J.L. Hayward

Treatment of early breast cancer: a report after ten years of a clinical trial.

A controlled clinical trial has been carried out to compare radical mastectomy with wide excision (extended tylectomy) in the treatment of early breast cancer. Only patients aged 50 and over were included and 370 entered the trial during a period of 10 years. Postoperative radiotherapy was given in each case. In patients with clinically involved axillary nodes there was a significantly higher incidence of local and distant recurrence in those having a wide excision, and the survival of these patients was significantly less than those who had a radical mastectomy. In patients with clinically uninvolved nodes, although there was a significantly higher incidence of local recurrence in those having a wide excision, there was no increased incidence of distant recurrence and the survival rate was similar to those having a radical mastectomy.

RELATION BETWEEN URINARY ANDROGEN AND CORTICOID EXCRETION AND SUBSEQUENT BREAST CANCER

Abstract The excretion of androsterone and aetiocholanolone is subnormal in women who subsequently develop breast cancer. The abnormality is found at all ages between 30 and 55 years and up to 9 years before diagnosis. Measurement of androgen metabolite excretion might be considered suitable for screening a normal population for women with a high risk of breast cancer.

Oestrogen receptors, sites of metastatic disease and survival in recurrent breast cancer

Two hundred and seventy eight patients with advanced breast cancer who had oestrogen receptor (ER) analyses performed on primary or recurrent tumours were studied. Oestrogen receptor (ER) positive (ER ≧ 5 fmole receptor/mg cytosol protein) tumours recurred significantly more commonly in bone and ER negative (ER < 5 fmole receptor/mg cytosol protein) tumours recurred significantly more often in liver and brain. Patients with ER positive tumours had a significantly better survival after relapse. ER analysis of either primary or recurrent tumour gives some indication of the natural history of breast cancer.

A comparison of intracavitary talc and tetracycline for the control of pleural effusions secondary to breast cancer

Forty-one patients with malignant pleural effusions secondary to breast cancer were randomly allocated to treatment with either intracavitary talc or intracavitary tetracycline. Of 33 evaluable patients, radiological control was achieved in 11/12 (92%) of the talc group compared with 10/21 (48%) of the tetracycline group (P = 0.022). Intracavitary talc provides effective palliation of metastatic pleural effusions secondary to breast cancer.

Assessment of axillary lymph node status.

Three methods of assessing axillary lymph node status were compared: In 149 patients assessed clinically, positive nodes were not detected in 31 (45%) of 69 patients with pathologic Stage II disease. Histologic examination of selected axillary nodes biopsied from 54 patients immediately prior to mastectomy, failed to detect metastatic disease in 11 (42%) of 26 patients with pathologic Stage II disease. Examination of lymph nodes in the axillary tail of 95 mastectomy specimens failed to diagnose axillary involvement in six (14%) of 43 patients with pathologic Stage II disease. Thus, none of the techniques determined the extent of axillary node involvement.

Prognosis in inoperable Stage III carcinoma of the breast

Abstract One hundred and eighty-four patients with inoperable Stage III breast cancer presenting to the Guys Hospital Breast Unit between 1961–1973 were treated initially by radiotherapy alone. The response rate was 60% but duration of response and survival were short. Seventy-two per cent of patients did not have prolonged control of local disease and 63% developed distant metastases. The association between certain prognostic variables and response to radiotherapy, subsequent development of metastases and survival was analysed statistically. The duration of response to radiotherapy showed no significant associations with any prognostic variable. Subsequent distant metastases occurred less often in patients responding to radiotherapy, having a subsequent mastectomy or if the duration of symptoms before presentation was long, but more frequently if the primary tumours were diffuse. Survival was shorter in patients who were early postmenopausal, had a short duration of symptoms or had diffusc primary tumours. Improved survival was associated with a good response to radiotherapy and, unexpectedly, with deep fixation of the primary tumour. Prognosis was not significantly associated with size of primary tumour or involvement of skin or lymph nodes. The effectiveness of combining variables in predicting prognosis is described. A further group of 30 patients, unsuitable for radiotherapy were treated primarily by additive endocrine therapy and had a median survival of 14 months. The clinical course of Stage III breast cancer is variable, there being two extremes: a slowly-growing, non-metastasising form and a more common, rapidly-growing, metastasising form. For prognosis to be improved, systemic therapy as part of the primary management of this disease may be necessary. Prognostic variables should be considered in the design and assessment of future clinical trials.

