胚系BRCA突变年轻乳腺癌术式选择对预后影响的Meta分析

背景与目的 携带胚系BReast CAncer基因（gBRCA）突变的年轻乳腺癌患者同时具有年轻与基因突变带来的双重风险。目前对于gBRCA突变早期乳腺癌患者是否可行保乳治疗目前尚无一致结论。本研究通过Meta分析探讨不同手术方式对gBRCA突变的年轻乳腺癌患者预后的影响，以及该影响是否有人种差异。方法 检索多个国外数据库，收集比较gBRCA突变早期乳腺癌患者行保乳手术与全乳切除术预后差异的临床研究，对无复发生存（RFS）、无转移生存（MFS）、乳腺癌特异性生存（BCSS）、总生存（OS）等指标进行Meta分析。结果 最终纳入6篇研究（中国2篇，欧美4篇），共2 140例gBRCA突变患者，中位年龄38~47岁。Meta分析结果显示，总体人群中，gBRCA突变患者行保乳手术较全乳切除术复发风险增高（RFS：HR=1.91，95% CI=1.03~3.54，P<0.05），但两种术式的MFS、BCSS、OS差异均无统计学意义（均P>0.05）；中国人群中，gBRCA突变患者行保乳手术较全乳切除术复发风险增高（RFS：HR=1.63，95% CI=1.10~2.41，P<0.05），两种术式的其余指标差异均无统计学意义（均P>0.05），欧美人群中，两种术式的上述指标差异均无统计学意义（均P>0.05）。结论 对于欧美人群，保乳手术不是gBRCA突变早期年轻乳腺癌术后预后的风险因素；但在中国人群中，gBRCA突变早期年轻乳腺癌患者行保乳手术可能具有更高的复发风险，需在术式选择的医疗决策时充分告知。     

保乳手术治疗BRCA1/2基因突变型乳腺癌的可行性

保乳手术作为乳腺肿瘤外科一种重要的手术方式,对于其是否适用于BRCA1/2基因突变型乳腺癌患者,目前仍存在争议.由于家族性乳腺癌患者仍然具有单侧多发和对侧发病的高风险,对BRCA1/2基因突变型乳腺癌患者不推荐实施保乳手术,推荐行乳腺全切术和/或Ⅰ期乳房成形手术.但如果BRCA 1/2基因突变型乳腺癌患者有强烈的保乳意愿,在充分告知可能存在风险的前提下,保乳手术也是可行的,但是应考虑双侧卵巢切除或他莫昔芬治疗,同时需要进行更多的干预措施预防对侧乳腺发病.     

钙化对乳腺癌保乳术后预测价值的探讨

目的探讨钙化对乳腺癌保乳术后局部复发、远处转移和总生存率的意义。 方法回顾性分析淄博市第一医院2004年1月至2014年5月204例接受保乳术乳腺癌患者临床资料及随访结果。依影像学钙化情况分为钙化组及无钙化组,依钙化形态及分布方式进行生存分析。 结果钙化组与无钙化组患者在肿瘤大小、组织学分级、区域淋巴结状态、激素受体及Her-2受体表达上差异无统计学意义。钙化组较无钙化组在局部复发、远处转移及乳腺癌相关死亡率上更高（RR 2.46、2.24、2.50,95% CI：1.11~5.44、1.19~4.24、1.06~5.86）。钙化形态亚组分析发现：大/粗钙化、仅超声提示钙化及无钙化患者较微小及多形性钙化患者局部无复发生存率（LRFS）及无病生存率（DFS）更低。钙化分布类型分析发现：线性或区段分布钙化（沿导管分布钙化）患者的LRFS（RR 6.20,95% CI：2.26~16.98）、DFS（RR 6.81,95% CI：2.86-16.20）及总生存率（OS）（RR 9.14,95% CI：2.53~33.00）较无钙化患者显著降低。钼靶上聚集钙化患者的LRFS、DFS及OS也较差,但与无钙化患者相比差异无统计学意义。线样/区段分布钙化的患者与无钙化、超声显示钙化及钼靶示良性钙化类型的患者相比,常伴有广泛导管内癌成分（EIC）。有EIC较无EIC患者的局部复发率更高,但在乳腺癌相关死亡率及远处转移率上差异无统计学意义。 结论乳腺癌伴钙化,尤其是沿导管分布钙化的患者接受保乳手术后局部复发率较高,并影响远期预后。仅超声提示钙化的患者保乳术后近期及远期预后不受影响。EIC是钙化患者保乳术后局部复发的预测指标之一。     

