Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Cancer. 2012 Feb 15;118(4):908-13. doi: 10.1002/cncr.26377. Epub 2011 Jul 14.
Germline TP53 mutations predispose to early onset breast cancer in women and are associated with Li-Fraumeni syndrome. Published data on the pathological characteristics of breast cancer among women with TP53 mutations is limited.
We retrospectively reviewed the clinical records of women who underwent genetic testing for suspected germline TP53 mutations and who were diagnosed with breast cancer between 2000 and 2011. The pathological characteristics of the breast tumors from patients testing positive for a mutation (cases) were compared with those testing negative (controls).
Patients who tested positive for germlineTP53 mutations (n = 30) were compared with controls (n = 79). Human epidermal growth factor receptor 2 (HER2) amplification and/or overexpression was found in 67% of the tumors from the cases, compared with 25% for the controls (P = .0001). Among patients with a mutation, 70% had estrogen receptor- and/or progesterone receptor-positive tumors, compared with 68% in the control group (P = .87). After adjusting for age at breast cancer diagnosis, having a HER2-positive tumor increased the odds of testing positive for a germline TP53 mutation (odds ratio, 6.9; 95% confidence interval, 2.6-18.2). For each yearly increment in age at breast cancer diagnosis, there was decreased likelihood of having a TP53 mutation of 5% (odds ratio, 0.95; 95% confidence interval0.91-0.99).
This study suggests an association between germline TP53 mutations and early onset HER2-positive breast cancer. If confirmed in a larger cohort, these results could guide genetic testing strategies, lead to chemoprevention trials incorporating HER2-targeted therapies, and elucidate some of the molecular pathways involved in breast cancer.
胚系 TP53 突变使女性易患早发性乳腺癌，并与 Li-Fraumeni 综合征相关。关于携带 TP53 突变的女性乳腺癌的病理特征的已发表数据有限。
我们回顾性地分析了 2000 年至 2011 年间接受疑似胚系 TP53 突变基因检测且诊断为乳腺癌的女性的临床记录。对突变阳性（病例）患者和突变阴性（对照）患者的乳腺肿瘤的病理特征进行了比较。
共比较了 30 例突变阳性患者和 79 例对照患者。病例组中有 67%的肿瘤存在人表皮生长因子受体 2（HER2）扩增和/或过表达，而对照组中仅有 25%（P =.0001）。在突变患者中，有 70%的肿瘤雌激素受体和/或孕激素受体阳性，而对照组中这一比例为 68%（P =.87）。在校正乳腺癌诊断年龄后，HER2 阳性肿瘤患者检测到胚系 TP53 突变的可能性增加了 6.9 倍（比值比，6.9；95%置信区间，2.6-18.2）。乳腺癌诊断年龄每增加 1 岁，TP53 突变的可能性就会降低 5%（比值比，0.95；95%置信区间 0.91-0.99）。
本研究提示胚系 TP53 突变与早发性 HER2 阳性乳腺癌之间存在关联。如果在更大的队列中得到证实，这些结果可以指导基因检测策略，开展包含 HER2 靶向治疗的化学预防试验，并阐明乳腺癌涉及的一些分子途径。
