遗传性乳腺癌：病理生物学、预后及BRCA1和BRCA2基因连锁关系

Hereditary breast cancer: pathobiology, prognosis, and BRCA1 and BRCA2 gene linkage.

作者信息

Marcus J N, Watson P, Page D L, Narod S A, Lenoir G M, Tonin P, Linder-Stephenson L, Salerno G, Conway T A, Lynch H T

机构信息

Department of Pathology, Creighton University School of Medicine, Omaha, Nebraska, USA.

出版信息

Cancer. 1996 Feb 15;77(4):697-709. doi: 10.1002/(sici)1097-0142(19960215)77:4<697::aid-cncr16>3.0.co;2-w.

DOI:10.1002/(sici)1097-0142(19960215)77:4<697::aid-cncr16>3.0.co;2-w

PMID:8616762

Abstract

BACKGROUND

The purpose of this investigation was to determine if there are pathobiologic differences between BRCA1-related and BRCA2-related hereditary breast cancer (HBC) and non-HBC.

METHODS

On the basis of linkage to chromosomes 17q or 13q and/or the presence of ovarian and male breast cancer, HBC families were classified as either "BRCA1-related" (26 families, 90 breast cancer pathology cases) or "Other" (26 families, 85 cases), in which most BRCA2 cases were likely to reside. Cases were compared with 187 predominantly non-HBC cases. Tumors were assessed for histologic type, grade, and ploidy and S-phase fraction by quantitative DNA flow cytometry. Clinical presentation and available follow-up data were obtained.

RESULTS

BRCA1-related and Other HBC patients each presented at lower stage (P = 0.003) and earlier age than non-HBC patients (mean, 42.8 years and 47.1 years vs. 62.9 years, P = 0.0001). Compared with non-HBC, invasive BRCA1-related HBC had a lower diploidy rate (13% vs. 35%; P = 0.002), lower mean aneuploid DNA index (1.53 vs. 1.73; P= 0.002), and strikingly higher proliferation rates (mitotic grade 3; odds ratio [OR]= 4.42; P= 0.001; aneuploid mean S-phase fraction 16.5% vs. 9.3%, P < 0.0001). Other HBC patients, including patients in two BRCA2- linked families, had more tubular-lobular group (TLG) carcinomas (OR = 2.56, P = 0.007). All trends were independent of age. A nonsignificant trend toward better crude survival in both HBC groups was age- and stage-dependent. Compared with Other HBC, BRCA1-related HBC patients had fewer recurrences (P = 0.013), a trend toward lower specific death rates, and fared no worse than breast cancer patients at large. Other HBC patients, despite neutral prognostic indicators, fared worse.

CONCLUSIONS

BRCA1-related HBCs are more frequently aneuploid and have higher tumor cell proliferation rates compared with Other HBC. Despite these adverse prognostic features, BRCA1-related HBC patients have paradoxically lower recurrence rates than Other HBC patients. The excess of TLG cancers in the "Other" HBC group may be associated with BRCA2 linkage.

摘要

背景

本研究的目的是确定BRCA1相关和BRCA2相关的遗传性乳腺癌（HBC）与非HBC之间是否存在病理生物学差异。

方法

基于与17号染色体或13号染色体的连锁关系和/或卵巢癌及男性乳腺癌的存在情况，HBC家系被分为“BRCA1相关”（26个家系，90例乳腺癌病理病例）或“其他”（26个家系，85例病例），其中大多数BRCA2病例可能包含在内。将这些病例与187例主要为非HBC的病例进行比较。通过定量DNA流式细胞术评估肿瘤的组织学类型、分级、倍性和S期分数。获取临床表现和可用的随访数据。

结果

BRCA1相关和其他HBC患者的就诊分期均低于非HBC患者（P = 0.003），且发病年龄更早（平均年龄分别为42.8岁和47.1岁，而非HBC患者为62.9岁，P = 0.0001）。与非HBC相比，侵袭性BRCA1相关HBC的二倍体率较低（13%对35%；P = 0.002），平均非整倍体DNA指数较低（1.53对1.73；P = 0.002），且增殖率显著更高（有丝分裂分级为3级；优势比[OR]= 4.42；P = 0.001；非整倍体平均S期分数为16.5%对9.3%，P < 0.0001）。其他HBC患者，包括两个与BRCA2连锁家系的患者，有更多的小管-小叶组（TLG）癌（OR = 2.56，P = 0.007）。所有趋势均与年龄无关。两个HBC组的粗生存率有改善的非显著趋势，且与年龄和分期有关。与其他HBC相比，BRCA1相关HBC患者的复发较少（P = 0.013），有特定死亡率较低的趋势，总体预后不比乳腺癌患者差。其他HBC患者尽管预后指标中性，但预后较差。