br zero The mean frailty score in patients
zero (51.4%). The mean frailty score in patients with breast cancer
Type of Treatment
3.6. Frailty Comparisons Between Pre- and Post-chemotherapy Time-points
for Patients With Breast Cancer and Non-cancer Controls
3.3. Comparison of Health Status Between Patients With Breast Cancer and We assessed whether chemotherapy had any effect on the frailty
Non-cancer Controls at the Post-chemotherapy Time-point
status of patients with breast cancer (Table 2 and Fig. 2). We found
At the post-chemotherapy time-point, a higher proportion of patients that post- versus pre-chemotherapy, a higher percentage of patients
of three. There were no differences in non-cancer controls within
3.4. Pre- to Post-chemotherapy Comparison of Health Status Between the similar time frame (Fig. 2D and Supplementary Table I). At the
Patients With Breast Cancer and Non-cancer Controls
post-chemotherapy time-point, compared to non-cancer controls, pa-
tients with breast cancer similarly reported more weakness, and ex-
In patients with breast cancer, from pre- to post-chemotherapy, haustion, along with slower gait speed and less engagement in
there was a significant increase in the proportion of patients physical activity.
Health status differences.
(Pre- vs Post-Chemo)
Sleep (Fairly & Very Bad)
Walk Speed b2 mph
KPS-Karnofsky Performance Status
Fig. 2. Frailty status comparisons. Contingency plots comparing mean frailty scores of a. patients with breast cancer to non-cancer controls at the pre-chemotherapy time-point, b. patients with breast cancer to non-cancer controls at the pre-chemotherapy time-point, c. pre-chemotherapy time-point to post-chemotherapy time-point for patients with breast cancer, d. pre-chemotherapy time-point to post-chemotherapy time-point for non-cancer controls.
3.7. Associations Between Pre-chemotherapy Cytokine and Receptor Levels and Post-chemotherapy Frailty in Patients With Breast Cancer and Non-cancer Controls
We determined whether the level of pre-chemotherapy cytokines and receptors were associated with post-chemotherapy frailty. We found that patients with pre-chemotherapy cytokine and U 46619 levels above the median had worse frailty scores post-chemotherapy than those with levels below the median [Fig. 3A: IL-6 (2.31 vs. 1.86; p = .027), Fig. 3B: sTNFRI (2.30 vs. 1.88; p = .039), and Fig. 3C: sTNFRII (2.30 vs. 1.88; p = .039)]. No association between levels of IL-6, sTNFRI, and sTNFRII was seen in non-cancer controls within a similar time frame (Fig. 4). This association was confirmed using a linear regression model, controlling for pre-chemotherapy frailty. In these models we found that pre-chemotherapy frailty was a significant predictor of post-chemotherapy frailty. Additionally, patients with pre-chemotherapy level of IL-6 and sTNFRI above the median were significantly (p b
.050) more frail than those below the median. There was a marginal association of the level of pre-chemotherapy sTNFRII with post-chemotherapy frailty after controlling for pre-chemotherapy frailty (p = .085). No association between levels of IL-6, sTNFRI, and sTNFRII was seen in non-cancer controls within the similar time frame after controlling for baseline frailty (Supplementary Table II).
There were no differences in the median pre-chemotherapy level of IL-6, TNFRI and TNFRII in patients receiving adjuvant versus neoadju-vant chemotherapy. The associations between the pre-chemotherapy level IL-6, TNFRI and TNFRII and post-chemotherapy frailty were consis-tent in patients receiving adjuvant chemotherapy; patients with higher pre-chemotherapy levels of IL-6, sTNFRI, and sTNFRII were more frail
after receiving chemotherapy. Similar results were obtained in the subgroup of patients who were age 65+ (data not shown).
In this secondary analysis of a multicenter longitudinal cohort study, we found that a diagnosis of breast cancer was associated with worse health status (increased pain, mood symptoms, and sleep disturbances as well as interference with exercise and activity) and elevated frailty prior to chemotherapy compared to age-matched non-cancer controls. We also found that chemotherapy worsened the health status and frailty of patients with breast cancer, despite the fact that patients eval-uated in this study were younger than those generally evaluated in frailty studies. In addition, we demonstrated that elevated pre-chemotherapy levels of the inflammatory molecules IL-6, sTNFRI, and sTNFRII were associated with increased frailty within one month of completing a chemotherapy regimen. To our knowledge, this is the first study to suggest that pre-chemotherapy levels of IL-6, sTNFRI and sTNFRII may be used to predict heightened frailty post-chemotherapy in patients with breast cancer.