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Blaes, Anne

https://orcid.org/0000-0002-5433-4810

Mayo Clinic

University of Minnesota

Citations 26

Race, Gene Expression Signatures, and Clinical Outcomes of Patients With High-Risk Early Breast Cancer
Kyalwazi, Beverly , Campbell, Michael J. , Chien, A. Jo , Forero-Torres, Andres , Ellis, Erin D. , Albain, Kathy S. , Haley, Barbara , Clark, Amy S. , Nanda, Rita , Yung, Rachel L. , Tripathy, Debasish , Edmiston, Kristen K., Viscusi, Rebecca K., Northfelt, Donald W. , Khan, Qamar J. , Asare, Smita , Wilson, Amy , Hirst, Gillian L. , Lu, Ruixiao , Symmans, W. Fraser , Yee, Douglas , Veer, Laura van ‘t , Esserman, Laura J. , Olopade, Olufunmilayo I. , Tripathy, Debu , Olopade, Olufunmilayo I , Symmans, W Fraser , Esserman, Laura J , Hirst, Gillian L , Yee, Douglas , Yau, Christina , Yoshimatsu, Toshio F. , Wallace, Anne M. , Pusztai, Lajos , Blaes, Anne , Boughey, Judy C. , Elias, Anthony , Isaacs, Claudine , Han, Hyo S , DeMichele, Angela , Veer, Laura J. van’t

JAMA Network Open | December 28, 2023 | Volume: 6 | Issue: 12 | Pages: e2349646

10.1001/jamanetworkopen.2023.49646 Get It

ImportanceThere has been little consideration of genomic risk of recurrence by breast cancer subtype despite evidence of racial disparities in breast cancer outcomes.ObjectiveTo evaluate associations between clinical trial end points, namely pathologic complete response (pCR) and distant recurrence–free survival (DRFS), and race and examine whether gene expression signatures are associated with outcomes by race.Design, Setting, and ParticipantsThis retrospective cohort study used data from the Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging and Molecular Analysis 2 (I-SPY 2) multicenter clinical trial of neoadjuvant chemotherapy with novel agents and combinations for patients with previously untreated stage II/III breast cancer. Analyses were conducted of associations between race and short- and long-term outcomes, overall and by receptor subtypes, and their association with 28 expression biomarkers. The trial enrolled 990 female patients between March 30, 2010, and November 5, 2016, with a primary tumor size of 2.5 cm or greater and clinical or molecular high risk based on MammaPrint or hormone receptor (HR)-negative/ERBB2 (formerly HER2 or HER2/neu)–positive subtyping across 9 arms. This data analysis was performed between June 10, 2021, and October 20, 2022.ExposureRace, tumor receptor subtypes, and genomic biomarker expression of early breast cancer.Main Outcomes and MeasuresThe primary outcomes were pCR and DRFS assessed by race, overall, and by tumor subtype using logistic regression and Cox proportional hazards regression models. The interaction between 28 expression biomarkers and race, considering pCR and DRFS overall and within subtypes, was also evaluated.ResultsThe analytic sample included 974 participants (excluding 16 self-reporting as American Indian or Alaska Native, Native Hawaiian or Other Pacific Islander, or multiple races due to small sample sizes), including 68 Asian (7%), 120 Black (12%), and 786 White (81%) patients. Median (range) age at diagnosis was 47 (25-71) years for Asian, 49 (25-77) for Black, and 49 (23-73) years for White patients. The pCR rates were 32% (n = 22) for Asian, 30% for Black (n = 36), and 32% for White (n = 255) patients (P = .87). Black patients with HR-positive/ERBB2-negative tumors not achieving pCR had significantly worse DRFS than their White counterparts (hazard ratio, 2.28; 95% CI, 1.24-4.21; P = .01), with 5-year DRFS rates of 55% (n = 32) and 77% (n = 247), respectively. Black patients with HR-positive/ERBB2-negative tumors, compared with White patients, had higher expression of an interferon signature (mean [SD], 0.39 [0.87] and −0.10 [0.99]; P = .007) and, compared with Asian patients, had a higher mitotic score (mean [SD], 0.07 [1.08] and −0.69 [1.06]; P = .01) and lower estrogen receptor/progesterone receptor signature (mean [SD], 0.31 [0.90] and 1.08 [0.95]; P = .008). A transforming growth factor β signature had a significant association with race relative to pCR and DRFS, with a higher signature associated with lower pCR and worse DRFS outcomes among Black patients only.Conclusions and RelevanceThe findings show that women with early high-risk breast cancer who achieve pCR have similarly good outcomes regardless of race, but Black women with HR-positive/ERBB2-negative tumors without pCR may have worse DRFS than White women, highlighting the need to develop and test novel biomarker-informed therapies in diverse populations.
Evaluation of symptom severity, tolerability, and physical function in the I-SPY2 trial.
Umashankar, Saumya , Musthafa, Mina, Jones, Tamia, Blevins, Kaylee, Brown, Thelma, Heditsian, Diane , Parker, Beverly, Brain, Susie, Simmons, Carol A., Ruddy, Kathryn J. , Mainor, Candace , Tevis, Sarah , Dunn, Imogene, Melisko, Michelle , Basu, Amrita B , Simmons, Carol, Hieken, Tina J. , Blaes, Anne , Rugo, Hope S. , Esserman, Laura J. , Hershman, Dawn L.

