Early-stage Breast Cancer Patients Research Articles

Abstract PO2-11-07: Early Integration of Exercise into Breast Cancer Care: The MSK Healthy Living Program

Abstract Background: In patients with early-stage breast cancer, quality of life (QoL) worsens within 3-6 months following diagnosis. Physical activity (PA) can mitigate the adverse effects of treatment and improve QoL, and low PA level is associated with cancer recurrence and mortality. However, PA interventions are not included in standard cancer care. Early intervention to increase PA levels may improve QoL during active cancer therapy. The Healthy Living Program (HLP) at Memorial Sloan Kettering Cancer Center (MSK) is a lifestyle and survivorship program that engages early-stage breast cancer patients at the time of diagnosis using lifestyle risk stratification and matched referrals. We investigated whether early exercise intervention through the MSK HLP impacts QoL within the first months after cancer diagnosis. Methods: At the time of diagnosis, patients complete a lifestyle questionnaire (LQ), which is a composite of validated instruments, including the Godin Leisure Time Exercise Questionnaire (GLTEQ). Patients not meeting PA guidelines per the GLTEQ are offered a referral to an exercise physiologist (EP). The EP creates an individualized, home-based exercise program using the FITT Principle (Frequency, Intensity, Time, and Type). Patients meet with the EP every 4 weeks for 16 weeks; if exercise recommendations continue to be unmet, the program is extended. The Functional Assessment of Cancer Therapy-Breast (FACT-B) and 36-Item Short Form Survey Instrument (SF-36) were completed at baseline and the 16-week follow-up. Results: 252 patients enrolled between April 2020 – February 2023, of whom 92 volunteered to complete the QoL assessments. Median age was 53 years [range 23-84]; 12/252 (13.0%) of patients had ductal carcinoma in situ, 60/252 (65.2%) had Stage 1 disease, 17/252 (18.5%) had Stage 2 disease, and 3/252 (3.1%) had Stage 3 disease. 29/252 (31.5%) received chemotherapy, 62/252 (67.4%) received radiation, and 79/252 (85.9%) received hormone therapy. The mean baseline FACT scores were FACT-B: 116, FACT-G: 87, and FACT-B Trial Outcome Index (TOI): 73. At the 16-week follow-up, all QOL scores remained stable from baseline (means FACT-B: 118, FACT-G: 89, and TOI: 75). Improvements were observed among the subscales of the SF-36 from baseline to follow-up. The largest improvements were observed in physical and emotional role function scores, with 22% and 13% improvements from baseline to follow-up, respectively. Conclusions: A clinically implemented exercise intervention embedded in standard of care prevented decreases in QoL and improved physical and emotional functioning during the initial course of adjuvant breast cancer therapy. These findings support early implementation of lifestyle modification after a breast cancer diagnosis. Citation Format: Kylie Rowed, Sherry Shen, Andrea Smith, Bridget Kelly, Rocco Magnoli, Stacie Corcoran, Melissa Emerzian, Cynthia Cruz, Erica Salehi, Cara Anselmo, Mark Robson, Neil Iyengar. Early Integration of Exercise into Breast Cancer Care: The MSK Healthy Living Program [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-11-07.

Abstract PO2-22-04: Median Five-Year Follow-Up Results from the Multi-Institution Trial for the Treatment of Early-Stage Breast Cancer Using Intra-Operative Electronic Brachytherapy

Abstract Background: An IRB-approved single arm prospective multi-institution trial was designed to determine the efficacy and outcome of single fraction 20 Gy intra-operative radiation therapy (IORT) using disposable balloon electronic brachytherapy at the time of breast conserving surgery for early-stage breast cancer (women at least 40 years old, infiltrating ductal carcinoma [IDC] or ductal carcinoma in situ [DCIS], single lesion no larger than 3 cm, pN0). Ipsilateral breast tumor recurrences (IBTR) at median 5-year follow-up, the primary protocol endpoint of the trial, would be analyzed with outcomes compared to reported whole breast radiation therapy (WBRT) results. Methods: Between May 2012–July 2018,1199 enrolled breast cancer patients at twenty-six national and international institutions were successfully treated per protocol with lumpectomy plus single 20 Gy fraction IORT using disposable balloon electronic brachytherapy. Data collection and retrospective chart review included demographics, treatment, histopathology, toxicity, IBTR (defined as recurrence in the lumpectomy cavity/index quadrant), and survival. Results: All subjects were successfully treated with a single 20 Gy fraction of IORT. IORT cohort characteristics of the treated subjects are summarized in Table 1. Sixty-six (5.5%) patients received subsequent unplanned risk-adjusted WBRT. At median 5.0-year follow-up (range 0.5 – 9 years), there were 42 (3.50%) IBTR. The original mean tumor size of patients with IBTR was 13.6mm (range 0.03 - 30mm). The mean time to IBTR was 47.6 months (range 12 – 98 months). There were 30 IBTR in patients originally diagnosed with IDC, and 12 IBTR among patients originally diagnosed with DCIS. Three patients originally diagnosed with IDC recurred as DCIS, while 4 patients with DCIS recurred as IDC. The remainder recurred with the same pathology as their original diagnoses. Sorting by 2017 ASTRO accelerated partial breast irradiation (APBI) criteria, there were 25 IBTR in patients categorized immediately following lumpectomy plus IORT as Suitable, 12 IBTR among patients categorized immediately following lumpectomy plus IORT as Cautionary, and 5 IBTR in patients categorized immediately following lumpectomy plus IORT as Unsuitable. Nine (0.75%) patients experienced new ipsilateral primary breast cancers, with 8 classified as Suitable and one as Cautionary using post-lumpectomy plus IORT ASTRO APBI criteria. Seventeen (1.4%) patients experienced acute serious adverse events (SAEs). These included 5 wound infections, 4 hematomas, 2 skin ulcerations, 2 cellulitis, 2 seromas, 1 skin necrosis, and 1 wound dehiscence. All SAEs resolved within 6 months of IORT. One patient died of breast cancer metastases at 3-year follow-up. One patient who was diagnosed with IBTR at 3-year follow-up died 3 years later from dementia. There were 45 unrelated patient deaths. Conclusions: At median 5.0-year follow-up, the 1199 early-stage breast cancer patients successfully treated in this multi-institution trial with a single 20 Gy fraction of IORT to the lumpectomy cavity at the time of partial mastectomy experienced an IBTR of 3.50%. This recurrence rate is acceptable when compared to the 0.9% - 2.5% IBTR reported for WBRT, given the benefits of IORT (convenience, decreased exposure to XRT, better cosmetic outcome, patient preference). Table 1. IORT cohort characteristics Citation Format: Barbara Schwartzberg, AM Nisar Syed, Ajay Bhatnagar, Sophia Rahman, Veronica Jones, Albert Chang, Todd Cockerham, Virginia Osborn, Robert Cohen, Charles Hodge, Christina Lopez-Penalver, Bapsi Chakravarthy, William Dooley, Chika Madu, Atsuko Okabe, Maen Farha, Andrea Madrigrano, Christopher Morrison, Geoffrey Neuner, Craig Wengler, Steven David, Katayoon Toosie, Bryon Stephens. Median Five-Year Follow-Up Results from the Multi-Institution Trial for the Treatment of Early-Stage Breast Cancer Using Intra-Operative Electronic Brachytherapy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-22-04.

