Population Of Breast Cancer Patients Research Articles

973 Managing Primary Endocrine Treatment (PET) in Breast Cancer Patients: An Audit of Resource Utilisation and Risks

Abstract Aim Primary endocrine treatment (PET) is considered in patients with oestrogen receptor (ER) positive breast cancer who decline or are deemed unfit for surgery. This treatment can affect bone density resulting in osteoporosis and risk of fractures. With increasing demand on resources, our aim was to examine clinical practices in this vulnerable patient group, balancing risks whilst ensuring good patient selection for treatments. Method We reviewed patients who had PET for ER positive breast cancer from a single consultant database in a district general hospital in South Wales between May 2018 and March 2023. We examined use of bone density (DEXA) scans, bone protection medications, outcomes, and complications. Results 48 patients were included, aged 50-95 years (median 80) and male: female (1:47). All were ER positive, excepting 2 with limited prognosis empirically started on treatment. Reasons for PET included patient choice (15%), palliative treatment (8%), co-morbidities (65%), late stage (4%) and other (8%). There were 27 deaths (54%), with mean time from diagnosis to death 14 months (range 1-50 months). 5 patients (10%) had DEXA scan and 16 (33%) were on bone protection. 3 patients had fractures whilst on PET, likely due to pre-existing conditions. Conclusions The frail breast cancer patient population has limited life expectancy and should not be over-investigated unnecessarily. It could be debated as to how much benefit bone protection provides, given the low fracture rate. Further studies are required to determine benefits of empirical bone protection in PET patients.

Racial differences in degrees of side effects to taxane based chemotherapy in patients with breast cancer.

e13726 Background: Taxane-based chemotherapy is well-established as a backbone of treatment for patients with breast cancer. While highly effective, all taxanes are known to cause peripheral neuropathy, with a high prevalence in obese patients. Other risk factors to developing peripheral neuropathy include older age, smoking, and hyperglycemia. Prior studies have shown that obesity is more prevalent in Black women compared with other racial group in the United States. Obese women have higher body surface areas and thus, tend to receive higher doses of chemotherapy. The higher total doses of taxanes received by obese women puts them at higher risks for developing peripheral neuropathy. We sought to evaluate the racial and BMI differences in rates of neuropathy in patients with breast cancer receiving taxanes. Methods: We created a 2-year database (2021-2022) of women diagnosed with breast cancer who received a taxane across a single health system. Data collected included age at diagnosis, self-identified race, breast cancer subtype, BMI, type of taxane, neuropathy, smoking and diabetes. Stratification analysis was performed using SAS Software 9.4. Results: The rate of neuropathy was 65.2% in White patients and 71.01% in Black patients (p=0.4649). The risk ratio between Black patients with neuropathy to White patients with was 1.26, 95% Cl (0.73-2.17), p=0.6525. In the total cohort of patients, regardless of neuropathy, 60.6% of Black patients had a BMI >30 compared with only 39.5% of White patients. Of those who had neuropathy, obesity was present in 64% of White patients and 65% of Black patients. Conclusions: The data presented here suggest that in a population of breast cancer patients treated with taxanes, there was a trend towards increased neuropathy in Black patients, but no increase in neuropathy based on BMI. Black women were more obese, which suggests that they are at increased risk for developing neuropathy. Factors such as universal effects of chemotherapy across races, comorbid conditions and insufficient sample size could have masked potential significant differences. Further research is needed to understand the complex elements influencing treatment responses in a diverse population. [Table: see text]

Interaction between VEGF-A and immune checkpoint targets in triple-negative breast cancer and mechanisms of immune evasion and tumor progression.

1096 Background: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment triple negative breast cancer (TNBC). However, not all patients with TNBC benefit from the addition of ICIs due to factors such as intrinsic and acquired resistance to ICIs, and complex interplay between tumor and immune cells in the tumor microenvironment (TME). Vascular endothelial growth factor (VEGF) promotes angiogenesis and potentially modulates tumor immune evasion. A phase I clinical trial has shown that a bispecific antibody to VEGF-A and PD-L1 produces encouraging tumor responses in advanced TNBC. In this study, we investigated the interaction between VEGF and various immune gene expression signatures including PD-L1 in a real-world breast cancer patient population. Methods: Comprehensive immune profiling, including the RNA-seq based gene expression assessment of 395 immune-associated genes, was performed on 120 formalin-fixed paraffin-embedded breast cancer samples. PD-L1 expression (Combined Positive Score, CPS ≥ 10%) was measured by immunohistochemistry (IHC; 22C3). Clinicopathologic variables were collected. Statistical associations between quantitative biomarkers, including 28 immune checkpoint genes, were calculated using Pearson correlations (r), and comparisons of quantitative biomarkers between groups were performed using the proportions test. For statistical significance, p<0.05 was required. Results: The study cohort included 29 patients (24.2%) with TNBC and 91 (75.2%) with non-TNBC (including ER+/HER2- and HER2+). Most patients had metastatic tumors (n=92, 76.7%) and invasive ductal carcinoma (n=83, 69.2%). Among the TNBC group, 21 patients had PD-L1 positive tumors (72.4%), defined by CPS ≥ 10.In non-TNBC, VEGF has significant, though weak (r<0.35) correlations with the expression of three checkpoint genes: AKT1 (r=0.35, p=0.00063), ICOS (r=0.34, p=0.00099), and TIM3 (r=0.29, p=0.0061). In TNBC, VEGF has significant, strong (r>0.47) correlations with the expression of three other checkpoint genes: PD-1 (r=0.47, p=0.0094), PD-L1 (r=0.57, p=0.0012), and PIK3CA (r=0.6, p=0.00051) However, in TNBC, VEGF gene expression does not have a statistical association with PD-L1 IHC (CPS ≥/< 10 (p=0.9)). Conclusions: Our findings suggest that there is an interplay between angiogenesis and an immunosuppressive tumor immune microenvironment in TNBC to a greater degree than in non-TNBCs. This supports the notion that angiogenesis mediators such as VEGF-A may enhance the expression of immunosuppressive checkpoint molecules, leading to immune evasion and tumor progression. Combination treatments of ICIs, especially anti-PD-1 therapy, with VEGF antibodies may be promising approaches to enhance the immune responses in TNBC, especially in tumors with CPS<10, where the current frontline treatment is cytotoxic chemotherapy.

