Evaluation of HER-2 neu oncoprotein expression as a prognostic indicator of local recurrence in conservatively treated breast cancer: A case-control study

Bruce G. Haffty, Felix Brown, Darryl Carter, Stuart D Flynn

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Abstract

Purpose: The purpose of this study is to determine the prognostic significance of overexpression of the HER-2 neu oncoprotein with respect to local relapse following conservative surgery and radiation therapy (CS+RT). Methods and Materials: Twenty consecutive patients who sustained a local recurrence as the first and only site of failure following CS+RT comprised the case population base for this study. Only patients who received no adjuvant systemic chemotherapy or tamoxifen were selected for analysis. Following the identification of 20 consecutive local-relapse patients, the patient database was searched for 20 matching control patients who did not sustain a local relapse. Each control patient was matched to the index case with respect to age, menopausal status, follow-up, primary histology, axillary nodal status, and primary tumor size. Both index cases and the matched control group received full course radiation therapy, to a total dose of 64 Gy to the tumor bed. The paraffin-embedded blocks of the original primary tumor of the local-relapse cases and the primary tumor of 20 matched controls were processed for immunohistochemical staining of the HER-2 neu oncoprotein. Each slide was rated on the 3-point scale, 0 representing no stain, 1+ indicating light staining, and 2+ denoted heavy staining (overexpression). Results: Of the 20 index cases, with each of the matched controls, 16 were evaluable for analysis. The 4 cases that were eliminated had inadequate paraffin-embedded material in either the case or the match control for adequate staining. By design of the study, the index case group and control group had similar ages (52 years index vs. 51.4 control), follow- up (10.8 years index vs. 10.5 years control), and histologies. For the immunostaining, a value of 2+ was considered to denote high activity and overexpression, and 0 and 1+ were considered negative values. Using these criteria, a total of 9 of the 16 index cases (56%) exhibited overexpression of HER-2 neu oncoprotein, and only 3 of the 16 control cases (18%) demonstrated high immunoreactivity. The difference in immunostaining between the index and control cases was statistically significant by a Pierson chi- square analysis at the p = 0.03 level. Conclusions: In this matched case- control study, overexpression of the HER-2 neu oncoprotein appears to have prognostic significance with respect to local relapse in the conservatively treated breast. The correlation of overexpression of HER-2 neu by multivariable analysis with other prognostic factors for local recurrence warrants further investigation. The clinical implications of the study are discussed.

Original languageEnglish (US)
Pages (from-to)751-757
Number of pages7
JournalInternational Journal of Radiation Oncology Biology Physics
Volume35
Issue number4
DOIs
StatePublished - Jul 1 1996
Externally publishedYes

Fingerprint

Oncogene Proteins
breast
Case-Control Studies
cancer
Breast Neoplasms
Recurrence
evaluation
Staining and Labeling
staining
Paraffin
tumors
Neoplasms
Histology
Radiotherapy
histology
paraffins
Control Groups
Tamoxifen
Adjuvant Chemotherapy
radiation therapy

Keywords

  • Conservative surgery
  • HER-2 neu
  • Local recurrence
  • Radiation therapy

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Radiation

Cite this

@article{3c35ae34d49d4416a0d8c71e5e4efcd8,
title = "Evaluation of HER-2 neu oncoprotein expression as a prognostic indicator of local recurrence in conservatively treated breast cancer: A case-control study",
abstract = "Purpose: The purpose of this study is to determine the prognostic significance of overexpression of the HER-2 neu oncoprotein with respect to local relapse following conservative surgery and radiation therapy (CS+RT). Methods and Materials: Twenty consecutive patients who sustained a local recurrence as the first and only site of failure following CS+RT comprised the case population base for this study. Only patients who received no adjuvant systemic chemotherapy or tamoxifen were selected for analysis. Following the identification of 20 consecutive local-relapse patients, the patient database was searched for 20 matching control patients who did not sustain a local relapse. Each control patient was matched to the index case with respect to age, menopausal status, follow-up, primary histology, axillary nodal status, and primary tumor size. Both index cases and the matched control group received full course radiation therapy, to a total dose of 64 Gy to the tumor bed. The paraffin-embedded blocks of the original primary tumor of the local-relapse cases and the primary tumor of 20 matched controls were processed for immunohistochemical staining of the HER-2 neu oncoprotein. Each slide was rated on the 3-point scale, 0 representing no stain, 1+ indicating light staining, and 2+ denoted heavy staining (overexpression). Results: Of the 20 index cases, with each of the matched controls, 16 were evaluable for analysis. The 4 cases that were eliminated had inadequate paraffin-embedded material in either the case or the match control for adequate staining. By design of the study, the index case group and control group had similar ages (52 years index vs. 51.4 control), follow- up (10.8 years index vs. 10.5 years control), and histologies. For the immunostaining, a value of 2+ was considered to denote high activity and overexpression, and 0 and 1+ were considered negative values. Using these criteria, a total of 9 of the 16 index cases (56{\%}) exhibited overexpression of HER-2 neu oncoprotein, and only 3 of the 16 control cases (18{\%}) demonstrated high immunoreactivity. The difference in immunostaining between the index and control cases was statistically significant by a Pierson chi- square analysis at the p = 0.03 level. Conclusions: In this matched case- control study, overexpression of the HER-2 neu oncoprotein appears to have prognostic significance with respect to local relapse in the conservatively treated breast. The correlation of overexpression of HER-2 neu by multivariable analysis with other prognostic factors for local recurrence warrants further investigation. The clinical implications of the study are discussed.",
keywords = "Conservative surgery, HER-2 neu, Local recurrence, Radiation therapy",
author = "Haffty, {Bruce G.} and Felix Brown and Darryl Carter and Flynn, {Stuart D}",
year = "1996",
month = "7",
day = "1",
doi = "10.1016/0360-3016(96)00150-2",
language = "English (US)",
volume = "35",
pages = "751--757",
journal = "International Journal of Radiation Oncology Biology Physics",
issn = "0360-3016",
publisher = "Elsevier Inc.",
number = "4",