Abstract ED03-03: Impact of exercise on breast cancer outcomes

Abstract Background: Exercise may improve breast cancer outcomes; however, current research is limited in its ability to inform clinical exercise trials and clinical oncology practice. The purpose of this presentation is to summarize the current research on exercise and breast cancer outcomes using a framework proposed to improve the clinical utility of this research. The Exercise as Cancer Treatment (EXACT) Framework organizes and characterizes the critical aspects of a clinical oncology setting to allow for a more systematic and clinically informative approach to the study of exercise as a cancer treatment. The EXACT Framework proposes that two key clinical oncology variables—tumor/disease status (i.e., primary tumor present, primary tumor removed, metastatic disease present) and treatment status (i.e., treatment naïve, actively being treated, previously treated)—are critical for understanding the effects of exercise on cancer outcomes, but few studies have addressed these variables. Application of the EXACT Framework to existing studies may improve their interpretation and identify directions for future research. Results: Presently, there are no adequately powered randomized controlled trials that have examined the effects of exercise on breast cancer outcomes in any clinical oncology scenario, although secondary analysis of smaller phase II trials have been reported. Preclinical research using rodent models has generally shown that exercise slows the growth and spread of treatment naïve breast tumors through various mechanisms including immune response, tumor metabolism, apoptosis, and DNA synthesis and repair. More recently, these preclinical studies have enhanced their clinical utility by including an existing cancer treatment in their design and have generally shown that exercise enhances the delivery and/or efficacy of concurrent cancer treatments through mechanisms related to improved tumor vasculature and perfusion. Most human evidence on exercise and breast cancer outcomes has been gleaned from secondary analysis of observational studies involving healthy cohorts or breast cancer survivor cohorts. These studies have generally included early-stage breast cancer patients who received heterogeneous cancer treatments. Physical activity data was typically collected either well before diagnosis and/or well after treatments. Overall, these studies have generally shown that higher prediagnosis and postdiagnosis physical activity are associated with a lower risk of breast cancer recurrence and mortality. Discussion: There is a disconnect between the clinical oncology scenarios addressed by animal and human studies of exercise and breast cancer outcomes. Moreover, most studies do not adequately address treatment combinations and sequencing. Future observational studies of exercise and breast cancer outcomes may improve their clinical utility by: (a) recruiting breast cancer patients with the same tumor/disease status receiving the same or similar first-line treatment protocols, (b) collecting detailed data on all planned and unplanned cancer treatments, (c) assessing exercise in relation to those cancer treatments (i.e., before, during, between, after) rather than in relation to the cancer diagnosis (i.e., various time periods before and after diagnosis), (d) collecting data on cancer-specific outcomes (e.g., disease response, progression, recurrence) in addition to mortality, and (e) conducting subgroup analyses based on cancer treatments received. Conclusions: Preclinical and observational studies may contribute important knowledge regarding the role of exercise as a cancer treatment; however, modifications to study design and analysis are necessary if they are to inform clinical research and practice. The ultimate goal of precision exercise oncology is to provide the right exercise prescription to the right breast cancer patient at the right time postdiagnosis. Citation Format: K. Courneya. Impact of exercise on breast cancer outcomes [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr ED03-03.

Abstract PO5-01-05: An Open-label, Single-center Study Assessing the Efficacy of PH-based Regimen as Neoadjuvant Therapy for HER2-positive Early-stage Breast Cancer: Integrating Genomic Features and Functional Imaging

