编者按：自第六届晚期乳腺癌国际共识会议（ABC6）以来，新型治疗药物不断出现，晚期乳腺癌治疗领域发生了很大的变化。在第七届晚期乳腺癌国际共识会议（ABC7）上，肿瘤瞭望特邀采访了丹娜法伯癌症研究所Eric P.Winer教授，请他为我们分享乳腺癌领域的治疗变化。

 

Eric P.Winer教授：转移性乳腺癌的治疗比早期乳腺癌更具挑战性，有些人可能在多年内一直受其困扰，其中大多数人的转移性乳腺癌最终会威胁生命。遗憾的是，患有转移性乳腺癌的妇女中只有极少数能够实现治愈。这是一个首要挑战。尽管多年来我们的治疗有明显进步，但仍然需要更优质、更有效、患者容忍度更高的治疗方法。一些治疗方法患者耐受性好，而另一些则具有更明显的副作用。因此，通过改进治疗方法来改善治疗效果是目前的重点。

 

另外，我觉得需要强调的另一个点是，无论男性还是女性转移性乳腺癌患者都需要与治疗团队建立紧密信任关系，其中包括肿瘤学家、护士和其他参与患者护理的专业人员。同时，这也能够让医生努力了解每位患者的独特需求。我坚信，通过与患者持续配合、建立良好的医患关系，能够提升我们的工作质量，从而确保患者能获得最佳的个性化医疗护理。

 

Oncology Frontier:What do you think are the biggest challenges facing breast cancer?How do you think these challenges will affect our treatment and management of breast cancer?

 

I think everyone realizes that this is about individuals who had metastatic breast cancer.So having metastatic breast cancer is a bigger challenge than having early stage breast cancer，because it’s an illness that people can live with at times for many，many years.But the vast majority of people ultimately will have metastatic breast cancer threaten their lives.There are still very few women who are cured if they have metastatic breast cancer.So right off，that’s a challenge.I think that our treatments have clearly improved over the years.But we still need better treatments.We need treatments that are more effective.And we need treatments that are better tolerated.Some of our treatments are quite well tolerated.Others tend to have far more in the way of side effects.And so it’s really about optimizing the care we provide to people by both improving on our therapy.

 

And then I’ll comment on one last issue，which is that I think that for the woman and occasionally man with metastatic breast cancer，that it’s really important to have a close relationship，a trusting relationship，with the team that’s taking care of you，with the oncologist，with the nurses，and others that work with that person.And at the same time，I think it’s a challenge for the clinicians to make sure they understand what the needs are of that patient.And I do believe that we can，as a field，do a better job by continuing to work with our patients and really partner with our patients so that we provide them with not only the best medical care，but the best medical care that’s right for them.

 

Eric P.Winer教授：我们很难预测ABC共识在未来的发展方向。但能够确信的是，对于HER2阳性和HER2低表达的乳腺癌患者来说，诸如trastuzumab deruxtecan（T-DXd）等突破性药物将带来重大变革。这些发现在ABC 6共识中是没有的，特别是关于HER2低表达乳腺癌的管理。此外，还有其他诸如capivasertib等新型AKT抑制剂。目前有研究正在探索三阴性乳腺癌的新疗法。类似Elacestrant这样的药物在携带雌激素受体突变的ER阳性乳腺癌患者中也显示出治疗潜力。在短短两年内，治疗方法的涌现让人对未来充满乐观。在我看来，每一年都有新的进展，变革的轨迹不断加速。这就像是一步步登上楼梯，每一年都让我们迈上更高的一层楼。最终目标是达到顶峰，希望在将来，不再有人会因乳腺癌而失去生命。

 

Oncology Frontier:There have been many new developments in advanced breast cancer since ABC6.How do you think the diagnosis and treatment of different molecular types of breast cancer(HR+，HER2+，TNBC)will change after the ABC7?

 

Oh，it’s a little hard to know how things will change in terms of our consensus statements.Clearly，drugs like trastuzumab deruxtecan，which，of course，was a major advance，particularly for patients with HER2-positive and HER2-low breast cancer，will be something that is a change because those were findings that weren’t available for ABC 6，certainly related to HER2-low breast cancer.But there are other drugs as well.We have new AKT inhibitors like capivasertib.We are in the course of looking at new therapies in triple-negative breast cancer.There are the drugs that seem to be effective in patients with ER-positive breast cancer who have estrogen receptor mutations，so drugs like elacestrant.So I think there have been a number of changes.And the fact that in just two short years we have all these new therapies is a reason to be really optimistic about the future，because from my perspective，every single year we keep having more and more，and the change from one year to the next keeps getting bigger.It’s as if we’re climbing up a set of stairs，and each year we go up a bigger and bigger stair.And ultimately we’ll be at the top，and hopefully that top will mean that no man or，in general，women，will have to lose their life from breast cancer.

 

Eric P.Winer教授：我们目前正在进行分子亚型的重新划分，特别是明确对肿瘤进行基因测序或肿瘤剖析的最佳时机。在乳腺癌中这类信息在越来越多的情况下能够提供有价值的见解。然而，我认为并不需要每次进行治疗变更时都重新评估肿瘤的分子特征。正如今天早些时候由Dr.Turner提到的，如果考虑进行血液活检，特别是检测循环肿瘤DNA，对于ER阳性乳腺癌患者而言，最佳时机可能是当患者在使用CDK4/6抑制剂后疾病进展时。我认为在评估肿瘤和个体的基因组方面，关键是在患者对治疗出现反应时进行这些测试，而不是在癌症治疗中出现恶化的时候。评估肿瘤的基因组学也是我们仍在研究的东西，像BRCA1和BRCA2基因突变等因素在治疗决策中将继续发挥重要作用，这使得基因组评估在未来愈发举足轻重。

 

Oncology Frontier:ADC drugs offer new treatment options for low HER2 expression.Optimizing the molecular typing of breast cancer also became a hot topic of discussion at this meeting.What do you think about this problem of molecular typing?

 

I think that we’re still trying to sort out just where we do molecular subtyping.And in particular where we do genetic sequencing or tumor profiling on the tumor itself.In breast cancer there are an increasing number of situations where this kind of information can be useful.But by no means do I think that every single time we make a treatment change that we have to reassess the molecular profile of the tumor.I think as Dr.Turner said earlier today，that if one is going to obtain，for example，a blood biopsy，looking at circulating tumor DNA，that probably the optimal time to do that，at least in a patient with ER-positive breast cancer，is when that patient has developed disease progression on a CDK4/6 inhibitor.And I think it is important when we’re looking for changes in the tumor to make sure that we get these tests not when someone is responding to therapy，but when their cancer is getting worse on therapy.So this is something we’re still working out，clearly evaluating the genomics of the tumor and，for that matter，of the person.Because，for example，BRCA1 and 2 mutations play a role in treatment decisions as well，germline mutations.These genomic assessments are going to become more and more important over time.

 

 

Eric P.Winer

2022-2023年美国临床肿瘤学会（ASCO）主席

哈佛大学医学院内科学教授

丹娜法伯癌症研究所首席临床策略官、医疗事务高级副院长

Susan F.Smith女性癌症乳腺肿瘤中心主任

乳腺癌研究Thompson资深研究者