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This study evaluated costs using an integrated managed care health care system of chemotherapy-related adverse events in patients with mBC. This analysis was also the first study to use EOC as the method to evaluate adverse events and costs and conduct a chart review to evaluate whether adverse events were related to chemotherapy. The costs of any adverse events related to chemotherapy overall are extremely substantial not only on the health care system but also emotionally on patients as well. Newer and innovative therapies are needed to help with alleviating these adverse events and reduce economic burden on any health plan or health system. In this study, hematological, gastrointestinal, and infection/pyrexia were most prevalent and incurred most cost. Prior studies may differ due to various databases used or different types of mBC patients. For example, Hassett et al7 reported fever/infection, neutropenia/thrombocytopenia, and dehydration as the most prevalent adverse events. The calculated cost of $12,907 per person per year was higher among women who received chemotherapy versus women who did not receive chemotherapy within 6 months of being diagnosed. Du et al8 reported frequencies of chemotherapy-related adverse events but not costs in a population of women with stage I through stage IV and ≥65 years of age. Most prevalent adverse events were anemia, neutropenia, and infection/fever.

The costs from previous studies maybe inflated from this study since they included chemotherapy and other medical services, such as laboratory tests, radiology, or other services within their costs. Previous studies have reported increase in costs with more adverse events due to hospitalizations, and we also observed a similar trend in this study where patients who have multiple EOC per adverse events category, incurred more costs, primarily driven by hospitalization rates.59 In this study, we also observed that anemia, neutropenia, nausea/vomiting, infection/pyrexia, and peripheral neuropathy were prevalent adverse events as demonstrated in previous studies.59 However, with differences in patient characteristics, and their individual prognosis, the rates vary. Prior studies all had different populations. Hurvitz et al5 and Hansen et al6 included patient populations from a commercial health plan younger than 65 years. Our population had both commercial and Medicare patients ≥18 years of age. Hassett et al7 used a sample of patient with mBC who were younger than 64 years. They also added expenditures for procedures or administration of chemotherapy medications, which were considered as ambulatory expenditures. The chemotherapy-related adverse events were identified using hospitalization or ER visit only. Du et al8 evaluated women with all stages of breast cancer, aged ≥65 years, and also used hospital visits to identify adverse events.

Overall, patients with mBC who receive chemotherapy are likely to experience an adverse event. These patients will incur higher costs to the health care system related to more health care visits, prescribing or administrating of other medications to alleviate the adverse events, and finally, cause a dose delay, dose discontinuation, or dose reduction to the chemotherapy regimen.18 All these impact the patient and health care system directly.


There are some limitations with the data. All adverse events were identified with diagnosis and procedural codes, and laboratory data were not used to confirm specific adverse events such as anemia, leukopenia, neutropenia, or thrombocytopenia. Differences between the adverse events identified in this study versus those reported by clinical trials may be due to differences in patients’ demographic characteristics, prognoses within their disease state, and the use of various diagnosis and procedure codes rather than direct clinical assessment. There could also be an underestimation of the other medications used to help treat these adverse events because we used the dispense date between each EOC that was created and not dates between the 2-week gap.

We included the most common adverse events in patients using chemotherapy from the literature and previous clinical trials; however, we did not include all adverse events. One common adverse event is fatigue, and since this is a patient-reported event, we could not identify fatigue using diagnosis codes. We did not evaluate human epidermal growth factor receptor 2-positive or -negative status or evaluate targeted therapies in our sample, thus our sample consisted of patients on chemotherapy only. We also evaluated our databases to identify first-line chemotherapy regimens 12 months prior index date and could only capture what was found in our pharmacy databases and capture any chemotherapy dispensed outside of KPSC if a patient filled their prescription at a non-KPSC facility. Some patients could have been exposed to taxane utilization or possible use of systemic therapy in the adjuvant setting not within KPSC; however, we retrieved all claims, and we required that patients had membership and drug benefit eligibility as well during 6 months prior to index date. The results may not be generalizable to those patients who received another type of treatment or targeted therapies, since we evaluated chemotherapy only. The costs could be underestimated since we only evaluated the cost of the visit and not how the EOC was managed, for example, we did not capture how long each outpatient or ER visit was and what type of management (laboratory work, X-rays, consultations by different staff, procedures, etc.) was performed during the visit. All these have additional costs attributed to the EOC, but this is not included in this study. Finally, when we evaluated adverse events, we could not report what grade (3 or 4) or apply a scale of severity to them; however, if a patient was admitted to the hospital, this was an assumption that it had a level of severity.