Identifying the Best Ki-67 Cut-Off for Determining Luminal Breast Cancer Subtypes Using Immunohistochemical Analysis and PAM50 Genomic Classification

Abstract

Background: A surrogate classification of breast cancer (BC) molecular subtypes based on immunohistochemistry (IHC) was established at the 13th St. Gallen International Breast Cancer Consensus (SG-BCC). The most controversial point of discussion was the difference between the luminal A and B subtypes. The Ki-67 cut-off that has been used to differentiate these BC subtypes is 14%; however, this cut-off was questioned. This study aimed to identifying the best Ki67 cut-off for determining the luminal BC by PAM50/Prosigna (NanoString Technologies, Seattle, Washington, USA). Methods: This study included females who were diagnosed with early-stage luminal BC between 2015–2020, and whose samples were subjected to genomic testing using PAM50. Results: A total of 143 samples were analysed. At the Ki-67 cut-off values of >14%; a correlation of 70.6%, with a sensitivity of 79.1% and a specificity of 55.8%; and a positive predictive value of 75.8% and negative predictive value of 60.4% were observed. When the Ki-67 cut-off was increased to >20%, the percentage of well-classified tumours based on IHC was 76.2%, increasing the agreement by 6.2%. The sensitivity was 93.4%, but the specificity was 46.1%. The positive predictive value was 75.2% while the negative predictive value was 80%, suggesting that IHC has a high probability of diagnosing luminal A and B. Conclusions: Increasing the Ki-67 cut-off to >20% leads to a better surrogate classification based on IHC and to a higher sensitivity in classifying the luminal subtypes. The authors propose that the cut-off for Ki-67, which is an independent factor, should be globally modified to >20%.

XPERT® breast cancer STRAT4 as an alternative method of identifying breast cancer phenotype in Cape Verde (preliminary results)

“…Commonly, 14% is the Ki67 cut-off that has been established for differentiating BC subtypes; however, in later studies this value has been questioned and a cut-off of 20% has been proposed [ 30 ]. Recently, Escala-Cornejo et al [ 35 ] to identify the best Ki67 cut-off for determining luminal BC Subtypes using immunohistochemical analysis and PAM50 Genomic Classification propose that the Ki67 cut-off should be globally modified to >20%. For this biomarker, significant variability in concordance rate has been noted, although this is not unforeseen given the challenges associated with Ki67 IHC evaluation.…”

Predictive factors of invasion in ductal carcinoma in situ diagnosed by core-needle biopsy

“…Positive hormonal receptor status was considered if the Estrogen Receptor (ER) or the Progesterone Receptor (PR) was ≥ 1%. Ki67 was classified as low if it was < 20% 17 , this cut-off point apparently better for classifying subrogate subtypes 18,19 .…”

Subtipos moleculares do carcinoma de mama: como diferem do ponto de vista prognóstico?

“…Cada valor possui sensibilidade e especificidade distintas, por isso a escolha de qual será adotado deve ser guiada pelo objetivo do médico e pelas particularidades do caso em avaliação (VODUC et al, 2010). Em análise de Escala-Cornejo et al (2022), foi verificado que o valor de 14% possui sensibilidade e especificidade mais homogêneos, contudo, considerou o ponto de corte 20% mais adequado para a subclassificação dos tumores luminais, pois apresenta maior sensibilidade, favorecendo o diagnóstico de Luminal A. Desse modo, seria possível reduzir a utilização de quimioterapia sem necessidade.…”