乳腺癌中BRCA1基因突变与雌激素受体的关系

目的探讨遗传性乳腺癌与卵巢癌易感基因(Hereditarybreastandovariancancersusceptibilitygene,BRCA1)基因突变、雌激素受体(Estrogenreceptor,ER)在乳腺癌中的作用以及二者之间的关系。方法选取64例乳腺癌患者标本作研究组,另取10例非癌乳腺组织标本作对照组。利用PCR-SSCP法和直接测序法检测BRCA1基因突变情况;利用SP(链霉菌抗生物素蛋白-过氧化物酶链接法)二步法检测ER,比较ER阳性组与ER阴性组BRCA1突变情况。结果10例非乳腺癌组织未检测出BRCA1基因突变。64例乳腺癌标本中检出BRCA1基因突变6例,突变率为9.4%。突变发生在5、12、17外显子上,均为错义突变,ER阳性44例,阳性率为68.75%(44/64)。ER阳性组中只有1例BRCA1突变(1/44),ER阴性组中有5例检出BRCA1突变(5/20),两组比较BRCA1突变率有显著差异性(P>0.05)。结论广西乳腺癌与BRCA1基因突变有关,BRCA1突变与雌激素受体有关,BRCA1基因突变病人雌激素阴性状态比非BRCA1基因突变病人多。     

BRCA1/BRCA2基因突变的乳腺癌患者特征分析

目的对钱塘江南岸地区BRCA1/BRCA2基因突变的乳腺癌患者特征进行分析,为国家及各地公共卫生主管部门制定乳腺癌防治方案奠定基础。方法选取2016年来萧山医院就诊18周岁以上女性由乳腺钼靶摄影或乳腺彩超及由病理学诊断为乳腺癌的98例患者,通过PCR和测序分析对BRCA1/BRCA2基因突变进行分析,对乳腺癌患者进行相关肿瘤标志物的检测,采用问卷调查的方式对乳腺癌患者进行流行病学调查。结果通过对98例乳腺癌患者BRCA1/2基因全外显子以及外显子内含子拼接区序列测序,共发现23例BRCA2基因缺失突变,所有突变位点均为首次发现。BRCA1/2基因突变乳腺癌患者相关肿瘤标志物具有一定差异。BRCA1/2基因突变的乳腺癌患者主要以中年妇女为主,此外与乳腺癌相关的疾病史对于BRCA1/2基因的突变也具有一定意义。结论钱塘江南岸地区的女性乳腺癌患者中BRCA1/BRCA2基因突变频率较高,且以中年妇女为主,应定期进行随访监测。     

上皮卵巢癌患者BRCA1/2和KRAS基因突变与预后的相关性

目的探讨上皮卵巢癌患者BRCA1/2和KRAS基因突变与预后的相关性,为上皮卵巢癌的治疗和预后提供理伦依据。方法选取2013年9月-2016年11月在该院产科确诊的70例上皮卵巢癌患者为研究对象,对其进行BRCA1/2和KRAS基因突变分析,并根据基因突变结果分为非突变BRCA1/2组、突变BRCA1/2组,非突变KRAS组、突变KRAS组。分析非突变BRCA1/2组、突变BRCA1/2组,非突变KRAS组、突变KRAS组的PFS、OS、3年生存率及临床特征资料。结果 BRCA1/2基因突变率为32.9%,KRAS基因突变率为8.7%;BRCA1/2、KRAS基因突变情况与分化程度、手术病理分期、细胞学分级、有无转移无相关性,差异无统计学意义(χ~2=0.88、0.96、1.01、1.13,0.97、1.24、2.11、1.01,P0.05);BRCA1/2、KRAS基因突变组对化疗敏感度高于非BRCA1/2、KRAS基因突变组,差异有统计学意义(χ~2=18.45、21.56,P0.05);BRCA1/2、KRAS基因突变组PFS、OS、3年生存率均高于BRCA1/2、KRAS基因非突变组,差异有统计学意义(χ~2=23.64、19.87、21.68,16.54、21.47、19.37,P0.05)。结论 BRCA1/2、KRAS基因突变使上皮卵巢癌患者对化疗药物敏感,预后较好,了解BRCA1/2、KRAS基因突变情况对上皮卵巢癌早期诊断及预后治疗具有重要意义。     

