New Tool Helps Predict Risk of Severe Chemotherapy Side Effects in Older People With Early-Stage Breast Cancer
Published on January 20, 2021
By combining eight factors, a new tool called the Cancer and Aging Research Group-Breast Cancer score, or CARG-BC score for short, helps predict whether older people diagnosed with early-stage breast cancer will have serious side effects from chemotherapy.
The research was published online on Jan. 14, 2021, by the Journal of Clinical Oncology. Read the abstract of “Development and Validation of a Risk Tool for Predicting Severe Toxicity in Older Adults Receiving Chemotherapy for Early-Stage Breast Cancer.”
About chemotherapy side effects
Chemotherapy medicines work by targeting rapidly dividing cells, such as cancer cells. But healthy cells in your blood, mouth, intestinal tract, nose, nails, vagina, and hair also divide rapidly. So chemotherapy affects them, too.
The side effects you may have from chemotherapy depend on the treatment regimen you're on, the amount of medicine you're getting, the length of treatment, and your general health.
Still, research shows that older people have a higher risk of more serious side effects from chemotherapy. This is true in part because older people are more likely to have other health conditions, such as high blood pressure, heart problems, or frailty.
An earlier study reported that more than 72% of people age 60 and older diagnosed with cancer said they would not want treatment that caused functional problems, even if the treatment improved survival.
The researchers wanted to do this study for two reasons. Although there are tools available to help determine the risk of chemotherapy side effects, most were developed using younger people and may not accurately predict side effects in older people. Also, the existing tools were developed in people with a variety of cancers and on many different chemotherapy regimens.
The CARG-BC score focuses specifically on chemotherapy for early-stage breast cancer in people age 65 and older.
“Though chemotherapy is an effective way to treat early-stage breast cancer, it also carries a risk of side effects,” Canlan Sun, M.D., senior author of the study and associate research professor at City of Hope, said in a statement. “There is a delicate balance between the benefits of chemotherapy and the harm of possible side effects. The development of severe chemotherapy toxicity not only can harm the patient, but it can also compromise an older adult's ability to complete the full course of chemotherapy, possibly reducing the potential benefit of the cancer treatment.”
About the study
The study included 473 people age 65 and older diagnosed with stage I to stage III breast cancer. All the people were scheduled to receive chemotherapy, either before or after surgery.
Chemotherapy before surgery is called neoadjuvant chemotherapy, and chemotherapy after surgery is called adjuvant chemotherapy.
Before the people in the study started chemotherapy, the researchers collected demographic information about their:
age
sex
race/ethnicity
education
marital status
household make-up
Overall:
the average age was 70.5
56.2% were married
75.5% were non-Hispanic white
72.1% lived with another person
72.2% had a college education or higher
The researchers also collected clinical information about:
their cancer stage
the estrogen, progesterone, and HER2 receptor status of the cancer
their white blood cell counts
their liver function values
their planned chemotherapy regimen
the length of their chemotherapy regimen
Overall:
36.2% had stage I breast cancer
42.9% had stage II breast cancer
20.9% had stage III breast cancer
23.7% had triple-negative (estrogen-, progesterone-, and HER2-negative) breast cancer
27.7% had HER2-positive breast cancer
33.8% received an anthracycline-based chemotherapy regimen; Adriamycin (chemical name: doxorubicin), Doxil (chemical name: liposomal doxorubicin), daunorubicin, Ellence (chemical name: epirubicin), and mitoxantrone are anthracycline chemotherapy medicines
about 50% were prescribed a chemotherapy regimen of 3 months or less
17.3% had chemotherapy before surgery
74.2% received medicine to promote white blood cell production, such as Neulasta (chemical name: pegfilgrastim), Neupogen (chemical name: filgrastim), or Zarxio (chemical name: filgrastim-sndz)
Both the researchers and the people in the study assessed what the researchers called “geriatric domains,” which included questions about:
ability to do daily activities, such as bathing and dressing
ability to do activities needed to maintain independence, such as managing money and making phone calls
time needed for a person to stand up, walk 10 feet, return to the chair, and sit back down
number of falls in the last 6 months
other health conditions
level of depression and anxiety
any unintentional weight loss in the last 6 months
ability to concentrate and remember things
The researchers followed the people through their chemotherapy treatment, recording any side effects that happened during each cycle.
The researchers wanted to determine the factors associated with side effects graded 3, 4, or 5:
grade 3 side effects are considered severe
grade 4 side effects are considered life-threatening or disabling
grade 5 side effects cause death
Overall, 138 people (48.7%) developed grade 3 to grade 5 side effects:
37.5% had grade 3 side effects
11.0% had grade 4 side effects
0.4% had grade 5 side effects
The most common grade 3 to grade 5 hematologic side effects (those affecting blood cells) were:
low red blood cell counts
low white blood cell counts
fever because of low white blood cell counts
The other most common grade 3 to grade 5 side effects were:
fatigue
infection
dehydration
One person in the study died from infection with a normal white blood cell count.
The researchers used statistical modeling to figure out which factors were linked to the risk of developing grade 3 to grade 5 side effects. They used information from 283 people in the study to develop the tool, and then they used information from the remaining 190 people to test the accuracy of the tool and validate it.
The CARG-BC score is calculated by looking at eight factors:
use of anthracycline chemotherapy
having stage II or stage III breast cancer
longer planned treatment time
abnormal liver function
low hemoglobin (hemoglobin is a protein molecule in red blood cells that carries oxygen from the lungs to the body’s tissues and takes carbon dioxide from the tissues back to the lungs)
more than one fall in the last 6 months
limited ability to walk
lack of social support
CARG-BC scores are divided into three risk groups:
0–5: low risk
6–11: intermediate risk
12 or greater: high risk
According to the researchers, the CARG-BC score can help people age 65 and older diagnosed with early-stage breast cancer and their doctors weigh the benefits of chemotherapy against quality-of-life concerns.
“Despite remarkable advances in cancer treatment, tools to characterize the toxicity of cancer therapies have remained virtually unchanged for the past 20 years,” Mina Sedrak, M.D., another author and deputy director of clinical trials for the Center for Cancer and Aging Research at City of Hope, said in a statement. “This is a new precision medicine tool. Rather than basing treatment decisions and care on demographic data for a disease, we now can offer each elderly, early-stage breast cancer patient individualized toxicity information that could help align treatment with their goals for lifestyle, quality of life, longevity and other priorities.”
What this means for you
If you’re 65 or older and have been diagnosed with early-stage breast cancer that will be treated with chemotherapy, you may want to talk to your doctor about this study.
When making treatment decisions, you and your doctor will consider a number of factors, including:
your age
the size of the cancer
the grade of the cancer
any other health conditions you have
your family history of cancer
your personal preferences
Adding the CARG-BC score to these factors can help you figure out your risk of serious side effects from chemotherapy, which can help you make a more informed decision about your treatment.
If you know your risk of serious side effects from chemotherapy is high, you and your doctor can talk about whether chemotherapy is the right treatment for you. You also can talk about chemotherapy treatment modifications, such as a lower dose or a longer time between cycles. Your doctor also could refer you for supportive care such as physical and occupational therapy before chemotherapy starts to closely monitor any side effects that start and immediately take steps to ease them.
Using the all the information available, you and your doctor can make the best treatment decisions for your unique situation.