Oncology Frontier: Can you explain how triple-negative breast cancer patients benefit more from platinum chemotherapy?

　　《肿瘤瞭望》：三阴性乳腺癌患者铂类化疗获益更多？

　　Dr Telli: This has been a big question for the past five or more years looking at the role of platinum drugs for patients with triple-negative breast cancer. Platinum drugs have been around a long time. In the US， cisplatin was first approved in the 1970s， so we learned these drugs were active in advanced breast cancer a long time ago. But over time， platinum fell out of favor in terms of the standard drugs we use to treat early and advanced stage patients with triple-negative tumors. There has been renewed interest though in looking at platinum in both of these settings based on the idea that triple-negative tumors (as well as those tumors arising inBRCAmutation carriers) may be more sensitive to platinum drugs than some other drugs like taxanes. There have been a number of studies reported in the last few years looking at platinums as add-ons to standard anthracycline and taxane drugs for patients with triple-negative breast cancer that are newly diagnosed. What we are seeing is that some of these drugs can increase the pathologic complete response rates in the neoadjuvant setting but whether this will ultimately translate into a long-term benefit is unclear. One thing that is clear is that certain patients benefit more， particularly those with BRCA mutations， and potentially other patients who don’t have BRCAmutations， but have a BRCA-like breast cancer. New tests to understand who those patients are are important. We also saw at the San Antonio meeting the results of a very important phase III study for patients with newly recurrent triple-negative breast cancer. This was a head-to-head study randomized between carboplatin and docetaxel.  In all patients， there was no significant difference in terms of response rate or progression free survival between the two drugs， but in the BRCAmutation carriers， response rates and progression free survival were substantially better for patients who received carboplatin. I think these data are really important. We haven’t had specifically good randomized trials for patients with advanced triple-negative breast cancer and I think these data show us that platinum is a good option for patients with a first recurrence of triple-negative breast cancer. It did appear in that study to also be less toxic than docetaxel. Certainly for patients with BRCAmutations， I would think this is a preferred option compared to docetaxel based on the results of this study. It has been a good year for triple-negative breast cancer.

　　Telli博士：在过去五年或更长时间里，“铂类药物对三阴性乳腺癌的作用”是个重要的研究话题。铂类药物已存在了很长时间。美国在20世纪70年代批准了顺铂，很久以前铂类药物是晚期乳腺癌治疗的热门药物，但随着时间的推移，铂类药物渐渐失宠，目前已经不是早晚期三阴性乳腺癌的标准用药。

　　但是，最新研究发现，与某些化疗药物（如紫杉烷类）相比，早晚期三阴性乳腺癌（包括BRCA突变肿瘤）对铂类药物更加敏感，目前铂类药物再次引发了研究者的兴趣。过去几年中，一些研究在蒽环类和紫杉类药物标准化疗方案中添加铂类药物治疗新诊断三阴性乳腺癌，结果显示新辅助化疗中加入某些铂类药物可提高病理完全缓解率（pCR），但还不清楚这种疗法的长期获益。可以确定的一点是，有一部分患者获益更多（尤其是那些BRCA突变患者，和没有BRCA突变的BRCA样乳腺癌）。找出铂类化疗获益最多的三阴性乳腺癌患者很重要。在2014年圣安东尼奥乳腺癌研讨会上，一项重要的随机、III期、头对头研究（TNT研究）显示，分别以卡铂和多西他赛治疗新复发三阴性乳腺癌，全部患者的分析结果显示，两种药物的应答率或无进展生存期（PFS）没有显著差异，但在BRCA突变患者中，卡铂治疗组的反应率和PFS大大改善，而且卡铂治疗毒性较小。目前还没有专门研究晚期三阴性乳腺癌铂类化疗的良好随机试验，但是以上研究数据显示，对于首次复发三阴性乳腺癌，铂类药物是一种很好的选择， BRCA突变患者优先考虑铂类化疗而非多西他赛。2014年是三阴性乳腺癌研究丰收的一年。