Abstract Background: Pathological complete response (pCR) has been demonstrated as a surrogate endpoint for disease-free and overall survival in HER2-positive early-stage breast cancer (EBC). Trastuzumab (H) plus pertuzumab (P) improved pCR rates in patients with HER2-positive early-stage breast cancer. Nevertheless, biomarkers to assess the effectiveness of this treatment in the neoadjuvant setting are still unclear. This study aims to evaluate the effectiveness of fluorodeoxyglucose positron emission tomography (18F-FDG-PET) and 68 Ga-Affibody HER2 Imaging PET (HER2-PET) in HER2 EBC neoadjuvant therapy, and to identify novel biomarkers for this regimen. Methods: HER2-positive EBC patients were prospectively recruited at Fudan University Shanghai Cancer Center between April 2020 and March 2022. All patients received the 1 dose of HP, followed by 6 cycles of docetaxel (T), carboplatin (Cb), and HP. We use FoundationOne to evaluate the genomic alterations before treatment. In addition, 18F-FDG-PET and HER2 PET were performed at baseline, after 1 cycle of HP, and after 6 cycles of TCbHP, to assess the effectiveness of these examinations in the prediction of pCR and correlation to disease burden. All patients were received surgery and completed 1 year of HP-based regimen in the adjuvant setting. Results: A total of 61 patients with a median age of 49 years were included. Among them, 93.5% of patients are node positive. 75.8% of the patients reported adverse events (AEs), primarily grade 1 and 2. The incidence of serious AEs was 6.6%. Patients exhibiting a greater than 40% reduction in SUVmax of 18-FDG-PET or HER2-PET scans from baseline to the fifth day after the initial HP treatment were classified as the treatment-sensitive group. The pCR rate for the 18-FDG-PET-sensitive group was 79.3%, while for the insensitive group was 48.1%. For HER2-PET scans, the pCR rate was 70.0% in the sensitive group and 59.3% in the non-sensitive group. To evaluate the potential biomarkers, 25 patients (13 pCR and 12 non-pCR) were evaluated with FoundationOne, with the identification of 1,321 somatic alterations. The most frequently altered genes were ERBB2 (100%), TP53 (96%), CDK12 (76%), MYC (56%), CCND1 (44%), PIK3CA (40%), and SRSF2 (36%). In the pCR group, we found PPM1D (38.5%) and RAD21 (38.5%) were altered more frequently than the non-pCR group. PIK3CA alterations were significantly reduced in pCR group, only 23% of cases are affected compared to 58.3% in non-pCR group. Patients were non-pCR had more MDM4 (41.7%) and ZNF217 (41.7%) alterations than pCR patients. Conclusion: The SUVmax value of 18-FDG-PET and HER2-PET scans are correlated well with the tumor burden and the residual disease in the HER2 EBCs. The reduction of SUVmax could predict pCR but need further exploration. Patients with alterations in PPM1D and RAD21 have a favorable response to the TCbHP regimen. Conversely, alterations in PIK3CA, MDM4, and ZNF217 are associated with treatment resistance. These results indicate the significance of 18-FDG-PET and HER2-PET in monitoring treatment effectiveness. The biomarker analysis in this study will help us understand the mechanism of HER2 positive breast cancer treatment resistance and assisting in tailoring personalized therapy. Clinical trial information: NCT04281641. Citation Format: Ming Chen, Benlong Yang, Sun Yuyun, Linxiaoxi Ma, Song Shaoli, Min He, Zhi-Ming Shao, Bingqiu Xiu, Jiong Wu. An Open-label, Single-center Study Assessing the Efficacy of PH-based Regimen as Neoadjuvant Therapy for HER2-positive Early-stage Breast Cancer: Integrating Genomic Features and Functional Imaging [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-01-05.

Impact of obesity on sentinel lymph node biopsy outcomes and survival in breast cancer patients: A single-center retrospective study.

Sentinel lymph node biopsy (SLNB) is a common choice for axillary surgery in patients with early-stage breast cancer (BC) who have clinically negative lymph nodes. Most research indicates that obesity is a prognostic factor for BC patients, but studies assessing its association with the rate of positive sentinel lymph nodes (SLN) and the prognosis of patients with early BC undergoing SLNB are limited. Between 2013 and 2016, 7062 early-stage BC patients from the Shanghai Cancer Center of Fudan University were included. Based on the Chinese Body Mass Index (BMI) classification standards, the patients were divided into three groups as follows: normal weight, overweight, and obese. Propensity score matching analysis was used to balance the baseline characteristics of the participants. Logistic regression analysis was used to determine the association between obesity and positive SLN rate. Cox regression analysis was used to investigate whether obesity was an independent prognostic factor for early-stage BC patients who had undergone SLNB. No significant association was observed between obesity and positive SLN rate in early-stage BC patients who had undergone SLNB. However, multivariate analysis revealed that compared to patients with normal BMI, the overall survival (hazard ratio (HR) 2.240, 95% confidence interval (CI) 1.27-3.95, p = 0.005) and disease-free survival (HR 1.750, 95% CI 1.16-2.62, p = 0.007) were poorer in patients with high BMI. Obesity is an independent prognostic factor for early-stage BC patients who undergo SLNB; however, it does not affect the positive SLN rate.

Efficacy and safety of Trastuzumab Emtansine in treating human epidermal growth factor receptor 2-positive metastatic breast cancer in Chinese population: a real-world multicenter study.

Trastuzumab emtansine (T-DM1) has been approved worldwide for treating metastatic breast cancer (mBC) in patients who have received first-line therapy, shown disease progression, and are human epidermal growth factor receptor 2 (HER2)-positive. T-DM1 received approval in China to treat early-stage breast cancer (BC) in 2020 and for mBC in 2021. In March 2023, T-DM1 was included in medical insurance coverage, significantly expanding the eligible population. This post-marketing observational study aimed to assess the safety and effectiveness of T-DM1 in real-world clinical practice in China. This study enrolled 31 individuals with HER2-positive early-stage BC and 70 individuals with HER2-positive advanced BC from 8 study centers in Shandong Province, China. The T-DM1 dosage was 3.6 mg/kg injected intravenously every 3 weeks until the disease advanced or the drug toxicity became uncontrollable, whichever occurred earlier. Additionally, efficacy and safety information on T-DM1 were collected. During the 7-month follow-up period, no recurrence or metastases were observed in patients who had early-stage BC. The disease control rate was 31.43% (22/70) in patients with advanced BC. The most common adverse effect of T-DM1 was thrombocytopenia, with an incidence of 69.31% (70/101), and the probability of Grade ≥ 3 thrombocytopenia was 11.88% (12/101). This real-world study demonstrated that T-DM1 had good efficacy and was well tolerated by both HER2-positive early-stage BC and mBC patients.

