Anthracycline (doxorubicin) and trastuzumab treatments for cancer patients have been known to cause cardiotoxicity. The current recommendations for prevention of cardiac events from cancer chemotherapies are largely based on opinion. The American Society of Clinical Oncology recommends active screening and prevention of modifiable cardiovascular risk factors. The risk factors are defined as tobacco use, high blood pressure, high cholesterol, alcohol use, obesity, and physical inactivity. Beta-adrenergic blockers and angiotensin converting enzyme (ACE) inhibitors/angiotensin receptor blockers (ARBs) have been the mainstay of treatment for heart failure patients with reduced left ventricular ejection fraction for many years. This review analyzed the use of beta-adrenergic blockers and ACE inhibitors/ARBs as protection against cardiomyopathy caused by anthracyclines and trastuzumab. Although many more studies are warranted, it was concluded that the addition of a beta-blocker early in the treatment of cancer patients who are undergoing anthracycline or trastuzumab treatment can have beneficial effects in preserving left ventricular ejection fraction and preventing chemotherapy-induced cardiotoxicity. The effects are more apparent in the short term. More studies of the long-term effects are warranted, as are the additive effects of using a beta-blocker and ACE inhibitor/ARB together to prevent chemotherapy-induced cardiotoxicity.

<b><i>Background:</i></b> The Oncotype DX Breast Cancer Assay is a 21-gene assay used to predict the likelihood of distant recurrence and the benefit of chemotherapy in patients with node-negative, tamoxifen-treated breast cancer. Prior studies demonstrated 7–19% discordance, or a difference between the recurrence score (RS) and tumor grade (TG) in breast cancer patients. BRCA mutated tumors (BRCA+) have been shown to be associated with higher RS as compared to BRCA-negative patients (BRCA–). <b><i>Objectives:</i></b> We developed a large Oncotype RS database to determine if the BRCA mutation status is associated with discordance. <b><i>Methods:</i></b> We identified 723 patients (32 [4%] mutation-positive and 691 [96%] mutation-negative patients) with early-stage, hormone-positive breast cancer treated between 2006 and 2018, with tumor characteristics available for analysis. Discordance was defined as one- or two-step difference between RS (low, intermediate, high risk) and TG (well [WD], moderately [MD], and poorly [PD] differentiated). Mutation positive was defined as BRCA1 deleterious mutation, BRCA2 deleterious mutation, BRCA mutation of unknown type, BRCA variant of undetermined significance (VUS) or other mutation (classified as other VUS). Number (%) or median were used to describe patient characteristics between groups and were compared by the Kruskal-Wallis test at a significance level of 5%. <b><i>Results:</i></b> Among these patients, there were 32 (4% of total) who were identified as mutation-positive. Of those patients, 16% had a documented deleterious mutation in BRCA1, 22% in BRCA2, 6% had a BRCA mutation of unknown type (either 1 or 2), 25% were BRCA VUS, and 31% other VUS (most commonly CHEK2 and ATM). The median RS was 23.5 in patients with deleterious BRCA mutations (1, 2 or unknown) versus 16 in patients in the BRCA-negative database, which was statistically significant (<i>p</i> &#x3c; 0.01). One- and two-step discordance was present in 46 and 8%, respectively, of patients with deleterious BRCA mutations versus 53 and 11%, respectively, in the BRCA-negative database. <b><i>Conclusions:</i></b> Patients with deleterious BRCA mutations demonstrated no difference in rates of discordance as compared to BRCA-negative patients. We further demonstrated that patients with BRCA-positive tumors display higher RS than patients with BRCA-negative tumors.

e12511 Background: The RSClin model, which incorporates the Oncotype Recurrence Score (RS) and clinicopathologic features, was recently developed to further tailor prognosis and prediction of chemotherapy benefit for patients with early-stage hormone positive (HR+) breast cancer (BC) (Sparano et al, 2020). The RSClin calculator is available online to assist treatment planning for situations where chemotherapy benefit is uncertain. Covariates include Oncotype RS, tumor grade, tumor size and patient age. The risk calculator generates a 10-year distant recurrence risk and absolute chemotherapy benefit. This tool may be especially helpful to determine treatment management for premenopausal patients with early-stage HR+ BC with intermediate risk (IR) Oncotype RS (16-25). We retrospectively applied RSClin to this patient population to determine if it would have changed treatment recommendations. Methods: We identified premenopausal women with node-negative early-stage BC with IR RS (16-25) within our large Oncotype database. Using the RSClin model, we selected >5% absolute chemotherapy benefit as a reasonable cutoff to recommend chemotherapy. We compared the treatment recommendation based on RSClin with the treatment previously recommended by breast oncologists at our large academic medical center in New York City. Results: There were 86 patients who met criteria with a median age of 46 years. Of these, 26 patients (30%) were recommended chemotherapy plus endocrine therapy (ET) and 60 (70%) were recommended ET alone. After applying the RSClin model (data available for 83/86 patients), 19 (23%) would have resulted in a change in treatment recommendation and 64 (77%) would have remained unchanged. Overall, 8 (10%) would have withheld chemotherapy when it was previously offered and 11 (13%) would have recommended chemotherapy when it was previously excluded. There were 8 (9%) secondary invasive breast events in this population, with 2 (2%) being ipsilateral, 3 (3%) being contralateral and 3 (3%) metastatic at a median follow up of 46.9 months. Conclusions: The RSClin model would have changed management of premenopausal patients with IR RS in 23% of patients. This model, although not yet prospectively validated, may help individualize therapy for patients with less definitive treatment plans. Using RSClin, we can aim to minimize recurrence rates and avoid unnecessary chemotherapy in selected patients. This model is easy to apply and will have important clinical utility moving forward.

