Prognostic Tool Can Guide Extended Endocrine Therapy in ER+ Breast Cancer

A prognostic tool based on simple tumor- and patient-based characteristics could be used to identify patients with hormone receptor–positive breast cancer who underwent 5 years of endocrine treatment and who might be at higher risk of late distant recurrence (DR), according to a new analysis.

In estrogen receptor (ER)-positive primary breast cancer, most patients are generally offered adjuvant endocrine therapy for 5 years. “More than 50% of recurrences occur after that time, and several studies have indicated that extending treatment beyond 5 years can improve disease outcome,” wrote study authors led by Mitch Dowsett, PhD, of Royal Marsden Hospital in London. That benefit of extended treatment, though, is relatively modest. “Few tools have been developed for selecting patients as candidates for extended endocrine therapy or alternatively identifying those who might be spared such therapy.”

The researchers developed a tool known as the Clinical Treatment Score post–5 years (CTS5) to help stratify those patients based on risk of DR. They trained the tool using the ATAC trial, which included 4,735 patients with ER-positive breast cancer randomized to receive either anastrozole alone or tamoxifen alone, and it was then validated in the BIG 1-98 trial, which included 6,711 patients randomized to receive either letrozole or tamoxifen.

The CTS5 included age, tumor size, nodal status, and disease grade; it divided patients into those with a low risk of 5- to 10-year DR (< 5%), intermediate risk (5% to 10%), and high risk (> 10%). The results of the study were published in the Journal of Clinical Oncology.

In the ATAC cohort, 42.0% of patients were categorized as low risk, while 31.3% were intermediate risk, and 26.7% were at high risk for late DR. The observed 5- to 10-year DR rates in these three risk groups were 2.5%, 7.7%, and 20.3%, respectively. The patients at intermediate risk had a 3.42-fold higher risk of late DR than the low-risk patients; for the high-risk group, there was a 9.43-fold higher risk.

The CTS5 was significantly prognostic for late DR in the ATAC cohort, with a hazard ratio (HR) of 2.47 (95% CI, 2.24–2.73; P < .001). The same was true in the BIG 1-98 validation cohort, with an HR of 2.07 (95% CI, 1.88–2.28; P < .001).

“We expect that the CTS5 tool reported and validated here will prove helpful to oncologists and patients in making a decision about continued treatment,” the authors concluded. “The integration of clinical pathologic features that are measured in all patients at diagnosis should mean that risk is calculable at little expense globally.” They noted that it may be possible in the future to combine this tool with multigene expression profiles to further refine prognostic ability.