《肿瘤瞭望》：对于HR阳性晚期乳腺癌，应怎样选择内分泌治疗方案？哪些患者可以首选内分泌治疗替代化疗？

　　William J. Gradishar教授：对于HR+MBC患者，我们往往倾向于应用内分泌治疗，并且我们试着将内分泌治疗的时间尽可能地延长。我们不将内分泌治疗作为首选一般是考虑患者肿瘤病灶较大、疾病进展快速，以及患者相关症状需尽快缓解等情况，即所谓内脏危像时，可能更适合优先应用化疗。但是仍然有很大一部分HR+MBC患者起始应用内分泌治疗，并且我们有很多不同的内分泌治疗方案可供选择。对于绝经后的女性来说，我们可以应用芳香化酶抑制剂(AI)，我们也可以选择他莫昔芬(TAM)。最近，陆续出现了内分泌治疗领域的多种新药，例如CD4/6抑制剂，还有mTOR抑制剂，如依维莫司。但是哪种药物作为一线治疗仍然存在争议。我认为现有数据提示，在绝经后的女性中将芳香化酶抑制剂(AI)与CD4/6抑制剂联用可能会使患者最大程度的获益。但我认为重要的是，如果患者不需要化疗，还可以考虑选择其它多种不同的内分泌治疗方案。如果患者在接受内分泌治疗时出现疾病进展，我们一般会考虑将更换另一种内分泌治疗方案。只有在患者肿瘤负荷加重或者疾病快速进展时，才建议变更为化疗。反之如果之前的内分泌治疗有效，应优先考虑更换为另一种内分泌治疗药物，直到用尽所有方案时才不得不换用用化疗。

　　《肿瘤瞭望》：对于HR+阳性早期乳腺癌患者来说，芳香化酶抑制剂联合戈舍瑞林vs他莫昔芬，您选择哪个内分泌治疗发难？或者这两种方案可以应用于哪些类型的患者？

　　William J. Gradishar教授：对于30-40岁的早期乳腺癌患者来说，我们可以对绝经前患者我们可以应用他莫昔芬(TAM)，对绝经后女性则应用芳香化酶抑制剂(AI)。最近有新的研究证据提示，如果患者抑制卵巢功能或进行了卵巢切除（卵巢去势），应用内分泌治疗，患者可能获益更多。因此，在非常年轻的患者中我们可以考虑卵巢去势，应用戈舍瑞林之类的药物或者进行卵巢切除术。所以，如果患者年龄小于35岁，即便她们接受了化疗，但她们的疾病风险更高、肿瘤更大且淋巴结阳性率更高，对于这些非常年轻的患者在完成化疗应该考虑卵巢去势，比方说应用戈舍瑞林，完成后再应用他莫昔芬(TAM)或芳香化酶抑制剂(AI)。如果患者年龄大于35岁，我们往往很少抑制患者的卵巢功能，因为从SOFT试验及TEXT试验的结果看，似乎非常年轻的患者从卵巢去势中中获益更多。

　　《肿瘤瞭望》：对于HR阳性乳腺癌患者来说，哪些患者可以从新辅助内分泌治疗中获益？新辅助内分泌治疗与化疗疗效有何差异？新辅助内分泌治疗的方案制定是否与辅助内分泌治疗相同？

　　William J. Gradishar教授：对内分泌治疗药物非常敏感的患者，我们会首先考虑使用新辅助内分泌治疗；对于绝经后、年龄比较大的患者，或者那些不适合化疗较年轻的患者，或当患者拒绝接受化疗的时，我们会考虑应用内分泌治疗。对于那些非常年轻的患者，我们通常会考虑进行卵巢抑制，然后应用他莫昔芬(TAM)或芳香化酶抑制剂(AI)。内分泌治疗持续时间也很重要，通常治疗时间需呀延长，仅仅3-4个月的时间就能观察到疗效。另外，我们会考虑患者是哪种类型的HR+乳腺癌。那些分期较低或者Luminal A型患者尽管采用新辅助化疗可能更易获得pCR或者应用了新辅助内分泌治疗未获得pCR，但是两种方案为患者带来的整体获益基本相当。所以，我们目前还无法完全确认那些对内分泌治疗非常敏感的HR阳性低分期的乳腺癌患者能否从化疗中显著获益。总之，选择合适的患者应用合适的治疗方案是非常重要的。

访谈原文

　　Oncology Frontier: What is the endocrine therapy strategy for ER positive advanced breast cancer? Prefer chemotherapy or endocrine therapy as the first choice?

