Cancer Cases Research Articles

Abstract PO5-07-04: Machine learning models can help physicians reduce unnecessary ultrasound guided breast biopsies

Abstract Background Breast ultrasound is widely used as a diagnostic tool, the weakness of the method though is a high false positive rate, leading to unnecessary biopsies. In recent years, machine learning (ML) is gaining attention for its excellent performance in image-recognition tasks. The objective of this study was to train and validate ML models to predict malignancy of breast masses identified by ultrasound using clinical features of the patients, image information from the ultrasound reports and attributes extracted from the images. Methods We prospectively collected clinical and ultrasonographic attributes as well as the images from 927 lesions classified as BI-RADS 2, 3, 4a, 4b, 4c, 5 and 6 submitted to percutaneous biopsy in four institutions. Images in PNG format were loaded with OpenCV library and converted to gray scale. A total of nine attributes were extracted from the annotated area. We trained and validated five ML algorithms (histogram gradient boosting, logistic regression, a pipeline of these two classifiers, stacking ensemble of several classifiers and lightgbm), randomly sampling 80% of the dataset for training and 20% for validation using a cross fold strategy. We trained and tested the models with five different combinations of the data collected and compared the performances. The model with the lowest mean errors was selected and the threshold tuned to minimize the cases that the model classified as benign and were truly cancer (“false not cancer”). Image preprocessing, attribute extraction, and traditional machine learning was performed in Python. Results The clinical characteristics of the patients and ultrasonographic attributes of the lesions withdrawn from the exam reports are described in Table 1. The biopsy results distribution across the BI-RADS classification of the ultrasound report is shown in Table 2 and are in accordance with the literature. Among the five tested models, the logistic regression was the one with the lowest mean errors and was selected to tune the thresholds minimizing “false not cancer” cases. Our target was up to 2% of this error to stay within the BI-RADS 3 classification and thus dismiss biopsy. Table 3 describes five different combinations of data used to construct the models. All these combinations had < 0.5% of "false not cancer”, way below the 2% threshold from the BI-RADS 3 category. The mean error of the models classifying benign lesions as cancer and inducing unnecessary biopsies varied from 22.7% to 23.3% depending on the combination of data used. Conclusions Machine learning models can potentially help physicians avoid unnecessary ultrasound guided breast biopsies using unsophisticated clinical features and attributes from the images missing < 0.5% of cancer cases. Table 1. Clinical characteristics of the included patients and ultrasound features of the breast lesions. Table 2. Histology (malignant or benign) distribution across BI-RADSⓇ classification. *We had five lesions missing this data. Table 3. Mean performances of the five models and parameters used to build them. Citation Format: Isabela Buzatto, Danilo Carlotti, Nilton Onari, Ana Luiza Faim, Sarah Recife, Licerio Miguel, Ruth Bonini, Liliane Silvestre, Lucas Figueira, Daniel Guimarães Tiezzi. Machine learning models can help physicians reduce unnecessary ultrasound guided breast biopsies [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 PO5-07-04.

Abstract PO3-13-03: RNAScope: a practical approach and promising alternative to immunohistochemistry to quantify HER2 expression in breast cancer

Abstract T-DXd has been approved by the FDA to treat patients with metastatic HER2-low and -positive breast cancer. The utility of current HER2 immunohistochemistry (IHC) assays in evaluating HER2-low tumors is not clear. A simple and objective method to evaluate HER2 expression in breast cancer is urgently needed. RNAScope can detect HER2 RNA levels by in situ hybridization using one regular unstained FFPE slide and processed using the Leica BOND-III autostainer that is readily available in many clinical laboratories. RNA level detected by RNAScope can be quantified by dots/cell using publicly available software. Therefore, RNAScope is a practical assay and could be a promising alternative to IHC to quantify HER2 levels in breast cancer. We evaluated HER2 levels in 605 breast cancer tissue microarray cores using RNAScope and the two most commonly used FDA approved HER2 IHC assays: Ventana PATHWAY (PATHWAY) and Dako HercepTest (HercepTest). Clinical data were available for 505 cores from 347 patients. RNA level (dots/cell) by RNAScope was quantified using publicly available software QuPath. IHC assays were scored as 0, ultralow (UL, >0% but ≤10% incomplete membranous staining), 1+, 2+ and 3+. In addition, HER2 protein levels (AQUA protein level) were quantified from 100 cores through regression analysis, using AQUA score against cell line arrays with pre-calibrated HER2 protein levels determined by mass spectrometry. We used ANOVA to assess the differences in RNAScope results among the five IHC scores, and linear regressions to correlate RNAScope with HER2 AQUA protein levels. We finally evaluated 41 RNAScope whole-slide images (IHC 1+: n=5; 2+: n=26; 3+: n=10) of metastatic tumors from 31 patients treated with T-DXd. No significant differences of RNAScope results were observed among the 0, UL, and 1+ cores in both IHC assays, indicating the current IHC assays cannot differentiate HER levels in HER2-low tumors. However, statistically significant differences (p < 0.0001) were found among the IHC 1+, 2+, and 3+ cores and higher RNAScope dots/cell was associated with higher stage of the tumors. There was a strong correlation (R2 = 0.610) between the RNAScope results and quantitative HER2 AQUA protein level in the 100 cores. There were significantly higher HER2 RNA levels in the 41 metastatic biopsies with higher IHC scores (p < 0.05). When we used RNAScope to measures HER2 levels in metastases right before T-DXd treatment, there was numerically (p=0.881) higher HER2 RNA levels in responders (5.60±8.82 dots/cell) vs non-responders (5.20±5.31). Interestingly, the HER2 RNA levels in bone metastases was statistically higher (p=0.030) in non-responders (5.24±2.87, n=3) than in responders (1.55±0.81, n=5); although number of patients was low. For the non-bone metastases (esophagus, lymph node, liver, brain, lung), HER2 RNAScope values were numerically higher (p=0.261) in responders (9.65±2.87, n=5) than non-responders (5.19±5.74, n=15). In these non-bone metastatic cases, the response rates by IHC scores were 100% in 1+ cases, 24% in 2+ and 33% in 3+. When we used AI assisted categories based on RNAScope results, the response rates were 20% in RNAScope 1+ cases, 20% in 2+, 50% in 3+ cases. Our study shows that current IHC assays are unable to differentiate HER2 levels between IHC 0 and 1+ breast cancer cases, which is a critical issue in properly identifying patients who will benefit from T-DXd treatment. RNAScope results strongly correlate with HER2 protein levels and showed similar RNA levels among IHC 0 and 1+ cases. RNAScope is a simple and objective assay to quantify HER2 levels by dots/cell using publicly available software and may help better identify which patients benefit from T-DXd treatment. Other factors besides HER2 level may also contribute to the response rate in patients treated with T-DXd. RNAScope results in association with immunohistochemistry (IHC) scores by PATHWAY, HercepTest, and in biopsies from patients treated with T-DXd (T-DXd cohort). XX XX No significant (ns) difference of RNAScope dots/cell were seen among 0, UL and 1+ cases by both PATHWAY and HercepTest assays. There were significant differences of dots/cell comparing 1+, 2+ and 3+ cases. Note: ns not significant (p>0.05), * p<0.05, *** p<0.001, **** p<0.0001 Citation Format: Xiaoxian Li, Ji-Hoon Lee, Yuan Gao, Jilun Zhang, Katherine Bates, David Rimm, Huina Zhang, Geoffrey Smith, Diane Lawson, Jane Meisel, Jenny Chang, Lei Huo. RNAScope: a practical approach and promising alternative to immunohistochemistry to quantify HER2 expression in breast cancer [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 PO3-13-03.