BRCA1基因单核苷酸多态性与广东汉族女性散发性乳腺癌易感相关性研究

目的探讨BRCA1基因启动子区rs799906位点和编码区rs799917位点单核苷酸多态性(single nucleotide polymorphism,SNP)与广东汉族女性散发性乳腺癌易感性的关系。方法利用Sequenom Mass Array iPLEX GOLD系统对107例散发性乳腺癌患者及93例健康对照者的BRCA1基因两个SNP位点(rs799906,rs799917)进行检测,并对检测结果进行χ2检验和非条件Logistic回归分析。结果 rs799906位点TT、TC和CC三种基因型在病例组和对照组的分布频率有差异(χ2=8.407,P=0.018)。相对TT基因型而言,TC杂合型能增加乳腺癌发生的危险性(OR=2.566;95%CI:1.101～5.983;P<0.05),但等位基因T和C的频率分布无显著差异(χ2=2.169,P=0.141)。rs799917位点CC、CT和TT三种基因型的频率和等位基因C和T的频率在病例组和对照组的分布均无显著性差异(χ2=3.994,P=0.136;χ2=0.903,P=0.342)。结论 BRCA1多态性位点rs799906TC杂合型与散发性乳腺癌发病风险有相关性;而rs799917位点多态性与散发性乳腺癌发病风险无相关性。     

乳腺癌组织中BRCA1/2、p65表达与HPV感染的相关性

目的 探究乳腺癌组织中乳腺癌易感基因1/2(BRCA1/2)、核因子κB亚基p65表达与人乳头状瘤病毒(HPV)感染的相关性。方法 选取2019年1月-2020年10月杭州市萧山区第一人民医院收治的乳腺癌患者184例为研究组,乳腺良性肿瘤患者60例为对照组,检测两组患者乳腺肿瘤组织HPV、BRCA1/2、p65表达情况,分析HPV、BRCA1/2、p65阳性表达与乳腺癌临床病理特征的关系。结果 研究组HPV、p65表达阳性率高于对照组,BRCA1、BRCA2表达阳性率低于对照组(P<0.05);乳腺癌淋巴结转移患者HPV阳性率高于淋巴结未转移患者(P<0.05);乳腺癌不同临床分期、淋巴结是否转移BRCA1、BRCA2、p65阳性率比较,差异有统计学意义(P<0.05); HPV阳性乳腺癌患者BRCA1、BRCA2阳性率低于HPV阴性患者(P<0.05),p65阳性率高于阴性患者(P<0.05)。结论 乳腺癌患者HPV、p65阳性率上调,BRCA1/2阳性率下调,且相互作用参与乳腺癌的发病与进展。     

朝鲜族和汉族妇女乳腺癌BRCA1的表达及临床意义

目的:探讨BRCA1基因蛋白在延边地区朝鲜族、汉族(简称朝、汉族)妇女乳腺癌中的表达及意义。方法:采用免疫组化SP法对72例乳腺癌(35例朝鲜族,37例汉族)、15例乳腺纤维腺瘤组织石蜡切片进行BRCA1检测,分析与临床病理特征的关系。结果:BRCA1蛋白在朝、汉族妇女乳腺癌病人中的表达率分别为62.9%、56.8%;在乳腺癌、乳腺纤维腺瘤组织中的表达率分别为59.7%和100%,乳腺癌组织中BRCA1基因表达水平低于良性肿瘤组织(P<0.05);乳腺癌组织中BRCA1的表达与组织学分级呈负相关(r=-0.418,P<0.05),与淋巴结转移数目、患者年龄及家族史均无明显相关。结论:BRCA1在朝、汉族妇女乳腺癌中的表达无显著性差异;其表达水平的下调在乳腺癌发生发展中有重要意义;表达的减弱与乳腺癌的病理学分级有关,提示预后差。     