Mutations and mortality in very young patients with breast cancer.

e13157 Background: Breast cancer diagnoses in young women have increased over the last 10 years. Despite decreasing mortality rates for breast cancer, disparities continue to exist for specific populations including Black women and premenopausal women. Recent studies observe a 41% increased death rate in Black women compared to White women, and a two-fold increased mortality in women younger than 50 years. Many biological and societal factors can affect breast cancer mortality. We sought to evaluate the relationship between germline mutations (GM), breast cancer subtype, and mortality based on race in a unique, young breast cancer patient population. Methods: We assembled a 10-year retrospective chart review (2012 to 2022) of 773 women diagnosed with breast cancer under the age of 40 in a regional health network. Data was collected from electronic medical records. Associations were assessed using the chi-square test using SAS version 9.4. Results: Out of the 773 patient information collected, 60% of patients were White, 36% Black, and 3% Other. A total of 675 patients had genetic results and 124 patients with documented GM. Of patients with GM, 48 were Black and 74 were White. 13 patients with germline mutations had documented deaths. There was no statistical link between germline mutations and mortality. Of the 13 patients, 4 (30%) were Black and 9 (70%) were White. There was no statistical difference amongst area deprivation index (ADI) quintiles for mortality in patients with GM. Of the 675 patients with genetics data, 72 patients without GM died which includes 31 Black patients, 38 White patients, 3 Other. Based on our data, there is a higher prevalence of germline mutations (60%) in White patients over Black patients and a descriptive predominance of mortality despite absence of statistical significance. More patients who resided in areas of higher ADI (2-4) with GM died than in areas of lower ADI. Conclusions: Our data demonstrates a descriptive prevalence in mortality among young White patients compared to young Black patients. Across the USA, the Black population is 13% and in Louisiana, that population is 33%. Given that our cohort population was 36% Black, it is noteworthy that we were unable to demonstrate a statistical mortality predominance among these young patients. [Table: see text]

Abstract PO5-08-11: Genetic Landscape of Early Breast Cancer in an Ashkenazi Jewish Cohort

Abstract Background: The Ashkenazi Jewish (AJ) population exhibits a distinctive mutation profile in BRCA1 and BRCA2 (BRCA1/2), characterized by 3 common founder mutations: BRCA1 185delAG, BRCA1 5382insC, and BRCA2 6174delT. These 3 mutations are associated with 10% of invasive breast cancer (BC) cases among AJ women. However, the frequency of non-founder pathogenic variants in BRCA1/2 and other BC-related genes in AJ women with BC remains unclear. Methods: This retrospective study included AJ patients diagnosed with stage I-II human epidermal receptor growth factor 2 negative BC between 2004-2022 at the Weill Cornell Breast Center. We collected clinicopathological characteristics and genetic information to determine the frequency of predisposing mutations in BC and non-BC related genes in AJ patients with early BC. We also analyzed the clinicopathological characteristics and outcomes of patients with and without germline mutations in these genes. Results: The study included 232 self-identified AJ patients, with 98% being females. The median age at BC diagnosis was 62 years (IQR: 50-70). Stage I and II cancers accounted for 68% and 32% of cases, respectively. Hormone receptor positivity (HR+) was observed in 71% of patients, while 29% had triple-negative tumors. Genetic testing was performed on 88% (n=203) of the patients, while 5% of patients declined to undergo genetic testing. Among the tested patients, 12% (n=25/203) had pathogenic variants in BRCA1 or BRCA2, with 44% and 16% of these corresponding to the BRCA1 and BRCA2 founder mutations, respectively. Testing beyond BRCA1/2 genes was conducted on 154 patients, and only 6% (n=9/154) were found to have pathogenic variants in CHEK2, while no mutations were detected in other prevalent BC-related genes, including PALB2 and ATM. Fourteen-percent of patients had pathogenic mutations in other genes including APC, CFTR, FH, DIS3L2, FANCC, MUTYH, NF1 and VHL. The frequency of pathogenic BRCA1/2 variants was inversely proportional to the age at BC diagnosis: 50% (n=8/16), 21% (n=8/39), 15% (n=6/40), and 3% (n=3/108) of patients diagnosed at age < 40, 40-49, 50-59, and >60 years, respectively, had a pathogenic variant in either BRCA1 or BRCA2. The frequency of founder mutations varied according to age at diagnosis: 63%, 75%, 17%, and 100% for patients aged < 40, 40-49, 50-59, and >60 years, respectively. Patients with BRCA1/2 mutations exhibited higher-risk clinicopathological features compared to those without mutations, including a higher proportion of high histological grade (88%), and triple-negative tumors (76%). Mastectomy was the primary surgical treatment for 56% and 23% of patients with and without BRCA1/2 mutations, respectively. No difference in disease-free survival was found between patients with and without BRCA1/2 mutations with a median follow up of 3 years (IQR: 1-4). Conclusions: In our cohort, 17% of AJ patients with early BC carried a pathogenic variant in a BC-related gene, with BRCA1/2 being the most commonly affected genes. The proportion of pathogenic variants in BRCA1/2 showed an inverse correlation with the age at BC diagnosis, reaching up to 50% in patients diagnosed under the age of 40. These findings contrast with the lower prevalence of pathogenic variants in BRCA1/2 (38%) reported in the existing literature for this age group. Additionally, 8% of patients had pathogenic variants in other tested cancer genes carrying a genetic predisposition to colorectal cancer (CRC). These findings contribute to our understanding of the genetic landscape of early BC in the AJ population and emphasize the importance of comprehensive genetic testing, particularly among young patients. These results also suggest the need for earlier and more frequent CRC screening in a population of BC patients that may not be adhering to recommended guidelines. Furthermore, our study provides insight into how this genetic landscape may vary when analyzing late-stage BC in women of AJ heritage. Citation Format: Laura Munoz Arcos, Eleonora Nicolò, Maira Pires, Letizia Pontolillo, Leticia Varella, Tessa Cigler, Eleni Andreopolu, Anne Moore, Ashley Schreier, Carlos Munoz-Zuluaga, Lisa Newman, Georgia Syrnioti, Massimo Cristofanilli. Genetic Landscape of Early Breast Cancer in an Ashkenazi Jewish 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 PO5-08-11.

