Crossover effects of estrogen receptor status on breast cancer-specific hazard rates by age and race

Background: Previous studies found that the risk of breast cancer-related death is greater in estrogen receptor (ER)-negative disease than in ER-positive disease within 5 years of diagnosis, but greater for ER-positive disease than for ERnegative disease more than 5 years after diagnosis. This phenomenon is referred to as ER-positive and -negative crossover. Our aim was to evaluate this crossover by determining the timing of the hazard of breast cancer death by patient, clinical, and tumor factors.

Methods: Patients with breast cancer diagnosed between 1990 and 2005 were identified from the Surveillance, Epidemiology, and End Results database. The cohort was evaluated by age at diagnosis, race, tumor ER status, tumor and nodal stage, and tumor grade. Disease-specific (DS) hazard rates were calculated.

Results: Of the 439,444 patients identified, 77.5% had ER-positive disease. Overall, ER-negative to ER-positive DS hazard rates crossed between the years 7 and 8 after diagnosis. Earlier crossover was linked to black or Hispanic race, young age (<40 years), or tumors that were larger, higher grade, or affected the nodes. Young black (<40 years) patients who had a T3/T4 tumor with positive nodes, grade III or undifferentiated, had the earliest crossover, in year 4.

Conclusions: The timing of crossover of death hazard for ER-positive and ER-negative disease varies by clinical and tumor factors. These findings may help guide recommendations regarding the duration of endocrine therapy for patients with ERpositive cancer.