A. P. Locker

Pathological prognostic factors in breast cancer. II. Histological type. Relationship with survival in a large study with long-term follow-up

The histological tumour type determined by current criteria has been investigated in a consecutive series of 1621 women with primary operable breast carcinoma, presenting between 1973 and 1987. All women underwent definitive surgery with node biopsy and none received adjuvant systemic therapy. Special types, tubular, invasive cribriform and mucinous, with a very favourable prognosis can be identified. A common type of tumour recognized by our group and designated tubular mixed carcinoma is shown to be prognostically distinct from carcinomas of no special type; it has a characteristic histological appearance and is the third most common type in this series. Analysis of subtypes of lobular carcinoma confirms differing prognoses. The classical, tubulo‐lobular and lobular mixed types are associated with a better prognosis than carcinomas of no special type; this is not so for the solid variant. Tubulo‐lobular carcinoma in particular has an extremely good prognosis similar to tumours included in the ‘special type’ category above. Neither medullary carcinoma nor atypical medullary carcinoma are found to carry a survival advantage over carcinomas of no special type. The results confirm that histological typing of human breast carcinoma can provide useful prognostic information.

c-erbB-2 oncoprotein expression in primary and advanced breast cancer.

Immunoreactivity for c-erbB-2 oncogene product expression has been investigated in patients with breast cancer using the polyclonal antibody 21N. Three series of patients were studied, 602 presenting with primary operable cancer, 57 with stage 3 and 123 with stage 4 disease. Representative tissue sections of each primary tumour were stained using a standard immunoperoxidase technique. Invasive tumour membrane immunoreactivity was assessed and identified in 15% of patients with primary operable cancer and 20% in the advanced breast cancer group. The results demonstrate a relationship between poorer survival and oncogene expression in all three patient groups. Patients in the primary operable cancer group with membrane oncoprotein expression had a poorer outcome, 35% 10-year survival, compared with those in which membrane expression was absent, 55% 10-year survival. The median survival of patients with stage 3 disease with c-erbB-2 membrane positivity was 17 months compared to 24 months with membrane negativity. In stage 4 disease median survival with membrane expression was 8.8 months compared to 19.7 months with no membrane expression. In addition in the series of primary cancers a correlation existed between histological grade and membrane immunoreactivity. Multivariate analysis showed histological grade to be a more powerful prognostic factor than c-erbB-2 protein expression. In conclusion, this study demonstrates, in a large series of patients presenting to one centre, that c-erbB-2 protein expression is a prognostic indicator in patients with primary operable and advanced breast disease.

Invasive lobular carcinomas of the breast: the prognosis of histopathological subtypes

One hundred and seventy-one cases of operable invasive lobular carcinoma, presenting over an 11-year period, were reviewed. Histological subtypes were investigated to determine differences in their clinical behaviour and whether these differences could be explained by histopathological features. Five subtypes were identified: mixed (45.6%), classical (30.4%), tubulo-lobular (13.5%), solid (6.4%) and alveolar (4.1%). The median follow-up period was 64 months and the median age 54 years. The 12-year actuarial survival rate was 100% for the tubulo-lobular subtype, but only 47% for the solid variant. Similar differences were found in the disease free interval, locoregional and distant metastatic rates between these two subtypes. The tubulo-lobular tumours were more likely to be of good histological grade and node negative. The other three subtypes did not differ significantly in their histopathological parameters, reflected in similar clinical behaviour. They occupied an intermediate position between the other two subtypes in terms of prognosis.

Cytological grading of breast carcinoma—a feasible proposition?

Fine needle aspiration cytology (FNAC) of the breast is widely used in the diagnosis of breast carcinoma. In some centres this is sometimes the only diagnostic procedure performed prior to definitive treatment. A grading system based on cytology would be helpful in the selection of patients for appropriate therapy. The aim of this study, therefore, was to devise such a system for grading breast carcinoma based on cytological features alone.

