Introduction At least four major categories of invasive breast cancer that are associated with different clinical outcomes have been identified by gene expression profiling: luminal A, luminal B, human epidermal growth factor receptor 2 (HER2) and basallike. However, the prevalence of these phenotypes among cases of ductal carcinoma in situ (DCIS) has not been previously evaluated in detail. The purpose of this study was to compare the prevalence of these distinct molecular subtypes among cases of DCIS and invasive breast cancer.

Background At least four major categories of invasive breast cancer have been reproducibly identified by gene expression profiling: luminal A, luminal B, HER2-type and basal-like. These subtypes have been shown to differ in their outcome and response to treatment. Whether this heterogeneity reflects the evolution of these subtypes through distinct etiologic pathways has not been clearly defined. Methods We evaluated the association between traditional breast cancer risk factors and risk of previously defined molecular subtypes of breast cancer in the Nurses’ Health Study. This analysis included 2,022 invasive breast cancer cases for whom we were able to obtain archived breast cancer tissue specimens. Tissue microarrays (TMAs) were constructed and slides were immunostained for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), cytokeratin 5/6 (CK5/6), and epidermal growth factor receptor (EGFR). Using immunostain results in combination with histologic grade, cases were grouped into molecularly defined subtypes. We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results We observed differences in the association between risk factors and subtypes of breast cancer. In general, many reproductive factors were most strongly associated with the luminal A subtype, although these differences were not statistically significant. Weight gain since age 18 showed significant differences in its association with molecular subtypes (p-heterogeneity=0.05) and was most strongly associated with the luminal B subtype (p-trend 0.001). Although there was not significant heterogeneity for lactation across subtypes, an inverse association was strongest for basal-like tumors (HR=0.6, 95%CI 0.4–0.8; p-heterogeneity=0.88). Conclusions These results support the hypothesis that different subtypes of breast cancer have different etiologies and should not be considered as a single group. Identifying risk factors for less common subtypes such as luminal B, HER2-type and basal-like tumors has important implications for prevention of these more aggressive subtypes.

Body fatness at young ages may be related to breast cancer risk independently of adult adiposity. The authors conducted a prospective analysis among 188,860 women (7,582 breast cancer cases) in the Nurses' Health Study (1988-2004) and Nurses' Health Study II (1989-2005) who recalled their body fatness at ages 5, 10, and 20 years using a 9-level pictogram (level 1: most lean; level 9: most overweight). Body fatness at young ages was inversely associated with risk of both premenopausal and postmenopausal breast cancer (per 1-unit increase in adolescent body fatness, relative risk (RR) = 0.88 and RR = 0.91, respectively; P(trend)< 0.0001). Among all women, the RR for adolescent body fatness of level 6.5 or higher versus level 1 was 0.57 (per 1-unit increase, RR = 0.90; P(trend) < 0.0001) and was unaffected by adjustment for current body mass index. The association was stronger for women with birth weights under 8.5 pounds (<3.9 kg) than for women with birth weights of 8.5 pounds or more (> or =3.9 kg) (per 1-unit increase, RR = 0.89 and RR = 0.94, respectively; P(interaction) = 0.04) and stronger for estrogen receptor-negative tumors than for estrogen receptor-positive tumors (per 1-unit increase, RR = 0.86 and RR = 0.92, respectively; P(heterogeneity) = 0.03). Body fatness at young ages has a strong and independent inverse relation to breast cancer risk throughout life.

BACKGROUNDStudies of patients with ductal carcinoma in situ (DCIS) “treated” by diagnostic biopsy alone have been rare, but provide important opportunities to gain insights into the natural history of these lesions.METHODSDuring a review of 1877 breast biopsy specimens in a nested case–control study of benign breast disease and breast carcinoma risk, the authors identified 13 biopsy specimens with DCIS that were originally diagnosed as benign. Because each of these women was initially given a benign diagnosis, they received no treatment beyond the diagnostic biopsy.RESULTSWhen compared with women with nonproliferative lesions, the odds ratio (OR) for the development of invasive breast carcinoma among those with retrospectively identified DCIS (n = 6) was 13.5 (95% confidence interval [CI], 3.7–49.7). The OR for the development of any subsequent invasive or in situ breast carcinoma event (n = 10) was 20.1 (95% CI, 6.1–66. 5). A retrospective review of these DCIS biopsy specimens revealed that the nuclear grade was low in four lesions, intermediate in six, and high in three. None showed comedo‐type necrosis. Invasive carcinomas developed among women with DCIS of all nuclear grades. All 10 breast carcinoma events (100%) were in the ipsilateral breast.CONCLUSIONSThese results provided further evidence that patients with DCIS who received no treatment beyond a diagnostic biopsy were at substantially increased risk for developing ipsilateral invasive breast carcinoma, and that the increased risk in this setting was seen in DCIS of low, intermediate, and high nuclear grades. Cancer 2005. © 2005 American Cancer Society.

Although clear BMI definitions of pediatric weight problems exist, a large percentage of overweight and obese patients remain undiagnosed. Diagnosis increased during the study period but remained low among overweight children, for whom early intervention may be more effective. Identification of overweight and obese patients is the first step in addressing this growing epidemic.

Introduction Body mass index (BMI) during adulthood is inversely related to the incidence of premenopausal breast cancer, but the role of body fatness earlier in life is less clear. We examined prospectively the relation between body fatness during childhood and adolescence and the incidence of breast cancer in premenopausal women.

Few studies have examined multiple risk factors for mortality or formally compared their associations across specific causes of death. The authors used competing risks survival analysis to evaluate associations of lifestyle and dietary factors with all-cause and cause-specific mortality among 50,112 participants in the Nurses' Health Study. There were 4,893 deaths between 1986 and 2004: 1,026 from cardiovascular disease, 931 from smoking-related cancers, 1,430 from cancers not related to smoking, and 1,506 from all other causes. Age, body mass index at age 18 years, weight change, height, current smoking and pack-years of smoking, glycemic load, cholesterol intake, systolic blood pressure and use of blood pressure medications, diabetes, parental myocardial infarction before age 60 years, and time since menopause were directly related to all-cause mortality, whereas there were inverse associations for physical activity and intakes of nuts, polyunsaturated fat, and cereal fiber. Moderate alcohol consumption was associated with decreased mortality. A model that incorporated differences in the associations of some risk factors with specific causes of death had a significantly better fit compared with a model in which all risk factors had common associations across all causes. In the future, this new model may be used to identify individuals at increased risk of mortality.

Breast cancer is the most common cancer diagnosis and the second leading cause of cancer death among women in the United States. Over 211,000 women and 1,600 men in the United States are diagnosed with breast cancer each year, and 40,000 Americans die of this disease annually. This chapter reviews the epidemiology of breast cancer. Topics covered include classification, demographic patterns, environmental factors, host factors, pathogenesis, and preventive measures.