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AstraZeneca announced recently that the US Food and Drug Administration (FDA) has approved use of its breast cancer drug tamoxifen (Nolvadex) to reduce the risk of invasive breast cancer in women with ductal carcinoma in situ (DCIS) following breast surgery and radiation.

CANTON,Ohio-Occult micrometastases may still be present after the standard 5 years of tamoxifen adjuvant hormonal treatment for patients with stage I or II breast cancer and receptor-positive tumors. Some of those micrometastases may be estrogen- or tamoxifen-sensitive, stated Terry Mamounas, MD, adding that this is a major reason the National Surgical Adjuvant Breast and Bowel Project (NSABP) has undertaken clinical trial NSABP B-33. The trial will compare 2 years of exemestane (Aromasin) to 2 years of placebo in postmenopausal, estrogen receptor-positive stage I-II breast cancer patients who are disease free after being on tamoxifen (Nolvadex) for 5 years.

HER2 is a member of the type I tyrosine kinase growth factor receptor family and participates in normal growth control mechanisms. It is overexpressed or amplified in 20% to 30% of breast cancers, as well as other carcinomas. HER2 overexpression is associated with adverse prognostic indicators in primary breast cancer, and a number of reports have shown that HER2-overexpressing breast cancer is linked to an increased rate of recurrence/metastases, and therefore, decreased disease-free and overall survival rates.

Abstracts #317 and #322 attest to the high degree of antitumor activity of docetaxel (Taxotere) in the management of locally advanced breast cancer. In abstract #317 the authors tested two hypotheses: first, that the administration of a non–cross-resistant cytotoxic regimen after induction or neoadjuvant chemotherapy improved the outcome of combined-modality treatment for both responders and nonresponders to neoadjuvant chemotherapy; and second, that the addition of docetaxel to a standard, anthracycline-containing regimen improved both clinical and pathologic response rates in locally advanced breast cancer.

Gemcitabine (Gemzar) has emerged from its initial clinical evaluation in patients with metastatic breast cancer as an effective antitumor agent. Its usual schedule of administration is weekly, and it is a very well-tolerated regimen. In combination with anthracyclines, the activity matches that of other commonly used multidrug regimens, including CMF (cyclophosphamide [Cytoxan, Neosar]/methotrexate/fluorouracil) or FAC (fluorouracil/doxorubicin [Adriamycin]/cyclophosphamide). When the taxanes became the most effective agents against breast cancer, two-drug and three-drug combinations with gemcitabine were initiated. This development was stimulated by the need to discover effective, non–cross-resistant regimens for patients previously exposed to anthracyclines and classical alkylating agents.

A phase I trial demonstrated that monthly docetaxel (Taxotere) and weekly gemcitabine (Gemzar) had both acceptable toxicity and encouraging antineoplastic activity in patients with previously treated advanced breast cancer. This phase II trial will determine the efficacy and toxicity of this regimen in advanced breast cancer patients who have measurable disease refractory to, or relapsed after, first-line or adjuvant chemotherapy.

Epirubicin (Ellence) is currently being studied in combination with the taxanes, such as docetaxel (Taxotere), in patients with advanced breast cancer. As a single agent, docetaxel has proven to be a very active drug in breast cancer, so the results of these combination trials are awaited with interest. Our experience has shown epirubicin/docetaxel to be a feasible and active combination in breast cancer.

The most efficacious primary chemotherapy regimens used to treat breast cancer contain anthracyclines. Unfortunately, a significant proportion of breast cancers fail to respond to such therapy. Therefore the aims of this study were (1) to determine the efficacy of primary docetaxel (Taxotere) in patients that initially fail to respond to anthracycline-based primary chemotherapy, and (2) to compare the efficacy of docetaxel with anthracycline-based primary chemotherapy in patients that are initially responsive to such therapy.

The degree of pathologic response of tumor to primary chemotherapy is of considerable prognostic importance in patients with breast cancer. The addition of docetaxel (Taxotere) to an anthracycline-based primary chemotherapy regimen has been shown to result in significantly improved pathologic breast cancer response. The identification of predictors of treatment response will permit cytotoxic regimens to be tailored to individual patient requirements and permit pathologic response rates to be improved.

The aim of this study was to assess the efficacy and toxicity of the combination of docetaxel (Taxotere) and vinorelbine (Navelbine), every 15 days, in anthracycline-pretreated metastatic breast cancer patients.

Docetaxel (Taxotere) and vinorelbine (Navelbine) are active agents in the treatment of metastatic breast cancer. Preclinical data suggest that there may be synergism between vinca alkaloids and taxane compounds. The current study evaluates the combination of docetaxel and vinorelbine with concurrent granulocyte colony-stimulating factor (G-CSF, filgrastim [Neupogen]) in anthracycline-refractory breast cancer. The objectives of this study are to determine the response rate, time to progression, survival, and toxicities of this regimen.

Weekly administration of taxanes as palliative treatment in metastatic breast cancer has been reported with significantly reduced hematologic toxicity and comparable efficacy to standard every-3-week protocols. This study update provides mature results with weekly docetaxel (Taxotere) in a larger patient population.