Breast Cancer Risk After Bilateral Prophylactic Oophorectomy in BRCA1 Mutation Carriers

Rebbeck, Timothy R.; Levin, Albert M.; Eisen, Andrea; Snyder, Carrie; Watson, Patrice; Cannon-Albright, Lisa; Isaacs, Claudine; Olopade, O. I.; Garber, Judy E.; Godwin, Andrew K.; Daly, Mary B.; Narod, Steven A.; Neuhausen, Susan L.; Lynch, Henry T.; Weber, Barbara

doi:10.1093/jnci/91.17.1475

Cited by 612 publications

(309 citation statements)

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“…33 Currently, nonsurgical chemoprevention options available for BRCA carriers are based on interrupting the estrogen-signalling pathway and implicate an important role of sex hormones in the etiology of the disease. Although the majority of BRCA1 (but not BRCA2) tumours are estrogen receptor negative, oophorectomy [34][35][36] and tamoxifen 37 have been shown to reduce the risk of breast cancer among carriers of either mutation. Based on this observation, alternative dietary and lifestyle strategies that minimize exposure to estrogen or alter the 2-OHE/16a-OHE ratio may also impact overall risk.…”

Section: Discussionmentioning

confidence: 99%

Coffee consumption and breast cancer risk among BRCA1 and BRCA2 mutation carriers

Nkondjock

Ghadirian

Kotsopoulos

et al. 2005

Intl Journal of Cancer

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Although there are several plausible biologic mechanisms whereby coffee consumption might influence the risk of breast cancer, epidemiologic evidence is limited. We assessed the association between coffee consumption and breast cancer risk among high-risk women who carry BRCA mutations. We performed a matched case-control analysis on 1,690 women with a BRCA1 or BRCA2 mutation from 40 centers in 4 countries. Average lifetime coffee consumption was estimated via a self-administered questionnaire. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression. After adjustment for potential confounders, the ORs for breast cancer in BRCA carriers who habitually drank 0, 1-3, 4-5 and 6 or more cups of coffee were 1.00, 0.90 (95% CI 0.72-1.12), 0.75 (95% CI 0.47-1.19) and 0.31 (95% CI 0.13-0.71; p-trend 5 0.02). The effect was limited to the consumption of caffeinated coffee. These results suggest that among women with BRCA gene mutation, coffee consumption is unlikely to be harmful and that high levels of consumption may in fact be related to reduced breast cancer risk. ' 2005 Wiley-Liss, Inc.Key words: BRCA1; BRCA2; breast cancer; coffee; case-control study Coffee is among the most widely consumed beverages in the world and is a major source of dietary caffeine. Over the last 2 decades, coffee and caffeine have been studied with regard to their potential role in breast cancer etiology. A number of animal studies have reported caffeine to both stimulate and to suppress breast tumors, depending upon the species and the phase of administration. 1 Coffee consumption (or caffeine intake) has been directly associated with plasma estradiol, estrone and sex hormone-binding globulin levels, and inversely associated with testosterone. 2,3 Coffee consumption also induces cell differentiation 4 and may inhibit mitosis. 5 These effects suggest that coffee consumption may affect breast cancer risk, but epidemiologic evidence supporting the association between coffee consumption and breast cancer risk is scant. A decrease in breast cancer risk in women with high levels of coffee consumption has been reported in several studies, 6,7 but other investigators have detected no relationship between coffee consumption and breast cancer risk. 1,8 It has been estimated that the risk of developing breast cancer among women with a mutation in BRCA1 or BRCA2 is as high as 80% by the age of 70. 9 Whether or not coffee affects BRCArelated breast cancer risk is currently unknown. To address this issue, we examined the association between coffee consumption and the risk of breast cancer among women with BRCA1 and BRCA2 gene mutations from 40 participating centers in 4 countries. Material and methods Study population and designThe study population has been described elsewhere. 10 Briefly, eligible study subjects included women who were currently alive and were known to be carriers of deleterious mutations of the BRCA1 or BRCA2 gene. These women were identified from 40 participating clinical cancer geneti...

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Section: Discussionmentioning

confidence: 99%

Coffee consumption and breast cancer risk among BRCA1 and BRCA2 mutation carriers

Nkondjock

Ghadirian

Kotsopoulos

et al. 2005

Intl Journal of Cancer

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“…Three studies have reported that prophylactic oophorectomy reduced the risk of developing breast cancer in BRCA1-mutation carriers by 50%. 102 However, the benefit of tamoxifen remains controversial. The protective effect of tamoxifen against breast cancer has been demonstrated in women with moderate risk factors, but the data specific for carriers of BRCA1 mutations remain unclear.…”

Section: Therapeutic Implicationsmentioning

confidence: 99%

The molecular pathology of hereditary breast cancer: genetic testing and therapeutic implications

