Lancet. 1997 May 24;349(9064):1505-10.
A few breast cancer cases are attributable to a hereditary predisposition to the disease. We aimed to compare the histological features of breast cancer in women carrying mutations in the susceptibility genes BRCA1 and BRCA2 with controls unselected for family history.
The morphological characteristics of specimens from 440 patients with familial breast cancer, including 118 in carriers of BRCA1 mutations and 78 in carriers of BRCA2 mutations, were compared with those from 547 age-matched controls, unselected for family history, by seven pathologists.
Cancers in carriers of BRCA1 (p < 0.0001) and BRCA2 mutations (p = 0.04) were, on average, of a higher overall grade than in controls. For example, the proportions in grade 3 were 66% of 139, 41% of 58 and 36% of 368 specimens, respectively. However, when the three grade indices were considered independently, breast cancers in BRCA1-mutation carriers showed more pleomorphism (p = 0.006), a higher mitotic count (p < 0.0001), and less tubule formation than controls (p = 0.006), whereas cancers in BRCA2-mutation carriers showed less tubule formation (p = 0.003), but no difference in pleomorphism or mitotic count. The occurrence of invasive lobular carcinoma and invasive ductal carcinoma was not significantly different between carriers of BRCA1 or BRCA2 mutations and controls. Medullary or atypical medullary carcinoma was, however, found more often in BRCA1 (13%, p < 0.0001) than in BRCA2-mutation carriers (3%) or controls (2%). Tubular carcinoma was less common in BRCA2-mutation carriers. The few mucoid carcinomas were all in familial cases. Carriers of BRCA1 mutations showed less ductal carcinoma in situ around the invasive lesion than controls (41 vs 56%, p = 0.001). Lobular carcinoma in situ was less common in familial cancers (p = 0.013), but differences were not significant for BRCA1-mutations or BRCA2-mutation carriers, separately.
The histology of breast cancers in predisposed women differs from that in sporadic cases, and there are differences between breast cancers in carriers of BRCA1 and BRCA2 mutations. The findings suggest that breast cancer due to BRCA1, has a different natural history to BRCA2 or apparently sporadic disease, which may have implications for screening and management.
少数乳腺癌病例可归因于该疾病的遗传易感性。我们旨在比较携带乳腺癌易感基因BRCA1和BRCA2突变的女性与未根据家族病史筛选的对照组女性乳腺癌的组织学特征。
7名病理学家将440例家族性乳腺癌患者标本的形态学特征，包括118例BRCA1突变携带者和78例BRCA2突变携带者，与547例未根据家族病史筛选的年龄匹配对照组进行比较。
BRCA1突变携带者（p<0.0001）和BRCA2突变携带者（p = 0.04）的癌症总体分级平均高于对照组。例如，三级标本的比例分别为139例中的66%、58例中的41%和368例中的36%。然而，当独立考虑这三个分级指标时，BRCA1突变携带者的乳腺癌表现出更多的多形性（p = 0.006）、更高的有丝分裂计数（p<0.0001），并且与对照组相比小管形成较少（p = 0.006），而BRCA2突变携带者的癌症小管形成较少（p = 0.003），但在多形性或有丝分裂计数方面没有差异。BRCA1或BRCA2突变携带者与对照组之间浸润性小叶癌和浸润性导管癌的发生率没有显著差异。然而，髓样或非典型髓样癌在BRCA1突变携带者中（13%，p<0.0001）比在BRCA2突变携带者（3%）或对照组（2%）中更常见。小管癌在BRCA2突变携带者中较少见。少数黏液癌均见于家族性病例。BRCA1突变携带者在浸润性病变周围的导管原位癌比对照组少（41%对56%，p = 0.001）。小叶原位癌在家族性癌症中较少见（p = 0.013），但分别在BRCA1突变携带者或BRCA2突变携带者中差异不显著。
易感女性乳腺癌的组织学与散发性病例不同，BRCA1和BRCA2突变携带者的乳腺癌之间也存在差异。研究结果表明，由BRCA1引起的乳腺癌与BRCA2或明显散发性疾病具有不同的自然史，这可能对筛查和管理有影响。
