The significance of circumscribed malignant mammographic masses in the surveillance of BRCA 1/2 gene mutation carriers

Breast cancers in gene mutation carriers may escape mammographic detection because of rapid growth and tumor expansion. Therefore, they may mimic benign lesions on the mammogram. Twenty-nine BRCA 1/2 mutation carriers under surveillance developed 31 breast cancers between 1994 and 2001 at a mean age of 44.2 years. Controls were 63 women with 67 breast cancers in the same period at a mean age of 53.8 years, also under surveillance because of a life time risk of at least 15%. In 26% of the carriers vs. 48% of the controls, mammography was the method that first suspected a malignancy. Seven radiologists performed a retrospective review of the original mammograms to establish technical assessment, with special attention for circumscribed lesions and estimated probability of malignancy. In the mutation carriers seven (23%) circumscribed non-calcified mammographic masses were found and three in the controls (4.5%) P=0.01. These masses were proven to be malignant. In both groups around 70% of these fast-growing circumscribed lesions were detected by the patients. The masses were situated in breasts with a good interpretable breast pattern. BRCA 1/2 mutation carriers had a significantly higher percentage of circumscribed non-calcified mammographic masses that proved to be malignant. These mammographic lesions in women at high risk should be described as at least Birads 0 and worked-up with ultrasound and needle biopsy.     

Breast tumor characteristics of <Emphasis Type="Italic">BRCA1</Emphasis> and <Emphasis Type="Italic">BRCA2</Emphasis> gene mutation carriers on MRI

The appearance of malignant lesions in BRCA1 and BRCA2 mutation carriers (BRCA-MCs) on mammography and magnetic resonance imaging (MRI) was evaluated. Thus, 29 BRCA-MCs with breast cancer were retrospectively evaluated and the results compared with an age, tumor size and tumor type matched control group of 29 sporadic breast cancer cases. Detection rates on both modalities were evaluated. Tumors were analyzed on morphology, density (mammography), enhancement pattern and kinetics (MRI). Overall detection was significantly better with MRI than with mammography (55/58 vs 44/57, P = 0.021). On mammography, lesions in the BRCA-MC group were significantly more described as rounded (12//19 vs 3/13, P = 0.036) and with sharp margins (9/19 vs 1/13, P = 0.024). On MRI lesions in the BRCA-MC group were significantly more described as rounded (16/27 vs 7/28, P = 0.010), with sharp margins (20/27 vs 7/28, P < 0.001) and with rim enhancement (7/27 vs 1/28, P = 0.025). No significant difference was found for enhancement kinetics (P = 0.667). Malignant lesions in BRCA-MC frequently have morphological characteristics commonly seen in benign lesions, like a rounded shape or sharp margins. This applies for both mammography and MRI. However the possibility of MRI to evaluate the enhancement pattern and kinetics enables the detection of characteristics suggestive for a malignancy.     

聚腺苷二磷酸核糖聚合酶-1抑制剂对乳腺癌易感基因突变乳腺癌细胞放射敏感性的影响及调控机制

目的 探讨聚腺苷二磷酸核糖聚合酶-1(PARP-1)的抑制剂3-氨基苯甲酰胺(3-aminobenzamide,3-AB)对于乳腺癌易感基因(BRCA)突变及非突变乳腺癌细胞放射敏感性的影响,探讨PARP-1和BRCA基因在照射引起的乳腺癌细胞DNA损伤修复中的作用及调控机制。方法 将BRCA突变乳腺癌细胞(MDA-MB-436)和BRCA非突变乳腺癌细胞(MDA-MB-231)分别分为对照组(CTRL)、单纯照射组(IR)、单纯用药组(3-AB)和药物联合照射组(3-AB+IR)。通过γ-H2AX免疫荧光焦点,检测DNA双链断裂的损伤情况;克隆形成实验检测细胞的放射敏感性;流式细胞仪检测细胞的凋亡率。结果 克隆形成实验显示,MDA-MB-436细胞较MDA-MB-231细胞放射敏感性明显升高,3-AB可增加两种细胞的放射敏感性。γ-H2AX免疫荧光焦点实验显示MDA-MB-436细胞与MDA-MB-231细胞相比DNA双链的损伤情况明显升高(t=4.57,P<0.05),而3-AB可进一步增加照射引起的DNA损伤,IR+3-AB组的MDA-MB-436细胞DNA损伤最明显(t=3.26,P<0.05)。流式细胞术结果显示,IR+3-AB组的凋亡率最高,且差异有统计学意义(t=3.81,P<0.05)。MDA-MB-436细胞相比MDA-MB-231细胞凋亡率明显增加(t=2.96,P<0.05)。结论 照射过程中,MDA-MB-436细胞比MDA-MB-231细胞产生更多的DNA损伤和凋亡,因此BRCA突变的乳腺癌细胞MDA-MB-436放射敏感性更强。而PARP-1抑制剂可进一步阻断照射引起的DNA损伤修复,从而增加MDA-MB-436的放射敏感性。     

乳腺癌改良根治术患者血清CYFRA21 1、TK1及CA15 3水平变化及其与术后复发的相关性研究

目的探讨乳腺癌改良根治术患者血清细胞角蛋白19片段（cytokeratin 19 fragment,CYFRA21-1）、胸苷激酶1（thymidine kinase 1,TK1）及癌抗原15-3（cancer antigen 15-3,CA15-3）水平变化及其与术后复发的相关性。方法选取2015年1月—2017年8月成都医学院第一附属医院行乳腺癌改良根治术患者125例作为乳腺癌组,选取同期体检的年龄、性别匹配的健康体检者125例作为对照组,检测乳腺癌组改良根治术前后及对照组血清CYFRA21-1、TK1及CA15-3水平,根据乳腺癌术后有无复发分复发组和未复发组,比较2组患者血清CYFRA21-1、TK1及CA15-3水平。结果乳腺癌TNM-Ⅰ期患者CYFRA21-1、TK1、CA15-3水平低于TNM Ⅱ期、Ⅲa期患者（P＜0.05）;TNM Ⅱ期低于Ⅲa期患者,差异有统计学意义（P＜0.05）;乳腺癌组术后CYFRA21-1、TK1、CA15-3水平低于术前（P＜0.05）,乳腺癌组手术前后CYFRA21-1、TK1、CA15-3水平均高于对照组,差异有统计学意义（P＜0.05）;截止随访时间29例复发,复发率23.2%。复发组血清CYFRA21 1、TK1、CA15-3水平显著高于未复发组,差异有统计学意义（P＜0.05）,Logistic回归分析显示,血清CYFRA21-1、TK1、CA15-3水平与术后复发存在关联性（P＜0.05）;ROC曲线分析显示,CYFRA21-1、TK1、CA15-3联合预测乳腺癌术后复发的特异度、敏感度高于单一指标检测。结论乳腺癌改良根治术后血清CYFRA21-1、TK1、CA15-3水平与术后复发有关。