Abstract P2-08-23: A combined score of tumour budding and tumour necrosis has prognostic value for cancer specific survival in both ER positive and ER negative primary operable breast cancer
Authors: Morrow ES , Gujam F , Mohammed Z , McMillan DC , Horgan PG , Roseweir AK , Edwards J 
Published: May 2019

Background: As new systemic therapies emerge for the treatment of breast cancer, new prognostic markers are required to help stratify patients into higher and lower risk groups to aid treatment decision making. Features of the tumour microenvironment, such as tumour necrosis, tumour-stroma percentage (TSP), and tumour budding have been shown to have prognostic value in some cancers. However, their role in breast cancer is unclear.

Methods: Patients who underwent surgery for primary operable breast cancer in 2 centres between 1995-2007 and who had paraffin-embedded tissue blocks available were identified. Clinicopathological details and survival data were obtained from patient records. Haematoxylin & Eosin-stained slides were visually assessed within a set visual field for TSP (&lt;50% or &gt;50% tumour stroma), tumour necrosis (&lt;25% or &gt;25% necrosis) and tumour budding (&lt;20 buds or &gt;20 buds). A combined score of tumour necrosis and tumour budding was then created. A score of 0 was assigned to tumours where both components were low, 1 to those where only one component was high, and 2 to those where both were high. Multivariate cox regression analysis was carried out for cancer specific survival (CSS).

Results: A breast cancer cohort of 1301 patients was utilised, from which 1186 H&E slides were scored for necrosis, TSP and tumour budding. Median follow up was 158 months (26-183) and there were 234 breast cancer deaths. In the full cohort, necrosis (p&lt;0.0001), high TSP (p=0.010) and high budding (p&lt;0.0001) were associated with CSS and all 3 were independently prognostic on multivariate analysis (necrosis HR 1.54, 95%CI 1.15-2.07, p=0.004; high TSP HR 1.49, 95%CI 1.12-1.98; p=0.006; high budding HR 1.38, 95%CI 1.02-1.87, p=0.035). In ER positive disease (n=826), necrosis was associated with worse CSS (p&lt;0.0001) and was independently prognostic (HR 1.46, 95%CI 1.03-2.08, p=0.033). In ER negative disease (n=359), necrosis, high TSP and high budding were associated with worse CSS (p=0.001, p=0.002, p&lt;0.0001 respectively) and were independently prognostic (necrosis HR 2.44, 95%CI 1.34-4.43, p=0.003; high TSP HR 1.64, 95%CI 1.06-2.53, p=0.026; high budding HR 2.47, 95%CI 1.56-3.89, p&lt;0.0001) . To assess if combining these markers added additional prognostic power a combined budding/necrosis score was established. This was associated with worse CSS in ER positive disease (p&lt;0.0001) and a score of 2 was independently associated with worse CSS compared to a score of 0 (HR 1.96, 95%CI 1.19-3.23, p=0.008). This was potentiated in node-negative patients (HR 5.14, 95%CI 2.18-12.08, p&lt;0.0001). In ER negative disease, an increasing score was associated with worse CSS (p&lt;0.0001) and was independently prognostic (combined score 1 vs. 0: HR 2.37, 95%CI 1.13-5.00, p=0.023; score 2 vs. 0: HR 5.93, 95%CI 2.62-13.40, p&lt;0.0001).

Conclusions: A combined score of tumour necrosis and budding shows promise as a readily-available prognostic tool to aid treatment decision making in primary operable breast cancer, both by stratifying risk in ER negative disease, and by identifying a high-risk group in ER positive, node negative disease.

Citation Format: Morrow ES, Gujam F, Mohammed Z, McMillan DC, Horgan PG, Roseweir AK, Edwards J. A combined score of tumour budding and tumour necrosis has prognostic value for cancer specific survival in both ER positive and ER negative primary operable breast cancer [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 P2-08-23.