甲状腺髓样癌术后生存影响因素分析及列线图的构建

背景与目的 目前用于评估甲状腺髓样癌（MTC）预后的主要方式采用TNM分期系统，但该系统不能个体化预测患者的预后。因此，需要建立专门针对MTC的精准预后指标体系。本研究分析影响MTC患者术后生存的因素，并构建MTC术后生存列线图。方法 选取2004—2015年SEER数据库MTC数据，共筛选出符合条件的1 884例患者纳入研究。将患者按3∶1随机分为训练集（1 413例）和验证集（471例），比较两组临床数据基线特征差异。采用单因素和多因素Cox回归模型筛选影响MTC生存的独立因素，Kaplan-Meier生存曲线分析其对预后的影响。基于Cox回归分析筛选出的结果建立MTC术后患者生存列线图。通过一致性指数（C-index）、ROC曲线、曲线下面积（AUC）、校准曲线和决策曲线分析（DCA）对列线图进行验证和评估。结果 单因素分析结果显示，性别、年龄、原发肿瘤分期、淋巴结转移、远处转移、是否甲状腺全切除、肿瘤是否侵犯甲状腺被膜、是否行放射治疗均影响患者预后（均P<0.05）；Cox回归分析结果显示，性别、年龄、远处转移、侵犯甲状腺被膜、是否行甲状腺全切除术、是否放疗为MTC患者的独立预后因素（均P<0.05）。Kaplan-Meier生存曲线显示，男性患者、年龄≥49岁、伴远处转移、肿瘤侵犯甲状腺被膜、未行甲状腺全切除术、接收放疗患者预后更差。用患者性别、年龄、远处转移、甲状腺被膜受侵、手术方式构建了MTC患者2、5、10年的生存列线图。该列线图训练集的C-index为0.755（95% CI=0.741~0.769），验证集为0.725（95% CI=0.699~0.769）。ROC曲线用于评估列线图的区分度，在训练集2、5、10年的AUC值分别为0.79、0.779、0.766；在验证集分别为0.78、0.725、0.733。校准曲线结果显示该列线图预测的生存率和实际生存率具有一致性。DCA将列线图与AJCC第6版TNM分期的临床相比，该列线图的在5年和10年生存评估中均显示出更大的净收益。结论 性别、年龄、远处转移、甲状腺被膜侵犯、手术方式是影响MTC患者生存的独立因素；MTC术后生存列线图模型在一定程度上能够更准确地进行患者个体生存预测，帮助临床医师做出适当的个体化临床决策。     

散发性乳腺癌中BRCA1和BRCA2基因突变的研究

目的检测BRCA1和BRCA2基因在散发性乳腺癌中的突变情况,探讨BRCA1和BRCA2基因突变与乳腺癌的关系。方法选取2000年12月至2005年9月收治的144例乳腺癌患者标本作实验组,另取非癌乳腺组织标本30例作对照组。用酚-氯仿抽提法提取DNA。针对各个外显子的碱基序列特征,设计有助于筛查基因碱基突变的聚合酶链反应（PCR）引物。每例DNA标本均用PCR扩增BRCA1基因的全部22个外显子和BRCA2基因的exon10和exon14两个外显子。分别将每例外显子的PCR扩增产物进行单链构象多态性分析,对泳动变位或出现异常区带的PCR扩增产物进行DNA测序。结果对照组未检测出BRCA1和BRCA2基因突变,实验组中检测出20例BRCA1基因碱基改变,总突变率为13．9％,其中错义突变率为11．1％。BRCA2基因exon10和exon14未检测出突变。结论BBCA1突变与乳腺癌密切相关,筛查BRCA1基因突变对于中国人群乳腺癌患病风险评估、早期诊断及基因治疗具有重要意义。     

