HER-2/neu amplification in benign breast disease and the risk of subsequent breast cancer

Azadeh Stark, Barbara S. Hulka, Scott Joens, Debra Novotny, Ann D. Thor, Lester E. Wold, Michael J. Schell, L. Joseph Melton, Edison T. Liu, Kathleen Conway

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Abstract

Purpose: The purpose of this study was to determine whether the presence of HER-2/neu gene amplification and/or overexpression in benign breast disease was associated with an increased risk of subsequent breast cancer. Patients and Methods: We conducted a nested case-control study of a cohort of women who were diagnosed with benign breast disease at the Mayo Clinic and who were subsequently observed for the development of breast cancer. Patients who developed breast cancer formed the case group, and a matched sample from the remaining cohort served as controls. Benign tissue samples from 137 cases and 156 controls and malignant tissues from 99 cases provided DNA or tissue for evaluation of HER-2/neu amplification and protein overexpression. Results: Among the controls, seven benign tissues (4.5%) demonstrated low- level HER-2/neu amplification, whereas 13 benign (9.5%) and 18 malignant (18%) tissue specimens from cases exhibited amplification. HER-2/neu amplification in benign breast biopsies was associated with an increased risk of breast cancer (odds ratio [OR] = 2.2; 95% confidence interval [CI], 0.9 to 5.8); this association approached statistical significance. The risks for breast cancer associated with benign breast histopathologic diagnoses were OR = 1.1 (95% CI, 0.6 to 1.9) for lesions exhibiting proliferation without atypia and OR = 1.5 (95% CI, 0.4 to 5.6) for the diagnosis of atypical ductal hyperplasia. For women having both HER-2/neu amplification and a proliferative histopathologic diagnosis (either typical or atypical), the risk of breast cancer was more than seven-fold (OR = 7.2; 95% CI, 0.9 to 60.8). Overexpression of the HER-2/neu protein product, defined as membrane staining in 10% or more of epithelial cells, was found in 30% of the breast tumors but was not detected in any of the benign breast tissues. Case patients who had HER2/neu gene amplification in their malignant tumor were more likely to have had HER-2/neu amplification in their prior benign biopsy (P = .06, Fisher's exact test). Conclusion: Women with benign breast biopsies demonstrating both HER-2/neu amplification and a proliferative histopathologic diagnosis may be at substantially increased risk for subsequent breast cancer.

Original languageEnglish (US)
Pages (from-to)267-274
Number of pages8
JournalJournal of Clinical Oncology
Volume18
Issue number2
StatePublished - Jan 2000

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Breast Diseases
Breast Neoplasms
erbB-2 Genes
Breast
Odds Ratio
Confidence Intervals
Gene Amplification
Biopsy
Carcinoma, Intraductal, Noninfiltrating
Case-Control Studies
Proteins
Research Design
Epithelial Cells
Staining and Labeling
Membranes
DNA

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Stark, A., Hulka, B. S., Joens, S., Novotny, D., Thor, A. D., Wold, L. E., ... Conway, K. (2000). HER-2/neu amplification in benign breast disease and the risk of subsequent breast cancer. Journal of Clinical Oncology, 18(2), 267-274.

HER-2/neu amplification in benign breast disease and the risk of subsequent breast cancer. / Stark, Azadeh; Hulka, Barbara S.; Joens, Scott; Novotny, Debra; Thor, Ann D.; Wold, Lester E.; Schell, Michael J.; Melton, L. Joseph; Liu, Edison T.; Conway, Kathleen.

In: Journal of Clinical Oncology, Vol. 18, No. 2, 01.2000, p. 267-274.