Lipid Nanoparticles as a Platform for miRNA and siRNA Delivery in Hepatocellular Carcinoma.

Liver cancer is the sixth most common cancer and the fourth leading cause of death worldwide. Hepatocellular carcinoma (HCC) comprises 75-80% of liver cancer cases. Therapeutic strategies for HCC are available and have been shown to prolong survival but not treat HCC. Gene expression and regulation are responsible for the pathogenesis and progression of HCC. Altering these genetic networks can impact cellular behaviors and in turn cure HCC. Single-stranded and double-stranded non-coding ribonucleic acid known as microRNA and small interfering RNA, respectively have been investigated as possible therapeutic options. Currently, efficient delivery systems that ensure cell-specific targeting and efficient transfection into tumor cells are still under investigation. Viral vectors have been studied extensively, but immunogenicity hinders their use as delivery systems. Non-viral vectors which include inorganic, lipid, or polymeric nanoparticles are promising delivery systems. However, there are a lot of challenges during the formulation of such systems to ensure efficient and specific delivery. In vitro and in vivo studies have investigated different LNPs to deliver miRNA or siRNA. In this review, we highlight the role of LNPs as a delivery system for miRNA and siRNA in HCC in addition to the latest results achieved using this approach.

Abstract PO4-17-01: Patient Perception and Decision-Making in HER2+ Early Breast Cancer Management: Insights from the ASKHER2 European Survey

Abstract Background Breast cancer remains the most prevalent cancer in women globally, with Human Epidermal Growth Factor Receptor 2 positivity (HER2+) observed in 15-30% of initial breast cancer cases. Adjuvant treatment for HER2+ early breast cancer has notably reduced mortality and recurrence rates. However, the heterogeneity of the disease and in conveying risk information by healthcare providers (HCPs) leaves many women uncertain about their individual risk of recurrence and potential treatment (tx) options. Evidence shows that fear of recurrence, uncertainty about prognosis, and inadequate risk/benefit information can affect patients' decisions during their tx phase. Therefore, it is important to better understand the perceptions, attitudes, and behaviors regarding the risk of recurrence in women with HER2+ early breast cancer. Methods A protocol-driven, direct-to-patient online survey (30 questions total) was administered in France, Germany, Italy, Portugal, Spain, and Sweden via patient advocacy groups and panels. Women aged 18 years and above with either early-stage (eBC) (stages I-III) or metastatic (mBC) (stage IV) as the result of recurrence from an initial diagnosis of locally advanced HER2+ breast cancer were eligible to participate. The implementation of soft quotas ensured a representative sample size. This abstract presents the results of the survey. Results A total of 622 participants completed the survey between July 2022 and February 2023. Majority of participants (70%) were between 40 and 65 years of age. Almost 85% had eBC (N=527), 62% had been diagnosed with HER2+ eBC for ≥ 2 years, and 68% were undergoing breast cancer tx at the time of the survey. The main worries and concerns that were reported by participants when asked about their tx plan were risk of recurrence (27%), fear of dying (22%) and risk of tx failure (14%). Among eBC participants, 40% perceived their personal risk of recurrence to be moderate, 18% perceived it to be high, while 21% did not know their personal risk. Most eBC participants (72%) preferred short and simple explanations from the medical team about the risk of cancer recurrence, while 4% preferred not to receive this information. Overall, 30% of participants said they had fully discussed the risk of recurrence with their doctor, while 20% had no discussion. Almost all participants (97%) wanted to be involved in their tx decision, 49% completely and 48% partially. To reduce this risk of recurrence, participants with eBC were willing to change their diet habits (77%), exercise more frequently (74%), take additional tx (65%) or undergo surgery (60%). Most participants (69%) were willing to take additional tx even if it would reduce their risk of recurrence by less than 50%. Participants were most willing to tolerate fatigue (53%), followed by hot flashes (51%) and joint pain (44%), as the most acceptable side effects if they had to take additional treatments with the potential benefit of reducing risk of recurrence. Conclusion The multinational large direct-to-patient ASKHER2 survey reflects participants’ experience and highlights concerns of patients with HER2+ breast cancer, notably on their recurrence risk. To mitigate this risk, patients exhibited a willingness to modify lifestyle habits and consider additional tx. A fraction of participants considered they had thoroughly discussed these risks with their HCPs, while the vast majority desired active involvement in their treatment decisions. These results underscore the ongoing need for HCPs to discuss the risk of recurrence in a clear way, addressing the full potential of treatment options in eBC and mBC, to enable patients to participate in this patient-centered approach of the decision-making process. Citation Format: Matteo Lambertini, Christian Jackisch, Olivier Trédan, Maria Vidal, Mário Fontes-Sousa, Antonios Valachis, Rosanna D’Antona, Marcelo Ruz, Eugenia Krone, Miriam Brice, Erwan Berjonneau, Soraia Matos, Olivia Dialla, Laure Guéroult-Accolas. Patient Perception and Decision-Making in HER2+ Early Breast Cancer Management: Insights from the ASKHER2 European Survey [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 PO4-17-01.

