Among postmenopausal women with hormone receptor-positive breast cancer, increasing age was associated with a higher risk of death from breast cancer regardless of competing mortality and independent of tumor and treatment characteristics, according to a study in the Feb. 8 issue of the Journal of the American Medical Association.

Breast cancer is the leading contributor to cancer mortality in women worldwide, and in the U.S. in 2008, 41 percent of these women were aged 65 years or older at diagnosis.

While observational data in patients have hinted at an age-specific association with mortality, data are often lacking regarding treatment and competing risks of death are more present in older populations, according to Willemien van de Water, MD, of Leiden University Medical Center in Leiden, the Netherlands, and colleagues. To analyze disease-specific mortality among postmenopausal patients, van de Water et al turned to the TEAM (Tamoxifen, Exemestane, Adjuvant, Multinational) trial, a randomized, phase 3 study conducted in postmenopausal breast cancer patients with estrogen or progesterone receptor–positive tumors.

The analysis included 9,766 patients enrolled in the TEAM trial between January 2001 and January 2006. Patients were categorized into three groups by age at diagnosis: younger than 65 years, 65 to 74 years and 75 years or older.

During median follow-up of approximately 5.1 years, there were a total of 1,043 deaths, and the proportion of deaths due to breast cancer compared with all-cause mortality lowered with increasing age. However, in multivariable analyses, disease-specific mortality increased with age for patients ages 65 to 74 years and patients 75 years or older compared with patients younger than 65 years

Overall, cumulative incidence of death due to breast cancer increased from 5.7 percent in patients younger than 65 years, 6.3 percent in patients 65 to 74 years of age, to 8.3 percent in patients 75 years or older. Increasing age was also associated with a higher risk of breast cancer relapse.

“Adjustment for both treatment and tumor characteristics did not eliminate the association between age and disease-specific mortality,” wrote the authors. “Consequently, other unknown factors might have contributed to our findings. Older patients might respond differently to a tumor than younger patients. In addition, older patients might respond differently to a certain therapy.”

The authors speculated that a possible underlying mechanism that may help explain the age-specific outcome in this relatively healthy population is that older patients may experience undertreatment, and in particular undertreatment of either chemotherapy or radiotherapy. A previous TEAM study analysis showed that patients aged 75 years or older frequently discontinued study medication. And radiotherapy after a wide local excision was administered less frequently among older patients. The researchers also pointed out that although 48 percent of patients aged 75 years or older had nodal involvement, only 5.2 percent received adjuvant chemotherapy.

“These data underline the need for age-specific breast cancer studies in order to improve breast cancer outcome in patients of all ages,” wrote van de Water et al. “Moreover, future detailed population-based and translational studies may increase insight into causal factors of higher disease-specific mortality and breast cancer relapse with increasing age.”