New Diagnosis Of Breast Cancer Research Articles

Kinetic Analysis and Metabolism of Poly(Adenosine Diphosphate-Ribose) Polymerase-1-Targeted 18F-Fluorthanatrace PET in Breast Cancer.

The poly(adenosine diphosphate-ribose) polymerase inhibitors (PARPi) have demonstrated efficacy in ovarian, breast, and prostate cancers, but current biomarkers do not consistently predict clinical benefit. 18F-fluorthanatrace (18F-FTT) is an analog to rucaparib, a clinically approved PARPi, and is a candidate biomarker for PARPi response. This study intends to characterize 18F-FTT pharmacokinetics in breast cancer and optimize image timing for clinical trials. A secondary aim is to determine whether 18F-FTT uptake in breast cancer correlates with matched frozen surgical specimens as a reference standard for PARP-1 protein. Methods: Thirty prospectively enrolled women with a new diagnosis of breast cancer were injected with 18F-FTT and imaged dynamically 0-60 min after injection over the chest, with an optional static scan over multiple bed positions starting around 70 min. Kinetic analysis of lesion uptake was performed using blood-pool activity with population radiometabolite corrections. Normal breast and normal muscle reference tissue models were compared with PARP-1 protein expression in 10 patients with available tissue. Plasma radiometabolite concentrations and uptake in tumor and normal muscle were investigated in mouse xenografts. Results: Pharmacokinetics of 18F-FTT were well fit by Logan plot reference region models of reversible binding. However, fits of 2-tissue compartment models assuming negligible metabolite uptake were unstable. Rapid metabolism of 18F-FTT was demonstrated in mice, and similar uptake of radiometabolites was found in tumor xenografts and normal muscle. Tumor 18F-FTT distribution volume ratios relative to normal muscle reference tissue correlated with tissue PARP-1 expression (P < 0.02, n = 10). The tumor-to-normal muscle ratio from a 5-min frame between 50 and 60 min after injection, a potential static scan protocol, closely corresponded to the distribution volume ratio relative to normal muscle and correlated to PARP-1 expression (P < 0.02, n = 10). Conclusion: This study of PARPi analog 18F-FTT showed that uptake kinetics invivo corresponded to expression of PARP-1 and that 18F-FTT quantitation is influenced by radiometabolites that are increasingly present late after injection. Radiometabolites can be controlled by using optimal image acquisition timing or normal muscle reference tissue modeling in dynamic imaging or a tumor-to-normal muscle ratio. Optimal image timing for tumor-to-normal muscle quantification in humans appears to be between 50 and 60 min after injection. Therefore, a clinically practical static imaging protocol commencing 45-55 min after injection may sufficiently balance 18F-FTT uptake with background clearance and radiometabolite interference for quantitative interpretation of PARP-1 expression invivo.

Traditional Chinese Medicine Herbs for Breast Cancer Prevention and Survival: A Narrative Review of Epidemiological Studies from Taiwan.

This review aims to describe the association of integrating traditional Chinese medicine (TCM) herbs into conventional medicine (CM) in preventing breast cancer and improving survival rates among breast cancer patients of Taiwan. Of 7 relevant studies, spanning 2014-2023, 4 investigated breast cancer risk in women with menopausal symptoms and other comorbidities. All 4 reported that TCM herbal use was associated with lower risks of developing breast cancer. Three studies investigated survival in newly-diagnosed breast cancer patients receiving CM. All reported that adjunctive TCM users had lower mortality rates than CM-only patients. However, the heterogeneity of study designs, populations, and interventions may limit the generalizability and robustness of the findings. TCM herbs may promote breast cancer prevention and survival when used alongside CM. More rigorous observational research and clinical trials in specific patient populations are needed to guide clinical decision-making.

Disparities in mental health screening for veteran women with a new diagnosis of breast cancer.