Abstract PO5-14-06: Transcriptomics-based drug screening in 3D ex vivo patient-drived breast cancer model and patient biopsy for personalized therapy

Abstract Breast cancer is a leading cause of cancer-related mortality for women worldwide. Hormone receptor-positive (HR+) breast tumors, which represent 70% of all breast cancer cases, are treated with endocrine therapy. However, not all patients benefit from this treatment regimen because of patient-to-patient variation. Therefore, high throughput drug screening system is warranted to enable personalized medicine. Patient-derived organoids, which serve as a screening platform, lose their hormone receptors and response upon ex vivo culturing, and may not be adequate models for HR+ breast tumors. Moreover, unidentified biological components in the widely-used basement membrane matrix, Matrigel, result in high batch-to-batch variations and poor reproducibility in organoid cultures. Here, we propose a hydrogel-based 3D ex vivo model with defined structural and chemical properties to test hormone and drug sensitivity of HR+ breast tumors from patient-derived xenografts (PDXs) and patient tumor biopsies using microfluidics. Our data demonstrate the feasibility of this model to preserve cell proliferation and hormone receptor expression over 7 days. We also demonstrate that responses to hormones and FDA-approved drugs are faithfully maintained in this model. Finally, to establish a high throughput hormone and drug testing workflow with transcriptomic readout, we multiplexed barcoded- and drug-treated tumor samples in a single experiment with bulk RNA-sequencing. Our preliminary data demonstrate patient-specific responses to hormones and drugs that correspond to patient genetic mutation profiles, treatment history, disease stages and subtypes. This platform also enables testing of drugs in clinical trials that shows promising therapeutic outcomes for breast cancer, such as CDK4/6i, AKTi, PARPi, mTORi and their combination with endocrine therapy, thanks to the high throughput of the screening system and the low consumption of patient-derived or patient tissue. Given the capability of combining this physiologically-relevant 3D ex vivo model with RNA-seq for HR+ breast tumors, this platform holds potential for high throughput compound testing and transcriptomic profiling of patient biopsies for personalized medicine. Citation Format: Yueyun Zhang, Carlos Henrique Venturi Ronchi, Giovanna Ambrosini, Yuanlong Liu, Patrick Aouad, Daria Matvienko, Christoph Merten, Cathrin Brisken. Transcriptomics-based drug screening in 3D ex vivo patient-drived breast cancer model and patient biopsy for personalized therapy [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 PO5-14-06.

Simulation of Boron Dose and Irradiation Time in Lung Cancer Treatment with Boron Neutron Capture Therapy (BNCT) Using MCNP-6

<p>Boron Neutron Capture Therapy (BNCT) is a cancer radiation treatment. This approach employs a boron carrier agent in the form of a chemical that is injected into the body and then travels to the cancer cells. In a lung cancer case study, BNCT treatment simulation was carried out using Monte Carlo N Particle (MCNP) software version 6.2. The goal of this study was to determine the most effective boron concentration and irradiation duration in lung cancer therapy utilizing the BNCT method. The geometry based on a phantom model created by Oak Ridge National Laboratory (ORNL). The simulated cancer geometry, which is placed in the right lung's middle lobe. The skin, ribs, and right lung are among the organs at risk. The skin, ribs, and right lung are among the organs at risk. The neutron source for the simulation is the collimator output from the Kartini Nuclear Reactor's thermal column. In this simulation, the variations in boron concentrations were 40 g/g, 45 g/g, 50 g/g, 55 g/g, and 60 g/g of cancer tissue at 5 g/g intervals. The researchers discovered a link between boron injection concentration and irradiation time, with higher boron injection concentrations resulting in shorter irradiation times. The volume of boron injected determines the effective dose absorbed by healthy tissue surrounding cancer cells. The effective boron concentration for lung cancer therapy is 60 g/g, with deterministic cell killing in the rib marrow and right lung. When utilizing a boron concentration of 60 g/g, the irradiation time is 20.4 minutes. Boron concentrations of 60 g/g are projected to create an effective irradiation time for BNCT-based lung cancer therapy based on the ALARA principle due to their shorter duration when compared to other concentration variations.</p>

Abstract PO2-08-07: Evaluating chemotherapy receipt and candidacy for PARP inhibitors in germline BRCA1/2 carriers with early and locally advanced breast cancer

Abstract Introduction: While enhanced breast screening of germline BRCA1/2 carriers results in earlier stage at diagnosis, the impact of tumour biology and BRCA mutation on chemotherapy receipt in early stage disease remains understudied. Methods: We retrospectively reviewed treatment administered following a first diagnosis of BRCA1/2-associated breast cancer between 2003-2023 at our institution. Chemotherapy receipt (neoadjuvant or adjuvant) was evaluated according to tumor size, biologic subtype, and BRCA mutation. Current guidelines for PARP inhibitor use were applied to estimate the proportion of affected BRCA1/2 carriers that would be deemed eligible for targeted therapy in the future. Results: Overall, 251 affected BRCA1/2 carriers were included; 137 (54.6%) BRCA1 (median age 40 years, range 19-72) and 114 (45.4%) BRCA2 (median age 43, range, 24-80 years). Chemotherapy was administered in 70.1% of index breast cancer cases and was significantly associated with clinical tumor size (36.7% T1a-T1b, 90.9% T1c, 95.2% T2, 95.3% T3-T4, p< 0.001), nodal status (71.8% cN0 vs. 100% cN1-2, p=0.004), and biologic subtype (90.0% TNBC vs. 75.0% ER+HER2-, p=0.02). BRCA1-associated breast cancers were less likely to present with DCIS or T1 tumours (%Tis/T1; 46.7% BRCA1 vs. 70.8% BRCA2, p< 0.001) and more likely to present with triple negative disease (71.4% BRCA1 vs. 24.6% BRCA2, p< 0.001). BRCA1 carriers were more likely to require chemotherapy for index breast cancer (81.8% BRCA1 vs. 56.1% BRCA2, p< 0.001). In subgroup analysis of early stage, T1N0 disease, chemotherapy was administered in 79.0% BRCA1 and 52.2% BRCA2 patients (p=0.03). If recent guidelines incorporating biologic subtype, nodal involvement, and response to neoadjuvant chemotherapy were retrospectively applied to the cohort, 33.6% would be deemed eligible for PARP inhibitors in the adjuvant setting, including 40.9% BRCA1 and 17.5% BRCA2 affected carriers (p < 0.001). Conclusion: Chemotherapy receipt is high in BRCA-associated breast cancers including in early stage, node-negative disease. Overall, one third of affected carriers are expected to be eligible for PARP inhibitors in the adjuvant setting. Future studies exploring how this information may impact decisions around risk-reducing mastectomy are warranted. Citation Format: Stephanie Wong, Carla Apostolova, Amina Ferroum, Basmah Alhassan, Ipshita Prakash, Mark Basik, Karyne Martel, Sarkis Meterissian, David Fleiszer, Nora Wong, Talia Malagon, William Foulkes, Jean-Francois Boileau. Evaluating chemotherapy receipt and candidacy for PARP inhibitors in germline BRCA1/2 carriers with early and locally advanced breast cancer [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 PO2-08-07.

