Moderate immunohistochemical expression of her-2 (2) without her-2 gene amplification is a negative prognostic factor in early breast cancer

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Abstract

Background. Human epidermal growth factor receptor (HER)-2 testing in patients with operable breast cancer is aimed at identifying candidates for adjuvant anti-HER-2 treatment. However, commonly defined "HER-2-" tumors express variable levels of the HER-2 protein, which can influence prognosis. We compared the clinical outcomes of operable breast cancer patients stratified according to a common HER-2 testing algorithm. Methods. We studied 1,150 women (median age, 58 years; range, 22-94 years) undergoing surgery for early breast cancer at our institution. HER-2 status was determined using the HercepTest™ (Dako, Glostrup, Denmark) and, when needed, by fluorescence in situ hybridization (FISH). Patients receiving adjuvant trastuzumab were excluded. The impact of HER-2 status on the disease-free survival (DFS) time was studied using multivariate Cox proportional regression analysis. Results. Four hundred-fifty seven (40%), 454 (39%), 116 (10%), and 123 (11%) patients were considered HER-2 0+, HER-2 1+, HER-2 2+/HER-2- by FISH, and HER-2+ (3+ or HER-2+ by FISH), respectively. Compared with a HER-2 0 or 1+ status, a HER-2 2-/HER-2+ by FISH status was associated with a worse DFS outcome on multivariate analysis. Compared with a HER-2+ status, a HER-2 2+/HER-2- status showed a time-dependent effect on the DFS probability, with an initial advantage that worsened every year by a factor of 1.649. Conclusion. A HER-2 2-/HER-2- status is an adverse prognostic factor in patients with operable breast cancer. Because of suggestions from randomized trials that the benefits of adjuvant trastuzumab may not be limited to patients with HER-2+ tumors, patients with a HER-2 2+/ HER-2- status are ideal candidates for studies testing this hypothesis.

Original languageEnglish
Pages (from-to)1418-1425
Number of pages8
JournalThe oncologist
Volume17
Issue number11
DOIs
Publication statusPublished - Nov 2012

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Gene Amplification
Breast Neoplasms
Fluorescence In Situ Hybridization
Disease-Free Survival
Denmark
Neoplasms
Multivariate Analysis
Regression Analysis
Proteins

Keywords

  • Breast cancer
  • Fluorescence in situ hybridization
  • Her-2
  • Immunohistochemistry
  • Prognosis

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

@article{542f8d30a4294681bd9a426a64cf7a92,
title = "Moderate immunohistochemical expression of her-2 (2) without her-2 gene amplification is a negative prognostic factor in early breast cancer",
abstract = "Background. Human epidermal growth factor receptor (HER)-2 testing in patients with operable breast cancer is aimed at identifying candidates for adjuvant anti-HER-2 treatment. However, commonly defined {"}HER-2-{"} tumors express variable levels of the HER-2 protein, which can influence prognosis. We compared the clinical outcomes of operable breast cancer patients stratified according to a common HER-2 testing algorithm. Methods. We studied 1,150 women (median age, 58 years; range, 22-94 years) undergoing surgery for early breast cancer at our institution. HER-2 status was determined using the HercepTest™ (Dako, Glostrup, Denmark) and, when needed, by fluorescence in situ hybridization (FISH). Patients receiving adjuvant trastuzumab were excluded. The impact of HER-2 status on the disease-free survival (DFS) time was studied using multivariate Cox proportional regression analysis. Results. Four hundred-fifty seven (40{\%}), 454 (39{\%}), 116 (10{\%}), and 123 (11{\%}) patients were considered HER-2 0+, HER-2 1+, HER-2 2+/HER-2- by FISH, and HER-2+ (3+ or HER-2+ by FISH), respectively. Compared with a HER-2 0 or 1+ status, a HER-2 2-/HER-2+ by FISH status was associated with a worse DFS outcome on multivariate analysis. Compared with a HER-2+ status, a HER-2 2+/HER-2- status showed a time-dependent effect on the DFS probability, with an initial advantage that worsened every year by a factor of 1.649. Conclusion. A HER-2 2-/HER-2- status is an adverse prognostic factor in patients with operable breast cancer. Because of suggestions from randomized trials that the benefits of adjuvant trastuzumab may not be limited to patients with HER-2+ tumors, patients with a HER-2 2+/ HER-2- status are ideal candidates for studies testing this hypothesis.",
keywords = "Breast cancer, Fluorescence in situ hybridization, Her-2, Immunohistochemistry, Prognosis",
author = "Valentina Rossi and Ivana Sarotto and Furio Maggiorotto and Paola Berchialla and Franziska Kubatzki and Nicoletta Tomasi and Stefania Redana and Rossella Martinello and Giorgio Valabrega and Massimo Aglietta and Riccardo Ponzone and Filippo Montemurro",
year = "2012",
month = "11",
doi = "10.1634/theoncologist.2012-0194",
language = "English",
volume = "17",
pages = "1418--1425",
journal = "Oncologist",
issn = "1083-7159",
publisher = "Wiley Blackwell",
number = "11",

