Abstract P4-01-17: Aggressive subgroups of metastatic triple-negative breast cancer: Inflammatory breast cancer and young patients in the Dana-Farber cell-free DNA cohort
Authors: Singh J , Asad S , Nock W , Zhang Y , Adams E , Damicis A , Parsons HA , Adalsteinsson VA , Winer EP , Lin NU , Partridge AH , Overmoyer B , Stover DG 
Published: May 2019

Abstract
Background: Relative to other metastatic breast cancer subtypes, metastatic triple-negative breast cancer (mTNBC) has a shorter duration of response to therapy and worse overall survival. Within mTNBCs, there is a prevailing belief that inflammatory breast cancer and young women tend to have among the most aggressive phenotypes. We investigated clinical and cell-free DNA (cfDNA) characteristics of inflammatory-mTNBC and young-mTNBC. We hypothesized that inflammatory-mTNBC may have distinct clinical and cfDNA characteristics, offering potential novel biomarker and therapeutic strategies.
Methods: 164 patients from the Dana-Farber metastatic triple-negative cell-free DNA cohort (Stover DG, et al J Clin Oncol 2018) were included in this secondary analysis. Patients were stratified into three groups: 1) inflammatory breast cancer ('IBC'); 2) non-IBC patients aged 45 years (yr) or younger at primary diagnosis ('non-IBC young'); and 3) non-IBC patients over age 45 yr at diagnosis. For each subset population, we evaluated clinicopathologic characteristics, sites of metastasis, survival outcomes, and cfDNA 'tumor fraction' – the fraction of DNA in circulation derived from tumor. Those patients with adequate cfDNA tumor content for high confidence copy number calls (n=101) were included in an analysis of copy number alterations.
Results: Among 164 patients with metastatic TNBC, 13.4% (22/164) had IBC, 37.8% (62/164) were non-IBC young, and 48.8% (80/164) were non-IBC and over 45 yr. Race and primary receptor status were similar. IBC patients were diagnosed at a higher stage (Chi-square p=0.0009) while non-IBC young patients were significantly more likely to harbor a BRCA mutation (Chi-square p=0.03). Analysis of metastatic sites revealed that IBC patients had significantly greater frequency of ipsilateral and contralateral breast chest wall recurrences (p=0.04 and p=0.046, respectively) while non-IBC young patients had the most frequent lung metastases (p=0.002). There were no significant differences in frequency of bone, brain, or liver metastases. cfDNA analyses showed that cfDNA 'tumor fraction' was highest in non-IBC young patients (ANOVA p=0.03 for maximum tumor fraction). Median overall survival from metastatic diagnosis was 22.9 months. IBC and non-IBC young patients had a worse prognosis relative to non-IBC patients over 45 yr (hazard ratio IBC=1.97, 95% CI 1.09-3.57; HR non-IBC young=1.60 95% CI 1.07-2.41; log-rank p=0.023). By subgroup, median overall survival from metastatic diagnosis for IBC was 15.2 months, non-IBC young 21.2 months, and non-IBC over 45 yr 31.2 months. Analyses of genome-wide copy number alterations from cell-free DNA will be presented.
Conclusions: Among metastatic TNBCs, IBC patients and non-IBC young patients have a significantly worse overall survival compared with non-IBC patients over 45 yr of age. Young patients have more frequent lung metastases and higher 'tumor fraction' of cfDNA. Confirmation of the reported findings is limited due to cohort size and may reflect referral bias.
Citation Format: Singh J, Asad S, Nock W, Zhang Y, Adams E, Damicis A, Parsons HA, Adalsteinsson VA, Winer EP, Lin NU, Partridge AH, Overmoyer B, Stover DG. Aggressive subgroups of metastatic triple-negative breast cancer: Inflammatory breast cancer and young patients in the Dana-Farber cell-free DNA cohort [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 P4-01-17.