129例辅助生殖技术子代儿童耳聋基因突变筛查

目的:了解辅助生殖技术(assisted reproductive technology,ART)子代儿童常见遗传性耳聋基因突变发生率。方法:随机选取2010年1月-2014年12月在中国科学技术大学附属第一医院行ART助孕成功的129例子代为研究对象,平均年龄为(4.37±0.92)岁,同时收集161例自然妊娠出生的子代血样。利用高通量测序法对研究对象的常见耳聋基因突变位点进行筛查。结果:129例ART子代共发现11例携带耳聋基因突变,包含12个基因位点的突变,而161例自然妊娠子代共发现9例携带耳聋基因突变,包含9个基因位点的突变,2组耳聋基因突变发生率比较差异无统计学意义(χ^2=0.962,P=0.327)。ART子代中GJB2突变携带者2例(1.55%),男女比例为1∶1;GJB3突变携带者3例(2.33%),男女比例为1∶2;SLC26A4突变携带者7例(5.43%),男女比例为5∶2;未发现线粒体12S r RNA基因突变携带者。1例有GJB2基因235delC位点和SLC26A4基因IVS7-2A>G位点双杂合突变。ART子代中,体外受精(IVF)组耳聋基因位点突变发生率为11.83%(11/93),胞浆内单精子注射(ICSI)组为2.78%(1/36),差异无统计学意义(χ^2=2.520,P=0.112);新鲜胚胎移植组为11.39%(9/79),冷冻胚胎移植组为6.00%(3/50),差异无统计学意义(χ^2=1.055,P=0.304)。结论:ART子代遗传性耳聋基因突变发生率与自然妊娠组子代相似;ART组以SLC26A4基因IVS7-2A>G位点突变阳性率最高。而受精方式以及移植新鲜或冻融胚胎对ART子代的遗传性耳聋的基因突变发生率无显著影响。     

129例辅助生殖技术子代儿童耳聋基因突变筛查

目的:了解辅助生殖技术(assisted reproductive technology,ART)子代儿童常见遗传性耳聋基因突变发生率。方法:随机选取2010年1月—2014年12月在中国科学技术大学附属第一医院行ART助孕成功的129例子代为研究对象,平均年龄为(4.37±0.92)岁,同时收集161例自然妊娠出生的子代血样。利用高通量测序法对研究对象的常见耳聋基因突变位点进行筛查。结果:129例ART子代共发现11例携带耳聋基因突变,包含12个基因位点的突变,而161例自然妊娠子代共发现9例携带耳聋基因突变,包含9个基因位点的突变,2组耳聋基因突变发生率比较差异无统计学意义(χ2=0.962,P=0.327)。ART子代中GJB2突变携带者2例(1.55%),男女比例为1∶1;GJB3突变携带者3例(2.33%),男女比例为1∶2;SLC26A4突变携带者7例(5.43%),男女比例为5∶2;未发现线粒体12S r RNA基因突变携带者。1例有GJB2基因235delC位点和SLC26A4基因IVS7-2AG位点双杂合突变。ART子代中,体外受精(IVF)组耳聋基因位点突变发生率为11.83%(11/93),胞浆内单精子注射(ICSI)组为2.78%(1/36),差异无统计学意义(χ2=2.520,P=0.112);新鲜胚胎移植组为11.39%(9/79),冷冻胚胎移植组为6.00%(3/50),差异无统计学意义(χ2=1.055,P=0.304)。结论:ART子代遗传性耳聋基因突变发生率与自然妊娠组子代相似;ART组以SLC26A4基因IVS7-2AG位点突变阳性率最高。而受精方式以及移植新鲜或冻融胚胎对ART子代的遗传性耳聋的基因突变发生率无显著影响。     

维吾尔族及汉族乳腺癌BRCA1基因突变检测及分析

[目的]研究新疆地区维吾尔族及汉族乳腺癌患者BRCA1基因(乳腺癌易感基因1)突变情况及突变位置。[方法]选取维吾尔族及汉族乳腺癌根治标本110例,对照组为32例维吾尔族及汉族乳腺良性病变(纤维腺病及纤维腺瘤)及乳腺癌旁非癌组织;运用PCR-SSCP和DNA序列测定的方法检测BRCA1基因的突变。[结果](1)110例维吾尔族及汉族散发性乳腺癌中BRCA1的突变率为10%;其中70例维吾尔族散发性乳腺癌BRCA1的突变率为12.86%;新疆早发性乳腺癌(≤35岁)中BRCA1基因的突变率高于新疆晚发性乳腺癌,差异有统计学意义(χ2=9.429,P﹤0.01)。维吾尔族早发性乳腺癌BRCA1突变率高于维吾尔族晚发性乳腺癌,差异有统计学意义(χ2=10.295,P﹤0.01)。(2)2例双侧乳腺癌中均检测出BRCA1基因的突变。(3)对照组32例维吾尔族及汉族乳腺癌旁非癌组织及乳腺良性病变中仅发现1例BRCA1基因核苷酸的多态性,110例新疆散发性乳腺癌中发现11例BRCA1基因核苷酸的多态性。[结论]BRCA1突变可能与新疆早发性乳腺癌尤其是维吾尔族早发性乳腺癌及双侧乳腺癌的发生密切相关。     

