## 5 Conclusions  
It is important, when translating results from murine models to human studies, to recollect that murine samples may represent late stages in cancer tumor progression. This study found tumor injection to the tibia led to many VOCs being dysregulated as early as the first week after injection. Some VOCs remained relatively constant over the course of the study, while others were insignificant early in the study but were dysregulated later in the study. This is hypothesized to be because of cancer progression and/or the formation of osteolytic lesions induced by mammary tumor injection/progression. It is hoped these findings can be translated into human research for early detection of breast cancer recurrence as 20-30% of patients with early breast cancer will experience relapse with distant metastatic disease and bone metastases being the most common presentation at the time of recurrence [2]. Further human research can be focused on finding if the urinary VOCs can be detected before the radiographic appearance of lesions on the bone scans or PET scans, or exploring if there is any correlation between the levels of VOCs and the extent of tumor burden. **Supplementary Materials:** The following are available online at [[https://www.mdpi.com/2072-669](https://www.mdpi.com/2072-669)]([https://www.mdpi.com/2072-669](https://www.mdpi.com/2072-669)) 4/13/6/1462/s1, Table S1: List of VOCs with p-value < 0.05 between Cancer Weeks 1-3 vs. Control (tumor presence) or Cancer Week 1 vs. Cancer Week 3 (tumor progression) with corresponding abbreviations, retention times and p-values for both comparisons (NS = no statistical significance, upward facing arrows show upregulation in all Cancer samples or in Cancer Week 3 while downward facing arrows signify downregulation, * denotes VOCs used for PCA in Figure 3b, underline denotes \(p\)-value < 0.05 between Cancer Week 1 and Week 3 after FDR adjustment, italics denotes \(p\)-value < 0.05 between Cancer and No Cancer after FDR adjustment). Table S2. Regression analysis results of individual 37 VOCs identified as significantly different (Cancer Week 1 and Week 3), standardized regression coefficients for the same 37 VOCs analyzed by PCR in Figure 5b and standardized regression coefficients for the 19 VOCs analyzed by PCR in Figure 5d. Figure S1: 2D LDA plot with Cancer Week 2 samples tested utilizing the LDA model initially built to discriminate Control, Cancer Week 1 and Cancer Week 3. **Author Contributions:** Conceptualization: M.A., H.Y. and A.P.S. ; Data curation M.W., P.G., J.V.G. and A.P.S. ; Formal analysis M.W., L.W., S.L., P.G., M.W., J.V.G. and A.P.S. ; Funding acquisition: M.A. and H.Y. ; Investigation M.K., M.A. and H.Y. ; Methodology: L.W., M.W., S.L., P.G., M.K., J.V.G. and A.P.S. ; Project administration: [PERSON], H.Y. and A.P.S. ; Resources: M.A., M.K. and H.Y. ; Supervision: [PERSON], H.Y., M.K., J.V.G. and A.P.S. ; Validation: [PERSON], P.G. and A.P.S. ; Visualization: [PERSON], M.W. and P.G. ; Roles/Writing--original draft: [PERSON], P.G. and A.P.S. ; Writing--review & editing: [PERSON], P.G., [PERSON], A.P.S., [PERSON], [PERSON], [PERSON] and M.A. All authors have read and agreed to the published version of the manuscript. **Funding:** This research was funded by U.S. National Institutes of Health (NIH)/National Institute of Arthritis and Musculoskeletal and Skin Diseases (grant # R01 AR052144) and the National Science Foundation (grant # 1852105 and 1502310). **Institutional Review Board Statement:** All experimental procedures followed the Guiding Principles in the Care and Use of Animals supported by the American Physiological Society and were approved by the Indiana University Animal Care and Use Committee (protocol code: SC292R; date of approval: 30 May 2019). No humans were utilized in this study. **Informed Consent Statement:** Not applicable. **Data Availability Statement:** The data presented in this study, are available on request from the corresponding author.