Abstract PO2-16-10: Characterising HER2-low status in metastatic breast cancer: a real-world retrospective study of patients at a metropolitan cancer centre in Australia

Abstract Background: Traditionally, breast cancer subtyping has described patients as HER2-negative or HER2-positive, with the latter being those in whom HER2-directed therapies are utilised. A proportion of HER2-negative cancers can be classified as “HER2-low” as they express IHC 1+ or 2+ and are non-amplified on in-situ hybridisation (ISH). Until recently, our widely available HER2-targeted therapies have proven to be ineffective in this subtype. The DESTINY-BREAST04 trial (Modi et al, NEJM 2022) showed progression-free and overall survival efficacy of HER2-directed therapy using the antibody-drug conjugate (ADC) trastuzumab deruxtecan (T-DXd) in HER2-low disease, suggesting a need to identify this population for selected therapy. This study evaluated a real-world population of metastatic breast cancer (MBC) patients treated according to traditional breast cancer subtypes to determine the frequency of HER2-low histology, with a focus on selection of first-line therapy. Methods: This retrospective audit identified patients being treated for MBC at a single tertiary hospital (Austin Health in Melbourne, Australia) over a 3.5 year period. Patients were identified from an electronic database, with a date of last follow-up as August 2022. Medical records were interrogated for clinicopathological information including review of pathology reports for breast cancer subtypes. Traditional breast cancer subtypes were defined as (i) ER positive and HER2-negative (HER2 0 or 1+, or 2+ and non-amplified); (ii) HER2-positive (HER2 3+ and/or amplified) and (iii) TNBC (negative for ER and PgR, and HER2 0 or 1+, or 2+ and non-amplified). Selection and duration of first-line treatment for MBC was also recorded. Results: Between March 2018 and August 2022, 202 MBC patients were identified. Based on traditional subtypes, 126 (62%) were ER positive and HER2-negative, 46 (23%) were HER2-positive, 26 (13%) were TNBC and 4 (2%) were unknown. In the total population, 87 (43%) were classified as having HER2-low disease based on retrospective pathology reports. HER2-low represented 61% of ER positive, HER2-non amplified patients and 45% of TNBC patients. Metastatic specimen data was known for 172 cases and of these, 95 patients (55%) were re-biopsied on metastatic progression. This occurred more commonly with HER2-positive (81%) and ER positive HER2-negative (78%) primaries. The most common change in subtype was loss of ER, which occurred in 7 patients (3%). Changes in HER2 status occurred in 29 (14%) of patients, most commonly as either an increase from 1+ to 2+ or decrease from 1+ to 0. HER2-low status remained consistent for 67% of patients who underwent biopsy on recurrence. For patients with ER positive HER2-negative MBC, first-line combination therapy with a CDK4/6 inhibitor + AI was preferred (51%), followed by single agent endocrine therapy (30%) and chemotherapy (17%). The majority (84%) of HER2-positive patients received first-line dual HER2 therapy (trastuzumab and pertuzumab) with taxane chemotherapy. Half of TNBC patients received upfront chemotherapy, with physician preference being capecitabine (45%). There was no significant difference in PFS between the HER2-low vs. HER2-0 cohorts, for either ER positive or TNBC subtypes. No patients in this series were treated based on HER2-low definition due to no funded access to such therapies at the time. Conclusion: HER2-low has emerged as an identifier for patients who may respond to HER2-directed therapies using ADCs such as T-DXd. However, its clinical significance as a discrete clinical subtype remains uncertain. In this retrospective audit, HER2-low patients were identified in both ER positive and TNBC subtypes. Dynamic changes in HER2 staining occurred infrequently. Further evaluation is needed to address whether HER2-low expression provides any prognostic value and whether prospective reporting of HER2-low status may alter how these new HER2-directed therapies are used in future. Citation Format: Michelle Li, Belinda Yeo. Characterising HER2-low status in metastatic breast cancer: a real-world retrospective study of patients at a metropolitan cancer centre in Australia [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 PO2-16-10.

Abstract PO3-10-02: Cardiovascular Risk Factors and Outcomes in Native Americans who have Received Chemotherapy and/or Radiation: A Retrospective Single-center Study

