The risk of breast cancer recurrence persists up to 32 years after a patient’s primary diagnosis, according to a study published in the Journal of the National Cancer Institute.

The results showed that patients with high lymph node burden, larger tumors, or estrogen receptor (ER)-positive disease had an increased risk of late recurrence.

For this study, researchers used Danish population-based and medical registries to investigate the incidence of breast cancer recurrence up to 32 years after primary diagnosis. The researchers also evaluated the association between tumor and patient characteristics at primary diagnosis and the risk of recurrence.

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The study included 20,315 women diagnosed with early breast cancer between January 1, 1987, and December 31, 2004, who did not have a recurrence or second cancer at 10 years after diagnosis.

From year 10 to 32 (a median follow-up of 17 years from diagnosis), 2595 patients experienced breast cancer recurrence. The incidence rate was 15.53 per 1000 person-years.

The cumulative incidence of breast cancer recurrence was 8.5% at 15 years, 12.5% at 20 years, 15.2% at 25 years, and 16.6% at 32 years. 

The cumulative incidence of recurrence 10 to 25 years after diagnosis increased with increasing lymph node involvement at baseline, ranging from 12.7% for patients with T1N0 disease to 24.6% for patients with T2N4-9 disease.

Conversely, the cumulative incidence of recurrence at 10 to 25 years decreased with increasing tumor grade. The incidence was highest in patients with grade I disease and involvement of 4 or more lymph nodes (37.9%) and lowest for patients with grade III disease without the involvement of lymph nodes (7.5%).

The cumulative incidence of recurrence at 10 to 25 years was 14.4% in patients with tumors measuring 20 mm or less and 15.5% in patients with larger tumors.

The risk of late recurrence was higher among patients younger than 40 years of age (hazard ratio [HR], 1.47; 95% CI, 1.22-1.78), those who underwent breast-conserving surgery vs mastectomy (HR, 1.38; 95% CI, 1.26-1.51), those with 4 or more positive lymph nodes (HR, 2.67; 95% CI, 2.31-3.08), those with tumors larger than 20 mm (HR, 1.23; 95% CI, 1.13-1.35), and those who received endocrine therapy (HR, 1.27; 95% CI, 1.13-1.43).

In contrast, the risk of late recurrence was lower among patients with grade III tumors (HR, 0.57; 95% CI, 0.48-0.66), those with ER-negative disease (HR, 0.68; 95% CI, 0.59-0.79), and those who received chemotherapy (HR, 0.84; 95% CI, 0.74-0.96).

“Our findings suggest that a subset of patients — with larger tumors, positive lymph nodes, or ER-positive disease — are at risk of late recurrence,” the researchers concluded. “Such patients may warrant extended surveillance, more aggressive treatment, or new therapies.”

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Pedersen RN, Esen BO, Mellemkjaer L, et al. The incidence of breast cancer recurrence 10-32 years after primary diagnosis. J Natl Cancer Inst. Published online November 8, 2021. doi:10.1093/jnci/djab202

This article originally appeared on Cancer Therapy Advisor