Among postmenopausal women who have hormone receptor–positive breast cancer, increasing age correlates with a rise in disease-specific mortality, independently of tumor, treatment, and patient characteristics, according to a report in the Feb. 9 issue of JAMA.
This increased cancer-specific mortality is particularly noteworthy because it occurs against a background in which other, competing causes of mortality are also increasing as these women age, said Dr. Willemien van de Water of the departments of surgical oncology and gerontology, Leiden (the Netherlands) University Medical Center, and associates.
To assess the relationship between aging and breast-cancer-specific mortality, the investigators analyzed data from the TEAM (Tamoxifen Exemestane Adjuvant Multinational) study, a phase III, randomized, open-label trial that had no upper age limit and included subjects up to 96 years old. The TEAM study involved 9,766 women who had estrogen receptor–positive tumors, progesterone receptor–positive tumors, or both, and were treated in Belgium, the Netherlands, the United Kingdom, Ireland, the United States, Japan, Greece, Germany, and France.
Because the 5-year TEAM trial found no significant differences in outcomes between the study groups and comparable mortality from other causes, it proved ideal for this post hoc analysis of disease-specific mortality, Dr. van de Water and colleagues said.
They divided the study subjects into three age groups: younger than 65 years (5,349 women; 55% of the entire cohort), 65-74 years (3,060 women; 31% of the cohort), and 75 years and older (1,357 women; 14% of the cohort).
The cumulative incidence of death from breast cancer rose from 5.7% in the youngest group to 6.3% in the intermediate group and 8.3% in the oldest group, the investigators said (JAMA 2012;307:590-7).
"Since tumor and treatment characteristics may be associated with disease-specific mortality, multivariable analyses were performed in an attempt to adjust for unequal distributions among age categories. ... Again, disease-specific mortality increased with age," with hazard ratios of 1.25 for patients aged 65-74 years and 1.62 for those aged 75 and older, compared with women younger than 65.
"To test the robustness of the age cut points, additional analyses were performed with age as a continuous variable, which confirmed an increased risk of breast cancer death per 10-year increase in age," they said.
Because there was a tendency for older patients to have larger tumors at diagnosis than did younger patients, additional analyses were performed to adjust for any residual confounding that might be related to tumor size. The results were unchanged.
Finally, the data were adjusted to account for mortality from competing causes such as infection, trauma, dementia, and cardiovascular disease. Again, the results were not affected by study subjects’ comorbidities.
This study was not designed to assess the reasons why breast-cancer mortality rises with increasing patient age, but the researchers proposed four possible underlying mechanisms.
First, older patients may be undertreated. Several other studies have shown that older age at diagnosis correlates with greater deviation from treatment guidelines for surgery, radiotherapy, chemotherapy, and endocrine therapy, as well as with more frequent cessation of medication.
Next, older patients may be more vulnerable to treatment-related toxicities. Third, tumor biology might be more aggressive in older patients. And fourth, polypharmacy, which is more common in older patients, might cause adverse interactions with anticancer therapies, rendering them less effective, Dr. van de Water and associates said.
The study findings "underline the need for age-specific breast cancer studies in order to improve breast cancer outcome in patients of all ages," they said.
The TEAM trial was supported by Pfizer. Dr. van de Water's associates reported ties to numerous industry sources.