JCO Oncology Practice | October 26, 2023 | Volume: 19 | Issue: 11_suppl | Pages: 369-369

10.1200/op.2023.19.11_suppl.369 Get It

369 Background: Patient-reported outcomes (PROs) are a valuable component to understand treatment tolerability and toxicity. We have implemented an electronic system for monitoring PROs and quality of life (QOL) for patients enrolled in the I-SPY2 trial, a phase II trial evaluating the effect of novel neoadjuvant therapies for breast cancer. We associated patient demographic factors with symptoms, decline in physical function (PF), and tolerability to treatment. Methods: Study population for this analysis includes 259 enrolled patients receiving combinations of experimental immunotherapy and chemotherapy. Patients completed PRO-CTCAE/PROMIS/FACT surveys reflecting symptom severity, symptom frequency, tolerability of drug, and physical function at baseline through follow up (12 months). CTCAE 5.0 was collected weekly at these timepoints to assess adverse events (AE). Odds ratio and regularized multi-variate regression was used to evaluate early symptoms predictive of a clinically significant decline in PF from baseline to post-treatment follow-up. Results: Of 259 patients, 160 (58%) were White, 13 (5%) were Asian, 26 (10%) were African American (AA), and 25 (9.3%) were Hispanic. 25% of all patients had a clinically significant decline in PF between baseline and pre-surgery/follow-up. Symptom predictors of decline included high frequency of diarrhea and severity of joint pain. African American (AA) patients had higher severity of joint pain than White patients (OR = 14.9, P < 0.05). Within the first 12 weeks of treatment, AA patients and non-white (NW) patients were more likely to report severe vomiting than White patients (OR =13.22 and 12.72, P< 0.05 and P< 0.03 respectively). Overall, patients that reported lower tolerance to therapy had higher grade of AE. While patients with low-grade adverse events were less bothered by their side effects at follow-up, higher grade adverse events such as hypothyroidism impacted distress levels by more than double. Conclusions: Among I-SPY2 participants, when higher grade of symptoms is persistent through follow up, it impacts physical function and tolerability even after end of therapy. Our study can allow physicians to be more diligent in active and post treatment monitoring. Clinical trial information: NCT01042379 .
A cross-institutional evaluation on breast cancer phenotyping NLP algorithms on electronic health records
Zhou, Sicheng , Wang, Nan , Wang, Liwei , Sun, Ju , Zhang, Rui , Blaes, Anne , Liu, Hongfang

Computational and Structural Biotechnology Journal | August 22, 2023 | Volume: 22 | Issue: No issue available | Pages: 32-40

10.1016/j.csbj.2023.08.018 Get It

Abstract Objective Transformer-based language models are prevailing in the clinical domain due to their excellent performance on clinical NLP tasks. The generalizability of those models is usually ignored during the model development process. This study evaluated the generalizability of CancerBERT, a Transformer-based clinical NLP model, along with classic machine learning models, i.e., conditional random field (CRF), bi-directional long short-term memory CRF (BiLSTM-CRF), across different clinical institutes through a breast cancer phenotype extraction task. Materials and methods Two clinical corpora of breast cancer patients were collected from the electronic health records from the University of Minnesota (UMN) and Mayo Clinic (MC), and annotated following the same guideline. We developed three types of NLP models (i.e., CRF, BiLSTM-CRF and CancerBERT) to extract cancer phenotypes from clinical texts. We evaluated the generalizability of models on different test sets with different learning strategies (model transfer vs locally trained). The entity coverage score was assessed with their association with the model performances. Results We manually annotated 200 and 161 clinical documents at UMN and MC. The corpora of the two institutes were found to have higher similarity between the target entities than the overall corpora. The CancerBERT models obtained the best performances among the independent test sets from two clinical institutes and the permutation test set. The CancerBERT model developed in one institute and further fine-tuned in another institute achieved reasonable performance compared to the model developed on local data (micro-F1: 0.925 vs 0.932). Conclusions The results indicate the CancerBERT model has superior learning ability and generalizability among the three types of clinical NLP models for our named entity recognition task. It has the advantage to recognize complex entities, e.g., entities with different labels.
Use of PROMIS to capture patient reported outcomes over time for patients on I-SPY2.
Jacob, Saya , Chattopadhyay, Aheli , Brain, Susie, Simmons, Carol A., Ruddy, Kathryn J. , Somani, Amrita B, Melisko, Michelle , Yu, Hongmei , Wolf, Denise M. , Simmons, Carol, Kang, Irene , Blaes, Anne , Hershman, Dawn L. , Esserman, Laura J.