老年患者肺癌根治术后谵妄的危险因素及列线图预测模型的建立

目的 探讨老年患者肺癌根治术后谵妄（POD）的危险因素,并在此基础上构建与验证预测POD发生风险的列线图模型。
方法 选择择期全麻下行肺癌根治术老年患者580例,男349例,女231例,年龄≥65岁,ASA Ⅰ—Ⅲ级。根据术后3 d内是否发生POD将患者分为两组：POD组与非POD组。通过Lasso回归筛选与POD发生相关的临床变量,并采用多因素Logistic回归分析确定独立危险因素,以此建立预测POD发生风险的列线图模型。分别通过C-index、校准曲线和受试者工作特征（ROC）曲线验证模型的区分度、一致性和准确性,并采用决策曲线分析（DCA）确定模型的临床实用性。
结果 有46例（7.93％）患者发生POD。多因素Logistic回归分析显示,年龄≥75岁、术前简易精神状态量表（MMSE）评分≤25分、术前预后营养指数（PNI）＜45、查尔森合并症指数（CCI）评分≥2分、鳞癌、术中低血压和手术时间≥3 h为POD的独立危险因素。以此构建的列线图模型经内部验证,该模型的C-index为0.864（95％CI 0.811～0.917）;校准曲线显示,该模型预测POD发生风险与实际POD发生风险平均绝对误差为0.038;ROC曲线显示,该模型预测POD发生风险的曲线下面积为0.866（95％CI 0.835～0.892）,敏感性86.96％,特异性73.78％;DCA分析显示该模型具有较好的临床实用性。
结论 年龄≥75岁、术前MMSE评分≤25分、PNI＜45、CCI评分≥2分、鳞癌、术中低血压和手术时间≥3 h是肺癌根治术老年患者POD的独立危险因素,依此构建的列线图模型对POD发生风险具有良好的预测效能。     

BRCA1在乳腺肿瘤中的表达及其临床意义

目的探讨乳腺癌易感基因（BRCA1）在乳腺癌和乳腺良性肿瘤中的表达及其临床意义。方法应用ABC免疫组化法检测52例乳腺癌、30例乳腺纤维腺瘤并上皮增生活跃和10例乳腺增生症患者中的BRCA1的表达。结果BRCA1在乳腺癌中的阳性表达率为38％（20／52），在乳腺纤维腺瘤中的阳性表达率为73％（22／30），而10例乳腺增生症患者BRCA1阳性率为90％（9／10）（Χ^2=14．78，P〈0．01），在乳腺癌患者中腋窝有淋巴结转移组的表达率明显低于无淋巴结转移组（Χ^2=15．42，P〈0．01），BRCA1的表达与肿瘤的组织学类型（Χ^2=0．156，P〉0．05）、肿块大小（Χ^2=0．587，P〉0．05）无关。结论BRCA1在乳腺癌的发生发展过程中有重要作用，可能成为临床对乳腺癌诊断和判断预后的一个重要指标，可能对乳腺癌的早期诊断及预防有重要意义。     

保留乳头乳晕皮下腺体切除加假体联合补片乳房一期重建与保乳整形手术治疗乳腺癌比较的单中心回顾性研究

背景与目的 中国女性乳腺癌发病年龄早,保乳手术和乳腺切除术后乳房重建是避免乳腺癌患者失去乳房的合理选择。近年来保乳整形术式的推广使得小乳房患者保乳术后仍能维持较好外形。使用假体联合钛网补片（TiLoop Bra）的乳房重建技术相对简单,便于推广,也能在乳房全切后较好重塑乳房外形。本研究通过回顾性分析评估两种方法在手术效果与满足患者术后美观需求方面的优劣,以期为临床决策提供参考。方法 回顾性分析2019年1月—2021年10月在中南大学湘雅医院乳腺外科接受以上两种手术的早期乳腺癌患者资料,其中接受保乳整形手术（保乳组）与保留乳头乳晕皮下腺体切除加假体联合补片一期乳房重建手术（乳房重建组）的患者各40例。收集患者的基本临床病理特征信息,两组的手术时间、术后留置引流管时间、术后住院时间、住院费用以及手术相关并发症等信息,使用Breast-Q量表评估患者术后满意度。结果 保乳组在手术时间、术后留置引流管时间、术后住院时间以及住院费用上均明显优于乳房重建组（均P<0.001）。乳房重建组乳头麻木的发生率明显高于保乳组（P<0.001）;乳房重建组发生皮瓣坏死4例,保乳组无皮瓣坏死发生,但差异无统计学意义（P=0.079）;两组间血肿、切口感染、脂肪坏死和组织挛缩的发生率差异均无统计学意义（均P>0.05）。两组患者的心理健康、身体健康、性健康及对乳房外形的满意度差异均无统计学意义（均P>0.05）。结论 两种手术方式的美学效果相似。皮瓣坏死为假体联合补片一期乳房重建中的严重并发症,背阔肌肌皮瓣覆盖创面可作为补救治疗手段。满足保乳手术适应证的患者,应优先考虑保乳整形的手术方式;存在保乳手术禁忌证的患者,但有乳房外形要求的,合理评估后实施保留乳头乳晕腺体切除加假体联合补片一期乳房重建也是一个可选方案。     