32例三阴性乳腺癌患者易感基因胚系突变分析

目的:应用全外显子测序技术初步探讨三阴性乳腺癌(TNBC)患者易感基因突变情况。方法:收集本院就诊的32例TNBC患者,均经临床手术病理确诊。采集患者外周血提取基因组DNA进行全外显子组测序,通过生物信息学分析筛选与乳腺肿瘤相关的易感基因变异。结果:32例TNBC患者中14例检测到BRCA1/2罕见变异,明确致病性或可疑致病变异6例,突变携带频率为18.8%。其中BRCA1:c.5468-1_5474del和c.4749_4750del是较常见的突变;BRCA2:c.6027A>C为新的变异;BRCA2:c.3794G>T、c.7901T>A,BRCA1:c.4616T>C首次在中国人群中发现。除了BRCA1/2变异外,还检测到83个乳腺肿瘤易感基因变异,每个患者携带2.6个变异。2个以上患者携带的乳腺癌易感基因包括ALK、APC、CDH1、PTCH2、RB1CC1、RAD51D、RAD54L、TSC1等。结论:BRCA1/2是TNBC患者最重要的易感基因,其他与DNA损伤修复相关的基因突变可能与TNBC患者的表型有一定的相关性。     

变性高效液相色谱分析技术对乳腺癌易感基因突变位点检测的敏感性和特异性

目的:探讨变性高效液相色谱分析技术对乳腺癌易感基因突变位点检测的敏感性和特异性。方法:收集202例诊断为原发性乳腺癌女性患者,同时采用PCR/DNA测序法和变性高效液相色谱分析技术检测BRCA1基因突变,以PCR/DNA测序法作为"金标准",评估变性高效液相色谱分析技术的敏感性和特异性。结果:202例乳腺癌标本中,PCR/DNA测序法发现BRCA1基因突变例数为76例,变性高效液相色谱分析技术结果,阳性73例,敏感性为96.1%;PCR/DNA检测结果为阴性126例,采用变性高效液相色谱分析技术,阴性120例,特异性为95.2%。两种检测方法敏感性和特异性无统计学差异(P=0.265,P=0.226)。结论:采用变性高效液相色谱分析技术检测乳腺癌易感基因BRCA1具有较高的敏感性和特异性,与传统检测方法相比,变性高效液相色谱分析技术具有较多的优点,值得推广。     

Evidence for further breast cancer susceptibility genes in addition to BRCA1 and BRCA2 in a population-based study.

We used data from a population based series of breast cancer patients to investigate the genetic models that can best explain familial breast cancer not due to the BRCA1 and BRCA2 genes. The data set consisted of 1,484 women diagnosed with breast cancer under age 55 registered in the East Anglia Cancer registry between 1991-1996. Blood samples taken from the patients were analysed for mutations in BRCA1 and BRCA2. The genetic models were constructed using information on breast and ovarian cancer history in first-degree relatives and on the mutation status of the index patients. We estimated the simultaneous effects of BRCA1, BRCA2, a third hypothetical gene BRCA3, and a polygenic effect. The models were assessed by likelihood comparisons and by comparison of the observed numbers of mutations and affected relatives with the predicted numbers. BRCA1 and BRCA2 could not explain all the familial clustering of breast cancer. The best-fitting single gene model for BRCA3 was a recessive model with a disease allele frequency 24% and penetrance 42% by age 70. However, a polygenic model gave a similarly good fit. The estimated population frequencies for BRCA1 and BRCA2 mutations were similar under both recessive and polygenic models, 0.024 and 0.041%, respectively. A dominant model for BRCA3 gave a somewhat worse fit, although the difference was not significant. The mixed recessive model was identical to the recessive model and the mixed dominant very similar to the polygenic model. The BRCA3 genetic models were robust to the BRCA1 and BRCA2 penetrance assumptions. The overall fit of all models was improved when the known effects of parity on breast and ovarian cancer risks were included in the model-in this case a polygenic model fits best. These findings suggest that a number of common, low-penetrance genes with additive effects may account for the residual non-BRCA1/2 familial aggregation of breast cancer, but Mendelian inheritance of an autosomal recessive allele cannot be ruled out.     