Real-world data of HER2-negative early breast cancer patients treated with anthracycline and/or taxane regimens in Japan

BackgroundAnthracycline- and taxane-based chemotherapy regimens are established treatments for human epidermal growth factor receptor (HER)2-negative early-stage breast cancer with high risk of recurrence. This study examined the prevalence of these chemotherapy regimens as perioperative therapy, the patterns of retreatment, and factors influencing prescription choices in Japan.MethodsThis observational cohort study focused on high-risk early-stage breast cancer patients not undergoing anti-HER2 therapy, utilizing data from a hospital-based claims database in Japan spanning from April 2008 to September 2021.ResultsOf 42,636 high-risk patients who underwent breast cancer surgery, 32,133 (75.4%) were categorized as having luminal-type (received endocrine therapy) and 10,503 (24.6%) as having triple-negative cancer (not receiving any endocrine therapies). Most patients (98.7%) with luminal-type breast cancer received perioperative therapy, and 40.3% of those received anthracycline/taxane. In the triple-negative group, 57.0% of all patients received perioperative therapy and of those, 93.4% received anthracycline/taxane. Being over 40 years old, having an early stage (clinical stage ≤ II), and receiving treatment in non-specialized facilities were associated with less use of anthracycline/taxane in the luminal-type group. For the triple-negative group, associated factors with less use of anthracycline/taxane included being over 60 years old, treatment in small hospital (capacity < 200 beds), and treatment in non-specialized facilities.ConclusionsApproximately half the patients in both the luminal-type and triple-negative groups were prescribed anthracycline and/or taxane for perioperative chemotherapy. The choice was associated with patient age, cancer stage, and the scale and specialization of the treatment facilities. This study sheds light on the current state of breast cancer treatment practices in Japan.

Early Stage Breast Cancer: Does Histologic Subtype (Ductal vs. Lobular) Impact 5 Year Overall Survival?

Histology is an important predictor of the behavior of breast cancer. We aim to study the impact of histology on the overall survival (OS) of breast cancer patients. We studied 11,085 breast cancer patients diagnosed with T1-T2 tumors, clinically node-negative and non-metastatic, from 2004 to 2019 included in the National Cancer Database. Kaplan-Meier curves, log-rank tests and Cox regression models were used to study the impact of histology and other variables on OS. In our patient population, 8678 (78.28%) had ductal cancer (IDC), while 2407 (21.71%) had lobular cancer (ILC). ILC patients were significantly more likely to be older, Caucasian, have a lower grade at diagnosis and be hormone receptor-positive compared to IDC patients. There was no statistically significant difference in the 5-year OS of early stage ductal (16.8%) and lobular cancer patients (16.7%) (p = 0.200). Patients of Hispanic and African American origin had worse OS rates compared to non-Hispanic and Caucasian patients, respectively. For node-positive disease, HER2+ tumors and triple-negative tumors, chemotherapy had a positive influence on OS (HR 0.85, 95% CI 0.77-0.93, p = 0.0012). Histology did not have a significant impact on the 5-year OS of early stage breast cancer patients.

Serum protein profiling reveals an inflammation signature as a predictor of early breast cancer survival

BackgroundBreast cancers exhibit considerable heterogeneity in their biology, immunology, and prognosis. Currently, no validated, serum protein-based tools are available to evaluate the prognosis of patients with early breast cancer.MethodsThe study population consisted of 521 early-stage breast cancer patients with a median follow-up of 8.9 years. Additionally, 61 patients with breast fibroadenoma or atypical ductal hyperplasia were included as controls. We used a proximity extension assay to measure the preoperative serum levels of 92 proteins associated with inflammatory and immune response processes. The invasive cancers were randomly split into discovery (n = 413) and validation (n = 108) cohorts for the statistical analyses.ResultsUsing LASSO regression, we identified a nine-protein signature (CCL8, CCL23, CCL28, CSCL10, S100A12, IL10, IL10RB, STAMPB2, and TNFβ) that predicted various survival endpoints more accurately than traditional prognostic factors. In the time-dependent analyses, the prognostic power of the model remained rather stable over time. We also developed and validated a 17-protein model with the potential to differentiate benign breast lesions from malignant lesions (Wilcoxon p < 2.2*10− 16; AUC 0.94).ConclusionsInflammation and immunity-related serum proteins have the potential to rise above the classical prognostic factors of early-stage breast cancer. They may also help to distinguish benign from malignant breast lesions.

Abstract LB009: Unveiling the significance of DARPP-32 and its partners, including GRB7 and DKK1, in breast cancer: Integrative insights from patient data and cell line transcriptomics

Abstract DARPP-32 plays a crucial role in regulating both protein-phosphatase-1 (PP-1) and protein kinase A (PKA), its function being reliant on its phosphorylation status. We have previously demonstrated that low DARPP-32 expression is associated with adverse survival of breast cancer patients, particularly those with oestrogen receptor (ER) positive disease; however, there is limited information on how DARPP-32 may alter breast cancer cell behaviour. We have recently published an integrative approach using patient data and cell line transcriptomics to understand the role of DARPP-32 in breast cancer. We analysed the transcriptome of T47D ER positive breast cancer cells following DARPP-32 knockdown, including treatments in combination with 17β-estradiol or PKA inhibitor fragment (6-22) amide. 202 differentially expressed transcripts were identified in DARPP-32 knock down cells and treatment of these cells with 17β-estradiol or PKA inhibitor fragment (6-22) amide led to the differential expression of 193 and 181 transcripts respectively. Differentially expressed transcripts were compared with genes identified as associated with DARPP-32 expression in 1980 breast cancer patients within the METABRIC cohort using an Artificial Neural Network approach (ANN). Several genes overlapped with those identified from cell line transcriptomics, including PTK7, TRAF5, and KLK6. Both DKK1 and GRB7 were identified as genes associated with DARPP-32 expression in patients using ANN, therefore protein expression was determined in a large cohort of early-stage breast cancer patients (n&amp;gt;1000). We demonstrated that DKK1 and GRB7 protein expression was significantly correlated with DARPP-32 Threonine-34 phosphorylation levels within the same samples (all P&amp;lt;0.05). We have now applied an ANN-based integrative data mining approach to identify genes with the largest effect on other genes resulting in an interactome map, which was based on genes identified within the cell line transcriptomics and original ANN. 1878 genes were identified for inclusion within an interactome map in the total patient cohort, whereas 1003 were identified in ER negative disease alone and 2144 in ER positive disease alone. Pathway enrichment analysis identified the ubiquitin proteosome pathway, the insulin pathway-protein kinase B signalling cascade and the RAS pathway. This study underscores the significance of DARPP-32, a central molecular switch, in breast cancer, elucidating its impact on patient prognosis and highlighting potential molecular targets for therapeutic intervention. The integrative approach combining patient data with cell line transcriptomics provides insights into the complex mechanisms underlying breast cancer progression and opens avenues for further research and targeted interventions. Citation Format: Behnaz Saidy, Richa Vasan, Megan-Rose Greener, Rosie Durrant, Adelynn Immanuel, Andrew Green, Emad Rakha, Ian Ellis, Graham Ball, Stewart Martin, Sarah J. Storr. Unveiling the significance of DARPP-32 and its partners, including GRB7 and DKK1, in breast cancer: Integrative insights from patient data and cell line transcriptomics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB009.

