Harvey, Jinky

Abstract Background: Taxane based chemotherapy (chemo) forms a critical part of breast cancer (BC) treatment in early and metastatic settings. Taxanes can cause peripheral neuropathy (CIPN)-sensory and motor, primarily of the hands and feet, resulting in quality of life decline and negaive impact on BC survival. Acral cryotherapy has shown benefit in reducing in in minimizing the incidence and severity ofcidence and severity of CIPN. However, these studies have included limited number of patients (pts) with inconclusive evidence to change US practice guidelines, have been primarily conducted in Asia, and did not include racially diverse patients. Methods: We conducted a single arm non randomized study at Mayo Clinic that included early BC pts who underwent standard of care paclitaxel or docetaxel based chemo. Pts had ECOG performance status 0-2, no sensory peripheral neuropathy at study entry and were able to give signed informed consent. Pts with metastatic BC, Raynaud's and peripheral vascular disease, cryoglobulinemia, cold intolerance, prior exposure to neurotoxic or taxane chemotherapy were excluded. Participating pts wore frozen gloves and socks (−20 to −10°C) on both hands and feet, 15 min before, during and until 15 min post taxane infusion. During chemo, grade (G) of CIPN (sensory) per CTCAE v5 was collected prior to each cycle of chemo, end of and 3 months after chemo. Schedule of events is listed in Table 1. Continuous variables were summarized using mean and standard deviation, and categorical variables were summarized with number and percentage of patients. Numeric variables were compared with t tests (paired and unpaired), and categorical variables were compared with Chi-Squared test for independent data and Mcnemar’s test for dependent data. All statistical tests were two-sided and were performed using R Statistical Software (version 4.1.2; R Foundation for Statistical Computing). Results: A total of 95 patients were included in this study. Median age is 54 years, 66.3% pts were White (W), 23.2% African American (AA), 4.2% Asian (A) and 4.2% Hispanic (H). Median BMI was 27.7. Most pts had stage I/II (75.8%), ER positive (64.9%) and HER2 negative (55.3%) BC and got adjuvant chemo (52.6%). Only 10.6% pts had diabetes, 55.3% used alcohol. Vitamin D3 use seen in 65.6%, B12 in 6.2% and folate, B12 and D3 in 6.2% pts. A total of 41 pts (44.1%) developed neuropathy at some point during chemo, of which 27 pts were W (43%), 10 pts AA (45%), 2 pts H, 1 Asian and 1 other. CIPN was G1 in 37 pts (90%). G2 CIPN was seen in 4 pts, at or after cycle 10 of weekly paclitaxel. Cold intolerance was seen in 24 pts (25%), G1 in 20 and G2 in 4 pts, all seen in cycle 1 with 1 pt withdrawal. Recovery to G0 was seen in 15 W pts at chemo end and 2 additional pts at 3 month after chemo. None of the AA pts, one H and one A pt had CIPN recovery to G0. In 4 AA pts who had G1 CIPN during chemo, G2 CIPN was noted at 3 month follow up. No Statistically significant differences in baseline characteristics and neuropathy results for W vs nonwhites (NW) were seen except Charleson score (p-value 0.023). Conclusion: Acral cryotherapy was found to be effective in reducing the incidence and severity of CIPN from taxane in our study. This is the only study with diverse racial/ethinic pt inclusion and incidence of CIPN was similar in W and NW. However, majority of G2 CIPN pts were AA and recovery to G0 CIPN was not seen in AA pts. Majority (63%) of W pts recovered to G0 at end of follow up. Analysis of objective testing of all pts is underway. Continued research into risk factors for AA pts to develop CIPN and its mitigation are warranted. XX XX Citation Format: Pooja Advani, Jinky Harvey, Ivy Vilches, Alex Hochwald, David Hodge, Amanda Arnold, Morgan Weidner, Dana Haley, Tanmayi Pai, Saranya Chumsri, Rohit Rao, Kostandinos Sideras, Cindy Tofthagen, Alvaro Moreno-Aspitia. Cryotherapy to Prevent Taxane-Induced Sensory Neuropathy of the Hands and Feet [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-12-10.

Abstract Background: Breast cancer (BC) patients are at significant risk of therapy-related cardiotoxicity, but prediction of which patients will experience cardiotoxicity and the severity of the outcome are lacking. We hypothesized that germline genetic variants are potential risk factors for cancer treatment-related cardiomyopathy (CTRC) and in this study, we focused on rare non-synonymous variants within 57 genes deemed causative of familial and sporadic forms of idiopathic cardiomyopathies. Methods: We developed a clinical database and biorepository for patients receiving any potentially cardiotoxic cancer therapy at Mayo Clinic Florida. Enrollment is ongoing and includes consent to access external records. Patient data is extracted from records at baseline, completion of treatment and then once per year. The clinical database includes the following datasets: demographics, pathology, chemotherapy, radiation, echocardiography, cardiac MRI, PET/CT scan, blood pressure, BMI, labs, treatment complications. Treatment complications includes pre-existing conditions (smoking, alcohol and drug use history, hypertension, diabetes, coronary artery disease, hyperlipidemia, prior stroke or myocardial infarction, peripheral vascular disease, renal failure); cardiac medications at baseline; cardiac side-effects; time to cardiotoxicity; cardiotoxicity interventions and outcomes. Exome sequencing was performed by the Mayo Clinic NGS core on the first 86 patients in the registry, average of ~120x read depth following Illumina’s standard protocol for the NovaSeq 6000 and S4 flow cell. Genomic variants were extracted for 57 genes known to be causative of dilated, hypertrophic and arrhythmogenic right ventricular cardiomyopathies and channelopathies. Putative risk variants in known cardiomyopathy genes were defined as non-synonymous variants with a frequency of < 0.0004 in the GnomAD database. We compared the number of patients with putative risk variants in those groups with and without CTRC. Results: 84/86 patients had BC diagnosis. Key characteristics are described in the table below. 60/86 (70%) patients had at least one putative risk variant in one of 31 genes (there were no risk variants identified in 27/57 genes). The average number of putative risk variants per patient within the CTRC group was higher than that observed in patients without CTRC (2.06 vs 1.62). Post-hoc analysis suggested this difference is largely from patients with >2 risk variants in the group who experienced CTRC (N=7/17, 41%) compared to those who did not (N=14/69, 20%), p=0.023. Conclusions: Rare missense variants in the causative genes of idiopathic cardiomyopathies are potential risk factors for CTRC and risk may be increased in patients with a higher burden of variants. Analysis of the genetic data from patients that continue to be accrued in this study, including effects of additional clinical risk factors will be undertaken to improve prediction of cardiotoxicity. Table 1 Distribution of putative cardiomyopathy genetic variants in 86 cancer patients with and without treatment-related cardiomyopathy, separated by treatment regimen Citation Format: Nadine Norton, Thien Nguyen, Joseph Reddy, Jinky Harvey, Morgan Weidner, Amanda Arnold, Lily Evans, Laura Vallow, Pooja Advani. Increased burden of genetic variants in idiopathic cardiomyopathy genes is associated with cancer therapy-related cardiomyopathy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-12-08.