Cornell, Lauren

As survival in breast cancer patients from newer therapies increases, concerns for chemotherapy-induced cardiotoxicity (CIC) have offset some of these benefits, manifesting as a decline in left ventricular ejection fraction (LVEF). Patients receiving anthracycline-based chemotherapy followed by trastuzumab are at risk for CIC. Previous research evaluating whether clinical biomarkers predict cardiotoxicity has been inconsistent. Recently, angiotensin II type 1 receptor (ATR1) and endothelin 1 (ET1) have been shown to play a role in breast tumor growth. We evaluated ATR1 and ET1 expression in breast cancer tissue and its association with CIC. A total of 33 paraffin-embedded breast tissue specimens from women with breast cancer treated with anthracycline-based chemotherapy and trastuzumab were analyzed by immunohistochemistry (IHC) and qRT-PCR. We found that ET1 expression was increased in patients with an LVEF ≤ 50% (p = 0.032) with a lower LVEF correlating with higher ET1 expression (r = 0.377, p = 0.031). In patients with a change in LVEF of greater than 10%, greater ET1 expression was noted compared to those without a change in LVEF (p = 0.017). Increased ET1 expression in breast tumor tissue is associated with reduced LVEF. Future studies need to examine whether ET1 may be a tissue biomarker that helps predict the risk of developing CIC in women with breast cancer.

Background: It is standard of care and an accreditation requirement to screen for and address distress and psychosocial needs in patients with cancer. This study assessed the availability of mental health (MH) and chemical dependency (CD) services at US cancer centers. Methods: The 2017–2018 American Hospital Association (AHA) survey, Area Health Resource File, and Centers for Medicare & Medicaid Services Hospital Compare databases were used to assess availability of services and associations with hospital-level and health services area (HSA)–level characteristics. Results: Of 1,144 cancer centers surveyed, 85.4% offered MH services and 45.5% offered CD services; only 44.1% provided both. Factors associated with increased adjusted odds of offering MH services were teaching status (odds ratio [OR], 1.76; 95% CI, 1.18–2.62), being a member of a hospital system (OR, 2.00; 95% CI, 1.31–3.07), and having more beds (OR, 1.04 per 10-bed increase; 95% CI, 1.02–1.05). Higher population estimate (OR, 0.98; 95% CI, 0.97–0.99), higher percentage uninsured (OR, 0.90; 95% CI, 0.86–0.95), and higher Mental Health Professional Shortage Area level in the HSA (OR, 0.99; 95% CI, 0.98–1.00) were associated with decreased odds of offering MH services. Government-run (OR, 2.85; 95% CI, 1.30–6.22) and nonprofit centers (OR, 3.48; 95% CI, 1.78–6.79) showed increased odds of offering CD services compared with for-profit centers. Those that were members of hospital systems (OR, 1.61; 95% CI, 1.14–2.29) and had more beds (OR, 1.02; 95% CI, 1.01–1.03) also showed increased odds of offering these services. A higher percentage of uninsured patients in the HSA (OR, 0.92; 95% CI, 0.88–0.97) was associated with decreased odds of offering CD services. Conclusions: Patients’ ability to pay, membership in a hospital system, and organization size may be drivers of decisions to co-locate services within cancer centers. Larger organizations may be better able to financially support offering these services despite poor reimbursement rates. Innovations in specialty payment models highlight opportunities to drive transformation in delivering MH and CD services for high-need patients with cancer.

