Calorie-providing nutrients and risk of breast cancer.

A case-control study was conducted in Italy to investigate the role of diet in breast cancer. Cases were 250 women with breast cancer, and controls were a stratified random sample of 499 women from the general population. A dietary history questionnaire was used to measure the intake of total fat, saturated fat, animal proteins, and other macronutrients. In multivariate analyses, the relative risks of breast cancer for women in the highest quintile of consumption of saturated fat and animal proteins were 3.0 (95% confidence interval, 1.9-4.7) and 2.9 (1.8-4.6), respectively. A reduced risk was found for women who derived less than 28% of calories from fat versus greater than 36%. A similarly reduced risk was found for women who derived less than 9.6% of calories from saturated fat or less than 5.9% from animal proteins. These data suggest that during adult life, a reduction in dietary intake of fat and proteins of animal origin may contribute to a substantial reduction in the incidence of breast cancer in population subgroups with high intake of animal products.

Breast cancer and alcohol consumption: a case-control study in northern Italy.

From 1983 to 1986, a population-based case-control study of alcohol and breast cancer (250 cases and 499 controls) was conducted in a grape-farming area of northern Italy, where wine consumption is widespread. In the study population, 30% of women were abstainers and 15% reported alcohol intakes of 30 g/day or more. After adjustment for potential confounders, no appreciable association was evident for alcohol consumptions as high as 40 g/day. Women reporting intakes of more than 40 g/day showed approximately a 2-fold increase in the risk of breast cancer (relative risk, 1.9; 95% confidence interval, 1.1-3.3). A 2-fold increase in risk was observed for consumptions of more than 40 g/day of alcohol from wine, the most common alcoholic beverage in this population. These findings suggest that an association between alcohol intake and breast cancer may exist. However, the moderate risk observed seems to be limited to the relatively small group of women consuming daily amounts of alcohol in excess of 40 g, the equivalent of about half a bottle of wine or more.

Mutations in the p53 gene in primary human breast cancers.

Twenty-six primary breast tumors were examined for mutations in the p53 tumor suppressor gene by an RNase protection assay and nucleotide sequence analysis of PCR-amplified p53 complementary DNAs. Each method detected p53 mutations in the same three tumors (12%). One tumor contained two mutations in the same allele. Single strand conformation polymorphism analysis of genomic DNA and complementary DNA proved more sensitive in the detection of mutations. Combining this technique with the other two a total of 12 mutations in the p53 gene were demonstrated in 11 tumors (46%), and a polymorphism at codon 213 was detected in another tumor. Loss of heterozygosity on chromosome 17p was detected by Southern blot analysis in 30% of the tumor DNAs. Not all of the tumors containing a point mutation in p53 also had loss of heterozygosity of the remaining allele, suggesting that loss of heterozygosity may represent a later event.

Cell proliferation of breast cancer evaluated by anti-BrdU and anti-Ki-67 antibodies: its prognostic value on short-term recurrences.

The prognostic value of breast cancer proliferative activity was evaluated in 385 women operated for primary, non-metastasised mammary carcinoma. Cell kinetics was measured using two immunohistochemical techniques. Cells in S-phase of cell cycle were labelled in vitro by incubation of fresh tissue fragments with 5-bromo 2-deoxyuridine (BrdU), a thymidine analogue. Nuclei of cells in active DNA synthesis were stained by an anti-BrdU monoclonal antibody (Mab). Cells in interphase and mitosis were detected with Ki-67, a Mab that is known to react with a nuclear antigen present in G1/S/G2/M phases of cell cycle, but not in resting cells. This reagent provides a means of evaluating the growth fraction of neoplastic cells. BrdU was incorporated in a proportion of tumour cells ranging from 0.1 to 65.5% (median 6.8%). In the panel of tumours presented in this report the median percentage of Ki-67 positive cells (Ki-67 score) was 9.0% (range 0.1-77%). The relationship between disease-free survival (DFS), BrdU labelling index, Ki-67 score and 13 different clinico-pathological variables was investigated by multivariate analysis, using the Cox proportional hazards model. Axillary node status (P = 0.009) and Ki-67 score (P = 0.038) emerged as independent prognostic factors. Nodal status and tumour growth fraction allowed division of patients into groups at different risk of relapse: tumours with a proliferative index below the median value showed a lower recurrence rate than tumours with a high proliferative activity (P < 0.001). In particular, no relapse occurred in pN0 patients bearing carcinomas with a Ki-67 labelling < 9.0% 4 years after surgery. These findings suggest that the evaluation of proliferative activity in breast cancer enhances the probability of correctly predicting outcome after surgery and could be of assistance in the planning of adjuvant therapies.

A community study of alcohol consumption and dietary habits in middle-aged Italian women.

