BRCA1 and BRCA2 mutations in Russian familial breast cancer

We have screened index cases from 25 Russian breast/ovarian cancer families for germ‐line mutations in all coding exons of the BRCA1 and BRCA2 genes, using multiplex heteroduplex analysis. In addition we tested 22 patients with breast cancer diagnosed before age 40 without family history and 6 patients with bilateral breast cancer. The frequency of families with germline mutations in BRCA was 16% (4/25). One BRCA1 mutation, 5382insC, was found in three families. The results of present study, and those of a separate study of 19 breast‐ovarian cancer families, suggest that BRCA1 5382insC is a founder mutation in the Russian population. Three BRCA2 mutations were found in patients with breast cancer without family history: two in young patients and one in patients with bilateral breast cancer. Four novel BRCA2 mutations were identified: three frameshift (695insT, 1528del4, 9318del4) and one nonsense (S1099X). © 2002 Wiley‐Liss, Inc.     

Founder BRCA1 and BRCA2 mutations in French Canadian ovarian cancer cases unselected for family history

The breast cancer susceptibility genes, BRCA1 and BRCA2, differ in their contribution to ovarian cancer. Recently, founder mutations in each of these genes were identified in Canadian breast cancer and breast ovarian cancer families of French ancestry. We have examined the prevalence of the founder mutations in a series of 113 French Canadian women with ovarian cancer unselected for family history. Germline mutations were found in eight of 99 invasive carcinomas and in none of the 14 tumors of borderline malignancy. Five cases carried the BRCA1 C4446T mutation and two cases carried the BRCA2 8765delAG mutation which are the most common mutations that have been described in French Canadian breast cancer and breast ovarian cancer families. All of these cases reported a family history of at least one first-degree relative with breast cancer, diagnosed below age 60 years, or with ovarian cancer. The identification of founder BRCA1 and BRCA2 mutations in ovarian cancer cases unselected for family history can facilitate carrier detection when the expected yield of a comprehensive screen may be low.     

Estimating survival rates after ovarian cancer among women tested for BRCA1 and BRCA2 mutations

Several studies have reported that women with ovarian cancer and a BRCA1 or BRCA2 mutations have better survival than women with ovarian cancer and no mutation. Potential reasons for this include possible differences in histologic subtype, stage, grade and response to chemotherapy, but some of the difference in survival may be due to systematic bias, i.e. a difference in survival rates for women who do and who do not undergo genetic testing. We estimated the survival rate in 1423 ovarian cancer patients from Ontario who had genetic testing and compared this with the survival rate for all 3367 ovarian cancer patients from the province from whom the tested sample was derived. Tested women had a 10‐year survival of 54.5%, compared to 35.8% for all patients in the province. We evaluated the extent to which three different methods of adjustment eliminated the observed difference. The adjusted rates for the tested cohort were closer to the provincial average, but each adjustment method resulted in a modest over‐estimate of 10‐year survival, ranging from 6.1% to 10.0%. The mortality advantage for tested women was due, in part, to a lower than expected mortality rate of tested women in the period following genetic testing.     

Contribution of the BRCA1 and BRCA2 mutations to breast cancer in Tunisia

Hereditary breast cancer accounts for 3–8% of all breast cancers, with mutations in the BRCA1 and BRCA2 genes responsible for up to 30% of these. To investigate the prevalence of BRCA1 and BRCA2 gene mutations in breast cancer patients with affected relatives in Tunisia, we studied 36 patients who had at least one first degree relative with breast and/or ovarian cancer Thirty-four 34 patients were suggestive of the BRCA1 mutation and two were suggestive of the BRCA2 mutation, based on the presence of male breast cancer detected in their corresponding pedigrees. Four mutations in BRCA1 were detected, including a novel frame-shift mutation (c.211dupA) in two unrelated patients and three other frameshift mutations – c.4041delAG, c.2551delG and c.5266dupC. Our study is the first to describe the c.5266dupC mutation in a non-Jewish Ashkenazi population. Two frameshift mutations (c.1309del4 and c.5682insA) were observed in BRCA2. Nineteen percent (7/36) of the familial cases had deleterious mutations of the BRCA1 or BRCA2 genes. Almost all patients with deleterious mutations of BRCA1 reported a family history of breast and/or ovarian cancer in the index case or in their relatives. Our data are the first to contribute to information on the mutation spectrum of BRCA genes in Tunisia, and we give a recommendation for improving clinical genetic testing policy.     

