62P KI67 in ER+HER2-negative pure invasive lobular breast carcinoma (ILC). What’s the best Ki67 threshold to differentiate prognosis?

To differentiate prognostic groups in patients with ER+HER2neg breast cancer (BC) Ki67 thresholds of 14% and 20% have been defined. However, most clinical research has been driven by outcomes of invasive carcinoma of no special type, with ILC underrepresented. Previous studies suggested a 4% Ki67 cut-off to distinguish prognostic groups in the ILC population (Carbogni BCRT 2016). We aim to study the best Ki67 threshold to categorize luminal A-like vs luminal B-like in ER+HER2neg pure ILC. Retrospective study including early-stage BC patients (pts) with ER+HER2neg pure ILC diagnosed from 2010 to 2015 at 2 sites (Vall d’Hebron University Hospital and Institut Català d’Oncologia-Hospitalet) and with tumor sample available. Local and central Ki67 values from surgical specimen (or initial biopsy for neoadjuvant treated-pts) were obtained. The primary endpoint were disease free-survival (DFS) and overall survival (OS). The log-rank statistic was used to select the optimal Ki67 cut-off. Overall, 275 pts were identified, median age: 61 years, postmenopausal (71.4%), stage I-II (73.4%), progesterone receptor (PgR) (78%), histology grade 1-2 (92.7%) and 34.5% receiving adjuvant chemotherapy. The median Ki67 values with local (n=257) and central (n=164) assessment were 12% and 13%, respectively (correlation= 0.63). Several factors such as pT, stage, PgR, and grade were associated with DFS and OS in the univariable analysis. Local Ki67 as a continuous variable was not associated with DFS (p=0.75), but showed a trend for association with OS (p=0.06). With local Ki67 values, cut-off from 10% to 24% showed similar results (using 10% as a cut-off, OS HR: 1.82, 95%CI 1.10-3.01, p=0.02). Central Ki67 as a continuous variable was not statistically associated with DFS (p=0.09) or OS (p=0.33). However, the optimal cut-off was identified at 10% allowing to separate two groups with different prognostic (Ki67% 10% vs <10%, HR: 2.37, 1.09-5.19, p=0.03). In our series of ILC median Ki67 was around 12%, with moderate concordance between local and central assessments. Lower Ki67 cut-off (10%) than those reported in overall population may better distinguish prognostic groups in ILC pts.