Abstract Introduction: There is scarce literature regarding cardiovascular risk factors and cardiovascular outcomes in Native American patients with breast cancer. Cardiovascular complications are known to be associated with cancer treatment. Certain medications, such as anthracyclines and HER-2 agents are directly cardiotoxic, while other modalities of treatment may lead to accelerated atherosclerosis. We have conducted a single-center retrospective study assessing cardiovascular risk factors and outcomes in Native American patients with breast cancer. Methods: Data was extracted from the UNM Comprehensive Cancer Center tumor registry and PowerChart. Charts were selected based on if the patient was registered as a Native American with a breast cancer diagnosis from 2010-2020. Inclusion criteria were age 18 or older, identified as Native American, received a diagnosis of breast cancer between 2010-2020, received at least one chemotherapeutic agent, endocrine therapy, or radiation therapy. Results: The study included 89 participants. The median age at the time of diagnosis of breast cancer was 55 years. All were female. Cardiovascular risk factors prior to undergoing treatment were reported as follows: Hypertension (55.3%); diabetes (46.1%); hyperlipidemia (35.3%); smoking (25%); obesity (52.6%). Before initiating treatment, 3.5% of Native American breast cancer patients in our study population had coronary artery disease. Cardiovascular disease incidence before and after undergoing treatment was as follows: myocardial infarction (1.2% vs 2.4%), stroke (4.7% vs 1.2%), heart failure with reduced ejection fraction (HFrEF) (2.3% vs 4.8%), heart failure with preserved ejection fraction (HFpEF) (1.2% vs 1.2%), peripheral arterial disease (1.2% vs 1.2%), atrial fibrillation or another arrhythmia (4.7% vs 5.9%). We also noted new diagnoses of hypertension and arrhythmia in 3.6% and 1.2% of our study patient population respectively after starting chemotherapy. 43% of all included patients had a transthoracic echocardiogram (TTE) or multigated acquisition scan (MUGA) recorded in the chart before chemotherapy and 45% had one afterward. Of those, when comparing ejection fraction between pre- and post-chemotherapy, a change in mean EF (61.9% vs 57.8%) was seen. 37 patients (41.6%) received treatment with an anthracycline or a Her-2 agent. Mean EF prior to treatment was 65.0%, and mean EF after treatment was 59.1%. Pre- and post-treatment rates of HFrEF were 0% and 5.7%, respectively. Discussion: Hypertension, diabetes, hyperlipidemia, smoking, and obesity are highly prevalent in the Native American patient population who are treated for a diagnosis of breast cancer. Our study showed a change in mean EF after treatment (61.9% vs. 57.8%) in our Native American breast cancer patient population. For those receiving an anthracycline or Her-2 agent, EF changed from 65.0% to 59.1% after treatment. High rates of HFrEF, new onset hypertension, and arrhythmias post-treatment were also noted. These findings suggest that a thorough cardiovascular risk assessment prior to starting a treatment regimen for breast cancer may be important. Multidisciplinary management with cardiology may be critical in the care for these patients. Further investigation of cardiovascular risk factors and outcomes after cancer treatment is warranted in this population. There are several limitations of our study, one being that this was a single-center study which does not represent the Native American population throughout the United States and Canada. The small sample size also limits the power of the study. Many patients after initial evaluation at our facility received care at outside facilities, which limits data on treatments received, studies performed (e.g. TTE and MUGA), or cardiovascular events. Citation Format: Conor Kirby, Jewel Meyer-Hagen, Paul Andre, Umair Khan, Nicholas Harris, Eduardo Davila, Mark Garcia, Jacklyn Nemunaitis. Cardiovascular Risk Factors and Outcomes in Native Americans who have Received Chemotherapy and/or Radiation: A Retrospective Single-center 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 PO3-10-02.

Abstract PO4-22-03: Intensity Modulated Proton Therapy (IMPT) for the Definitive Adjuvant Management of Women with Breast Cancer: A Single Institutional Experience of 5-Year Oncologic Outcomes

Abstract Purpose: There is limited data reporting the oncologic outcomes of breast cancer patients treated definitively with adjuvant proton beam therapy. Here we report a single institutional experience of oncologic outcomes, treating a predominantly vulnerable breast cancer patient population and compare these to historical standards primarily utilizing photon therapy. Materials and Methods: Unver IRB approval, we retrospectively reviewed 453 definitively treated breast cancer patients from 2016 – 2023 using adjuvant IMPT as part of their cancer care. Patients with recurrent disease, receiving re-irradiation, and those with less than 1-year of follow up were excluded from this analysis. Patients were treated with surgery and systemic therapies as per standards of care. Radiation therapy was administered using pencil beam scanning IMPT with daily image guidance. χ2 and Mann-Whitney U tests were performed to determine differences between select variables. Kaplan-Meier analysis and Cox proportional hazard models were used to analyze overall survival (OS). Results: With a median follow up of 22 months for the entire cohort, 453 patients were treated at XXXX as part of definitive adjuvant management for their breast cancer. Nearly 30% of patients self-identified as black (n=135), average patient age was 54 and 56% (n=255) self-identified as being married with approximately 25% (n=109) of patients having Medicare/Medicaid insurance. 198 patients (43.8%) had an intact breast and the remainder mastectomy of which 37.4% had reconstruction at the time of their radiation. 229 patients (50.7%) received neoadjuvant chemotherapy while 55 patients (12%) received concurrent chemotherapy which was either her2+ directed or Xeloda. The number of patients (%) corresponding to the AJCC 8th edition anatomical staging is as follows: Stage 0: 12 (2.7%); Stage I: 91 (20.1%); Stage 2: 197 (43.6%); Stage 3: 152 (33.6%). Median RT dose delivered for patients receiving comprehensive treatment was 50.4 Gy with 81% of patients receiving a boost to either scar, lumpectomy cavity and/or LN regions. Median RT dose delivered for patients receiving whole breast radiation was 42.56 Gy with a 10 Gy lumpectomy cavity boost. 5-yr OS by stage was 0: 100%; stage I: 98.8%; stage 2: 93.5%; stage 3: 90.8%. Five-year OS for black, white and other race patients were 85.3%, 95.8% and 96%, respectively (White as Ref: HR 3.176, 95% CI: 1.313-7.681, p=0.010 for black patients). For the entire cohort, patients with triple negative disease had a 5-yr OS of 80.4% (HR: 4.33, 95% CI 1.87-10.04, p< 0.001) and there was no difference in OS when insurance status was considered (p=0.378). Conclusions: To the best of our knowledge this represents the largest series of definitively treated breast cancer patients utilizing adjuvant proton therapy and the 5-year OS rates in our analysis coincide with published standards1. Results from the on-going randomized RADCOMP study will provide further guidance as to which patients benefit the most from proton therapy and will further support equivalent oncological outcomes when compared to photon therapy. 1. Weiss A, Chavez-MacGregor M, Lichtensztajn DY, et al. Validation study of the American Joint Committee on Cancer eighth edition prognostic stage compared with the anatomic stage in breast cancer. JAMA Oncol. 4(2):203-209, 2018. Citation Format: Elizabeth Nichols, Gurbani Singh, Desiree Lejano, Sarah McAvoy, Mark Mishra, Melissa Vyfhuis. Intensity Modulated Proton Therapy (IMPT) for the Definitive Adjuvant Management of Women with Breast Cancer: A Single Institutional Experience of 5-Year Oncologic 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 PO4-22-03.

