What’s new in breast cancer research? San Antonio conference goes hybrid for 2021

Heart-to-heart on cardiotoxicity of treatment

Fred Hutch public health researcher Dr. Heather Greenlee presented findings from the National Cancer Institute-funded Pathways Heart Study in a pair of spotlight poster sessions. The posters broke down the cardiovascular disease risk of different breast cancer therapies by body mass index and investigated the development of cardiometabolic risk factors (such as diabetes, high cholesterol or high blood pressure) following the use of endocrine, or anti-hormone, therapy.

“The impetus for this study is that many breast cancer treatments are cardiotoxic,” meaning they harm the heart, Greenlee said in her presentation on cardiovascular disease risk and BMI, “but it’s not well-established whether overweight and obesity further contributes to cardiovascular event outcomes” such as ischemic heart disease, heart failure/cardiomyopathy (disease of the heart muscle) or stroke.

Working in collaboration with investigators at Kaiser Permanente Northern California, the University of Washington and the Herbert Irving Comprehensive Cancer Center in New York, Greenlee and collaborators looked at the risk of developing cardiovascular disease after receiving different breast cancer treatments, including chemotherapies (anthracyclines, trastuzumab [Herceptin], taxanes and cyclophosphamide), radiation therapy, and endocrine therapy (aromatase inhibitor, tamoxifen). The analyses included women with breast cancer with normal weight, overweight and obesity.

After monitoring more than 13,000 women for an average of seven years, the researchers found that certain chemotherapy drugs and radiation to the left side of the body (where the heart is located) may confer a higher cardiovascular disease risk for normal-weight breast cancer survivors.

“Results showed the risk of specific cardiovascular disease events did vary by BMI category,” Greenlee said.

Findings showed women with normal weight who received anthracyclines had an increased risk of ischemic heart disease and heart failure/cardiomyopathy; normal weight women who received cyclophosphamide and left-sided radiation had an increased risk of heart failure/cardiomyopathy and stroke; and normal weight women who received taxanes had a higher risk of stroke.

Overweight women who received anthracyclines had a higher risk of heart failure and cardiomyopathy. Among obese women, however, Greenlee said receipt of any chemotherapy was associated with lower risk of stroke.  

Why the counterintuitive finding in obese women?

“There may be dose-capping at higher body weights,” Greenlee said of the cardioprotective effect in obese patients. “For many patients at higher BMI levels, the clinical recommendations are for patients to receive very high doses of anthracyclines, but many clinicians are hesitant to do that so they cap the doses. That’s one possibility. Another possibility is that it could have to do with the way the drugs are metabolized.”

Her team will conduct further analysis of specific dosages to see if this modifies the findings, she said.

Greenlee’s second Pathways Heart Study poster, which also relied on data from Kaiser Permanente Northern California, looked at whether women undergoing different types of endocrine therapy developed cardiometabolic risk factors, such as diabetes, high cholesterol or high blood pressure. People with these risk factors are more likely to develop a cardiovascular event such as heart attack or stroke.

Out of nearly 15,000 breast cancer survivors, most of whom were postmenopausal, the researchers found differences in the effects among pre- and post-menopausal women.

Among premenopausal women, the team found no associations between the use of either tamoxifen or aromatase inhibitors, or AIs, and new cardiometabolic risk factors. However, Greenlee noted that this lack of associations may be due to the relatively low number of premenopausal women in the study.

The findings were different in postmenopausal women. Among postmenopausal women, AI users had higher risk of developing dyslipidemia, compared to tamoxifen users. (Dyslipidemia is an abnormal blood level of lipids, or fats, such as cholesterol.) Neither therapy increased the risk of developing diabetes or high blood pressure.

“More work is needed to understand the implications of these associations on long-term cardiovascular health and how to best manage cardiometabolic risk factors in breast cancer survivors with a history of endocrine therapy use,” Greenlee said.

Comparing costs of surveillance 

Dr. Scott Ramsey, director of the Hutchinson Institute for Cancer Outcomes Research, was senior author on a poster comparing the cost of a new blood-based biomarker assay (or test), DiviTum TKa, to that of traditional monitoring technologies. The assay was created to monitor and predict whether a patient’s hormone-receptor-positive metastatic breast cancer responds to treatment.

HICOR researchers work to improve cancer prevention, detection and treatment in ways that will reduce the economic and human burden of cancer — and ultimately lead to better outcomes for patients. 

In this analysis, Ramsey and other researchers (including those from Biovica, the manufacturer) used simulation modeling to compare costs and outcomes for the DiviTum TKa assay plus standard monitoring practices vs. standard monitoring practices alone. They modeled a population of one million estrogen receptor-positive metastatic breast cancer patients who’d received first-line treatment with CDK4/6 inhibitors plus an aromatase inhibitor, or AI.

The researchers evaluated two scenarios. In one, use of the new assay reduced the frequency of traditional monitoring tools. Use of the new assay predicted 203 fewer CT scans, 93 fewer bone scans and 60 fewer biomarker tests in their million-person population over a three-year period.

In the other scenario they evaluated, the assay also predicted treatment would not help, one month in advance of when a scan would find a patient’s disease had progressed. In this scenario, use of the assay predicted treatment-related cost savings.

In conclusion, Ramsey said the use of DiviTum TKa has the potential to reduce the need for much of the traditional monitoring methods (think tumor marker tests, CT scans and bone scans).

“If it can also predict lack of benefit from costly CDK4/6 inhibitor therapy and clinicians act on that information in a timely fashion, this could result in less toxicity and cost savings to patients and health plans,” Ramsey concluded, noting that the net savings of adding this new test to cancer care were estimated to be three times the cost of the test itself.

“Following approval and commercial introduction of this test, future research on practice patterns will be necessary to validate our analysis,” he said.

Overdiagnosis in women

Biostatistician Dr. Ruth Etzioni led an NCI-funded study in collaboration with Dr. Marc Ryser from Duke University to pinpoint how many women using contemporary screening practices are overdiagnosed due to mammography finding a breast cancer that would not become symptomatic or otherwise cause harm.

Currently, there’s a lack of consensus. Estimates for overdiagnosis range from 0% to 54% due to data being collected from different types of studies and countries, and the use of varying screening methods, some of which, Etzioni said, are of questionable validity.

Using individual mammography screening and breast cancer diagnosis records from the Breast Cancer Surveillance Consortium, the researchers developed a mathematical model based on 36,000 screening participants, ages 50 to 74 years, who received nearly 83,000 total screenings using mammography. Out of that total, there were 718 breast cancer diagnoses.

Using their model, they found that with screening done every other year, the predicted overdiagnosis rate was 15.3% among screen-detected cancers. Six percent were due to the detection of slow-growing or inconsequential breast cancers, and 9.3% were due to “competing mortality,” meaning the cancer would not progress to a life-threatening stage before the patient died of other causes.

With annual screening, the overall predicted overdiagnosis rate was similar, at 14.6%.

All told, Etzioni said, “overdiagnosis was lower than reported in high-profile studies that that used excess incidence of breast cancer detected after, vs. before, mammography had been adopted."