Age and prognosis in breast cancer.
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Biomedical subjects
Publications and source records attributed to T J Powles.
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A phase-II study of vindesine was carried out in 23 patients with histologically proven advanced breast carcinoma. Toxicity was assessed in a further 24 patients with different tumour types. Treatment was given in a starting dose of 3 mg/m2 weekly by IV bolus, increasing by 1 mg weekly as toxicity allowed. The response rate in 21 evaluable patients w-th breast carcinoma was 29%. In 47 patients evaluable for toxicity, leukopaenia occurred in 45% and was dose-related; thrombocytopaenia was rare (4%); neurotoxicity occurred in 40%; constipation in 17%, alopoecia in 46% and an influenza-like syndrome in 21%. It was concluded that vindesine was a clinically active agent in breast carcinoma, with a spectrum of toxicity lying between those of vincristine and vinblastine.
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The diagnostic accuracy of clinical examination, xeromammography, and fine-needle aspiration cytology was compared with definitive histological findings in 255 breast lumps excised during one year. When suitable aspirates were obtained for cytological examination the diagnostic accuracy of aspiration cytology was higher than clinical examination or xeromammography. A diagnostic accuracy of 99% was achieved when all three screening tests were in agreement. As well as confirming a clinical diagnosis of malignancy, cytology is useful in identifying malignancy when clinical findings suggest that the tumour is benign. The availability of accurate cytology has affected patient management in many ways. Xeromammography did not enhance the diagnostic accuracy of clinical examination and aspiration cytology in patients presenting with a breast lump and, as a procedure with potential hazard, the benefit of routine xeromammography is questionable when an efficient cytological service is available.
42 patients with metastatic breast carcinoma were treated with aminoglutethimide, which inhibits adrenal steroid hormone synthesis. Treatment was stopped in 2 patients before response could be assessed; of the other 40, 15 (37.5%) had an objective response, 1 (2.5%) showed a response in bone but not in soft tissue, and 4 (10%) had complete or very great relief of metastatic bone pain but no radiological evidence of improvement. 19 (53%) of 36 patients with bone metastases responded to treatment (15 had X-ray evidence and 4 had pain relief), as did 5 (45%) of 11 patients with soft tissue metastases, 2 (25%) of 8 with malignant marrow infiltration, 1 (14%) of 7 with lung metastases, and none of 13 with liver metastases. Response was commonest in patients who had previously responded to other forms of endocrine therapy. Side-effects, usually mild and transient, occurred in a few patients; the most important were an initial period of somnolence in 9 patients and a rash in 5.
Two studies were performed to assess the accuracy of non-invasive methods in detecting intra-abdominal metastases from breast cancer. Firstly, the sites of spread detected at the time of first presentation with metastases were compared with the sites of spread shown at necropsy in the same patients. Although about two-thirds of the patients with bone and lung metastases at necropsy had had metastases detected at these sites when they first presented with metastases, only a third of the patients with liver metastases and none of those with other intra-abdominal metastases had had evidence of disease at first presentation with metastases. The second study confirmed a poor detection rate of liver and other intra-abdominal metastases in patients with breast cancer undergoing laparotomy and oophorectomy who were staged immediately before operation.Pre-mastectomy staging laparotomy should be considered in those patients with primary breast cancer who are most likely to have disseminated disease beyond the regional nodes. In the presence of occult gross metastases detected by staging laparotomy, mastectomy will not provide additional protection against loca recurrence of disease. Patients with occult gross metastases should also be excluded from studies on adjuvant chemotherapy (designed to treat micrometastases). Aggressive methods of staging are justified to protect the patient as far as possible against unnecessary mastectomy and to identify those patients who should be treated by therapeutic chemotherapy rather than adjuvant chemotherapy.
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Fifty patients with metastatic breast cancer were treated with a combination of vincristine, Adriamycin and prednisolone (VAP) at four weekly intervals. Response rates of 78% for soft tissue disease, 66% for parenchymal lung disease, 67% for liver disease, and 64% for pleural effusions were seen. Only 26% of patients with bone metastases showed an objective response. These figures are as good as any previously reported for chemotherapy of breast cancer.
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Nineteen biochemical parameters, most of which have been individually advocated as tumour-index-substances for breast cancer, were measured in 51 patients with breast disease, 42 of whom had active breast cancer. Seven of these parameters were raised in more than half of the 17 patients of the series with overt metastases; these were serum ferritin (88%), C-reactive protein (87%), carcinoembryonic antigen (81%), acid glycoprotein (75%), total alkaline phosphatase (64%), sialyl transferase (56%), andthe urinary hydroxyproline/creatinine ratio (73%). The incidence of biochemical abnormalities in patients in this group compared favourably with the results of physical methods of detecting metastases. 7 of 16 further patients without evidence of distant metastases, but who had a poor prognosis as judged by histology of the primary tumour and axillary lymph-nodes, had abnormalities of at least one of the seven parameters. 3 of these patients have relapsed within a year of mastectomy. The results suggest that these biochemical tests could assist in monitoring metastatic disease and could indicate at the time of mastectomy, patients who might benefit from immediate systemic therapy in addition to local treatment of their breast carcinomas.
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