The role of Ki67 in involved lymph nodes as a predictive biomarker for response to neoadjuvant chemotherapy in patients with early breast cancer.

Abstract

e12553 Background: Neoadjuvant chemotherapy (NACT) is a standard in early breast cancer (EBC) with an unfavorable tumor biology and pathologic complete remission (pCR) after NACT is indicating an improved prognosis. Ki67 is well established as a prognostic and predictive biomarker in early breast cancer and the association of high Ki67-results in breast tumors at the time of initial diagnosis and pCR after NACT is used for decision making for versus against NACT in daily routine in many countries. Data about associations of Ki67 in involved lymph nodes and response to NACT are missing. Methods: We conducted a retrospective analysis among patients in our database who had received NACT for EBC, had lymph node involvement verified by core cut biopsy and available data for pCR, age, estrogen and progesterone receptor (ER, PR) status, HER2neu status, Ki67 in the breast tumor and grading. Patients treated in clinical studies were excluded. Ki67 was measured in the archived material of biopsies from involved lymph nodes and the association between Ki67 in involved lymph nodes and response to neoadjuvant chemotherapy was analyzed. Results: 52 patients were included with regard to the criteria mentioned above, 21 had to be excluded because there was not enough lymph node biopsy material for Ki67 analysis. 7 (22.6) of the remaining 31 patients achieved a pCR and 11 (35.5%) achieved a nodal conversion to ypN0. Median Ki67 was 35% [3%, 85%] in involved lymph nodes and 40% [10%, 90%] in the breast. There was no significant correlation (Spearman Rho) between Ki67 in involved lymph nodes and pCR whereas there was for Ki67 in the breast (p = 0.046). The ROC-analysis resulted in a cut-off of 47% with the highest sensitivity for Ki67 in lymph nodes regarding prediction of nodal conversion. An analysis with a cut-off of Ki67 in involved lymph nodes of 47% predicted a nodal conversion in 60% of the cases (Chi-Square and Fisher’s Exact test; p = 0.0049). Conclusions: Our analysis supports Ki67 as a strong predictive biomarker regarding pCR after neoadjuvant chemotherapy. Although high Ki67 expression in involved lymph nodes is significantly associated with nodal conversion, it does not add clinically meaningful information to Ki67 in the breast.