| HER2 and Responsiveness of
Breast Cancer to Adjuvant Chemotherapy Kathleen I. Pritchard, M.D., for the National Cancer Institute of Canada Clinical Trials Group, NEJM 2006;354:2103 |
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| In the 1980s, trials of adjuvant
chemotherapy for breast cancer that compared regimens containing an anthracycline
(epirubicin or doxorubicin) with a combination of cyclophosphamide, methotrexate, and
fluorouracil (CMF) yielded inconsistent results. More than a decade later, the safety and
efficacy of an intensive regimen of cyclophosphamide, epirubicin, and fluorouracil (CEF)
as adjuvant therapy for breast cancer were demonstrated. In the National Cancer Institute
of Canada Clinical Trials Group (NCIC CTG) Mammary. (MA.5) randomized
trial involving premenopausal women with node-positive breast cancer, CEF was shown to be
superior to CMF5 and remained superior in terms of relapse-free survival and overall
survival after a median follow-up of 10 years. As compared with CMF,
however, CEF was associated with increased rates of alopecia, nausea, vomiting,
stomatitis, and neutropenia and febrile neutropenia; a temporary reduction in the quality
of life; and an increase in the risk of congestive heart failure (1.1 percent) and acute
leukemia (1.4 percent). Treatment with CEF is also considerably more expensive than CMF
therapy. It has been suggested that amplification of the gene for human epidermal growth factor receptor type 2 (HER2, also referred to as HER2/neu), overexpression of its product, or both in breast-cancer cells not only predicts responsiveness to trastuzumab but also identifies patients whose tumors will not respond to CMF and who could benefit from high-dose chemotherapy or from anthracycline-containing regimens. To pursue this suggestion, we studied formalin-fixed, paraffin-embedded specimens from all patients enrolled in the MA.5 trial to determine whether amplification of HER2, overexpression of HER2, or both in breast-cancer cells identifies women who could benefit from CEF, as compared with CMF. 710
premenopausal women with node-positive breast cancer who had received either
cyclophosphamide, epirubicin, and fluorouracil (CEF) or cyclophosphamide, methotrexate,
and fluorouracil (CMF) as adjuvant chemotherapy. HER2 amplification or overexpression was
evaluated with the use of fluorescence in situ hybridization, immunohistochemical
analysis, and polymerase-chain-reaction analysis. |
