Symptom Burden in Metastatic Breast Cancer

In 2012, approximately 39,510 women in the United States died of breast cancer. First-line treatment of metastatic breast cancer (MBC) yielded median survival of 20.5 months in recent phase 3 trials. The majority of patients develop MBC following a diagnosis of early stage disease; however, 5% to 8% of patients present with metastatic disease. HER2 and hormone status affect decisions relating to options for first-line treatment of MBC. Available options include chemotherapy, hormone therapy for hormone receptor positive patients, and targeted therapies such as trastuzumab and bevacizumab.

According to researchers, some patients fail to complete first-line therapy as intended. Noting that early treatment discontinuation (ETD) in the first line of therapy has not been widely studied, the researchers recently conducted a study to determine the role that treatment toxicities play in ETD and ways ETD differs by type of treatment. Study results were reported during a poster session at the American Society of Clinical Oncology 2013 Annual Meeting. The poster was titled Real-World Symptom Burden and Early Treatment Discontinuation in First-Line Metastatic Breast Cancer.

The primary end point of the retrospective medical record review was early treatment discontinuation (ETD), defined by any of the following, not accompanied by disease progression: (1) electronic medical record (EMR) that the patient discontinued early; (2) observed duration <EMR statement of intended length of therapy; (3) direct indication of early stopping of treatment; or (4) duration of therapy ≤6 weeks.

Regimen groups were defined as follows: (1) chemotherapy (without targeted therapy) ± hormone therapy (CT); (2) chemotherapy + targeted therapy ± hormone therapy (T) (targeted therapies included bevacizumab, trastuzumab, denosumab, and lapatinib); and (3) hormone therapy only (H).

The final study cohort included 797 patients. Mean age was 58.4 years, 62.1% were white. There were 340 patients in the chemo group, 349 in the targeted group, and 108 in the hormone group. Among all 3 groups, ETD occurred in 11.9% (n=95) of patients. The rates were highest in the CT group (15.3%), followed by 10.0% in the T group and 7.4% in the H group.

The study identified 21 clinically significant symptoms that predicted ETD: (1) fatigue, (2) physical pain, (3) hair loss, (4) numbness/tingling, (5) mouth sores/ulcers, (6) burning hands or feet, (7) chills, (8) nausea, (9) diarrhea, (10) difficulty breathing, (11) decreased appetite, (12) sore throat, (13) vomiting, (14) body weakness, (15) fever, (16) trouble concentrating, (17) trouble sleeping, (18) constipation, (19) joint pain, (20) muscle aches, and (21) feeling nervous. Two other symptoms were not clinically significant in predicting ETD: (1) reduced sexual enjoyment and (2) feeling sad or depressed.

In the composite symptom burden score (median 7.1) analysis, overall symptom burden was significant (hazard ratio [HR], 1.124; P<.001), indicating a 12.4% increased risk of ETD with each additional symptom.

Patients with 10+ symptom score had a significantly increased risk of ETD (HR, 3.09; P<.001) compared with patients with <5 symptom score. Patients with 15+ symptom score had the highest risk of ETD (HR, 5.875; P<.0001). Categorical analysis suggests that positivity on ≥50% of surveyed symptoms may represent a threshold for increasing the clinically relevant risk of ETD.