Contribution of BRCA1 and BRCA2 mutations to inherited ovarian cancer

A total of 283 epithelial ovarian cancer families from the United Kingdom (UK) and the United States (US) were screened for coding sequence changes and large genomic alterations (rearrangements and deletions) in the BRCA1 and BRCA2 genes. Deleterious BRCA1 mutations were identified in 104 families (37%) and BRCA2 mutations in 25 families (9%). Of the 104 BRCA1 mutations, 12 were large genomic alterations; thus this type of change represented 12% of all BRCA1 mutations. Six families carried a previously described exon 13 duplication, known to be a UK founder mutation. The remaining six BRCA1 genomic alterations were previously unreported and comprised five deletions and an amplification of exon 15. One of the 25 BRCA2 mutations identified was a large genomic deletion of exons 19-20. The prevalence of BRCA1/2 mutations correlated with the extent of ovarian and breast cancer in families. Of 37 families containing more than two ovarian cancer cases and at least one breast cancer case with diagnosis at less than 60 years of age, 30 (81%) had a BRCA1/2 mutation. The mutation prevalence was appreciably less in families without breast cancer; mutations were found in only 38 out of 141 families (27%) containing two ovarian cancer cases only, and in 37 out of 59 families (63%) containing three or more ovarian cancer cases. These data indicate that BRCA1 and BRCA2 are the major susceptibility genes for ovarian cancer but that other susceptibility genes may exist. Finally, it is likely that these data will be of clinical importance for individuals in families with a history of epithelial ovarian cancer, in providing accurate estimates of their disease risks.     

Androgen receptor expression in breast cancer patients tested for BRCA1 and BRCA2 mutations

Pristauz G, Petru E, Stacher E, Geigl J B, Schwarzbraun T, Tsybrovskyy O, Winter R & Moinfar F
(2010) Histopathology 57, 877–884 Androgen receptor expression in breast cancer patients tested for BRCA1 and BRCA2 mutations Aim: To assess the expression of receptors for androgen (AR), oestrogen (ER) and progesterone (PR) as well as human epidermal growth factor receptor type 2 (Her‐2/neu) status of breast carcinomas in breast cancer susceptibility gene (BRCA) BRCA1/2 mutation carriers and BRCA1/2 negative tested women. Methods: One hundred and thirty‐five breast cancers in women tested for BRCA1/2 mutations. Screening for BRCA1 and BRCA2 mutations was performed by direct sequencing of all BRCA1 and BRCA2 exons as well as the surrounding intronic sequences. Additionally, BRCA genes were analysed with multiplex ligation‐dependent probe amplification. Consecutive paraffin sections were examined immunhistochemically for AR, ER, PR and Her‐2/neu. Results: Of the 135 tumours, 43 (32%) were BRCA1‐related, 18 (13%) were BRCA2‐related and 74 (55%) were BRCA1/2‐negative. Seventy‐two per cent of the BRCA1‐related, 22% of the BRCA2‐related and 12% of the BRCA1/2‐negative tumours were triple (ER, PR, Her2neu)‐negative. Eighty‐four per cent of BRCA1 mutated cancers were high‐grade (G3) tumours. ARs were expressed in 30% (13 of 43) of BRCA1‐related, in 78% (14 of 18) in BRCA2‐related tumours and in 76% (56 of 74) in BRCA1/2 negative tumours. Twenty‐one per cent of ER‐negative BRCA1‐related tumours expressed androgen receptors. Conclusion: Approximately one in five BRCA1 mutated breast cancers negative for ER and PR express androgen receptors. Modulation of AR might open a new avenue for treating these high‐risk cancers.     