Journal of Clinical Oncology | June 4, 2023 | Volume: 41 | Issue: 16_suppl | Pages: 611-611

10.1200/jco.2023.41.16_suppl.611 Get It

611 Background: Patient reported outcomes (PROs) capture direct feedback from patients in clinical trials. The NIH Patient-Reported Outcomes Measurement Information System (PROMIS) is an open source and validated PRO platform. Data on PROMIS score trajectories over time for breast cancer patients undergoing neoadjuvant chemotherapy (NAC) are limited. Methods: We administered paper surveys to patients enrolled on the I-SPY2 trial, a multicenter, randomized phase 2 trial comparing novel agents to standard NAC in high-risk breast cancer. PRO domains included PROMIS Physical Function, Anxiety, Depression, Applied Cognition and Fatigue. Surveys were administered at baseline (post-consent), C1D1, inter-regimen (~12 wks into NAC), pre-surgery and at 1, 6, 12, and 24 months post-surgery. Responses were scored using the HealthMeasures Scoring Service to generate a standardized T score, with a score of 50 representing the general US population mean. Higher Anxiety, Depression and Fatigue scores represent worse symptoms; higher Physical Function and Applied Cognition scores represent better symptoms. We calculated average scores by time-point and compared changes from baseline to various grouped time points using a paired t-test. Results: From 1/2012 to 7/2020, 1631 patients enrolled in I-SPY 2 with 959 completing the baseline survey. 62% had at least two “on-treatment” surveys, and 52% had at least one follow-up time-point. Average baseline PROMIS scores for Physical Function, Anxiety, Depression, Applied Cognition and Fatigue were 46.7, 55.1, 47.2, 53.3 and 46.0 respectively. Between baseline and the latest on-treatment time point we observed improvement in Anxiety (-5.2) and worsening in Physical Function, Applied Cognition and Fatigue (-5.4, -6.9 and +8.2 respectively). Between baseline and the latest post-surgery time point, we saw improved Anxiety (-5.9) and worsened Physical Function, Applied Cognition and Fatigue (-5.9, -3.6 and +4.3). Depression changed minimally. Conclusions: Using PROMIS, patients on I-SPY2 experienced worse Physical Function, Applied Cognition and Fatigue but improved Anxiety during and after treatment compared to baseline. While changes in Applied Cognition and Fatigue recovered partially after treatment, Physical Function scores did not, suggesting potential for longer term impact on quality of life. Clinical trial information: NCT01042379 . [Table: see text]
Abstract P5-07-03: The Association Between Symptom Severity and Physical Function among Participants in I-SPY2
Umashankar, Saumya, Blevins, Kaylee, Northrop, Anna, Christofferson, Anika, Olunuga, Ebunoluwa , Cha, Jaeyoon , Mittal, Ananya , Molina-Vega, Julissa, Sit, Laura , Brown, Thelma, Parker, Bev, Heditsian, Diane , Brain, Susie, Simmons, Carol A., Taboada, Alessandra, Ruddy, Kathryn J. , Salvador, Carolina, Afghahi, Anosheh , Tevis, Sarah , Perlmutter, Jane , Kanaparthi, Sai, Melisko, Michelle , Basu, Amrita B , Umashankar, Saumya , Molina-Vega, Julissa , Simmons, Carol, Hieken, Tina J. , Salvador, Carolina, Mainor, Candace , Blaes, Anne , Kang, Irene , Rugo, Hope S. , Peterson, Garry, Weiss, Lisa T., Asare, Adam L. , Esserman, Laura J. , Hershman, Dawn L.