}

TY - JOUR

T1 - Evaluation of HER-2 neu oncoprotein expression as a prognostic indicator of local recurrence in conservatively treated breast cancer

T2 - A case-control study

AU - Haffty, Bruce G.

AU - Brown, Felix

AU - Carter, Darryl

AU - Flynn, Stuart D

PY - 1996/7/1

Y1 - 1996/7/1

N2 - Purpose: The purpose of this study is to determine the prognostic significance of overexpression of the HER-2 neu oncoprotein with respect to local relapse following conservative surgery and radiation therapy (CS+RT). Methods and Materials: Twenty consecutive patients who sustained a local recurrence as the first and only site of failure following CS+RT comprised the case population base for this study. Only patients who received no adjuvant systemic chemotherapy or tamoxifen were selected for analysis. Following the identification of 20 consecutive local-relapse patients, the patient database was searched for 20 matching control patients who did not sustain a local relapse. Each control patient was matched to the index case with respect to age, menopausal status, follow-up, primary histology, axillary nodal status, and primary tumor size. Both index cases and the matched control group received full course radiation therapy, to a total dose of 64 Gy to the tumor bed. The paraffin-embedded blocks of the original primary tumor of the local-relapse cases and the primary tumor of 20 matched controls were processed for immunohistochemical staining of the HER-2 neu oncoprotein. Each slide was rated on the 3-point scale, 0 representing no stain, 1+ indicating light staining, and 2+ denoted heavy staining (overexpression). Results: Of the 20 index cases, with each of the matched controls, 16 were evaluable for analysis. The 4 cases that were eliminated had inadequate paraffin-embedded material in either the case or the match control for adequate staining. By design of the study, the index case group and control group had similar ages (52 years index vs. 51.4 control), follow- up (10.8 years index vs. 10.5 years control), and histologies. For the immunostaining, a value of 2+ was considered to denote high activity and overexpression, and 0 and 1+ were considered negative values. Using these criteria, a total of 9 of the 16 index cases (56%) exhibited overexpression of HER-2 neu oncoprotein, and only 3 of the 16 control cases (18%) demonstrated high immunoreactivity. The difference in immunostaining between the index and control cases was statistically significant by a Pierson chi- square analysis at the p = 0.03 level. Conclusions: In this matched case- control study, overexpression of the HER-2 neu oncoprotein appears to have prognostic significance with respect to local relapse in the conservatively treated breast. The correlation of overexpression of HER-2 neu by multivariable analysis with other prognostic factors for local recurrence warrants further investigation. The clinical implications of the study are discussed.

AB - Purpose: The purpose of this study is to determine the prognostic significance of overexpression of the HER-2 neu oncoprotein with respect to local relapse following conservative surgery and radiation therapy (CS+RT). Methods and Materials: Twenty consecutive patients who sustained a local recurrence as the first and only site of failure following CS+RT comprised the case population base for this study. Only patients who received no adjuvant systemic chemotherapy or tamoxifen were selected for analysis. Following the identification of 20 consecutive local-relapse patients, the patient database was searched for 20 matching control patients who did not sustain a local relapse. Each control patient was matched to the index case with respect to age, menopausal status, follow-up, primary histology, axillary nodal status, and primary tumor size. Both index cases and the matched control group received full course radiation therapy, to a total dose of 64 Gy to the tumor bed. The paraffin-embedded blocks of the original primary tumor of the local-relapse cases and the primary tumor of 20 matched controls were processed for immunohistochemical staining of the HER-2 neu oncoprotein. Each slide was rated on the 3-point scale, 0 representing no stain, 1+ indicating light staining, and 2+ denoted heavy staining (overexpression). Results: Of the 20 index cases, with each of the matched controls, 16 were evaluable for analysis. The 4 cases that were eliminated had inadequate paraffin-embedded material in either the case or the match control for adequate staining. By design of the study, the index case group and control group had similar ages (52 years index vs. 51.4 control), follow- up (10.8 years index vs. 10.5 years control), and histologies. For the immunostaining, a value of 2+ was considered to denote high activity and overexpression, and 0 and 1+ were considered negative values. Using these criteria, a total of 9 of the 16 index cases (56%) exhibited overexpression of HER-2 neu oncoprotein, and only 3 of the 16 control cases (18%) demonstrated high immunoreactivity. The difference in immunostaining between the index and control cases was statistically significant by a Pierson chi- square analysis at the p = 0.03 level. Conclusions: In this matched case- control study, overexpression of the HER-2 neu oncoprotein appears to have prognostic significance with respect to local relapse in the conservatively treated breast. The correlation of overexpression of HER-2 neu by multivariable analysis with other prognostic factors for local recurrence warrants further investigation. The clinical implications of the study are discussed.

KW - Conservative surgery

KW - HER-2 neu

KW - Local recurrence

KW - Radiation therapy

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