Sandra A. Norman

Prevalence and Predictors of BRCA1 and BRCA2 Mutations in a Population-Based Study of Breast Cancer in White and Black American Women Ages 35 to 64 Years

Although well studied in families at high-risk, the roles of mutations in the BRCA1 and BRCA2 genes are poorly understood in breast cancers in the general population, particularly in Black women and in age groups outside of the very young. We examined the prevalence and predictors of BRCA1 and BRCA2 mutations in 1,628 women with breast cancer and 674 women without breast cancer who participated in a multicenter population-based case-control study of Black and White women, 35 to 64 years of age. Among cases, 2.4% and 2.3% carried deleterious mutations in BRCA1 and BRCA2, respectively. BRCA1 mutations were significantly more common in White (2.9%) versus Black (1.4%) cases and in Jewish (10.2%) versus non-Jewish (2.0%) cases; BRCA2 mutations were slightly more frequent in Black (2.6%) versus White (2.1%) cases. Numerous familial and demographic factors were significantly associated with BRCA1 and, to a lesser extent, BRCA2 carrier status, when examined individually. In models considering all predictors together, early onset ages in cases and in relatives, family history of ovarian cancer, and Jewish ancestry remained strongly and significantly predictive of BRCA1 carrier status, whereas BRCA2 predictors were fewer and more modest in magnitude. Both the combinations of predictors and effect sizes varied across racial/ethnic and age groups. These results provide first-time prevalence estimates for BRCA1/BRCA2 in breast cancer cases among understudied racial and age groups and show key predictors of mutation carrier status for both White and Black women and women of a wide age spectrum with breast cancer in the general population.

Hormone replacement therapy regimens and breast cancer risk

OBJECTIVE Hormone replacement therapy (HRT) has increased in the United States over the past 2 decades in response to reports of long‐term health benefits. A relationship between HRT and breast cancer risk has been observed in a number of epidemiological studies. In 2002, the Womens Health Initiative Randomized Controlled Trial reported an association between continuous combined HRT and breast cancer risk. The objective of this study was to examine the association between breast cancer risk and HRT according to regimen and duration and recency of use. METHODS A multicenter, population‐based, case‐control study was conducted in five United States metropolitan areas from 1994 to 1998. Analyzed were data from 3823 postmenopausal white and black women (1870 cases and 1953 controls) aged 35–64 years. Odds ratios (ORs) were calculated as estimates of breast cancer risk using standard, unconditional, multivariable logistic regression analysis. Potential confounders were included in the final model if they altered ORs by 10% or more. Two‐sided P values for trend were computed from the likelihood ratio statistic. RESULTS Continuous combined HRT was associated with increased breast cancer risk among current users of 5 or more years (1.54; 95% confidence interval 1.10, 2.17). Additionally, a statistically significant trend indicating increasing breast cancer risk with longer duration of continuous combined HRT was observed among current users (P = .01). There were no positive associations between breast cancer risk and other HRT regimens. CONCLUSION Our data suggest a positive association between continuous combined HRT and breast cancer risk among current, longer term users. Progestin administered in an uninterrupted regimen may be a contributing factor. Risk dissipates once use is discontinued.

Relation of regimens of combined hormone replacement therapy to lobular, ductal, and other histologic types of breast carcinoma†

The incidence of invasive lobular carcinoma has been increasing among postmenopausal women in some parts of the United States. Part of this may be due to changes in classification over time. However, the use of combined (estrogen and progestin) hormone replacement therapy (CHRT) also has increased during the last decade and may account in part for the increase in invasive lobular breast carcinoma.

The NICHD Women's Contraceptive and Reproductive Experiences Study: Methods and Operational Results

PURPOSE This paper presents methods and operational results of a population-based case-control study examining the effects of oral contraceptive use on breast cancer risk among white and black women aged 35-64 years in five U.S. locations. METHODS Cases were women newly diagnosed with breast cancer during July 1994 through April 1998. Controls were identified through random digit dialing (RDD) using unclustered sampling with automated elimination of nonworking numbers. Sampling was density-based, with oversampling of black women. In-person interviews were conducted from August 1994 through December 1998. Blood samples were obtained from subsets of cases and controls, and tissue samples were obtained from subsets of cases. A computerized system tracked subjects through study activities. Special attention was devoted to minimizing exposure misclassification, because any exposure-disease associations were expected to be small. RESULTS An estimated 82% of households were screened successfully through RDD. Interviews were completed for 4575 cases (2953 whites; 1622 blacks) and 4682 controls (3021 whites; 1661 blacks). Interview response rates for cases and controls were 76.5% and 78.6%, respectively, with lower rates for black women and older women. CONCLUSIONS The methodologic details of this large collaboration may assist researchers conducting similar investigations.

Morbidity and mortality of colorectal carcinoma surgery differs by insurance status

Uninsured and underinsured patients are reported to be at an increased risk for impaired access to healthcare, delayed medical treatment, and the receipt of substandard care. These differences in care may result in disparities in surgical outcomes among patients with different types of insurance. In the current study, the authors examined associations between the insurance provider and short‐term surgical outcomes after surgery for colorectal carcinoma and evaluated the extent to which two risk factors (comorbid disease and admission type) might explain any observed association.

