Genetic testing in an ethnically diverse cohort of high-risk women: a comparative analysis of BRCA1 and BRCA2 mutations in American families of European and African ancestry.

Context: Ten years after BRCA1 and BRCA2 were first identified as major breast cancer susceptibility genes, the spectrum of mutations and modifiers of risk among many ethnic minorities remain undefined.

Objectives: To characterize the clinical predictors, spectrum, and frequency of BRCA1 and BRCA2 mutations in an ethnically diverse high-risk clinic population and to evaluate the performance of the BRCAPRO statistical model in predicting the likelihood of a mutation.

Design, Setting, And Participants: Comparative analysis of families (white, Ashkenazi Jewish, African American, Hispanic, Asian) with 2 or more cases of breast and/or ovarian cancer among first- and second-degree relatives.

Effect of short-term hormone replacement therapy on breast cancer risk reduction after bilateral prophylactic oophorectomy in BRCA1 and BRCA2 mutation carriers: the PROSE Study Group.

Purpose: Bilateral prophylactic oophorectomy (BPO) is widely used for cancer risk reduction in women with BRCA1/2 mutations. Many premenopausal women choose to take hormone replacement therapy (HRT) after undergoing BPO to abrogate immediate symptoms of surgically-induced menopause. Thus, we evaluated whether the breast cancer risk reduction conferred by BPO in BRCA1/2 mutation carriers is altered by use of post-BPO HRT.

Age at menarche and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers.

Age at menarche is a strong and consistent predictor of breast cancer risk in the general population, but has not been well studied in women with a family history of breast cancer. We conducted this study to examine whether the presence of a deleterious BRCA1 or BRCA2 mutation influences age at menarche and to investigate whether or not there is an association between age at menarche and the risk of breast cancer in BRCA1 or BRCA2 mutation carriers. The presence of a deleterious BRCA1 or BRCA2 mutation did not appear to influence a woman's age at menarche.

Computerized texture analysis of mammographic parenchymal patterns of digitized mammograms.

Rationale And Objectives: Mammographic density and parenchymal patterns have been shown to be related to the risk of developing breast cancer. Thus, computerized texture analysis of breast parenchymal patterns on mammograms may be useful in assessing breast cancer risk.

Materials And Methods: A comparative evaluation was conducted of various computer-extracted texture features of mammographic parenchymal patterns of women with BRCA1/BRCA2 gene mutations and those of women at low risk of developing breast cancer.

Effect of pregnancy as a risk factor for breast cancer in BRCA1/BRCA2 mutation carriers.

Early age at first birth and multiparity have been associated with a decrease in the risk of breast cancer in women in the general population. We examined whether this relationship is also present in women at high risk of breast cancer due to the presence of a mutation in either of the 2 breast cancer susceptibility genes, BRCA1 or BRCA2. We performed a matched case-control study of 1,260 pairs of women with known BRCA1 or BRCA2 mutations, recruited from North America, Europe and Israel.

A comparison of bilateral breast cancers in BRCA carriers.

Background: Women with breast cancer and a BRCA mutation have a high risk of developing a contralateral breast cancer. It is generally believed that the two cancers represent independent events. However, the extent of concordance between the first and second tumors with respect to hormone receptor expression and other pathologic features is unknown.

Colorectal cancer and race: understanding the differences in outcomes between African Americans and whites.

Understanding the differences in the incidence and mortality rate between African Americans and whites with CRC remains a perplexing problem. There is clearly not any one factor that explains the observed differences. Clinicians are just beginning to understand the importance of tumor biology, genetics, and lifestyle risk factors in explaining differences in how CRCs present and how they behave.

Racial and ethnic disparities in breast cancer: a multilevel perspective.

Although the etiology of racial and ethnic disparities in breast cancer is complex, the studies reviewed here suggest many possible culprits. In the authors' model, outcomes at the cellular level reflect not only genetic constitution and the hormonal milieu but also the interactions of predictors at multiple levels. At the societal level, important predictors include toxin and hormone exposure, access to care, quality of care, and social support.

Breast cancer and race: a rising tide does not lift all boats equally.

African American women have a lower overall incidence of breast cancer but a higher overall mortality than do white women. African American women with breast cancer present for medical care at an earlier age, with more advanced stage disease, and with higher-risk tumor biology. While the advanced stage at presentation and higher-risk tumor biology appear to account for much of the excess mortality in African American women, differences persist even after controlling for these factors.

Phenotypic heterogeneity in multiple myeloma families.

Purpose: To describe a series of families with familial multiple myeloma (MM). Observations were used to generate hypotheses about the role of genetic factors, the mode of inheritance of these factors, and the association of other cancers with familial MM.

Patients And Methods: This observational study consisted of 39 families with multiple cases of MM or related disorders from four collaborating research centers.

Effect of Prior Bilateral Oophorectomy on the Presentation of Breast Cancer in BRCA1 and BRCA2 Mutation Carriers.

Purpose: To compare the presentation of invasive breast cancer in BRCA1 and BRCA2 mutation carriers with and without prior bilateral oophorectomy.

Patients And Methods: Women with a BRCA1 or BRCA2 mutation with the diagnosis of invasive breast cancer were identified from ten cancer genetics clinics. The medical history, medical treatment records and pathology reports for the breast cancers were reviewed.