Abstract PO2-28-09: Long-term Breast Cancer Risk Prediction in Black Women: External Validation of a Mammography-driven AI Model

Abstract Despite the demonstrated potential of artificial intelligence (AI) in breast cancer risk assessment for personalizing screening recommendations, further validation is required regarding AI model bias and generalizability. We performed external validation in Black women of a mammography-driven AI breast cancer risk model (Mirai) originally developed on screening cohorts primarily consisting of White women. In this institutional review board-approved, Health Insurance Portability and Protection Act (HIPAA)-compliant study under a waiver of consent, we retrospectively analyzed a case–cohort sample nested within the core academic breast cancer screening practice of BJC Healthcare, the hospital partner of Washington University in St. Louis. For the purposes of this validation study, relying on 2D digital mammography (DM) images, we focused on Black women presenting for annual DM screening (Selenia or Selenia Dimensions; Hologic) between 2008 and 2018. Eligible breast cancer cases were derived from all women with a breast cancer diagnosis (with associated biopsy-confirmed tumor pathology via institutional cancer registry) after negative (BI-RADS 1 or 2) DM screening 1 to 5 years prior to cancer diagnosis. We also identified a random sample of controls, defined as women who had negative (BI-RADS 1 or 2) DM screening, with 1 to 5 years of screening follow-up without a cancer diagnosis. Risk scores for all DM exams were calculated via the Mirai model. Performance was evaluated using concordance-index (C) analyses and associated 95% confidence intervals (CIs) for the entire cohort, as well as for study subgroups of invasive versus in-situ cancer and cancer molecular subtypes. We analyzed 1368 DM screening exams, including 672 DM exams from 391 women diagnosed with breast cancer (mean age, 58 years; standard deviation, 10 years) and 696 DM exams from 406 controls (mean age, 55 years; standard deviation, 10 years). The overall C-index was 0.62 [95% CIs 0.60–0.64] for all Black women, which was lower compared to previously reported validation results for Mirai in studies of similar design on predominantly White and racially diverse screening cohorts (C-index = 0.67-0.78). There was no evidence of a significant difference between invasive and in-situ cancer (C-index = 0.64 [95% CIs 0.61–0.66] vs. 0.64 [95% CIs 0.61–0.67]). Compared to other cancer molecular subtypes, performance was significantly higher among triple-negative (C-index = 0.67 [95% CIs 0.62–0.71]) and estrogen receptor (ER) negative cancer (C-index = 0.66 [95% CIs 0.61–0.70]). A previously developed mammography-driven AI model showed overall good performance in long-term breast cancer risk assessment in a dataset of Black women only, particularly for triple-negative and ER- cancer types. However, performance was lower compared to previously reported validation results from similar studies on predominantly White and racially diverse screening cohorts. Our results suggest that further refinements are needed towards more accurate breast cancer risk assessment in Black women. Long-term breast cancer risk prediction performance (C-indices) of Mirai in the full cohort of Black women and in study subgroups. Citation Format: Juanita Hernandez Lopez, Zhixin Sun, Shirin Shoushtari, Ulugbek Kamilov, Debbie Bennett, Aimilia Gastounioti. Long-term Breast Cancer Risk Prediction in Black Women: External Validation of a Mammography-driven AI Model [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 PO2-28-09.

Abstract PO5-13-09: Clinical usage of a CLIA accredited protein/phosphoprotein assay for breast cancer: Primary usage cases and significant findings in the HER2- setting

Abstract Background: A CLIA-accredited assay that measures the expression and/or activation levels of 32 clinically actionable protein and phosphoprotein analytes in clinical tissue biopsy samples was launched in January 2021. The current intended use population for the assay is for patients with late/advanced stage breast cancer wherein molecular profiling is being utilized for clinical decision making. Assessment of physician ordering practices, clinical use dynamics as well as protein/phosphoprotein actionability frequencies were determined for clinically actionable biomarkers. Methods: A total of 219 cases have been processed to date, with mean turn-around time of 16.4 days. The assay utilizes laser capture microdissection to enrich tumor epithelium from FFPE core needle biopsy and resection material coupled to reverse phase protein array. Results for each of the 32 analytes are generated by comparing each patient to a reference population and reported both as a relative quartile and as a continuous percentile compared to the reference population (0-100%). For the purposes of this analysis, significant expression/activation cutpoints were set at the 40th percentile threshold. Results: To date, clinicians have requested the test most frequently to identify potential therapeutic targets in patients with HER2-negative disease (84% of all tested patients, 36% were triple-negative). Despite the majority of cases being HER2-negative, we found that phosphorylated (p) HER2 (Y1248) was found to be activated in 17% of all HER2-negative cases and 19% of triple negative breast cancer cases (TNBC). pHER2 was concurrently activated with pHER3 (Y1289) in 15% (12/80) of TNBC cases and 13% (24/187) of all HER2-negative cases. pHER2 presented concurrently with pEGFR (Y1068 or T654) in 14% (11/80) of TNBC cases and 14% (26/187) of all HER2- cases. Expression of TROP2 was observed in 16% of HER2-negative patients including 11% of ER+/HER2- and 23% of TNBC cancers. MHCII expression, a recently described candidate predictive biomarker of anti-PDL1/PD1 response in TNBC, was found to be expressed in 29% of TNBC patients. Activation frequencies of other clinically relevant drug targets in HER2-negative disease such AKT and mTOR pathway activation was also assessed. We found that pAKT (S473 and/or T308) was activated in 7% of ER+/HER2- cases and 14% of TNBC. Concurrent with AKT activation, at least one additional member of the AKT-mTOR pathway (mTORC1 (S2448), 4E-BP1 (S65), p70S6K (T389), or S6RP (S235/S236) was co-activated in 50% and 45% of ER+/HER2- and TNBC cancers respectively. Conclusion: This initial assessment of a CLIA LDT protein/phosphoprotein assay utilized to date found that physicians most often order the test for advanced stage HER2-negative breast cancer. Activation/expression of clinically important protein drug targets with potential actionability in HER2-negative disease was observed in a significant number of cases and demonstrates the power of the assay to elucidate actionable targets for potential therapeutic intervention. Citation Format: Claudius Mueller, Brian Corgiat, Emanuel Petricoin, Kayla Sparks, Joyce O'Shaughnessy, Chelsea Gawryletz, Matthew Schwartz, Justin Davis. Clinical usage of a CLIA accredited protein/phosphoprotein assay for breast cancer: Primary usage cases and significant findings in the HER2- setting [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 PO5-13-09.

