Megestrol acetate in the treatment of metastatic breast cancer

There are many non-elucidated questions concerning cancer, especially of the breast, in which hormones are involved. The scope of this particular study is to bring more clarity on the role of the progestin megestrol acetate in the hormonal treatment of breast cancer. It should be kept in mind that this is a clinical study. Biochemical details mentioned in Chapter I serve primarily as a background for a better understanding of clinical effects. The study was done from 1974-1983 and 5 questions have provided the frame for this thesis: l. How effective is megestrol acetate in the treatment of metastatic breast cancer? (Chapter II) 2. What is the role of steroid receptors in the mechanism of action of megestrol acetate in inducing tumor regression? (Chapter III + IV) 3. Has the effect of megestrol acetate on some endocrine parameters any relation to tumor regression? What is the optimal dose? (Chapter V) 4. In what sequence of hormonal treatment should megestrol acetate be used? Is there a difference with regard to the age and/or menopausal state of the patient? (Chapter VI) S. Does the combination of megestrol acetate and tamoxifen have any additional effect on endocrine events; especially can megestrol acetate-induced hyperprolactinaemia be suppressed by the administration of tamoxifen? (Chapter VII) These questions are considered in the general discussion and summar

Weekly low-dose mitoxantrone plus doxorubicin as second-line chemotherapy for advanced breast cancer

Weekly low dose mitoxantrone (3 mg/m2) plus doxorubicin (8 mg/m2) was administered as second-line chemotherapy to 33 patients with advanced breast cancer. Four out of 28 evaluable patients (14%) obtained a partial response with a median duration of 34 weeks (range 18-67+ weeks), while 8 patients (29%) showed stable disease with a median duration of 28 weeks (range 11+-60 weeks). Gastrointestinal toxicity and alopecia were mild. Grade II and III leukopenia occurred in 63% of the courses without serious infectious disease. Four patients experienced an asymptomatic drop of 16-20% in the left ventricular ejection fraction (LVEF) after relatively low cumulative doses of each drug, and one patient with a history of pericarditis carcinomatosa and mediastinal irradiation developed a heart failure. In conclusion, this second-line combination treatment had moderate activity in breast cancer and caused only few subjective side effects, especially with respect to gastrointestinal symptoms

EBAG9/RCAS1 in human breast carcinoma: a possible factor in endocrine–immune interactions

EBAG9 has been recently identified as an oestrogen responsive gene in MCF-7 human breast carcinoma cells. EBAG9 is identical to RCAS1, a cancer cell surface antigen possibly involved in immune escape. In this study, we examined the expression of EBAG9/RCAS1 in human breast carcinomas using immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR). EBAG9 immunoreactivity was also associated with various clinicopathological parameters, including intratumoural infiltration of inflammatory cells, to examine the biological significance of EBAG9 in human breast carcinomas. EBAG9 immunoreactivity was detected in the entire surface and cytoplasm of carcinoma cells in 82 out of 91 invasive ductal carcinomas (90.1%). In non-neoplastic mammary glands, EBAG9 immunoreactivity was weakly present on the luminal surface of epithelial cells. Results from RT-PCR (n = 7) were consistent with those of immunohistochemistry. EBAG9 immunoreactivity was significantly associated with estrogen receptor (ER) α labelling index (P = 0.0081), and inversely associated with the degree of intratumoural infiltration of mononuclear cells (P = 0.0020), or CD3+ T lymphocytes (P = 0.0025). This study suggests that EBAG9 is produced via ER in carcinoma cells and inhibits the intratumoural infiltration of T lymphocytes in the context of a possible endocrine–immune interaction in human breast carcinomas. © 2001 Cancer Research Campaign http://www.bjcancer.co