Ruddy, Kathryn J.

AbstractObjectiveYoung breast cancer patients experience greater psychosocial distress compared with older patients, which raises concern for their risk of posttraumatic stress disorder (PTSD). We sought to characterize the prevalence of clinically significant symptoms of PTSD and associated factors among breast cancer survivors diagnosed at a young age.MethodsThe Young Women's Breast Cancer Study, an ongoing prospective cohort study, enrolled 1302 women diagnosed with breast cancer at age ≤ 40 between 2006 and 2016. Participants complete serial surveys, and we obtained additional information from medical record review. Socio‐demographics, anxiety and depression, social support, and psychiatric co‐morbidities and medications were assessed at study baseline (median, 5 months post‐diagnosis). We defined a participant as having clinically significant posttraumatic stress symptoms (PTSS) by scoring ≥50 on the PTSD Checklist‐Specific Version, administered on the 30‐month survey.ResultsAmong 700 women with stage 1‐3 disease, the prevalence of PTSS was 6.3% (95%CI = 4.5‐8.1). In multivariable analyses, PTSS was significantly associated with anxiety (OR 12.43, 95%CI = 5.81‐26.59, P < .0001) and stage 2 vs 1 disease (OR 2.26, 95%CI = 1.04‐4.93, P = .04). PTSS was inversely associated with having a college degree (OR 0.29, 95%CI = 0.13‐0.62, P = .002) and greater social support (OR 0.44, 95%CI = 0.21‐0.94, P = .03).ConclusionsWe found similar rates of cancer‐related PTSS in breast cancer survivors diagnosed at a young age compared with the general breast cancer population despite their well‐documented increased risk of overall distress. Nevertheless, factors associated with posttraumatic stress should be considered at diagnosis and in survivorship to identify young patients who may benefit from psychosocial resources.

Background: Clinician adherence to antiemetic guidelines for preventing chemotherapy-induced nausea and vomiting (CINV) caused by highly emetogenic chemotherapy (HEC) remains poorly characterized. The primary aim of this study was to evaluate individual clinician adherence to HEC antiemetic guidelines. Patients and Methods: A retrospective analysis of patients receiving HEC was conducted using the IBM Watson Explorys Electronic Health Record Database (2012–2018). HEC antiemetic guideline adherence was defined as prescription of triple prophylaxis (neurokinin-1 receptor antagonist [NK1 RA], serotonin type-3 receptor antagonist, dexamethasone) at initiation of cisplatin or anthracycline + cyclophosphamide (AC). Clinicians who prescribed ≥5 HEC courses were included and individual guideline adherence was assessed, noting the number of prescribing clinicians with >90% adherence. Results: A total of 217 clinicians were identified who prescribed 2,543 cisplatin and 1,490 AC courses. Patients (N=4,033) were primarily women (63.3%) and chemotherapy-naïve (92%) with a mean age of 58.6 years. Breast (36%) and thoracic (19%) cancers were the most common tumor types. Guideline adherence rates of >90% were achieved by 35% and 58% of clinicians using cisplatin or AC, respectively. Omission of an NK1 RA was the most common practice of nonadherence. Variation in prophylaxis guideline adherence was considerable for cisplatin (mean, 71%; SD, 29%; coefficient of variation [CV], 0.40) and AC (mean, 84%; SD, 26%; CV, 0.31). Conclusions: Findings showed substantial gaps in clinician adherence to HEC CINV guidelines, including a high variability across clinicians. Clinicians should review their individual clinical practices and ensure adherence to evidence-based CINV guidelines to optimize patient care.