Research output: Contribution to journalArticle

Stark, A, Hulka, BS, Joens, S, Novotny, D, Thor, AD, Wold, LE, Schell, MJ, Melton, LJ, Liu, ET & Conway, K 2000, 'HER-2/neu amplification in benign breast disease and the risk of subsequent breast cancer', Journal of Clinical Oncology, vol. 18, no. 2, pp. 267-274.
Stark A, Hulka BS, Joens S, Novotny D, Thor AD, Wold LE et al. HER-2/neu amplification in benign breast disease and the risk of subsequent breast cancer. Journal of Clinical Oncology. 2000 Jan;18(2):267-274.
Stark, Azadeh ; Hulka, Barbara S. ; Joens, Scott ; Novotny, Debra ; Thor, Ann D. ; Wold, Lester E. ; Schell, Michael J. ; Melton, L. Joseph ; Liu, Edison T. ; Conway, Kathleen. / HER-2/neu amplification in benign breast disease and the risk of subsequent breast cancer. In: Journal of Clinical Oncology. 2000 ; Vol. 18, No. 2. pp. 267-274.
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abstract = "Purpose: The purpose of this study was to determine whether the presence of HER-2/neu gene amplification and/or overexpression in benign breast disease was associated with an increased risk of subsequent breast cancer. Patients and Methods: We conducted a nested case-control study of a cohort of women who were diagnosed with benign breast disease at the Mayo Clinic and who were subsequently observed for the development of breast cancer. Patients who developed breast cancer formed the case group, and a matched sample from the remaining cohort served as controls. Benign tissue samples from 137 cases and 156 controls and malignant tissues from 99 cases provided DNA or tissue for evaluation of HER-2/neu amplification and protein overexpression. Results: Among the controls, seven benign tissues (4.5{\%}) demonstrated low- level HER-2/neu amplification, whereas 13 benign (9.5{\%}) and 18 malignant (18{\%}) tissue specimens from cases exhibited amplification. HER-2/neu amplification in benign breast biopsies was associated with an increased risk of breast cancer (odds ratio [OR] = 2.2; 95{\%} confidence interval [CI], 0.9 to 5.8); this association approached statistical significance. The risks for breast cancer associated with benign breast histopathologic diagnoses were OR = 1.1 (95{\%} CI, 0.6 to 1.9) for lesions exhibiting proliferation without atypia and OR = 1.5 (95{\%} CI, 0.4 to 5.6) for the diagnosis of atypical ductal hyperplasia. For women having both HER-2/neu amplification and a proliferative histopathologic diagnosis (either typical or atypical), the risk of breast cancer was more than seven-fold (OR = 7.2; 95{\%} CI, 0.9 to 60.8). Overexpression of the HER-2/neu protein product, defined as membrane staining in 10{\%} or more of epithelial cells, was found in 30{\%} of the breast tumors but was not detected in any of the benign breast tissues. Case patients who had HER2/neu gene amplification in their malignant tumor were more likely to have had HER-2/neu amplification in their prior benign biopsy (P = .06, Fisher's exact test). Conclusion: Women with benign breast biopsies demonstrating both HER-2/neu amplification and a proliferative histopathologic diagnosis may be at substantially increased risk for subsequent breast cancer.",
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AU - Stark, Azadeh

AU - Hulka, Barbara S.

AU - Joens, Scott

AU - Novotny, Debra

AU - Thor, Ann D.

AU - Wold, Lester E.

AU - Schell, Michael J.

AU - Melton, L. Joseph

AU - Liu, Edison T.

AU - Conway, Kathleen

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N2 - Purpose: The purpose of this study was to determine whether the presence of HER-2/neu gene amplification and/or overexpression in benign breast disease was associated with an increased risk of subsequent breast cancer. Patients and Methods: We conducted a nested case-control study of a cohort of women who were diagnosed with benign breast disease at the Mayo Clinic and who were subsequently observed for the development of breast cancer. Patients who developed breast cancer formed the case group, and a matched sample from the remaining cohort served as controls. Benign tissue samples from 137 cases and 156 controls and malignant tissues from 99 cases provided DNA or tissue for evaluation of HER-2/neu amplification and protein overexpression. Results: Among the controls, seven benign tissues (4.5%) demonstrated low- level HER-2/neu amplification, whereas 13 benign (9.5%) and 18 malignant (18%) tissue specimens from cases exhibited amplification. HER-2/neu amplification in benign breast biopsies was associated with an increased risk of breast cancer (odds ratio [OR] = 2.2; 95% confidence interval [CI], 0.9 to 5.8); this association approached statistical significance. The risks for breast cancer associated with benign breast histopathologic diagnoses were OR = 1.1 (95% CI, 0.6 to 1.9) for lesions exhibiting proliferation without atypia and OR = 1.5 (95% CI, 0.4 to 5.6) for the diagnosis of atypical ductal hyperplasia. For women having both HER-2/neu amplification and a proliferative histopathologic diagnosis (either typical or atypical), the risk of breast cancer was more than seven-fold (OR = 7.2; 95% CI, 0.9 to 60.8). Overexpression of the HER-2/neu protein product, defined as membrane staining in 10% or more of epithelial cells, was found in 30% of the breast tumors but was not detected in any of the benign breast tissues. Case patients who had HER2/neu gene amplification in their malignant tumor were more likely to have had HER-2/neu amplification in their prior benign biopsy (P = .06, Fisher's exact test). Conclusion: Women with benign breast biopsies demonstrating both HER-2/neu amplification and a proliferative histopathologic diagnosis may be at substantially increased risk for subsequent breast cancer.

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