Stark A, Hulka B S, Joens S, Novotny D, Thor A D, Wold L E, Schell M J, Melton L J, Liu E T, Conway K
Department of Epidemiology, Lineberger Comprehensive Cancer Center, The University of North Carolina, Chapel Hill, NC 27599, USA.
J Clin Oncol. 2000 Jan;18(2):267-74. doi: 10.1200/JCO.2000.18.2.267.
The purpose of this study was to determine whether the presence of HER-2/neu gene amplification and/or overexpression in benign breast disease was associated with an increased risk of subsequent breast cancer.
We conducted a nested case-control study of a cohort of women who were diagnosed with benign breast disease at the Mayo Clinic and who were subsequently observed for the development of breast cancer. Patients who developed breast cancer formed the case group, and a matched sample from the remaining cohort served as controls. Benign tissue samples from 137 cases and 156 controls and malignant tissues from 99 cases provided DNA or tissue for evaluation of HER-2/neu amplification and protein overexpression.
Among the controls, seven benign tissues (4.5%) demonstrated low-level HER-2/neu amplification, whereas 13 benign (9.5%) and 18 malignant (18%) tissue specimens from cases exhibited amplification. HER-2/neu amplification in benign breast biopsies was associated with an increased risk of breast cancer (odds ratio ¿OR = 2.2; 95% confidence interval ¿CI, 0.9 to 5.8); this association approached statistical significance. The risks for breast cancer associated with benign breast histopathologic diagnoses were OR = 1.1 (95% CI, 0.6 to 1.9) for lesions exhibiting proliferation without atypia and OR = 1.5 (95% CI, 0.4 to 5.6) for the diagnosis of atypical ductal hyperplasia. For women having both HER-2/neu amplification and a proliferative histopathologic diagnosis (either typical or atypical), the risk of breast cancer was more than seven-fold (OR = 7.2; 95% CI, 0.9 to 60.8). Overexpression of the HER-2/neu protein product, defined as membrane staining in 10% or more of epithelial cells, was found in 30% of the breast tumors but was not detected in any of the benign breast tissues. Case patients who had HER-2/neu gene amplification in their malignant tumor were more likely to have had HER-2/neu amplification in their prior benign biopsy (P =.06, Fisher's exact test).
Women with benign breast biopsies demonstrating both HER-2/neu amplification and a proliferative histopathologic diagnosis may be at substantially increased risk for subsequent breast cancer.
本研究旨在确定良性乳腺疾病中HER-2/neu基因扩增和/或过表达的存在是否与后续患乳腺癌风险增加相关。
我们对在梅奥诊所被诊断为良性乳腺疾病且随后接受乳腺癌发生情况观察的一组女性进行了巢式病例对照研究。患乳腺癌的患者组成病例组，其余队列中匹配的样本作为对照组。来自137例病例和156例对照的良性组织样本以及99例病例的恶性组织样本提供了用于评估HER-2/neu扩增和蛋白过表达的DNA或组织。
在对照组中，7个良性组织（4.5%）显示低水平HER-2/neu扩增，而病例组中有13个良性组织（9.5%）和18个恶性组织（18%）标本出现扩增。良性乳腺活检中HER-2/neu扩增与患乳腺癌风险增加相关（优势比[OR]=2.2；95%置信区间[CI]，0.9至5.8）；这种关联接近统计学显著性。与良性乳腺组织病理诊断相关的患乳腺癌风险，对于显示无异型性增生的病变，OR=1.1（95%CI，0.6至1.9），对于非典型导管增生的诊断，OR=1.5（95%CI，0.4至5.6）。对于同时具有HER-2/neu扩增和增生性组织病理诊断（典型或非典型）的女性，患乳腺癌的风险超过7倍（OR=7.2；95%CI，0.9至60.8）。HER-2/neu蛋白产物的过表达定义为10%或更多上皮细胞出现膜染色，在30%的乳腺肿瘤中发现，但在任何良性乳腺组织中均未检测到。恶性肿瘤中有HER-2/neu基因扩增的病例患者，其先前良性活检中更可能有HER-2/neu扩增（P=0.06，Fisher精确检验）。
良性乳腺活检显示HER-2/neu扩增且具有增生性组织病理诊断的女性，后续患乳腺癌的风险可能大幅增加。
