New Online Tool Aids Decisions on Breast Cancer Endocrine Tx

Liam Davenport

August 24, 2018

A novel online tool could allow clinicians to quickly and easily predict the long-term risk for distant recurrence among women with hormone receptor–positive breast cancer who have undergone 5 years of endocrine therapy and so help in deciding whether or not to continue treatment, say UK researchers.

The Clinical Treatment Score Post–5 Years (CTS5) was developed from an analysis of data of more than 11,000 women from two major clinical trials, using readily available disease measures. The patients had received hormonal therapy for 5 years.

Across the two datasets, the tool was able to identify 42% of women as being at low risk for a recurrence, for whom continuing endocrine therapy would be of little value.

Following the publication of the research in the July 1 issue of the Journal of Clinical Oncology, the team developed an online Web tool from the CTS5 for clinicians to use to make their own calculations.

This online tool was made available on August 24 at www.cts5-calculator.com.

Co–lead researcher Jack Cuzick, PhD, director, Wolfson Institute of Preventive Medicine, Queen Mary University of London, United Kingdom, said in a release: "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.

"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."

Co–lead researcher Mitch Dowsett, PhD, head of the Ralph Lauren Center for Breast Cancer Research, Royal Marsden Hospital, and professor of biochemical endocrinology at the Institute of Cancer Research, London, added that the tool "could improve clinical practice, benefiting breast cancer patients by avoiding potentially unnecessary extended treatment.

"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 added.

Noting that there are currently no other Web-based calculators, author Ivana Sestak, PhD, also of the Wolfson Institute of Preventive Medicine, said that their calculator "provides a very simple way of obtaining the risk of a late metastasis for each woman individually.

"It is very important to identify these women in the clinic, and the calculator provides help in the decision-making process," she said.

Dowsett added that, because the tool relies only on information that is already available from all women with hormone receptor–positive breast cancer, it "could be easily used across the UK and globally at other centers."

The researchers do acknowledge, however, that the data were derived from patients who started treatment before the introduction of trastuzumab (multiple brands), and so clinicians should be cautious of using the tool for patients who are eligible for this drug.

Endocrine Therapy for Longer Than 5 Years

In general, women with estrogen receptor (ER)–positive breast cancer are offered adjuvant endocrine therapy for 5 years. However, more than 50% of recurrences occur after that period, and it has been shown that extending treatment can improve outcomes.

The benefit is nevertheless relatively small, and patients may experience adverse effects, such as bone weakness and exacerbation of menopausal symptoms with longer periods of exposure.

With several factors having been linked to the late recurrence of hormone receptor–positive breast cancer, the researchers set out to develop a simple clinicopathologic tool that would estimate the risk faced by an individual patient.

They used data from the Arimidex, Tamoxifen, Alone or in Combination (ATAC) study, in which postmenopausal women with ER+ or ER-unknown early breast cancer were randomly assigned to receive anastrozole (Armidex, Ani Pharmaceuticals), tamoxifen (multiple brands), or the two together for 5 years.

The team identified 4735 women who had received anastrozole alone or tamoxifen alone, who were recurrence-free at 5 years, and for whom all clinicopathologic data were available.

The women were followed for a median of 9.8 years. The researchers used Cox regression analyses to develop the CTS5 prognostic score for the post-5-year risk for distant recurrence of breast cancer from the measured clinicopathologic parameters.

Subsequently, data on 6711 women from the BIG 1-98 trial were used to validate the prognostic performance of the score. These patients in that trial had been randomly assigned to receive letrozole (multiple brands), tamoxifen, or sequential therapy for 5 years. They had been followed for 8.1 years and were recurrence free.

The CTS5 tool, which incorporates information regarding age, tumor size, quadratic tumor size, and node status and grade, was found to be significantly prognostic for late distant recurrence in both the ATAC cohort (hazard ratio [HR], 2.47; P < .001) and the BIG 1-98 cohort (HR, 2.07; P < .001).

Using the ATAC training cohort, the researchers were able to categorize 42.0% of patients as being at low risk for late distant recurrence, 31.3% as being at intermediate risk, and 26.7% as being at high risk, at mean 5- to 10-year recurrence rates of 2.5%, 7.7%, and 20.3%, respectively.

When applied to the BIG 1-98 cohort, the proportions of low-, intermediate-, and high-risk patients were similar, at 42.6%, 31.8%, and 25.5%, respectively, as were the mean 5- to 10-year recurrence rates, at 3.6%, 6.9%, and 17.3%, respectively.

To arrive at the final CTS5 model, the team combined the two data sets, which allowed them to define new cutoff points for low, intermediate, and high risk.

The study was supported by the National Institute for Health Research Biomedical Research Center at the Royal Marsden National Health Service Foundation Trust, the Institute of Cancer Research, London, Cancer Research UK, and the Susan G. Komen Foundation. Dr Cuzick has received institutional research funding from AstraZeneca. Dr Dowsett has received honoraria from Pfizer, Myriad Genetics, and Roche; has had consulting or advisory roles with Roche/Genentech, GTx, and Radius Health; has received institutional research funding from AstraZeneca, Novartis, Pfizer, and Radius Health; and has received Institute of Cancer Research Rewards for Inventors. Dr Sestak has received honoraria from Myriad Genetics and NanoString Technologies and has had a consulting or advisory role with Myriad Genetics.

J Clin Oncol. 2018;19:1941-1948. Full text

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