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Tool predicts risk for late breast cancer recurrence

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September 19, 2018

An online prognostic tool accurately determined the risk for late distant recurrence among women with ER-positive breast cancer, according to a single-arm, prospective study.

The Clinical Treatment Score post-5 years (CTS5) tool could be used to determine whether patients should continue endocrine therapy 5 years after initial treatment.

“Hormone-sensitive breast cancer is one of the few cancers where late recurrence is common, and predicting who is at high risk is particularly important so that they can continue hormone treatment,” Jack Cuzick, PhD, director of the Wolfson Institute of Preventive Medicine and head of the Centre for Cancer Prevention Centre for Cancer Prevention at Queen Mary University of London, said in a press release. “While our ability to predict this type of cancer is highly likely to improve in the future, we're providing a simple tool which is available now, and is easily used and well tested.”

To develop CTS5 — a web-based calculator — researchers used the Arimidex, Tamoxifen, Alone or in Combination, or ATAC, dataset (n = 4,735) to determine rates of delayed metastasis 5 to 10 years after endocrine therapy.

CTS5 calculates a prognostic score for risk of distant recurrence after 5 years of endocrine therapy. Clinicians input each patient’s age, tumor size and tumor grade to get their estimated 5- to 10-year risk, as well as an estimated benefit from extending the patient’s hormone therapy.

The tool defines the risk for distant recurrence within the next 5 to 10 years as low (< 5%), intermediate (5% to 10%) or high (> 10%).

Cuzick and colleagues evaluated the validity of the tool among 6,711 postmenopausal women — derived from the BIG 1-98 dataset — with ER-positive breast cancer who had completed 5 years of endocrine therapy after breast cancer treatment.

The tool appeared significantly prognostic for late distant recurrence in the ATAC cohort (HR = 2.47; 95% CI, 2.24-2.73) and the BIG 1-98 validation cohort (HR = 2.07; 95% CI, 1.88-2.28).

The tool identified 43% of patients from the validation cohort as having low risk for distant recurrence between years 5 and 10 post-treatment, suggesting these patients could forgo extended endocrine therapy.

“What we have developed could improve clinical practice, benefiting breast cancer patients by avoiding potentially unnecessary extended treatment,” Mitch Dowsett, PhD, FMedSci, head of the Royal Marsden Ralph Lauren Centre for Breast Cancer Research and professor of biochemical endocrinology at The Institute of Cancer Research, said in a press release.

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Among patients deemed low risk in the validation cohort, researchers observed a distant recurrence rate of 3.6% (95% CI, 2.7-4.9) during years 5 to 10.

The tool categorized 63% of node-negative patients as low risk. Researchers observed a distant recurrence rate of 3.9% (95% CI, 2.9-5.3) among the low-risk, node-negative patients.

Twenty-four percent of patients with one to three positive nodes appeared low risk, and 1.5% (95% CI, 0.5-3.8) went on to develop distant recurrence.

Rates of distant recurrence increased to 6.9% (95% CI, 5.6-8.5) for those deemed intermediate risk, and 17.3% (95% CI, 14.8-20.1) for those deemed high risk, thus demonstrating correspondence with the predicted risk.

“Clinicians require expertise and the best tools to help them make crucial decision on treatment for patients, decisions that can make a difference to patients’ quality of life,” Dowsett said in the release. “This tool uses information that is already gathered in all patients, so could be easily used across the U.K. and globally at other centers.”

CTS5 appeared significantly prognostic among women who received chemotherapy (HR = 1.76; 95% CI, 1.46-2.13) and those who didn’t (HR = 2.2; 95% CI, 1.96-2.47).

Compared with multigene expression profiles and related risk scores, which can direct patient care at diagnosis, CTS5 is calibrated for application 5 years after diagnosis.

“Over the first 10 years of follow-up, clinicopathologic and molecular factors have nearly completely independent prognostic value, and their optimal use for prognosis requires their integration,” the researchers wrote. “It is near certain that the same is true for the 5- to 10-year period. CTS5 provides a straightforward starting point for combining with molecular scores.”

The risk calculator is available at www.cts5-calculator.com. – by Cassie Homer

Disclosures: Cuzick reports institutional research funding from AstraZeneca. Dowsett reports honoraria from Myriad Genetics, Pfizer and Roche; consultant/advisory roles with GTx, Radius Health and Roche/Genentech; institutional research funding from AstraZeneca, Novartis, Pfizer and Radius Health; and ties to the Institute of Cancer Research Rewards for Inventors. Please see the study for all other authors’ relevant financial disclosures.

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