Breast cancer contralateral

NB There is also conclusive evidence that this agent (tamoxifen) reduces the risk of contralateral breast cancer) 2,3,7,8-Tetrachlorodibenzo-para-dioxin [1746-01-6] (Vol. 69 1997)... 

Studies with fenretinide in woman with stage I breast cancer did not show an overall effect of decreasing the risk of contralateral breast cancer. A protective effect could only be observed in premenopausal women, probably due to the modulation of the insulin-like growth factor 1 (IGF-1) by fenretinide in this population. 

The agent currently being used clinically as a breast cancer chemoprevention agent is tamoxifen. In randomized trials of tamoxifen as an adjuvant treatment for breast cancer, women who received tamoxifen also were found to have a reduced incidence of contralateral primary breast carcinomas.16 A... 

Tamoxifen has been widely used in the adjuvant treatment of invasive breast cancer associated to surgery and chemotherapy. It has been shown to be effective in preventing new contralateral tumors and local or peripheral recurrences (Nolvadex Adjuvant Trial Organization 1983 Cuzick and Baum 1985 Abe et al. 1998). The overview comprised 37,000 women from 55 randomized trials and included events occurring more than 5 years after randomization. The effects... 

Cuzick J, Baum M (1985) Tamoxifen and contralateral breast cancer. Lancet ii 282... 

The observation that women with breast cancer receiving tamoxifen had a reduced incidence of contralateral cancer was the basis for the NSABP-PI study, a randomized, double-blind, placebo-controlled trial that began in 1992. The main objective was to ascertain whether tamoxifen might effectively reduce the risk for breast cancer in women with a high risk of developing this disease. A total of 13,388 women > 35 years old were randomized to either tamoxifen (20 mg/d) or placebo for 5 years. In 1998, the trial was prematurely interrupted as the hypothesis of the study was confirmed (Fisher et al. 1998). However, the reduction in breast cancer risk with tamoxifen was accompanied by an increase in the incidence of invasive endometrial cancer (mean RR = 2.53). The increased risk was seen principally among women > 50 years old with a RR of 4.01, while among women < 49 years old the RR was 1.21. 

Estrogen receptor-positive breast cancer in premenopausal and postmenopausal women responds equally to tamoxifen therapy (see Chapter 58). In addition, daily tamoxifen administration for 5 years is a successful therapy for the prevention of breast cancer in the contralateral breast in women who have already had one episode of breast cancer. 

Tamoxifen is a competitive partial agonist inhibitor of estradiol at the estrogen receptor and is extensively used in the palliative treatment of advanced breast cancer in postmenopausal women. It is a nonsteroidal agent (see structure below) that is given orally. Peak plasma levels are reached in a few hours. Tamoxifen has an initial half-life of 7-14 hours in the circulation and is predominantly excreted by the liver. It is used in doses of 10-20 mg twice daily. Hot flushes and nausea and vomiting occur in 25% of patients, and many other minor adverse effects are observed. Studies of patients treated with tamoxifen as adjuvant therapy for early breast cancer have shown a 35% decrease in contralateral breast cancer. However, adjuvant therapy extended beyond 5 years in patients with breast cancer has shown no further improvement in outcome. Toremifene is a structurally similar compound with very similar properties, indications, and toxicities. 

Both personal and family histories influence a woman s risk of developing breast cancer. A past medical history for breast cancer is associated with about a fivefold increased risk of contralateral breast cancer. Cancer of the uterus and ovary has also been associated with an increased risk of the development of breast cancer. Breast cancer is observed as part of cancer family syndromes in association with other tumors. Only 5% of breast cancer patients are thought to have a pedigree consistent with hereditary breast cancer. 

BREAST CANCER Tamoxifen is highly efficacious in the palliation of advanced breast cancer in women with ER-positive tumors and for hormonal treatment of both early and advanced breast cancer in women of aU ages. Response rates are -50% in women with ER-positive tumors and 70% for ER-positive, PR-positive tumors. Tamoxifen increases disease-free and overall survival a 5-year treatment period is more efficacious than shorter treatments. Tamoxifen reduces by 50% the risk of developing contralateral breast cancer in women at high risk and is approved for primary prevention in this setting. Prophylactic treatment should be hmited to 5 years. The most frequent side effect is hot flashes. Tamoxifen increases the risk of endometrial cancer and thromboembolic disease by two- to threefold. 

Basically, the potential indications are closely similar to those of breast MRl. The potential indications for CEDM include the evaluation of newly diagnosed breast cancer, to assess the extent of disease (Figs. 12.6 and 12.7) and to evaluate possible contralateral disease, a problem-solving method for better characterization when conventional mammography assessment is equivocal (Fig. 12.5), the evaluation of residual disease after a lumpectomy with positive margins, the evaluation of breast cancer recurrence, the detection of breast cancer in women with axillary metastasis. 

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