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Editorial for “Breast Magnetic Resonance Imaging Can Detect Ki67 Discordance Between Core Needle Biopsy and Surgical Samples”

Ki67 is a protein in humans encoded by the MKI67 gene and is expressed in all phases of the cell cycle other than the G0 phase, making it an excellent marker of cell proliferation. Despite difficulties standardizing methods for Ki67 assessment, the clinical value of Ki67 has been investigated extensively in breast cancer over the past few decades and has been shown to be useful in prognosis estimation, especially in the differentiation between Luminal A and Luminal B subtypes of breast cancer. With recent efforts to establish analytical validity and standardization of Ki67 appraisal, the biomarker will likely play a larger role in breast cancer treatment in the future. Most recently, the updated American Society of Clinical Oncology guidelines now mention that Ki67 combined with other parameters may be used in postmenopausal patients with Stage I-II breast cancer to guide adjuvant therapy decisions when multigene assays are not available. However, Ki67 is known to have lower concordance rates between core–needle biopsy and surgical samples than other immunohistochemistry markers of breast cancer such as estrogen receptor, progesterone receptor, or HER2. Researchers have mostly focused on clinical risk factors associated with discordant Ki67 values, such as tumor size or patient age. Yet, this is an area where breast MRI can be especially advantageous, as noninvasive assessment of the whole tumor is possible. Even without high-dimensional radiomic features, relatively simple qualitative and quantitative MRI features have been associated with prognosis or intratumoral heterogeneity in breast cancer. In this issue of JMRI, the article “Breast magnetic resonance imaging can detect Ki67 discordance between coreneedle biopsy and surgical samples” used conventional MRI features and ADC parameters to investigate whether preoperative breast MRI could be useful in predicting Ki67 discordance between core-needle biopsy and surgical samples. The included MRI features are those easily assessable in clinical practice, and ADC parameters were determined by drawing multiple 5 mm diameter ROIs on a representative slice to encompass the entire cross-section of the lesion. Of note, the authors did not define Ki67 discordance based on the 20% threshold but used K-means clustering analysis. Therefore, although 23% (50/217) of the included HR+/HER2 breast cancers were discordant when determining luminal A and B subtypes between the two samples, Ki67 discordance in this study would not necessarily indicate discordance in breast cancer subtypes. However, with further improvement in Ki67 measurement standardization and data from clinical trials, thresholds are prone to change and the absolute difference in Ki67 index values could gain further importance in the near future. Overall, 16.7% (61/365) of patients showed Ki 67 discordance, which could benefit from the model showing a sensitivity of 80%. ADC values have been reported to negatively correlate with the Ki67 index, especially when focusing on luminaltype breast cancer. Interestingly, although minimum ADC and ADC difference values were associated with Ki67 discordance, mean ADC values showed no association—suggesting that imaging parameters directly reflecting heterogeneity are more useful in predicting heterogeneity on the pathological level as well. Higher ADC differences have also been associated with higher Oncotype DX recurrence scores in node-negative luminal-type breast cancer and worse distant-metastasis free survival in invasive breast cancer Peritumoral edema, the other significant factor in this study, has also been associated in the previous literature with poor prognostic factors such as a larger lesion size, higher histologic grade and Ki-67 index, and lymphovascular invasion. Thus, the study’s results are in line with previous studies and provide further evidence that MRI features can noninvasively identify tumors with high intratumoral heterogeneity. Of note, tumor size showed no significant association with Ki67 discordance, suggesting that