222 Background: Compared to the general population, mental health disorders, including depression, are higher for Veteran women. Breast cancer (BC) is the most commonly diagnosed cancer in this population and up to 50% of women will experience depressive symptoms after diagnosis, associated with poor prognosis and survival. An increasing number of Veteran women live in rural areas, where access to behavioral health care may be limited. This study sought to evaluate rural disparities in mental health screening and follow-up evaluation after a new BC diagnosis. Methods: Women Veterans with a new BC diagnosis were identified between 2017 and 2021. Data for mental health screenings [Patient Health Questionnaire (PHQ)-2, PHQ-9, General Anxiety Disorder-7] were collected subsequent to the first BC diagnosis. Rurality was defined per the USDA Rural-Urban Commuting Area (RUCA) codes framework to determine rurality based on population density and commuting patterns. Data were abstracted from several large VA and non-VA datasets, including the Corporate Data Warehouse (CDW) Outpatient files, non-VA Care Medical and Pharmacy System files, Program Integrity Tool, and VA Informatics and Computing Infrastructure for Oncology. Rurality data was specified using CDW designations combined with ZIP-code-level USDA RUCA information. All categorical variables were analyzed using chi-square tests. Means were tested using t-tests. Results: 14,225 Veteran women with a new BC diagnosis were identified. The mean age was 63.4 (SD 11.7). The most common documented race was White (30.6%), followed by Black (15.7%). 59.6% lived in an urban setting as opposed to rural setting (40.4%). In the entire population, only 14% had a mental health screening within 3 months of a cancer diagnosis. Veteran women living in an urban setting were more likely to be screened compared to those living in a rural setting (17.4% vs 9.2%, p &lt; 0.001). For women screened within 3 months, most screened negative, regardless of rurality (76.1% rural, 75.7% urban). Of women who had a positive mental health screen within 3 months, only approximately one-third (31.8% rural, 34.2% urban) had additional screening regardless of rurality. However, for those with a negative initial screen, urban Veterans were more likely to have any additional screening (17% vs 10.2%, p = 0.001). PHQ-2 was the most common mental health screening tool used (73.8%) followed by a combination of PHQ-9 and GAD-7 (9.6%). Conclusions: Mental health screening within 3 months of breast cancer diagnosis is low for Veteran women. There is a significant difference in screening between rural and urban populations. It is critical to both improve mental health screening overall in this population and bridge the disparity gap between screening in rural and urban Veteran women. This may impact not only mental health but also breast cancer outcomes during the period encompassing treatment and survivorship.

Left ventricular global longitudinal strain is worse in BRCA mutation positive breast cancer patients prior to cancer treatment and premature menopause.

Breast cancer patients with mutations in human tumor suppressor genes BRCA1 and BRCA2 are at higher risk of cardiovascular disease (CVD) than the general population, as they are frequently exposed to cardiotoxic chemotherapy, anti-estrogen therapy, radiation, and/or oophorectomy for cancer-related treatment and prophylaxis. Animal and cell culture models suggest that BRCA mutations may play an independent role in heart failure. We sought to evaluate cardiac structure and function in female BRCA1 and BRCA2 mutation carriers with breast cancer compared to BRCA wildtype women with breast cancer. We performed a 1:2 age- and hypertension-matched retrospective cohort study comparing BRCA1 and BRCA2 mutation carriers (n = 38) versus BRCA wildtype controls (n = 76) with a new diagnosis of breast cancer. Echocardiographic data were obtained within 6months of breast cancer diagnosis and prior to chemotherapy, anti-estrogen therapy, radiation, or oophorectomy. Left ventricular global longitudinal strain (LV-GLS), a highly sensitive marker of LV function, was measured using QLab 15 (Philips Healthcare). In the total cohort of 114 patients with a new diagnosis of breast cancer, the median age was 45 ± 11years and the prevalence of hypertension was 8%. There were no differences in traditional cardiovascular disease risk factors between cases and controls. BRCA carriers had lower LV-GLS (-18.1% ± 4.7% vs. -20.1% ± 3.8%, p = 0.02) and greater right atrial area (12.9cm2 ± 2.7cm2 vs. 11.8cm2 ± 2.0cm2, p = 0.04) compared to controls; however, both LV-GLS and right atrial area were within the normal range. Compared to controls, BRCA carriers had a trend toward worse LV posterior wall thickness (0.89cm ± 0.15cm vs. 0.83cm ± 0.16cm, p = 0.06) although not statistically significant. In women with newly diagnosed breast cancer and prior to treatment, LV-GLS was worse in BRCA1 and BRCA2 mutation carriers compared to those with BRCA wildtype. These findings suggest that BRCA mutations may be associated with subtle changes in cardiac function. Whether differences in GLS translate to increased cardiovascular risk in women with BRCA mutations needs to be further characterized.

