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Lani · 05-18-2006, 11:40 AM

Research identifies most effective chemotherapy treatment for premenopausal women with HER2 positive breast cancers [Sunnybrook Health Sciences Centre]
A study led by Canadian Cancer Society researchers has found that premenopausal women with HER2 positive breast cancers have better overall survival and lower cancer recurrence rates when they are treated with an anthracycline-based chemotherapy. The findings are published in the May 18 issue of The New England Journal of Medicine.

The findings mean also that the two-thirds of premenopausal breast cancer patients whose tumours are not HER2 positive can be treated just as effectively with a less toxic chemotherapy regime.

"The results of this study are encouraging because they suggest that we can fine tune cancer treatments for specific groups of patients," says Dr. Barbara Whylie, CEO of the Canadian Cancer Society. "Because of these findings, we will be able to offer many breast cancer patients a treatment that is just as effective, but that has fewer side effects. That means a better quality of life for these women."

Dr. Kathleen Pritchard, chair of the breast cancer site group and head of clinical trials and epidemiology at Toronto Sunnybrook Regional Cancer Centre, the comprehensive cancer program at Sunnybrook Health Sciences Centre and the study's lead author, says, "This research suggests that we can target treatment and give each woman only the most effective treatment for her particular situation. If we begin by identifying certain factors, such as HER2, it helps us to make a clearer selection of the treatment that is needed."

In previous studies involving premenopausal women with lymph node-positive breast cancers who were treated with CEF, there was an 18 per cent increase in overall survival and a 30 per cent lower cancer recurrence rate over women who were treated with CMF. CEF is an anthracycline-based chemotherapy that is a combination of cyclophosphamide, epirubicin and fluorouracil. CMF is a combination of cyclophosphamide, methotrexate and fluorouracil. Dr. Pritchard and her team analyzed data and tissue samples from more than 700 women from one of these studies - a clinical trial funded by the Canadian Cancer Society - to clearly show that the survival benefits of CEF are actually limited almost entirely to patients whose tumours are HER2 positive.

Because CEF has more significant side effects, including increased rates of hair loss, nausea, vomiting and a small increase in the risk of congestive heart failure, doctors prefer to use CMF, if they can. HER2 breast cancers test positive for a protein called human epidermal growth factor receptor-2, which promotes the growth of cancer cells. One out of every three breast cancers produces an excess of HER2 due to a gene mutation. HER2 positive breast cancers tend to be more aggressive than other types of breast cancer.

ABSTRACT: HER2 and Responsiveness of Breast Cancer to Adjuvant Chemotherapy [New England Journal of Medicine; Subscribe]
Background: Amplification of the human epidermal growth factor receptor type 2 (HER2, also called HER2/neu) gene and overexpression of its product in breast-cancer cells may be associated with responsiveness to anthracycline-containing chemotherapy regimens.

Methods: In the randomized, controlled Mammary.5 trial, we studied 639 formalin-fixed paraffin-embedded specimens obtained from 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.

Results: Amplification of HER2 was associated with a poor prognosis regardless of the type of treatment. In patients whose tumors showed amplification of HER2, CEF was superior to CMF when assessed on the basis of relapse-free survival (hazard ratio, 0.52; 95 percent confidence interval, 0.34 to 0.80; P=0.003) and overall survival (hazard ratio, 0.65; 95 percent confidence interval, 0.42 to 1.02; P=0.06). For women whose tumors lacked amplification of HER2, CEF did not improve relapse-free survival (hazard ratio for relapse, 0.91; 95 percent confidence interval, 0.71 to 1.18; P=0.49) or overall survival (hazard ratio for death, 1.06; 95 percent confidence interval, 0.83 to 1.44; P=0.68). The adjusted hazard ratio for the interaction between treatment and HER2 amplification was 1.96 for relapse-free survival (95 percent confidence interval, 1.15 to 3.36; P=0.01) and 2.04 for overall survival (95 percent confidence interval, 1.14 to 3.65; P=0.02).

Conclusions: Amplification of HER2 in breast-cancer cells is associated with clinical responsiveness to anthracycline-containing chemotherapy.

