Abstract PD2-11: Ki-67 (30-9) scoring and differentiation in Luminal A and Luminal B breast cancer subtypes
Authors: Viale G , Hanlon Newell AE , Walker E , Bai I , Russo L , Dell'Orto P , Maisonneuve P 
Published: May 2019

Abstract
Introduction
Ki-67 labeling index is a powerful prognostic marker in breast cancer (BC). It is especially useful in assessing the risk of recurrence for estrogen receptor-positive (ER+) BC, where it may be considered a surrogate of the molecular assays for distinguishing Luminal A-like from Luminal B-like BCs. We evaluated the performance of the VENTANA anti Ki-67 (30-9) rabbit monoclonal antibody in assessing the risk of distant relapses for a large series of patients with ER+ BC treated and followed up in a single Institution.
Patients and Methods
The initial cohort (9415 patients) comprised all women operated on for early ER+, HER2-negative (HER2-) BC at the European Institute of Oncology (IEO), who did not receive neo-adjuvant treatment1. We subsequently restricted the cohort to 3986 patients operated on between 1998-2002 and for whom long-term follow-up data was available. A case-cohort was built by randomly selecting 17% of the above cohort (679 patients, including 84 with events). Additional 303 patients who developed an event (metastasis in distant organs or death due to BC as primary events) were added to this cohort.
Ki-67 was evaluated using the anti-Ki-67 (30-9) antibody (Ventana Medical Systems, Inc., Tucson, AZ) using OptiView IHC DAB detection on the BenchMark ULTRA advanced staining platform. The stained slides were evaluated using the scoring method described by the International Ki-67 in BC Working Group.
We considered “Luminal A-like” tumors that were ER+, HER2-, with Ki-67 &lt;14% or with Ki-67 14-19% and PgR ≥20%, and “Luminal B-like” ER+, HER2- tumors with Ki-67 14-19% and PgR &lt;20% or with Ki-67 ≥20%1.
The main outcome was distant disease-free survival (DDFS) and was calculated from the date of surgery to the date of any first event or last contact with the patient.
Cumulative incidence curves were drawn for patients in the sub-cohort and differences between BC subtypes were assessed using the log-rank test. Multivariable Cox regression with inverse sub-cohort sampling probability weighting was used to evaluate the risk of metastasis or death from BC across groups.
Results
In the sub-cohort, 400 (58.9%) patients had “luminal A-like” and 279 (41.1%) “luminal B-like” BC. The 10-year cumulative incidence of distant metastasis (or BC related death as first event) in the two groups were respectively 8.2% and 24.5% (log rank P&lt;0.0001)
In the whole case-cohort, multivariable analysis confirmed statistically significant increased risk of events for women with “Luminal B-Like” BC compared to women with “Luminal A-Like “BC (HR=1.97; 95% CI 1.38-2.79), after adjustment for pT, pN, PVI and menopausal status.
Conclusion
Ki-67 evaluated using the VENTANA anti-Ki67 (30-9) antibody, was able to stratify patients with endocrine responsive BC, maximizing the number of those classified as having 'Luminal A-like' intrinsic subtype for whom the use of cytotoxic drugs could be at large avoided.
Funding source: Ventana Medical Systems, Inc.
References
Maisonneuve P, Disalvatore D, Rotmensz N, et al. (2014) Proposed new clinicopathological surrogate definitions of luminal A and luminal B (HER2-negative) intrinsic breast cancer subtypes. Breast Cancer Res 16:R65
Citation Format: Viale G, Hanlon Newell AE, Walker E, Bai I, Russo L, Dell'Orto P, Maisonneuve P. Ki-67 (30-9) scoring and differentiation in Luminal A and Luminal B breast cancer subtypes [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr PD2-11.