The risk of breast cancer after giving birth.
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Biomedical subjects
Publications and source records attributed to W D Thompson.
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We have previously described the staining of normal follicle centre lymphoid cells by the rabbit polyclonal antibody to protein gene product 9.5 (PGP9.5), following an antigen unmasking step employing heat pretreatment. Applying this finding to a range of lymphomas to determine whether this phenomenon could have a role in identifying lymphomas of follicle centre origin revealed no relationship between type or grade of lymphoma and staining of neoplastic cells. Testing a range of normal tissues following antigen retrieval displayed increased sensitivity and a greater range of tissue positivity. Immunoblots of gel electrophoresed tonsil and brain extract were performed. Although subjecting these blots to antigen unmasking increased sensitivity, no novel epitopes, in terms of additional bands, appeared. This suggested that antibody specificity remained unaltered.
Previous studies using current or recent adult body weight and body mass index are inconclusive as to a possible effect of increased body mass on premenopausal breast cancer incidence. Only five studies have presented data on early adult body mass, and no study has reported these data for premenopausal bilateral breast cancer. Because premenopausal bilateral breast cancer is assumed to be partly genetic and partly environmental in origin, it is crucial to identify possible modifiable risk factors for this cancer. We present data on early adult body weight and body mass (Quetelet Index, QI) from a case-control study of 142 premenopausal bilateral breast cancer cases from Los Angeles County, California, Connecticut, and Quebec, Canada, and 229 sister controls. The odds ratio (and 95% confidence interval) of premenopausal breast cancer adjusted for age, education, alcohol consumption, and oral contraceptive use was 0.7 (0.3-1.4) for women in the highest tertile of QI at age 18. The results do not suggest that elevated body mass index at a young age increases the risk of premenopausal bilateral breast cancer, but lend only weak support to the hypothesis of an inverse association between body mass index and premenopausal breast cancer.
Mutation and abnormal expression of p53 was studied in 38 lymphomas [five Hodgkin's disease and 33 non-Hodgkin's lymphoma (NHL)]. CM1 polyclonal antibody was used to detect overexpression of p53. Three missense mutations were characterised in three cases of NHL after screening exons 5-8 of p53 of all the tumours with single-strand conformation polymorphism (SSCP) analysis. Only two out of three tumours with a missense mutation showed abnormal expression of p53 as measured by CM1. Conversely, seven out of nine tumours with positive CM1 staining had no point mutation demonstrated. Overexpression of p53 in the cases of NHL occurred in three out of twenty four low-grade tumours and five out of nine high-grade tumours (Kiel classification). The results suggest that abnormalities of p53 are commoner in high-grade than low-grade NHL, and that positive immunocytochemistry cannot be used to determine which tumours have mutations of p53.
Several reproductive factors have been found to be associated with breast cancer. Based on an immunologic rather than strictly hormonal interpretation of these observations, we hypothesized that, beyond the observed associations relating to pregnancy per se, multiple marriages would be found to protect women against breast cancer. We obtained cases and controls from linked records from the Utah Cancer Registry and genealogic records. A total of 2,414 women with newly diagnosed breast cancer and 9,138 individually matched controls were included. The unadjusted odds ratio for each marriage after the first was 0.81 [95% confidence interval (CI) = 0.68-0.97]. After adjustment for major reproductive factors, multiple marriages were still found to reduce the risk of breast cancer (odds ratio = 0.86; 95% CI = 0.72-1.03). The findings are consistent with the operation of an immunologic mechanism in the etiology of breast cancer and suggest that the gene/antigen responsible for this effect is quite common in males. Further empirical evaluation of the fetal antigen hypothesis seems warranted.
This paper reports a case of limited mandibular movement caused by the rare condition of bilateral coronoid hyperplasia. Dental surgeons should be aware of the possibility of this condition when encountering patients with movement problems in the mandible.