Cancer Research | March 2, 2023 | Volume: 83 | Issue: 5_Supplement | Pages: P5-07-03-P5-07-03

10.1158/1538-7445.sabcs22-p5-07-03 Get It

Abstract Background. Patient-reported outcomes (PROs) are increasingly recognized as a valuable component to understand treatment tolerability and toxicity among patients on clinical trials. We have implemented a system for monitoring patient reported outcomes (PROs), symptoms, and quality of life (QOL) using electronic PRO (ePRO) instruments for patients enrolled in the I-SPY2 trial. I-SPY2 is a phase II multi-site clinical trial evaluating the effect of novel neoadjuvant therapies for locally advanced breast cancer. We correlated patient demographic factors with symptoms, investigated the trajectory of symptoms throughout treatment, and sought to characterize symptoms associated with decline in physical function (PF). Methods. Our study population included 259 I-SPY2 patients that completed surveys on one of 9 study arms (including novel oral taxane/immunotherapy combinations, IV paclitaxel, checkpoint inhibitor+/- LAG3 inhibitor, and control IV paclitaxel +/- trastuzumab/pertuzumab). After the 12 week period of investigational agents, most patients received standard adriamycin and cyclophosphamide (AC). Symptom severity, frequency, and interference was assessed weekly using 33 items from the PRO-CTCAE item bank. PF was assessed using the NIH PROMIS instrument and was evaluated at baseline, inter-regimen (after 12 weeks of treatment), pre-surgery, and 1 and 6 months at follow-up. An odds ratio was used to assess univariate associations between age and race, and symptoms. Regularized multi-variate regression was used to evaluate early symptoms (prior to week 6) predictive of a clinically significant (&gt;5 point T-score) decline in PF from baseline to post-treatment follow-up among all races and age groups. Results. Of 259 patients (mean age (SD) = 46.8 (13.6)), 160 (58%) were White, 13 (5%) were Asian, 26 (10%) were African American (AA), 25 (9.3%) were Hispanic, and 35 (13.5%) self-reported “Other”. At baseline, AA patients had a higher severity of joint pain than White patients (OR = 14.9, P &lt; 0.05). During study treatment with paclitaxel and/or novel agent within the first 12 weeks of treatment, AA patients and non-white (NW) patients were more likely to report severe vomiting than White patients (OR =13.22 and 12.72, P&lt; 0.05 and P&lt; 0.03 respectively). During treatment with AC, NW patients were more likely to report higher severity of neuropathy than White patients (OR = 5.43, P&lt; 0.03). Among all patients, in analysis of early symptoms predictive of a clinically significant decline in PF between baseline and 1 month post treatment, predictors included high frequency of diarrhea, severity of itching, and severity of joint pain. Further analysis of symptom trajectories revealed that frequency of diarrhea reported rose sharply between baseline and Cycle 2 with 9 patients (7%) reporting occasional or frequent diarrhea to 39 patients (28%) reporting occasional to almost constant diarrhea and remained stable at that proportion for the remainder of treatment. Frequency of diarrhea declined slightly during AC (17%) and dropped to baseline levels by follow-up. In contrast, severity of joint pain persisted post-treatment, rising consistently from baseline through follow- up with 3 patients (2%) reporting moderate to severe joint pain at baseline to 18 patients (35%) reporting moderate to severe joint pain at follow-up. Conclusion. Among I-SPY2 participants, when higher grade of diarrhea is persistent (or uncontrolled), it impacts physical function even after end of therapy. In some cases, race was also a determinant in symptom trajectory, although a higher enrollment of AA and NW patients will enable more robust estimates to be computed. While some of these early symptom predictors are transient and resolve by the time of follow-up, others persist long-term and contribute more directly towards impaired physical function at follow-up. Citation Format: Amrita Basu, Saumya Umashankar, Kaylee Blevins, Anna Northrop, Anika Christofferson, Ebunoluwa Olunuga, Jaeyoon Cha, Ananya Mittal, Julissa Molina-Vega, Laura Sit, Thelma Brown, Bev Parker, Diane Heditsian, Susie Brain, Carol Simmons, Alessandra Taboada, Tina J. Hieken, Kathryn Ruddy, Carolina Salvador, Candace Mainor, Anosheh Afghahi, Sarah Tevis, Anne Blaes, Irene M. Kang, Jane Perlmutter, Hope Rugo, Sai Kanaparthi, Garry Peterson, Lisa T. Weiss, Adam Asare, Laura J. Esserman, Michelle Melisko, Dawn Hershman. The Association Between Symptom Severity and Physical Function among Participants in I-SPY2 [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-07-03.
Abstract P4-12-02: Improving patient-reported outcome data capture for clinical research: ePRO in ISPY 2, a phase 2 breast cancer study
Northrop, Anna, Christofferson, Anika, Melisko, Michelle , Sit, Laura , Olunuga, Ebunoluwa , Mittal, Ananya , Goldman, Adi, Brown, Thelma, Heditsian, Diane , Parker, Bev, Brain, Susie, Simmons, Carol A., Taboada, Alessandra, Ruddy, Kathryn J. , Salvador, Carolina, Afghahi, Anosheh , Tevis, Sarah , Melin, Susan A., Simmons, Carol, Hieken, Tina J. , Piltin, Mara A. , Cook, Kiri A. , Salvador, Carolina, Mainor, Candace , Blaes, Anne , Kang, Irene , Esserman, Laura J. , Asare, Adam L. , Hershman, Dawn L. , Basu, Amrita B