Abstract PO5-09-09: Incidence of Breast Cancer in Hispanic Women Across the US: A Focus on Texas

Abstract Introduction Breast cancer (BC) is one of the most common cancers affecting the female population in the United States, particularly among the Hispanic community. According to the CDC, the incidence rate of new breast cancer cases in Hispanic women is 95.6 per 100,000 annually, and the mortality rate is 13.7 per 100,000 women annually. Texas is home to one of the largest Hispanic communities in the US. By analyzing the prevalence, mortality, and access to healthcare services in Texas, we can shed light on the unique aspects of breast cancer within the Hispanic population. Overall, this study will provide valuable insights and identify potential avenues for reducing disparities and improving healthcare outcomes for Hispanic women affected by breast cancer. Materials and methods This study used comparative data from State Cancer Profiles on the CDC and NIH databases. The database was used to generate an overall comparison of breast cancer in Hispanic women across different US states. Comparison factors analyzed include incidence, mortality, insurance, and screening efforts. Significant differences were noted especially in Texas. Graphs and quantitative data for comparison factors were generated. This data is from 2015-2019 unless noted. Results The incidence of breast cancer in Hispanic women in Texas (TX) is 93.5 (Age-Adjusted Incidence Rate-cases per 100,000) with a CI of (92.2-94.8). The incidence of BC in Hispanic women in the US averages 99.0 with a CI of 98.7-99.9. From the incidence data, Hispanic women in Texas have a lower overall incidence of BC compared to the rest of the Hispanic females in the US. When analyzing the mortality rate, Hispanic women in TX have an Age-Adjusted Death Rate (deaths per 100,000) of 15.2 (CI of 14.7-15.8). In the US, Hispanic women have an Age-Adjusted Death Rate (deaths per 100,000) of 13.0 (CI of 13.4-13.9). To analyze preventative measures, a graph reporting mammogram use in 2020 by state was gathered. In TX 2020, the estimated age-adjusted prevalence of mammograms among Hispanic females from 50-74 years old was 75.0% (CI of 67.0%-81.7%). Nationally, the age-adjusted prevalence among Hispanic females 50-74 years who reported mammogram screening in 2 years was 79.7% (CI of 76.6 – 82.4). As for Texas insurance rates in 2020, Hispanic women under 65 years old, 27.4 % reported being uninsured. In comparison, other ethnicities such as African American (non-Hispanic) women, 16.5% reported to be uninsured, and white (non-Hispanic) women in Texas 11.8 % reported to be uninsured. Additionally, to further analyze if the lack of preventative measures was causing women to have a higher mortality rate, the instance of late-stage diagnosis of BC in Texan Hispanic women was analyzed. The age-adjusted incidence rate of late-stage breast cancer in Hispanic women was reported to be 33.4 (CI of 32.6-34.2) and the national incidence of late-stage BC in Hispanic women is 35.0 (CI of 35.1-35.8). Conclusion Even with Texas having one of the largest Hispanic communities, Hispanic women with breast cancer in Texas are faced with obstacles that lead to an increase in their mortality rate. As seen in the results, Hispanic women have less incidence of BC (including late stage) than their equivalent across the US but Hispanic women in TX have higher mortality rates in comparison. This is additionally accompanied by a decrease in insured women and a decrease in the utilization of cancer screenings. Lack of access to affordable healthcare and lack of regulatory cancer screenings cause Hispanic women to meet their premature death. Further analysis of the effects of affordable health care or further molecular investigation of this population is encouraged to research to fully conclude the reason behind this population's disparities. Citation Format: Catalina Esguerra, Kemely Santos Barbosa, Roy Khalife, Anthony Magliocco. Incidence of Breast Cancer in Hispanic Women Across the US: A Focus on Texas [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 PO5-09-09.

Abstract PO4-17-09: Epidemiological Analysis and Overall Survival of Male Breast Cancer in a Developing Middle Eastern Country Over 18 Years

Abstract Background: despite the profound rarity of breast cancer in males, it remains of importance given the associated morbidity and mortality, including the association with worse prognosis than female patients. Nonetheless, male breast cancer epidemiology remains poorly studied in middle eastern populations. Methodology: This retrospective cohort study examined male patients aged 15 to 85 years who were diagnosed with breast cancer between 2000 and 2018, using data from the Jordan Cancer Registry. Kaplan-Meier analysis was performed to assess the 5-year overall survival of the patients over time. Results: A total of 22,600 patients were diagnosed with breast cancer since 2000 in Jordan, of which 362 (1.6%) patients were males. 39.8% of male breast cancer cases occurred in the right breast, while the left breast was affected in 43.4% of the cases, and 3.3% of the cases were bilateral. Meanwhile, laterality was not mentioned in 13.5% of registry records. All male breast cancer cases were malignant in origin with the breast being the primary cancer. Most male patients had grade II (N=112, 30.9%) followed by grade III breast cancer (N=88, 24.3%). Among the male breast cancer cohort, 224 (62.2%) were treated with surgical intervention, 103 (28.8%) patients were given chemotherapy, 84 (23.4%) patients had radiotherapy and 24 (6.70%) patients had hormonal therapy. 27 patients died during the follow up period. The 5-year overall survival rate for the patients was 92.5% (95% CI, 89.9% to 95.3%). Conclusion: Breast cancer in middle eastern males tends to more commonly present in the left breast, and at a more advanced stage in comparison to females. Citation Format: Zaid Abdulelah, Ahmed Abdulelah, Abdulrahman Alhajahjeh, Ahmad Ghazzawi, Layla El-Amayreh, Hikmat Abdel-Razeq. Epidemiological Analysis and Overall Survival of Male Breast Cancer in a Developing Middle Eastern Country Over 18 Years [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 PO4-17-09.

Abstract PO5-08-12: Ethnic Admixture Affects Breast Cancer Incidence in Native Hawaiians: The Multiethnic Cohort

Abstract Background Native Hawaiians (NH) have the highest breast cancer incidence and the poorest survival of any ethnic group in Hawaii [1]. Since it has been shown that different ethnic groups have disparate risk of breast cancer in Hawaii and NHs are commonly of mixed ancestry, it is possible that the specific ethnic admixture may present an altered risk profile. For example, NH with Asian admixture was associated with higher risk for type 2 diabetes independent of known risk factors [2] compared to those without. The objective of this study was to calculate crude and age-adjusted breast cancer incidences by ethnic admixture group among participants of the Multiethnic Cohort (MEC). Methods: Based on self-reports, 106,525 eligible women were categorized by broad ethnic categories: Native Hawaiian, White, Black, Latino, and Japanese. In total there were 9257 breast cancer cases in the MEC cohort (1996-2019) at time of analysis. The Native Hawaiian population was further categorized into the following subgroups: Native Hawaiian only, Native Hawaiian & White, Native Hawaiian & Chinese, Native Hawaiian & White & Chinese. Crude and age-adjusted incidence rates (per 1000 person-years) were calculated for the various groups. The direct method of age adjustment using the US 2000 Standard population was used. Results: The ethnicity with the highest crude incidence were White=88.46, followed by Black=85.20, Latino=84.27, Japanese=84.90, and Native Hawaiian=81.28. However, after age-adjustment the highest were Japanese=159.1, White=153.8, Latino=148.3, Black=147.4, and Native Hawaiian=139.1. Crude incidence rates for Native Hawaiian ethnic admixture was found to be highest for Native Hawaiian & White=83.5, Native Hawaiian only=82.5, Native Hawaiian & Chinese=80.8, and Native Hawaiian & White & Chinese=80.4. After age adjustment, the highest was Native Hawaiian & Chinese=173.9, followed by Native Hawaiian & White=154.3, Native Hawaiian only=148.7, and finally Native Hawaiian & White & Chinese=120.8. Conclusion: These findings indicate that ethnic admixture in Native Hawaiians may be at elevated age-adjusted breast cancer incidence when compared to Native Hawaiian alone. When a woman was Native Hawaiian and Chinese the incidence was notably higher than any other group at 173.9 when compared to all Native Hawaiian=139.1. Furthermore, the group that had the lowest age-adjusted incidence was the mixed group of Native Hawaiian & White & Chinese=120.8 which seems to account for why the overall Native Hawaiian group=139.1 had one of the lowest incidence rates of the 5 major ethnic groups. 1. Loo, L.W., M. Williams, and B.Y. Hernandez, The high and heterogeneous burden of breast cancer in Hawaii: A unique multiethnic US Population. Cancer epidemiology, 2019. 58: p. 71-76. 2. Maskarinec, G., et al., Ethnic admixture affects diabetes risk in native Hawaiians: the Multiethnic Cohort. Eur J Clin Nutr, 2016. 70(9): p. 1022-7. Citation Format: Dustin Valdez, Arianna Bunnell, David Bogumil, Gertraud Maskarinec, John Shepherd. Ethnic Admixture Affects Breast Cancer Incidence in Native Hawaiians: The Multiethnic Cohort [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 PO5-08-12.

