a) Response

No endocrine treatment, either by hormone administration or by ablation, has ever been known to cure a patient with breast cancer. This is irrespective of whether the cancer has spread locally or distantly. Where treatment by conventional surgical methods is not possible, the principal aim of endocrine therapy in the advanced disease must be to palliate. In this context, palliation means not only the alleviation of distressing symptoms but also the reduction in size or the disappearance of active lesions. The resulting benefit can be so pronounced that the patient is restored to normal health for several years.

Castration need not be artificially induced to do this. The occurrence of the natural menopause in a patient who has carcinoma of the breast can cause the tumour to regress. Smithers (1952, 1953), reported three patients who had marked regression of the primary tumour following the natural menopause. But the menopause seldom occurs at the moment when it would be most helpful to a patient with breast cancer and so has to be induced artificially, either by surgical removal of the ovaries or by ovarian irradiation.

There are many conflicting reports of the remission rate that can be expected following castration. Principally this is because there has been no measure of agreement between various workers and centres on the criteria of a successful response. Indeed, in some reports, the criteria of response have not even been mentioned. Nissen-Meyer (1965), in his monograph on castration in female breast cancer, listed fifteen series, including a total of 2,221 patients, in which the remission rate varied between 15.2 per cent and 50 per cent. Such a variation could not be the result of different techniques of castration, nor of differences in the patient material available to each investigator. More likely, it is because each assessment was related to different criteria of success. Some physicians were satisfied that a response had occurred when the growth of a few lesions was retarded and there was relief from pain. Others required evidence that all lesions had diminished in size and that no new lesions had occurred — albeit for a very short time. Still others imposed a time limit on success and refused to accept a period of remission of less than six months.

Under these circumstances, it is impossible to say what is correct and what is incorrect. There is no right or wrong when a whole range of equally valid possibilities and variables is considered. Each worker has to choose his own criteria and be able to defend his choice.

There are two rules which most workers have adhered to in these investigations and about which there can be little controversy. Firstly, only objective evidence of remission should be accepted. This is not to infer that subjective remission, such as the relief of pain, is not important — particularly to the patient — but subjective remission can be so greatly affected by factors other than the treatment under test that its use as a measurement of response is quite unreliable. For example, relief from pain can be the result of enforced bed rest; apparent improvement in the patient’s appearance and well-being can be due to hospitalisation and good nursing; even the enthusiastic application of a new treatment can cause the patient to say she feels better. The decision that a remission has occurred must depend solely on the measureable improvement of lesions which can be either seen, palpated or demonstrated radiologically. These measurements should have been carried out at regular intervals and, on each occasion, compared both with the measurements taken at the previous examination and with the condition of the patient before treatment was applied.

Secondly, the criteria of response, which an observer accepts as proof of remission, must be declared with his results. These criteria should not be ambiguous, should be applicable to every case, and no exception should be made unless the reason is clearly stated.

It would be preferable to have an agreed set of rules for the assessment of palliative treatments for patients with advanced breast cancer. In 1965, an International Symposium was held to try to formulate such a set of rules. This did not prove possible at the time, but the Symposium at least made workers from many centres state exactly how they assessed the response of their patients. The report of the Symposium (Hayward and Bulbrook, 1966) described a few well-defined protocols.

An overall remission rate for ovarian ablation cannot be agreed without an accepted definition of remission, nor can a comparison between the results of two centres be accepted unless their protocols are identical (it is doubtful even then if such an exercise is worthwhile, considering the major differences that can occur in patient material). Therefore, after consideration of the world literature, the presumption of an overall percentage remission following castration can have only a restricted meaning. Nissen-Meyer (1965) in analysing a collected series of 2,221 patients, stated that 29.29 per cent experienced a remission. Lewison (1962) concluded his review on prophylactic and therapeutic castration by stating… “A review of the clinical results of therapeutic castration in pre-menopausal women with advanced breast cancer, indicates that oophorectomy is an effective palliative procedure in about 25 per cent of the patients.”

The surgeon, who wishes to know his patient’s chances of success, can accept these figures, but must understand the limits of the evidence on which they are based. Much of this difficulty could be avoided if there was an accepted international protocol for the assessment of response to the palliative treatment of advanced breast cancer — and there is a great need for this.

Table 1 shows details of 1,259 patients included in five reports of therapeutic castration. The remission rates vary from 15.2 per cent to 47.5 per cent—a...