Abstract PO3-23-02: Delays in breast cancer surgery during the COVID-19 pandemic: A population-based analysis

Abstract BACKGROUND: At various times during the COVID-19 pandemic, access to operating room resources were restricted in Ontario, Canada. This resulted in triaging of all non-urgent cases, including breast cancer (BC) surgery. Recent single institution studies have identified treatment delays during the immediate pandemic time period. The objective of this study was to assess the impact of the pandemic on wait times for breast cancer surgery at a population level. METHODS: We identified patients with a BC diagnosis between January 1, 2018 and November 30, 2021 in Ontario, Canada. Three cohorts were defined based on the following time periods: pre-pandemic (baseline) (January 2018 to 14 March 2020), immediate pandemic (March 15, 2020 to June 13, 2020), and peri-pandemic (June 14, 2020 to November 30, 2021). Time to event analysis was conducted for time to a patient’s first BC surgery. A subgroup analysis was conducted for patients who underwent neoadjuvant chemotherapy (NAC). RESULTS: The study cohort consisted of 36,639 patients with a new diagnosis of BC. Of them 30,862 patients underwent surgery (84.2%) within 18 months after diagnosis. The probability of BC patients undergoing surgery each month from their date of diagnosis was significantly lower (i.e. longer wait times) for patients diagnosed in the immediate and peri-pandemic period compared to patients diagnosed in the pre-pandemic period (log-rank P &amp;lt; 0.001). At eight weeks from date of diagnosis, the probability of having had surgery was 65.1% (95% CI: 64.5-65.8%) for patients diagnosed in the pre-pandemic period, 56.1% (95% CI: 53.6-58.6%) for immediate pandemic and 59.0% (95% CI: 58.2-59.8%) for peri-pandemic. Time for 80% of patients to have BC surgery was 5.4 months in the pre-pandemic, 5.9 months in the immediate pandemic, and 6.0 months in the peri-pandemic period. Among patients who received NAC (N=6,121; 16.7% of cohort), the probability of undergoing surgery in each month from the date of diagnosis was similar for patients diagnosed in the pre and peri-pandemic periods, but was higher (i.e. shorter wait time) for the cohort of patients diagnosed during the immediate pandemic time period (log-rank P &amp;lt; 0.001). At six months from date of diagnosis, the probability of surgery for patients who received NAC was 50.7% (95% CI: 48.9-52.5%), 61.6% (95% CI: 56.6-66.6%), and 50.9% (95% CI: 49.0-52.8%) for patients diagnosed in the pre-, immediate, and peri-pandemic periods respectively. Time for 80% NAC patients to have a surgery was 7.2 months in the immediate pandemic period, shorter than the 8.2 months in the pre-pandemic and 8.0 months in the peri-pandemic periods. CONCLUSIONS: In this large population-based study of BC patients in Ontario, we identified a delay in time to surgery in the immediate pandemic period that persisted into the peri-pandemic period. However, among patients receiving NAC there was a shorter wait time during the immediate pandemic and wait times for this group have returned to pre-pandemic levels. This is likely due to surgical prioritization of this group, despite pandemic related resource restrictions. Further research is needed to explore the regional variability and how use of neoadjuvant endocrine therapy interacted with surgical treatment timelines. Citation Format: Gary Ko, Amanda Roberts, Qing Li, Ning Liu, Toni Zhong, Eitan Amir, Anne Koch, Andrea Covelli, Vivianne Freitas, Emma Reel, Antoine Eskander, Tulin Cil. Delays in breast cancer surgery during the COVID-19 pandemic: A population-based analysis [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 PO3-23-02.

Abstract 3458: DNA methylation-predicted blood protein levels and breast cancer risk

Abstract Background: Blood DNA methylation (DNAm) profiles can be used to predict a variety of human physiologic traits that are associated with breast cancer incidence and plasma concentrations of over 100 proteins, including those involved in inflammation, coagulation, metabolism, and growth. DNAm predictions of circulating proteins, here referred to as “DNAm proteins,” may be useful in providing molecular insights into breast cancer etiology and could be a valuable resource for personalizing breast cancer risk prediction. Methods: The Sister Study is a nationwide, prospective cohort of 50,884 women with a family history of breast cancer designed to identify novel environmental and biological risk factors for breast cancer. Epigenome-wide DNAm data were previously generated using the HumanMethylation450 or MethylationEPIC arrays on baseline blood samples collected from two case-cohort samples, for a combined sample of 4,479 women. This sample included 2,151 (48%) women who were selected because they were diagnosed with breast cancer (1,673 invasive cancer and 478 ductal carcinomas in situ) in the 15 years (mean: 7.9 years) following blood draw. Blood levels of 109 DNAm proteins were estimated from DNAm profiles using the method developed by Gadd et al. (eLife, 2022). Weighted Cox regression models were used to estimate associations between these DNAm proteins and incident breast cancer; associations were considered statistically significant at a False Discovery Rate (q) ≤ 0.10. Results: In age and platform adjusted models, higher breast cancer rates were associated with higher DNAm-predicted blood concentrations of RARRES2, IGFBP4, and CCL21 and lower predicted concentrations of F7, SELL, CXCL9, CD48, and IL19. The strongest associations were observed for RARRES2 (per 1-SD increase, HR: 1.24, 95% CI: 1.10, 1.40, P= 6 × 10−4, q= 0.03) and F7 (per 1-SD increase, HR: 0.82, 95% CI: 0.74, 0.91, P= 3 × 10−4, q= 0.03). Estimates were similar after adjustment for known breast cancer risk factors and excluding those diagnosed within two years of their blood draw. Associations appeared stronger for invasive breast cancer. Conclusions: Using novel DNAm-based estimates of blood proteins, we identified associations between circulating proteins and breast cancer incidence. IGFBP4 and RARRES2 have previously been reported to be higher in newly-diagnosed breast cancer patients. We also identify new potential protein biomarkers related to immune response (CCL21, SELL, CXCL9, CD48, and IL19). Citation Format: Jacob K. Kresovich, Brett Reid, Doratha A. Byrd, Katie M. O'Brien, Zongli Xu, Clarice R. Weinberg, Dale P. Sandler, Jack A. Taylor. DNA methylation-predicted blood protein levels and breast cancer risk [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3458.