BRCA1 and BRCA2 mutations among familial breast cancer patients from Costa Rica

Gutiérrez Espeleta GA, Llacuachaqui M, García-Jiménez L, Aguilar Herrera M, Loáiciga Vega K, Ortiz A, Royer R, Li S, Narod SA. BRCA1 and BRCA2 mutations among familial breast cancer patients from Costa Rica. The contribution of mutations in BRCA1 and BRCA2 genes to the burden of breast cancer in Costa Rica has not been studied. We estimated the frequency of BRCA mutations among 111 Costa Rican women with breast cancer and a family history of breast cancer. These women were mainly from the metropolitan area of San José. A detailed family history was obtained from each patient and a blood sample was processed for DNA extraction. Mutations in BRCA1 and BRCA2 were sought using a combination of techniques and all mutations were confirmed by direct sequencing. Four different mutations were identified in five patients (four in BRCA2 and one in BRCA1) representing 4.5% of the total. Two unrelated patients were found to have a BRCA2 5531delTT mutation. Other BRCA2 mutations included C5507G and 6174delT. Only one BRCA1 mutation was found (C3522T). The family with the BRCA1 mutation had five cases of gastric cancer. Families with BRCA2 mutations were also reported to have cases of gastric and prostate cancers; however, the full range of cancers associated with BRCA1 and BRCA2 mutations in Costa Rica has not yet been established.     

Prevalence of BRCA1 and BRCA2 mutations in unselected breast cancer patients from Peru

The prevalence of BRCA1 and BRCA2 mutations among breast cancer patients in Peru has not yet been explored. We enrolled 266 women with breast cancer from a National cancer hospital in Lima, Peru, unselected for age or family history. DNA was screened with a panel of 114 recurrent Hispanic BRCA mutations (HISPANEL). Among the 266 cases, 13 deleterious mutations were identified (11 in BRCA1 and 2 in BRCA2), representing 5% of the total. The average age of breast cancer in the mutation‐positive cases was 44 years. BRCA1 185delAG represented 7 of 11 mutations in BRCA1. Other mutations detected in BRCA1 included: two 2080delA, one 943ins10, and one 3878delTA. The BRCA2 3036del4 mutation was seen in two patients. Given the relatively low cost of the HISPANEL test, one should consider offering this test to all Peruvian women with breast or ovarian cancer.     

BRCA1 and BRCA2 mutations in breast/ovarian cancer patients from central Italy

We report on the screening of the entire BRCA1/BRCA2 coding sequence by SSCP, PTT, and direct sequencing in 68 Italian families with recurrent breast or ovarian cancer. For each investigated proband, the probability of being carrier of a BRCA1/BRCA2 mutation was evaluated using the BRCAPRO software. We detected BRCA1/BRCA2 mutations in 8 patients (11.7%). However, if considering only patients with a carrier probability >10%, the detection rate was 36.8%, confirming the usefulness of the BRCAPRO software. One change (BRCA1 4172insT) was a novel mutation not reported in BIC database.     

中国上海家族性乳腺癌BRCA1和BRCA2基因的突变

目的研究上海地区家族性乳腺癌中BRCA1／BRCA2基因的突变位点及携带情况。方法研究对象来自35个汉族家族性乳腺癌家系，家系中至少有一个一级亲属乳腺癌患病史。共35例患者，其中13例发病年龄≤加岁。由静脉血提取基因组DNA，对BRCA1／BRCA2基因的全部编码序列进行扩增。扩增产物突变分析先由变性高效液相色谱分析进行筛查，之后进行DNA直接测序证实。结果在BRCA1基因中发现有4个突变位点，其中2个为新发现位点——拼接点突变（IVS17-1G〉T；IVS21＋1G〉C）；另两个为已报道的致病突变位点——移码突变（1100delAT；5640delA）。BRCA2基因的1个致病突变位点位于11号外显子上，为移码突变（5802delAATT）。另外，共发现有12个新的单核苷重复多态位点，都未引起氨基酸编码改变；其中，8个在BRCA1基因上，4个在BRCA2基因上。在家族性乳腺癌中，BRCA1突变频率（11．4％）高于BRCA2基因（2．9％）。结论新发现的2个BRCA1基因的拼接点突变可能是中国上海人群家族性乳腺癌的特有突变位点；在我国上海地区人群中，BRCA1基因突变起着比BRCA2基因更大的作用；该研究丰富了中国人群中BRCA基因的突变谱，并为未来的临床基因检测提供了筛查模式。     

Screening for BRCA1 and BRCA2 mutations in Eastern Finnish breast/ovarian cancer families

