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:
- marital status
- household make-up
- 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
- 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:
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.
Written by: Jamie DePolo, senior editor
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