针芯穿刺活检的地位和意义

　　Klimberg教授首先指出，当前在美国及其全球大部分地区，术前进行乳腺针芯穿刺活检（core needle biopsy，CNB）都成为了乳腺癌诊断的金标准。2001、2005和2009年举行的国际跨学科共识会议一致同意将乳腺病灶的经皮活检    术作为活检方法的金标准，如果病灶容易控制，则使用超声引导，如果超声检查见不到钙化，则实施立体定位活检。在美国，经皮CNB已几乎取代细针抽活检作为乳腺病灶的术前诊断方法，因为它能更明确地做出组织学诊断，并提供充足的组织用于预后标志物的检测。

　　CNB的优势主要有三方面：①避免重复手术。2014年的一项总结了超过160篇论文的循证报告表明，接受切开活检的女性与进行CNB的女性相比，前者接受重复手术的可能性升高了15倍。②方便制定手术计划。医生可在保乳手术与乳房切除和重建手术之前做出更恰当的选择，而且当活检结果为浸润性癌时，医生还可以提前计划前哨淋巴结活检。③降低切缘阳性率。有研究显示，若术前进行了CNB或其他诊断，在乳腺肿瘤切除术时实现切缘阴性的可能性更大。

　　在实施超声引导的CNB时，如CNB结果为良性且与影像学结果一致，可继续监视。若结果不明确或与影像学结果不一致，如CNB结果为良性但临床或影像学检查疑似恶性时，可重复经皮活检或手术切除活检以排除恶性可能。此外，CNB显示不典型增生（小叶或导管）或小叶原位癌或肿瘤，适合实施手术切除，此时因可能发生的采样错误而导致共存导管原位癌或侵袭性癌的比例高达30%。

　　孰先孰后：新辅助治疗和前哨淋巴结活检的顺序？

　　对于拟行新辅助治疗的患者，为更好地评估患者病情并指导其后续治疗，应该在新辅助治疗之前还是之后进行前哨淋巴结活检，对此临床医生有不少疑惑。对此，Klimberg教授认为仍然可结合CNB结果指导临床实践。对于确诊为乳腺癌的患者，需要对淋巴结受累情况进行评估。可在腋窝超声引导下行淋巴结CNB，若结果阳性，说明患者应先接受新辅助治疗（内分泌治疗或化疗）。对于小肿瘤（有利预后因素）患者，淋巴结是否受累是是否进行新辅助治疗的决定因素。治疗后前哨淋巴结的状态可用来确定治疗的有效率，约40%的患者可以转阴，这些患者无需再行腋窝淋巴结术。若CNB结果阴性，则可先进行前哨淋巴结分期，或基于乳腺癌分析确定最终的标准治疗。Klimberg教授认为在淋巴结无转移时，二者的先后顺序无区别。但新辅助治疗后再进行活检，其结果的准确性不如新辅助治疗前的活检。

　　Klimberg教授所在机构曾开展了一项回顾性研究，研究包括95例患者接受腋窝US引导CNB的患者。这些患者中32%为腋窝临床阳性（32%）。腋窝US引导CNB的灵敏度和特异性分别为90%和100%，与术前行前哨淋巴结活检相比大幅节省医疗费用和资源。

　　肿瘤异质性导致穿刺位点结果不一致时的临床应对及改善

　　乳腺癌具有异质性，这个异质性不仅见于不同的肿瘤细胞克隆之间，同样也可表现在转移灶和原发灶之间。若转移灶和原发灶穿刺结果不一致时应以哪个结果作为指导呢？Klimberg教授指出，“应选择最坏的那个结果来指导治疗，也就是说我们总是选择预后最差的那个。”例如，受体丢失是转移灶和原发灶直接最常见的区别之一，如雌激素受体、孕激素受体转阴或是转换成其他受体如HER-2阳性，此时，针对阳性结果进行治疗比不治疗更好。

　　而为了减少肿瘤异质性的干扰，获得更全面、充分的肿瘤评估结果，Klimberg教授认为主要对策是采集多个穿刺样本。她认为“空芯针穿刺至少需要获取10个组织样本。我们知道，肿瘤不是单一的克隆，它们是多因素的，所以我认为最好的方法是取到好的样本。”

访谈原文

　　Interview with Suzanne Klimberg

　　Oncology Frontier: Is core needle biopsy the diagnosis standard of breast cancer in the United States? What is the proportion of core needle biopsy in preoperative diagnosis? And finally， what are the advantages of core needle biopsy for the individual treatment of breast cancer?

　　Professor Klimberg: So， in the United States—or anywhere—the gold standard should be core needle biopsy ahead of time. I say that because if you get a core needle biopsy ahead of time， it cuts down on the number of secondary procedures that you have to have. In fact， one study of over 160 papers showed that a woman who doesn’t have a core needle biopsy is 15 times more likely to have a second procedure because she didn’t have the needle biopsy ahead of time. It allows you to plan what you want， because you have a choice of breast conservation versus mastectomy and reconstruction. If you know that you have an invasive cancer， it allows you to plan a sentinel lymph node biopsy ahead of time. So， this is extremely important. And then the third thing is that if you know the diagnosis ahead of time or you’ve done a needle biopsy ahead of time， it’s been shown in studies that you are much more likely to have free margins， or clear margins， from a lumpectomy.

　　Oncology Frontier: In order to better assess the patient’s condition and guide the subsequent treatment， do you think that a sentinel lymph node biopsy should be done before or after neoadjuvant treatment?

　　Prof. Klimberg: Well， this comes back to core needle biopsy. We also love to look at—with ultrasound—the sentinel lymph node. Once we know we have a cancer we look at the lymph node， and if we think we need to or it looks suspicious， we biopsy it with a needle also. That allows us to take the patient to neoadjuvant. That is， for us， a determining factor in small， what look to be favorable， tumors.  If they’ve already travelled to the lymph node and it’s positive， then we’d go to neoadjuvant—either hormonal or chemotherapy—first. That allows the sentinel lymph node to determine whether it’s going to have an effect or not， and in 40 percent of patients， it can convert to negative. So it’s very important because those patients then don’t need an axillary node dissection. So， we use the core needle biopsy. If the lymph node doesn’t look suspicious， we do a sentinel lymph node ahead of time. I don’t think it makes a difference， though， if it does not appear to be involved. We go by the primary， and we might go ahead and do a neoadjuvant， and do a sentinel lymph node after. But we do know that after chemotherapy， it’s not quite as accurate as before chemotherapy.

　　Oncology Frontier: How do you avoid tumor heterogeneity in breast cancer tissue biopsy? If the immunohistochemistry results of the breast tissue and sentinel lymph node are not the same， which one should we choose to guide a more accurate treatment?

　　Prof. Klimberg: Well， the one we choose to guide the treatment is the one that looks the worst. So we always take the one with the worst prognosis. For example， we do know that there is heterogeneity， that the primary—once it’s metastasized—doesn’t always stay the same; the main thing it does is lose receptors. So， if it becomes receptor negative， for example， with estrogen progesterone negative or it switches the other way and is HER2-positive， we have treatments that are better for those than not. And so， you would always take the worst one. It wouldn’t matter whether it was the primary or the lymph node.

　　And the second part of your question was: how to avoid tumor heterogeneity in breast cancer tissue biopsy? I think the main way that we do that is when we do a needle biopsy， we take multiple cores. I think you should take at least 10 cores out of a biopsy， which means 10 pieces of tissue. I think， in that way—especially if you take them from different areas of the tumor— you’re more likely to get a good look at that tumor in its entirety. But we know that tumors are not a single clone， that they are multifactorial. So， I think the best way is to take a good sample of them.