摘要目的：分析乳腺癌易感基因1（ BRCA1）和乳腺癌易感基因2（ BRCA2）阴性家族性乳腺癌的临床病理特征及与新辅助化疗疗效的关系。方法收集2003年10月至2012年12月北京大学肿瘤医院乳腺中心收治的原发性乳腺癌患者6200例，对全部患者进行BRCA1和BRCA2基因突变检测后，排除BRCA1和BRCA2基因突变患者，将5842例BRCA1和BRCA2阴性乳腺癌患者分为家族性乳腺癌（480例）和散发性乳腺癌（5362例），比较家族性乳腺癌和散发性乳腺癌患者的临床病理特征和新辅助化疗后的病理完全缓解（ pCR）率，并分析影响新辅助化疗疗效的因素。结果在BRCA1和BRCA2阴性乳腺癌中，4．4％的家族性乳腺癌患者的发病年龄≤30岁，明显高于散发性乳腺癌患者（2．6％，P＝0．020）；5．0％的家族性乳腺癌患者发生双侧乳腺癌，明显高于散发性乳腺癌患者（2．7％，P＝0．004）。 BRCA1和BRCA2阴性家族性乳腺癌患者在≤30岁时发生乳腺癌的风险为散发性乳腺癌的1．73倍，BRCA1和BRCA2阴性家族性乳腺癌患者发生双侧乳腺癌的风险为散发性乳腺癌的1．91倍。在接受新辅助化疗的2964例BRCA1和BRCA2阴性乳腺癌患者中，家族性乳腺癌的pCR率为21．7％，明显高于散发性乳腺癌（14．0％，P＝0．001）。肿瘤≤2 cm（ P＝0．012）、组织学分级为Ⅲ级（ P＜0．001）、三阴性乳腺癌（ P＜0．001）及BRCA1和BRCA2阴性家族性乳腺癌（ P＝0．001）均为影响BRCA1和BRCA2阴性乳腺癌患者pCR率的独立因素。结论与BRCA1和BRCA2阴性散发性乳腺癌比较，BRCA1和BRCA2阴性家族性乳腺癌具有独特的临床病理特征，表现为早发性乳腺癌比例高，双侧乳腺癌比例高；且BRCA1和BRCA2阴性家族性乳腺癌患者对新辅助化疗敏感。

abstractsObjective To explore the relationship of clinicopathological features and response to neoadjuvant chemotherapy in women with BRCA1 and BRCA2 mutation-negative familial breast cancer. Mte hods A total of 6 200 women with breast cancer were treated at our hospital from October 2003 to December 2012.All subjects underwent genetic testing for BRCA1 and BRCA2 genes.Patients with BRCA1 and BRCA2 mutations were excluded.This cohort of 5 842 patients with BRCA1 and BRCA2 mutation-negative breast cancer was classified as two groups: familial breast cancer patients ( n=480) and sporadic breast cancer patients ( n=5 362) .The clinicalpathological data and response to neoadjuvant chemotherapy of the 480 patients with BRCA1 and BRCA2 mutation-negative familial breast cancer and the 5 362 patients with BRCA1and BRCA 2 mutationn-egative sporadic breast cancer were compared retrospectively .Then the influencing factors of response to neoadjuvant chemotherapy were analyzed.Resu lts Among the BRCA1 and BRCA2 mutation-negative breast cancer patients, 4.4%of the patients were diagnosed before 30 years of age&nbsp;in the familial breast cancer group, significantly higher than that of 2.6%in the sporadic breast cancer group ( P=0.020 ) .5.0% of the patients in the familial breast cancer group had bilateral breast cancer, significantly higher than that of 2.7%in the sporadic breast cancer group ( P=0.004 ) .Compared with BRCA1 and BRCA2 mutation-negative sporadic breast cancer patients, the relative risk of early-onset breast cancer (≤30 years) and bilateral breast cancer were 1.73 and 1.91, respectively, significantly higher than that in the BRCA1 and BRCA2 mutation-negative familial breast cancer cases ( P=0.020 and P=0.004) .2 964 patients in this cohort of 5 842 case sreceived neoadjuvant chemotherapy.The pathologic complete response (pCR) rate was significantly higher in the BRCA1 and BRCA2 mutation-negative familial breast cancer group than in the BRCA1 and BRCA2 mutation-negative sporadic breast cancer group (21.7%vs.14. 0%,P=0.001) .Independent factors associated with pCR in BRCA1 and BRCA2 mutation-negative breast cancer patients were tumor size less than 2 cm ( P=0.012) , histologic gradeⅢ( P<0.001) , triple-negative breast cancers (P<00.01 ), and BRCA1 and BRCA2 mutation-negative familial breast cancer(P=0.001). Conclusions Compared with BRCA1 and BRCA2 mutation-negative sporadic breast cancer, BRCA1 and BRCA2 mutation-negative familial breast cancer is more likely diagnosed before the age of 30 years and has a higher risk to develop bilateral breast cancer.BRCA1 and BRCA2 mutation-negative familial breast cancers are more likely to respond to neoadjuvant chemotherapy than BRCA1 and BRCA2 mutation-negative sporadic breast cancer.