胃癌患者预后相关影响因素的列线图模型构建及验证

背景与目的 中国胃癌疾病负担较重且预后影响因素较多,有关量化和综合评估预后风险的研究较少。因此,本研究基于列线图探究炎症指标中性粒细胞/淋巴细胞比率（NLR）和血小板/淋巴细胞比率（PLR）对胃癌患者预后生存的意义,并将其纳入列线图与传统TNM分期进行预后评估效能比较。方法 回顾性纳入2013年6月—2018年6月在中国科学技术大学第一附属医院胃肠外科接受胃癌根治切除术的胃癌患者作为训练组（n=300）,同时从胃肠外科另一病区纳入接受相同手术处理的胃癌患者作为验证组（n=100）。通过医院电子病历系统采集患者的年龄、性别、肿瘤类型、肿瘤部位、侵袭深度和淋巴结转移（LNM）等信息;术前3 d收集外周静脉血数据,并计算NLR和PLR,通过ROC曲线确定NLR（1.98）和PLR（134.87）的最佳临界点。术后2年内每3个月随访1次,2年后每6个月随访1次。采用Cox比例风险模型计算暴露与结局指标的关联,根据多因素分析结果识别影响胃癌预后的独立风险因素,纳入列线图后通过C-指数在训练组和验证组评估列线图的稳定性。最后,基于ROC曲线下面积（AUC）比较列线图和传统TNM分期的预测效能。结果 训练组男性患者220例（73.3%）,验证组男性患者69例（69.0%）,训练组平均年龄（62.52±10.61）岁,验证组平均年龄（63.67±10.21）岁。两组除肿瘤类型、分化程度和侵袭深度外,其他基线特征差异无统计学意义;训练组中位生存时间（OS）为28个月,1、3、5年OS率分别为63.5%、43.0%和35.1%;验证组中位OS为32个月,1、3、5年OS率分别为58.9%、41.6%和31.7%。单因素Cox回归分析显示,年龄、病理分型、肿瘤分化程度、侵袭深度、存在LNM、NLR、PLR和CEA水平均与OS有关（均P<0.05）。经过多因素调整后,存在LNM、术前NLR>1.98、PLR>134.87和癌胚抗原（CEA）≥5 μg/L的患者OS显著缩短（均P<0.01）。校准曲线结果显示列线图模型在训练组（C-指数=0.81）和验证组（C-指数=0.75）的拟合度良好。此外,列线图模型预测训练组1、3、5年OS率的AUC值（0.865,0.855,0.827）高于TNM分期（0.677,0.690,0.683）;验证组1、3、5年OS率的AUC值（0.856,0.788,0.725）高于TNM分期（0.781,0.691,0.605）。结论 NLR和PLR是预测胃癌患者术后生存的独立风险因素,基于两者构建的列线图可以较为准确地预测行胃切除术胃癌患者的1、3、5年OS率,为临床医师提供更精确的治疗、护理决策证据。     

