Abstract P5-10-03: Breast cancer diagnosed in young women ≤ age 35: Importance of germline mutations and cancer subtypes on treatment outcomes
Authors: Tsai ML , Knaack M , Martone P , Krueger J , Baldinger SR , Lillemoe TJ , Susnik B , Grimm E , Rueth N , Swenson KK 
Published: May 2019

Abstract
Background: While breast cancer is rare in women ≤ age 35, patients in this age group are more frequently diagnosed with aggressive cancer subtypes and pathologic germline mutations in cancer susceptibility genes than older patients. Higher recurrence and mortality rates in young breast cancer patients may be related to differences in tumor biology, pathologic mutation status, host characteristics or treatment.
Specific Aims: The primary purpose of this retrospective study was to evaluate germline mutation status, breast cancer subtypes, and other associated risk factors that may impact recurrence-free and overall survival in patients diagnosed with breast cancer at age ≤ 35.
Methods: This was a retrospective review of all breast cancer cases diagnosed in women ≤ age 35 (n= 306) at Allina Health facilities from the years of 2000 – 2017. We collected information on germline mutation status, histopathologic tumor characteristics (including grade, hormone receptor status, human epidermal growth factor receptor 2 [HER2] status, molecular subtype), pregnancy-associated cancers (within a year of diagnosis), treatment, and recurrence-free and overall survival in this cohort. Kaplan Meier analyses were conducted for recurrence-free and overall survival by mutation status and molecular subtype.
Findings: With a mean follow-up of 6.5 years, the overall survival rate was 88.2%, with a recurrence-free survival rate of 85.2%. A total of 69.3% of patients obtained genetic testing, and 26.9% of those patients had high-risk pathologic mutations, particularly breast cancer gene (BRCA)1 and BRCA2. There were no significant differences in recurrence-free or overall survival between patients with high-risk genetic mutations as compared to those with low-risk/no mutations. However, the definitive surgery and chemotherapy use did vary by mutation status; patients with high-risk mutations were more likely to have bilateral mastectomies and receive chemotherapy (p = 0.002 and p = 0.04, respectively). Kaplan Meier analysis showed that survival was impacted by breast cancer molecular subtype; patients with Luminal B cancer had the lowest overall survival followed by HER2 positive and triple negative cancers (p = 0.05). Other factors associated with decreased survival included cancer stage, angiolymphatic invasion, tumor grade, and pregnancy-associated diagnoses (within a year of diagnosis).
Conclusions: Our study shows that patients with high-risk genetic mutations (primarily BRCA1 and BRCA2) were more likely to receive chemotherapy and bilateral mastectomies. Patients with high-risk mutations had similar rates of survival and recurrence-free survival compared to patients without mutations in this study despite an increased risk of overall recurrence and subsequent cancer. In spite of their young age at diagnosis, nearly a third of patients in this study did not receive genetic testing; these results may have impacted treatment and outcomes. Patients diagnosed with Luminal B subtype had the lowest overall survival. Pregnancy-associated breast cancer diagnoses were associated with decreased survival in this age cohort.
Citation Format: Tsai ML, Knaack M, Martone P, Krueger J, Baldinger SR, Lillemoe TJ, Susnik B, Grimm E, Rueth N, Swenson KK. Breast cancer diagnosed in young women ≤ age 35: Importance of germline mutations and cancer subtypes on treatment outcomes [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 P5-10-03.