Department of Medicine, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Johannesburg, 2193, South Africa.
Department of Surgery, School of Clinical Medicine, Faculty of Health Sciences, University of Kwa-Zulu Natal, Durban, 4001, South Africa.
Breast Cancer Res Treat. 2023 May;199(1):1-12. doi: 10.1007/s10549-023-06886-3. Epub 2023 Mar 3.
Breast cancer is a heterogeneous disease with different gene expression profiles, treatment options and outcomes. In South Africa, tumors are classified using immunohistochemistry. In high-income countries multiparameter genomic assays are being utilized with implications for tumor classification and treatment.
In a cohort of 378 breast cancer patients from the SABCHO study, we investigated the concordance between tumor samples classified by IHC and the PAM50 gene assay.
IHC classified patients as ER-positive (77.5%), PR-positive (70.6%), and HER2-positive (32.3%). These results, together with Ki67, were used as surrogates for intrinsic subtyping, and showed 6.9% IHC-A-clinical, 72.7% IHC-B-clinical, 5.3% IHC-HER2-clinical and 15.1% triple negative cancer (TNC). Typing using the PAM50 gave 19.3% luminal-A, 32.5% luminal-B, 23.5% HER2-enriched and 24.6% basal-like. The basal-like and TNC had the highest concordance, while the luminal-A and IHC-A group had the lowest concordance. By altering the cutoff for Ki67, and realigning the HER2/ER/PR-positive patients to IHC-HER2, we improved concordance with the intrinsic subtypes.
We suggest that the Ki67 be changed to a cutoff of 20-25% in our population to better reflect the luminal subtype classifications. This change would inform treatment options for breast cancer patients in settings where genomic assays are unaffordable.
乳腺癌是一种具有不同基因表达谱、治疗选择和预后的异质性疾病。在南非,肿瘤采用免疫组织化学进行分类。在高收入国家,正在利用多参数基因组检测,这对肿瘤分类和治疗具有影响。
在 SABCHO 研究的 378 例乳腺癌患者队列中,我们研究了通过免疫组化和 PAM50 基因检测分类的肿瘤样本之间的一致性。
免疫组化将患者分为 ER 阳性(77.5%)、PR 阳性(70.6%)和 HER2 阳性(32.3%)。这些结果与 Ki67 一起用作内在亚型的替代物,显示出 6.9%的 IHC-A-临床、72.7%的 IHC-B-临床、5.3%的 IHC-HER2-临床和 15.1%的三阴性乳腺癌(TNC)。使用 PAM50 进行分型得到 19.3%的 luminal-A、32.5%的 luminal-B、23.5%的 HER2 富集和 24.6%的基底样。基底样和 TNC 具有最高的一致性,而 luminal-A 和 IHC-A 组具有最低的一致性。通过改变 Ki67 的截止值,并将 HER2/ER/PR 阳性患者重新与 IHC-HER2 对齐,我们提高了与内在亚型的一致性。
我们建议在我们的人群中将 Ki67 的截止值更改为 20-25%,以更好地反映 luminal 亚型分类。这一改变将为基因组检测不可负担的环境中的乳腺癌患者提供治疗选择。