Small Non-Coding RNAs and Their Role in Locoregional Metastasis and Outcomes in Early-Stage Breast Cancer Patients.

Deregulation of small non-coding RNAs (sncRNAs) has been associated with the onset of metastasis. We evaluated the expression of sncRNAs in patients with early-stage breast cancer, performing RNA sequencing in 60 patients for whom tumor and sentinel lymph node (SLN) samples were available, and conducting differential expression, gene ontology, enrichment and survival analyses. Sequencing annotation classified most of the sncRNAs into small nucleolar RNA (snoRNAs, 70%) and small nuclear RNA (snRNA, 13%). Our results showed no significant differences in sncRNA expression between tumor or SLNs obtained from the same patient. Differential expression analysis showed down-regulation (n = 21) sncRNAs and up-regulation (n = 2) sncRNAs in patients with locoregional metastasis. The expression of SNHG5, SNORD90, SCARNA2 and SNORD78 differentiated luminal A from luminal B tumors, whereas SNORD124 up-regulation was associated with luminal B HER2+ tumors. Discriminating analysis and receiver-operating curve analysis revealed a signature of six snoRNAs (SNORD93, SNORA16A, SNORD113-6, SNORA7A, SNORA57 and SNORA18A) that distinguished patients with locoregional metastasis and predicted patient outcome. Gene ontology and Reactome pathway analysis showed an enrichment of biological processes associated with translation initiation, protein targeting to specific cell locations, and positive regulation of Wnt and NOTCH signaling pathways, commonly involved in the promotion of metastases. Our results point to the potential of several sncRNAs as surrogate markers of lymph node metastases and patient outcome in early-stage breast cancer patients. Further preclinical and clinical studies are required to understand the biological significance of the most significant sncRNAs and to validate our results in a larger cohort of patients.

Clinical and Analytical Validation of Two Methods for Ki-67 Scoring in Formalin Fixed and Paraffin Embedded Tissue Sections of Early Breast Cancer.

Proliferation determined by Ki-67 immunohistochemistry has been proposed as a useful prognostic and predictive marker in breast cancer. However, the clinical validity of Ki-67 is questionable. In this study, Ki-67 was retrospectively evaluated by three pathologists using two methods: a visual assessment of the entire slide and a quantitative assessment of the tumour margin in 411 early-stage breast cancer patients with a median follow-up of 26.8 years. We found excellent agreement between the three pathologists for both methods. The risk of recurrence for Ki-67 was time-dependent, as the high proliferation group (Ki-67 ≥ 30%) had a higher risk of recurrence initially, but after 4.5 years the risk was higher in the low proliferation group. In estrogen receptor (ER)-positive patients, the intermediate Ki-67 group initially followed the high Ki-67 group, but eventually followed the low Ki-67 group. ER-positive pN0-1 patients with intermediate Ki-67 treated with endocrine therapy alone had a similar outcome to patients treated with chemotherapy. A cut-off value of 20% appeared to be most appropriate for distinguishing between the high and low Ki-67 groups. To summarize, a simple visual whole slide Ki-67 assessment turned out to be a reliable method for clinical decision-making in early breast cancer patients. We confirmed Ki-67 as an important prognostic and predictive biomarker.

Comparison of clinical characteristics between ACOSOG Z0011-eligible cohort and sentinel lymph node-positive breast cancer patients in Hong Kong.

The American College of Surgeons Oncology Group (ACOSOG) Z0011 trial resulted in de-escalation of axillary surgery among early-stage breast cancer patients with low-volume sentinel lymph node (SLN) disease undergoing breast-conserving surgery and radiation therapy. Nevertheless, the mastectomy rate in the Chinese population remains high. This study compared the clinical characteristics of the ACOSOG Z0011-eligible cohort with SLN-positive breast cancer patients in Hong Kong. This retrospective analysis of a prospectively maintained database at a university-affiliated breast cancer centre in Hong Kong was performed from June 2014 to May 2019. The database included all patients with clinical tumour (T) stage T1 or T2 invasive breast carcinoma, no palpable adenopathy, one or two positive SLNs on histological examination, and no prior neoadjuvant systemic treatment. Comparisons were made between the mastectomy and breast-conserving treatment groups in our cohort, along with the sentinel-alone arm in the ACOSOG Z0011 trial. One hundred and seventy-one patients met the inclusion criteria: 112 underwent mastectomy and 59 underwent breast-conserving treatment. Our mastectomy group had higher prevalences of T2 tumours (P<0.001), lymphovascular invasion (P<0.001), and SLN macrometastases (P=0.004) compared with the ACOSOG Z0011 cohort. However, in our patient population, mean pathological size slightly differed between the mastectomy and breast-conserving treatment groups (2.2 cm vs 1.8 cm; P=0.005). Other histopathological features were similar. This study demonstrated that clinicopathological features were comparable between SLN-positive breast cancer patients undergoing mastectomy and those undergoing breast-conserving treatment. Low-risk SLN-positive mastectomy patients may safely avoid completion axillary lymph node dissection.

