Distant recurrence rates in early-stage breast cancer decreased in RCTs after the 2000s

Women with early-stage breast cancer (BC) entering randomized controlled trials (RCTs) after the 2000s have reduced rates of distant recurrence vs the 1990s, a patient-level pooled analysis by the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) has shown.

“Women with oestrogen receptor [ER]–positive early-stage BC remain at risk of distant recurrence for >20 years after diagnosis. Little data are available on distant recurrence risk for ER-negative BC,” wrote the researchers. [Lancet 2024;404:1407-1418]

In the pooled analysis, the researchers used patient-level data (n=155,746; 151 RCTs) from the EBCTCG database to compare rates of distant recurrence for patients with newly diagnosed early-stage BC enrolled in RCTs in 1990–1999 (before the 2000s) vs those enrolled in 2000–2009 (after the 2000s). The analysis included both women with ER-positive BC (n=114,811) and those with ER-negative BC (n=40,935).

Lower risks of recurrence in both ER+ & ER- tumours

Women with early-stage BC enrolled in RCTs after the 2000s had markedly lower 10-year risks of distant recurrence vs those enrolled earlier. Specifically, for ER-positive cases, the distant recurrence risks were 11.7–15.4 vs 20.5 percent for the respective periods. The corresponding risks for ER-negative cases were 18.2–21.5 vs 29.7 percent.

The shapes of the recurrence curves differed; the risk of distant recurrence in the ER-positive group remained constant beyond 5 years after diagnosis and enrolment, whereas about 80 percent of the recurrences occurred in the first 5 years in the ER-negative group.

After adjustment for therapy, patients with ER-positive and ER-negative disease enrolled between 2000 and 2009 were found to have a 25 and 19 percent lower risk of distant recurrence, respectively, vs those enrolled between 1990 and 1999.

More recently diagnosed patients likely to have N0 disease

“A significant proportion of the improvement [in distant recurrence risk] can be explained by changes in the population of women in these trials,” pointed out the researchers.

The proportion of women with N0 disease entering RCTs increased after the 2000s (ER-positive cases: from 36.7 to 53.7 percent; ER-negative cases: from 43.0 to 55.7 percent). Ten-year distant recurrence risks during 2000–2009 vs 1990–1999 were as follows:

• N0 disease: 7.3 vs 10.1 percent for ER-positive disease and 11.9 vs 18.3 percent for ER-negative disease;
• N1–3: 14.7 vs 19.9 percent for ER-positive disease and 22.1 vs 31.9 percent for ER-negative disease;
• N4–9 positive nodes: 28.5 vs 39.6 percent for ER-positive disease and 36.5 vs 47.8 percent for ER-negative disease.

Improved adjuvant treatments

More effective adjuvant endocrine therapies (eg, aromatase inhibitors, longer endocrine therapy duration) have been introduced into standard care, which may explain the improved trial outcomes over the years.

“Our study reflected current standards of care by excluding patients assigned to take endocrine therapy for <5 years. Had we included patients with shorter treatment, the unadjusted improvements in outcomes for patients with ER-positive disease diagnosed in 2000–2009 vs 1990–1099 would likely have been even greater,” commented the researchers.

“More recently introduced adjuvant treatments, such as immune checkpoint inhibitors, poly [ADP-ribose] polymerase inhibitors, and novel anti-HER2 treatments, have the potential to further reduce distant tumour recurrence rates,” added the researchers.