Richard J. Kaufman

Angiosarcoma and other vascular tumors of the breast.

Vascular tumors of the breast, with the exception of perilobular hemangiomas, are generally considered to be malignant. The pathologic and clinical features of 40 patients with angiosarcoma of the breast and 12 with other vascular tumors of the breast were reviewed. Three general histologic patterns of growth were identified among the angiosarcomas and were found to correlate closely with prognosis. Whereas 10 of the 13 patients in histologic Group I were alive and free of disease with an average follow-up of nearly 6 years, only two of 16 Group III patients were free of disease, and 14 have died. The six Group II patients had a survival similar to those in Group I. In this series the disease-free survival at 3 years was 41% and at 5 years 33%, much better than that reported in previous reviews of mammary angiosarcoma. The data also indicated that adjuvant chemotherapy, specifically actinomycin D, is effective in some and possibly all patients with angiosarcoma of the breast. The 12 other vascular lesions had distinctly different morphologic features, a benign clinical course, and should probably not be viewed as angiosarcomas. However, total excision of all vascular lesions of the breast is essential in order to determine both the diagnosis and the appropriate therapy.

Prevalence, predictors, and course of anticipatory nausea in women receiving adjuvant chemotherapy for breast cancer

Factors related to the prevalence, prediction, and course of anticipatory nausea (AN) in women (n = 77) receiving adjuvant chemotherapy for breast cancer were examined. Using a prospective longitudinal research design, patients were interviewed both before and after each chemotherapy infusion. Fifty‐seven percent of the patients developed AN. These patients were characterized by more severe gastrointestinal side effects following the initial infusion and greater expectations for experiencing chemotherapy‐related nausea. A more rapid development of AN was related to a history of experiencing nausea across a greater variety of situations, higher IV drug doses, and less infusion‐related anxiety at the initial infusion. Although AN occurred intermittently across treatment sessions, severity was constant. Results provided strong support for the hypothesis that classical conditioning processes are instrumental in AN acquisition. The role of anxiety in the development of AN is considered as are clinical implications for the prevention of AN and recommendations for future research.

Endocrine consequences of CMF adjuvant therapy in premenopausal and postmenopausal breast cancer patients

The effect of CMF adjuvant therapy (cyclophosphamide, methotrexate, and 5‐fluorouracil) on endocrine function was investigated in breast cancer patients. CMF therapy resulted in suppression of ovarian function in some premenopausal patients but pituitary function and adrenal function were unaffected. There was an inverse relation between age and duration of treatment required to induce ovarian suppression. Although amenorrhea was achieved within 2–4 months in patients aged 40 years or older, younger women required larger cumulative doses of cytotoxic drugs to induce ovarian dysfunction. Patients younger than 30 years of age continued to menstruate with no major alteration in hormonal levels resulting from the cytotoxic drugs. CMF therapy had no significant effect on hormonal levels in postmenopausal patients indicating that in this group therapeutic response is not mediated via the endocrine system.

Treatment of advanced male breast cancer.

The modalities used to treat 27 male patients with metastatic breast cancer at Memorial Hospital from 1957–1979 are reviewed. The overall objective orchiectomy response rate was 48% (11/23). The median response was 11 months (6–96 months). The median survival in responders was 58 months, whereas the median survival in orchiectomy failures was 24 months. Four patients had estrogen receptor protein determinations (ERP). Two positive ERP patients and one borderline ERP patient responded (18–34 months). One ERP‐negative patient failed orchiectomy. The number of major ablations in this series (two responses/two adrenalectomies, two failures/two hypophysectomies) does not permit conclusions, although review of the literature suggests that major ablation may be valuable in patients responding to orchiectomy. Two of three patients who refused ablative therapy responded (three months, ten months) to single agent provera. Administering stilbesterol to the ten‐month responder and to the patient who failed provera resulted in two additional responses (four months, continuing, and 22 months). Of six patients who failed orchiectomy and subsequently received chemotherapy, four patients responded (7–40 months). The median survival in these patients was 40 months (33–44 months). This review supports the importance of orchiectomy in the treatment of metastatic male breast cancer. Although the numbers are small, these data suggest that estrogen receptor determinations may be useful in selecting patients for orchiectomy. Selective additive hormone therapy may be useful in patients who refuse orchiectomy. Chemotherapy may provide worthwhile palliation in patients who fail orchiectomy.

Combined modality treatment of locally advanced breast cancer: adjuvant combination chemotherapy with and without doxorubicin

Forty-one women with non-metastatic but locally advanced breast cancer were treated by modified radical or radical mastectomy, and were then randomized to receive one of two adjuvant chemotherapy regimens. Regimen A consisted of 6 months of cyclophosphamide, adriamycin, and fluorouracil (CAF) followed by 6 months of cyclophosphamide, methotrexate, fluorouracil, vincristine, and prednisone (CMFVP). Regimen B was 12 months of CMFVP. Patients were stratified for estrogen-receptor status, and all patients with a positive estrogen receptor value received tamoxifen 20 mg bid in addition to the chemotherapy. Eight of 21 patients radomized to Regimen A are alive and free of disease, whereas only 1 of 20 patients on Regimen B is well. A trend toward improved disease-free survival favoring Regimen A was observed (P = .05), although a significant difference in overall survival has not been demonstrated. Our findings support the continued study of adriamycin-containing regimens in the adjuvant setting and in combined modality therapy of locally advanced breast cancer.

Advanced breast cancer - additive hormonal therapy.

Increased response rates with nonhormonal combination chemotherapy have led many oncologists to deprecate the use of hormonal therapy in the management of advanced breast cancer. The estrogen and progesterone receptor assay, on the one hand, has restimulated the enthusiasm for hormonal therapy when positive, but conversely when negative suggests that their use is precluded from further consideration. The authors thoughts on the continuing employment of additive hormonal therapy for almost all patients, either singly or in combination with other hormonal and nonhormonal drugs, with minimal restrictions imposed by hormonal assays or sites of disease will be presented. A short review of estrogen, androgens, progestins, Teslac®, and corticosteroids will be offered. The ease of administration of hormones and the increase in recurrent disease survival in responders compared with nonhormonal therapy strongly indicate that additive hormonal therapy still has a major role in the management of the advanced breast cancer patient.

Association of disease-free survival and percent of ideal dose in adjuvant breast chemotherapy.

The relationship between percent of ideal dose and disease‐free survival was examined in 256 Stage II and III patients who participated in a 2‐year breast adjuvant chemotherapy trial consisting of cyclophosphamide, methotrexate, and 5‐fluorouracil (CMF) given postoperatively. When analyzed analogously to previous work, the results confirmed a dose‐response relationship: that is, there appeared to be an improved disease‐free survival for patients receiving higher doses of adjuvant chemotherapy. The major criticism of such an analysis is its bias. This bias was addressed by considering only patients who were still receiving therapy at 6, 12, and 24 months; then, the dose‐response relationship was no longer seen. Although causality cannot be inferred, the apparent differences in disease‐free survival among the dose groups can be attributed to recurrences in the first 2 years among patients receiving lower doses of chemotherapy.