Abstract P2-09-32: Ki-67 index value and progesterone receptor status predict prognosis and suitable treatment in node-negative breast cancer patients with estrogen receptor positive and HER2 negative tumors
Authors: Arima N , Nishimura R , Osako T , Nishiyama Y , Okumura Y , Fujisue M , Toyozumi Y 
Published: February 2018

Abstract
Background: Breast cancer is no longer a single disease with high molecular heterogeneity. Gene profiling has identified at least 4 subtypes: Luminal A, Luminal B, HER2-enriched and basal-like breast cancer. Moreover, immunohistochemistry (IHC) classification is now considered a surrogate for establishing breast cancer subtypes. In previous report Luminal A was defined as ER and PgR positive, HER2 negative, Ki-67 low and recurrence risk low based on the multi-gene-expression assay. The distinction between Luminal A-like and Luminal B-like can be made by either using a high Ki-67 value (≥20%) or a low PgR value (&lt; 20%). In this study, patients with ER positive, HER2 negative and negative node were classified into 4 groups according to the PgR and the Ki-67 status (cutoff points: 20%) and examined retrospectively in relation to clinicopathological findings including the recurrence score (RS) and disease-free survival (DFS).
Methods: A total of 1866 invasive breast cancer patients from November 2001 to November 2016 were included in this study. The cases were classified as follows; LA as high PgR/low Ki-67 (850 cases), LB1 as high PgR/high Ki-67 (553 cases), LB2 as low PgR/high Ki-67 (226 cases), and LB3 as low PgR/low Ki-67 (237 cases). Out of all these cases, 1510 were treated with endocrine therapy alone. The median follow-up period was 78.1 months. Moreover, 23 of the cases underwent a 21-gene expression assay and the RS (&lt; 25 and &gt; 26) was compared with our classification.
Results: The median age was 57.4 years (range: 25 - 94). T1 tumors were more common in the LA group and rare in the LB2 group. Nuclear grade 3 and p53 overexpression were significantly correlated with LB2. Endocrine therapy alone was performed in 87.4% (LA), 77.4% (LB1), 58.8% (LB2) and 86.9% (LB3), retrospectively. There were significant differences in DFS between the LA group (5y DFS: 98%, 10 y DFS: 95.9%) and the LB2 group (5y: 89.9%, 10y: 83.6%; p&lt;0.0001) or LB1 (5y: 94.9%, 10y: 89.5%; p&lt;0.0001), but there was no difference with the LB3 group (5y: 98.6%, 10y: 94.7%; p=0.88). In the cases with endocrine therapy alone, LA showed a similar DFS with LB3 (p=0.25). LB2 had a significantly worse DFS in all the cases and in the cases with endocrine therapy. Chemotherapy was administered to cases with a higher nuclear grade in combination with endocrine therapy. In the LB2 group, there was no difference in DFS between the cases with endocrine therapy and in the cases with chemo-endocrine therapy. Moreover, most of the cases with LA (1/1) and LB1 (15/16) had a RS of &lt;25, and all of the LB2 (6/6) cases had a RS of &gt;26.
Conclusion: The patients with LA and LB3 (both: Ki-67&lt;20%) had a favorable DFS even in the endocrine therapy alone group. However, LB1 and LB2 (both: Ki-67≥20%) had a poorer DFS. Moreover, LB2 (PgR&lt;20% and Ki-67≥20%) was significantly correlated with a higher degree of malignancy and benefited from chemotherapy. LA and LB3 with low Ki-67 values were considered to be a part of the Luminal A group. These data suggest that PgR and the Ki-67 status are useful in predicting prognosis and deciding the treatment strategy for patients with ER-positive and HER2 negative breast cancer.
Citation Format: Arima N, Nishimura R, Osako T, Nishiyama Y, Okumura Y, Fujisue M, Toyozumi Y. Ki-67 index value and progesterone receptor status predict prognosis and suitable treatment in node-negative breast cancer patients with estrogen receptor positive and HER2 negative tumors [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-09-32.