Toxicity Index, patient-reported outcomes, and persistence of breast cancer chemotherapy-associated side effects in NRG Oncology/NSABP B-30

Abstract

Adjuvant chemotherapy improves breast cancer survival but is associated with bothersome short- and long-term toxicity. Factors associated with toxicity, especially subacute toxicity up to 2 years following chemotherapy, have not been fully elucidated. The NRG Oncology/NSABP B-30 clinical trial compared 3 different doxorubicin-, cyclophosphamide-, and docetaxel-based chemotherapy regimens given over 3-6 months. Patients with hormone receptor-positive breast cancer received subsequent adjuvant endocrine therapy. From baseline through 24 months, 2156 patients completed questionnaires serially. We used multivariable probabilistic index models to identify factors associated with acute (>0-12 months) and subacute (>12-24 months) difficulties with pain, cognition, vasomotor symptoms, and vaginal symptoms. For all symptom domains, presence of symptoms prior to chemotherapy initiation were associated with symptoms in the subacute period (all p < 0.001). In addition, different combinations of patient factors and breast cancer treatments were associated with increased likelihood of pain, vasomotor, and vaginal symptoms in the subacute period. Consideration of pre-treatment symptoms and patient factors, as well as treatments for breast cancer, can facilitate identification of groups of patients that may experience symptoms following completion of chemotherapy. This information may be important for treatment-decision-making when alternative regimens are equivalent in benefit.

Fig. 1. CONSORT diagram.

A doxorubicin, C cyclophosphamide, QOL quality of life, T docetaxel.

Fig. 2. Violin plots demonstrating the distribution of Toxicity Index in the acute (blue) and subacute (orange) time periods for each symptom domain.

Red circles represent the median, and black bars represent the interquartile range. A pain. B cognition. C vasomotor. D vaginal.

Fig. 3. Forest plots demonstrating results of Multivariable Probabilistic Index Models for the cumulative Toxicity Index (TI) for the symptom domains during the acute and subacute time periods.

Comparison A < B denotes the probability that the cumulative TI for B is higher than that for A. When the probability is >0.5, B is more likely to be associated with the symptom domain, whereas when the probability is <0.5, A is more likely to be associated with the symptom domain. A pain domain. Acute (blue, N = 2075 patients) and subacute (red, N = 1791) time periods. B cognition domain. Acute (blue, N = 2078 patients) and subacute (red, N = 1793) time periods. C vasomotor domain. Acute (blue, N = 2075 patients) and subacute (red, N = 1791) time periods. D vaginal domain. Acute (blue, N = 2068 patients) and subacute (red, N = 1781) time periods. A doxorubicin, BMI body mass index, C cyclophosphamide, CI confidence interval, NH Non-Hispanic, T docetaxel, TI toxicity index.