Division of Clinical Cancer Genetics, City of Hope, Duarte, CA, 91010, USA.
Breast Cancer Res Treat. 2011 Nov;130(1):281-9. doi: 10.1007/s10549-011-1570-7. Epub 2011 May 21.
The immunophenotype of BRCA-associated breast cancer has been studied in predominantly non-Hispanic whites (NHW). We evaluated the pathological characteristics of BRCA-associated invasive breast cancer in Hispanics. A case-control study was conducted on breast cancers from Hispanic and NHW women who enrolled in an IRB-approved registry and underwent BRCA gene analysis. BRCA negative controls (41 Hispanic, 39 NHW) were matched on age and ethnicity to BRCA positive cases (39 Hispanic, 35 NHW). A tissue array was constructed to characterize the expression of estrogen receptor (ER), progesterone receptor (PR), HER2, Ki-67 and p53 by immunohistochemistry. Mean age at diagnosis was 37.1 years (range 24-59) for Hispanics (80% with Mexican ancestry) and 40.1 years (range 21-63) for NHW (P = 0.03). Hispanic BRCA1 cases were more likely than BRCA negative controls to have tumors that were ER-negative (P < 0.001) and PR-negative (P = 0.001), had higher levels of Ki-67 (P = 0.001) and p53 expression, and lower levels of HER2 overexpression. When stratified by genes, there were no significant differences in expression of ER, Ki-67, HER2, and p53 by ethnicity among mutation carriers. However, a significantly higher proportion of BRCA-positive Hispanics had PR-negative tumors compared to BRCA-positive NHW (80 vs. 57%, OR = 2.9, 95% CI 1.0-8.1, P = 0.04). Hispanic BRCA-associated breast cancers were found to have the unique immunophenotype associated with BRCA mutations; however, there was a trend toward a difference in PR expression among Hispanic BRCA1 and BRCA2 cases. Additional research on the molecular mechanisms involved in the loss of PR in this population is warranted as it could have important implications for the treatment and prevention of breast cancer in Hispanics.
BRCA 相关乳腺癌的免疫表型已在主要为非西班牙裔白人(NHW)中进行了研究。我们评估了西班牙裔人群中 BRCA 相关浸润性乳腺癌的病理特征。对在经过 IRB 批准的注册处登记并进行 BRCA 基因分析的西班牙裔和 NHW 女性的乳腺癌进行了病例对照研究。BRCA 阴性对照(41 名西班牙裔,39 名 NHW)按年龄和种族与 BRCA 阳性病例(39 名西班牙裔,35 名 NHW)相匹配。构建组织微阵列以通过免疫组织化学法表征雌激素受体(ER)、孕激素受体(PR)、HER2、Ki-67 和 p53 的表达。西班牙裔(80%有墨西哥血统)的诊断时平均年龄为 37.1 岁(范围 24-59),NHW 为 40.1 岁(范围 21-63)(P=0.03)。与 BRCA 阴性对照相比,BRCA1 病例的肿瘤更可能为 ER 阴性(P<0.001)和 PR 阴性(P=0.001),Ki-67 水平更高(P=0.001),p53 表达水平更低,HER2 过表达水平更低。按基因分层,突变携带者中,种族之间 ER、Ki-67、HER2 和 p53 的表达无显着差异。然而,与 BRCA 阳性的 NHW 相比,BRCA 阳性的西班牙裔人群中 PR 阴性肿瘤的比例显着更高(80%比 57%,OR=2.9,95%CI 1.0-8.1,P=0.04)。发现 BRCA 相关的乳腺癌具有与 BRCA 突变相关的独特免疫表型;然而,BRCA1 和 BRCA2 病例中 PR 表达存在差异的趋势。需要对该人群中 PR 缺失的分子机制进行更多研究,因为这可能对西班牙裔人群的乳腺癌治疗和预防具有重要意义。