Maksimenko Jelena, Irmejs Arvids, Nakazawa-Miklasevica Miki, Melbarde-Gorkusa Inga, Trofimovics Genadijs, Gardovskis Janis, Miklasevics Edvins
Oncology Institute, Riga Stradins University, Riga, LV-1012, Latvia.
Oncol Lett. 2014 Jan;7(1):278-284. doi: 10.3892/ol.2013.1684. Epub 2013 Nov 14.
Triple-negative breast cancer (TNBC) is proposed to be an immunohistochemical surrogate of the basal-like breast cancer subtype. In spite of the relative chemosensitivity of this cancer subtype, it is characterized by aggressive clinical behavior; therefore, a further subclassification of TNBC is required to develop new targeted treatment. In previous studies, a strong correlation between mutation-associated tumors and TNBC has been identified. The aim of the present study was to investigate the prognostic significance of carrying two germline founder mutations (4153delA and 5382insC) in patients with TNBC in the Latvian population. A total of 78 consecutive mutation-negative and 38 mutation-positive invasive TNBC patients in stage I-IV with no history of ovarian or other primary advanced cancers, who had undergone definitive surgery and genetic testing between 2005 and 2011, were deemed eligible for study. Relapse rates and breast cancer-specific survival (BCS) outcomes were compared between mutation carriers and non-carriers. Univariate and multivariate analyses Cox proportional-hazards models were used to compute independent predictors of survival outcomes. No statistically significant differences were identified in relation to tumor size, T stage, stage, Ki-67 status and tumor differentiation grade between the two groups. The median follow-up period was 36 months for mutation carriers and 41 months for non-carriers. A higher proportion of mutation non-carriers experienced distant recurrence compared with that of mutation carriers (P<0.03). mutation carriers had a significantly higher BCS than non-carriers (94.9 vs. 76.9%; P<0.02). In the univariate analyses, -positive status was associated with decreased risk of distant recurrence (HR, 0.228; 95% Cl, 0.052-0.997; P<0.049) and breast cancer-specific mortality (HR, 0.209; 95% Cl, 0.048-0.902; P<0.036). In the multivariate analysis Cox proportional-hazards model, -positive status was an independent favorable prognostic factor for distant recurrence-free survival (HR, 3.301; 95% Cl, 1.102-9.893; P<0.033). In conclusion, results of the present study demonstrate that positive founder mutation status in TNBC, with no evidence of ovarian or other cancer type in advanced stage, significantly improves prognosis.
三阴性乳腺癌(TNBC)被认为是基底样乳腺癌亚型的免疫组化替代物。尽管该癌症亚型具有相对的化疗敏感性,但其临床行为具有侵袭性;因此,需要对TNBC进行进一步的亚分类以开发新的靶向治疗方法。在先前的研究中,已确定突变相关肿瘤与TNBC之间存在密切关联。本研究的目的是调查在拉脱维亚人群中携带两种种系始祖突变(4153delA和5382insC)的TNBC患者的预后意义。2005年至2011年间,共有78例连续且无突变的I-IV期浸润性TNBC患者以及38例有突变的患者,这些患者均无卵巢或其他原发性晚期癌症病史,且均接受了根治性手术和基因检测,被认为符合研究条件。比较了突变携带者和非携带者的复发率和乳腺癌特异性生存(BCS)结果。使用单变量和多变量分析Cox比例风险模型来计算生存结果的独立预测因子。两组在肿瘤大小、T分期、分期、Ki-67状态和肿瘤分化等级方面未发现统计学上的显著差异。突变携带者的中位随访期为36个月,非携带者为41个月。与突变携带者相比,非突变携带者发生远处复发的比例更高(P<0.03)。突变携带者的BCS明显高于非携带者(94.9%对76.9%;P<0.02)。在单变量分析中,阳性状态与远处复发风险降低相关(HR,0.228;95%CI,0.052-0.997;P<0.049)以及乳腺癌特异性死亡率降低相关(HR,0.209;95%CI,0.048-0.902;P<0.036)。在多变量分析Cox比例风险模型中,阳性状态是远处无复发生存的独立有利预后因素(HR,3.301;95%CI,1.102-9.893;P<0.033)。总之,本研究结果表明,在TNBC中,无晚期卵巢或其他癌症类型证据的始祖突变阳性状态可显著改善预后。