Blood transfusion and survival in colorectal cancer.

PURPOSE: This study examined the effect of blood transfusion on the prognosis of patients undergoing surgery for colorectal cancer. METHODS: Potentially curative resections for colorectal cancer were performed in 266 patients who were followed prospectively, with a minimum follow-up of 41 months. They were divided into transfused (n = 121) and nontransfused (n = 145) groups according to their perioperative blood transfusion requirements. RESULTS: There were significantly more rectal tumors (chi 2 = 9.5, df = 1, P = 0.002) and fixed tumors (chi 2 = 4.5, df = 1, P = 0.03) in the transfused group. There was no statistically significant difference between the two groups with regard to recurrence-free survival (chi 2 = 1.1, df = 1, P = 0.3) and overall survival (chi 2 = 2.8, df = 1, P = 0.09). CONCLUSION: In this study we have found no statistically significant effect of perioperative blood transfusion on the prognosis of colorectal cancer patients.

Ideas in pathology. Ductal carcinoma in situ of the breast: a proposal for a new simplified histological classification association between cellular proliferation and c-erbB-2 protein expression.

UNLABELLED: The diagnosis of ductal carcinoma in situ of the breast (DCIS) has become common with the advent of breast screening programs. METHODS: Proliferation indices (S-phase fraction) were studied in 76 cases of pure DCIS. Tumors were classified according to conventional criteria and also according to a novel simplified classification based on cellular necrosis and morphology. This new classification defines three distinct tumor groups: pure comedo in 19 (25.0%) cases, DCIS with necrosis (non-pure comedo) in 21 (27.6%) patients, and DCIS without necrosis in 36 (47.4%) of cases, the latter group comprising largely classical cribriform or micropapillary architectural subtypes. RESULTS: Flow cytometric DNA analysis showed a significantly higher S-phase fraction in comedo DCIS than in the subgroup of DCIS tumors without necrosis (P < 0.01 [anova]). A preliminary analysis of disease recurrence and disease-free survival in a large series of 391 cases of pure DCIS showed that of 181 cases of pure comedo DCIS there were 19 local recurrences at the 7-year stage (82% 7-year disease-free survival), with 5 local recurrences in 51 cases of DCIS with necrosis (non-pure comedo) (85% 7-year disease-free survival) and only 6 local recurrences in the 159 cases of the DCIS-without-necrosis subgroup (94% 7-year disease-free survival). The chi 2 value for the frequency of disease recurrence of all cases of DCIS with necrosis (i.e., combining the groups of comedo DCIS and DCIS with necrosis (non-pure comedo)) as compared to DCIS without histological evidence of necrosis was 5705 (df = 2; P = 0.0001), and the chi 2 for disease-free survival of types of DCIS with necrosis as compared to cases without necrosis was 178 (df = 2; P = 0.0001). This analysis indicates that the histological presence of necrosis appears to be a relatively powerful predictor of increased disease recurrence and poorer disease-free survival after treatment for DCIS. CONCLUSIONS: Necrosis in DCIS in the absence of pure classical comedo morphology is a feature of more biologically aggressive in situ breast cancer with an intermediate proliferative fraction as compared with the high proliferative fraction of pure comedo DCIS and the low proliferative fraction of DCIS without necrosis. There was no significant difference in DNA ploidy (diploid or aneuploid) between the subgroups as assessed by chi 2 analysis. Further larger studies are required to establish if DCIS with necrosis (non-pure comedo) also shows a greater tendency to local recurrence after breast conservation treatment than do subtypes of DCIS without necrosis. DCIS with necrosis (non-pure comedo) should be adopted as a distinct histological subgroup of DCIS in future clinical studies of in situ mammary carcinoma.

Ki67 immunoreactivity in breast carcinoma: relationships to prognostic variables and short term survival.

Immunoreactivity of the monoclonal antibody Ki67, which recognizes an antigen expressed in cells active in the cell cycle, has been investigated by immunocytochemistry in a series of 67 primary breast cancers. The percentage of tumour cell nuclei stained by Ki67 (labelling index) was related to tumour histological grade, mitotic frequency, oestrogen receptor status and tumour type. No correlation was found with patient age, tumour size or lymph node stage. A high Ki67 labelling index was significantly associated with diminished patient survival and disease-free interval, which demonstrates an important role for this monoclonal antibody as a prognostic marker in breast cancer.

An evaluation of differences in prognosis, recurrence patterns and receptor status between invasive lobular and other invasive carcinomas of the breast.

One-hundred-and-seventy-one patients with invasive lobular carcinomas have been matched with 342 patients with non-lobular invasive carcinomas for lymph node stage, tumour differentiation and patient age on a one to two basis. The two groups were investigated for differences in prognostic factors, survival, disease-free interval, metastatic patterns, receptor status, response to endocrine therapy after distant metastases and bilateral cancer rates. Patients with lobular carcinomas survived significantly longer than patients with carcinomas of no specific type, particularly in survival from the time of diagnosis of distant metastases; lobular carcinomas more often responded to endocrine treatment for systemic disease. Lobular cancers had a significantly higher rate of local recurrence, particularly after treatment by excision and breast irradiation. No differences were found between the two groups with respect to regional or distant recurrence rates, distant organ involvement patterns, distant metastatic free intervals and receptor status. Bilateral cancer was more frequent in patients with lobular carcinoma.

A prospective study of patient choice in treatment for primary breast cancer.

One hundred and sixty-three patients with primary breast cancer were prospectively studied. Using recently developed selection criteria 91 patients were offered a choice of treatment. Forty-one chose to undergo conservation treatment and 47 chose to undergo simple mastectomy. In those women who were offered a choice of treatment there was a significant tendency for younger patients to choose breast conserving treatment.

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.

