Oncology Frontier: Could you talk about how to reduce the long-term effects of chemotherapy in young women with early-stage breast cancer?

　　《肿瘤瞭望》：如何降低化疗对年轻的早期乳腺癌患者的长期影响？

　　Dr Rugo: Long-term toxicity is a big issue. We treat women， the majority of whom are going to be cured of their breast cancer， and then we want them to go back and lead a healthy life as if we never gave them all that nasty chemotherapy. But some of the women do have significant toxicities. Those include the toxicities we think about with chemotherapy like neuropathy or cardiac toxicity (which is quite uncommon) or the fatigue， which gradually resolves. But one of the toxicities that can really be irreparable and create significant damage for young women is permanent ovarian suppression and infertility. For these young women who develop particularly hormone receptor negative cancers， it is a really big deal. Hormone receptor positive disease is complicated by the need for adjuvant hormone therapy as well， not that it is any less of a big deal. At a recent ASCO meeting， we saw an interesting trial called the POEMS study that looked at the addition of a GnRH agonist to standard chemotherapy for hormone receptor negative invasive breast cancer in premenopausal women and it showed that ovarian preservation was higher in terms of having menses a year out in women who had ovarian suppression versus those who didn’t. Also more of those women were able to have successful pregnancies. Although the trial was much smaller than it originally intended to be (which is an unfortunate problem with trials where people don’t want to be at the wrong end of the stick and even when we don’t know what the right end is anyway)， we still saw some very intriguing results and I think that has become a new standard for young women with ER-negative disease. How we translate this into patients with ER-positive disease is a big question. At the same time， we saw the SOFT and TEXT data maybe suggesting that ovarian suppression would be better. SOFT and TEXT are intriguing because there was an Austrian breast cancer study group trial that showed that if you didn’t receive chemotherapy but you received ovarian suppression， then either tamoxifen or exemestane were fine. But there were more overweight women and in those women it appeared that ovarian suppression didn’t work as well. All of this ties into how we deal with fertility and toxicity in young women. Recently I have been thinking that in young women where I am using ovarian suppression， I might start with tamoxifen and if they tolerate it well， switch over to an aromatase inhibitor after some period of time because the combination of ovarian suppression and aromatase inhibitor can be quite difficult to manage. Even though it wasn’t shown very well in SOFT and TEXT， it has been everybody’s experience in practice.

　　Rugo教授：长期毒性是一个大问题。我们所治疗的大部分患者的乳腺癌疾病都被治愈了，我们希望她们能够像从前一样有健康的人生，就像她们从未进行过那些痛苦的化疗一样。但是其中一些患者的确出现了明显的毒副作用。其中包括化疗导致的毒副作用，如神经毒性、心脏毒性（都不常见）或乏力，而乏力可以逐步缓解。但其中有一种毒副作用的确是不可逆的，会对年轻女性导致严重的伤害，就是永久的卵巢抑制和不育。对于那些比较特殊的、激素受体阴性的年轻女性，这确实是一个大问题。

　　激素受体阳性乳腺癌也是复杂的，需要辅助激素治疗，问题也并不小。在最近的ASCO会议中，我们看到一个有意思的研究，POEMS试验，它观察了对于绝经前激素受体阴性的侵袭性乳腺癌患者，在标准化疗方案基础上加用促性腺激素释放激素激动剂的作用。结果显示，相对于未使用此方法的患者而言，这个方法能更好地保护闭经1年、有卵巢抑制的女性的卵巢功能，成功怀孕的比例更高。虽然这个试验规模较原本计划要小得多（这对于一个试验来说是很不幸的——受试者不愿进入效果不好的试验组，即便那时候我们也不知道哪个组的效果好），但我们仍然看到了一些令人感兴趣的结果。我认为这个方案已经成为ER受体阴性患者的标准方案。如何将此方法应用于ER受体阳性的患者上目前是一个大课题。

　　与此同时，我们看到SOFT试验和TEXT试验的数据提示卵巢抑制可能更好。SOFT和TEXT的试验结果令人感兴趣，因为曾有一个奥地利乳腺癌研究组的试验显示如果患者没有接受化疗而接受了卵巢抑制，那么无论他莫昔芬还是依西美坦都可选用。但是也有很多超重患者，在这类人群中卵巢抑制的效果也不佳。所有这些都集中到如何处理年轻女性生育与毒副作用这个问题上来。最近我一直在思考，对于应用卵巢抑制治疗的女性，我开始可能会使用他莫昔芬，如果患者耐受良好，在应用一定时间后换用芳香化酶抑制剂，因为卵巢抑制和芳香化酶抑制剂的联合应用会很难管理。尽管在SOFT试验和TEXT试验中这种方案并非最佳，它还是每个人在临床都会应用的方法。