Micrometastases in bone marrow in patients with primary breast cancer: evaluation as an early predictor of bone metastases.

The bone marrow of 307 patients with primary breast cancer was examined for tumour cells by immunocytochemistry using an antiserum to epithelial membrane antigen. Micrometastases were found in 81 cases (26.4%) and their presence was related to various poor prognostic factors: spread to lymph nodes, vascular invasion, T stage, and pathological size. The median duration of follow up was 28 months. Seventy five patients relapsed, 60 at distant sites. Of these 60 patients, 26 had micrometastases detected at presentation and 34 were free of micrometastases initially. The relapse free interval was significantly shorter for patients with micrometastases, and these patients had a shorter survival. Analysis of the sites of relapse showed that the test predicted bone metastases only. Thus 10 out of 19 patients (53%) who developed bone metastases at first relapse had micrometastases at presentation compared with only 41 out of 288 patients (14%) who remained free of bone metastases or relapsed in non-skeletal sites. The presence of micrometastases detected at the time of initial surgery in a patient with primary breast cancer is a useful predictor of early relapse in bone and may help in selecting patients for subsequent systemic treatment.

Detection of micrometastases in patients with primary breast cancer.

An immunocytochemical method was used to screen smears obtained at primary surgery from multiple bone-marrow sites in 110 patients with breast cancer; at this time other techniques did not reveal metastases. Tumour cells were detected in the bone-marrow of 31 (28%) patients. The number of cells detected ranged from 1 to greater than 500; none was detected in conventionally stained smears. Patients in whom conventional criteria indicated a very poor prognosis seemed more likely to have such micrometastases. A further follow-up period is required to determine whether patients with micrometastases relapse earlier than those in whom no tumour cells are demonstrable.

The spread of breast cancer: importance of the intrathoracic lymphatic route and its relevance to treatment.

Detailed necropsies were performed on 26 individuals who had died of disseminated breast carcinoma, to assess the frequency of spread to the lungs, pleura and pericardium, and to determine the likely routes of spread to these sites. Tumour was present in the lung parenchyma in 67% of the lungs examined, in the visceral pleura in 75% and the parietal pleura in 50%. Although even small deposits of pleural tumour were invariably visible to naked-eye examination, lung parenchymal involvement was almost invariably microscopic, despite its frequently extensive distribution. This finding draws attention to the difficulties of clinical staging with respect to lung metastases. Tumour in lymphatics predominated over that in blood vessels in both lung and pleura and this, together with the widespread mediastinal lymphnode infiltration found, suggests that the lymphatic system forms the dominant route of spread of breast carcinoma to the thorax. The possible role of mediastinal lymphatics in the dissemination of breast cancer to bone and liver is also discussed. Our findings suggests that the fields of adjuvant irradiation after primary surgery should include the mediastinal lymphatic network.

Clinical examination, xeromammography, and fine-needle aspiration cytology in diagnosis of breast tumours.

The diagnostic accuracy of clinical examination, xeromammography, and fine-needle aspiration cytology was compared with definitive histological findings in 255 breast lumps excised during one year. When suitable aspirates were obtained for cytological examination the diagnostic accuracy of aspiration cytology was higher than clinical examination or xeromammography. A diagnostic accuracy of 99% was achieved when all three screening tests were in agreement. As well as confirming a clinical diagnosis of malignancy, cytology is useful in identifying malignancy when clinical findings suggest that the tumour is benign. The availability of accurate cytology has affected patient management in many ways. Xeromammography did not enhance the diagnostic accuracy of clinical examination and aspiration cytology in patients presenting with a breast lump and, as a procedure with potential hazard, the benefit of routine xeromammography is questionable when an efficient cytological service is available.

Failure to detect intra-abdominal metastases from breast cancer: a case for staging laparotomy.

Two studies were performed to assess the accuracy of non-invasive methods in detecting intra-abdominal metastases from breast cancer. Firstly, the sites of spread detected at the time of first presentation with metastases were compared with the sites of spread shown at necropsy in the same patients. Although about two-thirds of the patients with bone and lung metastases at necropsy had had metastases detected at these sites when they first presented with metastases, only a third of the patients with liver metastases and none of those with other intra-abdominal metastases had had evidence of disease at first presentation with metastases. The second study confirmed a poor detection rate of liver and other intra-abdominal metastases in patients with breast cancer undergoing laparotomy and oophorectomy who were staged immediately before operation.Pre-mastectomy staging laparotomy should be considered in those patients with primary breast cancer who are most likely to have disseminated disease beyond the regional nodes. In the presence of occult gross metastases detected by staging laparotomy, mastectomy will not provide additional protection against loca recurrence of disease. Patients with occult gross metastases should also be excluded from studies on adjuvant chemotherapy (designed to treat micrometastases). Aggressive methods of staging are justified to protect the patient as far as possible against unnecessary mastectomy and to identify those patients who should be treated by therapeutic chemotherapy rather than adjuvant chemotherapy.