Reproductive factors and subtypes of breast cancer defined by hormone receptor and histology

Reproductive factors are associated with reduced risk of breast cancer, but less is known about whether there is differential protection against subtypes of breast cancer. Assuming reproductive factors act through hormonal mechanisms they should protect predominantly against cancers expressing oestrogen (ER) and progesterone (PR) receptors. We examined the effect of reproductive factors on subgroups of tumours defined by hormone receptor status as well as histology using data from the NIHCD Womens Contraceptive and Reproductive Experiences (CARE) Study, a multicenter case–control study of breast cancer. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) as measures of relative risk using multivariate unconditional logistic regression methods. Multiparity and early age at first birth were associated with reduced relative risk of ER + PR + tumours (P for trend=0.0001 and 0.01, respectively), but not of ER − PR − tumours (P for trend=0.27 and 0.85), whereas duration of breastfeeding was associated with lower relative risk of both receptor-positive (P for trend=0.0002) and receptor-negative tumours (P=0.0004). Our results were consistent across subgroups of women based on age and ethnicity. We found few significant differences by histologic subtype, although the strongest protective effect of multiparity was seen for mixed ductolobular tumours. Our results indicate that parity and age at first birth are associated with reduced risk of receptor-positive tumours only, while lactation is associated with reduced risk of both receptor-positive and -negative tumours. This suggests that parity and lactation act through different mechanisms. This study also suggests that reproductive factors have similar protective effects on breast tumours of lobular and ductal origin.

Older age predicts a decline in adjuvant chemotherapy recommendations for patients with breast carcinoma: evidence from a tertiary care cohort of chemotherapy-eligible patients.

The appropriate use of adjuvant chemotherapy for elderly women with breast carcinoma remains controversial. Efficacy data in women age ≥ 70 years are scarce, resulting in a lack of clear guidelines for patients in this age group. Although several studies have demonstrated decreasing use of chemotherapy with age, none specifically examined its use in an elderly cohort of patients who were deemed eligible for such therapy based on consensus guidelines, simultaneously examining the impact of comorbidity and previous history of malignant disease on these recommendations.

Risk Factors for Lymphedema after Breast Cancer Treatment

Background: As cancer treatments evolve, it is important to reevaluate their effect on lymphedema risk in breast cancer survivors. Methods: A population-based random sample of 631 women from metropolitan Philadelphia, Pennsylvania, diagnosed with incident breast cancer in 1999 to 2001, was followed for 5 years. Risk factor information was obtained by questionnaire and medical record review. Lymphedema was assessed with a validated questionnaire. Using Cox proportional hazards models, we estimated the relative incidence rates [hazard ratios (HR)] of lymphedema with standard adjusted multivariable analyses ignoring interactions, followed by models including clinically plausible treatment interactions. Results: Compared with no lymph node surgery, adjusted HRs for lymphedema were increased following axillary lymph node dissection [ALND; HR, 2.61; 95% confidence interval (95% CI), 1.77-3.84] but not sentinel lymph node biopsy (SLNB; HR, 1.04; 95% CI, 0.58-1.88). Risk was not increased following irradiation [breast/chest wall only: HR, 1.18 (95% CI, 0.80-1.73); breast/chest wall plus supraclavicular field (+/− full axilla): HR, 0.86 (95% CI, 0.48-1.54)]. Eighty-one percent of chemotherapy was anthracycline based. The HR for anthracycline chemotherapy versus no chemotherapy was 1.46 (95% CI, 1.04-2.04), persisting after stratifying on stage at diagnosis or number of positive nodes. Treatment combinations involving ALND or chemotherapy resulted in approximately 4- to 5-fold increases in HRs for lymphedema [e.g., HR of 4.16 (95% CI, 1.32-12.45) for SLNB/chemotherapy/no radiation] compared with no treatment. Conclusion: With standard multivariable analyses, ALND and chemotherapy increased lymphedema risk whereas radiation therapy and SLNB did not. However, risk varied by combinations of exposures. Impact: Treatment patterns should be considered when counseling and monitoring patients for lymphedema. Cancer Epidemiol Biomarkers Prev; 19(11); 2734–46. ©2010 AACR.

Reproductive factors and risk of breast carcinoma in a study of white and African-American women.

Few studies have investigated the association between reproductive factors and the risk of breast carcinoma among African‐American women. The authors assessed whether the number of full‐term pregnancies, age at first full‐term pregnancy, and total duration of breastfeeding were associated with similar relative risk estimates in white and African‐American women in a large multicenter, population‐based case–control study of breast carcinoma.

Sister-chromatid exchanges in association with occupational exposure to ethylene oxide.

Sister-chromatid exchange (SCE) frequencies in employees potentially exposed to ethylene oxide (ETO) were compared with those in unexposed control groups. Three worksites where the previous environmental control of ETO was known to have differed were chosen. Within these worksites, subjects were categorized into high potential exposed, low potential exposed and control groups. An additional community control group was obtained. Blood samples for chromosome studies of peripheral lymphocytes were drawn at several time points over a period of 24 months. The effects on SCE of age, sex, smoking habits and reader variation were considered. Worksites I, II and III, respectively, represented increasing levels of exposure. At Worksite III large differences among groups persisted over 24 months. At Worksite II, the SCEs in the high potential exposed workers were higher than those in the other groups. At no time was the low potential exposed group at Worksite II statistically significantly higher in mean SCE than the worksite controls. No consistent differences among groups were noted in Worksite I.