Article

HER2 and Response to Paclitaxel in Node-Positive Breast Cancer

Duke University, Durham, North Carolina, United States
New England Journal of Medicine (Impact Factor: 54.42). 10/2007; 357(15):1496-506. DOI: 10.1056/NEJMoa071167
Source: PubMed

ABSTRACT The status of human epidermal growth factor receptor type 2 (HER2) in breast-cancer cells predicts clinical outcomes in women who receive adjuvant anthracycline-based chemotherapy. We hypothesized that HER2 positivity predicts a benefit from adjuvant doxorubicin doses above standard levels, from the addition of paclitaxel after adjuvant chemotherapy with doxorubicin plus cyclophosphamide, or from both.
We randomly selected 1500 women from 3121 women with node-positive breast cancer who had been randomly assigned to receive doxorubicin (60, 75, or 90 mg per square meter of body-surface area) plus cyclophosphamide (600 mg per square meter) for four cycles, followed by four cycles of paclitaxel (175 mg per square meter) or observation. Tissue blocks from 1322 of these 1500 women were available. Immunohistochemical analyses of these tissue specimens for HER2 with the CB11 monoclonal antibody against HER2 or with a polyclonal-antibody assay kit and fluorescence in situ hybridization for HER2 amplification were performed.
No interaction was observed between HER2 positivity and doxorubicin doses above 60 mg per square meter. HER2 positivity was, however, associated with a significant benefit from paclitaxel. The interaction between HER2 positivity and the addition of paclitaxel to the treatment was associated with a hazard ratio for recurrence of 0.59 (P=0.01). Patients with a HER2-positive breast cancer benefited from paclitaxel, regardless of estrogen-receptor status, but paclitaxel did not benefit patients with HER2-negative, estrogen-receptor-positive cancers.
The expression or amplification, or both, of HER2 by a breast cancer is associated with a benefit from the addition of paclitaxel after adjuvant treatment with doxorubicin (<60 mg per square meter) plus cyclophosphamide in node-positive breast cancer, regardless of estrogen-receptor status. Patients with HER2-negative, estrogen-receptor-positive, node-positive breast cancer may gain little benefit from the administration of paclitaxel after adjuvant chemotherapy with doxorubicin plus cyclophosphamide.

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    • "Conversely, HER-2 positive/HR negative tumors relapse more commonly within the first 5 years. Moreover, sites of relapse are different, since bone and soft tissue are more common in ER positive disease, conversely, visceral sites are more frequently observed in ER negative subset, and sensitivity to some chemotherapy drugs, i.e. paclitaxel, may be different between the two subsets [57] [58] [59]. A recent evaluation of 1187 early breast cancers compared disease characteristics among different groups according to HR and HER-2 status. "
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    • "This observation should be attributed to the incorporation of taxanes (both docetaxel and paclitaxel), which was the main difference between the two regimens; whether this effect represents a greater sensitivity of CTCs to taxanes or it is an additive effect of the chemotherapy agents is unknown. This observation is in agreement with several recent clinical data indicating the superiority of taxane-containing regimens in the adjuvant setting and could be explained by the fact that incorporation of taxanes in the adjuvant treatment is more pronounced in patients with HER2-positive tumours (Hayes et al, 2007; Ellis et al, 2009). Several studies have shown that CTCs express HER2/c-neu (Wulfing et al, 2010) irrespectively of the HER2 status of the primary tumours (Pestrin et al, 2009). "
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    • "Despite initial reports that TNBC might not ben - efit from taxanes , the addition of paclitaxel to AC ( doxorubicin , cyclophosphamide ) was associated with increased disease - free survival ( DFS ) rates ( p = 0 . 002 ) in patients with TNBC [ Hayes et al . 2007 ] . This benefit has also been confirmed by other groups both in node - positive and node - negative TNBC patients [ Hugh et al . 2009 ; Martin et al . 2010 ; Roche et al . 2006 ] ."
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