Enhancing breast cancer outcomes with machine learning-driven glutamine metabolic reprogramming signature.

This study aims to identify precise biomarkers for breast cancer to improve patient outcomes, addressing the limitations of traditional staging in predicting treatment responses. Our analysis encompassed data from over 7,000 breast cancer patients across 14 datasets, which included in-house clinical data and single-cell data from 8 patients (totaling 43,766 cells). We utilized an integrative approach, applying 10 machine learning algorithms in 54 unique combinations to analyze 100 existing breast cancer signatures. Immunohistochemistry assays were performed for empirical validation. The study also investigated potential immunotherapies and chemotherapies. Our research identified five consistent glutamine metabolic reprogramming (GMR)-related genes from multi-center cohorts, forming the foundation of a novel GMR-model. This model demonstrated superior accuracy in predicting recurrence and mortality risks compared to existing clinical and molecular features. Patients classified as high-risk by the model exhibited poorer outcomes. IHC validation in 30 patients reinforced these findings, suggesting the model's broad applicability. Intriguingly, the model indicates a differential therapeutic response: low-risk patients may benefit more from immunotherapy, whereas high-risk patients showed sensitivity to specific chemotherapies like BI-2536 and ispinesib. The GMR-model marks a significant leap forward in breast cancer prognosis and the personalization of treatment strategies, offering vital insights for the effective management of diverse breast cancer patient populations.

Stability analysis of fractional order breast cancer model in chemotherapy patients with cardiotoxicity by applying LADM

AbstractBreast cancer is the most common type of cancer in women. Chemotherapy is primarily used for patients with stage 2 to 4 breast cancer. Most chemotherapy drugs are effective at destroying rapidly growing and proliferating cancer cells. However, drugs also damage normal, rapidly growing cells, which can lead to serious side effects. Breast cancer treatment with chemotherapy can affect heart health. Side effects of chemotherapy on the heart are called cardiotoxicity. Therefore, we have constructed a mathematical model from the breast cancer patient population. In this article, we utilize the Caputo–Fabrizio fractional order derivative for mathematical modeling of the breast cancer stages in chemotherapy patients. The use of Caputo–Fabrizio fractional derivative provides a more valuable insight into the complexity of the breast cancer model. The stability of the fractional order model is also proven by the $\mathscr{P}$ P -stable approach of the fixed point theorem. Also, the numerical simulations are performed via Laplace Adomian decomposition method to establish the dependence of the breast cancer dynamics on the order of the fractional derivatives. Based on the geometric results in the figures, we can conclude that the magnitude of the fractional order has a considerable impact on the days, which the maximum or minimum of the system solutions are reached, with a shift in the time at which this happens as the fractional order decreases from 1. However, it is obvious that the solutions of Caputo–Fabrizio fractional model approach the relevant results of the classical integer order system, when the fractional order approaches to 1.

Health-state utility of patients with HER2-positive breast cancer in Vietnam: A multicenter cross-sectional study.

Patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer may have poor prognoses and short overall and disease-free survival. Most previous studies focused on assessing the quality of life and health-state utility of the general population of breast cancer patients. The number of studies for HER2-positive breast cancer patients is negligible. This study investigated the health-state utility and its associated factors among Vietnamese patients with HER2-positive breast cancer. We conducted face-to-face interviews with 301 HER2-positive breast cancer patients to collect data. Their health-state utility was measured via the EQ-5D-5L instrument. The Mann-Whitney U and Kruskal-Wallis tests were employed to compare the differences in utility scores between two groups and among three groups or more, respectively. Factors associated with patients' heath-state utility were identified via Tobit regression models. Pain/discomfort (56.1%) and anxiety/depression (39.5%) were the two issues that patients suffered from the most, especially among metastatic breast cancer patients. The severity of distress (depression, anxiety, and stress) in patients was relatively mild. Of 301 patients, their average utility score was 0.86±0.17 (range: 0.03-1.00), and the average EQ-visual analogue scale (VAS) score was 69.12±12.60 (range: 30-100). These figures were 0.79±0.21 and 65.20±13.20 for 102 metastatic breast cancer patients, significantly lower than those of 199 non-metastatic cancer patients (0.89±0.13 and 71.13±11.78) (p<0.001), respectively. Lower health-state utility scores were significantly associated with older age (p = 0.002), lower education level (p = 0.006), lower monthly income (p = 0.036), metastatic cancer (p = 0.001), lower EQ-VAS score (p<0.001), and more severe level of distress (p<0.001). Our findings showed a significant decrement in utility scores among metastatic breast cancer patients. Patients' health-state utility differed by their demographic characteristics (age, education level, and income) and clinical characteristics (stage of cancer and distress). Their utility scores may support further cost-effectiveness analysis in Vietnam.

Fertility concerns and treatment decision-making among national sample of young women with breast cancer.