Examines associations of selected demographic, insurance, health care, health history, and health practice variables with frequency of screening mammograms received during the past 5 years. Telephone interviews were conducted with 350 women aged 40 through 69, never diagnosed with breast cancer, and identified through random digit dialing in Connecticut. Of 10 variables showing bivariate associations with receiving mammograms as frequently as recommended by National Cancer Institute guidelines, younger age, having a first-degree relative with breast cancer, and having annual clinical breast examinations were statistically significant independent predictors in logistic regression analyses of regular utilization of mammography during the past 5 years. In additional logistic analyses, having regular clinical breast exams maintained a strong effect on the odds both of having any mammograms and, among respondents reporting any mammograms, of having the recommended number during the past 5 years. Frequency of breast self-examination was unrelated to frequency of mammograms.
BACKGROUND: Several studies have found that daughters born to older mothers have an elevated risk of breast cancer, and an endocrine hypothesis, among others, has been developed to explain these findings. Three recent studies have failed to find a consistent maternal age effect, indicating a need for further exploration of this issue. PURPOSE: We used Utah breast cancer records linked to genealogical records to investigate maternal and paternal age and other maternal reproductive factors in relationship to the daughter's risk of breast cancer. METHODS: The study group consisted of 2414 breast cancer case patients and 9138 individually matched control subjects. Breast cancer diagnoses were ascertained through the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. The case patients and control subjects were born between 1875 and the end of 1947, and the mean age at diagnosis of the case patients was 65.9 years. RESULTS: No consistent effect for maternal or paternal age was found, except possibly among women who were firstborn children (odds ratio [OR] = 1.42 for a 10-year differential in maternal age; 95% confidence interval [CI] = 1.00-2.00). Further examination of the data indicated that mothers of case patients experienced long intervals between marriage and their first birth but not between subsequent births, and they went on to have fewer children. For each year of delay between the mother's marriage and first birth, the odds of breast cancer in the daughter increased 1.05-fold (95% CI = 1.01-1.10). CONCLUSIONS: We found no evidence of a consistent maternal age effect with regard to breast cancer risk in the daughter, but we did find evidence that the mothers of women who go on to get breast cancer have a reproductive pattern that could suggest some form of underlying infertility. IMPLICATIONS: These findings widen the epidemiologic support for the fetal antigen hypothesis, which is an immunogenetic explanation for the relationships between reproductive factors and breast cancer risk. That hypothesis provides strategies for the identification of breast cancer genes and the eventual development of a breast cancer vaccine.
It has been recognized for some time that a family history of breast cancer is associated rather strongly with a woman's own risk of developing the disease. Recent segregation analyses of population-based data on familial patterns provide evidence for a rare autosomal dominant allele that increases a carrier's susceptibility to breast cancer. The estimated proportion of breast cancer patients who carry this allele declines sharply with age at diagnosis. Empirical estimates of the risk associated with particular patterns of family history of breast cancer indicate the following: (1) having any first-degree relative with breast cancer increases a woman's risk of breast cancer 1.5-3-fold, depending on age, (2) having multiple first degree relatives affected is associated with particularly elevated risks, (3) having a second-degree relative affected increases the risk by approximately 50%, (4) affected family members on the maternal side and the paternal side contribute similarly to the risk, (5) a family history of breast cancer is associated with bilateral disease, and (6) breast cancer in males is associated with breast cancer in female relatives in much the same way as is breast cancer in women. Ovarian cancer clearly has been shown to be associated with breast cancer in families, and genetic linkage has provided strong evidence for a breast-ovarian cancer gene located somewhere on chromosome 17q. At the population level, having a first degree relative with ovarian cancer may be at least as predictive of a woman's risk for developing breast cancer as is having a second-degree relative with breast cancer. Considerably weaker evidence points to a possible familial relationship between breast and endometrial cancer and between breast cancer in women and prostatic cancer in males. The clinical applications of the genetic epidemiology of breast cancer are complicated by uncertainty as to the efficacy of mammographic screening in women under the age of 50. For the vast majority of women with a positive family history, the epidemiologic evidence does provide the basis for offering considerable reassurance in that risks are not extremely high. For that rather small subgroup at exceptionally high risk, realistic estimates of the magnitude of absolute risk over the next 10-20 years may be more informative and less alarming than lifetime probabilities.
