The effect of the alteration in the endocrine status on breast cancer

Abstract

It is the purpose of this thesis to show how the problem of the physiological action of the secretions of the gonads has been gradually elucidated, and how; as a result of earlier work, alterations in the normal hormone balance of the body have come to be utilised in the treatment of carcinoma of the breast.

The extensive literature on the subject has been reviewed, and it has been shown how the knowledge gained from animal experiments has been added to the information obtained from clinical observation, so that At the present day we have some idea how to help patients who are otherwise beyond the reach of any other form of therapy..

The development of the work in Edinburgh has been outlined. Over 500 cases have been reviewed in the present series and the conclusions reached are in the main in accord with those reported in the .literature. These may be briefly summarised.

There is no indication that hormone therapy cures carcinoma of the breast, and even from a palliative point of view, radiotherapy to localised metastases is more likely to give a better result and more lasting relief.

Where hormone therapy is indicated it has been found that ovarian irradiation is of value in pre- menopausal patients. 10.07% of all patients treated showed a good response and 11.41% a fair response.

The administration of stilboestrol dipropionate gives a good response in 9.635 and a fair response in 20.18%. Women in the late fifties and over respond best. The dosage found most useful was 5 mgm. twice a day on alternate months.

Other synthetic oestrogens, dienoestrol and triphenylchlorethyÍene, have been found to have some beneficial effect. They do not seem to have such a marked action as stilboestrol, but the numbers, especially in the triphenylchlorethylene group, are small.

No response was seen in any case treated with progesterone, but here again the numbers were too small to allow of a definite opinion.

Testosterone, with or without bilateral oophorectómy, may be of value in women of all ages. In this series no dramatic response was found, but again the numbernso treated was small and the total dosage - about 2000 mgm. - was smaller than the doses reported in the literature as most likely to give a good response.

Various findings either do not agree completely with those reported in the literature or have not been specially noted before.

All types of metastases, including those in bone, have on occasions responded to stilboestrol. Radiological evidence of response in bone has not been found in the literature.

Using testosterone, response in soft tissue metastases has been found here more frequently than in osseous metastases. Others have reported response more frequently in bony lesions.

The response to stilboestrol has been found to be less favourable after ovarian irradiation. This has not been noted particularly before.

No correlation has been found here between response and histological type.

The possible mode of action has been discussed. Various theories put forward by other observers have been mentioned.

It has been concluded that the most likely mode of action is by an alteration of the endocrine balance of the patient. The stability of the endocrine status therefore determines response in the first place. This may be modified by an inherent disturbance of steroid metabolism such as is occasioned by liver dysfunction. It may also be modified by previous ovarian irradiation.

A further important factor lies in the nature of the tumour itself. Some tumours may be more sensitive than others to changes in the balance of the sex hormones.

Finally various suggestions are made as to how the subject may be further studied and the work extended.