Diagnosis of breast cancer in young women has been shown to affect their decision-making with regard to fertility and family planning. Limited data are available from populations across the U.S. regarding this issue; thus, we sought to describe fertility concerns and efforts to preserve fertility in a national clinical trial population of young breast cancer patients. The young and strong study was a cluster-randomized controlled trial testing an intervention program for young women with breast cancer. Patients were surveyed within 3 months after diagnosis and at 3, 6, and 12 months after. Surveys asked about sociodemographics, psychosocial domains, fertility concerns, and fertility preservation strategies. Univariable and multivariable models were used to investigate sociodemographic, clinical, and psychosocial predictors of fertility concerns. Of 467 women from 54 clinical sites across the U.S. (14 academic, 40 community), 419 were evaluable regarding fertility concerns. Median age was 40 years (range 22-45), 11% were Black, 6% Hispanic, and 75% had children. Tumor stage was I (35%), II (51%), or III (14%); 82% received chemotherapy. At time of the treatment decision, 133 (32%) participants had fertility concerns, among whom 47% indicated this affected their treatment decisions. Sixty percent of participants reported having discussed fertility with their physician. Twenty percent of those with fertility concerns used fertility preservation strategies. History of difficulty becoming pregnant and younger age were associated with higher odds of fertility concerns in multivariable modeling. Many young women with newly diagnosed breast cancer are concerned about fertility in a way that impacts their treatment decisions. Concerns were discussed, but few used fertility preservation strategies. These findings have implications for counseling young patients.

Abstract A083: Initiation and persistence of hormone therapy in endocrine positive breast cancer at an urban safety-net hospital

Abstract Background: Evidence demonstrates inequities in receipt and persistence of hormone therapy among breast cancer patient populations based on race, ethnicity, insurance, and language. Institutions where patients seek cancer care may have an impact on receipt of treatment. It is unknown whether safety net hospitals, servicing a vulnerable patient population, exhibit inequities in receipt of hormone therapy for breast cancer. Study Design: We performed a retrospective study of patients diagnosed with all stages of hormone positive (ER+ and/or PR +) breast cancer treated at a safety net institution over the five year period from January 1, 2009 to December 31, 2013. The initiation of and persistence of hormone therapy were assessed by race, ethnicity, insurance status, and primary language. Persistence of therapy was defined as defined as at least 3 prescriptions (90 day supply) or more than 1 visit after start of treatment documenting taking treatment. Results: A total of 599 women were identified. The median age was 59 years, 58% were non-White, 32% were non-English-speaking, and 35% had Medicaid or no insurance. A total of 506 (84%) were started on hormone therapy. In multivariate regression analysis, the rate of endocrine therapy initiation was associated with higher stage at diagnosis, post-menopausal status, and HER2 negative status. Non-white race, Hispanic/Latino ethnicity, non-English-language, and Medicaid/no insurance were not significantly associated with or without initiation of hormone therapy. 93% of patients started on hormone therapy had evidence of continued treatment, 91% had evidence of continued treatment at 1 year, 75% finished their recommended course of hormone therapy. Conclusion: At an urban safety-net hospital, we do not observe inequities in the initiation of endocrine therapy for breast cancer by race, ethnicity, insurance, or language. Persistence of therapy was similar to nationally reported data. Additional research by hospital type, and granular reasons for non-adherence are warranted. Citation Format: Quinn S. Solfisburg, Brendin R. Beaulieu-Jones, Michael R. Cassidy, Naomi Y. Ko. Initiation and persistence of hormone therapy in endocrine positive breast cancer at an urban safety-net hospital [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr A083.

Post-Mastectomy Implant Complications in the Hispanic Breast Cancer Patient Population.

The purpose was to analyze the impact of post-mastectomy radiation therapy (PMRT) on implant-based breast reconstruction (IBR) in self-identified Hispanic patients compared to non-Hispanic counterparts. We retrospectively reviewed patients who underwent IBR between January 1, 2017 and December 31, 2019 at a single hospital system. Patients were cisgender women, assigned female at birth, 18 years or older, and underwent mastectomy with immediate IBR +/- PMRT. We compared characteristics between Hispanic and non-Hispanic patients, assessing capsular contracture and implant loss rates. Multivariable analysis was performed to identify factors associated with complications. A total of 317 patients underwent mastectomy and reconstruction. Of these patients, 302 underwent a total of 467 mastectomies with IBR, and these 467 procedures were included in the analysis of complications. Complications occurred in 175 breasts (37.5%), regardless of PMRT. Seventy-two of the 302 patients (24%) received PMRT to one breast. The overall rates of capsular contracture, implant loss, and overall complications did not vary significantly between Hispanic and non-Hispanic patients (p=0.866, 0.974, and 0.761, respectively). When comparing only irradiated patients, there was a trend towards increased implant loss and overall complication rates in Hispanic versus non-Hispanic patients (p=0.107 and 0.113, respectively). Following PMRT the rate of any complication was 71% in Hispanic women and 53% in non-Hispanic women. Our study illuminates a trend towards higher complication rates after PMRT in Hispanic versus non-Hispanic patients. Further studies are needed to understand why Hispanic patients may have more side effects from radiation therapy.

Complication Avoidance of Reconstruction Implant Radiation Therapy (CARIT): A Retrospective Case-Cohort Analysis.