　　Professor William J. Gradishar: Patients with metastatic diseases that have documented hormone receptor positive breast cancer， we always preferentially use anti-hormonal therapy or endocrinal therapy and we try to continue this for as long as possible. The circumstances where we may not choose endocrine therapy are largely based on the bulk of the disease， the pace of the disease， and how symptomatic the patient is as a result to where the disease is located， so patients experiencing what we refer to as a visceral crisis is maybe more appropriate for chemotherapy， but the vast majority of patients with metastatic hormone receptor positive disease could probably start with anti-hormone therapy and we have a number of different options， obviously post-menopause women we can use eromatase inhibitors， we also have tamoxifen for vestren and more recently we have drugs that we can add to anti-hormonal therapy like CD46 inhibitors， drugs like mTOR inhibitors that include evalines， which drug goes first is often debatable， I think we have now data that suggest that combining certainly in the post-menopausal women eromatase inhibitor + CD46 inhibitor may confer the greatest benefit， but I think the key point is that if a patient doesn’t require chemotherapy， any other number of different options of anti-hormone therapy would be considered， if the patient develop disease progression on an anti-hormone therapy then we will typically consider switching to an alternative anti-hormone therapy at that point and the only circumstance where that may not be recommended is if the patient have significant disease burden or the disease is rapidly progressing that maybe a reason to switch to chemotherapy， but if the disease had responded to prior anti-hormone therapy， and you have other options that are anti-hormone that could be considered， we will always preferentially go from one anti-hormone therapy to another until you exhaust at which point you will have to go to chemotherapy.

　　Oncology Frontier: For hormone receptor positive early stage breast cancer patients， AI plus goserelin vs tamoxifen， which do you， prefer to choose? Or， these two kinds of treatment are applicable to what kind of patient.

　　Professor William J. Gradishar: Patients with early stage disease， again we have options that include tamoxifen which has been available for 30 or 40 years， in post menopause women we have eromatase inhibitors， and more recently we have supportive data that suggest that if you suppress or ablate the ovaries， and then add an additional anti-hormone therapy， it may provide even additional benefit， so where we will consider using ovarian suppression， drugs like goserelin or doing a oophorectomy would be in a very youngest patient， so if somebody develop breast cancer under the age of 35， they have higher risk disease， bigger tumor， positive nodes， although they may get chemotherapy， if they continue demonstrating after the completion of chemotherapy and there are very young， we would consider suppressing their ovaries and that can be done with a goserelin and once that’s accomplished， you could add tamoximen or neuromatacin inhibitor， if the patient is older that 35 we are less likely to be enthusiastic about suppressing the ovaries because from the SOFT and TEXT trials， the benefit seemed to be greatest in the very youngest patients.

　　Oncology Frontier: For hormone receptor positive advanced breast cancer patients， what kinds of people would be benefit from the neoadjuvant endocrine therapy? How about the clinical effect of neoadjuvant endocrine therapy compared to neoadjuvant chemotherapy? The treatment principle such as drug selection order， time， and dose are the same as adjuvant endocrine therapy?

　　Professor William J. Gradishar: The use of neodjuvant endocrine therapy can be considered， we usually consider it obviously number one in patients with strongly hormone-sensitive tumors， and number 2 usually in postmenopausal women， older women， and in those even younger women where chemotherapy is either not a good idea， or they refuse or they are not interested， in those individuals we could consider anti-hormone therapy. In the very youngest patients we usually would consider suppressing their ovaries and then adding either tamoxifen or neuromatacin inhibitors and the duration of the therapy is important as well， it has to be extended as often， not just 3 or 4 months， to see the real effect. The other consideration is what kind of hormone receptor positive disease is it， so patients that have lower grade， so more luminal A type breast cancers are the most likely to benefit， we’ve also learned that if you compare chemotherapy to anti-hormone therapy， even though you may be more likely to achieve a pathologic complete remission with chemotherapy， even in those who get anti-hormone therapy and do not achieve a complete pathological response， the overall outcome looks very much the same， so it’s not entirely clear that chemotherapy offers a significant benefit in that very selected population with very sensitive hormone receptor positive with low grade breast cancers， so again， selection is important but it can’t be considered.