M. A. Chaudary

Inadequacy of iridium implant as sole radiation treatment for operable breast cancer

In order to avoid a prolonged course of external irradiation as part of breast conservation therapy, 27 patients received an iridium implant to the primary tumour bed as sole radiation treatment. Surgery was standardised comprising tumourectomy and axillary clearance. Using a rigid implant afterloading with iridium192 wires, 55 Gy was delivered on a continuous basis over 5 days. After 6 years median follow-up, relapse of cancer within the treated breast has occurred in 10 of the 27 patients (37%). Compared with historical controls treated by similar surgery and iridium192 implant (20 Gy) with external radiotherapy (46 Gy), there was a significantly increased breast relapse rate in those treated by iridium implant alone. However, the incidence of distant metastases and overall survival was similar. Thus, a continuous iridium192 implant delivering 55 Gy in 5 days is not an effective means of achieving local control in patients with operable breast cancer.

Timing of surgery during menstrual cycle and survival of premenopausal women with operable breast cancer

Timing of operation in relation to menstrual phase might affect outlook in premenopausal women with operable breast cancer. We examined the records of 249 such women treated between 1975 and 1985, and compared overall and recurrence-free survival in those whose operation was 3-12 days after their last menstrual period (LMP) (group 1, n = 75) with those in whom it was 0-2 or 13-32 days after LMP (group 2, n = 174). Overall and recurrence-free survival were greatly reduced in group 1 women (p less than 0.001 for both). Actuarial survival at 10 years was 54% in group 1 versus 84% in group 2. This effect was independent of other factors, was of much the same importance as nodal status in multivariate analysis, was largely confined to histologically node-positive cases, seemed to be greater in women with small tumours (less than or equal to 2 cm), and was seen in patients with oestrogen-receptor positive and negative tumours. Thus phase of menstrual cycle at operation is of great importance for long-term outlook in premenopausal women with breast cancer.

Iridium implant treatment without external radiotherapy for operable breast cancer: a pilot study

A pilot study has been conducted to examine a new approach to the treatment of operable breast carcinoma. 27 patients with tumours measuring up to 4 cm in diameter have been treated by tumourectomy, axillary clearance and high dose iridium-192 implant (55 Gy) without any external beam radiotherapy. This enabled the entire local primary treatment of the breast carcinoma to be given in five days. The technique was compatible with adjuvant chemotherapy for those with involved axillary nodes. Local complications have been few and locoregional control has to date been satisfactory. With a relatively short median follow-up of 27 months, cosmesis was objectively rated as good or excellent in over 80% of cases and subjectively rated good/excellent in 96%. High dose brachytherapy now requires testing in a prospective clinical trial to determine whether it is as effective as standard breast conservation techniques for management of early breast cancer.

Paget's disease of the nipple: a ten year review including clinical, pathological, and immunohistochemical findings.

Thirty-five women with biopsy-proven Pagets disease of the nipple were treated over a 10 year period at the Breast Cancer Unit, Guys Hospital. Twenty-four (69%) patients had Pagets disease without a palpable mass in the breast; eleven (31%) presented with a palpable mass and Pagets disease of the nipple. Definitive treatment consisted of modified radical mastectomy in 32 patients, radiotherapy only in 2, and one patient had no definitive treatment.All 11 patients with Pagets disease and an associated lump proved to have invasive ductal carcinoma; five also had associated positive axillary nodes. Nine of the 23 patients with nipple changes only, treated by mastectomy, also had invasive carcinoma; three of these had positive axillary nodes. The remaining 14 patients with nipple changes only were found to have in situ ductal carcinoma, which was extensive in the majority of cases.In 13 cases, histological sections of the nipple were examined by immunohistochemical staining which showed that the Pagets cells expressed a keratin phenotype that was specifically characteristic of simple epithelial cells as seen in glandular epithelium. This was quite unrelated to the normal keratin phenotype of the surrounding skin keratinocytes.Clinical, pathological, and immunohistochemical data suggest a mammary origin of the abnormal cells in Pagets disease of the nipple. Mastectomy appears to be the treatment of choice.

The diagnostic value of testing for occult blood.

