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Objective: To evaluate the potential etiologic heterogeneity of breast cancer by examining whether associations with reproductive and other personal characteristics differed by p53 protein expression status. Methods: Data from the Carolina Breast Cancer Study, a population-based, case–control study of 861 cases and 790 controls, were utilized. Immunohistochemical staining for the p53 protein was performed on 638 archived tumor specimens; 46% of cases were classified as p53+. Two separate unconditional logistic regression models were used to calculate odds ratios (OR) and 95% confidence intervals (CI) for p53+ and p53− breast cancer relative to controls for reproductive and other personal characteristics. Analyses were performed separately for younger (≤45 years) and older (>45 years) women. Results: Risk factor profiles largely overlapped for p53+ and p53− breast cancer, with the exception of oral contraceptive (OC) use among younger women and a family history of breast cancer. Prolonged OC use was more strongly associated with p53+ breast cancer [OR 3.1 (95% CI: 1.2–8.1) than p53− breast cancer (OR 1.3 (95% CI: 0.6–3.2)] among younger women only. A first-degree family history of breast cancer was associated with p53+ breast cancer among younger women [OR 1.5 (95% CI: 1.0–2.2)] and older women [OR 1.4 (95% CI: 0.9–2.3)], but not p53− breast cancer in either age-group. Conclusions: These results provide little evidence of breast cancer heterogeneity as classified by p53 expression status. However, although not statistically significant, OC use among younger women and family history of breast cancer may operate through a pathway involving p53 alterations to increase risk of breast cancer.

Objective: To assess risk factors for breast cancer among very young compared to older premenopausal women. Methods: Between 1990 and 1992 a population-based case–control study conducted in Atlanta, GA, Seattle/Puget Sound, WA, and central NJ interviewed 3307 premenopausal women aged 20–54 years. Logistic regression models estimated adjusted relative risks (RR) and 95% confidence intervals (CI) for each of three 10-year age groups. Results: Among the youngest age group (

Objective: To examine the relation between breast cancer risk and job history among women 20–44 years of age who participated in a multi-center, population-based, case–control study. Methods: Participants consisted of women newly diagnosed with breast cancer (1642) and controls identified by random-digit dialing (1494). Details about the three longest jobs were collected and coded by an industrial hygienist. Odds ratios and 95% confidence intervals were calculated and adjusted for age, study site, and other breast cancer risk factors. Results: Several occupational and industrial categories were found to influence breast cancer risk. Stratification of the study population by parity revealed differences in breast cancer risk between the two groups for several occupational categories, including teachers, librarians or counselors (increased risk only among parous women) and natural scientists and mathematicians (decreased risk only among nulliparous women). Conclusions: This is among the first population-based case–control studies to examine occupational history and breast cancer risk in young women, with the ability to consider a wide array of potential confounders, including reproductive characteristics. This study provides further evidence of an increased breast cancer risk for several occupations and industries. Other findings were not as strongly supported by previous investigations.

Objectives: To evaluate the associations of dietary macronutrients, food groups, and eating patterns with risk of breast cancer in a population-based case–control study. Methods: In this study among women 20–44 years of age, 568 cases with breast cancer and 1451 population-based controls were included. They completed a detailed in-person interview, a self-administered food-frequency questionnaire and were measured for anthropometric indices. Logistic regression was used to estimate odds ratios (OR) and their 95% confidence intervals (CI) of breast cancer, adjusted for age, study site, race, education, alcohol consumption, oral contraceptive usage, smoking status, and body mass index. Results: There was no association between breast cancer risk and intake of calories, macronutrients, or types of fat. Risk of breast cancer was unrelated to intakes of a variety of food groups, including red meats, dairy, high-fat snacks and desserts, or foods high in animal fat. Increased risk was observed for high intake of a food group composed of sweet items, particularly sodas and desserts. Risk increased linearly with percent of calories from sweets and frequency of sweets intake. Consumption of sweets 9.8 or more times per week compared with

Objectives: Few studies have examined methods by which breast cancers are detected, and only one study has been published on predictors of those methods. This study examined patterns and predictors of breast cancer detection methods during 1990–1992 among women age 20–44. Methods: In-person interview and medical record data were obtained during a population-based case–control study of 1619 women newly diagnosed with breast cancer in three areas of the United States (US). Results: Seventy-one percent of the cancers were identified by self-detection, 9% by routine clinical breast exam (CBE), and 20% by routine mammography. Cancers detected by mammography and CBE, but not those detected by breast self-exam, were much more likely to be early-stage. Detection by mammography increased with age, and a history of mammography use was associated with detection by mammography or CBE. Several commonly studied predictors of screening utilization in the US population were associated with CBE detection, but were less clearly related to or unrelated to mammography detection. Conclusion: Findings suggest that, during the 1990s in the US, most breast cancers among women under age 45, including those age 40–44, were self-detected. Few factors other than age and prior screening are verified predictors of method of breast cancer detection.

