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Who Needs a Taxane? Tailoring Breast Cancer Therapy

Women with HER2-positive tumors benefited from paclitaxel therapy, regardless of the ER status of the tumors.

Tailoring adjuvant therapy for early-stage breast cancer patients is an important goal for medical oncologists for two reasons: A substantial fraction of patients might not require adjuvant therapy to lower their risk for recurrence, and identifying optimal therapies for those who do require adjuvant therapy could improve clinical outcomes. Investigators have focused on molecular markers and gene expression in tumor tissues to identify patients whose prognoses and, potentially, outcomes from particular systemic therapies might differ. Examples include patients whose breast cancers express estrogen receptors (ERs), who likely would benefit from endocrine therapies, and patients with HER2-overexpressing tumors, who would benefit from adjuvant anti-HER2 therapy (i.e., trastuzumab [Herceptin]).

Approximately 5 years ago, results of a clinical trial (CALGB 9344; J Clin Oncol 2003; 21:976) involving 3121 breast cancer patients suggested that addition of 4 cycles of paclitaxel to 4 cycles of doxorubicin and cyclophosphamide (AC), compared with AC alone, lengthened disease-free survival (DFS) and overall survival of axillary node–positive patients. The standard of care for axillary node–positive patients changed immediately, with rapid adoption of paclitaxel plus AC. Nevertheless, much debate ensued, focused on whether all patients, or just a subset, benefited from paclitaxel.

In a new analysis of tissue from 1322 randomly selected CALGB 9344 patients, ER and HER2 status was assessed for each sample with immunohistochemical analyses and with fluorescence in situ hybridization (FISH). The principal analysis was based on a model that included receipt or nonreceipt of paclitaxel therapy, doxorubicin dose, number of axillary lymph nodes, tumor size, menopausal status, ER and HER2 status, and an interaction term for HER2 positivity and receipt of paclitaxel therapy.

When all patients were evaluated as one group, the hazard ratios for recurrence and for death were 0.59 (P=0.01) and 0.57 (P=0.01), respectively, when paclitaxel treatment and HER2–positive status were present. An analysis of paclitaxel’s benefit, based on HER2 and ER status, showed that treatment with paclitaxel was associated with longer DFS in patients with HER2-positive tumors, regardless of their ER status. In the largest subgroup of patients (>50%), whose tumors were ER-positive and HER2-negative, paclitaxel was not beneficial.

Comment: This study involved a chemotherapy regimen that is no longer commonly used. Specifically, administering paclitaxel every 3 weeks has been supplanted by administering paclitaxel weekly or biweekly in a "dose-dense" schedule. Whether these contemporary treatment schedules confer benefit to ER-positive, HER2-negative patients cannot be determined from this analysis. Another issue, noted in an accompanying editorial, is that HER2-positive patients in the HERA trial who did not receive a taxane as a component of their adjuvant therapy (74% of patients) benefited from adjuvant trastuzumab (N Engl J Med 2005; 353:1659). The HERA result reminds us that virtually all patients with HER2-positive, axillary node–positive cancers receive trastuzumab and that the exact type of adjuvant chemotherapy, from an efficacy standpoint, might be less important now. Nevertheless, the current analysis provides useful information as we seek to refine treatment recommendations for patients with early-stage breast cancer.

— William J. Gradishar, MD

Published in Journal Watch Oncology and Hematology October 10, 2007

Citation(s):

Hayes DF et al. HER2 and response to paclitaxel in node-positive breast cancer. N Engl J Med 2007 Oct 11; 357:1496.

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• Medline abstract (Free)

Moore A. Breast-cancer therapy — looking back to the future. N Engl J Med 2007 Oct 11; 357:1547.

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• Medline abstract (Free)