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PATIENTS who have undergone complete hypophysectomy in the treatment of carcinoma of the breast hardly ever show subsequent improvement when treated with hormones such as androgens, oestrogens or cortisone analogues. This clinical observation supports the conclusion, in most experimental animals, that after hypophysectomy there is little or no response by breast tissue to stimulation with oestrogens. Apart from general care and analgesics the palliation of patients with advanced carcinoma of the breast uncontrolled by pituitary ablation is therefore limited to radiotherapy, the cytotoxic drugs and possibly 3-methylcholanthrene (Huggins and McCarthy, 1957). The effect of hypophysectomy, though satisfactory in over 50 per cent of patients, seldom lasts longer than three to four years (Luft et al., 1958; Ray and Pearson, 1956; Baron et al., 1958). Very often the general condition of these patients is surprisingly good at the time of relapse or when it becomes clear that hypophysectomy has not been beneficial. Attempts at further treatment are sometimes justified. Because hormones are ineffective and in the majority of cases radiotherapy is contra-indicated, we have studied the effect of the aklylating agent triethylene thiophosphoramide (thiotepa). Shay and his colleagues (Shay et al., 1953; Shay and Sun, 1955) first suggested that thiotepa might be of benefit to patients with metastatic carcinoma of the breast. Subsequently Bateman and her colleagues (Bateman, 1955; Bateman and Larsen, 1956) reported improvement in up to 85 per cent of patients so treated. It appears that thiotepa is relatively more effective in the treatment of mammary and ovarian carcinoma than in lymphomas such as Hodgkin's disease or leukaemias.

Triethylene Thiophosphoramide in the Treatment of Previously Hypophysectomised Patients with Carcinoma of the Breast