Propensity score matching as an effective strategy for biomarker cohort design and omics data analysis.

Analysis of omics data that contain multidimensional biological and clinical information can be complex and make it difficult to deduce significance of specific biomarker factors. We explored the utility of propensity score matching (PSM), a statistical technique for minimizing confounding factors and simplifying the examination of specific factors. We tested two datasets generated from cohorts of colorectal cancer (CRC) patients, one comprised of immunohistochemical analysis of 12 protein markers in 544 CRC tissues and another consisting of RNA-seq profiles of 163 CRC cases. We examined the efficiency of PSM by comparing pre- and post-PSM analytical results. Unlike conventional analysis which typically compares randomized cohorts of cancer and normal tissues, PSM enabled direct comparison between patient characteristics uncovering new prognostic biomarkers. By creating optimally matched groups to minimize confounding effects, our study demonstrates that PSM enables robust extraction of significant biomarkers while requiring fewer cancer cases and smaller overall patient cohorts. PSM may emerge as an efficient and cost-effective strategy for multiomic data analysis and clinical trial design for biomarker discovery.

Sociodemographic, clinical characteristics, and treatment patterns of endometrial cancer cases in Puerto Rico during the period 2009 to 2015: A retrospective study.

Over the past decades, the rising incidence rates of endometrial cancer have made it a significant public health concern for women worldwide. Treatment strategies for endometrial cancer vary based on several factors such as stage, histology, the patient's overall health, and preferences. However, limited amount of research on treatment patterns and potential correlations with sociodemographic characteristics among Hispanics is available. This study analyzes the treatment patterns for patients diagnosed with endometrial cancer in Puerto Rico. A secondary database analysis was performed on endometrial cancer cases reported to the Puerto Rico Central Cancer Registry-Health Insurance Linkage Database from 2009 to 2015 (n = 2,488). The study population's sociodemographic and clinical characteristics were described, along with an overview of the therapy options provided to patients receiving care on the island. Logistic regression models were used to evaluate the association of sociodemographic/clinical characteristics with treatment patterns stratified by risk of recurrence. In our cohort, most patients were insured through Medicaid and had a median age of 60 years. Almost 90% of patients received surgery as the first course of treatment. Surgery alone was the most common treatment for low-risk patients (80.2%). High-risk patients were more likely to receive surgery with radiotherapy and chemotherapy (24.4%). Patients with Medicare insurance were five times (HR: 4.84; 95% CI: 2.45-9.58; p < 0.001) more likely to receive surgery when compared with patients insured with Medicaid. In contrast, those with private insurance were twice as likely to receive surgery (HR: 2.38; 95% CI: 1.40-4.04; p = 0.001) when compared to those with Medicaid. These findings provide insight into the treatment patterns for endometrial cancer in Puerto Rico and highlight the importance of considering factors such as disease risk when making treatment decisions. Addressing these gaps in treatment patterns can contribute to effective management of endometrial cancer.

Abstract PO5-24-06: Genomic findings in metastatic breast cancer

Abstract Introduction: Although metastatic breast cancer is the second leading cause of cancer death in women, the genomic findings in metastatic breast cancer are not as well characterized as those of primary breast cancers. Metastatic tumors are genetically heterogenous, enriched for resistance mutations, and often lack targetable alterations. Improved understanding of the molecular mechanisms that drive metastatic disease of all receptor subtypes is required to identify possible molecular targets and to develop new targeted therapies in an effort to reduce the mortality. Methods: A cohort of 50 metastatic breast cancer cases (n=33 ER+/PR+, n=3 ER+/HER2+, n=3 ER-/HER2+ n=11 TNBC) sequenced at our medical center between 2018-2023 was evaluated, and the molecular findings of the major subtypes were analyzed. Genomic data included mutations, copy number alterations, tumor mutation burden and microsatellite instability. Results: The most frequent somatic alteration were PIK3CA mutations, involving 17/33 of ER+/PR+/HER- tumors, 5/11 TNBC tumors and 5/6 HER+ cases. TP53 mutations (frameshift and missense) were more frequently identified in TNBC and HER2+ cases (p&amp;lt; 0.05). Recurrent CCND1, FGFR1 and MYC copy number amplifications were seen almost exclusively in hormone receptor positive/HER2- tumors (p &amp;gt;0.05). ESR1 mutations involved 15% of the ER positive cancers and were frequently associated with co-occurring CCND1 and FGFR1 copy number gains. Significant genomic losses that drive tumorigenesis were also detected. Both CDKN2a and PTEN deletions were found in ER/PR positive disease, as well as triple negative tumors. Genomic deletions associated with worse outcomes such as TP53 and DICER1 were also detected. ERBB2 amplification was 100% concordant with our immunohistochemical and FISH results for the 6 HER2 positive cases. All 50 cases demonstrated a low tumor mutation burden and were microsatellite stable. Conclusion: We detected driver alterations that involve multiple pathways including estrogen receptor signaling, PI3K/AKT/MTOR, the cell cycle, and receptor tyrosine kinases. The genomic alterations are enriched for resistance mechanisms, like ESR1 mutations and FGFR1 gains that mediate resistance to endocrine treatment, as well as PIK3CA, also implicated in both endocrine and HER2-targeting therapy resistance. Of particular interest, were the amplifications detected in the ER+/PR+ tumors, such as CCND1 on chromosome 11q, FGFR1 on 8p and MYC on 8q, which were detected in almost half (45%) of our hormone receptor positive cohort. Some of the identified driver amplifications also define a subset of the Integrated Molecular Subtypes (Curtis et al., Nature; 486(7403): 346–352), i.e., Clusters 2, 6 and 9 that are typically hormone receptor positive but associated with either a very poor prognosis (Cluster 2) or an intermediate prognosis (Clusters 6 and 9), unlike the copy neutral ER positive tumors or those with the classic 1p and 16q alterations. Therefore, copy number profiling of advanced-stage breast cancers may be a useful tool for determining prognosis, identifying possible targetable driver pathways and selecting appropriate patients for molecularly guided clinical trials. Citation Format: Kimberly Cole, Melissa Tjota, Jeremy Segal, Peng Wang, Susanne Crespo-Ramos. Genomic findings in metastatic breast cancer [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 PO5-24-06.

