Risk for Breast Cancer Recurrence Persists Past 30 Years

M. Alexander Otto, MMS, PA

November 16, 2021

For the first time, new data show that risk for breast cancer recurrence extends past 30 years.

The data come from a Danish study involving 20,315 women who were treated for early operable breast cancer between 1987 and 2004, and all of whom were disease-free at 10 years.

Further follow-up showed that 2595 women had a breast cancer recurrence more than 10 years after their primary diagnosis.

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

Recurrence risk was greatest early in the study period.

Women who had primary tumors larger than 20 mm, lymph node-positive disease, and estrogen receptor-positive tumors were at higher risk for late recurrence.

"Such patients may warrant extended surveillance, more aggressive treatment, or new therapy approaches," said the investigators, led by Rikke Pedersen, MD, a PhD candidate in epidemiology at Aarhus University Hospital in Denmark.

"Our observed high cumulative incidence of late breast cancer recurrence is a concern given the increasing prevalence of long-term survivors." Among other things, a new model to better select women for prolonged surveillance is needed, they said.

The new findings were published online November 8 in the Journal of the National Cancer Institute (NCI).

This study confirms previous investigations, but it is the first to report that breast cancer can recur more than 30 years after diagnosis, note the authors of an accompanying editorial, Serban Negoita, MD, DrPH, and Esmeralda Ramirez-Peña, PhD, MPH, both from the National Cancer Institute.

The caveat is that treatment has evolved considerably since the women in the study were diagnosed, so the prognostic value of the findings with current treatment regimens is uncertain, they note. Some studies haven't found a recurrence benefit for aggressive upfront treatment, but those studies had shorter follow-ups.

Research into the issue is "increasingly important" to guide clinical management and counsel women who are living longer after their primary diagnosis, they comment.  

Further Details from the Study

Data for the study came from the Danish Breast Cancer Group clinical database and other national databases. The researchers focussed on women who were disease-free at 10 years after their primary diagnosis, which was stage I or II disease. Median age was 55 years.

Cumulative incidence for breast cancer recurrence was highest for grade 1 tumors with four or more positive lymph nodes (37.9% 10-25 years after the primary diagnosis) and was lowest for patients with grade 3 disease and no involved lymph nodes (7.5%).

The finding of higher recurrence incidence with lower grade tumors goes against some previous reports, the researchers commented. It may be that  some tumors considered lower risk decades ago, and treated accordingly, would be considered higher risk in more recent times.

The cumulative incidence of late recurrence was also higher in younger patients and those treated with breast-conserving surgery instead of mastectomy, the team reported.

Adjusted hazard ratios followed the incidence trends, with higher hazards of recurrence for women diagnosed before age 40 as well as those who had breast-conserving surgery, four or more positive lymph nodes, and primary tumors 20 mm or more across.

The work was funded by the Danish Cancer Society and Aarhus University. Lead author Pedersen reports no disclosures, but co-authors report ties to Amgen, Novo Nordisk, Roche, and other companies. The editorialists have disclosed no relevant financial relationships.

J Natl Cancer Inst. Published online November 8, 2021. Abstract, Editorial

M. Alexander Otto is a physician assistant with a master's degree in medical science, and an award-winning medical journalist who has worked for several major news outlets before joining Medscape. He is an MIT Knight Science Journalism fellow. Email: aotto@mdedge.com

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