Patients are increasingly offered implant-based reconstruction prior to radiotherapy. However, it is unclear if the radiation treatment technique itself impacts upon toxicity. We performed this study to compare outcomes following implant-based reconstruction amongst breast cancer patients treated with a standard radiotherapy technique that irradiates the entire chest wall versus a novel technique which uses a smaller clinical target volume (CTV) to spare the implant. Need for corrective surgery, capsular contracture, and cosmetic outcomes were evaluated, with the hypothesis that the novel technique would result in fewer adverse outcomes and less need for corrective surgery. A retrospective case-cohort analysis of 57 patients who had post-mastectomy, implant-based reconstruction was conducted. Patients with invasive mammary carcinoma (IMC) or ductal carcinoma in-situ (DCIS) who were treated either with the novel radiotherapy technique (n = 26) or standard PMRT (n = 31) were included. Patient demographics such as age, BMI, TNM stage, implant size, hormone receptor status, and radiation course was collected. Primary endpoint was the need for corrective surgery within two years and cosmetic outcomes, measured using the Baker Classification Scale for capsular contracture and the Modified Harvard Harris Cosmetic Scale. Secondary endpoint was radiation-induced toxicity measured using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE). Cosmesis and toxicity were evaluated at 3 months post-radiation, 1 year, and after 13 months. Unpaired t-tests were used to compare need for corrective surgery, cosmesis (Baker Grade 2 or higher and Harvard Harris "Good" or worse), and toxicity (NCI CTCAE Grade 2 or higher). For the primary endpoint, need for corrective surgery, there was no significant difference between the novel and standard groups (two-sided p = 0.378, CI -0.38-0.14). The other primary endpoint of cosmesis, measured with the Baker scale and Harvard Harris, was also not significantly different (two-sided p = 0.147, CI -0.06-0.45), with the Harvard Harris cosmesis differences remaining insignificant across the 3 month, 1 year, and greater than 13 month periods (two-sided p = 0.854, 0.351, 0.468, respectively). The secondary endpoint, toxicity, was not significantly different between the novel and standard PMRT groups across 3 months and 1 year time periods (two-sided p = 0.328, 0.323, respectively). We will also be reporting the analysis for predictive factors related to toxicity, need for corrective surgery and cosmesis. Compared with standard PMRT, the novel technique was not significantly different in rates of reoperation, toxicity and cosmetic outcomes. Better understanding the factors involved in PMRT outcomes for breast cancer patients with implant-based reconstructions will aid in the development of standardized approaches to treating the breast cancer patient population.

Homologous Recombination Deficiency Across Subtypes of Primary Breast Cancer.

Homologous recombination deficiency (HRD) is highly prevalent in triple-negative breast cancer (TNBC) and associated with response to PARP inhibition (PARPi). Here, we studied the prevalence of HRD in non-TNBC to assess the potential for PARPi in a wider group of patients with breast cancer. HRD status was established using targeted gene panel sequencing (360 genes) and BRCA1 methylation analysis of pretreatment biopsies from 201 patients with primary breast cancer in the phase II PETREMAC trial (ClinicalTrials.gov identifier: NCT02624973). HRD was defined as mutations in BRCA1, BRCA2, BRIP1, BARD1, or PALB2 and/or promoter methylation of BRCA1 (strict definition; HRD-S). In secondary analyses, a wider definition (HRD-W) was used, examining mutations in 20 additional genes. Furthermore, tumor BRCAness (multiplex ligation-dependent probe amplification), PAM50 subtyping, RAD51 nuclear foci to test functional HRD, tumor-infiltrating lymphocyte (TIL), and PD-L1 analyses were performed. HRD-S was present in 5% of non-TNBC cases (n = 9 of 169), contrasting 47% of the TNBC tumors (n = 15 of 32). HRD-W was observed in 23% of non-TNBC (n = 39 of 169) and 59% of TNBC cases (n = 19 of 32). Of 58 non-TNBC and 30 TNBC biopsies examined for RAD51 foci, 4 of 4 (100%) non-TNBC and 13 of 14 (93%) TNBC cases classified as HRD-S had RAD51 low scores. In contrast, 4 of 17 (24%) non-TNBC and 15 of 19 (79%) TNBC biopsies classified as HRD-W exhibited RAD51 low scores. Of nine non-TNBC tumors with HRD-S status, only one had a basal-like PAM50 signature. There was a high concordance between HRD-S and either BRCAness, high TIL density, or high PD-L1 expression (each P < .001). The prevalence of HRD in non-TNBC suggests that therapy targeting HRD should be evaluated in a wider breast cancer patient population. Strict HRD criteria should be implemented to increase diagnostic precision with respect to functional HRD.

Identification of four candidates circulating microRNAs in plasma as a potential biomarker for early-stage breast cancer diagnosis in Vietnamese women

Breast cancer is the most commonly occurring malignant neoplasm among the female population. This study aims to ascertain novel biomarkers that may prove advantageous in the early detection of breast cancer. The present investigation involved a comparative analysis of the plasma expression of four distinct microRNA (namely, miR-425-5p, miR-142-3p, miR-9-3p and miR-15b-5p) in a cohort of 80 Vietnamese patients who were newly diagnosed with breast cancer. The expression levels of these microRNA were compared with those of 80 healthy individuals who served as controls. The plasma total RNA was extracted and the miRNA expression levels were assessed using Stem-loop RT-qPCR followed by statistical analysis. According to the findings of our study, the plasma levels of four microRNAs namely miR-425-5p, miR-142-3p, miR-9-3p and miR-15b-5p, were significantly reduced in both breast cancer patients in stage 0-I and the general breast cancer patient population as compared to healthy controls. The diagnostic accuracy of both miR-9-3p levels and miR-15b-5p levels was satisfactory with 74% and 88% values respectively. The combined effect of miR-425-5p/miR-142-3p/miR-9-3p/miR-15b-5p revealed the highest level of diagnostic precision, attaining a rate of 98% and an area under the curve value of 0.98 (with a sensitivity of 87.5% and specificity of 100%). In summary, the microRNAs miR-425-5p, miR-142-3p, miR-9-3p and miR-15b-5p exhibit potential as non-invasive diagnostic biomarkers for breast cancer, particularly in the initial stages of the disease.

Serum-derived extracellular vesicles from breast cancer patients contribute to differential regulation of T-cell-mediated immune-escape mechanisms in breast cancer subtypes.

