Surveillance of BRCA1 and BRCA2 mutation carriers with magnetic resonance imaging, ultrasound, mammography, and clinical breast examination

Context  Current recommendations for women who have a BRCA1 or BRCA2 mutation are to undergo breast surveillance from age 25 years onward with mammography annually and clinical breast examination (CBE) every 6 months; however, many tumors are detected at a relatively advanced stage. Magnetic resonance imaging (MRI) and ultrasound may improve the ability to detect breast cancer at an early stage. Objective  To compare the sensitivity and specificity of 4 methods of breast cancer surveillance (mammography, ultrasound, MRI, and CBE) in women with hereditary susceptibility to breast cancer due to a BRCA1 or BRCA2 mutation. Design, Setting, and Participants  A surveillance study of 236 Canadian women aged 25 to 65 years with BRCA1 or BRCA2 mutations who underwent 1 to 3 annual screening examinations, consisting of MRI, mammography, and ultrasound at a single tertiary care teaching hospital between November 3, 1997, and March 31, 2003. On the day of imaging and at 6-month intervals, CBE was performed. Main Outcome Measures  Sensitivity and specificity of each of the 4 surveillance modalities, and sensitivity of all 4 screening modalities vs mammography and CBE. Results  Each imaging modality was read independently by a radiologist and scored on a 5-point Breast Imaging Reporting and Data System scale. All lesions with a score of 4 or 5 (suspicious or highly suspicious for malignancy) were biopsied. There were 22 cancers detected (16 invasive and 6 ductal carcinoma in situ). Of these, 17 (77%) were detected by MRI vs 8 (36%) by mammography, 7 (33%) by ultrasound, and 2 (9.1%) by CBE. The sensitivity and specificity (based on biopsy rates) were 77% and 95.4% for MRI, 36% and 99.8% for mammography, 33% and 96% for ultrasound, and 9.1% and 99.3% for CBE, respectively. There was 1 interval cancer. All 4 screening modalities combined had a sensitivity of 95% vs 45% for mammography and CBE combined. Conclusions  In BRCA1 and BRCA2 mutation carriers, MRI is more sensitive for detecting breast cancers than mammography, ultrasound, or CBE alone. Whether surveillance regimens that include MRI will reduce mortality from breast cancer in high-risk women requires further investigation.      

Variation of breast cancer risk among BRCA1/2 carriers

Context  The risk of breast cancer in BRCA1 and BRCA2 mutation carriers has been examined in many studies, but relatively little attention has been paid to the degree to which the risk may vary among carriers. Objectives  To determine the extent to which risks for BRCA1 and BRCA2 carriers vary with respect to observable and unobservable characteristics. Design, Setting, and Participants  Probands were identified from a population-based, case-control study (Women’s Environmental Cancer and Radiation Epidemiology [WECARE]) of asynchronous contralateral breast cancer conducted during the period of January 2000 to July 2004. Participants previously diagnosed with contralateral breast cancer or unilateral breast cancer were genotyped for mutations in BRCA1 and BRCA2. All participants had their initial breast cancer diagnosed during the period of January 1985 to December 2000, before the age of 55 years. Main Outcome Measure  Incidence of breast cancer in first-degree female relatives of the probands was examined and compared on the basis of proband characteristics and on the basis of variation between families. Results  Among the 1394 participants with unilateral breast cancer, 73 (5.2%) were identified as carriers of deleterious mutations (42 with BRCA1 and 31 with BRCA2). Among the 704 participants with contralateral breast cancer, 108 (15.3%) were identified as carriers of deleterious mutations (67 with BRCA1 and 41 with BRCA2). Among relatives of carriers, risk was significantly associated with younger age at diagnosis in the proband (P = .04), and there was a trend toward higher risk for relatives of contralateral breast cancer vs unilateral breast cancer participants (odds ratio, 1.4 [95% confidence interval, 0.8-2.4]; P = .28). In addition, there were significant differences in risk between carrier families after adjusting for these observed characteristics. Conclusion  There exists broad variation in breast cancer risk among carriers of BRCA1 and BRCA2 mutations.      

Prevalence of pathogenic BRCA1 mutation carriers in 5 US racial/ethnic groups

Esther M. John, PhD; Alexander Miron, PhD; Gail Gong, PhD; Amanda I. Phipps, MPH; Anna Felberg, MS; Frederick P. Li, MD; Dee W. West, PhD; Alice S. Whittemore, PhD

JAMA. 2007;298(24):2869-2876.

Context  Information on the prevalence of pathogenic BRCA1 mutation carriers in racial/ethnic minority populations is limited.

Objective  To estimate BRCA1 carrier prevalence in Hispanic, African American, and Asian American female breast cancer patients compared with non-Hispanic white patients with and without Ashkenazi Jewish ancestry.

