Oestrogen-receptor status and sites of metastasis in breast cancer.

The oestrogen receptor (RE) status of the primary tumour has been assessed in 466 of a consecutive series of 550 patients with primary operable breast cancer. All patients were followed up (without treatment) until the development of recurrence or metastases. Distant metastases have so far occurred in 124 patients and 82 have had symptomatic local or regional recurrence. A significant correlation exists between the RE status of the primary tumour and subsequent patterns of metastasis. Symptomatic metastases to regional lymph nodes are more common with RE- cancers. There is no significant difference in either time of onset or total incidence of distant metastases between patients with RE+ and RE- tumours. Distribution of distant metastases is influenced by RE status: RE+ tumours tend to recur in bone, RE- tumours show affinity for viscera

A comparison of the clinical metastatic patterns of invasive lobular and ductal carcinomas of the breast.

Seventy seven patients with metastases from an invasive lobular carcinoma of the breast have been compared with 72 consecutive metastatic ductal carcinomas. There was no difference in the metastatic free interval between the two groups. A distinct pattern of clinical presentation of metastases was seen; hepatic (P = 0.01) and peritoneal metastases (P = 0.0003) occurred more commonly in lobular tumours. Bilateral cancers were more common in the lobular group (P = 0.01). No difference was seen in terms of meningeal and pulmonary metastases. Survival after metastases was significantly longer in patients with metastatic lobular carcinoma (P = 0.02)

Objective measurement of therapeutic response in breast cancer using tumour markers.

In 65 patients with systemic breast cancer, a biochemical response index using three tumour markers in combination, carcinoembryonic antigen (CEA), carbohydrate antigen 15-3 (CA 15-3) and erythrocyte sedimentation rate (ESR), allowed objective biochemical assessment of response to endocrine therapy. Changes in these three markers at 2, 4 and 6 months showed a highly significant correlation with UICC assessed response at 6 months. At 4 months, changes in these three markers resulted in a selectivity of 93%, with a sensitivity of 92% and a specificity of 82%. Survival of groups of patients assessed biochemically or by UICC criteria for non-progression or progression showed no significant difference. The advantage of the biochemical assessment are that it is objective and reproducible. The assessment gives similar information to the UICC assessment but can be carried out earlier. Changes in the three markers appears to reflect the dynamics of change in tumour mass in response to systemic therapy in contrast to the UICC criteria which reflect structural change

Epithelial mucin core antigen (EMCA) in assessing therapeutic response in advanced breast cancer--a comparison with CA15.3.

We report a comparative study of CA 15.3 and EMCA (epithelial mucin core antigen) in 77 consecutive women with newly diagnosed UICC assessable metastatic breast cancer, 59 patients received hormones and 18 chemotherapy. Assessments of response were made prior to commencing therapy and repeated 2 monthly. Sites of metastatic disease included bone (34), pulmonary (8), bone and pulmonary (14) and visceral (21). Using a cut-off of 33 U ml-1 changes in EMCA at 2, 4 and 6 months showed a highly significant correlation (P < 0.001) with UICC assessed response at 6 months; selectivity 70%, sensitivity 80%, specificity 91%, positive predictive value 84%; negative predictive value 89% at 2 months. Corresponding values for CA 15.3: selectivity 89%, sensitivity 85%, specificity 91%, PPV 92% and NPV 91%. Four of eight patients unassessable by CA 15.3 were assessable by EMCA; four patients expressed neither marker. EMCA appears to reflect tumour bulk and may be useful in monitoring therapy in patients with advanced breast cancer. With an easier and more robust assay format than CA 15.3, EMCA is potentially a more useful marker

Relationship between oestrogen-receptor content and histological grade in human primary breast tumours.

A series of 300 patients presenting consecutively with primary operable breast cancer has been studied. A significant correlation was found between oestrogen-receptor (ER) content and histological grade: the better-differentiated tumours rarely lacked receptor. This correlation was significant only in women defined as post-menopausal. Data on early recurrence of disease indicate a worse prognosis for women in whom primary tumours are ER-

P-glycoprotein expression in locally advanced breast cancer treated by neoadjuvant chemotherapy.

Using immunohistochemistry and the monoclonal antibody C219 we have investigated P-glycoprotein expression in 26 locally advanced breast cancers. Twenty four patients had received four cycles of chemotherapy (mitozantrone, mitomycin-C and methotrexate) prior to mastectomy; two received tamoxifen. Twelve tumours exhibited an objective response to the chemotherapy. A background pattern of isolated weakly positive (1+) stromal staining (myofibroblast) was observed in seven tumours, two of which had been treated by tamoxifen alone. Two of the tumours treated by induction chemotherapy showed positive staining (1+) within a very small number of isolated tumour cells (maximum of three) and macrophages. The significance of this staining is not clear although C219 may simply be cross reacting with myosin. We have failed to demonstrate a clear clinical utility for C219 in breast cancer, particularly regarding the identification of patients in whom MDR chemotherapy be avoided once metastases develop

A prognostic index in primary breast cancer.

From a multiple-regression analysis of prognostic factors and survival in a series of 387 patients with primary breast cancer, a prognostic index has been constructed, based on lymph-node stage, tumour size and pathological grade. This index is more discriminating than lymph-node stage alone, and enables a larger group of patients to be identified with a very poor prognosis

Early-onset breast cancer--histopathological and prognostic considerations.

Young age at diagnosis is claimed to be a prognostic factor in the natural history of breast cancer. Of 2879 patients aged < 70 years treated for primary operable breast cancer (< 5 cm diameter) at Nottingham City Hospital between 1973 and 1993, 120 were less than 35 years of age at diagnosis. Histopathological and prognostic variables were compared between patients aged < 35, 35-50 and 51-70 years. A significant reduction in metastasis disease-free survival and actuarial survival was seen in breast cancer patients aged < 35 years compared with the two older age groups. Patients aged < 35 years at diagnosis presented more frequently with high-grade cancers and vascular invasion. No differences were seen for tumour size or lymph node stage. The Nottingham Prognostic Index (NPI) was used to stratify cancers in each age group. Because of the tendency to high grade, a greater percentage of patients aged < 35 years fell into the poor-prognosis group. Within each prognostic group, no difference in actuarial survival was seen between age groups. The association of young age at diagnosis with a worse prognosis in this series is explained by a higher proportion of poorly differentiated cancers; age itself had no influence on the prognosis of the individual