Mortality rates among early-stage hormone receptor-positive breast cancer patients: a population-based cohort study in Denmark.

BACKGROUND: Indications for adjuvant endocrine treatment of breast cancer have gradually increased over the past several years. We aimed to define subgroups of patients who may or may not benefit from adjuvant endocrine therapy. METHODS: A population-based cohort of systemically untreated breast cancer patients (N = 3197) were identified within the registry of the Danish Breast Cancer Cooperative Group (DBCG). The patients were node negative and had estrogen receptor-positive and/or progesterone receptor-positive tumors (except medullary tumors) and were further characterized by the following risk factors: aged 35-74 years (grouped into 5-year categories) at surgery, tumor size (≤20 mm), and histopathology (grade 1 ductal carcinoma, grade 1 or 2 invasive lobular carcinoma, other or unknown histopathology). Standardized mortality ratios (SMRs) were calculated based on the mortality rate (observed number of deaths per 100,000 person-years) among patients relative to the mortality rate in the general population of women (expected number of deaths per 100,000 person-years). The association between standardized mortality ratio and risk factors were analyzed in univariate and multivariable Poisson regression models. All findings were validated in a subsequent DBCG cohort of breast cancer patients (N = 2710). RESULTS: The median follow-up after surgery was 14.8 years. In the study population there were 970 deaths compared with expected death of 737 women, which was an excess mortality of 233 deaths (SMR = 1.32, 95% CI = 1.24 to 1.40). Mortality rates were 2356 per 100,000 person-years in the study population and 1790 per 100,000 person-years in the general population of women. The mortality rate was associated with larger tumor size (11-20 mm tumors vs 1-10 mm tumors, SMR = 1.42, 95% confidence interval [CI] = 1.31 to 1.53 vs. SMR = 1.12, 95% CI = 1.00 to 1.26). The mortality rate was also associated with age (35-59 years, SMR > 1) compared with that in the general population of age-matched women, except for a small subgroup of patients (aged 60-74 years, tumors ≤10 mm, grade 1 ductal carcinoma, and grade 1 or 2 lobular carcinoma: adjusted relative risk = 1.02, 95% CI = 0.89 to 1.16.). CONCLUSIONS: A small subgroup of breast cancer patients who were 60 years or older and had hormone-responsive early-stage tumors up to 10 mm, and received no systemic adjuvant therapy, were not at increased risk of mortality compared with women in this age-group in the general population.

Population-based study of peritumoral lymphovascular invasion and outcome among patients with operable breast cancer.

BACKGROUND: Lymphovascular invasion has been associated with poor prognosis in women with breast cancer, but it is unclear whether the presence of lymphovascular invasion should be considered sufficient to reclassify breast cancer patients who are at a low risk of recurrence into a high-risk category. METHODS: Of the 16,172 patients with operable breast cancer who were entered into the Danish Breast Cancer Cooperative Group Registry from January 1, 1996, to December 31, 2002, lymphovascular invasion was classified at primary diagnosis in 16,121 patients as present (n = 2453, 15%) or as absent (n = 13,206, 82%). Patients with at least one of the risk criteria (positive lymph nodes, tumor size > 2 cm, high grade, hormone receptor-negative tumor, or younger than 35 years) were assigned to the high-risk group; the other patients were assigned to the low-risk group. All procedures, including report forms, central review, and querying, were specified in advance. Kaplan-Meier analyses were used to estimate disease-free intervals and overall survival rates among patients with and without lymphovascular invasion, and multivariable analysis was used to adjust for differences in baseline characteristics and therapy. All statistical tests were two-sided. RESULTS: Complete follow-up was achieved for 15,659 patients. The median estimated potential follow-up was 6.4 years for invasive disease-free interval and 7.7 years for overall survival. Invasive disease-free interval and overall survival were statistically significantly associated with lymphovascular invasion within the high-risk group (hazard ratio [HR] for invasive disease = 2.29, 95% confidence interval [CI] = 2.14 to 2.45, P < .001; and HR for death = 2.42, 95% CI = 2.25 to 2.61, P < .001) but not within the low-risk group. At 5 years after surgery, 65.4% (95% CI = 63.5% to 67.3%) and 85.2% (95% CI = 84.5% to 85.9%) of those in the high-risk group with and without lymphovascular invasion were alive; 98.1% (95% CI = 87.6% to 99.7%) and 94.1% (95% CI = 93.2% to 94.8%) of those in the low-risk group with and without lymphovascular invasion were alive. These differences persisted in a multivariable analysis, and for overall survival, a statistically significant interaction (P = .03) was observed between lymphovascular invasion and risk group. CONCLUSIONS: In this prospective population-based study, lymphovascular invasion was not an independent high-risk criterion. Lymphovascular invasion should not by itself be considered sufficient to move patients from a low-risk group to a high-risk group.