<b><i>Background:</i></b> The Oncotype DX Recurrence Score (ODx RS) is the most widely adopted genomic assay used to guide treatment for patients with early-stage, hormone-positive (HR+) breast cancer (BC), with higher scores predicting greater risk of recurrence and benefit from chemotherapy. Patients with ODx RS &#x3e;25 typically recieve adjuvant chemotherapy; however, data regarding efficacy of chemotherapy for reducing recurrence in this population have been mixed. <b><i>Objectives:</i></b> This study aimed to evaluate outcomes of patients with early-stage HR+ BC with high-risk ODx RS (26–30 and ≥31) in order to assess treatment patterns and outcomes. We hypothesized that the benefit of chemotherapy in these groups may be minimal and that select patients may forgo chemotherapy in favor of more aggressive endocrine therapy and ovarian suppression. <b><i>Methods:</i></b> We performed a retrospective analysis of 515 patients with early-stage, HR+ BC with high-risk ODx RS 26–30 and ≥31 treated between 2006 and 2018. Patients were stratified by RS: low-risk (≤10), intermediate-risk (11–25), and high-risk (≥26). The Kaplan-Meier method was used to estimate the time to secondary invasive breast events (SIBE) or distributions overall and among different RS groups with the log rank test used to compare distributions between groups. <b><i>Results:</i></b> Rates of chemotherapy administration were 7% among the low-risk group, 18% among the intermediate-risk group, and 83% among high-risk patients with 41 SIBE (8%) reported. When stratified by ODx RS, 5-year rates of SIBE were 4%, 6%, and 16% for low-risk, intermediate-risk, and high-risk RS, respectively. Among the 27 lymph node (LN)-negative patients with ODx RS 26–30, 74% received chemotherapy. The 5-year rate of SIBE was 25% among patients who received chemotherapy and 33% among those who did not (<i>p</i> = 0.5489). Among the 23 LN-negative patients with ODx RS ≥31, 91% of patients received chemotherapy. The 5-year rate of SIBE was 0% both with and without chemotherapy. <b><i>Conclusions:</i></b> There was no statistically significant difference in SIBE for patients with high-risk ODx RS based on chemotherapy treatment. More aggressive endocrine therapy with ovarian suppression has become an alternative to chemotherapy among patients with intermediate-risk ODx RS (16–25). This approach may be useful among patients with high-risk ODx RS, with additional studies needed in this patient population.

Background: The Oncotype DX ® (ODX) is a genomic assay that provides clinicians with a prediction of benefit of chemotherapy in node-negative, tamoxifen-treated breast cancer. However, the relationship between ODX recurrence score (RS) and diabetes, a common comorbidity in breast cancer patients, has been inadequately described in the literature. Specifically, the association of diabetes treatment with metformin and RS is inconclusive, with different studies reporting conflicting results. Because diabetes has been associated with higher RS, it has been suggested that management of diabetes with metformin in breast cancer patients may be associated with a lower RS. Objectives: We studied a large cohort of early-stage, hormone-positive breast cancer patients to determine if there is an association between RS and metformin treatment. Methods: In this study, we retrospectively examined the medical records of 514 early-stage, hormone-positive breast cancer patients who had oncotype testing performed between 2007 and 2017. Number (%) or median were used to describe the patients' characteristics between groups and were compared by the Kruskal-Wallis test at a significance level of 5%. Results: Of this cohort, 67 (13%) had a diabetes diagnosis at the time of breast cancer diagnosis, including both diabetes mellitus and pre-diabetes. The median RS for non-diabetic patients was 16 and the median RS for diabetic patients was 15. This difference was not significant, nor was there a statistical difference in RS between diabetic patients taking metformin (median RS = 15) and diabetic patients not taking metformin (median RS = 15). These results held true even when controlling for BMI. Conclusions: We conclude that neither diabetes diagnosis nor metformin use is associated with a difference in oncotype RS in this population of diabetic patients.