Abstract Background: Multiple studies have identified an association between diagnosis of breast cancer and post-diagnosis psychological distress. Some have taken a step further, identifying predictive markers of distress in diagnosed patients and interventions to minimize post-diagnosis distress. Data regarding pre-diagnosis psychological distress and its impact on surgical decision making and clinical outcomes in the breast cancer population are limited. Here, we assessed pre-diagnosis major life stressors and breast cancer outcomes in a single-center population. Methods: Patients with newly diagnosed stage 0-3 breast cancer seen at Mayo Clinic Florida between June 11, 2018, and October 7, 2019, were included. Prior to their initial visit, patients were administered a voluntary telephone survey regarding the incidence of major life events and stressors during the 18 months preceding their diagnosis. Demographic data including age and ethnicity were also included. Subsequent clinical outcomes were obtained through retrospective chart review. Clinical outcomes were assessed with descriptive statistics. Chi-square tests were used to compare subgroups, with p < 0.05 considered statistically significant. Results: Of 469 patients seen for a new breast cancer diagnosis, 222 patients completed the intake survey and met inclusion criteria. Median age was 60 (27-84) years. 80.6% of patients were white, 7.7% were black, 5.4% were Asian/Pacific Islander, and 2.3% were Latino. Over 95% endorsed having some form of social support. 51.3% reported experiencing a major life event prior to breast cancer diagnosis. Of these patients (n = 114), 43.9% denoted this stressor as family-related, as compared to 20.2% citing non-breast cancer illness, 14.9% claiming relationship stress, and 14% describing employment-related stress. Only 1.8% endorsed stress caused by financial concerns. Multiple major life events were reported by 10.8% of all included patients. Subgroup analysis of the patients with pre-diagnosis stress revealed a similar demographic distribution to the overall sample. Compared to the subgroup without pre-diagnosis stress (n = 108), there were more patients with carcinoma in situ and stage T3/T4 disease (21.1% versus 13.0%, p = 0.11) and 11.4% versus 10.2%, p = 0.77), respectively) in the subgroup with pre-diagnosis stress, although these differences were not statistically significant. More patients with pre-diagnosis stress elected to undergo mastectomy (34.2% versus 22.2%, p = 0.048) as compared to the group without stress. Conclusions: With over half of sample patients reporting pre-diagnosis major life stressors, psychological distress is prevalent prior to breast cancer diagnosis and should be considered as a factor for early intervention, such as psychological and financial counseling, during breast cancer evaluation. The sample population was predominantly white and resource-rich in terms of financial and social support, highlighting a need for characterization of pre-diagnosis psychological distress in more ethnically diverse and/or resource-limited settings. Although additional study is recommended, current data suggest possible associations between pre-diagnosis psychological distress and treatment decision making, particularly the decision to pursue mastectomy. Citation Format: Tanmayi Pai, Laura Vallow, Danushka Seneviratne, Dawn Mussallem, Lauren Cornell. Pre-diagnosis major life stressors and breast cancer outcomes [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS9-46.

e13002 Background: Despite improvement in survival in breast cancer patients from advanced therapies, rates of chemotherapy-induced cardiotoxicity manifesting as a decline in left ventricular ejection fraction (LVEF) have offset some of these benefits in patients receiving anthracycline-based chemotherapy followed by trastuzumab. Results suggesting clinical biomarkers predict cardiotoxicity are inconsistent. Recently, expression of angiotensin II type 1 receptor (ATR1) and endothelin 1 (ET1) has shown to play a role in breast tumor growth. We sought to evaluate whether the presence of ATR1 and ET1 in breast cancer tissue using immunohistochemistry (IHC) and qRT-PCR can predict chemotherapy-induced cardiotoxicity. Methods: We hypothesized that elevated expression of ATR1 and ET1 in tumor tissue is associated with chemotherapy-induced cardiotoxicity (LVEF < 50%) compared to tissue from controls. Preliminarily, 34 paraffin-embedded breast tissue specimens from women with breast cancer treated with anthracycline-based chemotherapy and trastuzumab were retrieved for analysis. IHC and qRT-PCR for expression of ATR1 and ET1 was performed on all specimens. Results: We found that ET1 expression was significantly increased in patients with an LVEF < 50%. In addition, we noted the lower the LVEF, the higher the ET1 expression (p = 0.03). We also found patients with a change in LVEF of greater than 10% had more ET1 expression compared to those without a change in LVEF (p = 0.05). We did not find a significant relationship between ATR1 and LVEF. Conclusions: Increased ET1 expression in breast tumor tissue may predict cardiotoxicity. Our findings may aid in future research using novel biomarkers to predict breast cancer patients at risk for developing chemotherapy-induced cardiotoxicity. In addition, targeted therapies to these biomarkers may potentially help prevent the development of cardiotoxicity.