2005

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Cancer arising in carriers of mutations in the BRCA1 and BRCA2 genes differs from sporadic breast cancer of age-matched controls and from non-BRCA1/2 familial breast carcinomas in its morphological, immunophenotypic and molecular characteristics. Most BRCA1 carcinomas have the basal cell phenotype, a subtype of highgrade, highly proliferating, estrogen receptor-and HER2-negative breast carcinomas, characterized by the expression of basal or myoepithelial markers such as basal keratins, P-cadherin, epidermal growth factor receptor, etc. This phenotype is rarely found in BRCA2 carcinomas, which are of higher grade than sporadic age-matched controls, but tend to be estrogen receptor-and progesterone receptor-positive. The expression of the cell-cycle proteins cyclins A, B1 and E and SKP2 is associated with a BRCA1 phenotype, whereas cyclin D1 and p27 expression is associated with BRCA2 carcinomas. Recent studies have shown that hereditary carcinomas that are not attributable to BRCA1/2 mutations have phenotypic similarities to BRCA2 tumors, but tend to be of lower grade and proliferation index. Somatic mutations in the BRCA genes are rarely found in hereditary tumors; by contrast, BRCA1 and BRCA2 loss of heterozygosity (LOH) is found in almost all BRCA1 and BRCA2 carcinomas, respectively. Furthermore, all types of hereditary breast carcinomas have a low frequency of HER2 expression. Finally, comparative genomic hybridization studies have revealed differences in chromosomal gains and losses between genotypes. The pathological and molecular features of hereditary breast cancer can drive specific treatments and influence the process of mutation screening. In addition, detecting molecular changes such as BRCA1/2 LOH in nonatypical cells obtained by random fine-needle aspiration, ductal lavage or nipple aspirate fluid may help to earlier identify carrier women who are at an even higher risk of developing breast carcinoma. Keywords: hereditary breast cancer; BRCA1; BRCA2; molecular pathology; histopathology; immunohistochemistry It is currently estimated that 5-10% of all breast cancers are hereditary and attributable to mutations in high-penetrance susceptibility genes, but only two of these have been identified: BRCA1 (OMIM 113705) 1 and BRCA2 (OMIM 600185). 2 BRCA1 mutations are associated with families with breast and ovarian cancer, while families with male breast tumors are associated with mutations in the BRCA2 gene.While early estimates suggested that BRCA1 and BRCA2 mutations were responsible for 75% of multiple-case breast cancer families and for the majority of families with multiple breast and ovarian cancers, 3,4 recent data have shown that these percentages may have been overestimated. In fact, the percentage of high-risk families associated with mutations in these genes seems to be around 25% in all series investigated, including the Spanish population. 5 Mutations are found in a high percentage (about 45%) of families with breast and ovarian tumors, while the mutation rate in families with only breast can...

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“…Identification of these individuals before they present with cancer is important since prophylactic surgery can reduce morbidity and mortality in these individuals (Struewing et al, 1995;Rebbeck et al, 1999;Hartmann et al, 1999;Hartmann et al, 2001;Meijers-Heijboer et al, 2001;Kauff et al, 2002;Rebbeck et al, 2004). Unfortunately, genetic testing is expensive, family history of breast cancer is common and BRCA mutations are rare (Ford et al, 1994;Peto et al, 1999;Antoniou et al, 2002).…”

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confidence: 99%

Evaluation of models to predict BRCA germline mutations

et al. 2006

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The selection of candidates for BRCA germline mutation testing is an important clinical issue yet it remains a significant challenge. A number of risk prediction models have been developed to assist in pretest counselling. We have evaluated the performance and the inter-rater reliability of four of these models (BRCAPRO, Manchester, Penn and the Myriad-Frank). The four risk assessment models were applied to 380 pedigrees of families who had undergone BRCA1/2 mutation analysis. Sensitivity, specificity, positive and negative predictive values, likelihood ratios and area under the receiver operator characteristic (ROC) curve were calculated for each model. Using a greater than 10% probability threshold, the likelihood that a BRCA test result was positive in a mutation carrier compared to the likelihood that the same result would be expected in an individual without a BRCA mutation was 2.10 (95% confidence interval (CI) 1.66 -2.67) for Penn, 1.74 (95% CI 1.48 -2.04) for Myriad, 1.35 (95% CI 1.19 -1.53) for Manchester and 1.68 (95% CI 1.39 -2.03) for BRCAPRO. Application of these models, therefore, did not rule in BRCA mutation carrier status. Similar trends were observed for separate BRCA1/2 performance measures except BRCA2 assessment in the Penn model where the positive likelihood ratio was 5.93. The area under the ROC curve for each model was close to 0.75. In conclusion, the four models had very little impact on the pre-test probability of disease; there were significant clinical barriers to using some models and risk estimates varied between experts. Use of models for predicting BRCA mutation status is not currently justified for populations such as that evaluated in the current study.

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Breast Cancer Risk After Bilateral Prophylactic Oophorectomy in BRCA1 Mutation Carriers

Cited by 612 publications

References 13 publications

Coffee consumption and breast cancer risk among BRCA1 and BRCA2 mutation carriers

Coffee consumption and breast cancer risk among BRCA1 and BRCA2 mutation carriers

The molecular pathology of hereditary breast cancer: genetic testing and therapeutic implications

Evaluation of models to predict BRCA germline mutations

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