Objectives: Epidemiologic studies provide evidence for increased breast cancer risk among women with prolonged exposure to endogenous estrogens and progesterone. Menstrual cycle characteristics, such as early menarche, rapid initiation of regular ovulatory cycles, short cycle length, and more days of flow, all potentially contribute to higher cumulative ovarian hormone exposure. Methods: We assessed the associations between these characteristics and breast cancer risk in a population-based, case–control study of 1505 controls and 1647 newly diagnosed cases, all younger than 45 years of age. Results: Compared to women with menarche at ≥15 years, we observed some increase in risk for women with younger ages at menarche, although those with very early ages were not at particularly high risk [odds ratio (OR) = 1.5, 95% confidence interval (CI) = 1.1–1.9 for menarche at age 12 and OR = 1.2, 95% CI = 0.9–1.7 for menarche at age ≤10]. Women who reported having regular menstrual cycles within 2 years of menarche were at increased breast cancer risk (OR = 1.7, 95% CI = 1.2–2.3), compared to those never having regular cycles. Stratification by current body mass index revealed slightly stronger associations with menstrual characteristics among thinner women ( 28.8 kg/m2). Conclusions: These findings suggest that future studies should focus on clarifying how the interrelated effects of body size and menstrual factors, such as age at menarche and cycle regularity, contribute to breast cancer etiology.

Objective: The incidence of esophageal adenocarcinoma has risen rapidly in the past two decades, for unknown reasons. The goal of this analysis was to determine whether gastroesophageal reflux disease (GERD) or the medications used to treat it are associated with an increased risk of esophageal or gastric cancer, using data from a large population-based case–control study. Methods: Cases were aged 30–79 years, newly diagnosed with esophageal adenocarcinoma (n = 293), esophageal squamous cell carcinoma (n = 221), gastric cardia adenocarcinoma (n = 261), or non-cardia gastric adenocarcinoma (n = 368) in three areas with population-based tumor registries. Controls (n = 695) were chosen by random digit dialing and from Health Care Financing Administration rosters. Data were collected using an in-person structured interview. Results: History of gastric ulcer was associated with an increased risk of non-cardia gastric adenocarcinoma (OR 2.1, 95% CI 1.4–3.2). Risk of esophageal adenocarcinoma increased with frequency of GERD symptoms; the odds ratio in those reporting daily symptoms was 5.5 (95% CI 3.2–9.3). Ever having used H2 blockers was unassociated with esophageal adenocarcinoma risk (OR 0.9, 95% CI 0.5–1.5). The odds ratio was 1.3 (95% CI 0.6–2.8) in long-term (4 or more years) users, but increased to 2.1 (95% CI 0.8–5.6) when use in the 5 years prior to the interview was disregarded. Risk was also modestly increased among users of antacids. Neither GERD symptoms nor use of H2 blockers or antacids was associated with risk of the other three tumor types. Conclusions: Individuals with long-standing GERD are at increased risk of esophageal adenocarcinoma, whether or not the symptoms are treated with H2blockers or antacids.

Objectives: The relation between benign ovarian tumors (BOTs) and nutrients, primarily dietary fat, was examined using case–control data.

Objectives: To evaluate whether heavy cigarette smoking as a teenager or long-term smoking increases breast cancer risk or, alternatively, whether smoking acts as an anti-estrogen and reduces risk.

Methodologic investigations have addressed selection and recall biasin case-control studies of diet and breast cancer, whereas the effect ofdisease progression and medical treatment on estimates of dietary intake hasbeen largely overlooked. In a multicenter, population-based case-controlstudy of breast cancer in the United States, 1,588 newly diagnosed cases and1,451 controls completed a self-administered food-frequency questionnaire.Initial evaluation suggested increased risk related to high intakes ofcalories, carbohydrates, fat, and protein. All nutrient associations werediminished after adjustment for calories. Evaluation by stage of diseaserevealed no relation of calories to risk among women with in situ disease,but elevated risks among women with localized (odds ratio [OR] = 1.33, 95percent confidence interval [CI] = 1.0-1.7 highest cf lowest quartile) orregional and distant disease (OR = 1.79, CI = 1.3-2.4). Further evaluationshowed that the increased risk a ssociated with calories was restricted tocases who reported having been treated with chemotherapy (OR = 1.66, CI =1.3-2.1). A gradient of increasing risk with time interval from diagnosis tointerview suggested the chemotherapy regimen itself and not necessarilycharacteristics of tumors requiring this treatment was responsible for theobserved increased risk. These results indicate that epidemiologic studies ofdiet and breast cancer, particularly among young women, should evaluatepossible bias related to post-diagnosis influences.