Gschwantler-Kaulich Daphne, Tan Yen Y, Fuchs Eva-Maria, Hudelist Gernot, Köstler Wolfgang J, Reiner Angelika, Leser Carmen, Salama Mohamed, Attems Johannes, Deutschmann Christine, Zielinski Christoph C, Singer Christian F
Department of Obstetrics and Gynecology, Cancer Comprehensive Center, Medical University of Vienna, Vienna, Austria.
QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
PLoS One. 2017 Mar 2;12(3):e0172911. doi: 10.1371/journal.pone.0172911. eCollection 2017.
Even though trastuzumab is an effective therapy in early stage Her-2+ breast cancer, 40-50% of advanced Her-2+ breast cancer patients develop trastuzumab resistance. A potential resistance mechanism is aberrant downstream signal transmission due to loss of phosphatase and tensin homologue (PTEN). This study investigated the relationship between the expression of PTEN and trastuzumab response in Her-2 overexpressing metastatic breast cancer patients.
Between 2000 and 2007, 164 patients with Her-2+ metastatic breast cancer received trastuzumab-based therapy in our institution. We analyzed PTEN status by immunohistochemistry of 115 available tumor tissues and analyzed associations with other histopathological parameters, response rate, progression free survival (PFS) and overall survival (OS) with a median follow-up of 60 months.
Eighty patients were PTEN positive (69.6%) and 35 patients PTEN negative (30.4%). We found a significant association of the expression of PTEN and p53 (p = 0.041), while there was no association with grading, hormone receptor status, IGFR or MIB. We found significantly more cases with progressive disease under trastuzumab-based therapy in patients with PTEN positive breast cancers (p = 0.018), while there was no significant correlation with PFS or OS.
In Her-2-positive metastatic breast cancers, PTEN positivity was significantly associated with progressive disease, but not with PFS or OS.
尽管曲妥珠单抗是早期Her-2阳性乳腺癌的有效治疗方法，但40%-50%的晚期Her-2阳性乳腺癌患者会出现曲妥珠单抗耐药。一种潜在的耐药机制是由于磷酸酶和张力蛋白同源物（PTEN）缺失导致的异常下游信号传导。本研究调查了PTEN表达与Her-2过表达转移性乳腺癌患者曲妥珠单抗反应之间的关系。
2000年至2007年期间，164例Her-2阳性转移性乳腺癌患者在我们机构接受了基于曲妥珠单抗的治疗。我们通过对115份可用肿瘤组织进行免疫组织化学分析PTEN状态，并分析其与其他组织病理学参数、反应率、无进展生存期（PFS）和总生存期（OS）的相关性，中位随访时间为60个月。
80例患者PTEN阳性（69.6%），35例患者PTEN阴性（30.4%）。我们发现PTEN表达与p53之间存在显著相关性（p = 0.041），而与分级、激素受体状态、IGFR或MIB无相关性。我们发现PTEN阳性乳腺癌患者在基于曲妥珠单抗的治疗下疾病进展的病例明显更多（p = 0.018），而与PFS或OS无显著相关性。
在Her-2阳性转移性乳腺癌中，PTEN阳性与疾病进展显著相关，但与PFS或OS无关。
