Abstract
BackgroundInsomnia is a frequent complaint in patients with cancer. Sleep problems can affect immune functioning in healthy individuals. Our aim was to evaluate the association between sleep disturbance and the risk of febrile neutropenia, leukopenia and infections in patients treated with chemotherapy in an adjuvant setting for breast cancer.MethodologyThis is a retrospective study using the Canadian Cancer Trial Group data collected for the MA.21 trial, in which three adjuvant chemotherapy regimens (CEF, EC-T dose dense or AC-T) were compared in 2104 patients with node positive or high-risk node negative breast cancer. A total of 1731 patients had completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) and 1727 patients had completed the Breast Cancer Chemotherapy Questionnaire (BCQ) quality of life questionnaires, which both include a question about sleep difficulties. The primary definition for patients with insomnia was a score of three (quite a bit) or greater at Question 11 (Have you had trouble sleeping? with answers ranging from one (not at all) to four (very much)) on the EORTC QLQ-C30 questionnaire. We compared patients classified as having “clinical insomnia” based on their response to this question with patients considered “good sleepers”. The primary endpoint was the risk of febrile neutropenia. Secondary endpoints were the risks of grade one or more leukopenia, neutropenia and infection. ResultsFebrile neutropenia was more frequent in patients with sleep problems compared with those without, with 16.3% and 12.2% of patients having at least one episode in each group respectively (p value = 0.01 in the univariate analysis (table 1)). However, after adjustment for potential confounders in the multi-variate analysis, it was not statistically significant with an odds ratio of 1.07, a 95% confidence interval of 0.76-1.50 and a p value of 0.71. Similarly, no statistically significant difference in the risk of leukopenia could be demonstrated in the multi-variate analysis for patients with sleep problems with an odds ratio of 0.92 a 95% confidence interval of 0.69-1.24 and a p value of 0.59. No significant association could be found between sleep problems and neutropenia and infections. In an unplanned exploratory analysis, chemotherapy dose reductions were significantly more frequent in patients with sleep problems with 30.6% in this group compared to 21.8% in good sleepers, with a p value <0.0001. ConclusionWhile our univariate analysis suggested an increased risk of febrile neutropenia and leucopenia in patients with sleep problems, after adjustment for confounders, we could not show a statistically significant association in women undergoing adjuvant chemotherapy for high-risk locoregional breast cancer.
Characteristics . | Sleep problem= yes . | Sleep problem = no . |
---|---|---|
Febrile neutropenia | ||
No | 781 (83.7%) | 701 (87.8%) |
Yes | 152 (16.3%) | 97 (12.2%) |
P-value | 0.01 | |
White blood cell count (WBC) | ||
Grade 0 | 157 (16.8%) | 141 (17.7%) |
Grade 1 | 135 (14.5%) | 138 (17.3%) |
Grade 2 | 184 (19.7%) | 186 (23.3%) |
Grade 3 | 214 (22.9%) | 173 (21.7%) |
Grade 4 | 243 (26.1%) | 160 (20.1%) |
P-value | 0.02 | |
Neutropenia | ||
Grade 0 | 778 (83.4%) | 700 (87.7%) |
Grade 1 | 0 (0%) | 1 (0.1%) |
Grade 2 | 2 (0.2%) | 0 (0%) |
Grade 3 | 152 (16.3%) | 96 (12.0%) |
Grade 4 | 1 (0.1%) | 1 (0.1%) |
P-value | 0.014 | |
Infection | ||
Grade 0 | 619 (66.4%) | 564 (70.7%) |
Grade 1 | 68 (7.3%) | 62 (7.8%) |
Grade 2 | 158 (16.9%) | 110 (13.8%) |
Grade 3 | 87 (9.3%) | 61 (7.6%) |
Grade 4 | 1 (0.1%) | 1 (0.1%) |
P-value | 0.24 | |
Chemotherapy delay | ||
No | 1 (0.1%) | 12 (1.5%) |
Yes | 932 (99.9%) | 786 (98.5%) |
P-value | 0.0008 | |
Chemotherapy dose reduction | ||
No | 648 (69.4%) | 624 (78.2%) |
Yes | 285 (30.6%) | 174 (21.8%) |
P-value | < 0.0001 |
Characteristics . | Sleep problem= yes . | Sleep problem = no . |
---|---|---|
Febrile neutropenia | ||
No | 781 (83.7%) | 701 (87.8%) |
Yes | 152 (16.3%) | 97 (12.2%) |
P-value | 0.01 | |
White blood cell count (WBC) | ||
Grade 0 | 157 (16.8%) | 141 (17.7%) |
Grade 1 | 135 (14.5%) | 138 (17.3%) |
Grade 2 | 184 (19.7%) | 186 (23.3%) |
Grade 3 | 214 (22.9%) | 173 (21.7%) |
Grade 4 | 243 (26.1%) | 160 (20.1%) |
P-value | 0.02 | |
Neutropenia | ||
Grade 0 | 778 (83.4%) | 700 (87.7%) |
Grade 1 | 0 (0%) | 1 (0.1%) |
Grade 2 | 2 (0.2%) | 0 (0%) |
Grade 3 | 152 (16.3%) | 96 (12.0%) |
Grade 4 | 1 (0.1%) | 1 (0.1%) |
P-value | 0.014 | |
Infection | ||
Grade 0 | 619 (66.4%) | 564 (70.7%) |
Grade 1 | 68 (7.3%) | 62 (7.8%) |
Grade 2 | 158 (16.9%) | 110 (13.8%) |
Grade 3 | 87 (9.3%) | 61 (7.6%) |
Grade 4 | 1 (0.1%) | 1 (0.1%) |
P-value | 0.24 | |
Chemotherapy delay | ||
No | 1 (0.1%) | 12 (1.5%) |
Yes | 932 (99.9%) | 786 (98.5%) |
P-value | 0.0008 | |
Chemotherapy dose reduction | ||
No | 648 (69.4%) | 624 (78.2%) |
Yes | 285 (30.6%) | 174 (21.8%) |
P-value | < 0.0001 |
Citation Format: Audreylie Lemelin, Josée Savard, Michelle Chen, Margot Burnell, Mark N Levine, Lois Shepherd, Bingshu E Chen, Julie Lemieux. Evaluation of sleep problems and their association with febrile neutropenia, leucopenia and infections in women receiving adjuvant chemotherapy for breast cancer in the Canadian Cancer Trials Group MA.21 trial [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD12-01.