HER2 protein and gene variation between primary and metastatic breast cancer: Significance and impact on patient care

Alessandra Fabi, Anna Di Benedetto, Giulio Metro, Letizia Perracchio, Cecilia Nisticò, Franco Di Filippo, Cristiana Ercolani, Gianluigi Ferretti, Elisa Melucci, Simonetta Buglioni, Isabella Sperduti, Paola Papaldo, Francesco Cognetti, Marcella Mottolese

Research output: Contribution to journalArticle

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Abstract

Purpose: To analyze HER2 status in primary breast cancer (PBC) 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 in situ hybridization (SISH), and FISH, in a series of 137 tumors, building up a tissue microarray to concurrently analyze each single PBC and metastatic (MBC) on the same slide. Results: HER2 status was discordant in 14 cases (10%): 12 negative in PBC and positive in metastases and two positive in PBC 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 nonamplified cases. Conversely, of the 23 amplified PBC, 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.

Original languageEnglish
Pages (from-to)2055-2064
Number of pages10
JournalClinical Cancer Research
Volume17
Issue number7
DOIs
Publication statusPublished - Apr 1 2011

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erbB-2 Genes
Patient Care
Breast Neoplasms
Neoplasm Metastasis
Silver
In Situ Hybridization
Chromosomes, Human, Pair 17
Multiplex Polymerase Chain Reaction
Proteins
Hormones
Gene Dosage
Research Design
Immunohistochemistry
Phenotype
Polymerase Chain Reaction
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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HER2 protein and gene variation between primary and metastatic breast cancer : Significance and impact on patient care. / Fabi, Alessandra; Di Benedetto, Anna; Metro, Giulio; Perracchio, Letizia; Nisticò, Cecilia; Di Filippo, Franco; Ercolani, Cristiana; Ferretti, Gianluigi; Melucci, Elisa; Buglioni, Simonetta; Sperduti, Isabella; Papaldo, Paola; Cognetti, Francesco; Mottolese, Marcella.

In: Clinical Cancer Research, Vol. 17, No. 7, 01.04.2011, p. 2055-2064.

Research output: Contribution to journalArticle

Fabi, A, Di Benedetto, A, Metro, G, Perracchio, L, Nisticò, C, Di Filippo, F, Ercolani, C, Ferretti, G, Melucci, E, Buglioni, S, Sperduti, I, Papaldo, P, Cognetti, F & Mottolese, M 2011, 'HER2 protein and gene variation between primary and metastatic breast cancer: Significance and impact on patient care', Clinical Cancer Research, vol. 17, no. 7, pp. 2055-2064. https://doi.org/10.1158/1078-0432.CCR-10-1920
Fabi, Alessandra ; Di Benedetto, Anna ; Metro, Giulio ; Perracchio, Letizia ; Nisticò, Cecilia ; Di Filippo, Franco ; Ercolani, Cristiana ; Ferretti, Gianluigi ; Melucci, Elisa ; Buglioni, Simonetta ; Sperduti, Isabella ; Papaldo, Paola ; Cognetti, Francesco ; Mottolese, Marcella. / HER2 protein and gene variation between primary and metastatic breast cancer : Significance and impact on patient care. In: Clinical Cancer Research. 2011 ; Vol. 17, No. 7. pp. 2055-2064.
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T1 - HER2 protein and gene variation between primary and metastatic breast cancer

T2 - Significance and impact on patient care

AU - Fabi, Alessandra

AU - Di Benedetto, Anna

AU - Metro, Giulio

AU - Perracchio, Letizia

AU - Nisticò, Cecilia

AU - Di Filippo, Franco

AU - Ercolani, Cristiana

AU - Ferretti, Gianluigi

AU - Melucci, Elisa

AU - Buglioni, Simonetta

AU - Sperduti, Isabella

AU - Papaldo, Paola

AU - Cognetti, Francesco

AU - Mottolese, Marcella

PY - 2011/4/1

Y1 - 2011/4/1

N2 - Purpose: To analyze HER2 status in primary breast cancer (PBC) 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 in situ hybridization (SISH), and FISH, in a series of 137 tumors, building up a tissue microarray to concurrently analyze each single PBC and metastatic (MBC) on the same slide. Results: HER2 status was discordant in 14 cases (10%): 12 negative in PBC and positive in metastases and two positive in PBC 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 nonamplified cases. Conversely, of the 23 amplified PBC, 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.

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