HER2 change between primary and metastatic breast cancer 1 HER2 PROTEIN AND GENE VARIATION BETWEEN PRIMARY AND METASTATIC BREAST CANCER: SIGNIFICANCE AND IMPACT ON PATIENT CARE

Purpose: To analyze HER2 status in primary breast cancer (BC) compared with correspondent metachronous metastases and to investigate whether BC phenotype may be predictive of change in HER2 expression. Experimental Design: HER2 was investigated by immunohistochemistry, silver (SISH) and fluorescent in situ hybridization (FISH), in a series of 137 tumors, building up a tissue microarray to concurrently analyze each single primary and metastatic BC on the same slide. Results: HER2 status was discordant in 14 cases (10%): 12 negative in primary BC and positive in metastases and 2 positive in primary BC and negative in metastases (p=0.04). These findings were confirmed by a PCR based test termed Multiplex Ligation-dependent Probe Amplification (MLPA). HER2 status changed in hormone receptor-positive BC more frequently than in negative ones (p= 0.002). In addition, we evaluated HER2 gene and chromosome 17 copy number by SISH in the 123 cases with unchanged HER2 status during progression. We found consistent HER2 gene copy number stability in the 100 non-amplified cases. Conversely, of the 23 amplified primary BC, 13 (57%) demonstrated a significant increase in the HER2 gene and chromosome 17 copy number in their paired metastases (p=0.01), as defined by SISH (k= 0.54, p <0.0001) and MLPA. Patients who changed HER2 status from negative to positive, presented significant longer time to progression when treated with trastuzumab compared to those who were untreated (p=0.04). Conclusions: When feasible, HER2 reassessment in metastatic lesions should be carefully taken into account, especially for metastases coming from primary hormone receptor-positive BC. Research. on November 11, 2017. © 2011 American Association for Cancer clincancerres.aacrjournals.org Downloaded from Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on February 9, 2011; DOI: 10.1158/1078-0432.CCR-10-1920