Abstract Background: Cardiac toxicity (CT) in the form of left ventricular systolic dysfunction is a well-known complication of anti-HER2 therapy. Prior clinical trial data has suggested potential factors associated with increased risk for CT. We sought to develop a clinical risk prediction model from real world patients to better identify patients who may be at higher risk for CT. Methods: Patients treated with anti-HER2 agents at all Mayo Clinic sites from Jan 2008 to July 2015 were reviewed. Patient data including age, race, body mass index, comorbidities, smoking history, baseline ejection fraction (EF), presence of left ventricular hypertrophy (LVH), prior cancer treatments, number of anti-HER2 agents used, and cardiac medication use were recorded. Factors were compared in patients with and without development of CT. Cox regression models were used to identify univariate and multivariate predictors of CT. A risk score was then assigned based on the final multivariable model. Results: 604 patients were included in final analysis. Median follow-up 2.9 yrs; median age: 57 yr; baseline EF: 64%. One yr CT rate was 7%. Independent predictors of CT were age, baseline EF, LVH, and anthracycline use (C index=0.74). Based on model coefficient, scores of 1, 1, 2 and 3 were assigned to age&gt;55, EF &lt;60%, anthracycline exposure and LVH, respectively. Two random samples of 300 patients were created out of the original cohort for internal validation of the risk score model. In each, the risk score was found to be a highly significant predictor for CT with C index of 0.72 {HR 2.13 (95% CI 1.57-2.90), p &lt;0.001} and 0.77 {HR 2.45 (95% CI 1.74-3.44), p &lt;0.001}. Conclusions: Patients with risk factors of older age, lower baseline EF, anthracycline use and LVH are at increased risk for CT when treated with anti-HER2 agents. Using a risk prediction model at therapy initiation may enhance identification of patients who benefit from cardiology referral, closer cardiac monitoring, and/or prophylactic treatment while on anti-HER2 targeted therapy. Table 1. Multivariable Cox regression model predicting cardiac dysfunctionParameterParameter EstimateHR (95%CI)p valueScoreAge &gt;550.909552.48(1.27, 4.84)0.00751EF&lt;600.634361.89(1.01, 3.53)0.04751Anthracycline Exposure1.046132.85(1.48, 5.46)0.00162Baseline LVH1.633565.12(2.04,12.85)&lt;0.0013 Citation Format: Pooja P Advani, Lauren Cornell, Zhuo Li, Jordan Ray, Catalina Sanchez, Armando Villanueva, Taryn Smith, Alvaro Moreno-Aspitia. A validated clinical risk prediction model for cardiac toxicity in patients treated with antiHER2 agents [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-14-14.

43 Background: Strategies to detect and treat breast cancer continue to improve, and as such, the number of survivors has grown dramatically. To date, there has not been a well-established model to provide cohesive care for breast cancer survivors. Care often feels fragmented and important issues are overlooked due to lack of continuity. The adoption of Survivorship Care Plans has aimed to fill this gap in care, but the literature still demonstrates that our patients’ needs are not being met. Methods: We present a comprehensive model for breast cancer care, within a multidisciplinary breast center, which incorporates consistent management from time of diagnosis through survivorship. This model utilizes the appointment of a dedicated breast internist that meets with each patient at the time of diagnosis and again assumes care at time of survivorship. The breast internists or “onco-generalists” have specialized training in breast cancer/survivorship and work alongside the entire multidisciplinary team. This unique approach incorporates individualized surveillance, integrative management of late treatment effects, and appropriate risk reducing lifestyle education. Results: The inclusion of a dedicated breast internist into survivorship care has been the standard within our center for over 10 years. With this model, we have found that survivorship care is more holistic with a focus on the patients’ overall needs. There is dedicated time to individualized risk assessment, appropriate surveillance, and modifiable risk factor education. The model also allows for incorporation of integrative medicine including mindfulness, acupuncture, and massage therapy to improve quality of life for patients. With this model, patients do not feel the abandonment that is so often experienced by survivors, but rather they feel empowered to enter their new life as a survivor. Conclusions: Continuity of care during and after breast cancer treatment remains a significant issue. By designating an internist with specialized breast training who initially meets with patients upfront, we have been able to create a more integrative approach to survivorship care, which encompasses the patients’ needs both surrounding and outside of their cancer diagnosis.