Recurrence of estrogen-receptor-positive early-stage breast cancer after endocrine therapy associated with TN status at diagnosis

Patients with stage T1 disease had a 13% risk of distant recurrence with no nodal involvement, 20% risk with involvement of one to three nodes, and 34% risk with involvement of four to nine nodes.


Long-term recurrence of early-stage breast cancer after adjuvant endocrine therapy is associated with tumor diameter and nodal (TN) status at diagnosis, according to a new study.

Researchers from the Early Breast Cancer Trialists' Collaborative Group (EBCTCG) performed a meta-analysis involving 62,923 women diagnosed with estrogen-receptor-positive early-stage breast cancer before age 75 years who had been scheduled to receive five years of endocrine therapy. The women continued to be followed at five years and had no recurrent disease or second case of cancer. The goal of the study was to examine the association of TN status, tumor grade, and other factors at diagnosis with outcomes over five to 20 years in women with early-stage breast cancer. Main outcome measures were rate of distant recurrence, rate of any breast cancer event (defined as distant recurrence, loco-regional recurrence, or contralateral new primary tumor), and rate of death from breast cancer. The study results were published in the Nov. 9 New England Journal of Medicine.

All of the women in the study had data available on TN status, and 69% had data available on tumor grade. Throughout the study period, the rate of breast cancer recurrence was steady, and risk for distant recurrence was strongly associated with original TN status. Patients with stage T1 disease had a 13% risk of distant recurrence if they had had no nodal involvement, 20% risk with involvement of one to three nodes, and 34% risk with involvement of four to nine nodes. For patients with stage T2 disease, these risks were 19%, 26%, and 41%, respectively. A similar link was seen between original TN status and risk for death from breast cancer but not between original TN status and risk for contralateral breast cancer.

Data on tumor grade and presence of Ki-67 antibody were available in 69.3% and 12.7% of patients, respectively. These two variables were strongly correlated with each other and had moderate predictive value for distant recurrence. However, progesterone-receptor and human epidermal growth factor receptor type 2 (HER2) status, which were available in 86.0% and 24.5% of patients, respectively, did not appear to be predictive. For patients who had stage T1 disease and no nodal involvement, absolute risk for distant recurrence over the study period was 10% for low-grade disease, 13% for moderate-grade disease, and 17% for high-grade disease. Respective corresponding risks for any recurrence or contralateral breast cancer were 17%, 22%, and 26%.

The authors noted that the study involved women who were scheduled to receive five years of endocrine therapy rather than those who completed treatment. Among other limitations, they also pointed out that approximately 50% of the patients in their study received a diagnosis of breast cancer before 2000 and that diagnosis, staging, and treatment have since improved. However, they concluded that women who had estrogen-receptor-positive early-stage breast cancer have a persistent risk for recurrence and death for at least 20 years after their original diagnosis, even after five years of adjuvant endocrine therapy.

The authors noted that their findings have implications for strategies addressing long-term follow-up of these patients and highlight the need for renewed attention to reducing late disease recurrence. “Recognition of the magnitude of the long-term risks of [estrogen-receptor]-positive disease can help women and their health care professionals decide whether to extend therapy beyond 5 years and whether to persist if adverse events occur,” the authors wrote.