High HER2/Centromeric Probe for Chromosome 17 Fluorescence In Situ Hybridization Ratio Predicts Pathologic Complete Response and Survival Outcome in Patients Receiving Neoadjuvant Systemic Therapy With Trastuzumab for HER2-Overexpressing Locally Advanced Breast Cancer

Abstract

Key Words. HER21 breast cancer x HER2/centromeric probe for chromosome 17 fluorescence in situ hybridization ratio x Trastuzumab x Predictive factor x Pathologic complete response ABSTRACTBackground. The present study was performed to determine whether the human epidermal growth factor receptor-related 2 (HER2)/centromeric probe for chromosome 17 fluorescence in situ hybridization (FISH) ratio is a predictor of a pathologic complete response (pCR), recurrence-free survival (RFS), and/or overall survival (OS) in patients receiving neoadjuvant systemic treatment (NST) with trastuzumab (NST-T) for HER21 locally advanced breast cancer (LABC). Patients and Methods. The present retrospective study included 555 patients with HER21 LABC who had undergone NST and definitive surgery (1999)(2000)(2001)(2002)(2003)(2004)(2005)(2006)(2007)(2008)(2009)(2010)(2011)(2012); 373 had concurrently received trastuzumab. HER2-positivity was considered present with an immunohistochemical score of 31 and/or HER2 FISH ratio of $2.0. We used logistic regression analysis and Cox proportional hazard modeling to determine whether a high HER2 FISH ratio,

Prognostic significance of equivocal human epidermal growth factor receptor 2 results and clinical utility of alternative chromosome 17 genes in patients with invasive breast cancer: A cohort study

“…Of the 46 cases, 43.5% showed 2 1 HER2 protein expression (equivocal results), and 47.8% were negative (11). Only 2 cases were positive (31), and these cases remained equivocal/unchanged with the use of SMS/RARA genes. No correlation was found between the distribution of IHC scores and HER2 FISH results before and after the use of alternative Ch17Ps (P 5 .24; Table 2).…”

“…In one study, the pathological complete response rate for trastuzumab‐based neoadjuvant therapy was significantly higher for high‐amplification tumors (defined as > 10 signals per nucleus) versus low‐amplification tumors (defined as 6‐10 signals per nucleus; 56% vs 22%; P = .005) . Other studies have shown that a high HER2/CEP17 ratio is a significant predictor of progression‐free survival in patients with metastatic breast cancer treated with chemotherapy and trastuzumab, and a ratio ≥ 7.0 was also a predictor of a pathological complete response in patients with locally advanced breast cancer who received neoadjuvant chemotherapy and trastuzumab . However, in National Surgical Adjuvant Breast and Bowel Project (NSABP) trial B‐31, no significant association between the HER2 copy number and a benefit from adjuvant trastuzumab was found, and even patients with normal gene copy numbers appeared to benefit from trastuzumab .…”

“…Furthermore, the treatment response to targeted therapy may vary with the HER2 copy numbers or the HER2/CEP17 ratio. [29][30][31][32][33] In one study, the pathological complete response rate for trastuzumab-based neoadjuvant therapy was significantly higher for high-amplification tumors (defined as > 10 signals per nucleus) versus lowamplification tumors (defined as 6-10 signals per nucleus; 56% vs 22%; P 5 .005). 29 Other studies have shown that a high HER2/CEP17 ratio is a significant predictor of progression-free survival 30 in patients with metastatic breast cancer treated with chemotherapy and trastuzumab, and a ratio 7.0 was also a predictor of a pathological complete response in patients with locally advanced breast cancer who received neoadjuvant chemotherapy and trastuzumab.…”

“…Only 2 of our 46 cases showed 3 + protein overexpression, and the remaining cases were distributed among 1 + and 2 + protein expression, regardless of the changes in the HER2 gene status resulting from the use of alternative Ch17Ps ( P = .24). Furthermore, the treatment response to targeted therapy may vary with the HER2 copy numbers or the HER2/CEP17 ratio . In one study, the pathological complete response rate for trastuzumab‐based neoadjuvant therapy was significantly higher for high‐amplification tumors (defined as > 10 signals per nucleus) versus low‐amplification tumors (defined as 6‐10 signals per nucleus; 56% vs 22%; P = .005) .…”

“…29 Other studies have shown that a high HER2/CEP17 ratio is a significant predictor of progression-free survival 30 in patients with metastatic breast cancer treated with chemotherapy and trastuzumab, and a ratio 7.0 was also a predictor of a pathological complete response in patients with locally advanced breast cancer who received neoadjuvant chemotherapy and trastuzumab. 31 However, in National Surgical Adjuvant Breast and Bowel Project (NSABP) trial B-31, no significant association between the HER2 copy number and a benefit from adjuvant trastuzumab was found, and even patients with normal gene copy numbers appeared to benefit from trastuzumab. 32 In a subsequent analysis, 33 using a gene expression profile, the authors developed a model that could predict the degree of benefit from trastuzumab and also demonstrated that that patients with HER2negative tumors belong to the moderate-benefit group.…”