erbB-2 and response to doxorubicin in patients with axillary lymph node- positive, hormone receptor-negative breast cancer

Soonmyung Paik, John Bryant, Chanheun Park, Bernard Fisher, Elizabeth Tan-Chiu, David Hyams, Edwin R. Fisher, Marc E Lippman, D. Lawrence Wickerham, Norman Wolmark

Research output: Contribution to journalArticle

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Abstract

Background: Overexpression of the erbB-2 protein by breast cancer cells has been suggested to be a predictor of response to doxorubicin. A retrospective study was designed to test this hypothesis. Methods: In National Surgical Adjuvant Breast and Bowel Project protocol B-11, patients with axillary lymph node-positive, hormone receptor-negative breast cancer were randomly assigned to receive either L-phenylalanine mustard plus 5- fluorouracil (PF) or a combination of L-phenylalanine mustard, 5- fluorouracil, and doxorubicin (PAF). Tumor cell expression of erbB-2 was determined by immunohistochemistry for 638 of 682 eligible patients. Statistical analyses were performed to test for interaction between treatment and erbB-2 status (positive versus negative) with respect to disease-free survival (DFS), survival, recurrence-free survival (RFS), and distant disease-free survival (DDFS). Reported P values are two-sided. Results: Overexpression of erbB-2 (i.e., positive immunohistochemical staining) was observed in 239 (37.5%) of the 638 tumors studied. Overexpression was associated with tumor size (P = .02), lack of estrogen receptors (P = .008), and the number of positive lymph nodes (P = .0001). After a mean time on study of 13.5 years, the clinical benefit from doxorubicin (PAF versus PF) was statistically significant for patients with erbB-2-positive tumors - DFS: relative risk of failure (RR) = 0.60 (95% confidence interval [CI] = 0.440.83), P = .001; survival: RR = 0.66 (95% CI = 0.47-0.92), P = .01; RFS: RR = 0.58 (95% CI = 0.42-0.82), P = .002; DDFS: RR = 0.61 (95% CI = 0.44- 0.85), P = .003. However, it was not significant for patients with erbB-2- negative tumors DFS: RR = 0.96 (95% CI = 0.75-1.23), P = .74; survival: RR = 0.90 (95% CI = 0.69-1.19), P = .47; RFS: RR = 0.88 (95% CI = 0.67-1.16), P = .37; DDFS: RR = 1.03 (95% CI = 0.791.35), P = .84. Interaction between doxorubicin treatment and erbB-2 overexpression was statistically significant for DFS (P = .02) and DDFS (P = .02) but not for survival (P = .15) or RFS (P = .06). Conclusions: These data support the hypothesis of a preferential benefit from doxorubicin in patients with erbB-2-positive breast cancer.

Original languageEnglish
Pages (from-to)1361-1370
Number of pages10
JournalJournal of the National Cancer Institute
Volume90
Issue number18
StatePublished - Sep 16 1998
Externally publishedYes

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Doxorubicin
Disease-Free Survival
Lymph Nodes
Hormones
Confidence Intervals
Breast Neoplasms
Survival
Fluorouracil
Recurrence
Melphalan
Neoplasms
Phenylalanine
BRCA2 Protein
Estrogen Receptors
Breast
Retrospective Studies
Immunohistochemistry
Staining and Labeling
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Paik, S., Bryant, J., Park, C., Fisher, B., Tan-Chiu, E., Hyams, D., ... Wolmark, N. (1998). erbB-2 and response to doxorubicin in patients with axillary lymph node- positive, hormone receptor-negative breast cancer. Journal of the National Cancer Institute, 90(18), 1361-1370.

erbB-2 and response to doxorubicin in patients with axillary lymph node- positive, hormone receptor-negative breast cancer. / Paik, Soonmyung; Bryant, John; Park, Chanheun; Fisher, Bernard; Tan-Chiu, Elizabeth; Hyams, David; Fisher, Edwin R.; Lippman, Marc E; Wickerham, D. Lawrence; Wolmark, Norman.

In: Journal of the National Cancer Institute, Vol. 90, No. 18, 16.09.1998, p. 1361-1370.