Familial aggregation is thought to account for 5-10% of all breast cancer cases, and high penetrance breast and ovarian cancer susceptibility genes BRCA1 and BRCA2 explain < or =20% of these. Hundreds of mutations among breast/ovarian cancer families have been found in these two genes. The mutation spectrum and prevalence, however, varies widely among populations. Thirty-six breast/ovarian cancer families were identified from a population sample of breast and ovarian cancer cases among a relatively isolated population in Eastern Finland, and the frequency of BRCA1/BRCA2 germline mutations were screened using heteroduplex analysis, protein truncation test and sequencing. Five different mutations were detected in seven families (19.4%). Two mutations were found in BRCA1 and three in BRCA2. One of the mutations (BRCA2 4088insA) has not been detected elsewhere in Finland while the other four, 4216-2nt A-->G and 5370 C-->T in BRCA1 and 999del5 and 6503delTT in BRCA2, are recurrent Finnish founder mutations. These results add to the evidence of the geographical differences in distribution of Finnish BRCA1/BRCA2 mutations. This screen also provides further evidence for the presumption that the majority of Finnish BRCA1/BRCA2 founder mutations have been found and that the proportion of BRCA1/BRCA2 mutations in Finnish breast/ovarian cancer families is around 20%.     

Contribution of BRCA1 and BRCA2 germline mutations to the incidence of early-onset breast cancer in Cyprus

In Cyprus, the prevalence of breast cancer associated with BRCA1 and BRCA2 mutations in young women is unknown. In this study, we present the results of mutational analysis of the BRCA1 and BRCA2 genes in 26 Cypriot women diagnosed with breast cancer by the age of 40. The entire coding regions, including splice sites, of the BRCA1 and BRCA2 genes were sequenced using cycle sequencing. We identified four pathogenic mutations: two in BRCA1 [c.1840A>T (K614X), c.5310delG (5429delG)] and two in BRCA2 [c.3531-3534delCAGC (3758del4), c.8755delG (8984delG)] in six of 26 unrelated patients. The BRCA2 mutation c.3531-3534delCAGC (3758del4) is novel and the BRCA1 mutation c.1840A>T (K614X) is reported for the first time in Cypriot patients. The BRCA2 Cypriot founder mutation c.8755delG (8984delG) was detected in three unrelated patients. Additionally, we identified one novel BRCA1 missense mutation, two novel polymorphisms and three novel intronic variants of which BRCA1 c.4185+3A>G (IVS12+3A>G) may be pathogenic. Of the six BRCA1/2 mutation carriers, only four had a family history. These results show that the prevalence of BRCA1 and BRCA2 mutations in Cypriot women diagnosed with early-onset breast cancer is high. We conclude that Cypriot women with early-onset breast cancer should be offered BRCA1/2 testing irrespective of their family history.     

Development and testing of a decision aid for breast cancer prevention for women with a BRCA1 or BRCA2 mutation

For women who carry a mutation in BRCA1 or BRCA2, the risk of breast cancer is up to 87% by the age of 70. There are options available to reduce the risk of breast cancer; however, each option has both risks and benefits, which makes decision making difficult. The objective is to develop and pilot test a decision aid for breast cancer prevention for women with a BRCA1 or BRCA2 mutation. The decision aid was developed and evaluated in three stages. In the first stage, the decision aid was developed and reviewed by cancer genetics experts. The second stage was a review of the decision aid by women with a BRCA1 or BRCA2 mutation for acceptability and feasibility. The final stage was a pre-test--post-test evaluation of the decision aid. Twenty-one women completed the pre-test questionnaire and 20 completed the post-test questionnaire. After using the decision aid, there was a significant decline in mean decisional conflict scores (p = 0.001), a significant improvement in knowledge scores (p = 0.004), and fewer women uncertain about prophylactic mastectomy (p = 0.003) and prophylactic oophorectomy (p = 0.009). Use of the decision aid decreased decisional conflict to levels suggestive of implementation of a decision. In addition, knowledge levels increased and choice predisposition changed with fewer women being uncertain about each option. This has significant clinical implications as it implies that with greater uptake of cancer prevention options by women with a BRCA1 or BRCA2 mutation, fewer women will develop and/or die of hereditary breast cancer.     

