Classical cyclophosphamide, methotrexate, and fluorouracil chemotherapy is more effective in triple-negative, node-negative breast cancer: Results from two randomized trials of adjuvant chemoendocrine therapy for node-negative breast cancer

Marco Colleoni, Bernard F. Cole, Giuseppe Viale, Meredith M. Regan, Karen N. Price, Eugenio Maiorano, Mauro G. Mastropasqua, Diana Crivellari, Richard D. Gelber, Aron Goldhirsch, Alan S. Coates, Barry A. Gusterson

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Abstract

Purpose: Retrospective studies suggest that primary breast cancers lacking estrogen receptor (ER) and progesterone receptor (PR) and not overexpressing human epidermal growth factor receptor 2 (HER2; triple-negative tumors) are particularly sensitive to DNA-damaging chemotherapy with alkylating agents. Patients and Methods: Patients enrolled in International Breast Cancer Study Group Trials VIII and IX with node-negative, operable breast cancer and centrally assessed ER, PR, and HER2 were included (n = 2,257). The trials compared three or six courses of adjuvant classical cyclophosphamide, methotrexate, and fluorouracil (CMF) with or without endocrine therapy versus endocrine therapy alone. We explored patterns of recurrence by treatment according to three immunohistochemically defined tumor subtypes: triple negative, HER2 positive and endocrine receptor absent, and endocrine receptor present. Results: Patients with triple-negative tumors (303 patients; 13%) were significantly more likely to have tumors > 2 cm and grade 3 compared with those in the HER2-positive, endocrine receptor-absent, and endocrine receptor-present subtypes. No clear chemotherapy benefit was observed in endocrine receptor-present disease (hazard ratio [HR], 0.90; 95% CI, 0.74 to 1.11). A statistically significantly greater benefit for chemotherapy versus no chemotherapy was observed in triple-negative breast cancer (HR, 0.46; 95% CI, 0.29 to 0.73; interaction P = .009 v endocrine receptor-present disease). The magnitude of the chemotherapy effect was lower in HER2-positive endocrine receptor-absent disease (HR, 0.58; 95% CI, 0.29 to 1.17; interaction P = .24 v endocrine receptor-present disease). Conclusion: The magnitude of benefit of CMF chemotherapy is largest in patients with triple-negative, node-negative breast cancer.

Original languageEnglish
Pages (from-to)2966-2973
Number of pages8
JournalJournal of Clinical Oncology
Volume28
Issue number18
DOIs
Publication statusPublished - Jun 20 2010

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Methotrexate
Fluorouracil
Cyclophosphamide
Breast Neoplasms
Drug Therapy
Progesterone Receptors
Estrogen Receptors
Neoplasms
Therapeutics
Triple Negative Breast Neoplasms
Alkylating Agents
Retrospective Studies
Recurrence
DNA

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

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Classical cyclophosphamide, methotrexate, and fluorouracil chemotherapy is more effective in triple-negative, node-negative breast cancer : Results from two randomized trials of adjuvant chemoendocrine therapy for node-negative breast cancer. / Colleoni, Marco; Cole, Bernard F.; Viale, Giuseppe; Regan, Meredith M.; Price, Karen N.; Maiorano, Eugenio; Mastropasqua, Mauro G.; Crivellari, Diana; Gelber, Richard D.; Goldhirsch, Aron; Coates, Alan S.; Gusterson, Barry A.

In: Journal of Clinical Oncology, Vol. 28, No. 18, 20.06.2010, p. 2966-2973.

