乌鸦传媒

The number of breast cancer cases in the U.S. is growing annually, and a greater than 50% increase in diagnoses is expected from 2011 to 2030. The number of cases diagnosed in women ages 70 to 84 is from 24% to 35%. Despite the benefit of adjuvant chemotherapy in improving survival in high-risk, early stage breast cancer, it is sometimes underutilized in older patients due to the concern and risk for chemotherapy toxicity.

Unfortunately, there are limited tools currently available to accurately establish risk. Furthermore, existing models to assess performance status -- i.e., Karnofsky Performance Score (KPS) and Eastern Cooperative Oncology Group performance status (ECOG) -- were developed and validated in younger patients. The current Cancer and Aging Research Group (CARG) Chemotherapy Toxicity Tool was created in a population with differing cancer types, stages, and chemotherapy regimens and may be challenging to apply to specific cancer types.

In a new study aimed to develop and validate a model that can predict Grade 3-5 chemotherapy toxicities in patients 65 years of age and older with early stage breast cancer. A Grade 3 adverse event (AE) is severe; Grade 4 AE is life-threatening, and Grade 5 AE is death related to the AE. The authors have proposed the Cancer and Aging Research Group -- Breast Cancer (CARG-BC) score, which combines eight clinical and geriatric variables to determine whether a patient is of low, intermediate, or high risk of developing grade 3-5 chemotherapy toxicity.

A total of 501 patients across 16 U.S. institutions consented to participate in the Hurria Older PatiEnts (HOPE) with Breast Cancer Cohort Study. The first 300 patients were in the development cohort and the last 201 patients were in the external validation cohort.

Both clinical and geriatric variables were collected, including both a healthcare provider portion and a patient portion. The healthcare provider variables included KPS, Timed Up & Go Test, Blessed Orientation-Memory-Concentration Test, weight, height, body mass index, and unintentional weight loss. The patient portion consisted of self-reported measures of functional status, comorbidities, medications, nutrition, psychological state, and social support or function.

The primary outcome of the study was grade 3-5 chemotherapy toxicity or AE as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v 4.0). Secondary outcomes collected included treatment modifications, reduced relative dose intensity, and hospitalizations.

The mean age of the patients was 70.5, and 59% were ages 65-70. The majority had stage I/II cancer; 23.7% of participants had triple-negative breast cancer, and 27.7% had HER-2 positive disease. Approximately one third of patients received an anthracycline-based regimen, and nearly 75% of the patients received primary prophylaxis with white blood cell growth factor.

Nearly 50% of patients developed grade 3-5 toxicities: 37.5% had a grade 3 toxicity, 11% had a grade 4 toxicity, and 0.4% had a grade 5 toxicity. The most common hematologic toxicities were anemia, neutropenia, and neutropenic fever. The most common non-hematologic toxicities were fatigue, infection with a normal neutrophil count, and dehydration.

The final model includes the following eight predictors:

• Stage II/III breast cancer

• Planned anthracycline-based regimen

• Planned duration of treatment greater than 3 months

• Abnormal liver function

• Anemia (≤13 g/dL in males; ≤12 g/dL in females)

• At least one fall in the past 6 months

• Limited ability to walk more than 1 mile

• Lack of someone to give good advice in a crisis

Risk scores are assigned to each variable, allowing the calculation of the CARG-BC score, which has been stratified into three risk groups based on predictive probability of toxicity: low risk (0-5), intermediate risk (6-11), and high risk (≥12).

The under the receiver operating characteristic curve (AUC) for this model was 0.75 (95% CI 0.70 to 0.81) in the development cohort and 0.69 (95% CI 0.62 to 0.77) in the validation cohort; there was no statistically significant difference between the two (P=0.15). The overall AUC for the CARG-BC score was 0.73 (95% CI, 0.68 to 0.77). The risk of chemotherapy toxicity increased with a higher risk score. When compared with patients in the low-risk category, those in the intermediate-risk and high-risk groups were much more likely to have grade 3-5 toxicity, unplanned dose reduction, dose delay, early discontinuation of therapy, and hospitalization.

Overall, this study demonstrates that the CARG-BC score is a helpful predictive tool for the development of grade 3-5 chemotherapy toxicity in older adults with early stage breast cancer.

This is an important study for several reasons. The decision to treat older adults with adjuvant chemotherapy is often a difficult one and requires the balancing of chemotherapy benefits with treatment risks as well as with the patient's underlying medical history and comorbidities. The CARG-BC model is superior to KPS as well as to the generalized CARG toxicity tool.

Specifically, this model not only assesses geriatric-related issues such as falls, anemia, and social support but also applies breast cancer-specific factors.

It is imperative that we utilize a geriatric assessment tool in oncology practice. Future studies could look at evaluating this model in even older patients as nearly 60% of the participants in this study were between the ages of 65 and 70.

This is an excellent tool to help predict severe and life-threatening toxicity from chemotherapy in older adults with early stage breast cancer and help aid in shared decision-making for clinicians and patients.

Eleonora Teplinsky, MD, is head of Breast Medical Oncology at Valley Health System in Paramus, New Jersey, and clinical assistant professor at Icahn School of Medicine at Mount Sinai.

Read the study here and an interview about it here.