Cancer Research | March 8, 2022 | Volume: 82 | Issue: 4_Supplement | Pages: P4-12-02-P4-12-02

10.1158/1538-7445.sabcs21-p4-12-02 Get It

Abstract Introduction: Advances in technology and internet capability have provided an opportunity for efficient collection of Patient Reported Outcomes (PRO) during medical treatment. Here we describe the development and implementation of a system for monitoring patient reported adverse events (AEs) and quality of life (QoL) using electronic PRO (ePRO) instruments for patients enrolled on the Investigation of Serial studies to Predict Your Therapeutic Response with Imaging And moLecular analysis (I-SPY 2 TRIAL), a phase II adaptive platform clinical trial for locally advanced breast cancer. Methods: We designed an ePRO system to increase the accuracy of patient-reported QoL and AE data collection with the intent to act on symptoms in real time. Using the OpenClinica electronic data capture system, we developed rules-based logic to build automated ePRO surveys, customized to the I-SPY 2 treatment schedule. Weekly surveys contained a maximum of 126 validated, branching logic questions from the Patient Reported Outcomes Measurement Information System (PROMIS®) Health Measures and the National Cancer Institute’s Patient Reported Outcomes - Common Terminology Criteria for Adverse Events (PRO-CTCAE™) instruments. We piloted ePROs at the University of California, San Francisco (UCSF) to evaluate compatibility with a variety of I-SPY 2 patient scenarios (e.g., dose delays). We then staggered rollout of the ePRO system to 22 I-SPY 2 sites to ensure technological feasibility. In order to improve accuracy of data collection, we utilized real-time tracking and developed a Clinical Research Coordinator (CRC) training manual, which integrated workflow diagrams with technical solutions. CRCs were trained using remote video sessions. Results: The UCSF ePRO pilot began in September of 2020. Over 9-months, we accrued 43 I-SPY 2 patients (average age of 43.8 years), whose interactions with the ePRO system informed design improvements. Of the patients who received a baseline ePRO survey, the completion rate was 75.9% (average age of 44.2 years). This represents an increase from the 15-20% baseline completion rate for the 360 UCSF I-SPY 2 patients who received paper-based PRO surveys between May 2012 - January 2019. As of June 2021, the ePRO system was operational at all 22 I-SPY 2 sites. The UCSF pilot revealed that engagement with patients at critical timepoints improved survey completion. CRCs facilitated patient participation by sending instructional emails and communicating with patients weekly. We tracked data completeness using a Patient Tracking report, which displayed each patient’s survey completion history. This real-time tool enabled CRCs to identify patients who had not completed ePRO surveys prior to their visit, so they could be provided a tablet computer to complete the survey in the clinic. After introducing tablets into the workflow at UCSF, patient completion of the baseline survey increased from 75.9% to 80%. Conclusion: The transition from paper to electronic QOL and AE data collection improves the ability of patients to complete PRO surveys, but the process must also be optimized and integrated into clinical workflow and trial conduct. In the future, we will present additional results highlighting the feasibility of multilingual ePRO integration into I-SPY 2. ePRO also provides a new opportunity for data analysis, as well as the potential to reduce high grade toxicity through early intervention. It will allow us to assess QoL and AE data by drug regimen, site, provider, and study treatment. The creation of clinician-facing reports also enables access to patient responses in real-time. By implementing ePRO within I-SPY 2, we not only increase efficiency and accuracy of patient-reported data collection, but also improve quality of care and patient safety. Citation Format: Anna Northrop, Anika Christofferson, Michelle Melisko, Laura Sit, Ebunoluwa Olunuga, Ananya Mittal, Adi Goldman, Thelma Brown, Diane Heditsian, Bev Parker, Susie Brain, Carol Simmons, Alessandra Taboada, Kathryn J Ruddy, Tina Hieken, Mara Piltin, Kiri Cook, Carolina Salvador, Candace Mainor, Anosheh Afghahi, Sarah Tevis, Anne Blaes, Irene Kang, Susan Melin, Laura Esserman, Adam Asare, Dawn L Hershman, Amrita Basu. Improving patient-reported outcome data capture for clinical research: ePRO in ISPY 2, a phase 2 breast cancer study [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-12-02.
Abstract GS4-02: Analysis of clinical outcomes and expression-based immune signatures by race in the I-SPY 2 trial
Kyalwazi, Beverly , Olopade, Olufunmilayo, Chien, A. Jo , Forero‐Torres, Andres , Ellis, Erin M. , Albain, Kathy S. , Haley, Barbara , Elias, A. , Clark, Amy S. , Nanda, Rita , Yung, Rachel L. , Edmiston, Kristen K., Viscusi, Rebecca K., Northfelt, Donald W. , Khan, Qamar J. , Sanil, Ashish, Asare, Smita , Wilson, Amy , Hirst, Gillian L. , Melisko, Michelle , Perlmutter, Jane , Rugo, Hope, Symmans, Fraser, Veer, Laura van ‘t , Berry, Donald A. , Hirst, Gillian L , Yau, Christina , Olopade, Olufunmilayo I. , Wallace, Anne M. , Pusztai, Lajos , Ellis, Erin, Blaes, Anne , Boughey, Judy C. , Isaacs, Claudine , Han, Hyo S , Tripathy, Debu , Berry, Scott , Hylton, Nola M. , Symmans, W. Fraser , Veer, Laura J. van’t , Esserman, Laura J.

