Abstract P6-08-43: Histological grade provides significant prognostic information in the discrimination between luminal A-like and luminal B-like HER-2 normal subtypes of breast cancer according to St Gallen 2013
Authors: Ehinger Anna , Malmström Per , Bendahl Pär-Ola , Elston Christopher W , Falck Anna-Karin , Forsare Carina , Grabau Dorthe , Rydén Lisa , Stål Olle , Fernö Mårten 
Published: May 2015

Objective: According to St Gallen recommendations from 2013, estrogen receptor (ER), progesterone receptor (PR), HER-2, and Ki-67 defines two subtypes of ER-positive and HER-2 normal breast cancer (BC): Luminal A-like and Luminal B-like. Patients with Luminal B-like BC are often recommended chemotherapy in addition to endocrine therapy, whereas endocrine therapy may be sufficient for patients with Luminal A-like BC. Histological grade (G) 1, 2 and 3 are not included in the St Gallen recommendations. Our unpublished data from a series of 161 premenopausal N0 BC patients with long-term follow-up show that the classification of Luminal A-like vs Luminal B-like HER-2 normal BC is strongly associated to G. Luminal A-like BC is often G1 or G2 and Luminal B-like BC is usually G2 or G3. We also found that the few G3 (n=6) Luminal A-like cases had a prognosis more similar to Luminal B-like and that the few G1 (n=2) Luminal B-like HER-2 normal cases had a prognosis more similar to Luminal A-like. The aim of this study is to evaluate in other cohorts if these findings can be confirmed.

Methods: G and St Gallen subtypes were evaluated in three BC cohorts from altogether 547 pre- and postmenopausal chemotherapy naïve T1-2N0-N1M0 patients. The endpoint was distant disease-free survival with 10 years of follow-up. We compared the Luminal A-like and the Luminal B-like HER-2 normal subtype definition according to the original St Gallen recommendation from 2013 based on ER, PR, HER-2 and Ki-67 (St Gallen 2013) with our proposal, where ER-positive, HER-2 normal, G1 BC is defined as Luminal A-like, independent of Ki-67 and PR, and ER-positive, G3 BC is defined as Luminal B-like, independent of Ki-67 and PR (St Gallen 2013+G). The importance of Ki-67 and PR for subtyping was thus restricted to G2 BC.

Results: The hazard ratio (HR) between Luminal B-like HER-2 normal (n=185) and Luminal A-like (n=362) defined according to St Gallen 2013+G, was 2.3 (95% confidence interval (CI) 1.6-3.4; p&lt;0.0001) compared to 1.6 (95% CI: 1.1-2.4; p=0.025) according to St Gallen 2013. Twenty-five patients, classified as Luminal B-like HER-2 normal with St Gallen 2013 were G1 and consequently reclassified as Luminal A-like with St Gallen 2013+G. None of these twenty-five patients developed metastases during the follow-up period. Thirty-eight patients showed the opposite pattern (G3 Luminal A-like with St Gallen but Luminal B-like according to St Gallen 2013+G). Seventeen of these patients developed distant metastases already during the first five years.

Conclusion: Our findings strongly suggest that ER-positive, HER-2 normal, and G1 BC is a good prognosis group, independent of Ki-67 and PR, and should be treated as Luminal A-like BC, whereas ER-positive, HER-2 normal, and G3 BC should be considered as a worse prognosis group, independent of Ki-67 and PR, and should be treated as Luminal B-like BC. Based on our findings the importance of Ki-67 and PR is restricted to G2 BC for the discrimination between Luminal A-like and Luminal B-like HER-2 normal subtypes of BC.

Citation Format: Anna Ehinger, Per Malmström, Pär-Ola Bendahl, Christopher W Elston, Anna-Karin Falck, Carina Forsare, Dorthe Grabau, Lisa Rydén, Olle Stål, Mårten Fernö. Histological grade provides significant prognostic information in the discrimination between luminal A-like and luminal B-like HER-2 normal subtypes of breast cancer according to St Gallen 2013 [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-08-43.