George R. Blumenschein

The natural history of breast cancer patients with brain metastases

One hundred one breast cancer patients with brain metastases (BM) were reviewed. The median survival from BM was 4.0 months. Seventy percent were receiving chemotherapy at the diagnosis of BM and 43% were showing a clinical response. Prolonged survival was seen in patients who underwent surgical resection, those with the brain as site of first metastasis, and those with a long free interval who survived the initial 5 months after BM. Long‐term survivors (>18 months from BM) demonstrated indolent disease by all parameters measured.

Treatment for meningeal carcinomatosis in breast cancer.

Forty breast cancer patients with meningeal carcinomatosis were treated with a combined program of whole brain irradiation therapy with intrathecal and intraventricular methotrexate and citrovorum factor rescue. Responses were seen in 26 patients (65%); 13 patients (35%) failed to respond. The median survival time for the responding patients was six months, and for the nonresponders, one month. Factors affecting response and survival included pretreatment spinal fluid glucose, protein, and duration of CNS‐related symptomatology prior to onset of therapy. In contrast, pretreatment CSF tumor cell count, CEA and initial CNS functional status did not appear to have prognostic significance. The authors conclude that following intensive therapy there can be much improvement in the quality of life and disease‐free survival in breast cancer patients with meningeal carcinomatosis.

Male breast cancer. A natural history study

Eighty‐seven cases of male breast cancer seen over a 30‐year period were reviewed. The overall observed and corrected five‐year survival rates of 42% and 53% correspond well with the results in other series. Factors predicting disease‐free interval and survival included size of primary lesion, ipsilateral axillary status, and presence of ulceration, which appear to be similar to those observed for female breast cancer. Eighteen patients (21%) had a second primary tumor (seven with cutaneous malignancies) and were of an older age group with a higher incidence of positive family history of breast cancer as well as other tumors. The overall prognosis of breast cancer in males does not appear to be less favorable than that in females. Cancer 44:748‐754, 1979.

Immunotherapy with BCG administered by scarification: standardization of reactions and management of side effects.

The method of administering BCG by scarification is described in detail. A system of classifying the intensity of local reactions is proposed to standardize administration. The experience of the M. D. Anderson Hospital involving over 2700 patients is reviewed. Administration of BCG by scarification has been accomplished with safety and has been well tolerated and accepted. The most commonly observed side effects are discussed as well as their management. Cancer 42:2293–2303, 1978.

FAC + BCG as Adjuvant Therapy in Breast Cancer: An 8-Year Update

In January 1974, the Medical Breast Service at M.D. Anderson Hospital began investigation of a combination of fluorouracil, doxorubicin (adriamycin), and cyclophosphamide (FAC) as adjuvant therapy for stage II and III breast cancer. Earlier results of these studies have been published [1–3]. Here the results of the initial study are presented, with the median follow-up of FAC-treated patients being 85 months. As this is the first adjuvant program utilizing FAC with such long-term follow-up, it seemed important to review the results of stage II and III patients so treated.

Regulation of breast tumor growth by high dose estrogen is independent of the presence of estrogen receptors

Summary17β-estradiol stimulated the clonogenic growth of four established human breast tumor cell lines independent of the estrogen receptor status of the cells. Likewise, tamoxifen citrate, a nonsteroidal antiestrogen, inhibited thein vitro growth of both estrogen receptor-negative and estrogen receptor-positive cell lines to a similar degree. These findings indicate that, at pharmacologic doses, the growth stimulatory and inhibitory effects of estrogen and antiestrogens are not necessarily mediated by hormone-specific receptors.

Systemic Therapy of Metastatic Breast Cancer: A Review of the Current Trends

This paper reviews the different options of systemic therapy available for the management of patients with metastatic breast cancer. Endocrine therapy with tamoxifen, aminoglutethimide, progestins or androgens are useful for approximately one half of the patients either before or after chemotherapy. Combination chemotherapy is effective in approximately 75% of the patients and offers the best palliation for the majority of the patients. Adriamycin-containing regimens have resulted in slightly superior results than combination regimens which exclude adriamycin from first line chemotherapy. Secondary chemotherapy is useful only in 25-30% of the patients and responses usually do not last longer than 4-6 months. With carefully planned and properly sequenced treatment approaches, patients with metastatic breast cancer have a median survival of 2 years and a 5-year survival of 10-15%.

Significance of drug dose, timing and radiotherapy in adjuvant therapy of breast cancer.

In the past decade, many adjuvant chemotherapy trials in operable breast cancer have been conducted. The results of these trials have answered a number of questions, but have also raised new issues. Among other issues, results have suggested that relapse-free survival was dependent on the dose of cytotoxic drugs and the timing of initiation of chemotherapy [1, 2]. Routine postoperative irradiation was shown to have a detrimental effect on the efficacy of adjuvant chemotherapy [2, 3]. At M.D. Anderson Hospital, since 1974, a combination of fluorouracil, doxorubicin (adriamycin), and cyclophosphamide (FAC) has been utilized following regional therapy in patients with operable breast cancer. In this paper the dose of cytotoxic drugs, timing of initiation of chemotherapy, and the role of routine postoperative irradiation are evaluated.

Autologous and homologous immunofluorescent antibody to established breast cancer cell lines.

SummaryIndirect immunofluorescence tests were performed on 14 established human breast cancer cell lines using sera from a variety of subjects. Autologous reactions were studied on 10 cell lines, with positive reactions demonstrable in 8. Tests using sera from a randomly selected population of breast cancer patients showed reactivity in 40 to 66% depending on the target cell line used. Reactivity to other nonbreast cancer cell lines was rare. Several control populations were tested, including normal blood bank donors, persons with benign breast disease, and persons with other forms of cancer; immunofluorescent antibody was detected much less frequently in sera from these populations than those from the breast cancer group. Positive reactions remained in spite of absorption of serum with heterophile antigens, normal human breast tissue, and AB+ red blood cells. Thus established cell lines of human breast cancer possess antigens commonly recognized by sera from breast cancer patients.

Immunology and Immunotherapy of Human Breast Cancer

The discovery of tumor-specific antigens and tumor-specific immune responses in both animals and humans with malignant disease has increased understanding of the host defense mechanisms in the etiology and pathogenesis of cancer. However, before these tumor-specific immunological phenomena were clearly documented in man, it was strongly suspected that host defense mechanisms or their failure played a role in the etiology and pathogenesis of tumors. As these tumor-specific immune mechanisms were discovered in man, the concept of immunological surveillance was developed.(1)