3 ？ 正常细胞在急骤的BRCA1功能丧失下难以生存，如纯合的BRCA1突变可导致小鼠早期胚胎死亡 loss of wild-type BRCA1是否是BRCA1-associated breast tumors 发生的始动环节，BRCA1突变相关肿瘤究竟是如何演变的。BRCA1相关联的乳腺癌常同时伴有其他基因的体系突变，如P53，PTENBRCA1突变携带者的正常细胞常呈现出异常的表型，如单倍剂量不足（haploinsufficiency）
10 Loss of PTEN was the first event in 28/55 tumors, followed by mutation in p53 or BRCA1 LOH with about equal probability; Mutation in p53 was the second most common first event in 17/55 tumors, almost followed by BRCA1 LOH. BRCA1 LOH was the least common first event in 10/55, only followed by p53mutation sometimes.
11 loss of PTEN was the first event 的pathway 1改变的多为TNBC，TP53 or BRCA1 LOH为第一事件的pathway 2 肿瘤多为luminal。
13 瘤内异质性The loss of wild-type BRCA1 may not be the first event in most BRCA1-associated breast tumors, and even in tumors that display apparent loss of the wild-type BRCA1 allele, not all tumor cells showed this change.
16 单倍定量不足Loss of BRCA1在BRCA1-associated的乳腺癌中很少是 the first event ，乳腺上皮细胞中BRCA1单倍定量不足（haploinsufficient ）为BRCA1突变乳腺癌风险增加提供了很好的解释。
17 Ki67, 增值标记物, PR-潜在的促分裂因子；Immunofluorescence检测发现： significantly more Ki67+, PR+, and Ki67+ PR+ cells in contralateral normal breast tissue of BRCA1 mutation carriers diagnosed with breast cancer compared with that observed in controls.
19 During the analysis of Ki67+ cells, we noticed occasional multipolar mitoses in normal breast tissues from BRCA1 mutation carriers, suggesting aberrant centrosome function. We found significantly higher (P ≤0.01) numbers of cells with more than 2 centrosomes in BRCA1 mutation carriers compared with controls