Recurrent mutations of BRCA1 and BRCA2 in Poland: an update

Three founder alleles of BRCA1 (C61G, 4153delA, 5382insC) were reported in Poland in 2000, and these three mutations have comprised the standard testing panel used throughout the country. However, since 2000, other recurrent mutations of BRCA1 and BRCA2 have been reported. To establish if the inclusion of one or more of these mutations will increase the sensitivity of the standard test panel, we studied 1164 Polish women with unselected breast cancer diagnosed at age of 50 or below. All women were genotyped for 12 recurrent mutations of BRCA1 and BRCA2. We identified a mutation in 83 of 1164 patients (7.1%) including 61 women with one of the original three mutations (C61G, 4153delA, 5382insC) and 22 women with a different mutation (1.9%). Three new mutations (3819del5, 185delAG and 5370C>T) were seen in multiple families. By including these three mutations in the extended panel, the mutant frequency increased from 5.2 to 6.7%. Polish women with breast cancer diagnosed at age of 50 or below should be screened with a panel of six founder mutations of BRCA1 (C61G, 4153delA, 5382insC, 3819del5, 185delAG and 5370C>T).     

Risk factors for detecting germline BRCA1 and BRCA2 founder mutations in Ashkenazi Jewish women with breast or ovarian cancer

We ascertained 184 Ashkenazi Jewish women with breast/ovarian cancer (171 breast and 13 ovarian cancers, two of the former also had ovarian cancer) in a self-referral study. They were tested for germline founder mutations in BRCA1 (185delAG, 5382insC, 188del11) and BRCA2 (6174delT). Personal/family histories were correlated with mutation status. Logistic regression was used to develop a model to predict those breast cancer cases likely to be germline BRCA1/BRCA2 mutation carriers in this population. The most important factors were age at diagnosis, personal/family history of ovarian cancer, or breast cancer diagnosed before 60 years in a first degree relative. A total of 15.8% of breast cancer cases, one of 13 ovarian cancer cases (7.7%), and both cases with ovarian and breast cancer carried one of the founder mutations. Age at diagnosis in carriers (44.6 years) was significantly lower than in non-carriers (52.1 years) (p<0.001), and was slightly lower in BRCA1 than BRCA2 carriers. Thirty three percent of carriers had no family history of breast or ovarian cancer in first or second degree relatives. Conversely, 12% of non-mutation carriers had strong family histories, with both a first and a second degree relative diagnosed with breast or ovarian cancer. The predicted values from the logistic model can be used to define criteria for identifying Ashkenazi Jewish women with breast cancer who are at high risk of carrying BRCA1 and BRCA2 mutations. The following criteria would identify those at approximately 10% risk: (1) breast cancer <50 years, (2) breast cancer <60 years with a first degree relative with breast cancer <60 years, or (3) breast cancer <70 years and a first or second degree relative with ovarian cancer.     

Recurrent BRCA1 and BRCA2 germline mutations in ovarian cancer: a founder mutation of BRCA1 identified in the Chinese population

Previous mutational analysis for BRCA gene mutations in sporadic ovarian cancer occurring in Chinese patients in Hong Kong identified six germline BRCA1 mutations and one germline BRCA2 mutation, six of which were novel (Khoo et al., 2000). Knowledge of BRCA gene mutations in the Chinese population is relatively scant. In this study, we focussed on whether any of these mutations could be recurrent in our Chinese population, making use of archival paraffin embedded tissue. A consecutive series of 214 ovarian cancer cases, half of Southern Chinese origin from Hong Kong whilst the other half of Northern Chinese origin from Beijing were used for the study. We identified one further novel mutation, 1081delG, in BRCA1. This was found to occur in two unrelated individuals with shared haplotype as revealed by allelotype analysis, thus demonstrating founder effect. Two other recurrent mutations were also identified, the 2371-2372delTG mutation in BRCA1 and the 3337C>T mutation in BRCA2 recurring in two and three unrelated individuals respectively, giving an overall prevalence 4.7% of recurrent BRCA mutations in ovarian cancer in the Southern Chinese population. Most importantly, all our recurrent mutation carriers were identified from Southern Chinese patients from Hong Kong whilst such mutations were absent in samples from the Northern Chinese. Our findings indicate possible heterogeneity in the BRCA genotype between Northern and Southern Chinese. The identification of a founder mutation and two recurrent mutations moreover, has important implications towards screening strategies for breast and ovarian cancer among Chinese of southern ancestral origin who are now dispersed throughout the world.     