Abstract 1207: Immune subtyping identifies a subset of HR+HER2- early-stage breast cancer patients with a very high likelihood of response to neoadjuvant immunotherapy (IO): Results from 5 IO arms of the I-SPY2 TRIAL

Abstract Background: Neoadjuvant immunotherapy (IO) has become standard of care for early-stage triple negative breast cancer (TNBC). I-SPY2 was the first randomized trial to examine the efficacy of IO therapy in high-risk HR+HER2- breast cancer, where most IO arms showed improved efficacy relative to control. We also previously showed immune-gene expression signatures associate with pathologic complete response (pCR) in HR+HER2- treated with IO; and developed a clinically applicable Immune classifier (ImPrint) predicting response to IO that is now being used in I-SPY2.2 as part of the Response Predictive Subtypes. Here we report the performance of ImPrint in HR+HER2- patients from 5 IO arms. Methods: 204 HR+HER2- (MammaPrint high risk) patients from 5 IO arms (anti-PD1, anti-PDL1/PARPi, anti-PD1/TLR9 dual-IO, and anti-PD1 +/- LAG3 dual-IO) and 191 patients from the control arm were included in this analysis. Patients were classified ImPrint+ (likely sensitive) vs. ImPrint- (likely resistant), by Agendia, Inc, using pre-treatment mRNA. Performance of ImPrint for predicting pCR to IO was characterized and compared to that of MammaPrint (ultra) High2 risk (MP2) and tumor grade (III). Based on the DRFS of pCR vs. non-pCR HR+HER2-/ImPrint+ patients (median follow up ~4.5yr), we predicted the DRFS in the IO vs. control arms using an exponential model as a function of the pCR rates. Results: Overall, the pCR rate over the 5 IO arms was 33%. 28% of HR+HER2- patients were ImPrint+; and pCR rates with IO were 76% in ImPrint+ vs. 16% in ImPrint-, with the highest pCR rate &amp;gt;90% in a dual-IO arm. In the control arm, pCR rates were 33% in ImPrint+ and 8% in ImPrint-. Based on the pCR rates in the IO vs. control (76% vs. 33%), the predicted DRFS of HR+HER2-/ImPrint+ patients are 91% vs 80% at 5 years, respectively. This translates to a risk reduction of 52% for the IO arm relative to standard chemotherapy in HR+HER2-/ImPrint+ patients. We also compared MP2 and tumor grade (III) to ImPrint+ as pCR predictors, as these markers have been used or proposed as selection markers for neoadjuvant IO trials in HR+HER2-. The pCR rates for MP2, Grade III, at 56%, 45%, respectively, are much smaller than that for ImPrint+ at 75% pCR; thus ImPrint appears to be a more precise predictive biomarker for neoadjuvant IO therapy in the HR+HER2- breast cancers. Conclusion: These results suggest that a subset of high risk HR+HER2- breast cancers is highly sensitive to immunotherapy, and by using a specific and sensitive selection strategy patients could achieve pCR rates similar to what is seen with best neoadjuvant therapies in TNBC and HER2+ (i.e., pCR rate &amp;gt; 65-70%). ImPrint, an FDA IDE-enabled assay currently being further evaluated in I-SPY2, may represent the way to identify patients for IO that best balances likely benefit vs risk of serious immune-related adverse events. Citation Format: Denise M. Wolf, Christina Yau, Lajos Pusztai, Rita Nanda, Jo Chien, Erica Stringer-Reasor, Rebecca Shatsky, Claudine Isaacs, MInetta Liu, Hyo Han, Hatem Soliman, Michael Campbell, Annuska Glas, Andrei Barcaru, Lorenza Mittempergher, Midas Kuilman, Lamorna Brown Swigart, Gillian Hirst, Hongmei Yu, Philip Beineke, Amrita Basu, I-SPY2 Investigators, Douglas Yee, W. Fraser Symmans, Angela DeMichele, Jane Perlmutter, Amy Delson, Laura Huppert, Hope Rugo, Amy Clark, Nola Hylton, Paula Pohlmann, Laura Esserman, Laura van 't Veer. Immune subtyping identifies a subset of HR+HER2- early-stage breast cancer patients with a very high likelihood of response to neoadjuvant immunotherapy (IO): Results from 5 IO arms of the I-SPY2 TRIAL [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1207.

Abstract 5534: Needle biopsy induces pro-metastatic progression and systemic dissemination of estrogen receptor-positive breast cancer cells through the COX-2/PGE2 cascade

Abstract Breast cancer is the most commonly diagnosed malignancy in the U.S. and over two-thirds of invasive breast cancer cases are diagnosed early stage. However, 15-year survival rates for early-stage breast cancer remain in the range of 70-77%. Mounting evidence showed an increased risk of disease progression and mortality among early-stage breast cancer patients whose surgery was delayed over 60 days after the diagnostic biopsy. Yet, the mechanism(s) underlying the rapidly increased mortality due to delay of surgery after diagnosis remains unknown. Our cohort analyses of early-stage breast cancer patients reveal the emergence of a significantly rising mortality risk when the biopsy-to-surgery interval was extended beyond 53 days. Additionally, histology of post-biopsy tumors shows prolonged retention of a metastasis-permissive wound stroma dominated by M2-like macrophages capable of promoting cancer cell epithelial-to-mesenchymal transition and angiogenesis by secretion of transforming growth factor beta 1 (TGF-β1) and vascular endothelial growth factor (VEGF). We show that needle biopsy promotes systemic dissemination of cancer cells through a mechanism of sustained activation of the cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) cascade, which favors M2-polarization and its associated pro-metastatic changes, but are abrogated by oral treatment with COX-2 inhibitors in estrogen receptor-positive (ER+) syngeneic mouse tumor models. Therefore, we conclude that needle biopsy of ER+ breast cancer provokes progressive pro-metastatic changes, which may explain the mortality risk posed by surgery delay after diagnosis. Also, our data may provide a rationale for a pharmacologic strategy to inhibit the COX-2/PGE2 cascade in cases when delay of surgery is unavoidable. Citation Format: Hiroyasu Kameyama, Macall Leslie, Reese Simmons, Yunguang Sun, Misung Yi, Priya Dondapati, John F. Langenheim, Kar-Ming Fung, Inna Chervoneva, Hallgeir Rui, Takemi Tanaka. Needle biopsy induces pro-metastatic progression and systemic dissemination of estrogen receptor-positive breast cancer cells through the COX-2/PGE2 cascade [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5534.

