Effect of tamoxifen on serum cholesterol and lipoproteins during chemohormonal therapy.

The effect of tamoxifen on serum cholesterol, high density lipoprotein cholesterol (HDL-cholesterol), low density lipoprotein cholesterol (LDL-cholesterol) and the ratio of LDL-cholesterol to HDL-cholesterol (LDL-C/HDL-C) was investigated in breast cancer patients undergoing therapy for advanced disease. Longitudinal studies in 24 patients treated with tamoxifen (10 mg, twice daily) indicated average decreases in total serum cholesterol (17%) and LDL-cholesterol (27%), whereas the effect of tamoxifen on HDL-cholesterol varied with the individual patient. There was a significant decrease in the LDL-C/HDL-C ratio (33%) consistent with a decreased risk for coronary artery disease. This beneficial influence of tamoxifen on risk factors associated with cardiovascular disease was evident in both premenopausal and postmenopausal patients whether tamoxifen was administered alone or in combination with cytotoxic chemotherapy.

CA 15-3 and carcinoembryonic antigen in the clinical evaluation of breast cancer.

The individual and combined value of CA 15-3 and carcinoembryonic antigen (CEA) as breast cancer tumor markers was investigated in longitudinal studies. Patients included women at high risk for recurrence after primary therapy or undergoing treatment for metastatic disease. During follow-up, recurrent disease was documented in 33 of 39 (85%) patients including 11 with local recurrence and 22 with distant metastases. At the time recurrence was first documented by objective criteria 23 of 33 (70%) of the patients presented with abnormal CA 15-3 levels (greater than 36.7 U/ml) compared with 19/33 (58%) with abnormal CEA levels (5 ng/ml). Tumor marker elevations predominated in patients with advanced disease indicating that CA 15-3 and CEA are not reliable for the detection of early breast cancer. Both markers were helpful in monitoring therapeutic response since antigen levels correlated closely with disease status.

The treatment of metastatic breast cancer.

While metastatic breast cancer is not curable, it is treatable. Its treatment is associated with a relatively high rate of success, and patients are able to maintain a good quality of life for periods ranging from a few months to several years. This knowledge should encourage both the patient and the oncologist to maintain treatment as long as potentially effective therapeutic methods are available. Progress is ongoing both in the development of new forms of treatment and in new ways of using and combining already existing therapeutic modalities. There is still no established "best" or "only" first treatment of metastatic breast cancer. When secondary and later treatment is to be undertaken, the task of selecting the most appropriate treatment becomes even more complex. It is only through controlled clinical trials that useful therapeutic guidelines will develop. Treatment is a joint endeavor involving both the physician and the patient. Communication must remain open. In the final stages of the illness, treatment should be directed toward the relief of distressing symptoms and anxiety.

CA 549 as a marker in breast cancer.

CA 549 is one of several carcinoma associated mucin antigens proposed as a breast cancer tumor marker. In this study, the performance characteristics of the CA 549 assay were validated and the clinical utility of the test was compared with that of other breast cancer markers including CA 15-3, CA M26, CA M29 and carcinoembryonic antigen. The upper limit of normal was established as 15.5 U/ml based on data for 250 control subjects apparently free of disease. Overall, CA 549 had a low negative predictive value (0.51) due to a low sensitivity in the detection of early breast cancer. However, the test had a high positive predictive value (0.93) reflecting a high specificity for the disease. In 56 patients with advanced breast cancer, the sensitivity was 0.71 for CA 549 alone and 0.79-0.84 for CA 549 combined with any of the other markers studied.

Evaluation of CA M26, CA M29, CA 15-3 and CEA as circulating tumor markers in breast cancer patients.

The clinical utility of CA M26 and CA M29 was studied in 116 breast cancer patients and compared with results for CA 15-3 and carcinoembryonic antigen (CEA). The highest sensitivities for breast cancer detection were achieved with CA 15-3 (0.60) and CEA (0.56), but this was compromised by a relative lack of specificity (0.87 and 0.88 for CA 15-3 and CEA, respectively). Sensitivities attained with CA M26 (0.47) and CA M29 (0.53) were lower, but there was an excellent specificity (1.00) for each assay in this series of benign patients. Tumor marker elevations were appreciable with advanced disease such that 82 of 91 patients (90%) with active metastatic breast cancer exhibited at least one abnormal test value. Longitudinal studies demonstrated that CA M26, CA M29, CA 15-3 and CEA complement each other and combinations of these markers reflect disease status better than individual tests.

Chemohormonal therapy and endocrine function in breast cancer patients.

The administration of CMFVP (cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, and prednisone) results in profound alterations in hormonal profiles of premenopausal women due to a reduction in ovarian and adrenal secretion of estrogens and androgens. Cytotoxic chemotherapy results in ovarian suppression as documented by decreases in estradiol with concomitant elevations in pituitary gonadotrophins, whereas the addition of prednisone to the cytotoxic regimen results in significant decreases in androgen levels due to adrenal suppression. In postmenopausal women, CMFVP also results in significant decreases in estrogens and estrogen precursors due to suppression of adrenal steroid metabolism. Continuous low-dose prednisone administration during cytotoxic chemotherapy appears to be more effective than an intermittent high-dose schedule in achieving and sustaining adrenal suppression. However, complete elimination of adrenal steroidogenesis does not occur in all cases since measurable amounts of adrenal steroids remain in the serum throughout chemohormonal therapy. The administration of tamoxifen plus CMFVP is associated with hyperestrogenemia in younger premenopausal patients which persists until the onset of ovarian suppression.