Background: Identification of cancer-specific genes from breast cancer cells was instrumental in the advancement of targeted breast cancer therapy. However, with genomic heterogeneity within the breast cancer and evolution of cancer over time, genomic sequencing obtained from a single biopsy site may not capture the complete genomic profile. Thus, circulating cell-free DNA (cfDNA), isolated from plasma, is potentially a non-invasive source of identifying cancer-specific genomic alterations and may provide comprehensive genomic data throughout a patient's clinical course as they undergo anti-cancer therapy. Method: We performed a retrospective chart review of 100 patients with stage 4 or high-risk stage 3 breast cancer who were tested for cfDNA genomic alterations. The most common actionable cancer specific genomic alterations were identified. In 23 patients who also had genomic analysis from tumor DNA (tDNA), an analysis using the Cohen's Kappa statistic was performed to determine the degree of agreement between genomic alterations found in tDNA and cfDNA. The proportion of patients with clinical disease progression between two cohorts determined by change in mutant allele frequency was compared using two-sided Fisher's exact test. Patients who received targeted therapy based on the identified genomic alteration were followed to determine response to therapy. Results: In cfDNA of 100 breast cancer patients, the most commonly found cancer specific genomic alterations were TP53, PIK3CA, EGFR amplification, and ERBB2 amplification, with incidence rates 27%, 22%, 9%, and 7%, respectively. In tDNA of 23 patients, incidence rates were 65%, 26%, 9%, and 13%. PIK3CA and ERBB2 amplification demonstrated robust agreement between tDNA and cfDNA (Cohen's Kappa= 0.64 and 0.77, respectively). TP53 and EGFR amplification demonstrated poor agreement between tDNA and cfDNA (Cohen's Kappa= 0.18 and 0.33, respectively). There were 22 patients who had baseline and post-therapy mutant allele frequency measurements of TP53 and PIK3CA. Directional change of mutant allele frequency was closely associated with patient's response to therapy (p=0.0017). 8 out of 8 patients (100%) who had progression of disease had increase in mutant allele frequency. 10 out of 14 patients (71%) of patients who responded to therapy had decrease in mutant allele frequency. 6 patients who were found to have ERBB2 amplification were initiated on anti-HER2 cancer therapy. 5 of 6 patients (83%) had clinical response to therapy, while one patient had progression of disease. 3 patients who were found to have EGFR amplification (2 in cfDNA, 1 in tDNA) were initiated on anti-EGFR therapy. 2 of 3 patients (67%) had clinical response to therapy, while one patient had progression of disease. Conclusion: There is no definite agreement between genomic alterations found in tDNA and those found in cfDNA. Whether this is due to tumor heterogeneity or tumor evolution over time with administration of anti-cancer treatment remains unknown. However, identification of selected cancer specific genomic alterations from cfDNA may be a non-invasive tool to monitor disease progression and response to breast cancer therapy. Citation Format: Liang DH, Patel A, Ensor JE, Patel TA, Chang JC, Rodriguez AA. Cell-free DNA as molecular tool for monitoring disease progression and response to therapy in breast cancer patients. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-03-05.

Background: For patients with MBC, there is currently no evidence that changing therapy on the basis of biomarker results improves outcome. Clinical benefit of treatment is defined as complete response, objective response, or stable disease as determined by RECIST criteria on radiological evaluation. Serial measurements of serum biomarkers such as CA2729 and CTCs have proven unsuccessful in predicting clinical benefit. Circulating tumor DNA(ctDNA) has emerged as a potential biomarker that may predict response to therapy or progression of disease. The present retrospective study was conducted to evaluate the relationship between change in ctDNA with clinical benefit determined by clinical and radiological evaluations of patients with MBC patients. Methods: We conducted a retrospective, single-institutional study to determine if serial monitoring of ctDNA allele frequency levels predict clinical benefit of a treatment. 55 patients with measurable MBC who had serial monitoring of ctDNA between August 2014 and May 2016 were included. The median age was 55.9 (27–94) years). Clinical outcomes were determined as per standard guidelines. The analysis was performed on all cases that had serial measurements of ctDNA with no change in therapy in between and the repeat blood draw was done within 30 days of repeat radiographic evaluation. The dataset contained 125 observations from 48 unique patients. The relationship between the change in ctDNA and clinical benefit was analyzed using a generalized linear model with a random subject effect to account for the intrapatient dependence occurring from obtaining multiple evaluations from the same patient. A logit link function was used akin to logistic regression