Patient Characteristics and Outcome Differ in Clinical Trial vs General Population Elderly Patients With Hormone Receptor–Positive Breast Cancer
In a study reported in the Journal of the National Cancer Institute, van de Water et al found that Dutch women with hormone receptor–positive breast cancer aged ≥ 65 years at diagnosis who were treated in a clinical trial had significantly fewer comorbid diseases, higher socioeconomic status, smaller tumors, and lower histologic grade compared with counterparts in the general population. The investigators also found that survival was significantly poorer among general population patients aged ≥ 75 years.
Study Details
The study compared characteristics and outcomes of breast cancer patients aged ≥ 65 years in the Tamoxifen Exemestane Adjuvant Multinational trial (n = 1,325) with those in unselected patients aged ≥ 65 years in the general population (n = 1,056). All patients had hormone receptor–positive breast cancer with nodal involvement, tumor > 3 cm, or histologic grade 3 tumor of 1 to 3 cm, had completed local therapy, and had no distant metastases.
Patients were categorized according to age 65 to 74 years (852 trial patients and 467 general population patients) and age ≥ 75 years (473 trial patients and 589 general population patients).
Differences in Characteristics and Treatment
For both the 65-to-74 year and ≥ 75 year age groups, patients who participated in the trial had fewer comorbid diseases, higher socioeconomic status, smaller tumors, and lower histologic grade (all P < .001 for trends). There was no significant difference in either age group in nodal status.
Patients age ≥ 75 years in the general population were significantly less likely to receive breast-conserving surgery (12.7% vs 24.1%, P < .001). Compared with trial patients (all receiving endocrine therapy as part of the trial), significantly fewer general population patients received endocrine therapy, with only 82% of patients in both age groups receiving such treatment despite their hormone receptor–positive status (P < .001 for both). Chemotherapy use was more common among patients in the general population (11.1% vs 7.4%, P = .054, in 65-to-74 year age group; 3.2% vs 0.0%, P < .001 in the ≥ 75 year group).
Mortality and Distant Recurrence
Five-year cumulative mortality rates for trial patients vs general population patients were 14% vs 19% among those aged 65 to 74 years and 28% vs 48% among those ≥ 75 years. On univariate analysis, overall mortality was significantly lower in trial patients among both those aged 65 to 74 years (hazard ratio [HR] = 0.65, 95% confidence interval [CI] = 0.50–0.86) and those aged ≥ 75 years (HR = 0.49, 95% CI = 0.39–0.60).
The difference in the younger patient group was explained by imbalance in patient, tumor, and treatment characteristics, as shown by the lack of significant difference between trial and general population patients in multivariate analysis adjusting for histologic grade, T stage, nodal stage, most extensive surgery, radiotherapy, endocrine therapy, chemotherapy, socioeconomic status, comorbidity, age, and year of diagnosis (HR = 1.08, P =.69). However, the difference between trial patients and general population patients remained significant in multivariate analysis among patients aged ≥ 75 years (HR = 0.72, P = .02).
Hazard ratios for 5-year risk of distant recurrence for trial patients vs general population patients were 0.72 (P = .05) and 0.87 (P = .45) in the 65-to-74 year age group and the ≥ 75 year group, respectively, on univariate analysis, with multivariate analysis showing no differences between the two groups (HR = 1.17, P = .51, in younger patients; HR = 1.33, P = .28, in older patients).
The investigators concluded, “Breast cancer trial participants aged 75 years or older do not represent elderly breast cancer patients of corresponding age from the general population, which hampers the external validity of a trial.”
Gerrit-Jan Liefers, MD, PhD, of Leiden University Medical Center, is the corresponding author for the Journal of the National Cancer Institute article.
The study was funded by the Dutch Cancer Society. The study authors reported no potential conflicts of interest.
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