TAMOXIFEN IN BREAST CANCER: WHO SHOULD RECEIVE SYSTEMIC CHEMOTHERAPY OR HORMONAL THERAPY?

Premenopausal versus Postmenopausal Patients We have seen that the decision about whether to treat with systemic chemotherapy or hormonal therapy is dictated by a number of factors, which include the size of the tumor at diagnosis, menopausal status, and the degree to which the cancer has spread to other areas such as the lymphatic channels and axillary nodes. From numerous studies performed since the mid-1970s, we know that systemic chemotherapy is very effective in reducing the risk of cancer recurrence, particularly in premenopausal patients. Hormonal therapy has been substantially less effective in this population.

Originally, premenopausal women were excluded from studies evaluating the efficacy of tamoxifen in breast cancer. It was believed that the high circulating levels of estrogen in their blood would interfere with tamoxifen's ability to block the estrogen receptor. Several clinical trials evaluating tamoxifen's use in premenopausal patients have shown response rates of up to 30 percent, however, which is approximately the response rate observed following removal of the ovaries in such patients. In estrogen-receptor-positive premenopausal patients, the response rate is higher; approximately 40 percent of the patients responded, a rate consistent with the results achieved by ovariectomy in this group.

Thus recent trials indicate that tamoxifen may be a satisfactory 36 Tamoxifen in Breast Cancer alternative to surgical ovariectomy in premenopausal patients, particularly in the setting of advanced or metastatic disease. Adjuvant tamoxifen may also significantly reduce the risk of breast cancer recurrence in premenopausal patients, but to date significant improvement in overall survival has been observed only in patients older than 50 years.

In postmenopausal patients, the efficacy of systemic chemotherapy in prevention of breast cancer recurrence has been controversial. Most physicians feel that patients of this age should receive more effective forms of hormonal therapy, particularly if their tumor tissue contains either estrogen or progesterone receptors. Increasing evidence indicates, however, that some postmenopausal patients benefit from the use of certain systemic chemotherapy combinations. In this group of patients, both systemic chemotherapy and hormonal agents may be used in combination.

In summary, systemic chemotherapy is most often used in premenopausal patients, whereas hormonal therapy is more commonly used in postmenopausal patients. Combination therapy (hormonal plus systemic chemotherapy) can be used in both populations, however.

Patients with Node-Positive and Node-Negative Breast Cancer Chemotherapy was first shown to be effective in patients with breast cancer that had spread to the axillary lymph nodes. This form of treatment appears to be most effective in patients who have one to three positive nodes, but is also beneficial to those with four or more involved nodes. In "node-negative" patients (in whom the cancer has not yet spread to the lymph nodes), most cures are by surgery or other forms of local therapy alone. But approximately 20 to 30 percent of node-negative patients may develop a breast cancer recurrence and eventually die of metastatic disease. It is difficult to determine who in this subset of patients is most at risk for recurrence and therefore most likely to benefit from chemotherapy. In general, patients who have invasive tumors greater than one centimeter in diameter are given systemic chemotherapy. Factors that may increase the risk of recurrence include a very large tumor at initial diagnosis, estrogen-receptor-negative status, and a tumor that is identified by the pathologist as aggressive (poorly differentiated) or rapidly proliferating. Typically, tumors with a large number of cells that are actively dividing (a high percentage of cells in S-phase) are considered more aggressive than tumors with a low fraction of cells in S-phase.

Tamoxifen's role in the treatment of breast cancers that are in situ (preinvasive) or that have minimal (microscopic) invasion beyond the ducts or lobes is still being debated. Most physicians feel that the risk of tumor recurrence after surgery in this group of patients is relatively low and that it is not worth the risk of potential side effects from chemotherapy. Current clinical studies using tamoxifen in patients with estrogen-receptor-positive tumors that are node negative suggest that tamoxifen is effective in reducing recurrence regardless of patient age.

Patients Who Are Estrogen Receptor Positive In general, an estrogen-receptor-positive patient will be offered tamoxifen, particularly if she is postmenopausal. If a patient has cancer that has spread to the lymph nodes, chemotherapy may also be given. Some oncologists prescribe tamoxifen for patients who are estrogen receptor negative.

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