and a compound symmetric correlation structure was assumed. Results: 68.8% of the cases were hormone receptor-positive, 18.8% HER2-positive, and 27.1% TNBC. The treatments received were 58.4% hormonal therapy, 31.2% chemotherapy, 26.4% included anti-HER2 therapy, 2 cases were on targeted therapy, and 1 case was not on any treatment. Three patients had stage 4 disease in complete remission. ctDNA analysis was repeated on average 4 days prior to radiological evaluation. The average time between repeat assessments was 108.5 days. 93% of the patients had a genomic alteration detected at some point during their course of disease. The most common mutations detected were TP53 41.7%, PIK3CA 35.4%, ESR1 18.8%, and ERBB2 amplifications 6.3%. A dichotomized change in ctDNA is a significant predictor of clinical benefit (p < 0.0001). The intrapatient correlation is estimated to be 0.273 for the transformed variable. The model yields a predicted probability of clinical benefit of 26.9% when the increase in ctDNA is greater than or equal to 0.5 and when the increase in ctDNA is less than 0.5, the a predicted probability of clinical benefit is 78.4%. The concordance of change in ctDNA and change in CA 27-29 was 76.2%. Conclusions: Serial evaluation of serum ctDNA may be useful to evaluate molecular response to treatment which may correlate with clinical benefit and potentially guide treatment decisions. Early indication that a chosen therapy is not effective may lead to avoidance of overtreatment and initiation of an alternative regimen. Further, prospective studies are needed. Citation Format: Patel A, Mukherjee A, Hwang D, Ensor J, Patel TA, Chang JC, Rodriguez AA. Serial monitoring of circulating tumor DNA in patients with metastatic breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-02-06.

BACKGROUND: A review of the literature identifies high levels of anxiety and depression as adverse effects of oncology diagnosis and treatment, even for patients with curable cancers such as early stage breast cancer (ESBC). Studies have reported that music therapy yields remarkable, multi-dimensional benefits on an individual's mood and state of mind. The purpose of this trial is to evaluate the impact of personalized music therapy (PMT) in reducing anxiety and other adverse mental health symptoms experienced by patients receiving chemotherapy treatment for ESBC. ELIGIBILITY: Females ≥ 18 years diagnosed with ESBC (Stage I-III) initiating intravenous chemotherapy as their only oncology treatment modality who report anxiety ≥ 4 on a numerical rating scale of 0-10. TRIAL DESIGN: This is a 4-week, two-arm, randomized (1:1) trial evaluating the anti-anxiety benefits of PMT for women with ESBC initiating intravenous (IV) chemotherapy. The patients randomized to the experimental group will participate in 30-minute PMT sessions conducted by a Licensed Musical Therapist (LMT). Initial PMT will occur within 1 hour of the patient's first chemotherapy infusion (C1D1), then once weekly for the remaining 3 weeks of the trial. Patients randomized to the control group will be referred to the medical oncologist for standard of care (SOC) anxiety treatment. Outcomes will be measured via the Generalized Anxiety Disorder Assessment (GAD-7), the Center for Epidemiologic Studies Depression Scale (CES-D), the Pittsburgh Sleep Quality Index (PSQI), and the Symptom Inventory Tool-M.D. Anderson Symptom Inventory (SIT-MDASI) to be completed by both cohorts at baseline and regular intervals for the duration of the study. AIMS: The primary endpoint is to determine the impact of PMT during chemotherapy treatment on patient reported anxiety (GAD-7). Secondary endpoints will determine the impact of PMT during chemotherapy treatment on patient reported depression (CES-D), sleep disturbances (PSQI), and quality of life (SIT-MDASI). STATISTICAL METHODS/TARGET ACCRUAL: Patients will be randomized to receive either PMT or SOC using the Pocock-Simon dynamic allocation method to balance tumor stage between the arms. With 30 patients in each arm and approximate target accrual of 60, the study achieves 80.0% power to detect a 0.65 standard deviation unit effect size of the change in scale measure between baseline and 4 weeks at the 0.05 significance level using a one-sided two-sample t-test. GAD-7 change will be compared between the two arms using a two-sample t-test (Pooled Standard error or Satterthwaite approximation as appropriate). The secondary outcomes include CES-D, PSQI, and SIT-MDASI for which a longitudinal analysis of subscale scores will be conducted using a generalized linear mixed-effects model with fixed effects for treatment group and time. All statistical analyses will be conducted using SAS 9.3 [SAS Institute Inc., Cary, NC, USA]. Statistical significance will be defined as p < 0.05. Citation Format: Toole Jr. M, Bendinger GM, Ensor Jr. JE, Alvarez Tapias C, Smith E, McGuire E, Rados K, McNight JE, Pabbathi H, Panicker R, Johnson AT, Lammersfeld C, Alvarez RH. A randomized study of personalized music therapy for patients with early stage breast cancer receiving chemotherapy [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT3-08-01.