e24133 Background: The impact of chemotherapy-induced nausea and vomiting (CINV) on work loss and activity impairment is important to patients yet not well described in literature. We sought to evaluate CINV-related work loss and activity impairment and their associations with CINV duration. Methods: In a prospective CINV prophylaxis trial of oral or intravenous netupitant/palonestron (NEPA) + dexamethasone (DEX) (12mg day 1 only) for patients with breast cancer receiving anthracycline + cyclophosphamide (AC), we defined CINV as vomiting or use of rescue medication during days 1-5 after AC. Pre-specified endpoints included CINV duration (0-5 days), patient reported CINV-associated work loss (Work Productivity and Activity Impairment survey), and CINV-related impaired activity [0 (none) - (worst) Likert scale] for chemotherapy cycles 1 and 2. CINV-related work loss and activity impairment could involve nausea with or without vomiting or rescue medication use. We categorized CINV duration as 1-2 days (d) or ≥3 d, and compared results using the chi-squared test. We report here on the first 2 cycles. Results: Survey data was captured for 792 cycles in 402 female patients including 132 (32.8%) employed patients. Mean age was 55.4. CINV was observed in 173 (21.8%) of total cycles. CINV-related work loss was reported in 26 (3.3% of all cycles, 15.0% of cycles with CINV, 38.2% of employed patient cycles with CINV) while 142 had related activity impairment. When we categorized cycles by CINV duration, CINV-related work loss was seen in 25.9% of 81 cycles with ≥3 d CINV duration vs. 5.4% for 92 cycles of 1-2 d of CINV (p < 0.001); mean scores of CINV-related impaired activity were 5.0 for ≥3 d CINV vs 3.0 for 1-2 d CINV (p < 0.001). Conclusions: Despite guideline recommended prophylaxis, CINV occurred in > 20% of AC cycles. In cycles with CINV, CINV-related work loss occurred in 38.2% for employed patients while activity impairment occurred in 82.1% for all patient cycles. The majority of CINV lasted 1-2 d. Notably, ≥3 d of CINV was associated with considerably higher levels of work loss and activity impairment suggesting that duration may be a meaningful measure of CINV impact. Clinical trial information: NCT03403712 . [Table: see text]

e24103 Background: Many of the 200,000 patients diagnosed with breast cancer (BC) annually in the United States receive anthracycline-based therapy, increasing their risk of future congestive heart failure. N-terminal brain natriuretic peptide (NT-proBNP) has been used as a biomarker of asymptomatic cardiac dysfunction in the general population and is of interest to identify patients who might benefit from echocardiography during survivorship. This study aimed to assess how age, baseline comorbidities, and time since BC diagnosis impact NT-proBNP levels after anthracycline-based chemotherapy. Methods: This retrospective study, using samples collected in our ongoing prospective Mayo Clinic Breast Disease Registry, included 20 survivors of non-metastatic BC patients per year for each of the first 5 years after anthracycline-based chemotherapy (n=100 total). NT-pro-BNP levels were assessed using a Roche immunoassay. Cardiac risk factors were obtained by chart review. Multivariable linear regression models assessed associations between NT-proBNP values and these independent variables: baseline cardiac risk factors (including hypertension, hyperlipidemia, obesity, diabetes mellitus, and smoking), tumor ER status (surrogate for possible endocrine therapy), time between diagnosis and serum collection, T and N status, use of trastuzumab, and age. Results: The mean age at the time of BC diagnosis was 52.2 (SD 9.8). 13% of tumors were human epidermal growth factor receptor (HER2)-positive and 71% were estrogen receptor (ER) positive. NT-proBNP was elevated in 34%. Mean NT-BNP level was higher (p=0.047) for those in years 4-5 (158 pg/mL) compared to those in years 1-3 (106 pg/mL) (See Table.) Models revealed years from diagnosis to serum draw (p=0.026), older age (p=0.006), more cardiac risk factors (p=0.064), and N2-3 (p=0.001) were associated with elevated NT-pro-BNP level. Use of trastuzumab, ER status, and tumor size were not associated with NT-proBNP. Conclusions: NT-proBNP is elevated in 1/3 of survivors who received anthracycline therapy for BC. As expected, cardiac risk factors and advancing age are associated with higher NT-proBNP. NT-proBNP values >300 were only found in patients who were 4-5 years after diagnosis. Additional research will be needed to further define the diagnostic and prognostic merit of NT-proBNP in survivors after receipt of anthracycline therapy. [Table: see text]