BACKGROUND: Improvements in screening techniques have made significant contributions to the early detection of breast cancer. Physicians thus face the task of providing appropriate screening schedules for their patients. One group for whom this is particularly important are those women with a family history of breast cancer. METHODS: In this report, data from the Cancer and Steroid Hormone Study, a population-based, case-control study conducted by the Centers for Disease Control, are used to provide age-specific risk estimates of breast cancer for women with a family history of breast cancer. The data set includes 4730 patients with histologically confirmed breast cancer age 20-54 years and 4688 control subjects who were frequency matched to patients by geographic region and 5-year age intervals. The data set also includes family histories of breast cancer in mothers and sisters of both patients and control subjects. RESULTS: Genetic models fit previously to these data by the authors have provided evidence for a rare autosomal dominant allele that results in increased susceptibility to breast cancer. In addition, these models predict that women who carry the allele are at greater risk of developing breast cancer at any age than are women who do not carry the allele. The increase in risk in carriers versus noncarriers does, however, decrease with increasing age. Based on the parameters of this model, age-specific risks for a woman with one or more relatives affected with breast cancer at various ages at onset are given. CONCLUSIONS: These tables can be used for the purpose of counseling women at high risk of breast cancer development, that is, women with a family history of breast cancer.
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A total of 212 consecutive fine-wire localization breast biopsies in 202 patients were performed on impalpable mammographically suspicious lesions. Preoperative fine-needle aspiration cytology was performed on 159 lesions and was valuable in planning the extent of the fine-wire localization biopsy. All 212 target lesions were accurately biopsied during the initial surgery. Overall, 134 lesions were malignant and 78 benign (benign:malignant ratio 1:1.72), with fewer biopsies for benign lesions performed in screened patients (benign:malignant ratio 1:2.43) than in those with symptoms (ratio 1:1). Breast conservation was achieved in 72 patients (80 per cent) with screen-detected in situ or invasive carcinoma and in 19 of 37 presenting via a symptomatic clinic. In 160 of 202 patients (79 per cent) the initial fine-wire localization biopsy was diagnostic and therapeutic.
The rabbit polyclonal antibody to protein gene product 9.5 (PGP9.5) will detect the L1 isoenzyme of ubiquitin carboxy-terminal hydrolase (UCH), which is a marker for neurones and neuroendocrine tissue. We re-evaluated this antibody using the technique of non-enzymatic antigen retrieval (boiling sections in citrate buffer, heated by microwave oven) followed by streptavidin-biotin-peroxidase staining. Due to the fortuitous choice of appendix as positive control material containing small nerves, we found strong, repeatable cytoplasmic and nuclear staining of lymphoid follicle centre cells in addition to neural tissue. This effect could be repeated on other lymphoid tissues and was not dependent on microwave heating, but did require boiling in an ionic buffer solution. Staining was also observed with a fresh batch of antibody and with four of the five different batches of antibody which were supplied to us. This pattern was not obtained in fresh tissue, in fixed material following trypsinization, or by increasing the primary antibody concentration. We suggest that the boiling of sections in citrate buffer is exposing an epitope for the anti-PGP9.5 antibody which is inaccessible in the native or fixed state and therefore we would recommend retesting of antibody specificity following non-enzymatic retrieval of antigen.
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The purposes of this study were to determine whether exposure of the vestigial male breast to ionizing radiation is associated with an increase in risk of breast cancer and, if so, to determine whether the apparent effects on risk in men are similar to those reported for women. A population-based case-control study of breast cancer in men was conducted in 10 geographic areas of the United States. Information on possible prior exposure to ionizing radiation, and on other potential risk factors for breast cancer, was obtained from personal interviews of 227 cases and 300 controls who were recruited from October 1983 to September 1986. Evidence from this study that ionizing radiation can cause breast cancer in men includes: a modest trend of increasing risk with frequency of chest X-rays; an increase in risk in men with three or more radiographic examinations, especially if received prior to 1963; and an increase in risk in men who received X-ray treatments to the chest and adjacent body areas. Risk was increased only from 20 to 35 years after initial exposure from either radiographic examinations or X-ray treatments, and declined after three to four decades since last exposure, suggesting a wave of increased risk of finite duration following exposure. The doses of radiation received could not be estimated precisely, but those from diagnostic procedures were likely similar to those received by prepubertal females in prior studies, and the results of those and the present investigation are compatible. The carcinogenic effects of ionizing radiation may be similar in the male and prepubertal female breast.