腰椎术后手术部位感染的危险因素分析及列线图模型建立

目的 探讨开放性腰椎后入路手术患者术后手术部位感染（SSI）的相关危险因素,并建立与验证术后SSI的列线图风险预测模型。
方法 选择2017年1月至2021年12月行开放性腰椎后入路手术的患者920例,男422例,女498例,年龄≥18岁,BMI≥18.5 kg/m²,ASA Ⅰ—Ⅳ级。将患者按照7∶3随机分为训练数据集和验证数据集,并基于训练数据集建立预测模型。采用Lasso回归结合二元Logistic回归最终筛选的预测因素构建列线图模型。使用C指数、校准曲线及决策曲线（DCA）等对列线图模型的区分度、校准度及临床适用度进行分析评估。
结果 本研究中发生SSI的有17例（1.85%）,训练集中有10例（1.55%）,验证集中有7例（2.54%）。列线图模型中的预测因素包括术前低白蛋白血症（OR=36.928,95%CI 6.585～235.997,P<0.001）、肥胖（BMI≥28.0 kg/m²）（OR=4.994,95%CI 1.202～24.781,P=0.032）和术后3天内切口渗出（OR=6.133,95%CI 1.473～28.775,P=0.014）。该模型的C指数为0.879（95%CI 0.760～0.998）。校准曲线显示良好的一致性。DCA曲线分析显示当SSI发生风险阈值＞1%时,该列线图更具临床价值。
结论 术前低白蛋白血症、肥胖及术后3 d内切口渗出是行开放性腰椎后入路患者术后发生SSI的危险因素,基于以上危险因素构建的风险预测模型可以较好地预测术后SSI的发生。     

Cáncer de mama contralateral y recurrencia en portadoras BRCA1/2 y no portadoras con alto riesgo de cáncer de mama hereditario tras mastectomía bilateral

IntroductionContralateral prophylactic mastectomy (CPM) has been reported to reduce risk of contralateral breast cancer (CBC) by at least 90%.In addition, BRCA carriers presents higher risk of ipsilateral recurrence and a second primary tumor.The aim is to evaluate risk of CBC and recurrence and to analyze predictive factors in BRCA1/2 mutation carriers and non-carriers at high-risk of hereditary breast cancer patients.MethodsRetrospective observational study. 46 patients underwent bilateral mastectomy during 2004-2018.ResultsCohort comprised 9 patients BRCA1,12 BRCA2 and 25 at high-risk without mutation. Median follow-up 79 months. 16 patients recently diagnosed and 30 previously treated by breast cancer whom underwent CPM at second time (because of later detection of BRCA mutation in 10 cases). The external lateral incision was most frequent surgical technique. In all patients immediate reconstruction was performed.In CPM pieces, 4 in situ carcinoma, 3 invasive and 1 atypical hyperplasia were found. The incidence of occult contralateral cancer was 15.2%. Recurrence was observed in 5 patients a media of 21.2 months after surgery. FSD was 83.74 months and OS 84.33 months. Regression models identified BRCA1/2 mutation and high risk without mutation as significant occult tumor predictive factors while tumor size ≥ 2 cm was predictive of recurrence.ConclusionsIn our series we found a10.8% recurrence despite CPM and 7 patients (15.2%) would have developed a CBC in subsequent years.     

Bilateral nipple-sparing mastectomy and breast reconstruction in BRCA1 mutation-positive simultaneous bilateral breast cancer: A case study

BackgroundMutation-positive patients who develop unilateral breast cancer require different treatments, such as prophylactic mastectomy of the contralateral breast, from those used for other breast cancer patients. If a mutation is found before surgery, it is necessary to consider a surgical procedure that includes reconstruction. For BRCA mutation-positive patients, a suitable treatment must be selected. In Japan, a test for BRCA mutation has been covered by health insurance since 2020, making it possible to preoperatively test patients who are suspected of being positive. We report a case of simultaneous bilateral breast cancer that was found to be BRCA mutation-positive preoperatively and underwent bilateral subcutaneous mastectomy and breast reconstruction.Case presentationA 57-year-old woman was admitted to our hospital after a breast cancer screening revealed a mass in the left breast. She had a family history of breast cancer, including her sister, aunt, and cousin. She was suspected of being malignant with a mass on both sides of her breast on imaging. She underwent needle biopsy and was diagnosed as having bilateral invasive ductal carcinoma, for which she was placed on preoperative chemotherapy. Due to the strong family history of bilateral breast cancer, the patient was recommended to undergo a BRCA gene-mutation test and she consented. The result was positive for BRCA1 mutation. Although it was judged that bilateral breast-conserving surgery was sufficiently possible, bilateral subcutaneous mastectomy and breast reconstruction were performed based on BRCA mutation-positive status.DiscussionPerforming a preoperative BRCA test may change the surgical procedure.BRCA tests are beneficial to patients, but the timing of the tests is important. Care must be taken not to force the patient.ConclusionsKnowing whether the patient is BRCA mutation-positive is extremely important for selecting surgical procedures and treatment methods. BRCA testing should be recommended for patients who are strongly suspected of being positive, but the decision should be the patient’s. It is therefore necessary to provide accurate information and engage in a dialogue with the patient, but the medical staff should not pressure the patient to have the test.     