Research output: Contribution to journalArticle

Colleoni, Marco ; Cole, Bernard F. ; Viale, Giuseppe ; Regan, Meredith M. ; Price, Karen N. ; Maiorano, Eugenio ; Mastropasqua, Mauro G. ; Crivellari, Diana ; Gelber, Richard D. ; Goldhirsch, Aron ; Coates, Alan S. ; Gusterson, Barry A. / Classical cyclophosphamide, methotrexate, and fluorouracil chemotherapy is more effective in triple-negative, node-negative breast cancer : Results from two randomized trials of adjuvant chemoendocrine therapy for node-negative breast cancer. In: Journal of Clinical Oncology. 2010 ; Vol. 28, No. 18. pp. 2966-2973.
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abstract = "Purpose: Retrospective studies suggest that primary breast cancers lacking estrogen receptor (ER) and progesterone receptor (PR) and not overexpressing human epidermal growth factor receptor 2 (HER2; triple-negative tumors) are particularly sensitive to DNA-damaging chemotherapy with alkylating agents. Patients and Methods: Patients enrolled in International Breast Cancer Study Group Trials VIII and IX with node-negative, operable breast cancer and centrally assessed ER, PR, and HER2 were included (n = 2,257). The trials compared three or six courses of adjuvant classical cyclophosphamide, methotrexate, and fluorouracil (CMF) with or without endocrine therapy versus endocrine therapy alone. We explored patterns of recurrence by treatment according to three immunohistochemically defined tumor subtypes: triple negative, HER2 positive and endocrine receptor absent, and endocrine receptor present. Results: Patients with triple-negative tumors (303 patients; 13{\%}) were significantly more likely to have tumors > 2 cm and grade 3 compared with those in the HER2-positive, endocrine receptor-absent, and endocrine receptor-present subtypes. No clear chemotherapy benefit was observed in endocrine receptor-present disease (hazard ratio [HR], 0.90; 95{\%} CI, 0.74 to 1.11). A statistically significantly greater benefit for chemotherapy versus no chemotherapy was observed in triple-negative breast cancer (HR, 0.46; 95{\%} CI, 0.29 to 0.73; interaction P = .009 v endocrine receptor-present disease). The magnitude of the chemotherapy effect was lower in HER2-positive endocrine receptor-absent disease (HR, 0.58; 95{\%} CI, 0.29 to 1.17; interaction P = .24 v endocrine receptor-present disease). Conclusion: The magnitude of benefit of CMF chemotherapy is largest in patients with triple-negative, node-negative breast cancer.",
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T1 - Classical cyclophosphamide, methotrexate, and fluorouracil chemotherapy is more effective in triple-negative, node-negative breast cancer

T2 - Results from two randomized trials of adjuvant chemoendocrine therapy for node-negative breast cancer

AU - Colleoni, Marco

AU - Cole, Bernard F.

AU - Viale, Giuseppe

AU - Regan, Meredith M.

AU - Price, Karen N.

AU - Maiorano, Eugenio

AU - Mastropasqua, Mauro G.

AU - Crivellari, Diana

AU - Gelber, Richard D.

AU - Goldhirsch, Aron

AU - Coates, Alan S.

AU - Gusterson, Barry A.

PY - 2010/6/20

Y1 - 2010/6/20

N2 - Purpose: Retrospective studies suggest that primary breast cancers lacking estrogen receptor (ER) and progesterone receptor (PR) and not overexpressing human epidermal growth factor receptor 2 (HER2; triple-negative tumors) are particularly sensitive to DNA-damaging chemotherapy with alkylating agents. Patients and Methods: Patients enrolled in International Breast Cancer Study Group Trials VIII and IX with node-negative, operable breast cancer and centrally assessed ER, PR, and HER2 were included (n = 2,257). The trials compared three or six courses of adjuvant classical cyclophosphamide, methotrexate, and fluorouracil (CMF) with or without endocrine therapy versus endocrine therapy alone. We explored patterns of recurrence by treatment according to three immunohistochemically defined tumor subtypes: triple negative, HER2 positive and endocrine receptor absent, and endocrine receptor present. Results: Patients with triple-negative tumors (303 patients; 13%) were significantly more likely to have tumors > 2 cm and grade 3 compared with those in the HER2-positive, endocrine receptor-absent, and endocrine receptor-present subtypes. No clear chemotherapy benefit was observed in endocrine receptor-present disease (hazard ratio [HR], 0.90; 95% CI, 0.74 to 1.11). A statistically significantly greater benefit for chemotherapy versus no chemotherapy was observed in triple-negative breast cancer (HR, 0.46; 95% CI, 0.29 to 0.73; interaction P = .009 v endocrine receptor-present disease). The magnitude of the chemotherapy effect was lower in HER2-positive endocrine receptor-absent disease (HR, 0.58; 95% CI, 0.29 to 1.17; interaction P = .24 v endocrine receptor-present disease). Conclusion: The magnitude of benefit of CMF chemotherapy is largest in patients with triple-negative, node-negative breast cancer.

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