A One Year Audit of Fine Needle Aspiration Cytology For the Pre-Operative Diagnosis of Breast Disease

In 1988, 985 patients presenting with breast disease, most with a palpable abnormality, were investigated by the triple approach (clinical examination, imaging and fine needle aspiration cytology [FNAC]). Using FNAC, 28% of patients were diagnosed as having carcinoma, 45% benign disease, 4% had suspicious cytology and 3% equivocal cytology. the remaining 20% had inadequate aspirates. Two false positive diagnoses of carcinoma were made (a false positive rate of 0.7%); one was a case of high grade non‐Hodgkins lymphoma and the other a papillary lesion with epithelial atypia. the false negative rate was 6.4%. of these 49 patients, six had carcinoma‐in‐situ and 19 had low grade tumours. the absolute and complete sensitivities for the diagnosis of carcinoma in this series were 84.7% and 91.9% respectively and the absolute and complete specificities 99.7% and 98.3%, respectively. These figures compare favourably with those from other centres and confirm the efficacy of FNAC as part of the triple approach to the diagnosis of breast disease. the use of FNAC has resulted in a reduction in the numbers of Trucut and frozen section biopsies performed. Eighty three per cent of the patients with benign disease diagnosed by the triple approach have avoided excision biopsy, none of whom have subsequently been found to have carcinoma. Eighty patients with advanced breast carcinoma were spared operative intervention.

Early experience in breast cancer screening: emphasis on development of protocols for triple assessment

Abstract The early experience of the Nottingham Breast Screening Service participating in the prevalent round of the UK National Health Service Breast Screening Programme is presented. Over a 3-year-period management protocols have been developed and refined. These protocols are based on the principle of multidisciplinary triple assessment, including imaging, clinical evaluation and fine needle aspiration cytology (FNAC). Throughout this period screening performance indicators well within the national guidelines were achieved. In addition, recall for assessment rates fell from 12% to 3.4%, the benign-to-malignant biopsy ratio falling from 1:1 to 0.3:1, while the cancer detection rate of 7 per 1000 women screened was maintained. A progressive increase in diagnostic specificity was achieved while retaining cancer detection sensitivity. Overall, 60% of carcinomas were diagnosed by FNAC. Using the Nottingham Prognostic Index, 47% of cancers were in the good prognostic group, previously shown to correlate with a 10 year survival of 83%. These results are encouraging and suggest that a significant mortality benefit can be predicted for screen detected breast cancers. The adoption of a multidisciplinary triple assessment increases the specificity of the screening test without compromising sensitivity.

Mammography in the pre-operative assessment and post-operative surveillance of patients treated by excision and radiotherapy for primary breast cancer.

To evaluate the place of mammography in the selection of patients for excision and radiotherapy for primary breast cancer a detailed analysis of pre-operative mammograms was performed in (i) a study group of 37 patients who developed local recurrence; (ii) a matched control group with a median local recurrence free survival of 57 months. There were significantly more multifocal tumours in the study group. Tumours were significantly larger (P = 0.02) and closer to the nipple (P = 0.008) in the study group compared to the control group. Regular follow-up mammograms were available in 26 of the study group. Twenty-one patients had mammographic evidence of either residual or recurrent tumour. We conclude that pre-operative mammography is essential in the selection of patients for excision and radiotherapy. Following treatment, mammography is useful in detecting residual or recurrent disease.

The Nottingham Breast Self-Examination Project

The Nottingham breast self-examination (BSE) project forms a part of the British Trial of Early Detection of Breast Cancer which compares mammographic screening, BSE and control areas. Presented here is an analysis of the Nottingham figures. A total of 89,000 women aged 40-64 were invited for lectures in BSE and 28,000 attended (42%); the corrected attendance allowing for register inaccuracies is around 55%. In women invited for education since the scheme began in 1979 (study) 751 cancers have been diagnosed. The 751 cancers occurring in the same health district and age group, working chronologically backwards from 1979 have been identified (control). Prognostic factors (size, node involvement and grade) are improved in the study group; however, at the present time of follow-up the case survival curves do not separate. A case control study shows that women aged 50-65 who attended for education have a relative risk of death from breast cancer of 0.66 (0.45-0.97) in comparison with those who did not attend (p = 0.025). The figure for women aged 40-49 is 0.85 (0.50-1.46). A programme of BSE is cheap to run, may give a survival advantage and should be added to mammographic screening programmes, especially when the interval is beyond 18 months.