Research output: Contribution to journalArticle

Paik, S, Bryant, J, Park, C, Fisher, B, Tan-Chiu, E, Hyams, D, Fisher, ER, Lippman, ME, Wickerham, DL & Wolmark, N 1998, 'erbB-2 and response to doxorubicin in patients with axillary lymph node- positive, hormone receptor-negative breast cancer', Journal of the National Cancer Institute, vol. 90, no. 18, pp. 1361-1370.
Paik, Soonmyung ; Bryant, John ; Park, Chanheun ; Fisher, Bernard ; Tan-Chiu, Elizabeth ; Hyams, David ; Fisher, Edwin R. ; Lippman, Marc E ; Wickerham, D. Lawrence ; Wolmark, Norman. / erbB-2 and response to doxorubicin in patients with axillary lymph node- positive, hormone receptor-negative breast cancer. In: Journal of the National Cancer Institute. 1998 ; Vol. 90, No. 18. pp. 1361-1370.
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title = "erbB-2 and response to doxorubicin in patients with axillary lymph node- positive, hormone receptor-negative breast cancer",
abstract = "Background: Overexpression of the erbB-2 protein by breast cancer cells has been suggested to be a predictor of response to doxorubicin. A retrospective study was designed to test this hypothesis. Methods: In National Surgical Adjuvant Breast and Bowel Project protocol B-11, patients with axillary lymph node-positive, hormone receptor-negative breast cancer were randomly assigned to receive either L-phenylalanine mustard plus 5- fluorouracil (PF) or a combination of L-phenylalanine mustard, 5- fluorouracil, and doxorubicin (PAF). Tumor cell expression of erbB-2 was determined by immunohistochemistry for 638 of 682 eligible patients. Statistical analyses were performed to test for interaction between treatment and erbB-2 status (positive versus negative) with respect to disease-free survival (DFS), survival, recurrence-free survival (RFS), and distant disease-free survival (DDFS). Reported P values are two-sided. Results: Overexpression of erbB-2 (i.e., positive immunohistochemical staining) was observed in 239 (37.5{\%}) of the 638 tumors studied. Overexpression was associated with tumor size (P = .02), lack of estrogen receptors (P = .008), and the number of positive lymph nodes (P = .0001). After a mean time on study of 13.5 years, the clinical benefit from doxorubicin (PAF versus PF) was statistically significant for patients with erbB-2-positive tumors - DFS: relative risk of failure (RR) = 0.60 (95{\%} confidence interval [CI] = 0.440.83), P = .001; survival: RR = 0.66 (95{\%} CI = 0.47-0.92), P = .01; RFS: RR = 0.58 (95{\%} CI = 0.42-0.82), P = .002; DDFS: RR = 0.61 (95{\%} CI = 0.44- 0.85), P = .003. However, it was not significant for patients with erbB-2- negative tumors DFS: RR = 0.96 (95{\%} CI = 0.75-1.23), P = .74; survival: RR = 0.90 (95{\%} CI = 0.69-1.19), P = .47; RFS: RR = 0.88 (95{\%} CI = 0.67-1.16), P = .37; DDFS: RR = 1.03 (95{\%} CI = 0.791.35), P = .84. Interaction between doxorubicin treatment and erbB-2 overexpression was statistically significant for DFS (P = .02) and DDFS (P = .02) but not for survival (P = .15) or RFS (P = .06). Conclusions: These data support the hypothesis of a preferential benefit from doxorubicin in patients with erbB-2-positive breast cancer.",
author = "Soonmyung Paik and John Bryant and Chanheun Park and Bernard Fisher and Elizabeth Tan-Chiu and David Hyams and Fisher, {Edwin R.} and Lippman, {Marc E} and Wickerham, {D. Lawrence} and Norman Wolmark",
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T1 - erbB-2 and response to doxorubicin in patients with axillary lymph node- positive, hormone receptor-negative breast cancer

AU - Paik, Soonmyung

AU - Bryant, John

AU - Park, Chanheun

AU - Fisher, Bernard

AU - Tan-Chiu, Elizabeth

AU - Hyams, David

AU - Fisher, Edwin R.

