It is estimated that breast cancer will kill 28,100 American women this year. This disease is the major cause of cancer death in women in the United States and the leading cause of death from all causes among women aged 40 to 44. If the disease is localized in the breast, 82 percent of patients survive 5 years or longer, but if the cancer has spread to adjacent tissues, the 5-year survival is only 47 percent.

Radical mastectomy, or complete removal of the involved breast, underlying pectoral muscle, and lymph node areas into which the breast drains, is the usual method of treatment. However, if the disease is so widespread as to be inoperable, radiotherapy is sometimes employed.

Patients whose disease is beyond the scope of the conventional treatments may respond to attempts to alter the hormonal environment by surgical removal of the ovaries, adrenal glands, or pituitary gland, and/or administration of hormones.

Male and female sex hormones as well as adrenal cortical hormones, such as cortisone, inhibit advanced breast cancer. Male hormones, or androgens, produce objective regression of disease in approximately 20 percent of patients; estrogens are given to postmenopausal patients only, and produce regression in an estimated 36 percent of them. Estrogens are relatively more effective on the soft tissue of breast cancer and androgens, on bone metastases. Hormones may produce undesirable side effects, including masculinization by androgens and uterine bleeding by estrogens.

Breast Cancer 28

The major cause of cancer death among United States women, breast cancer, will take 28,000 lives this year.

Other cancer drugs, such as alkylating agents (cyclophosphamide, nitrogen mustard, thioTEPA, and TEM), produce temporary improvement in one-fifth to one-half of patients treated after hormonal agents fail to stop the spread of disease. Vinblastine, an alkaloid extract, also may produce transient benefits.

5-Fluorouracil (5-FU) has proved useful in many patients, as it often induces remission when other drugs have failed. A report in 1966 noted that a group of patients receiving 5-FU survived an average of 10 1/2 months longer than a group treated similarly with one or more of the standard treatments (surgery, irradiation, hormones). The drug is especially toxic in patients previously treated with alkylating agents or extensive irradiation of the pelvic area.

Scientists at New York University reported in 1959 that methotrexate given orally once a day induced objective improvement in about 30 percent of patients with widespread disease. In 1968 another group of scientists reported that the drug given every 6 hours in 5-day courses produced objective remissions in 15 of 33 patients (45 percent) refractory to hormone therapy; the remissions lasted an average of 9 months. Evaluation of methotrexate in a larger series of patients seems to be indicated.

Use of a combination of methotrexate and thioTEPA was also reported during 1968. Objective responses were produced by giving the two drugs in individualized dosage schedules with continuous administration of testosterone, vitamin B 12, and modest doses of corticosteroid hormones. 5-FU was added in the presence of liver metastasis, and cyclophosphamide often substituted for thioTEPA if there were bone metastases. Of 113 patients treated, 60 percent of those who were hormone-resistant showed a response, as did 80 percent of those not previously given hormone therapy.

Combination chemotherapy using chlorambucil and a hormonal compound, prednisolone, was evaluated in another group of patients with disseminated disease most of whom had previously undergone radical mastectomy. Twenty-four of 71 patients (33 percent) had objective regressions averaging 17.4 months and a mean survival time of almost 2 years.