlassino; Paola Cassoni; Achille Pich; Filippo Montemurro; Marcella Mottolese; Anne Vincent-Salomon; Frédérique Penault-Llorca; Enzo Medico; Charlotte K Y Ng; Giuseppe Viale; Anna Sapino Journal: Am J Surg Pathol Date: 2018-09 Impact factor: 6.394