Feasibility of Prospective Assignment of Initial Method of Detection of Breast Cancer: A Multicenter Pilot Study

ObjectiveTo determine the feasibility of standardized, prospective assignment of initial method of detection (MOD) of breast cancer by radiologists in diverse practice settings. MethodsThis multicenter, retrospective study analyzed the rate of assignment of MOD in four geographically varied health systems. A universal protocol for basic MOD assignment was agreed upon by the authors before start of the pilot study. Radiologists at each site were instructed how to assign MOD. Charts were then reviewed to determine the frequency and accuracy of MOD assignment for all cases subsequently diagnosed with breast cancer. When available, data regarding frequency of tumor registry abstraction were also reviewed for frequency and accuracy. ResultsA total of 2,328 patients with a new diagnosis of breast cancer were evaluated across the sites over the study period. Of these patients, initial MOD was prospectively assigned by the radiologist in 94% of cases. Of the cases in which MOD was assigned, retrospective review confirmed accurate assignment in 96% of cases. ConclusionsProspective, standardized assignment of initial MOD of breast cancer is feasible across different practice sites and can be accurately captured in tumor registries. Standard collection of MOD would provide critical data about the impact of screening mammography in the United States.

Dose-Dense Chemotherapy Regimen for Breast Cancer Associated with Significant Decline in Ovarian Reserve.

Purpose: To determine the impact of dose-dense chemotherapy administration on ovarian reserve in women undergoing treatment for breast cancer. Patients and Methods: We conducted a retrospective cohort study of reproductive age women who underwent dose-dense chemotherapy regimens with doxorubicin hydrochloride and cyclophosphamide with or without paclitaxel for a new diagnosis of breast cancer. We compared pre- and post-treatment serum antimullerian hormone (AMH) levels and assessed changes in AMH over time. Results: Fifty-seven patients met inclusion criteria. Median pre-treatment AMH was 2.9 ng/mL, whereas post-treatment AMH was 0.1 ng/mL, demonstrating a dramatic reduction in AMH levels after treatment with a dose-dense regimen. This change was independent of age and was sustained over 12 months from treatment completion. Conclusions: Dose-dense chemotherapy regimens for breast cancer lead to marked and sustained decreases in AMH irrespective of patient age.

Implementation of a visual aid to improve disease comprehension in patients with new breast cancer diagnoses.

358 Background: Studies have shown that patients with new cancer diagnoses are overwhelmed due to the large amount of information presented at their initial oncology visit. Inability to meet these high informational demands has been associated with poorer outcomes. Most patient education is done verbally despite data showing that patients only retain 14% of verbal communication compared to 85% of information with visual aids. The aim of this study was to determine if implementation of a visual educational tool on breast cancer diagnosis and treatment would improve comprehension in patients with new diagnoses. Methods: We designed an educational tool to visually depict breast cancer subtype, stage, and treatment plan. We recruited English-speaking patients with new diagnoses of breast cancer who were seen for an initial oncology visit at the Mount Sinai Dubin Breast Center. Patients were randomized to receive the visual aid (intervention) or continue with standard-of-care (control). For patients randomized to the intervention arm, the oncologist used the visual aid to provide education on their diagnosis and treatment plan during the visit. All patients completed a survey at their initial visit and approximately 1 month after diagnosis. The survey included demographic information, patient preferences, and assessment of their understanding of diagnosis and treatment. The worksheet and surveys were piloted with 5 patients with breast cancer and modified based on their feedback. A knowledge score was calculated based on their survey responses with scores ranging from 2 (low knowledge) to 6 (all questions answered correctly). We utilized paired t-test to compare the means of knowledge scores at initial visit and 1 month follow up. Results: Twenty female patients were enrolled from 2022-2023 with a median age of 61 years. Ten patients were randomized to the intervention arm and 10 to the control arm. The initial mean knowledge score of the control group was 4.9 and the follow up mean score was 5.6 (P = 0.11). The initial mean score of the intervention group was 5.3 whereas the follow up mean score was 5.6 (P = 0.84). There was no significant difference between the intervention group and the control group (P = 0.944). An increase in overall scores was noted from initial to follow up survey in all groups. There was a complete elimination of all low scores (&lt; 3) across both groups in the follow up survey. Conclusions: Education at the initial visit improves understanding of breast cancer diagnosis and treatment. Our study demonstrated a standardized informational tool did not improve understanding when compared to individualized teaching with their oncologist. However, our study was limited to a single breast cancer center with a small sample size and English-speaking patients. Next steps include translation of the educational tool into additional languages, as well as expansion of this study to a larger patient population.