RAD51 135G／C单核苷酸多态与中国汉族家族性乳腺癌BRCA基因突变频率的分析

目的探讨RAD51 135G／C单核苷酸多态与中国汉族家族性乳腺癌人群BRCA基因突变的关系。方法本研究检测了200例汉族家族性乳腺癌先证者的BRCA基因的胚系突变，并对患者的RAD51 135G／C单核苷酸多态进行基因型分析。结果在200例先证者中检测到31例BRCA基因的突变，15例发生在BRCA1基因上，16例发生在BRCA2基因上。RAD51次等位基因c的分布频率在BRCA1突变者、BRCA2突变者和无突变者中相似。尽管RAD51 135GC／CC在BRCA1突变携带者中呈现出更高的频率，但与BRCA2突变携带者相比。差别无显著意义。结论RAD51 135G／C单核苷酸多态不能反映中国汉族乳腺癌人群BRCA基因突变的状态。     

Comparison of CTS5 risk model and 21-gene recurrence score assay in large-scale breast cancer population and combination of CTS5 and recurrence score to develop a novel nomogram for prognosis prediction

BackgroundBreast cancer is the most common malignancy in women. Clinical models such as Oncotype DX recurrence score (RS) and Clinical Treatment Score post–5 years (CTS5) model for survival prediction are crucial for clinical practice. However, it remains unclear whether CTS5 or RS would be a more powerful clinical model for recurrence risk evaluation. Therefore, we conducted the present study to compare the performance of CTS5 risk model and RS on different recurrence evaluation. And we further integrated the two models into a novel nomogram to improve the power for prognosis prediction.MethodsFemale patients with invasive hormone receptor positive breast cancer in the Surveillance, Epidemiology, and End Results Program (SEER) database with RS data available were included. The clinicopathological data were directly extracted from SEER database. Participants were divided into three subsets according to recurrence timing (<36 months, between 36 and 60 months, and >60 months) for model evaluation. Survival receiver operating characteristic curve and C-index were calculated to evaluate discrimination. Calibration curve were used to visual inspection for calibration. Model comparison was assessed by net reclassification index (NRI) method. Nomogram prognostic model was developed with the combination of CTS5 score and RS and also included other critical clinicopathological parameters.ResultsIn total, 64044 breast cancer patients were enrolled for analysis. The number of patients with survival <36 months (early recurrence subset), 36–60 months (intermediate recurrence subset) and >60 months (late recurrence subset) were 64044, 36878 and 15926, respectively. For model discrimination, CTS5 model was superior to RS for overall survival (OS) prediction (likelihood ratio test P < 0 0.001). RS model showed better performance for breast cancer specific survival (BCSS) in late recurrence subsets and worse performance in early and intermediate recurrence subsets than CTS5 (likelihood ratio test P < 0 0.001). For calibration, CTS5 model was superior to RS model for OS, which overestimated the recurrence risk in low-risk subgroup. Both models overestimated the risk for BCSS. In either early/intermediate/late recurrence patient subsets, there was no significant difference in NRI between two models in terms of both BCSS and OS, indicating the two models had comparable prognostic value. The nomogram which combined these two models largely improved the discrimination and calibration power (C-index 0.70–0.72).ConclusionsOur study proved the CTS5 risk model had comparable prognostic value as RS in HR + breast cancer patients. And the novel nomogram model had better discrimination and calibration than both CTS5 and RS, and future large-scale clinical trials are warranted for further validation.     

The prevalence of germline BRCA1 and BRCA2 mutations in young women with breast cancer undergoing breast-conservation therapy

BACKGROUND: Germline mutations of BRCA1 and BRCA2 increase the risk for breast cancer. Mutation carriers selecting breast-conservation therapy (BCT) for treatment of operable breast cancer experience a higher rate of new primary breast cancers. We sought to determine the frequency of BRCA1/BRCA2 mutations in women who underwent BCT. Genetic testing results were compared with the prior probability of mutations in either gene. METHODS: Eighty-nine patients age 39 or younger entered the study. Genetic testing was performed for BRCA1 and BRCA2 and the BRCAPRO model determined the probability of carrying a mutation. RESULTS: Eight mutations were discovered (prevalence, 9.0%). Twenty (22%) uncharacterized sequence variants were found. The prior probability of carrying a mutation was 14%. Mutation carriers had a higher prior probability (.49) compared with women with uncharacterized variants (.09) or with normal genes (.11). CONCLUSIONS: BRCA1 and BRCA2 mutations are common (9%) among unselected young breast cancer patients undergoing BCT.     