Breast cancer risk in Ashkenazi BRCA1/2 mutation carriers: effects of reproductive history

BACKGROUND: Younger age at first birth and greater parity generally reduce the risk of developing breast cancer, but whether this reduced risk holds in women with a mutation in the BRCA1 or BRCA2 gene is unknown. METHODS: In a Washington DC community-based study conducted in 1996, we tested 5318 Ashkenazi Jews for three BRCA1/2 founder mutations and identified 120 mutation carriers. Applying an extension of the "kin-cohort" analysis, we compared the effects of reproduction on breast cancer risk in carriers and noncarriers. We also used a case-case analysis among 288 participants who had been diagnosed with breast cancer. RESULTS: In noncarriers, the estimated relative risk (RR) of breast cancer rose 5% with each 5-year increment in age at first birth (RR = 1.05; 95% confidence interval [CI] = 0.97-1.15). By contrast, the estimated risk in mutation carriers fell with each 5-year increment in age (RR = 0.65; 95% CI = 0.37-1.16). Among the 288 participants who were breast cancer survivors themselves, the comparison of carriers with noncarriers also showed no protection associated with early birth in the presence of a mutation in BRCA1 or BRCA2. CONCLUSIONS: It is not yet clear whether the recognized breast cancer risk factors operate in the same way in women who carry a mutation in the BRCA1 or BRCA2 genes.     

乳腺癌患者发病的影响因素分析

目的 探讨基本情况、遗传、生育、疾病和饮食等因素与乳腺癌发生的关系,分析乳腺癌的影响因素.方法 选取2015年1月至2015年9月在中国福利会国际和平妇幼保健医院收治的168例术后病理确诊的乳腺癌患者为观察组,选取168例在体检门诊进行乳腺检查并排除乳腺癌者为对照组,比较两组研究对象的临床资料.结果 两组受试者在年龄、BMI、婚姻情况、医疗保险、高血压病史及患病时间、糖尿病病史及患病时间组间比较差异均无统计学意义(t/χ2值分别为1.317、1.511、0.203、1.080、0.056、0.828、0.000、0.020,均P>0.05).两组患者在文化程度及职业资料比较上,差异具有统计学意义(χ2值分别为23.875、21.212,均P<0.05).两组患者在受挫折后情绪、自觉健康状况、与12个月之前相比的体重变化、采取措施控制体重、初潮年龄、是否绝经、避孕药物使用及乳腺癌家族史比较上,差异具有统计学意义(χ2值分别为18.900、14.915、29.031、10.826、11.664、18.185、4.626、14.696,均P<0.05).饮食方面两组患者在食用杂粮、猪肉、羊肉、虾、禽类、海产品、奶及奶制品、黄豆及其制品、新鲜蔬菜、水果、腌制食品、蛋类比较上,差异均具有统计学意义(χ2值4.189~46.672,均P<0.05),两组患者在食用大米、牛肉、鱼类、酒类、抽烟差异均无统计学意义(χ2值0.412~3.178,均P>0.05).近两年内遭受过比较大的挫折情绪不佳、采取措施控制体重、初潮年龄早、绝经晚、服用过避孕药物、乳腺癌家族史、食用猪肉和羊肉均是乳腺癌发病的危险因素(OR值1.642~7.471,均P<0.05),母乳喂养、食用杂粮、食用奶及奶制品、食用黄豆及其制品、食用新鲜蔬菜和水果均是乳腺癌发病的保护因素(OR值0.627~0.862,均P<0.05).结论 近两年内遭受过比较大的挫折情绪不佳、采取措施控制体重、初潮年龄早、绝经晚、服用过避孕药物、乳腺癌家族史、食用猪肉和羊肉均是乳腺癌发病的危险因素,母乳喂养、食用杂粮、食用奶及奶制品、食用黄豆及其制品、食用新鲜蔬菜和水果均是乳腺癌发病的保护因素.     

