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%.

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