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国际视野丨Steven Narod教授:双侧乳房切除术与乳腺癌死亡率——临床指南的再思考

作者:肿瘤瞭望   日期:2024/8/29 12:18:49  浏览量:2817

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“肿瘤瞭望”特邀Steven Narod教授分享他的最新研究成果,以期为乳腺癌的预防、诊断和治疗提供更多的思考和指导。

编者按:近年来,双侧乳房切除术作为一种预防对侧乳腺癌的手术方式,受到了一定程度的关注和应用。然而,关于双侧乳房切除术在预防乳腺癌死亡方面的实际效果仍存在争议。近日,多伦多大学达拉拉纳公共卫生学院Steven Narod教授在JAMA Oncology上发表了题为《Bilateral Mastectomy and Breast Cancer Mortality》的研究论文,“肿瘤瞭望”特邀Steven Narod教授分享他的最新研究成果,以期为乳腺癌的预防、诊断和治疗提供更多的思考和指导。
 
01
《肿瘤瞭望》:您的研究指出,尽管双侧乳房切除术显著降低了对侧乳腺癌的发生风险,但并未降低乳腺癌的死亡率。这是否意味着我们需要重新评估双侧乳房切除术的临床指南和患者的咨询过程?

Steven Narod教授:这一发现无疑对患者的选择产生了影响。目前,临床指南并不普遍推荐进行双侧乳房切除术,除非患者是BRCA1或BRCA2基因突变的携带者,这种情况下可能会考虑例外。目前,选择接受双侧乳房切除术的女性患者大多是基于她们自主的选择。医生很少主动推荐这种手术方式。医生和临床指南通常指出,对于患有对侧乳腺癌的患者,双侧乳房切除术并非必要选择。而我们的研究结果也支持当前的临床指南。因此,这项研究的结果并不会导致临床指南的更改,但我认为我们的研究会为医生和患者提供更多双侧乳房切除术的理论基础,以及潜在的风险和获益。
 
Oncology Frontier:Your study indicates that although bilateral mastectomy significantly reduces the risk of contralateral breast cancer,it does not reduce breast cancer mortality.Does this mean that we need to reassess the clinical guidelines and patient counseling process for bilateral mastectomy?
 
Dr.Steven Narod:Certainly I think it impacts on the patient’s choice.The current guidelines do not recommend bilateral mastectomy for patients,a possible exception is for BRCA1 and BRCA2 mutation carriers.Women now get a bilateral mastectomy do so at their own choice.It’s very rarely recommended by the doctor.In fact,the doctor and the guidelines suggest not to do the bilateral mastectomy,and I think our study confirms that that’s a reasonable guideline.So it won’t change the guideline,but I think it will give the doctors and the patients more information about what’s behind the rationale for doing it by that on this tech to me,and what are the expected risks and benefits.
 
02
《肿瘤瞭望》:在您的研究中,是否有特定的患者亚组,例如基于年龄、肿瘤特征或遗传因素,对于双侧乳房切除术的反应与总体人群有显著不同?

Steven Narod教授:在本研究中,我们综合考察了不同患者群体在接受双侧乳房切除术后的治疗效果。研究的长期生存分析结果显示,双侧乳房切除术对大多数患者的生存率并没有表现出显著差异。然而,值得注意的是,占所有乳腺癌15%的乳腺浸润性小叶癌(一种具有特定病理特征的乳腺癌类型)患者,在接受双侧乳房切除术后生存率有所提高。
 
对于最常见的乳腺癌类型,如导管癌,我们的研究并未发现接受双侧乳房切除术与常规治疗方法之间存在明显差异。此外,我们也对不同年龄和不同种族的患者进行了比较分析,结果表明,这些因素对于双侧乳房切除术的疗效并没有显著影响。因此,对于大多数患者而言,选择治疗方案时还需综合考虑个体差异、癌症特征以及患者的个人偏好。
 
Oncology Frontier:In your study,were there specific patient subgroups,such as based on age,tumor characteristics,or genetic factors that responded significantly differently to bilateral mastectomy compared to the overall population?
 
Dr.Steven Narod:Overall we didn’t see an overall effect for the bilateral mastectomy.There was one exception though,the 15 percent or so of women with lobular breast cancer,which is a certain feature,a certain kind of breast cancer,did appear to have a slight improvement in survival with bilateral mastectomy.But for the most common kind of cancer,like ductal cancer,there was no difference,and for age groups and for race there was no difference.
 
03
《肿瘤瞭望》:考虑到双侧乳房切除术可能带来的心理和生理影响,您的研究是否评估了这种手术对患者长期生活质量的影响?

Steven Narod教授:本研究并未直接涉及双侧乳房切除术对患者长期生活质量影响的问题。我们的研究是一项基于美国国家癌症研究监测、流行病学和结果(SEER)数据库收集的数据进行的长期生存分析。然而,我的其他研究证实,选择进行双侧乳房切除术的患者大约占8%,或在非常年轻的患者群体中达20%,报告了术后生活质量有所提升。
 
我认为这是可以理解的。选择双侧乳房切除术的患者通常是出于对乳腺癌复发的担忧和焦虑。对这些患者而言,通过手术切除两侧乳房似乎意味着癌症不会再复发。我们对这些患者进行的访谈显示,他们对于能够进行双侧乳房切除术感到非常感激,对手术结果也感到非常满意。大多数患者都能获得良好的乳房重建效果,这不仅帮助他们重建了良好的身体形象,也恢复了身体的对称性,对他们的心理健康和生活质量有着积极的影响。
 
Oncology Frontier:Considering the potential psychological and physiological impacts of bilateral mastectomy,did your study assess the impact of this surgery on patients’long-term quality of life?
 