Abnormal urinary steroid excretion and subsequent breast cancer. A prospective study in the Island of Guernsey.

Abstract A prospective study of a normal population was undertaken, to investigate a possible association between abnormal urinary hormone excretion and the subsequent development of breast cancer. Over 5 years, 4850 24-hour specimens of urine were collected from women on Guernsey between the ages of 35 and 55. Nineteen of these women have since developed breast cancer. The results show that in a substantial proportion of the cancer patients, the excretion of androgen (aetiocholanolone) and corticosteroid metabolites (17-hydroxycorticosteroids) was abnormal. The abnormality was multidirectional and, when compared with controls, tended to deviate further from the control mean values than did the individual controls. This deviation was statistically significant.

Locally advanced breast cancer: The contribution of cytotoxic and endocrine treatment to radiotherapy. An EORTC breast cancer co-operative group trial (10792)

Patients with locally advanced carcinoma of the breast were randomized to receive either radiotherapy alone, radiotherapy + endocrine therapy, radiotherapy + chemotherapy or radiotherapy + endocrine therapy + chemotherapy. In 363 evaluable patients, time to first progression was delayed significantly by both endocrine treatment and chemotherapy, the greatest effect being achieved by the combination of endocrine treatment and chemotherapy. This effect was almost entirely due to a major effect of systemic treatment on time to loco-regional progression, for which the result is highly significant, rather than time to distant metastasis in which only a non-significant trend was observed. For survival, a trend was seen in favour of the combination of hormone treatment and chemotherapy, but this effect did not achieve statistical significance. This trial suggests that current endocrine and cytotoxic treatments are only of marginal value in improving the prognosis in locally advanced breast cancer.

Pleural effusion in breast cancer: A review of 105 cases

This paper reviews 105 patients with breast cancer who had a pleural effusion as a direct consequence of metastatic disease. The mean lag time between diagnosis of primary tumor and presentation of the effusion was 41.5 months. Mean survival time after development of an effusion was 15.7 months. Of the 99 patients with unilateral breast tumors, 50% had ipsilateral effusions, 40% were contralateral, and 10% were bilateral. Forty‐two percent of the patients had pleural effusion as the first evidence of recurrence.

Combined chemotherapy and radiotherapy for locally advanced breast cancer

Abstract To test the feasibility of combining radiotherapy and chemotherapy as the primary management of locally advanced breast cancer, 24 patients were allocated to receive either 4 courses of adriamycin and vincristine (AV) followed by radiotherapy, followed by 8 courses of cyclophosphamide, methotrexate and 5 -florouracil (CMF) (group A) or radiotherapy followed by 4 courses of AV followed by 8 courses of CMF (group B). The objective regression rate after AV and radiotherapy was 10/12 ( 83% ) in group A and 11/12 ( 92% ) in group B, but the subsequent relapse rate was high being 6/12 ( 50% ) in group A and 7/12 ( 58% ) in group B. The pattern of relapse, duration of objective regressions and survival in groups A and B were the same. No serious adverse side effects arose from combining chemotherapy and radiotherapy in either group. In a retrospective comparison of groups A and B with patients treated previously by radiotherapy alone, the median duration of response in this series of 33 months was significantly longer than in patients treated by radiotherapy alone ( 10.5 months ); P ≤ 0.001. Although the survival experience of the combined groups A and B (median 36 months ) was higher than that in the previous series (25 months) this difference is not statistically significant. While these retrospective comparisons give rise to optimism that combining radiotherapy and chemotherapy may be helpful in the treatment of locally advanced breast cancer, prospective randomized controlled trials are now necessary to determine whether a true improvement in results can be achieved by this approach.