Cancer Research | March 8, 2022 | Volume: 82 | Issue: 4_Supplement | Pages: GS4-02-GS4-02

10.1158/1538-7445.sabcs21-gs4-02 Get It

Abstract Background Transcriptomic immune-related gene signatures have been associated with achievement of pathologic complete response (pCR) and prognosis in the neoadjuvant setting. I-SPY 2 is a multicenter, phase 2 platform trial using response-adaptive randomization within subtypes defined by receptor status (HR/HER2) and MammaPrint (MP) risk to evaluate novel agents as neoadjuvant therapy for women with high-risk breast cancer. Given racial disparities in mortality from breast cancer and the paucity of racial demographic data from clinical trials, we aimed to evaluate the association between racial groups and baseline characteristics, including expression-based subtypes and immune signatures, treatment response, and prognosis of patients enrolled in the I-SPY 2 TRIAL. Methods Our study population included 990 I-SPY 2 patients. 15 patients identified as part of a racial group with &lt;10 patients enrolled in the trial and were excluded from analysis. Pre-treatment expression data was available for 971 patients. Follow-up data was available for 907 patients; median follow-up time of 4.4 yrs. Chi-square test was used to assess associations between racial groups and pre-treatment SBR grade, HR/HER2 defined subtypes, intrinsic subtype (defined by BluePrint 80-gene molecular subtyping) and residual cancer burden (RCB) class. Logistic regression was used to evaluate race association with pCR. Cox proportional hazard modeling was used to assess the association between racial groups and event free survival (EFS) in a univariate setting, adjusting for pCR status. Association between racial groups and 28 expression signatures related to immune, proliferation, ER and HER2 pathway was analyzed using ANOVA with post-hoc Tukey test in the overall population and in each receptor subtype. Results Of 975 patients included in our analysis, 787 (81%) were White, 68 (7%) were Asian, and 120 (12%) were Black or African American. No significant associations between race and pre-treatment SBR grade (p=0.49), HR/HER2 defined subtypes (p=0.09), or expression-based subtypes (p=0.25) were observed. pCR rates do not significantly differ by racial groups (Odds ratio of pCR relative to White: 1.00 for Asian and 0.89 for Black or African American); and no significant differences in RCB class distribution by race was observed (p=0.88). Event free survival was not associated with patient racial group in a univariate Cox model (Hazard ratio relative to White: 1.10, p=0.73 for Asian and 1.37, p=0.13 for Black or African American). Among the 28 expression signatures evaluated, four were differentially expressed among racial groups within the overall population (F-test p&lt;0.05): IFN module, B cell signature, Dendritic cell signature, and Mitotic score. Pairwise comparisons between racial groups with post-hoc Tukey test identified significant differences in IFN module expression between Black or African American vs. White (p=0.019) and Dendritic cell signature expression between Asian vs White (p=0.047). Among patients in the TNBC subtype, three signatures (dendritic cell signature, macrophage signature and ERBB2 module) were differentially expressed between Black or African American and White patients (p=0.002, 0.016 and 0.007). Conclusion Our analysis demonstrates that among women with high risk breast cancer, race does not affect subtype specific response rates nor event free survival. Distribution of subtypes previously shown to be associated with pCR in the I-SPY2 trial did not significantly differ among racial groups indicating race is less likely than tumor biology to predict response. The decreased expression of immune signatures observed in Black or African American women with TNBC suggests possible differential sensitivity to immunotherapy plus combination chemotherapy. Tumor immune multiplex studies are underway to further investigate. Citation Format: Beverly Kyalwazi, Christina Yau, Olufunmilayo Olopade, A. Jo Chien, Anne Wallace, Andres Forero-Torres, Lajos Pusztai, Erin Ellis, Kathy Albain, Anne Blaes, Barbara Haley, Judy Boughey, Anthony Elias, Amy Clark, Claudine Isaacs, Rita Nanda, Hyo Han, Rachel Yung, Debu Tripathy, Kristen Edmiston, Rebecca Viscusi, Donald Northfelt, Qamar Khan, Ashish Sanil, Scott Berry, Smita Asare, Amy Wilson, Gillian Hirst, Nola Hylton, Michelle Melisko, Jane Perlmutter, Hope Rugo, Fraser Symmans, Laura van ‘t Veer, Donald Berry, Laura Esserman. Analysis of clinical outcomes and expression-based immune signatures by race in the I-SPY 2 trial [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr GS4-02.
Defining cardiovascular toxicities of cancer therapies: an International Cardio-Oncology Society (IC-OS) consensus statement
Herrmann, Joerg , Lenihan, Daniel J. , Armenian, Saro H. , Barac, Ana , Blaes, Anne , Cardinale, Daniela , Carver, Joseph R. , Dent, Susan , Ky, Bonnie , Lyon, Alexander R. , Fradley, Michael G. , Ganatra, Sarju , Curigliano, Giuseppe , Mitchell, Joshua D. , Minotti, Giorgio , Lang, Ninian N. , Liu, Jennifer E. , Neilan, Tomas G. , O’Quinn, Rupal, Pusic, Iskra , Porter, Charles , Reynolds, Kerry L. , Ruddy, Kathryn J. , Valent, Peter , Lenihan, Daniel , Armenian, Saro H , Carver, Joseph , López-Fernández, Teresa , Fradley, Michael G , Ganatra, Sarju , Curigliano, Giuseppe , Mitchell, Joshua D , Minotti, Giorgio , Lang, Ninian N , Nohria, Anju , Porter, Charles , Thavendiranathan, Paaladinesh , Barac, Ana , Blaes, Anne H , Ky, Bonnie , Valent, Peter , Lyon, Alexander R , López‐Fernández, Teresa