AU - Lippman, Marc E

AU - Wickerham, D. Lawrence

AU - Wolmark, Norman

PY - 1998/9/16

Y1 - 1998/9/16

N2 - Background: Overexpression of the erbB-2 protein by breast cancer cells has been suggested to be a predictor of response to doxorubicin. A retrospective study was designed to test this hypothesis. Methods: In National Surgical Adjuvant Breast and Bowel Project protocol B-11, patients with axillary lymph node-positive, hormone receptor-negative breast cancer were randomly assigned to receive either L-phenylalanine mustard plus 5- fluorouracil (PF) or a combination of L-phenylalanine mustard, 5- fluorouracil, and doxorubicin (PAF). Tumor cell expression of erbB-2 was determined by immunohistochemistry for 638 of 682 eligible patients. Statistical analyses were performed to test for interaction between treatment and erbB-2 status (positive versus negative) with respect to disease-free survival (DFS), survival, recurrence-free survival (RFS), and distant disease-free survival (DDFS). Reported P values are two-sided. Results: Overexpression of erbB-2 (i.e., positive immunohistochemical staining) was observed in 239 (37.5%) of the 638 tumors studied. Overexpression was associated with tumor size (P = .02), lack of estrogen receptors (P = .008), and the number of positive lymph nodes (P = .0001). After a mean time on study of 13.5 years, the clinical benefit from doxorubicin (PAF versus PF) was statistically significant for patients with erbB-2-positive tumors - DFS: relative risk of failure (RR) = 0.60 (95% confidence interval [CI] = 0.440.83), P = .001; survival: RR = 0.66 (95% CI = 0.47-0.92), P = .01; RFS: RR = 0.58 (95% CI = 0.42-0.82), P = .002; DDFS: RR = 0.61 (95% CI = 0.44- 0.85), P = .003. However, it was not significant for patients with erbB-2- negative tumors DFS: RR = 0.96 (95% CI = 0.75-1.23), P = .74; survival: RR = 0.90 (95% CI = 0.69-1.19), P = .47; RFS: RR = 0.88 (95% CI = 0.67-1.16), P = .37; DDFS: RR = 1.03 (95% CI = 0.791.35), P = .84. Interaction between doxorubicin treatment and erbB-2 overexpression was statistically significant for DFS (P = .02) and DDFS (P = .02) but not for survival (P = .15) or RFS (P = .06). Conclusions: These data support the hypothesis of a preferential benefit from doxorubicin in patients with erbB-2-positive breast cancer.

AB - Background: Overexpression of the erbB-2 protein by breast cancer cells has been suggested to be a predictor of response to doxorubicin. A retrospective study was designed to test this hypothesis. Methods: In National Surgical Adjuvant Breast and Bowel Project protocol B-11, patients with axillary lymph node-positive, hormone receptor-negative breast cancer were randomly assigned to receive either L-phenylalanine mustard plus 5- fluorouracil (PF) or a combination of L-phenylalanine mustard, 5- fluorouracil, and doxorubicin (PAF). Tumor cell expression of erbB-2 was determined by immunohistochemistry for 638 of 682 eligible patients. Statistical analyses were performed to test for interaction between treatment and erbB-2 status (positive versus negative) with respect to disease-free survival (DFS), survival, recurrence-free survival (RFS), and distant disease-free survival (DDFS). Reported P values are two-sided. Results: Overexpression of erbB-2 (i.e., positive immunohistochemical staining) was observed in 239 (37.5%) of the 638 tumors studied. Overexpression was associated with tumor size (P = .02), lack of estrogen receptors (P = .008), and the number of positive lymph nodes (P = .0001). After a mean time on study of 13.5 years, the clinical benefit from doxorubicin (PAF versus PF) was statistically significant for patients with erbB-2-positive tumors - DFS: relative risk of failure (RR) = 0.60 (95% confidence interval [CI] = 0.440.83), P = .001; survival: RR = 0.66 (95% CI = 0.47-0.92), P = .01; RFS: RR = 0.58 (95% CI = 0.42-0.82), P = .002; DDFS: RR = 0.61 (95% CI = 0.44- 0.85), P = .003. However, it was not significant for patients with erbB-2- negative tumors DFS: RR = 0.96 (95% CI = 0.75-1.23), P = .74; survival: RR = 0.90 (95% CI = 0.69-1.19), P = .47; RFS: RR = 0.88 (95% CI = 0.67-1.16), P = .37; DDFS: RR = 1.03 (95% CI = 0.791.35), P = .84. Interaction between doxorubicin treatment and erbB-2 overexpression was statistically significant for DFS (P = .02) and DDFS (P = .02) but not for survival (P = .15) or RFS (P = .06). Conclusions: These data support the hypothesis of a preferential benefit from doxorubicin in patients with erbB-2-positive breast cancer.

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