A new tool for predicting the risk of severe chemotherapy toxicity in older adults with early-stage breast cancer outperforms existing models and should help older patients and physicians make treatment decisions with more confidence, according to investigators.
They devised and tested the tool, called the Cancer and Aging Research Group–Breast Cancer (CARG-BC) score, in two cohorts of patients aged 65 years or older with stage I-III breast cancer.
The area under the curve for predicting grade 3-5 toxicity was 0.75 in the development cohort and 0.69 in the validation cohort, for a combined AUC of 0.73.
The CARG-BC score outperformed both Karnofsky performance status (AUC, 0.50) and the Cancer and Aging Research Group Chemotherapy Toxicity Tool (AUC, 0.56).
CARG-BC risk groups were also associated with hospitalizations, dose modifications, and early termination of treatment.
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To calculate a patient’s CARG-BC score, the researchers added up points assigned to eight independent predictors of grade 3-5 chemotherapy toxicity:
Planned anthracycline use (1 point)
Stage II or III disease (3 points)
Planned treatment duration longer than 3 months (4 points)
Abnormal liver function (3 points)
Low hemoglobin level (3 points)
A fall in the previous 6 months (4 points)
Limited ability to walk more than 1 mile (3 points)
Lack of social support (3 points)
Patients with scores of 0-5 have a low risk, those with scores of 6-11 have an intermediate risk, and those with scores of 12 or above have a high risk of grade 3-5 toxicity.
Patient Characteristics and Results
There were 283 patients in the development cohort and 190 in the validation cohort. There were no significant demographic, disease, or treatment differences between the cohorts.
All patients had a mean age of 70.5 years, 36.2% had stage I disease, 42.9% had stage II, and 20.9% had stage III disease. Three-quarters of patients were non-Hispanic White, and 99.4% were women. Roughly a third of patients had received an anthracycline-based regimen.
Overall, about a quarter of patients had an unplanned dose reduction (24%), dose delay (26%), stopped treatment early (24%), or were hospitalized during treatment (23%). All of these occurrences were more likely in intermediate- and high-risk patients versus low-risk patients (P < .001).
In the development cohort, 19% of low-risk patients, 54% of intermediate-risk patients, and 87% of high-risk patients developed grade 3-5 chemotherapy toxicity.
Compared with the 93 patients in the low-risk group, the odds of toxicity was almost 5 times greater for the 159 intermediate-risk subjects, and 28 times greater for the 30 high-risk subjects.
In the validation cohort, grade 3-5 toxicity rates were 27% in the low-risk group, 45% in the intermediate-risk group, and 76% in the high-risk group.
This study had its limitations, including that a majority of subjects (72.2%) had a college education, and the validation cohort was accrued from the same 16 institutions as the development cohort.
“Further validation in a more diverse population should be considered,” the investigators wrote.
A “Useful” Tool for Guiding Therapy
The investigators noted that chemotherapy is a complex decision for older adults with stage I-III breast cancer. While it may be indicated, chemotherapy is underused often because of the higher risk of severe toxicity in older people.
“Unfortunately, older adults aged 65 and over, who comprise about half of all breast cancer diagnoses, are significantly less likely to be offered chemotherapy compared to younger patients – sometimes because their doctors fear they won’t be able to tolerate it,” investigator Mina Sedrak, MD, of City of Hope National Medical Center in Duarte, Calif., said in a press release.
The CARG-BC score may be useful to direct therapy in older adults with early-stage breast cancer, the investigators wrote. They noted that intensifying supportive care and developing modified treatment regimens may be appropriate for patients at higher risk for toxicity.
“Although this score should not be used as the only factor in deciding whether to administer and/or alter the dose or schedule of chemotherapy, the CARG-BC score can be used to facilitate this complex decision-making process, along with clinical judgment and patient preferences,” they wrote.
“I think this is a great tool. [It] will be helpful to me to have a more accurate conversation with geriatric patients about the actual risk/benefit ratio for chemotherapy in early breast cancer,” said Amy Tiersten, MD, of Mount Sinai Hospital in New York, when asked for comment.
“If routinely implemented, it may help reduce age bias and also identify older patients who may look well but may be vulnerable and quickly decompensate while undergoing treatment,” said Lidia Schapira, MD, of Stanford (Calif.) University. “Importantly, it can be used to guide conversations about trade-offs and to start a frank conversation about an older patient’s fears and concerns about treatment.”
This research was funded by the National Institute on Aging, the Breast Cancer Research Foundation, and the Center for Cancer and Aging at City of Hope. The investigators, Schapira, and Tiersten had no relevant disclosures.