Methods of analysis of results from case-control studies have evolved considerably since the 1950s. These methods have helped to improve the validity of the conclusions drawn from case-control research and have helped to ensure that the available data are utilized to their fullest extent. Logistic regression modeling, in its various forms, has become by far the most frequently applied method for multivariable analysis of case-control studies. As with any type of statistical modeling, the appropriateness of its formulation can be verified only partially through examination of the data themselves, and cautious interpretation has been urged (80-83). In this article, I have concentrated on methods that are extremely well suited to the evaluation of fairly specific etiologic issues, where one or two particular exposures are designated as being of a priori interest. In situations where a large number of associations are examined for possible case-control differences, additional complexities arise. Several authors have argued strongly against statistical adjustment for "multiple comparisons" in such situations (6, 7, 84). However, recent work suggests that, when background information is limited, certain forms of multiple-comparison procedures can be useful, specifically within a decision-analysis framework (85-87). Further methodological work relevant to the analysis of case-control studies is needed in at least two important areas. First, as discussed above, we need additional methods for conducting analyses that take appropriate account of the considerable error to which measurements in case-control studies are subject. Only with such methods available can estimates from case-control studies be confidently employed for elucidating pathogenesis, for developing policy, and for individual decision-making. Second, there has been a renewed effort in recent years to clarify the nature of causal effects and to relate these to the typically calculated epidemiologic parameters (88-92). As this work develops further, it is likely that the analysis of case-control studies will be enriched.
Recent reports suggest that subjects who are heterozygous for the ataxia-telangiectasia gene are at increased risk of breast cancer. We conducted linkage analyses of 64 families with premenopausal bilateral breast cancer using DRD2, a marker linked to the ataxia-telangiectasia locus at 11q22-23. We assumed a model with dominant transmission of breast cancer. Lod scores summed over all families provided strong evidence against tight linkage (e.g., a lod score of -6.08 at theta = 0.00001), although a single family provides suggestive evidence of tight linkage to DRD2. Evidence against linkage to 11q was strongest among families that may involve the BRCA1 breast cancer susceptibility gene on 17q21. However, we did not observe evidence of linkage to 11q among the remaining subgroup with neither a family history of ovarian cancer nor the appearance of linkage to 17q21.
Despite the increasing world-wide popularity of contraceptive intra-uterine devices (IUDs), their potential long-term effects on the risk of developing endometrial carcinoma have been poorly studied. This paper reports on the relationship between intra-uterine contraception and endometrial cancer by analyzing epidemiological data from a large, multicenter, population-based, case-control study of epithelial endometrial cancer. Cases were 437 women, 20 to 54 years of age, with histologically confirmed epithelial endometrial cancer ascertained through 6 population-based cancer registries in the United States. Controls were 3200 women selected at random from the populations of these areas. The age- and parity-adjusted odds ratio (OR) for the association between ever having used intra-uterine contraception and endometrial cancer was 0.51 (95% confidence interval (CI) 0.3-0.8). Although the protective effect increased with duration of use, a dose-response relationship among users was not statistically demonstrable. The association did not vary significantly with age at first or last IUD use or with time elapsed since first or last IUD use. Years of education significantly modified the effect of intra-uterine contraception. Thus, intra-uterine contraception appeared to be strongly protective for women with at least 13 years of education (OR = 0.29, 95% CI, 0.15-0.6). It is proposed that intra-uterine contraception exerts its protective effect through local structural and biochemical changes in the endometrium that may alter endometrial sensitivity and response to circulating estrogen and progesterone.