}

TY - JOUR

T1 - Moderate immunohistochemical expression of her-2 (2) without her-2 gene amplification is a negative prognostic factor in early breast cancer

AU - Rossi, Valentina

AU - Sarotto, Ivana

AU - Maggiorotto, Furio

AU - Berchialla, Paola

AU - Kubatzki, Franziska

AU - Tomasi, Nicoletta

AU - Redana, Stefania

AU - Martinello, Rossella

AU - Valabrega, Giorgio

AU - Aglietta, Massimo

AU - Ponzone, Riccardo

AU - Montemurro, Filippo

PY - 2012/11

Y1 - 2012/11

N2 - Background. Human epidermal growth factor receptor (HER)-2 testing in patients with operable breast cancer is aimed at identifying candidates for adjuvant anti-HER-2 treatment. However, commonly defined "HER-2-" tumors express variable levels of the HER-2 protein, which can influence prognosis. We compared the clinical outcomes of operable breast cancer patients stratified according to a common HER-2 testing algorithm. Methods. We studied 1,150 women (median age, 58 years; range, 22-94 years) undergoing surgery for early breast cancer at our institution. HER-2 status was determined using the HercepTest™ (Dako, Glostrup, Denmark) and, when needed, by fluorescence in situ hybridization (FISH). Patients receiving adjuvant trastuzumab were excluded. The impact of HER-2 status on the disease-free survival (DFS) time was studied using multivariate Cox proportional regression analysis. Results. Four hundred-fifty seven (40%), 454 (39%), 116 (10%), and 123 (11%) patients were considered HER-2 0+, HER-2 1+, HER-2 2+/HER-2- by FISH, and HER-2+ (3+ or HER-2+ by FISH), respectively. Compared with a HER-2 0 or 1+ status, a HER-2 2-/HER-2+ by FISH status was associated with a worse DFS outcome on multivariate analysis. Compared with a HER-2+ status, a HER-2 2+/HER-2- status showed a time-dependent effect on the DFS probability, with an initial advantage that worsened every year by a factor of 1.649. Conclusion. A HER-2 2-/HER-2- status is an adverse prognostic factor in patients with operable breast cancer. Because of suggestions from randomized trials that the benefits of adjuvant trastuzumab may not be limited to patients with HER-2+ tumors, patients with a HER-2 2+/ HER-2- status are ideal candidates for studies testing this hypothesis.

AB - Background. Human epidermal growth factor receptor (HER)-2 testing in patients with operable breast cancer is aimed at identifying candidates for adjuvant anti-HER-2 treatment. However, commonly defined "HER-2-" tumors express variable levels of the HER-2 protein, which can influence prognosis. We compared the clinical outcomes of operable breast cancer patients stratified according to a common HER-2 testing algorithm. Methods. We studied 1,150 women (median age, 58 years; range, 22-94 years) undergoing surgery for early breast cancer at our institution. HER-2 status was determined using the HercepTest™ (Dako, Glostrup, Denmark) and, when needed, by fluorescence in situ hybridization (FISH). Patients receiving adjuvant trastuzumab were excluded. The impact of HER-2 status on the disease-free survival (DFS) time was studied using multivariate Cox proportional regression analysis. Results. Four hundred-fifty seven (40%), 454 (39%), 116 (10%), and 123 (11%) patients were considered HER-2 0+, HER-2 1+, HER-2 2+/HER-2- by FISH, and HER-2+ (3+ or HER-2+ by FISH), respectively. Compared with a HER-2 0 or 1+ status, a HER-2 2-/HER-2+ by FISH status was associated with a worse DFS outcome on multivariate analysis. Compared with a HER-2+ status, a HER-2 2+/HER-2- status showed a time-dependent effect on the DFS probability, with an initial advantage that worsened every year by a factor of 1.649. Conclusion. A HER-2 2-/HER-2- status is an adverse prognostic factor in patients with operable breast cancer. Because of suggestions from randomized trials that the benefits of adjuvant trastuzumab may not be limited to patients with HER-2+ tumors, patients with a HER-2 2+/ HER-2- status are ideal candidates for studies testing this hypothesis.

KW - Breast cancer

KW - Fluorescence in situ hybridization

KW - Her-2

KW - Immunohistochemistry

KW - Prognosis

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