Dr.Steven Narod:Not in this study.This was a statistical study that we used data that was collected in the United States.However,my other research would confirm that those patients who choose to have the bilateral mastectomy,which is about 8 percent of all patients,or 20 percent of very young patients,who do have a bilateral mastectomy,do report an improved quality of life.And I think that makes sense because those who choose to have the bilateralistic technique usually do so because they’re unduly anxious or concerned about getting another breast cancer in the same breast and in the opposite breast.So for them,removing both breasts is reassuring that they won’t get another cancer.Our interviews with these patients have almost invariably shown that they’ve been very grateful for the opportunity to have the bilateral mastectomy and satisfied with the outcome,whether or not they had reconstructive surgery.Most of these patients will have their breasts best reconstructed,so it does give them a good body image and a sense of symmetry.
 
04
《肿瘤瞭望》:您的研究结果对于当前乳腺癌治疗策略有哪些启示,特别是关于对侧乳腺癌风险评估和预防措施?

Steven Narod教授:我认为我们的研究已经发现了一些关键的临床问题,同时也存在对乳腺癌本质的理论问题探讨,包括乳腺癌的起始时刻及其扩散机制。研究显示,对侧乳腺癌患者的死亡风险显著增加,从13%上升至30%。这表明,对侧乳腺癌是一个明显的预后不良因素。然而,预防对侧乳腺癌并没有降低患者的死亡风险。这一发现引导我得出结论:对侧乳腺癌可能并不具备真正的扩散特性,而是初始癌症的生物学特性的体现。
 
这篇关于对侧乳腺癌的研究论文,实际上是我们系列研究中的一个组成部分。这些研究都得出了一致的结论,我将这些成果总结在近期出版的一本新书里,书名为《公平的审判:乳腺癌的基础》。相信这本书一定会引起人们的广泛兴趣,因为其全面覆盖了乳腺癌的多个方面,包括其起源、传播方式,以及本文中提到的一些悖论和矛盾等,均在书中进行了更深入的探讨。
 
 
这本书提到的主要悖论是,如果对侧乳腺癌增加了死亡风险,理论上预防应该能够降低这一风险。然而,我们的研究并未观察到预防措施对降低死亡风险有明显效果。这引出了另一个更加引人深思且可能更加复杂的问题:既然预防对侧乳腺癌并不能直接降低死亡风险,为何早期筛查却对降低患者死亡风险有更好的效果?
 
这本书正是对这些看似矛盾的现象提出了挑战,它对我们关于乳腺癌早期诊断的传统观点提出质疑。也许,是时候重新审视那些我们认为构成乳腺癌基础的真正要素了。我希望这本书能够帮助我们阐明研究结果,并对乳腺癌的研究和治疗产生更广泛的影响。
 
Oncology Frontier:What are the implications of your study’s findings for current breast cancer treatment strategies,particularly regarding the assessment of contralateral breast cancer risk and preventive measures?
 
Dr.Steven Narod:Well,I think there are clinical questions that we’ve gone into,but there’s also kind of a theoretical question about the nature of breast cancer,when it starts and how it spreads.We did find that women who got a contralateral breast cancer had a much higher chance of dying of breast cancer.The risk went up from like 13 percent to 30 percent.So getting a new breast cancer is a poor prognostic factor,but preventing it didn’t reduce the risk of dying,which leads me to conclude that this new breast cancer is not really capable of spread,but is a marker that there’s an underlying process going on.
 
This paper on the contralateral breast cancer is really one chapter in a series of studies we’ve done which come to the same conclusion,and it’s summarized recently in a book which I just published called"A Fair Trial:The Foundations of Breast Cancer,"which I think people would be interested in.(link:https://a.co/d/2I6YIlC)It covers all aspects of breast cancer:how it originates,how it spreads,and some of the paradoxes and contradictions that show up in this paper are dealt with further in that book.
 
The main paradox,I think,is if the contralateral cancer raises your chance of dying and preventing it should reduce your chance of dying,but we didn’t see that.It raises another question,of course,which is more intriguing and maybe more puzzling,which is if preventing the cancer doesn’t reduce your chance of dying,why would detecting it early through screening be more successful?So this book really challenges our conventional view of how breast cancer is detected in our early diagnosis,and maybe it’s time to re-examine some of the real fundamentals about what we think underlies the basis of breast cancer.I hope this helps clarify the findings of the study and its broader implications for breast cancer research and treatment.
 
▌参考文献:
 
1.Giannakeas V,Lim D W,Narod S A.Bilateral Mastectomy and Breast Cancer Mortality[J].JAMA oncology,2024.
 
2.Narod S.A Fair Trial the Foundations of Breast Cancer.Gatekeeper Press.2024 https://a.co/d/2I6YIlC

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