The risk of ovarian cancer after breast cancer in BRCA1 and BRCA2 carriers.

Objective: To estimate the risk of ovarian cancer after a primary diagnosis of breast cancer among women with a BRCA1 or BRCA2 mutation and to identify host and treatment-related factors that might modify the risk.

Patients And Methods: Patients were 491 women with stage I or stage II breast cancer, diagnosed from 1975 to 2000 and for whom a BRCA1 or BRCA2 mutation had been identified. Patients were followed from the initial diagnosis of breast cancer until either ovarian cancer, prophylactic oophorectomy, death, or 2002.

Chromosome band 16q22-linked familial AML: exclusion of candidate genes, and possible disease risk modification by NQO1 polymorphisms.

Analyses of chromosomal translocation and inversion breakpoints in sporadic acute myeloid leukemias have identified many transcription factors as playing a role in leukemogenesis. Studies of families with a Mendelian predisposition to hematological malignancies have identified the gene coding for the transcription factor RUNX1 as a leukemia-predisposing gene involved in the first steps of leukemogenesis. Using two families, another autosomal dominant familial leukemia locus was linked to chromosome band 16q22 where the CBFB gene maps.

Fourier components of inhomogeneously broadened water resonances in breast: a new source of MRI contrast.

High spectral and spatial resolution (HiSS) MR data were acquired at 1.5 T using echo-planar spectroscopic imaging from patients with suspicious breast lesions. The water resonances in small voxels are inhomogenously broadened and often have distinct components.

Contralateral breast cancer in BRCA1 and BRCA2 mutation carriers.

Purpose: To estimate the risk of contralateral breast cancer in BRCA1 and BRCA2 carriers after diagnosis and to determine which factors are predictive of the risk of a second primary breast cancer.

Patients And Methods: Patients included 491 women with stage I or stage II breast cancer, for whom a BRCA1 or BRCA2 mutation had been identified in the family. Patients were followed from the initial diagnosis of cancer until contralateral mastectomy, contralateral breast cancer, death, or last follow-up.

Computerized analysis of mammographic parenchymal patterns for assessing breast cancer risk: effect of ROI size and location.

The long-term goal of our research is to develop computerized radiographic markers for assessing breast density and parenchymal patterns that may be used together with clinical measures for determining the risk of breast cancer and assessing the response to preventive treatment. In our earlier studies, we found that women at high risk tended to have dense breasts with mammographic patterns that were coarse and low in contrast. With our method, computerized texture analysis is performed on a region of interest (ROI) within the mammographic image.

Estrogen receptor status in BRCA1- and BRCA2-related breast cancer: the influence of age, grade, and histological type.

Purpose: BRCA1-related breast cancers are more frequently estrogen receptor (ER) negative than are either BRCA2-related or nonhereditary breast cancers. The relationship between ER status and other clinical features of hereditary breast cancers has not been well studied.

Experimental Design: ER status, grade, and histological tumor type were evaluated in 1131 women with invasive breast cancer, ascertained at 10 centers in North America.

Efficacy of risk-reducing salpingo-oophorectomy in women with BRCA-1 and BRCA-2 mutations.

Recognizing the emerging role of genetics in clinical care, in 1996 the American Society of Clinical Oncology established a Task Force on Cancer Genetics Education to develop educational opportunities and resources for its members. These efforts, and recent advances in the understanding of genetic predisposition to breast and ovarian cancers, have resulted in growing numbers of women participating in genetic testing protocols. The first prospective clinical trial involving women with known BRCA-1 and BRCA-2 mutations was recently published.

Bilateral prophylactic mastectomy reduces breast cancer risk in BRCA1 and BRCA2 mutation carriers: the PROSE Study Group.

Purpose: Data on the efficacy of bilateral prophylactic mastectomy for breast cancer risk reduction in women with BRCA1 and BRCA2 (BRCA1/2) mutations are limited, despite the clinical use of this risk-management strategy. Thus, we estimated the degree of breast cancer risk reduction after surgery in women who carry these mutations.

Patients And Methods: Four hundred eighty-three women with disease-associated germline BRCA1/2 mutations were studied for the occurrence of breast cancer.

MYC is amplified in BRCA1-associated breast cancers.

Purpose: Germ-line mutations in the BRCA1 tumor suppressor gene predispose to early onset breast cancers with a distinct phenotype characterized by high tumor grade, aneuploidy, high proliferation rate, and estrogen receptor-negativity. The molecular mechanisms and cooperative oncogenes contributing to multistep tumor progression in cells lacking BRCA1 are not well defined. To examine whether C-MYC (MYC), a transforming oncogene associated with genetic instability, contributes to multistep tumor progression in BRCA1-associated breast cancer, we have analyzed tumors from women with hereditary BRCA1-mutated and sporadic breast cancers.

Disruption of the expected positive correlation between breast tumor size and lymph node status in BRCA1-related breast carcinoma.

Background: A positive correlation between breast tumor size and the number of axillary lymph nodes containing tumor is well established. It has been reported that patients with BRCA1-related breast carcinoma are more likely than patients with nonhereditary breast carcinoma to have negative lymph node status. Therefore, the authors questioned whether the known positive correlation between tumor size and lymph node status also was present in women with BRCA1-related breast carcinomas.