Saghir Hani, Veerla Srinivas, Malmberg Martin, Rydén Lisa, Ehinger Anna, Saal Lao H, Vallon-Christersson Johan, Borg Åke, Hegardt Cecilia, Larsson Christer, Haidar Alaa, Hedenfalk Ingrid, Loman Niklas, Kimbung Siker
Division of Oncology, Department of Clinical Sciences, Lund University, SE-223 81 Lund, Sweden.
Department of Hematology, Oncology and Radiation Physics, Lund University Hospital, SE-221 85 Lund, Sweden.
Cancers (Basel). 2022 Aug 18;14(16):4000. doi: 10.3390/cancers14164000.
In early breast cancer, a preoperative core-needle biopsy (CNB) is vital to confirm the malignancy of suspected lesions and for assessing the expression of treatment predictive and prognostic biomarkers in the tumor to choose the optimal treatments, emphasizing the importance of obtaining reliable results when biomarker status is assessed on a CNB specimen. This study aims to determine the concordance between biomarker status assessed as part of clinical workup on a CNB compared to a medically untreated surgical specimen. Paired CNB and surgical specimens from 259 patients that were part of the SCAN-B cohort were studied. The concordance between immunohistochemical (IHC) and gene expression (GEX) based biomarker status was investigated. Biomarkers of interest included estrogen receptor (ER; specifically, the alpha variant), progesterone receptor (PgR), Ki67, HER2, and tumor molecular subtype. In general, moderate to very good correlation in biomarker status between the paired CNB and surgical specimens was observed for both IHC assessment (83-99% agreement, kappa range 0.474-0.917) and GEX assessment (70-97% agreement, kappa range 0.552-0.800), respectively. However, using IHC, 52% of cases with low Ki67 status in the CNB shifted to high Ki67 status in the surgical specimen (McNemar's = 0.011). Similarly, when using GEX, a significant shift from negative to positive ER (47%) and from low to high Ki67 (16%) was observed between the CNB and surgical specimen (McNemar's = 0.027 and = 0.002 respectively). When comparing biomarker status between different techniques (IHC vs. GEX) performed on either CNBs or surgical specimens, the agreement in ER, PgR, and HER2 status was generally over 80% in both CNBs and surgical specimens (kappa range 0.395-0.708), but Ki67 and tumor molecular subtype showed lower concordance levels between IHC and GEX (48-62% agreement, kappa range 0.152-0.398). These results suggest that both the techniques used for collecting tissue samples and analyzing biomarker status have the potential to affect the results of biomarker assessment, potentially also impacting treatment decisions and patient survival outcomes.
在早期乳腺癌中，术前粗针穿刺活检（CNB）对于确认疑似病变的恶性程度以及评估肿瘤中治疗预测和预后生物标志物的表达以选择最佳治疗方案至关重要，这凸显了在对CNB标本进行生物标志物状态评估时获得可靠结果的重要性。本研究旨在确定在临床检查中作为一部分对CNB评估的生物标志物状态与未经医学处理的手术标本之间的一致性。对来自SCAN - B队列的259例患者的配对CNB和手术标本进行了研究。研究了基于免疫组织化学（IHC）和基因表达（GEX）的生物标志物状态之间的一致性。感兴趣的生物标志物包括雌激素受体（ER；具体为α变体）、孕激素受体（PgR）、Ki67、HER2和肿瘤分子亚型。总体而言，对于IHC评估（一致性83 - 99%，kappa范围0.474 - 0.917）和GEX评估（一致性70 - 97%，kappa范围0.552 - 0.800），配对的CNB和手术标本之间在生物标志物状态上均观察到中度至非常好的相关性。然而，使用IHC时，CNB中Ki67低表达状态的病例中有52%在手术标本中转变为高表达状态（McNemar检验 = 0.011）。同样，使用GEX时，在CNB和手术标本之间观察到ER从阴性到阳性有显著转变（47%）以及Ki67从低到高有显著转变（16%）（McNemar检验分别为0.027和0.002）。当比较在CNB或手术标本上进行的不同技术（IHC与GEX）之间的生物标志物状态时，在CNB和手术标本中ER、PgR和HER2状态的一致性通常都超过80%（kappa范围0.395 - 0.708），但Ki67和肿瘤分子亚型在IHC和GEX之间显示出较低的一致性水平（一致性48 - 62%，kappa范围0.152 - 0.398）。这些结果表明，用于收集组织样本和分析生物标志物状态的技术都有可能影响生物标志物评估的结果，这也可能会影响治疗决策和患者生存结局。