Design, Setting, and Participants  We estimated race/ethnicity-specific prevalence of BRCA1 in a population-based, multiethnic series of female breast cancer patients younger than 65 years at diagnosis who were enrolled at the Northern California site of the Breast Cancer Family Registry during the period 1996-2005. Race/ethnicity and religious ancestry were based on self-report. Weighted estimates of prevalence and 95% confidence intervals (CIs) were based on Horvitz-Thompson estimating equations.

Main Outcome Measure  Estimates of BRCA1 prevalence.

Results  Estimates of BRCA1 prevalence were 3.5% (95% CI, 2.1%-5.8%) in Hispanic patients (n = 393), 1.3% (95% CI, 0.6%-2.6%) in African American patients (n = 341), and 0.5% (95% CI, 0.1%-2.0%) in Asian American patients (n = 444), compared with 8.3% (95% CI, 3.1%-20.1%) in Ashkenazi Jewish patients (n = 41) and 2.2% (95% CI, 0.7%-6.9%) in other non-Hispanic white patients (n = 508). Prevalence was particularly high in young (<35 years) African American patients (5/30 patients [16.7%]; 95% CI, 7.1%-34.3%). 185delAG was the most common mutation in Hispanics, found in 5 of 21 carriers (24%).

Conclusions  Among African American, Asian American, and Hispanic patients in the Northern California Breast Cancer Family Registry, the prevalence of BRCA1 mutation carriers was highest in Hispanics and lowest in Asian Americans. The higher carrier prevalence in Hispanics may reflect the presence of unrecognized Jewish ancestry in this population.

     

动态增强磁共振成像对乳腺癌的诊断

目的探讨乳腺癌动态增强磁共振成像（dynamic contrast-enhanced magnetic resonance imaging，DCE．MRI）的表现及诊断价值。方法回顾性分析经手术病理证实的22例乳腺癌患者的MRI资料，总结乳腺癌的DCE．MRI表现。病例在术前均行MRI平扫及动态增强扫描。结果21个病灶有毛刺征象；16个病灶呈边缘强化，6个病灶表现为整体不均匀强化。最大信号强度投影法（MIP）像上17个病灶周边可见粗大扭曲的或细小密集的血管影。时间-信号强度曲线上，15个病灶呈Ⅲ型曲线，7个表现为Ⅱ型曲线。结论乳腺癌的DCE-MRI特征性表现有毛刺征、边缘强化及Ⅲ型曲线，DCE-MRI对乳腺癌的诊断有较高的临床价值。     

磁共振成像在乳腺疾病诊断中的应用

近年来研究表明，磁共振成像(MRI)检查对乳腺疾病的诊断有很大的潜力。运用正确的扫描方法，掌握乳腺各类疾病的MRI特点，充分认识乳腺MRI的优势，了解其发展前景，为提高乳腺疾病诊断，特别是乳腺癌诊断的准确率有重要意义，并为乳腺疾病的正确治疗提供更多信息。     

新疆遗传性乳腺癌BRCA1／2基因突变检测的研究

目的通过对新疆82例遗传性乳腺癌 BRCA基因突变检测,了解新疆遗传性乳腺癌 BRCA1/2基因突变位点及携带情况。方法以来自新疆地区的82例符合遗传性乳腺癌标准的患者为研究对象,通过外周静脉血提取基因组 DNA,对 BRCA1/2基因的全部编码序列进行扩增。BRCA1/2基因突变分析由变性高效液相色谱分析（DHPLC）进行预筛,结果进行DNA测序证实。统计分析 BRCA1/2基因突变情况。结果82例遗传性乳腺癌,共发现8例（9．76％）BRCA基因突变,其中 BRCA1突变4例,BRCA2突变4例;4例 BRCA突变（2073delA移码突变、W372X无义突变、6873delCTCC移码突变、9481delA移码突变）在BIC数据库中未见报道。在三阴性乳腺癌中BRCA1突变率高（5/30,16．7％）。结论遗传性乳腺癌 BRCA基因突变率高于散发性乳腺癌;三阴性乳腺癌BRCA1突变的比例高;在新疆多民族地区未发现BRCA基因突变热点。     

The emerging role of breast magnetic resonance imaging

The barriers to magnetic resonance imaging (MRI) in the staging and diagnosis of breast cancer are being resolved through merging technologies and the new ability to perform MRI-guided biopsies. Detailed spatial resolution and excellent sensitivity are the strengths of this modality, whereas specificity is the primary challenge, requiring a strong commitment by the interested radiologist. While the original indication for breast MRI was in the evaluation of implant integrity, this modality is now recommended for: mapping tumor extent in newly diagnosed breast cancer patients, diagnosing breast cancer when conventional imaging is complex and indeterminate, and possibly for screening high-risk patients who have dense mammograms. A breast-dedicated magnetic resonance unit offers several advantages, including the first commercially available biopsy device. RODEOtm software (ROtating Delivery of Excitation Off-resonance) is an anticipated upgrade to this breast-dedicated unit, offering such a high degree of sensitivity and resolution that improved detection of Ductal Carcinoma In Situ will be possible.     