11012 Background: The proportion of women in the field of hematology and oncology (H&O) has increased over recent decades, but representation by women in leadership positions remains a challenge. Our aim was to examine representation of winners of recognition awards by gender and race from the major international hematology and oncology societies. Methods: Published award recipients from the seven major H&O societies were reviewed, with 26 years of data included (1994-2019). Awardee demographics and academic rank were collected and included in the analysis. Gender was determined based on awardee full name and verified by public data. Chi-square and Cochran-Armitage tests were used to analyze the data. Results: Over the past 26 years, 942 awards were presented at the 7 major H&O societies. We excluded 27 gender specific awards from the analysis. Of the 915 awardees included in analysis, award recipients were overwhelmingly men (77.9%) and non-Hispanic white (84.7%). Gender breakdown by society is described in table. ESMO and ASTRO represented the lowest distribution of women at 9.1% and 11.1%, respectively. Women awardees received 30.3% of the awards categorized as humanistic and education-related, while only receiving 16.0% of awards in the basic sciences category (p<0.01). The Cochran-Armitage test demonstrated an upward trend in the number of women awardees, from 10% between 1994-1998 to 25.6% between 2014-2019 (p=0.0004). Over the past five years, the average proportion of women medical oncologists was 35.6% per the AAMC. In this time period, women oncologists have received only 24.0% of all awards, suggesting the awardees included in the study period do not represent the proportion women in the field (p=0.00424). Black, Hispanic, and Asian awardees represented 3.7%, 3.3%, and 6.8% of the total awardees, respectively. Of the 64 Black and Hispanic awardees, 60.9% of the awards were for investigating healthcare disparities and only 4.6% were given for basic science research. Conclusions: During our study period, women physicians and investigators were less likely to receive recognition awards from the seven major H&O societies compared to men. We also observed a considerable low proportion of minority awardees in all oncology subspecialties. While the proportion of women awardees has increased over time, significant underrepresentation remains. [Table: see text]

e14018 Background: Cancer survival rates are improving. Therefore, management of cardiovascular complications has now become a crucial clinical concern. Cardio-oncology is the sub-specialty that assists in the overall management of cancer patients in a multi-disciplinary manner. Mayo Clinic cardio-oncology practice was initiated to work closely with our oncology colleagues for early detection of cardiovascular complications in response to cancer-therapy. Majority of the patients visit our cardio-oncology clinic once, we thought it is important to study the group of patients that visited frequently due to cardiovascular complications. Aim: To evaluate the most common cardiovascular complication in patients with 2 or more visits to our cardio-oncology clinic. Methods: From 2012-2017, there were > 2500 patients visits to our clinic, with 24 patients having 2 or more visits. Data including patients’ demographics, ethnicity, chemotherapeutic medications, primary cancer type, cardiovascular risk factors, echocardiography and clinical outcomes were collected. Cardiotoxicity was defined as the decrease in left ventricular ejection fraction (LVEF) of > 10% to a value of < 53%. Heart failure was diagnosed based on Framingham’s criteria or by a cardiologist. Results: There were 19 women (80%) and 5 men (20%). Median age at the time of diagnosis was 56 years [19-76]. The most common malignancy was breast cancer (70%), followed by B-cell lymphoma (12%) and acute myeloid leukemia (8%). Thirty percent had > 2 risk factors for cardiovascular disease. 75% of the patients had an LVEF of < 53, of these 67% developed heart failure with 58% preserved and 42% reduced ejection fraction. Those with heart failure had received a mean anthracycline dose of 305 ± 91.8mg/m2. With initiation of ACEI, B-Blockers, and diuretics (GDMT) 79% showed recovery of LVEF to ≥53 during the follow up. Conclusions: In our experience, most patients who were seen at least twice in the cardio-oncology clinic for heart failure had received a dose of > 300mg/m2 anthracycline. With GDMT over 75% of the patients recovered. Care in the cardio-oncology clinic plays a key role in optimizing these clinical outcomes.

1044 Background: Trastuzumab is well-demonstrated to be associated with cardiotoxicity (typically reduced ejection fraction), most commonly in patients who also receive anthracycline. The vascular effects of trastuzumab and anthracycline are understudied; we aimed to compare change in endothelial function during and after trastuzumab and to assess how anthracycline receipt affects this. Methods: This is an observational prospective study of women with newly diagnosed HER2-positive breast cancer. All participants underwent baseline evaluation of endothelial function testing by use of the EndoPAT2000 device approximately every three months over the subsequent 18 months after the initiation of HER2-directed therapy +/- anthracycline. The primary endpoint was change in endothelial function over time using the reactive hyperemia index (RHI). Framingham Risk Score (FRS) and lower RHI are both known to be independent predictors of future cardiovascular events in the general population. RHI deterioration was defined as a 20% reduction from baseline RHI to any available follow-up RHI assessment. Univariate analyses assessed if age, FRS, baseline RHI, and RHI deterioration differed between recipients and non-recipients of anthracycline using the Wilcoxon test. A multivariate logistic model evaluated FRS, age, and anthracycline receipt as possible independent predictors of RHI deterioration. Results: Among 38 eligible patients who consented and completed baseline assessments in addition to at least one follow-up assessment, 17 (45%) subsequently received anthracycline. 145 total follow-up RHI assessments were available overall (5 per patient on average). There were no differences between recipients and non-recipients of anthracyclines with regard to age [mean 49 years (SD 12) vs 53 years (SD 11); p=0.25], baseline FRS [mean 1.0 (SD 1.0) vs 1.5 (SD 1.4); p= 0.28] or baseline RHI [mean 2.4 (SD 0.6) vs 2.1 (SD 0.7); p=0.09]. RHI deterioration was more common for anthracycline recipients (mean 43% vs 21%; p=0.004), and in the multivariate model, anthracycline use was the only independent predictor of RHI deterioration (odds ratio: 2.8; 95% confidence interval: 1.35-6.07; p=0.006). Conclusions: This study suggests that endothelial dysfunction is more common after combined anthracycline and HER2-directed therapy than after HER2-directed therapy alone. RHI should be further studied as a possible early biomarker of cardiovascular toxicity in patients receiving treatment for breast cancer.