05-18-2006, 11:40 AM	#2
Lani Senior Member Join Date: Mar 2006 Posts: 4,783	more on the New England Journal of Medicine article Research identifies most effective chemotherapy treatment for premenopausal women with HER2 positive breast cancers [Sunnybrook Health Sciences Centre] A study led by Canadian Cancer Society researchers has found that premenopausal women with HER2 positive breast cancers have better overall survival and lower cancer recurrence rates when they are treated with an anthracycline-based chemotherapy. The findings are published in the May 18 issue of The New England Journal of Medicine. The findings mean also that the two-thirds of premenopausal breast cancer patients whose tumours are not HER2 positive can be treated just as effectively with a less toxic chemotherapy regime. "The results of this study are encouraging because they suggest that we can fine tune cancer treatments for specific groups of patients," says Dr. Barbara Whylie, CEO of the Canadian Cancer Society. "Because of these findings, we will be able to offer many breast cancer patients a treatment that is just as effective, but that has fewer side effects. That means a better quality of life for these women." Dr. Kathleen Pritchard, chair of the breast cancer site group and head of clinical trials and epidemiology at Toronto Sunnybrook Regional Cancer Centre, the comprehensive cancer program at Sunnybrook Health Sciences Centre and the study's lead author, says, "This research suggests that we can target treatment and give each woman only the most effective treatment for her particular situation. If we begin by identifying certain factors, such as HER2, it helps us to make a clearer selection of the treatment that is needed." In previous studies involving premenopausal women with lymph node-positive breast cancers who were treated with CEF, there was an 18 per cent increase in overall survival and a 30 per cent lower cancer recurrence rate over women who were treated with CMF. CEF is an anthracycline-based chemotherapy that is a combination of cyclophosphamide, epirubicin and fluorouracil. CMF is a combination of cyclophosphamide, methotrexate and fluorouracil. Dr. Pritchard and her team analyzed data and tissue samples from more than 700 women from one of these studies - a clinical trial funded by the Canadian Cancer Society - to clearly show that the survival benefits of CEF are actually limited almost entirely to patients whose tumours are HER2 positive. Because CEF has more significant side effects, including increased rates of hair loss, nausea, vomiting and a small increase in the risk of congestive heart failure, doctors prefer to use CMF, if they can. HER2 breast cancers test positive for a protein called human epidermal growth factor receptor-2, which promotes the growth of cancer cells. One out of every three breast cancers produces an excess of HER2 due to a gene mutation. HER2 positive breast cancers tend to be more aggressive than other types of breast cancer. ABSTRACT: HER2 and Responsiveness of Breast Cancer to Adjuvant Chemotherapy [New England Journal of Medicine; Subscribe] Background: Amplification of the human epidermal growth factor receptor type 2 (HER2, also called HER2/neu) gene and overexpression of its product in breast-cancer cells may be associated with responsiveness to anthracycline-containing chemotherapy regimens. Methods: In the randomized, controlled Mammary.5 trial, we studied 639 formalin-fixed paraffin-embedded specimens obtained from 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. Results: Amplification of HER2 was associated with a poor prognosis regardless of the type of treatment. In patients whose tumors showed amplification of HER2, CEF was superior to CMF when assessed on the basis of relapse-free survival (hazard ratio, 0.52; 95 percent confidence interval, 0.34 to 0.80; P=0.003) and overall survival (hazard ratio, 0.65; 95 percent confidence interval, 0.42 to 1.02; P=0.06). For women whose tumors lacked amplification of HER2, CEF did not improve relapse-free survival (hazard ratio for relapse, 0.91; 95 percent confidence interval, 0.71 to 1.18; P=0.49) or overall survival (hazard ratio for death, 1.06; 95 percent confidence interval, 0.83 to 1.44; P=0.68). The adjusted hazard ratio for the interaction between treatment and HER2 amplification was 1.96 for relapse-free survival (95 percent confidence interval, 1.15 to 3.36; P=0.01) and 2.04 for overall survival (95 percent confidence interval, 1.14 to 3.65; P=0.02). Conclusions: Amplification of HER2 in breast-cancer cells is associated with clinical responsiveness to anthracycline-containing chemotherapy.