Abstract 4846: Geographic and physician-level variation in the use of hypofractionated radiotherapy for breast cancer in the U.S.: A cross-classified multilevel analysis

Abstract Hypofractionated whole-breast irradiation (HF-WBI), a radiotherapy with a larger dose per fraction and a shorter schedule for early-stage breast cancer patients post breast-conserving surgery, shows equivalent safety and efficacy compared to conventionally fractionated whole-breast irradiation (CF-WBI) regarding local recurrence and disease-free survival. While several countries have set HF-WBI as the preferred standard of care for these patients, its uptake in the U.S. has lagged behind expectations. We used the Health Care Cost Institute (HCCI) database 2008-2017, covering a third of the U.S. employer-sponsored insurance population, to identify early-stage breast cancer patients. Patients were clustered at different geographic levels (Census region, state, core-based statistical area (CBSA), hospital referral region of Dartmouth Atlas, and zip code) and the radiation oncologist level. These two levels are cross-nested. We used a Bayesian cross-classified multilevel logistic model to simultaneously model the geographic units variability and physician-level variability in HF-WBI use across the U.S. Variation metrics included intracluster correlation coefficient (ICC) and median odds ratios (MOR). ICC with a value of 0 is equivalent to MOR of 1, indicating identical outcomes across all levels. After accounting for these variations in the cross-classified multilevel model framework, we evaluated the association between HF-WBI use and clinical and demographic factors.Our study included 79,747 women (74.0%) who underwent CF-WBI and 27,999 (26.0%) who received HF-WBI. HF-WBI adoption increased over time (2008-2017). Variability across radiation oncologists (ICC = 0.272, MOR = 2.88) was notably larger than geographic areas variability. Variability across CBSA (ICC = 0.097, MOR = 1.76) was the strongest among all the geographic levels. The variation in HF-WBI use was mainly attributed to physician-level variability (ICC=0.222, MOR=2.59) based on the cross-classified multilevel model. No substantial differences were found between young (aged 64 or younger with commercial health plans) and older patients (aged 65 or older with Medicare Advantage plans) in terms of both geographic and physician-level variations. After accounting for variability in radiation oncologists and CBSAs, older age, non-reception of chemotherapy, and several community-level factors, including longer distance from home to facility and higher community education level, were associated with a higher likelihood of HF-WBI use. These results may lend insights into potential facilitators/barriers to HF-WBI uptake. Future studies can further investigate the impact of the 2018 American Society for Radiation Oncology (ASTRO) guideline and the Covid-19 pandemic on HF-WBI use, which would illuminate potential improvements of healthcare practices. Citation Format: Yijia Sun, Loren Saulsberry, Chuanhong Liao, Donald Hedeker, Dezheng Huo. Geographic and physician-level variation in the use of hypofractionated radiotherapy for breast cancer in the U.S.: A cross-classified multilevel analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4846.

Carbon nanoparticles versus patent blue dye for detection of sentinel lymph node in patients with early breast cancer

Background Sentinel lymph nodes biopsy (SLNB) has replaced axillary lymph node dissection (ALND) in a considerable percentage of patients with early-stage breast cancer which was a great advance in preventing many surgical complications and enhancing their health welfare. Although there are different sentinel lymph nodes (SLNs) tracers with different identification rates, there is no agreement about the idealistic method. Aim The study was designed to compare carbon nanoparticles and patent blue v dye regarding SLNs detection rate, number of SLNs, time of detection, metastatic SLNs, cost, and safety in patients with early breast cancer and clinically node-negative axilla. Patients and methods A total of 40 patients with axillary lymph node-negative early-stage breast cancer patients were divided into two groups and subjected to carbon nanoparticles and patent blue V dye in group A and group B, respectively. Patients who were pregnant or lactating had node-positive axilla (N1-3) or metastatic breast cancer (M1) or had neoadjuvant chemotherapy were excluded. Results The mean age was 48.3±9.5 and 47 ±8.9, while the mean BMI of 33.3±4.8 and 32.834±4.862, the SLN detection rates were 95% and 90% in groups A and B, respectively. A total of 128 sentinel lymph nodes (SLNs) were removed from patients in the two groups (65 with Carbon Nanoparticles and 63 with patent blue dye). The mean number of SLNs was 3.4±0.7 (range, 2–5) and 3.5±1.2 (range, 2–7), mean time of SLNs detection was 13.5±4.5 (range, 7–22) and 12.7± 3.6 (range, 7–18 min) between group A and B, respectively. Conclusion There is no significant difference between carbon nanoparticles and patent blue dye regarding axillary SLNs in early breast cancer regarding identification rate, number of SLNs, time of detection, metastatic SLNs, cost, and safety with slight preference to carbon nanoparticles regarding postoperative skin staining and Egyptian market availability.

Abstract 2416: Personalized minimal residual disease detection using tumor-derived structural variants in cell-free DNA

Abstract We demonstrate development and technical validation of a novel approach for analysis of plasma circulating-tumor DNA (ctDNA) for residual disease detection and monitoring that offers improvements over existing technologies. ctDNA in blood can be leveraged to monitor treatment response, detect cancer recurrence, and inform treatment decisions for cancer patients. However, accurate detection and quantification of ctDNA is technically challenging due to low concentration of plasma DNA, especially in the adjuvant setting. Most current assays rely on interrogating multiple patient-specific point mutations to achieve exquisite limits of detection but struggle with polymerase errors, sequencing artifacts and limited conversion of input DNA. To overcome these challenges, we developed an approach called Structural Variant Enrichment and Normalization (SVEN) that targets patient-specific genomic rearrangements to achieve sensitive detection and quantification of plasma ctDNA. This method leverages intrinsic features of tumor-derived structural variants (SVs) to improve enrichment and confidence of detection at low tumor fraction through multiplexed PCR and amplicon-based next generation sequencing. To evaluate the assay, we performed whole genome sequencing of DNA from two breast cancer cell lines, as well as matched FFPE tumor and buffy coat samples from 21 early-stage breast cancer patients. We identified consensus SVs, and designed multiplexed SV-specific primers for each subject. We then conducted PCR amplification of cell-free DNA followed by sequencing, amplicon identification, and quantification. Analytical validation was conducted using 284 replicates of cell line dilutions from 1% to 0.003%, and 5 to 40 ng of input. We developed multiplexed assays targeting 25 and 32 SVs across two cell lines, and 3 - 43 SVs across breast cancer patients (median 23 per patient). 91% and 42% of PCR targets were successfully validated for cell lines and FFPE samples respectively. Cell line dilutions demonstrated a sensitivity of 89% at 0.003% tumor fraction with 10 ng input or more. Tumor fractions measured using SVEN agreed with known values (R2 = 0.989). Application of validated panels to patient plasma samples and tumor/germline dilutions is ongoing. SVEN is a novel approach for tumor-guided ctDNA detection and quantification with potential relevance for residual disease detection. On-going studies are investigating the performance of this approach for ctDNA detection in patients with early and locally advanced breast cancer treated with neoadjuvant therapy. Citation Format: Bradon R. McDonald, Kirsten L. Dennison, Amanda L. Schussman, Stephanie M. McGregor, Barbara A. Pockaj, Muhammed Murtaza. Personalized minimal residual disease detection using tumor-derived structural variants in cell-free DNA [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2416.

