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The treatment of both early and advanced breast cancer continues to pose significant challenges. Despite advances in local and systemic therapy, breast cancer remains the second leading cause of cancer mortality among women (NCCN^® Practice Guidelines in Oncology - v.2.2002). However, the introduction of new agents — including new chemotherapies and new combinations, such as incorporation of Taxotere (docetaxel) — has now generated considerable optimism among clinical investigators. At the recent American Society of Clinical Oncology (ASCO) 2002 meeting, data were presented that both answer outstanding questions regarding the appropriate management of patients with breast cancer and point the way toward targeted therapies in the near future.

In the last decade, Taxotere has emerged as one of the most effective cytotoxic agents against advanced breast cancer, with substantial activity both as a single agent and in combination. In particular, there has been substantial interest in evaluating Taxotere-anthracycline combinations, based on the drugs' single-agent activity, lack of complete clinical cross-resistance, and relatively non-overlapping side effect profiles, including no increased cardiac toxicity. Recently, the TAC regimen (Taxotere 75 mg/m², doxorubicin [Adriamycin, Adiblastine, Adriablatina, Doxil, and others] 50 mg/m², and cyclophosphamide [Cytoxan, Cytokan, Endoxon, Neosar, Neosar For Injection] 500 mg/m²) was developed as an alternative to standard FAC chemotherapy (5-flourouracil [Adrucil, Efudex, Fluroplex] 500 mg/m², doxorubicin 50 mg/m², and cyclophosphamide 500 mg/m²) in the adjuvant setting (BCIRG 001). The first planned interim analysis at 36 months follow-up was reported at this meeting, showing superiority of TAC over FAC in terms of disease-free survival as well as overall survival, in particular, in the prospectively defined group of patients with one to three positive nodes. Further follow-up will help us confirm the role of this Taxotere-based combination in the early treatment of breast cancer.

The neoadjuvant setting is emerging as an important modality for early-stage breast cancer therapy, allowing improved locoregional management as well as early identification of patients who are sensitive to given therapies (concept of predictivity) for which the observation of a complete pathologic response with negative lymph nodes may play a key role. In this regard, the abstract by Hurley et al. reports a promising high complete pathologic response with the combination of trastuzumab (Herceptin), Taxotere and cisplatin (Platinol, Asiplatin). As well, the large German GEPARD-DUO trial conducted by von Minckwitz et al. confirms that both sequential and dose-dense Taxotere-anthracycline based chemotherapies are effective and well tolerated. The 24-week sequential schedule achieved a higher rate of complete pathologic response, breast-conserving surgery and negative lymph nodes than the eight-week dose-dense regimen. Additionally, Mamounas et al. presented data on the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-27 trial, in which the addition of neoadjuvant Taxotere in sequence after four courses of doxorubicin-cyclophosphamide (AC) improved significantly the rate of complete pathologic response (25.6% vs. 13.7%, p<0.001). Dr. Mamounas presented the data on the value of sentinel node biopsies versus axillary node dissection. The success rate for identification and removal of the sentinel lymph node was 85% and the false negative rate was 11%.

The weekly use of taxanes has shown promise recently, in particular, in terms of toxicity profile. Climent et al. presented the preliminary results of a randomized phase II trial comparing weekly to every three-week Taxotere in advanced breast cancer. As expected, the toxicity profile appeared more favorable for the weekly regimen, while preliminary efficacy data showed no difference between the two arms.

Three abstracts were devoted to the fundamental problem of identifying reliable predictive markers for chemotherapy, in order to better select subpopulations of patients who could benefit from the chemotherapy. Minton et al. demonstrated that STAT-3 activation does not appear to predict the response to Taxotere and doxorubicin therapy. Retrospective analysis of the TAX 303 trial (doxorubicin vs. Taxotere in first-line therapy of advanced breast cancer) suggests that Taxotere is more effective than doxorubicin in patients with human epidermal growth factor receptor 2 (HER-2)-positive tumors. And finally, Chang et al. presented some important data on molecular profiling of gene expression, which appears promising in identifying new methods to predict the efficacy of given chemotherapies, allowing us to potentially reduce unnecessary treatments.

Additionally, Piccart et al. presented new perspectives on the combination of Taxotere with new promising biologic therapies to integrate novel targeted therapies in the management of breast cancer.

Tailoring therapy to the biology of the disease and the selection of adapted therapies will lead to individualized treatments and will allow us to go farther in the control and modification of breast cancer.

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