Intracellular communication within the tumour is complex and extracellular vesicles (EVs) have been identified as major contributing factors for the cell-to-cell communication in the local and distant tumour environments. Here, we examine the differential effects of breast cancer (BC) subtype-specific patient serum and cell-line derived EVs in the regulation of T cell mediated immune responses. Ultracentrifugation was used to isolate EVs from sera of 63 BC patients, 15 healthy volunteers and 4 human breast cancer cell lines. Longitudinal blood draws for EV isolation for patients on neoadjuvant chemotherapy was also performed. Characterization of EVs was performed by Nanoparticle Tracking Analysis (NTA), transmission electron microscopy (TEM) and immunoblotting. CD63 staining was performed on a tissue microarray of 218 BC patients. In-house bioinformatics algorithms were utilized for the computation of EV associated expression scores within The Cancer Genome Atlas (TCGA) and correlated with tumour infiltrating lymphocyte (TIL) scores. In vitro stimulation of PBMCs with EVs from serum and cell-line derived EVs was performed and changes in the immune phenotypes characterized by flow cytometry. Cytokine profiles were assessed using a 105-plex immunoassay or IL10 ELISA. Patients with triple negative breast cancers (TNBCs) exhibited the lowest number of EVs in the sera; whilst the highest was detected in ER+HER2+ cancers; reflected also in the higher level of CD63+ vesicles found within the ER+HER2+ local tumour microenvironment. Transcriptomic analysis of the TCGA data identified that samples assigned with lower EV scores had significantly higher abundance of CD4+ memory activated T cells, T follicular cells and CD8 T cells, plasma, and memory B cells; whilst samples with high EV scores were more enriched for anti-inflammatory M2 macrophages and mast cells. A negative correlation between EV expression scores and stromal TIL counts was also observed. In vitro experiments confirmed that circulating EVs within breast cancer subtypes have functionally differing immunomodulatory capabilities, with EVs from patients with the most aggressive breast cancer subtype (TNBCs) demonstrating the most immune-suppressive phenotype (decreased CD3+HLA-DR+ but increased CD3+PD-L1 T cells, increased CD4+CD127-CD25hi T regulatory cells with associated increase in IL10 cytokine production). In depth assessment of the cytokine modulation triggered by the serum/cell line derived exosomes confirmed differential inflammatory cytokine profiles across differing breast cancer subtypes. Studies using the MDA-231 TNBC breast cancer cell-line derived EVs provided further support that TNBC EVs induced the most immunosuppressive response within PBMCs. Our study supports further investigations into how tumour derived EVs are a mechanism that cancers can exploit to promote immune suppression; and breast cancer subtypes produce EVs with differing immunomodulatory capabilities. Understanding the intracellular/extracellular pathways implicated in alteration from active to suppressed immune state may provide a promising way forward for restoring immune competence in specific breast cancer patient populations.

The Association Between Meningioma and Breast Cancer

A potential relationship between meningioma and breast cancer was suggested 70 years ago. However, to date, no conclusive evidence is available on this topic. To provide a comprehensive review of the literature on the association of meningioma with breast cancer, supported by a meta-analysis. A systematic PubMed search was performed up to April 2023 to identify articles on the association of meningioma with breast cancer. The following key words were used strategically: meningioma, breast cancer, breast carcinoma, association, relation. All studies reporting women diagnosed with meningioma and breast cancer were identified. The search strategy was not limited by study design or publication date but only included articles in English. Additional articles were identified via citation searching. Studies reporting a complete population of meningiomas or breast cancer patients throughout a specific study period and a proportion of patients with a second pathology could be used for the meta-analysis. Data extraction was performed by 2 authors in accordance with the Preferred Reporting Items for Systematic Reviews (PRISMA) statement. Meta-analyses regarding both populations were performed using a random-effects model. Risk of bias was assessed. The main measures were whether there was an increased prevalence of breast cancer in female patients with meningioma and whether there was an increased prevalence of meningioma in female patients with breast cancer. A total of 51 retrospective studies (case reports, case series, and cancer registry reports) describing 2238 patients with both diseases were identified; 18 studies qualified for prevalence analyses and meta-analysis. The random-effects meta-analysis (13 studies) revealed a significantly greater prevalence of breast cancer in female patients with meningioma than in the overall population (odds ratio [OR], 9.87; 95% CI, 7.31-13.32). Meningioma incidence in patients with breast cancer (11 studies) was greater than that in the baseline population; however, the difference according to the random-effects model was not statistically significant (OR, 1.41; 95% CI, 0.99-2.02). This large systematic review and the meta-analysis on the association between meningioma and breast cancer found nearly 10-fold higher odds of breast cancer in female patients with meningioma compared with the general female population. These findings suggest that female patients with meningioma should be screened more intensively for breast cancer. Further research is required to identify the factors causing this association.

Using SMS technology to improve quality of life and symptom management in the breast cancer patient population: A feasibility study.

e13619 Background: Cancer patients experience a wide range of negative side effects/symptoms from chemotherapy and radiation including pain, dehydration, nausea/vomiting, and diarrhea/constipation. Symptoms are distressing and decrease the overall quality of life and increase unnecessary hospitalizations and emergency visits. Symptom management and quality of life may be improved by using Short Message System (SMS) texting in cardiac and diabetic patient populations. The technology may also decrease costs for unnecessary emergency department (ED) visits by breast cancer patients. The purpose of this study was to determine if an SMS texting service can improve quality of life by improving symptom management. A secondary purpose was to evaluate if texting decreases emergency visits by breast cancer patients. Methods: This IRB-approved, consented study implemented an SMS texting program for breast cancer patients. Participants received two texts per day during their chemotherapy treatment period (6 months), one text being informational regarding symptom management and the second was one of encouragement and inspiration. Participants were called bi-weekly to complete the Distress Thermometer for Patients (NCCN). ED visits and/or hospital admission rates for the sample were collected. An exit interview measured satisfaction with the program in quantitative measures and theme analysis for qualitative measures. Twenty patients participated in this study, with 13 included in the data analysis. Results: SMS texting provided a change in treatment for symptom management in 40% of patients. Overall satisfaction with the SMS program was at the 89th percentile. Almost all participants felt supported and cared for due to bi-weekly calls by the investigators. Only 10% of the participants visited the emergency department, which is lower than historical averages. Data concerning the distress thermometer proved to be non-informative. Conclusions: SMS texting is feasible and easily integrated into the care of breast cancer patients. Texting technology may provide engagement with the care team leading to changes and improvement in symptom management during chemotherapy treatment. Further study of texting technology providing interactive abilities for patient-reported outcomes is warranted.