European Heart Journal | September 10, 2021 | Volume: 43 | Issue: 4 | Pages: 280-299

10.1093/eurheartj/ehab674 Get It

Abstract The discipline of Cardio-Oncology has seen tremendous growth over the past decade. It is devoted to the cardiovascular (CV) care of the cancer patient, especially to the mitigation and management of CV complications or toxicities of cancer therapies, which can have profound implications on prognosis. To that effect, many studies have assessed CV toxicities in patients undergoing various types of cancer therapies; however, direct comparisons have proven difficult due to lack of uniformity in CV toxicity endpoints. Similarly, in clinical practice, there can be substantial differences in the understanding of what constitutes CV toxicity, which can lead to significant variation in patient management and outcomes. This document addresses these issues and provides consensus definitions for the most commonly reported CV toxicities, including cardiomyopathy/heart failure and myocarditis, vascular toxicity, and hypertension, as well as arrhythmias and QTc prolongation. The current document reflects a harmonizing review of the current landscape in CV toxicities and the definitions used to define these. This consensus effort aims to provide a structure for definitions of CV toxicity in the clinic and for future research. It will be important to link the definitions outlined herein to outcomes in clinical practice and CV endpoints in clinical trials. It should facilitate communication across various disciplines to improve clinical outcomes for cancer patients with CV diseases.
A Randomized Phase IIb Study of Low-dose Tamoxifen in Chest-irradiated Cancer Survivors at Risk for Breast Cancer
Palomares, Melanie R. , Hageman, Lindsey , Chen, Yanjun , Landier, Wendy , Smith, Kandice, Umphrey, Heidi , Reich, Caroline A., Zamora, Kathryn , Armenian, Saro H. , Bevers, Therese B. , Henderson, Tara O. , Korde, Larissa A. , Melin, Susan A., Merajver, Sofía D. , Overholser, Linda , Pruthi, Sandhya , Wong, F. Lennie , Landier, Wendy , Smith, Kandice , Zamora, Kathryn W , Armenian, Saro H , Hudson, Melissa M , Garber, J. E. , Bhatia, Smita , Blaes, Anne , Hodgson, David , Hudson, Melissa M. , Garber, Judy E.

