Molecular Subtypes and Pathogenic Germline Mutations Vary by Ethnicity in Young Women Treated With Breast-Conserving Surgery and Radiation Therapy

Abstract

Historically, young age has been associated with higher rates of locoregional recurrence following breast-conserving surgery and radiation therapy. A greater proportion of Hispanic, African American (AA), and Asian women are diagnosed at a young age compared with Caucasian women. The primary objective of this study was to characterize the distributions of molecular subtypes and pathogenic germline variants in different ethnicities of young women treated with breast-conserving surgery and radiation therapy (BCT). From January 1, 2000 through December 31, 2015, 253 women aged 50 or younger at diagnosis were treated with BCT at our institution. Radiation consisted of tangential fields to the whole breast in all patients. A boost to the tumor bed and radiation to the regional lymph nodes was delivered at the discretion of the treating physician. Systemic therapy consisted of hormone therapy with or without ovarian suppression, chemotherapy, and/or targeted biologic therapies such as Trastuzumab. Molecular subtype was approximated by immunohistochemistry (IHC) receptor status. 180(71%) of these patients underwent genetic testing and 62 (25%) had expanded gene panel testing of 6-70 cancer susceptibility genes beyond BRCA 1 and 2. Fisher’s exact test was used for molecular subtype comparisons between ethnicities. Locoregional control (LRC), disease-free survival (DFS), and overall survival (OS) were estimated using the Kaplan-Meier method. This cohort was comprised of 61% Caucasian, 25% Asian, 10% Hispanic, and 4% AA women. Distributions of molecular subtype by ethnicity were as follows: Caucasians (63% luminal A, 16% luminal B, 2% Her2(+), 19% basal); Asians (65% luminal A, 21% luminal B, 5% Her2(+), 10% basal); Hispanics (31% luminal A, 15% luminal B, 54% basal); AA (44% luminal A, 33% luminal B, 22% basal). There were significant differences in molecular subtype distributions between Hispanic women with Caucasian (p=0.002) and Asian women (p<0.001). In a subset of 142 patients treated from 2000-2011 with a median follow-up of 6.5 years, 5-year LRC, DFS, and OS were 97%, 93%, and 97%, respectively. Univariate analyses found no statistically significant associations between molecular subtype with LRC, DFS, and OS. Pathogenic mutations were detected in 15 (8%) patients and were distributed by ethnicity as follows: Caucasians (11: APC(2), BARD1, BRCA1(3), BRCA2, CHEK2(2), MUTYH, PALB2); Hispanics (2: BRCA1, PALB2); Asians (1: MUTYH); AA (1: PALB2). Expanded panel testing was not routinely performed at our institution until 2013 and its utility in risk stratification is the subject of future investigation. A heterogeneous distribution of molecular subtypes and germline variants appeared to vary by ethnicity in young women treated with BCT.