An analysis of 270 patients undergoing microdochectomy for nipple discharge from a single identifiable duct, and without an associated lump, revealed that occult cancers were all accompanied by hemoglobin positive discharge. A simple method of detecting the presence of hemoglobin in the discharge is described. The incidence of cancer was found to be 5.9%. In order of frequency, intraduct papilloma, duct ectasia, cystic disease, and carcinoma accounted for over 90% of the cases. Six patients in whom no malignancy was seen in the microdochectomy specimen subsequently developed cancer in the ipsilateral breast. A close follow-up of all patients with hemoglobin positive discharge and in whom no cause for the discharge is demonstrated at microdochectomy is stressed.

Treatment of operable breast cancer in the elderly: a randomised clinical trial EORTC 10850 comparing modified radical mastectomy with tumorectomy plus tamoxifen

We have examined the outcome of older patients with operable breast cancer treated in a randomised trial by either standard surgery or less extensive surgery and tamoxifen. There were 236 participants aged >/=70 years, randomised to either modified radical mastectomy MRM (n=120) or wide local excision (WLE) and tamoxifen (T) 20 mg daily (n=116). Survival curves were estimated using the Kaplan-Meier method and multivariate analyses were performed using Coxs proportional hazards model. Endpoints were survival and time to first relapse or progression, loco-regional progression, time to distant progression and progression-free survival. No significant difference was seen in terms of progression-free survival, but there were significantly more loco-regional relapses in the WLE+T group. In contrast, there were more distant metastases in the MRM group, but with a similar overall survival in both groups. The results of this trial give cautious support for the use of WLE+T for selected older women.

Assessment of skin dose and its relation to cosmesis in conservative treatment of early breast cancer

A conservation technique has been developed for the treatment of early breast cancer which involved removal of the tumor, axillary clearance, tumor site implantation with Iridium-192 wires for a boost dose and subsequent treatment of the breast with radical megavoltage external beam therapy. Although the cosmetic results were satisfactory in the majority of the patients, for some it was rated as fair or poor. One variable factor which could have carried some morbidity was the dose of radiation received by the skin. In 51 patients, doses were measured at several points over the treated breast using Thermoluminescent Dosimetry (TLD) at the time of the iridium implant and during the subsequent external beam therapy. Development of skin pigmentation, oedema, and fibrosis were unrelated to the dose received by the skin but the findings suggested that doses greater than 50 Gy to the skin increased the possibility of late (greater than 24 months) telangiectasia over the boosted area. Treatment of tumors in the lower half of the breast, or in large breasts, was associated with a higher incidence of poor cosmesis. This may have been the result of varying posture on the interstitial dose distribution from the Iridium-192 wires and comparison of dose distribution in both supine and erect positions was carried out.

Serum progesterone at the time of surgery and survival in women with premenopausal operable breast cancer

Serum progesterone and oestradiol levels have been measured in 210 premenopausal women with operable breast cancer on samples taken within 3 days of tumour excision. There was no relation between oestradiol level and time since last menstrual period, nor any effect of oestradiol value on prognosis. However, serum progesterone levels were related to the phase of the cycle as determined by time since last menstrual period. When divided on a basis of levels > 1.5 ng/ml (luteal phase) and < or = 1.5 ng/ml, it was found that there was no difference in survival between the two groups among 117 axillary node negative cases. However, in the 93 patients with positive axillary nodes, higher progesterone levels were associated with significantly better survival. Thus, serum progesterone levels at the time of surgery may affect the prognosis of premenopausal node positive patients with operable breast cancer.

Tamoxifen protects against steroid-induced bone loss

As part of a clinical trial of adjuvant endocrine treatment in postmenopausal women with operable breast cancer serial bone density measurements have been performed by dual photon absorptiometry. Tamoxifen alone was given to 26 women, and 20 received additional prednisolone. By 24 months after entry there was no significant difference between mean bone density of the two groups, nor any significant change from baseline levels. There was a mean gain of 0.46% in the tamoxifen group and 1.95% in those given additional prednisolone. Thus the predicted steroid-induced bone loss was inhibited by tamoxifen. This may be of more general use in prevention of osteoporosis in patients requiring long-term steroid treatment.

Angiosarcoma of the skin overlying an irradiated breast

SummaryA case of angiosarcoma of the breast which developed six and a half years after treatment for carcinoma of the same breast is reported. As a result of radiotherapy the breast manifested signs of chronic lymphedema prior to development of angiosarcoma. Although the aetiology in this case is uncertain, there was a past history of childhood naevus regressing spontaneously. Angiosarcoma is a well known complication following radiotherapy and lymphedema, and is likely to be seen more frequently as conservation treatment is used more commonly for patients with early breast cancer.