Abstract P2-05-14: Young breast cancer patients (<40 yo) have unfavorable subtypes, higher stage and worse survival

Abstract

BACKGROUND: Over the last 40 years, the incidence of breast cancer in young women in the U.S. has been relatively low and stable, but the absolute number of young women with breast cancer is increasing because of the growing population. Some epidemiological studies have shown that breast cancer diagnosed before age 40 have significantly worse overall 5-year survival. Disease free survival is also inferior in young women, and they have more aggressive cancers in general. This study aims to validate these findings using genomic analysis of large databases. MATERIALS AND METHODS: The Cancer Genome Atlas (TCGA; n= 1095) and the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC; n=1894) were used for analysis. We divided the database into the Young (<40 yo) and Non-Young (>40 yo) cohorts, based on age at diagnosis. The following analysis will give the TCGA and METABRIC results in each category, respectively. RESULTS: There were 8.9% (98) and 6% (116) patients who were found to be Young. In the Young cohort, 69.5% (64) and 37.9% (44) were ER(+), whereas 77.9% (742) and 79.5% (1415) in the Non-Young cohort were ER(+). Further, 60.8% (56) and 31.9% (37) were PR(+) in the Young cohort, compared to 68.4% (641) and 54.4% (972) in the Non-Young cohort. Her2(+) cancers were noted in 22.2% (12) and 25% (29) in the Young cohort, whereas 22.6% (152) and 11.6% (207) were Her2(+) in the Non-Young cohort. Our group developed a pipeline to calculate PAM50 from the RNA-Seq dataset. Utilizing this calculated PAM50 in TCGA, we found that there were less Luminal A and B patients in the Young cohort, 41.6% (42) and 17.8% (18) compared to 49.7% (377) and 22.9% (174) in the Non-Young cohort. This was also the case in METABRIC where 17.2% (20) and 9.5% (11) were Luminal A and B, compared to 36.9% (659) and 25.2% (450) in the Non-Young group. In contrast, there were more basal-like subtypes in the Young group, 17.8% (18) and 28.4% (33), as compared to the Non-Young group, 16.1% (122) and 9.3% (166). These results agree with previous epidemiological studies that showed that hormone receptor positive tumors increase and basal-like subtypes decrease with age. The number of Stage I patients was lower in Young patients 13.5% (13) and 25.3% (22), than in Non-Young patients 17.3% (169) and 34.4% (453). Similarly, there were less Stage II patients in the Young 54.2% (52) and 58.6% (51) compared to 58.3% (569) and 56.9% (749) in the Non-Young. This reverses in Stage III where the incidence is increased in the Young at 31.2% (30) and 16.1% (14) compared to 22.4% (219) and 7.7% (101) in the Non-Young. Young patients had a lower median disease-free survival than Non-Young patients (NA vs 214.7 mo, p=0.027); however, there was no statistical significance in median survival. Young patients had a lower median disease-specific survival than non-young patients of 221.1 months vs 282.6 months (p=0.00123) in METABRIC. CONCLUSION: We used large datasets to examine survival in very young breast cancer patients (<40 yo) vs older patients and found that young patients are likely to have unfavorable subtypes, higher stage, and a lower overall survival and DFS as compared to their older counterparts. Further analysis with genomics is needed. Citation Format: Young JS, Kawaguchi T, Yan L, Qi Q, Liu S, Takabe K. Young breast cancer patients (<40 yo) have unfavorable subtypes, higher stage and worse survival [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 P2-05-14.