Abstract 6632: Adipocyte death drives dormant breast cancer cell reactivation

Abstract Despite significant responses to initial treatments, upwards of 30% of breast cancer patients will experience a recurrence of their disease. Unfortunately, there are few clinical features that predict which patients will recur, relegating patients and their doctors to a wait-and-see approach where they must remain vigilant. Recent studies have reported that the presence of disseminated tumor cells (DTCs) in the bone marrow of early-stage breast cancer patients predicts a higher chance of recurrence and that obese patients experience 35%-40% higher rates of recurrence than lean patients. Interestingly, in addition to increased adipocyte size, obese patients experience higher rates of adipocyte apoptosis, macrophage recruitment to adipocyte tissue, and increased inflammation, shown as the formation of crown-like structures (CLSs). Given the rising prevalence of obesity, the need for mechanistic studies to elucidate its contribution to breast cancer dormancy and recurrence is urgent. To investigate how microenvironmental changes associated with obesity affect breast cancer dormancy, we utilized a well-established syngeneic mouse model of ER+ breast cancer dormancy (D2.0R). We found that D2.0R cells remained dormant in the visceral fat of wildtype mice but were reactivated upon adipocyte death due to obesity or genetic manipulation, and this reactivation required the recruitment of macrophages. To understand why macrophages were recruited to the adipose tissue and how they led to dormant tumor cell reactivation, we profiled the microenvironmental changes in visceral fat using single-cell RNA-sequencing and found that the infiltrating macrophages exhibited unique pro-inflammatory and lipid regulatory phenotypes. Further investigation revealed that macrophages activated the integrin-focal adhesion kinase (FAK) pathway in dormant D2.0R cells and the inhibition of integrin and FAK inhibited this activation. Given tumor cells can metastasize to visceral fat depots in breast cancer patients, our findings provide an important model to determine what drives dormant tumor cell growth in adipose tissue. Our study provides novel insights into how tumor microenvironment (TME) impacts breast cancer dormancy and also highlights the importance of adipose tissue as a unique reservoir that potentiates cancer relapse. Citation Format: Xiaoyu Yuan, Qihao Ren, Sheila A. Stewart. Adipocyte death drives dormant breast cancer cell reactivation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6632.

Abstract 2135: Racial disparities in symptom burden among women receiving early stage breast cancer chemotherapy

Abstract Purpose: The purpose of this study was to compare prevalent symptoms (pain, fatigue, and physical function) and changes over time between Black and White women undergoing chemotherapy for early-stage breast cancer (ESBC) employing a longitudinal, repeated measures design over the course of ESBC. Methods: Data collected as per protocol of 1R01MD012245, comparing racial differences in chemotherapy tolerance and dose modifications during chemotherapy treatment at baseline, midpoint, and endpoint, tailored to each patient's individual chemotherapy schedule. Race was collected by patient self-report and chart review. Symptom burden (fatigue, pain, and physical functioning) was measured by the PROMIS-29 Profile v 2.0). Area deprivation was measured using the Area Deprivation Index (ADI). Linear mixed models were used to assess racial differences in symptom burden across timepoints, and changes in symptom burden over time, adjusting for ADI. Results: A total of 147 patients participated in this study (36% Black and 64% white). Pain: Black patients reported significantly higher pain scores than White patients at pretherapy (MD=3.7, p=.034), midpoint (MD=5.8, p: 0.002), and endpoint (MD=7.8, p&amp;lt;.001). Even after adjusting for area deprivation, this disparity persisted (F(1, 390)=29.43, p&amp;lt;.001), with Black patients having higher pain scores at midpoint (MD=4.7, p: 0.02) and endpoint (MD=7.8, p&amp;lt;.001). Pain scores worsened over time for Black patients, increasing significantly by the end of chemotherapy (MDT1-T3 =6.2, p=.010; MDT2-T3=5.8, p=.024). No significant changes in pain scores were observed over time among White patients. Fatigue: After adjusting for area deprivation, fatigue significantly increased at the endpoint (MDT1-T3=8.9, p&amp;lt;.001) for Black patients. Among White patients, fatigue increased at midpoint (MDT1-T2=5.7) and continued to worsen at the endpoint (MDT1-T3=10.1, p&amp;lt;.001; MDT2-T3=4.3, p=.017). Physical Function: Black patients had significantly lower physical function than White patients at the midpoint (MD=4.0, p=.027). By the end of chemotherapy, physical function deteriorated significantly for Black patients (MDT1-T3=7.8, p&amp;lt;.001), and White patients (MDT1-T3=7.7, p&amp;lt;.001; MDT2-T3=4.8, p=.002). Correlations between the ADI and symptom severity and physical function revealed that living in more deprived areas was associated with greater pain severity (r=-.227, p=.002, 56.3 vs. 50.1) and worse physical function (r=-.190, p=-.035, 40.6 vs. 42.4) at the completion of chemotherapy. Conclusions: The findings indicate that race and area deprivation are associated with symptom trajectories over the course of ESBC chemotherapy. Further research is warranted on how to best assess and relieve symptom burden among Black ESBC patients so that existing disparities in treatment and treatment outcomes are not perpetuated. Citation Format: Elham Nasrollahi, Hiba Abujaradeh, Susan Mazanec, Julia O'Brien, Isabelle M. Schlemmer, Margaret Rosenzweig. Racial disparities in symptom burden among women receiving early stage breast cancer chemotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2135.