BRCA1 and BRCA2 in Indian breast cancer patients

Incidence of breast cancer in Indian women is not as high as in Western countries, nonetheless age-adjusted incidence rates (AAR) have risen from 17.9 to 24.9 per 100,000 from 1965 to 1985. Although these rates are still approximately one quarter to one third of incidence rates in North America and Europe, respectively, due to the large population of women at risk, nearly 80,000 new cases were diagnosed in India in 2000. Although identification of BRCA1 and BRCA2 has greatly increased our understanding of breast cancer genetics in populations of Western European descent, the role of these genes in Indian populations remains unexplored. Analysis of a series of 20 breast cancer patients from North India with either family history of breast and/or ovarian cancer (2 or more affected first degree relatives) or early age of onset (<35 years) led to identification of two novel splice variants (331+1G>T; 4476+2T>C) in BRCA1 (10%). In addition, two BRCA2 missense variants were each identified in more than one patient (two unrelated individuals each) and likely represent population-specific polymorphisms.     

High proportion of missense mutations of the BRCA1 and BRCA2 genes in Japanese breast cancer families

Mutations in either of two recently identified genes, BRCA1 and BRCA2, are thought to be responsible for approximately two-thirds of all cases of autosomal-dominantly inherited breast cancer. To examine the nature and frequency of BRCA1 and BRCA2 mutations in Japanese families exhibiting a high incidence of breast cancer, we screened 78 unrelated families in this category for mutations of these two genes. Examining the entire coding sequences as well as exon–intron boundaries of both genes by polymerase chain reaction (PCR) single-strand conformation polymorphism (SSCP) and multiplex-SSCP analysis, we identified possible disease-causing alterations in BRCA1 among affected members of 15 families and in BRCA2 in another 14 families. In 15 of those 29 families, the affected individuals carried missense mutations, although most germline mutations reported worldwide have been deletions or nonsense mutations. Our results, indicating that missense mutations of BRCA1 and BRCA2 tend to predominate over frameshifts or nonsense mutations in Japanese breast cancer families, will contribute signifi-cantly to an understanding of mammary tumorigenesis in Japan, and will be of vital importance for future genetic testing. Received: September 4, 1997 / Accepted: October 28, 1997     

Prevalence of founder BRCA1 and BRCA2 mutations in unselected French Canadian women with breast cancer

The frequency of BRCA1 and BRCA2 mutations in women with breast cancer varies according to the age at diagnosis, family history of cancer, and ethnicity/country of origin. We set out to estimate the frequency of seven previously described founder mutations in BRCA1 and BRCA2 in all eligible French Canadian women diagnosed with invasive breast cancer at one Montreal hospital over a 20-month period. One hundred and ninety-two patients were eligible and 127 (66.2%) provided blood for genetic testing. We identified 4 women who carried a founder mutation (3.1%, 95% confidence interval 0.9-7.9%) in this population. Interestingly, all the mutations were in BRCA2. The mean age at diagnosis for mutation carriers was 51.2 years (range 49.1-53.5). Two of these 4 cases were lobular invasive carcinomas and 2 were ductal carcinomas, histological grade 1 or 2. Despite a small tumor size (< or =20 mm), axillary nodal involvement was present in 3 women. Estrogen receptors were strongly expressed in all cases. Two of the 4 cases reported a strong family history of breast cancer, but a family history of site-specific breast cancer was a relatively poor indicator of the presence of BRCA2 mutations. The absence of BRCA1 mutations may be a result of chance, but may also reflect different geographical origins of the most common BRCA1 mutations within the French Canadian population.     

The risk of breast cancer in BRCA1 and BRCA2 mutation carriers without a first‐degree relative with breast cancer

The objective of this study was to estimate the lifetime risk of breast cancer in women with a BRCA1 or BRCA2 mutation with and without at least 1 first‐degree relative with breast cancer. A total of 2835 women with a BRCA1 or BRCA2 mutation were followed. Age‐ and gene‐specific breast cancer rates were calculated. The relative risks of breast cancer for subjects with a family history of breast cancer, compared to no family history were calculated. The mean age at baseline was 41.1 years, and they were followed for a mean of 6.0 years. The estimated penetrance of breast cancer to age 80 years was 60.8% for BRCA1 and 63.1% for BRCA2. For all BRCA carriers, the penetrance of breast cancer to age 80 for those with no first‐degree relative with breast cancer was 60.4% and 63.3% for those with at least 1 first‐degree relative with breast cancer. The risk of breast cancer for BRCA carriers with no first‐degree relative with breast cancer is substantial, and as a result, clinical management for these women should be the same as those for women with an affected relative.