Abstract PO4-15-03: Quantitative Measurement of TROP2 via Chromogenic Immunohistochemistry in Breast Cancer

Abstract Sacituzumab govitecan (SG) is an antibody-drug conjugate that targets human trophoblast cell-surface antigen 2 (TROP2), which is expressed in over 90% of breast cancer cases (Zaman et al, 2019). By delivering the cytotoxic SN-38 (topoisomerase I inhibitor) to TROP2 expressing breast cancer cells, SG showed promising antitumor activities in clinical trials and is now an approved treatment for triple-negative breast cancer (TNBC) and hormone receptor (HR)-positive HER2-negative breast cancer in the metastatic setting. Despite the prevalent expression of TROP2 in breast cancer, the objective response rates reported from clinical trials were about 30%, indicating the need for a diagnostic test that can identify which patients are likely to benefit from therapy. Although the drug is approved without a companion diagnostic assay, recent data from the TROPiCS-02 trial has shown that TROP2-low (H-score &amp;lt; 100) showed a non-significant hazard ratio for benefit from SG. In the same study, patients treated with SG with H-score &amp;gt;100 showed a significant hazard ratio for benefit compared to physician’s choice (Tolaney et al, ASCO 2023). This suggests that TROP2 expression level is associated with SG response and that a threshold for TROP2 expression level may aid patient selection. Although over 90% of breast cancer patients were considered TROP2-positive by IHC, the expression level of TROP2 was never quantitatively assessed in large breast cancer cohorts. Here we describe a quantitative chromogenic immunohistochemistry (IHC) assay with a cell line standard. Mass spectrometry was used to measure TROP2 peptide concentrations in the six standard cell lines, and the correlation between the mass spectrometry and IHC data for each cell line was then used to convert chromogenic signals to concentrations of TROP2 protein (fmol/mm2). The antibody used in this assay was rigorously validated, and the antibody concentration was optimized for the best signal-to-noise ratio. The optical density (OD) of chromogenic staining was measured using QuPath 0.4.3 (Qymia extension) by identifying the tumor area via object classifiers and manual editing and then calculating the area-normalized sum of OD. Collectively, this assay can measure up to 29.1 fmol/mm2 of TROP2. By applying this assay to two serial retrospective primary breast cancer cohorts from Yale University, we quantitatively measured TROP2 expression levels in 332 clinical cases. Not surprisingly, over 90% of cases showed some chromogenic signal, with a median TROP2 concentration of 2.1 fmol/mm2 and a maximum of 10.5 fmol/mm2. TROP2 expression levels showed no significant association with clinicopathologic characteristics including race, stage, BRCA mutation status, molecular subtype, HER2 IHC levels, and outcome. Further work is underway to optimize the assay toward the goal of determination of whether there is a quantitatively definable threshold for TROP2 expression below which patients are unlikely to benefit from SG or other TROP2-targeted therapies. Citation Format: Mengni He, Matthew Liu, Thazin Aung, Sneha Burela, Katherine Bates, Charles Robbins, David Rimm. Quantitative Measurement of TROP2 via Chromogenic Immunohistochemistry in Breast Cancer [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 PO4-15-03.

Abstract PO4-25-06: SerMa (Seroma of the Mammary gland) pilot - Is there a possible link between macrophage-based immune response and age?

Abstract Background The primary objective of the SerMa pilot study was to identify possible immunological or inflammatory factors related to seroma formation after mastectomy in cases with primary breast cancer. Preliminary data suggest a distinct association between age and seroma formation. The work presented here investigates therefore a possible link between age and differences in the microenvironment represented by tumor-associated macrophages. The latter have been characterized by the expression of CD68 and CD163 receptors, that are markers of cells from the monocyte/macrophage lineage with known clinical implications. Methods Tumor tissue of 80 primary breast cancer cases of the SerMa pilot study was available for further analyses. Immunohistochemistry based on antibody staining against CD68 and CD163 was used and due to the mean age of 63 years two groups were formed and compared: patients aged under 63 and patients aged 63 and older. The number of macrophages (standardized manually quantified) was compared in these two groups regarding seroma formation. Results Seroma formation occurred significantly more frequently with older age of the patient (p &amp;lt; 0.001). For the overall cohort, the number of CD68-positive macrophages was significantly increased (p=0.036) in patients with seroma formation, as well as for CD163 (p=0.027). The macrophage polarization was shown to be independent of tumor biological characteristics (p &amp;gt; 0.130). However, closer examination revealed an age-dependent effect of the macrophage polarization. In the group 63 years and older, there was no significant difference in the number of CD68- or CD163-positive macrophages (p = 0.610 and p = 0.425, respectively) in relation to seroma formation. A significant effect was seen in this analysis only in patients younger than 63 regarding CD163 (p &amp;lt; 0.001) and a non-significant trend for CD68 (p = 0.065). Conclusions These data demonstrate an age-dependent significant correlation of CD163 positive macrophages measured in the tumor environment with seroma formation in the breast after mastectomy. For CD68 positive macrophages a trend was seen, but didn’t reach statistical significance due to the small number of cases. These data show a different immunological response in tumor tissue depending on age and therefore support the thesis that seroma formation is primarily related to immunological/inflammatory processes. In the future, detection of CD163-positive macrophages in the tumor microenvironment could therefore be considered a marker for patients under 63 years at increased risk of seroma. The planned international SerMa study (EUBREAST 5) will have to show whether these results can be transferred to a prospective design with higher case number. Citation Format: Melitta Koepke, Felicitas Schneider, Christina Kuhn, Mathis Wild, Mariella Schneider, Nicole Pochert, Claudia Traidl-Hoffmann, Jacqueline Sagasser, Christian Dannecker, Christian Hinske, Maggie Banys-Paluchowski, Michael Untch, Thorsten Kühn, Udo Jeschke, Nina Ditsch. SerMa (Seroma of the Mammary gland) pilot - Is there a possible link between macrophage-based immune response and age? [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 PO4-25-06.