514 Background: The 21- gene Breast Recurrence Score predicts benefit from adjuvant chemotherapy in estrogen receptor positive (ER+), HER-2 negative (-) breast cancer (BC). We aimed to examine whether the 21-gene assay predicts response to neoadjuvant chemotherapy (NAC). Methods: We identified patients with stage I-III ER+/HER2− BC treated with NAC from the Young Women's Breast Cancer Study, a prospective cohort of women diagnosed with BC at age ≤ 40 years. The 21-gene assay was performed on tumor specimens removed prior to NAC either as part of clinical care or retrospectively for research. Pathologic complete response (pCR) was defined as no residual invasive tumor (ypT0/is ypN0). The relationship between Recurrence Score result (RS) and pCR was evaluated using logistic regression modeling. Results: 76 women in the cohort had undergone NAC for ER+, HER2- BC and were eligible for this analysis: 5 had undergone clinical 21-gene assay testing, 71 had banked specimens retrospectively tested. Median age at diagnosis was 36.7 (24.3-40). Most tumors were of ductal histology (78%), high grade (51%), progesterone receptor (PgR) positive (86%), ≥T2 (88%), clinically node positive (74%), and anthracycline and taxane containing protocols were administered in 86% of cases. RS ranged between 5-75 with 50% > 25 and only 4 < 11. Mean RS was significantly higher among tumors achieving pCR vs. non-pCR response (51.9 vs. 26.6, pwilcoxon= 0.0005). pCR rate in patients with RS > 25 was 21% (8/38) vs. 5% in patients with RS < 25 (2/38), with both pCRs in the <25 group in patients with RS 21-25. In univariable analysis, PgR negativity (odds ratio (OR) 5.62, 95% confidence interval (CI) 1.27-24.89, p = 0.02), high grade (OR 9.03, 95%CI 1.07-76.32, p = 0.04) and higher RS as a continuous variable (OR 1.08, 95%CI 1.04-1.13, p = 0.0003) were associated with a greater likelihood of pCR. In multivariable analysis only RS remained significantly associated with pCR (OR: 1.07, 95%CI 1.01-1.12, p = 0.01): a 7% increase in the odds of pCR for every 1-point increase in RS. Conclusions: In young women with ER+, HER2- BC who received NAC, higher pretreatment RS was associated with an increased likelihood of pCR. Genomic expression profiling assays may have a role in decision-making in young women in need of neoadjuvant therapy. For women with low likelihood of benefiting from NAC, alternative approaches are clearly warranted. Given the demonstrated efficacy of neoadjuvant endocrine therapy in post-menopausal women, further evaluation in young women should be pursued.

Abstract We evaluated the joint associations between a new 313-variant PRS (PRS313) and questionnaire-based breast cancer risk factors for women of European ancestry, using 72 284 cases and 80 354 controls from the Breast Cancer Association Consortium. Interactions were evaluated using standard logistic regression and a newly developed case-only method for breast cancer risk overall and by estrogen receptor status. After accounting for multiple testing, we did not find evidence that per-standard deviation PRS313 odds ratio differed across strata defined by individual risk factors. Goodness-of-fit tests did not reject the assumption of a multiplicative model between PRS313 and each risk factor. Variation in projected absolute lifetime risk of breast cancer associated with classical risk factors was greater for women with higher genetic risk (PRS313 and family history) and, on average, 17.5% higher in the highest vs lowest deciles of genetic risk. These findings have implications for risk prevention for women at increased risk of breast cancer.