Risk models for familial ovarian and breast cancer

We investigated risk models for the inherited susceptibility of breast and ovarian cancer, using data from both high-risk families and a population based series of ovarian cancer. The first data set consisted of 112 families containing two or more relatives with epithelial ovarian cancer. BRCA1 and BRCA2 germline mutations were detected in 50% of these families. The second study involved 374 ovarian cancer cases, unselected for family history, who had DNA samples analyzed for BRCA1 mutations. Twelve women were found to be carriers. We constructed genetic models for ovarian and breast cancer using the computer program MENDEL. In the first study, we modeled the effects of BRCA1 and BRCA2 simultaneously and allowed for a third gene predisposing to ovarian cancer. None of the models fitted gave significant evidence for a third gene. Population frequencies of BRCA1 and BRCA2 mutations were estimated to be 0. 00128 and 0.00172, respectively. Our results suggest that BRCA1 and BRCA2 may be sufficient to explain the majority of familial ovarian cancer and that families without mutations can be explained by sensitivity of mutation testing and chance clusters of sporadic cases. Using data on the families of the 12 mutation carriers in the second study, we estimated age-specific ovarian and breast cancer risks for BRCA1 mutation carriers. Under the best-fitting model, the cumulative ovarian cancer risk was 66% by age 70, and the corresponding breast cancer risk was 45%. The high penetrance estimate for ovarian cancer, compared with other studies, suggests that modifying genetic or environmental factors may be important determinants of risk.     

Screening of women at high risk for breast cancer

A woman may be at high risk of breast cancer because of a strong family history of breast cancer or because she carries a mutation in the BRCA1 or BRCA2 gene. The annual risk for women in this category is between 1% and 2% and the lifetime risk of breast cancer among gene carriers may approach 80%. Several recent trials have reported that the sensitivity of MRI for imaging breast cancer greatly exceeds that of conventional mammography, but no study has yet determined that annual MRI reduces breast cancer-specific mortality. Women with breast cancer and a BRCA1 mutation typically develop aggressive breast cancers and the prognosis is relatively poor for women with small node-negative breast cancers (compared to non-carriers) in particular, if chemotherapy is not given. It is hoped that annual MRI screening combined with appropriate treatment will result in decreased mortality for this and other groups of high-risk women. MRI-based screening for women at moderate risk is a topic of great interest—MRI has not yet been endorsed in moderate risk women because of the high cost of screening and because the specificity of the screening test is not yet determined in this subgroup.     

BRCA1和BRCA2在乳腺疾病中的表达和意义

目的通过检测乳腺癌易感基因1(BRCA1)和乳腺癌易感基因2(BRCA2)在乳腺增生病、乳腺癌癌前病变、乳腺癌中的表达,探讨BRCA1和BRCA2在乳腺癌发生、发展中的作用。方法切除的原发病灶共90例,经福尔马林固定、石蜡包埋,常规切片,应用免疫组织化学技术(IHC),检测乳腺增生病、乳腺癌癌前病变、乳腺癌中的BRCA1和BRCA2表达情况。结果(1)BRCA1和BRCA2在乳腺增生病、乳腺癌癌前病变、乳腺癌中阳性表达率依次递减,在三者中的表达有显著性差异(P<0.05)。(2)BRCA1和BRCA2的表达相互之间无显著性差异(P>0.05)。结论乳腺上皮中BRCA1和BRCA2的表达减少对乳腺癌的发生、发展具有重要作用。对BRCA1和BRCA2的检测有利于筛选出乳腺癌高危人群,早期发现乳腺癌。但BRCA1和BRCA2在乳腺癌中的表达无相关性。     

In cases of familial ovarian cancer, always consider the risk of breast cancer

A family history of ovarian cancer without breast cancer can be a pitfall in interpreting the high breast cancer risks. A family with high breast and ovarian cancer risks due to a BRCA1 or BRCA2 mutation, can present itself with ovarian cancer only. In three women, 43, 50 and 61 years of age, there was a family history of ovarian cancer. In the youngest woman breast carcinoma was diagnosed and she was referred for genetic counseling and DNA mutation analysis. She was identified with a pathogenic mutation in BRCA1 and decided for regular breast examination and prophylactic adnectomy. The 50-year-old woman presented with ovarian cancer and was found to have a BRCA1 mutation. She received surgery and chemotherapy for her ovarian cancer and regular examination of the breasts. The third woman at risk could be reassured, since she did not carry the BRCA1 mutation that was found in her affected sister. Because the patients and their family members can benefit from regular surveillance and prophylactic surgery, it is of great importance to identify the high breast cancer risks as well as the high ovarian cancer risks in these families.