Abstract PS13-02: Clinical Outcome and Patients’ Characteristics of Breast Cancer Diagnosed During Pregnancy: A Retrospective Single Institutional Study

Abstract Background: Breast cancer (BC) is considered the second most common malignancy affecting pregnant women. Treatment of this condition is complex due to the potential risks it poses to both the fetus and mother. In this study, we report on the incidence, clinicopathological characteristics, management, and the outcomes of patients diagnosed with breast cancer during pregnancy in a tertiary care institution in Saudi Arabia. Patients and methods: This is a single-institution retrospective cohort analysis. We reviewed the medical records of all breast cancer cases in pregnant women that were diagnosed and treated at a a tertiary care center in Saudi Arabia, during the period from 2001 to 2017. We used Fisher’s exact test, chi-square, and Kaplan-Meier (KM) method for various analyses. Demographic data, treatment received, response, and prognostic factors were analyzed. The study was approved by the institutional review board at our center. Results: One hundred seventy-three patients met the search criteria. Median age at diagnosis was 34 (IQR: 30 – 38) years. Of these patients, 100 (58%) had invasive ductal carcinoma (IDC), 42 (24%) had IDC with ductal carcinoma in situ (DCIS), and 15 (20%) had other types. One hundred forty-two (82%) had pathological grades 2 and 3. Hormone receptors were positive in 90 (52%) patients, negative in 79 (45.7) patients and unknown in 4 (2.3%) patients. Her2/neu receptor status was positive in 67 (38.7%) patients and negative in 96(55.5%) patients. Forty five (26%) patients had triple negative disease.Stages I, II,III and IV were identified in 7(4%), 47 (27.2%), 54 (31.3%) and 51 (29.5%) patients respectively. Ninety (52%) and 75 (43%) patients received neoadjuvant and adjuvant anthracycline, platinum or taxane based chemotherapy. After being implemented in different international and our institutional guidelines, anti-Her2/neu therapies were given in 35 (20.2%) patients. The median overall survival (OS) was 127 months. Univariate analysis had shown statistically significant correlation between clinical stage, hormonal status, and overall survival. Conclusion: Breast cancer diagnosed during pregnancy is associated with poor outcomes. Breast cancer awareness and screening programs are essential for early detection and proper management thereby leading to better outcomes. Citation Format: Mahmoud A Elshenawy, Emaan Haque, Ahmed Badran, Adhar AlSayed, Taher Twegieri, Dahish Ajarim, Wafa Khayal, Osama Al Malik, Amal Al Hefdhi, Tusneem El Hassan, Syed Saad Akhtar, Meshari Al Zahrani, Saba Al Aklabi, Kausar Suleman. Clinical Outcome and Patients’ Characteristics of Breast Cancer Diagnosed During Pregnancy: A Retrospective Single Institutional Study [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 PS13-02.

Role of Early Left Atrial Functional Decline in Predicting Cardiotoxicity in HER2 Positive Breast Cancer Patients Treated With Trastuzumab

Trastuzumab is widely used in HER2 breast cancer. However, it may cause left ventricular (LV) dysfunction. A decrease in LV global longitudinal strain (GLS) has been previously demonstrated to be a good predictor of subsequent cancer therapy related dysfunction (CTRCD). Left atrial morphological remodeling during Trastuzumab therapy has also been shown. The aim of this study is exploring the relationship between early changes in left atrial function and the development of Trastuzumab-induced cardiotoxicity. Consecutive patients with diagnosis of HER2+non-metastatic breast cancer treated with Trastuzumab were prospectively enrolled. A clinical, conventional, and advanced echocardiographic assessment was performed at baseline and every three months, until a one-year follow-up was reached. One-hundred-sixteen patients completed the 12 months follow-up, 10 (9%) cases of CTRCD were observed, all after the sixth month. GLS and LVEF significantly decreased in the CTRCD group at 6 months of follow-up, with an earlier (3 months) significant worsening in left atrial morpho-functional parameters. Systolic blood pressure, early peak atrial longitudinal strain (PALS), peak atrial contraction (PACS) and left atrial volume (LAVI) changes resulted independent predictors of CTRCD at multivariable logistic regression analysis. Moreover, early changes in PALS and PACS resulted good predictors of CTRCD development (AUC 0.85; p = 0.008, p < 0.001 and 0.77; p = 0.008, respectively). This prospective study emphasizes that the decline in PALS and PACS among trastuzumab-treated patients could possibly increase the accuracy in identifying future CTRCD in non-metastatic HER2 breast cancer cases, adding predictive value to conventional echocardiographic assessment.

Abstract PO2-03-03: The Significance of Cavity Shave Margins in Breast Carcinoma on Margin Status and Re-excision Rates

Abstract Context: The comparative outcomes of breast conserving surgery (BCS) with and without cavity shave margins are not well established. We aim to evaluate the impact of each procedure on final margin status and rate of re-excision. Design: A total of 529 breast cancer cases from our institution between 2013-2015 were included. Demographic and clinicopathological data including procedure type, tumor type, grade, margins status, and re-excision rates were collected. H&amp;E slides of positive margins (tumor on ink) were reviewed by two pathologists. Appropriate statistical analysis was performed. Results: Out of 529 breast cancer cases, 125 were Ductal Carcinoma in situ (DCIS), 152 were Invasive Ductal Carcinoma (IDC) and 252 had both pathologies. The median age of patients was 59 years (range: 24-90). Patients who underwent excision with shave margins were 162 (35 DCIS, 56 IDC, 71 both) while excision without shave margins were 367 (90 DCIS, 96 IDC, 181 both). Re-excision rates were significantly lower 1) in patients who underwent BCS with cavity shave margins compared to those without (OR 0.32, p&amp;lt; 0.001) and 2) in patients who did not require lymph node excision compared to those who did (OR 4.26, p&amp;lt; 0.001). Additionally, patients who had DCIS had a higher rate of re-excision than those with invasive cancer only (OR 5.17, P&amp;lt; .001). After adjusting for type of tumor, patients who underwent cavity shaving compared to those who did not, no significant difference was seen in tumor at margins (OR 0.73, p=0.282) or tumor within 2mm (OR 1.14, p=0.512) from margins. However, patients with IDC who underwent cavity shave had a higher proportion of negative tumor at the margins (76.5% vs. 67.0%; p=0.051). We found that patients who had an invasive carcinoma (IC) had a lower risk of having tumor at the margin or within 2 mm from the margin than those with DCIS or DCIS+IC, (p&amp;lt; .05). Conclusions: Our data shows that BCS with cavity shave margins is superior with regards to negative margin and re-excision rates when compared to without cavity shave margins. Citation Format: Fadi Zaiem, Anna Numi, Mira Kheil, Asem AbuJamea, Deepti Jain, Omar Abbas, Lauren Larson, Noor Suleiman, Saleh Al-Juburi, Sanaa Awada, Ragad Almsaddi, Hyejeong Jang, Seongho Kim, Nagla Salem, Lydia Choi, Sudeshna Bandyopadhyay, Sunil Jaiman, Rouba Ali-Fehmi. The Significance of Cavity Shave Margins in Breast Carcinoma on Margin Status and Re-excision Rates [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 PO2-03-03.