The impact of young age at diagnosis (age <40 years) on prognosis varies by breast cancer subtype: A U.S. SEER database analysis

Purpose: Women under 40 years old are at increased risk for developing human epidermal growth factor receptor 2 (HER2) positive or triple negative subtype and more advanced breast cancer, yet young age itself has also historically been an independent prognostic factor.

Methods: Using the Surveillance, Epidemiology, and End Results (SEER) Program, we examined data for 271,173 women with stage I-III breast cancer between 2010 and 2015. Using Fine and Gray regression models to account for competing risks, we examined the risk of breast cancer-specific death by age and clinical subtypes, considering grade, hormone receptor (HR) and HER2 status, adjusting for demographic, clinical and treatment variables.

Results: Of 271,173 women eligible for analysis, 14,109 were <40 years of age. Women under 40 years old were more likely to be non-white, uninsured, and to have higher stage, higher grade, HER2-positive and triple-negative subtype disease (all, p < 0.001). Compared to women ages 40-60, women ages <40 had higher breast cancer mortality (hazard ratio, 1.8; 95% confidence interval (CI) 1.6-1.9) in unadjusted analysis. In models controlling for demographic, clinical and treatment factors, young age was significantly associated with an increased risk of breast cancer mortality among women with HR-positive, lower grade disease (hazard ratio 1.7; 95% CI 1.4-2.1) but not for women with high grade/HR-positive, HER2-positive, or triple-negative disease. Women age >75 had increased breast cancer mortality in all subtypes.

Conclusion: With modern clinical subtyping, age under 40 remains independently associated with worse outcomes in 30 months follow-up only in HR-positive, lower grade disease.