Reliability of the Ki67-Labelling Index in Core Needle Biopsies of Luminal Breast Cancers is Unaffected by Biopsy Volume.

BACKGROUND: Assessing prognostic and predictive factors like the Ki67 labelling index (Ki67-LI) in breast cancer core needle biopsies (CNB) may be hampered by undersampling. Our aim was to arrive at a representative assessment of Ki67-LI in CNB of luminal breast cancers by defining optimal cutoffs and establishing the minimum CNB volume needed for highest concordance of Ki67-LI between CNB and subsequent surgical excision biopsy (SEB). METHODS: We assessed the Ki67-LI in CNB and subsequent SEB of 170 luminal breast cancers according to two counting methods recommended by the International Ki67 in Breast Cancer Working Group and applied the cutoffs to distinguish low and high proliferation given by the St Gallen 2013 and 2015 consensus, respectively. We then compared CNB volume characteristics for cases with concordant and discordant Ki67-LI between CNB versus SEB. RESULTS: Highest concordance (75%, κ = 0.44) between CNB and SEB was achieved using the method that assesses the average tumor Ki67-LI and a cutoff of 20%. No significant differences were found between cases with concordant and discordant Ki67-LI in CNB versus SEB for number of biopsy cores, total core length, tumor tissue length, or total CNB or tumor tissue area size in the CNB for two various cutoffs. CONCLUSIONS: A concordance of 75% between CNB and SEB can be achieved for the Ki67-LI using a method assessing average Ki67-LI at the threshold of 20%. Increasing CNB volume did not result in improved agreement rates, indicating that reliability of Ki67 levels in CNB of luminal breast cancers is unaffected by CNB volume.

Pathological non-response to chemotherapy in a neoadjuvant setting of breast cancer: an inter-institutional study.

To identify markers of non-response to neoadjuvant chemotherapy (NAC) that could be used in the adjuvant setting. Sixteen pathologists of the European Working Group for Breast Screening Pathology reviewed the core biopsies of breast cancers treated with NAC and recorded the clinico-pathological findings (histological type and grade; estrogen, progesterone receptors, and HER2 status; Ki67; mitotic count; tumor-infiltrating lymphocytes; necrosis) and data regarding the pathological response in corresponding surgical resection specimens. Analyses were carried out in a cohort of 490 cases by comparing the groups of patients showing pathological complete response (pCR) and partial response (pPR) with the group of non-responders (pathological non-response: pNR). Among other parameters, the lobular histotype and the absence of inflammation were significantly more common in pNR (p < 0.001). By ROC curve analyses, cut-off values of 9 mitosis/2 mm(2) and 18% of Ki67-positive cells best discriminated the pNR and pCR + pPR categories (p = 0.018 and < 0.001, respectively). By multivariable analysis, only the cut-off value of 9 mitosis discriminated the different response categories (p = 0.036) in the entire cohort. In the Luminal B/HER2- subgroup, a mitotic count <9, although not statistically significant, showed an OR of 2.7 of pNR. A lobular histotype and the absence of inflammation were independent predictors of pNR (p = 0.024 and <0.001, respectively). Classical morphological parameters, such as lobular histotype and inflammation, confirmed their predictive value in response to NAC, particularly in the Luminal B/HER2- subgroup, which is a challenging breast cancer subtype from a therapeutic point of view. Mitotic count could represent an additional marker but has a poor positive predictive value.