Clinical Cancer Research | December 3, 2020 | Volume: 27 | Issue: 4 | Pages: 967-974

10.1158/1078-0432.ccr-20-3609 Get It

Abstract Purpose: Low-dose tamoxifen reduces breast cancer risk, but remains untested in chest-irradiated cancer survivors—a population with breast cancer risk comparable with BRCA mutation carriers. We hypothesized that low-dose tamoxifen would be safe and efficacious in reducing radiation-related breast cancer risk. Patients and Methods: We conducted an investigator-initiated, randomized, phase IIb, double-blinded, placebo-controlled trial (FDA IND107367) between 2010 and 2016 at 15 U.S. sites. Eligibility included ≥12 Gy of chest radiation by age 40 years and age at enrollment ≥25 years. Patients were randomized 1:1 to low-dose tamoxifen (5 mg/day) or identical placebo tablets for 2 years. The primary endpoint was mammographic dense area at baseline, 1 and 2 years. IGF-1 plays a role in breast carcinogenesis; circulating IGF-1 and IGF-BP3 levels at baseline, 1 and 2 years served as secondary endpoints. Results: Seventy-two participants (low-dose tamoxifen: n = 34, placebo: n = 38) enrolled at a median age of 43.8 years (35–49) were evaluable. They had received chest radiation at a median dose of 30.3 Gy. Compared with the placebo arm, the low-dose tamoxifen arm participants had significantly lower mammographic dense area (P = 0.02) and IGF1 levels (P &lt; 0.0001), and higher IGFBP-3 levels (P = 0.02). There was no difference in toxicity biomarkers (serum bone-specific alkaline phosphatase, lipids, and antithrombin III; urine N-telopeptide cross-links) between the treatment arms. We did not identify any grade 3–4 adverse events related to low-dose tamoxifen. Conclusions: In this randomized trial in chest-irradiated cancer survivors, we find that low-dose tamoxifen is effective in reducing established biomarkers of breast cancer risk and could serve as a risk-reduction strategy.
Cardiovascular Care of the Oncology Patient During COVID-19: An Expert Consensus Document From the ACC Cardio-Oncology and Imaging Councils
Baldassarre, Lauren A. , Yang, Eric H. , Cheng, Richard K. , DeCara, Jeanne M. , Liu, Jennifer E. , Rudski, Lawrence , Strom, Jordan B. , Barac, Ana , Bucciarelli‐Ducci, Chiara , Lenneman, Carrie , Villarraga, Hector R. , Ismail‐Khan, Roohi , Ky, Bonnie , Leja, Monika, Scherrer‐Crosbie, Marielle , Liu, Jennifer E , Rudski, Lawrence G , Strom, Jordan B , Thavendiranathan, Paaladinesh , Barac, Ana , Zaha, Vlad G , Bucciarelli-Ducci, Chiara , Ellahham, Samer , Deswal, Anita M , Lenneman, Carrie , Villarraga, Hector R , Blaes, Anne H , Ismail-Khan, Roohi , Ky, Bonnie , Scherrer-Crosbie, Marielle , Yang, Eric , Cheng, Richard , Dent, Susan , Blaes, Anne

JNCI: Journal of the National Cancer Institute | November 3, 2020 | Volume: 113 | Issue: 5 | Pages: 513-522

10.1093/jnci/djaa177 Get It

Abstract In response to the coronavirus disease 2019 (COVID-19) pandemic, the Cardio-Oncology and Imaging Councils of the American College of Cardiology offers recommendations to clinicians regarding the cardiovascular care of cardio-oncology patients in this expert consensus statement. Cardio-oncology patients—individuals with an active or prior cancer history and with or at risk of cardiovascular disease—are a rapidly growing population who are at increased risk of infection, and experiencing severe and/or lethal complications by COVID-19. Recommendations for optimizing screening and monitoring visits to detect cardiac dysfunction are discussed. In addition, judicious use of multimodality imaging and biomarkers are proposed to identify myocardial, valvular, vascular, and pericardial involvement in cancer patients. The difficulties of diagnosing the etiology of cardiovascular complications in patients with cancer and COVID-19 are outlined, along with weighing the advantages against risks of exposure, with the modification of existing cardiovascular treatments and cardiotoxicity surveillance in patients with cancer during the COVID-19 pandemic.