This population-based study examines whether dietary intake in middle-aged Italian women is influenced by alcohol drinking habits. The 499 participants were interviewed using a dietary history questionnaire designed to investigate alcohol consumption. Mean intake of total and non-alcohol energy increased progressively within categories of increasing alcohol consumption (less than 5, 5-19, 20-39, 40+ g/day). Mean body weight and Quetelet index (kg/m2), however, decreased with increasing alcohol consumption. Once the disparities in energy intake were reduced by computing intake densities, the data suggest that moderate and heavy drinkers have dietary habits similar to those of abstainers or light drinkers. These findings were confirmed by multiple linear regression analyses in which the confounding effects of age, place of residence, occupation, and Quetelet index were taken into account. Increasing alcohol consumption appeared associated only with a modest decrease in the intake of fibre, beta-carotene, and vitamin C. These findings do not support the hypothesis that the observed protection from coronary artery disease among moderate drinkers is related to a chronic reduction in the intake of carbohydrates and fat, at least in middle-aged women.

Evidence for a second tumor suppressor gene on 17p linked to high S-phase index in primary human breast carcinomas.

The short area of chromosome 17 is a frequent target for deletions in human tumors, including breast cancer. We have investigated by restriction fragment polymorphism analysis the pattern of loss of heterozygosity (LOH) at four loci on 17p13.1-17pter in a panel of 110 primary human breast carcinomas. A copy of the p53 gene was lost in 23% of the informative cases. Point mutations in the p53 gene were statistically associated with LOH at the same locus (p = 0.003) but not at other loci on 17p13.3-17pter. A second region bordered by the loci D17S5/D17S28 (17p13.3) and D17S34 (17pter) is also affected by LOH, independent of point mutations in the p53 gene. We propose the presence of a second tumor suppressor gene within this region. In support of this hypothesis is the significant association (p = 0.005) between LOH at the D17S5/D17S28, but not at the TP53 or D17S34 loci, and tumors having a high S-phase index.

Genetic and molecular heterogeneity of breast cancer cells.

We have undertaken a systematic study of primary human breast tumor DNAs to identify and characterize frequently occurring somatic mutations. Loss of heterozygosity (LOH) was found on chromosomes 1p (37%), 1q (20%), 3p (30%), 7 (41%), 13q (30%), 17p (49%), 17q (29%) and 18q (34%) in our tumor DNA panel. Specific subsets of tumors could be defined based on the particular collection of mutations they contained. One goal of these studies has been to determine whether there is a significant association between specific mutations and clinical parameters of the disease. We have found that LOH on chromosome 17p in tumor DNAs is associated with breast tumors having a high proliferative index and that LOH on chromosome 7 is associated with patients having a poor prognosis. Our analysis of chromosome 17 suggests that there may be as many as four tumor suppressor genes affected in primary human breast tumors.

Risk of breast cancer, diet and internal migrations in northern Italy.

The protective effect of birth in southern Italy as opposed to other regions was evaluated in a population-based case-control study of diet and breast cancer among residents in the province of Vercelli. Cases were 250 women with breast cancer diagnosed during 1983-1984 and controls 499 women randomly selected from the general population. The crude relative risk of breast cancer for women born in the south was 0.76 (95% confidence interval, 0.43-1.3). After adjustment for dietary and other potential confounders in multivariate analyses, the protective effect of place of birth disappeared (RR 1.0; 95% CI, 0.57-1.9). The study indicates that north-south differences in the incidence of breast cancer in Italy may in large part be attributed to different dietary habits.

Cancer of the breast in women born in southern Italy and who migrated to the city of Torino.

Individual demographic data of 459 women living in Torino with incident breast cancer diagnosed in 1979 were compared with those of a random sample of 1800 women drawn from the list of residents in the same city. Among women aged 25-44 and 45+ years, age-adjusted odds ratios for birth in southern Italy were respectively 1.3 (95% CL, 0.1-2.1) and 0.7 (95% CL, 0.5-0.9). In women aged 45+ years, odds ratios increased with length of residence in Torino.

Incidence of breast cancer in Piedmont: 1979-1981.

A population-based survey of histologically diagnosed breast cancer was carried out among residents in Piedmont. A total of 5267 incident cases occurring in 1979-1981 was collected, corresponding to an age-standardized (on the world population) incidence rate of 49.5/100,000 per year. Rates (standardized on the population of Piedmont in 1981) were highest in the city of Torino (112.4/100,000 per year) and lowest in the province of Cuneo (67.5), whereas in the other provinces they ranged between 85.3 and 90.0. Estimation of rates in the 54 Local Health Authorities of Piedmont detected up to 2-fold differences between adjacent areas. A correlation was found between rates and size of the population of town of residence. Comparison with age-specific incidence rates from the Cancer Registry of the nearby province of Varese suggested a loss of nonhistologically confirmed cases selectively in older age groups. The distribution of cases diagnosed in 1979 by histologic type is presented. The proportion of diagnoses reported in terms which were consistent with the 1978 WHO Histological Typing of Breast Tumours was 61.3%. It was highest among cases identified in Pathology Services located in University Hospitals and/or diagnosing more than 50 breast cancers per year.