Flow cytometric and histological analysis of ductal carcinoma in situ of the breast.

Using archival paraffin wax embedded tumour we have investigated histological grade, DNA ploidy, S phase fraction and proliferative index in 74 patients with symptomatic ductal carcinoma in situ (DCIS) of the breast. Nine patients developed local recurrence, six invasive in character. No patients with the cribriform subtype of DCIS developed local recurrence. The cribriform subtype showed a significantly lower rate of DNA aneuploidy and a lower proliferative index than the other subtypes. Cribriform tumours were almost exclusively well differentiated in contrast with the comedo and solid variants. Our results suggest the cribriform variant is less aggressive than other subtypes of DCIS. This has possible implications for management of these lesions.

Evaluation of the prognostic value of triple node biopsy in early breast cancer.

The prognostic information obtained by triple node biopsy (low axillary, apical axillary and internal mammary nodes) in 693 patients with early breast cancer has been reviewed. Results show that tumour site within the breast influenced which nodal groups were involved. The low axillary node contributed the most useful prognostic information. The involved apical node carried the worst prognosis. Either the internal mammary node or a low axillary node when positive alone carried the same prognostic weight. When both nodes were positive the prognosis declined to the level associated with apical node positivity. A double node biopsy of the low axillary node and either the apical or the internal mammary node gave the same maximum prognostic information as a triple node biopsy. The triple node biopsy technique can be used to divide patients into groups with vastly different prognoses.

DNA ploidy in fibroadenomas (abstract).

There is now a considerable body of literature reporting DNA quantification in a variety of malignancies. There have been few reports, however, of such measurements in benign lesions.

c-myc oncogene product expression and prognosis in operable breast cancer.

The 62 kDa protein product of the c-myc oncogene (p62 c-myc) is thought to be involved in the control of normal cellular proliferation and differentiation. We have measured oncoprotein levels using a flow cytometric assay in 141 operable breast cancers and have correlated levels with prognostic variables, patient survival and disease free intervals. High levels of p62 c-myc were associated with well differentiated tumours. There was no correlation with tumour DNA index, lymph node or oestrogen receptor status. C-myc oncoprotein levels were not predictive of patient survival or disease free interval. This relationship of oncoprotein levels with tumour histological grade is in keeping with the suggestion that the c-myc oncogene is important in the control of cellular differentiation. The other findings imply that measurement of c-myc oncoprotein levels does not yield useful prognostic information.

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.

Factors influencing local recurrence after excision and radiotherapy for primary breast cancer.

Between November 1979 and December 1986, 263 patients were treated for primary breast cancer by local excision and radiotherapy at the City Hospital, Nottingham. Local recurrence within the treated breast occurred in 56 patients (21 per cent), in 18 (6.8 per cent) of whom it was gross and uncontrollable. An analysis of clinicopathological features shows patient age, nodal status, tumour size, presence of definitive vascular invasion, adjacent ductal carcinoma in situ and grade to be predictive of local recurrence. A Cox's multivariate analysis of these factors shows the first four to be independently significant. The factors can be combined as a prognostic index which allows identification of patients at high risk of local recurrence. On the basis of these findings we have altered our selection policy for patients suitable for breast conservation.

Results from a seven-year programme of breast self-examination in 89,010 women.

This report presents the results of a study into the effect of breast self-examination (BSE) in a large defined population within the City of Nottingham since 1979. We have examined the effect of breast self-examination in a group of patients invited to attend for education in BSE compared with a group of historical controls. No overall survival advantage has been demonstrated for the study group but within the latter group patients who had attended for instruction in BSE had a significantly better actuarial survival at 13 years than those who did not (P less than 0.001). Patients in the study group presented with significantly smaller tumours which were more likely to be of better histological grade and lymph node stage. A case-control study has demonstrated the value of attendance for BSE particularly in post-menopausal women. Although BSE is not as sensitive as mammographic screening, patients who practise it present with more favourable tumour characteristics and its value in post-menopausal women supports its use as an adjunct to mammographic screening.

In situ carcinoma of the breast.

The optimal management of ductal carcinoma in situ of the breast is controversial. With the introduction of the National Mammographic Breast Screening Programme the condition will be encountered more frequently. We have reviewed 76 patients from a 12-year period treated by one surgeon (R.W.B.) at the Nottingham City Hospital. Fifty-nine patients had either ductal carcinoma in situ or lobular carcinoma in situ; 17 patients had Paget's disease. The mean age at diagnosis was 54 years and the commonest mode of presentation was with a palpable breast lump. Pre-operative mammography was performed in 31 patients with ductal carcinoma in situ and 28 were reported as showing malignancy. Patients with a lesion in the breast parenchyma were treated either by mastectomy (simple, subcutaneous or 'wedge'--see text) or by lumpectomy and radiotherapy. Patients with Paget's disease were treated by simple mastectomy, wedge mastectomy or a cone excision of the nipple and underlying tissue. The mean follow-up period was 65 months. Patients treated by any of the procedures less than simple mastectomy had a significant chance of developing local recurrence. A detailed histological review was made and grade, microinvasion, calcification, necrosis and completeness of excision were assessed for each tumour. None of these factors was correlated with subsequent local recurrence.

Mammography in symptomatic breast disease.

The contribution of mammography to the diagnosis of breast cancer was examined in 5080 patients with various breast symptoms. There were 562 breast cancers within this group. The sensitivity of mammography was 88%. Only 18 cancers were detected by mammography alone, and of these 3 were in the other breast. 7 of the remaining 15 cancers had clinical signs which would have been pursued to open biopsy in the absence of mammography. Clinical examination is of paramount importance in the management of patients with symptomatic breast disease. Mammography is most useful when applied in specific situations rather than to screen every patient with breast symptoms.

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.