散发性乳腺癌患者BRCA1基因突变检测

目的:研究散发性乳腺癌患者中,乳腺癌易感基因-1(BRCA1)的突变情况,并探讨其临床意义。方法:采用聚合酶链反应-单链构像多态性分析(PCR-SSCP)、标记染色双脱氧末端法DNA测序,对27例散发性乳腺癌患者以及正常对照组8例进行BRCA1基因全序列外显子突变检测。结果:27例患者中发现1例第16外显子基因突变,突变率为3.7%(1/27例);突变形式为4804C→G,突变结果引起单个氨基酸改变,使编码子1562由精氨酸代替脯氨酸。结论:在散发性乳腺癌患者中BRCA1基因突变率较低(3.7%),BRCA1可能通过突变以外的调节方式起作用。     

家族性乳腺癌患者115例的BRCA1和BRCA2基因突变检测

目的 研究中国家族性乳腺癌患者中BRCA1/2基因突变的发生率和特性.方法 研究对象为来自全国4个乳腺癌医疗中心的115例家族性乳腺癌患者(包括前期研究的35例),应用DHPLC和DNA序列测定技术对这些患者进行BRCA1/2基因全编码区的突变检测.结果 在115例患者中,共发现11例BRCA1基因突变和3例BRCA2基因突变,总的突变发生率为12.2%.根据家系中乳腺癌患者个数分层后,突变携带率差异无统计学意义.但是携带BRCA1/2基因突变的家系中先证者和所有乳腺癌患者的平均发病年龄显著早于突变阴性的家系(P＜0.01),同时家系中年轻的乳腺癌患者越多,突变携带率就越高.结论 在中国家族性乳腺癌患者中,患者的发病年龄能有效地预测BRCA1/2基因突变的携带率,但是家系中乳腺癌患者个数的预测功能却较差.     

3．0T磁共振在乳腺成像中的应用

目的探讨3.0T磁共振在乳腺成像中,的应用价值,优化扫描序列和参数。方法使用GE3．0T磁共振扫描仪和8通道乳腺线圈对42名乳腺疾病患者进行乳腺MR成像,从图像质量和病灶显示数哥上对其应用价值进行评价。结果所有患者均获得了具有诊断意义的图像。42例患者共检出45处病变,其中恶性3例,共5处病变：良性34例,共40处病变。结论3.0T MR乳腺成像,合理的扫描方案可以缩短扫描时间、提高图像质量。多序列联合应用更有利于疾病的诊断和鉴别诊断。     

乳腺假体并发症的Silicone序列MRI特征

目的 分析乳腺假体植入术后并发症的MRI表现,探讨其诊断价值.方法 回顾性分析本院2013年6月至2015年6月收治的9例乳腺假体MRI特征.结果 ①假体退行性样改变:Silicone-Sup序列上表现为片状不规则混杂信号或气泡样无信号结节.②假体包膜挛缩、假体变形移位:表现为假体边缘呈波浪状,囊壁增厚.③假体破裂(分囊内破裂和包膜破裂):囊内破裂Silicone-only序列表现囊内曲线状、弧线状低信号;包膜破裂表现为假体包膜连续性中断、假体周围间隙内存在结节状或片状假体信号.结论 MRI是诊断乳腺假体并发症的首选方法,视野全面,无需压迫,诊断准确率高.     

Role of breast magnetic resonance imaging in difficult diagnostic situations.

In some patients with breast disease, mammography and ultrasonography can provide only limited diagnostic information. Magnetic resonance imaging of the breast has high sensitivity and specificity and can play a significant diagnostic role in problem situations. Patients who are most likely to benefit are those with (i) axillary adenopathy of unknown primary origin, (ii) possible tumour recurrence after surgery or radiotherapy, (iii) lesions overlying implants, or (iv) those requiring staging of lobular or multifocal carcinoma.     

乳腺肿瘤MRI动态增强模式研究

目的研究乳腺良恶性肿瘤的MRI动态增强模式特点。方法手术病理证实的乳腺肿瘤23例24个病灶,其中恶性13例14个病灶,良性10例10个病灶。采用PHILIPSinteraAchieva1.5T磁共振机行平扫和动态增强扫描加减影技术。分别用强化时间-信号曲线类型,1、2、4、8min强化率,峰值强化率,峰值强化时间来分析良恶性肿瘤的特点。结果动态增强减影显示全部病灶。恶性肿瘤的强化时间-信号曲线类型有A型7.1%(1/14)、B型78.6%(11/14)、C型14.3%(2/14);良性肿瘤有B型30.0%(3/10)、C型70.0%(7/10)。良恶性肿瘤的早期(1、2min)强化率的差异存在统计学意义(P<0.05)。而4、8min强化率和峰值强化率无统计学意义(P>0.05)。峰值强化时间在2min内100%为恶性;在2～4min间50.0%为恶性、50.0%为良性;>8min者20.0%为恶性、80.0%为良性。结论有效结合形态学和动态增强曲线类型、早期强化率和峰值强化时间可以提高乳腺良恶性肿瘤的诊断准确率。