Prognostic significance of germline BRCA mutations in patients with HER2-POSITIVE breast cancer

BackgroundHER2-positive breast cancers are rare amongst BRCA mutation carriers. No data exist regarding clinicopathological characteristics and prognosis of this subgroup of patients.Materials and methodsUsing a retrospective matched cohort design, we collected data from 700 women who were diagnosed with operable invasive breast cancer from January 2006 to December 2016 and were screened for germline BRCA mutations. Clinicopathological features and survival rates were analyzed by BRCA and HER2 status.ResultsOne hundred and fifteen HER2-positive/BRCA mutated cases were evaluated in comparison to the three control groups: HER2-positive/BRCA wild type (n = 129), HER2-negative/BRCA mutated (n = 222), HER2-negative/BRCA wild type (n = 234). HER2-positive breast cancers were more likely to have high histologic grade and high proliferation rate than HER2-negative neoplasms, regardless of BRCA mutation status. An interaction between BRCA mutations and HER2-positive status was found to correlate with worse survival after adjusting for prognostic variables (HR = 3.4; 95% CI: 1.3–16.7).ConclusionsCo-occurrence of BRCA mutations and HER2-positive status is a poor prognostic factor in patients with early or locally advanced breast cancer. This finding may be a proof of concept that a combined pharmacological intervention directed to these targets could be synergistic.     

BRCA status,molecular markers,and clinical variables in early,conservatively managed breast cancer

Conservatively treated premenopausal breast cancer has a higher rate of local relapse as well as an increased genetic predisposition to cancer. The current study's purpose was to evaluate the interactions between BRCA-1/2 status and molecular biologic markers in a cohort of conservatively managed breast cancer patients. Seventy-six premenopausal women treated with breast-conserving surgery and radiation therapy were this study's focus. All patients were treated with wide local excision with or without axillary dissection, followed by radiation to the intact breast. Systemic therapy was administered as clinically indicated. All patients in this study had an available paraffin block from the primary tumor and agreed to undergo complete sequencing of the BRCA-1 and BRCA-2 genes. The primary breast tumor tissue from each patient was immunohistochemically stained for estrogen receptor (ER), progesterone receptor (PR), p53, HER-2/neu, and Proliferating Cell Nuclear Antigen (PCNA). Of the 76 patients tested for BRCA, 50 patients had wild-type BRCA-1 and BRCA-2, 15 had variants of unclear significance, 6 had deleterious mutations in BRCA-1, and 5 had deleterious mutations in BRCA-2. p53 positivity correlated with deleterious mutations in BRCA-1 (p = 0.023), but not in BRCA-2. Though not significant, there was a trend for ER and PR negativity to correlate with BRCA-1 mutation (p = 0.087 and 0.054, respectively); there were no correlations between ER, PR, and BRCA-2. Though not significant, all 11 tumors with BRCA mutations were HER-2/neu negative. Patients with BRCA mutations have a unique molecular profile. These data can be helpful in understanding differences in the biologic behavior of patients with familial breast cancers.     

散发性乳腺癌BRCA1基因的表达及其临床意义

目的　探讨BRCA1基因蛋白在汉族散发性乳腺癌中的表达及其临床病理意义。方法　采用免疫组化SP法对 5 1例乳腺癌石蜡切片组织进行BRCA1检测 ,并分析它与临床病理指标及c erbB 2表达的关系。　结果　BRCA1蛋白定位于癌细胞核 ,其失表达和低表达率为 49%。BRCA1蛋白表达下调与c erbB 2表达相关 (tr=4 15 5 ,P <0 0 5 ) ,与组织学分级、肿块大小、淋巴结转移数目及患者年龄均无明显相关。　结论　BRCA1蛋白表达的检测可在一定程度上反映基因的改变 ,可作为乳腺癌易感性初筛的手段。