Direct and indirect effects of COVID-19 on short-term mortality of breast cancer patients.

We studied the COVID-19 impact in newly-diagnosed breast cancer (7,349 patients in 2019, and 5,563 in 2020). In 2020 there were two diagnostic drops: -37.2% (March-May), -15.8% (October-December). Early-stage at presentation (76.4% vs. 74.4%, p=0.0013), conserving surgery (71.0% vs. 67.0%, p<0.0001), chemotherapy (86.2% vs. 53.4%, p<0.0001), and radiotherapy (65.7% vs. 42.1%, p<0.0001) decreased in 2020 compared to 2019. COVID-19 occurred in 250 patients (4.49%). The time-dependent COVID-19 effect was associated with mortality (multivariable Cox analysis HR [95% CI] 2.26 [1.35-3.74]; p=0.0018). Survival within the year of diagnosis was 97.6% in 2020 and 98.3% in 2019; 30-day mortality was 1.13% in 2020 (1.07 in uninfected patients), and 0.61% in 2019. The year of diagnosis lost its prognostic relevance after adjusting for stage and treatment. These findings emphasize the critical role of continuity of care, which was disrupted during the pandemic, and underscore the need for policies minimizing treatment initiation delay in newly diagnosed breast cancer patients.

Lymph Node Positivity: Indication for Preoperative MRI?

The purpose was to determine what factors help predict benefit from preoperative MRI. We conducted an IRB approved retrospective review of patients with breast cancer who underwent preoperative MRI (2018-2021). Patients were divided into a cohort of no new disease detected on MRI versus new disease detected. Of 420 patients with a new diagnosis of breast cancer who underwent preoperative MRI, 17% had new multicentric, multifocal, or contralateral disease detected. There was no difference between the two cohorts for age (p = 0.23), race (p = 0.45), family history (p = 0.47), breast density (p = 0.14), or hormone status (p = 0.90). In multivariate analysis, age (p = 0.61, OR 0.99), race (p = 0.58, OR 1.26), family history (p = 0.54, OR 0.82), breast density (p = 0.83, OR 0.87), grade (p = 0.87, OR 1.09), tumor size (p = 0.37, OR 0.92), and use of neoadjuvant therapy (p = 0.41, OR 0.72) were not predictive of detection of additional new disease. Presence of positive nodes on ultrasound or mammogram was associated with new or multifocal disease on MRI (p = 0.0005, OR 3.48). Pre-MRI positive nodes increased the likelihood of detection of new disease (p = 0.0002, OR 3.04). Preoperative MRI resulted in more extensive surgery than indicated for 22.2% of the no new disease detected cohort and 6.9% of the new multicentric disease cohort (p < 0.001). Patients with nodal disease detected in their evaluation are more likely to have new multifocal, multicentric, or contralateral disease detected on MRI. The use of preoperative MRI may be particularly helpful in patients with node-positive disease in identifying additional disease that would alter surgical management.

Lactation Education for Surgeons: American Society of Breast Surgeons (ASBrS) Survey Demonstrates Strong Member Interest in Expanded Training.

The availability and extent of breastfeeding-specific surgical training has not been previously described. We aimed to survey breast surgeons on their lactation education and desire for additional knowledge. Members of the American Society of Breast Surgeons were invited via email to anonymously complete an electronic survey from 27 October 2021 to 23 January 2022. The survey content included demographic information, sources of lactation education, and desired topics and methods for further training. Descriptive statistics were used to analyze the data. A total of 2698 surveys were delivered and 542 (20.1%) completed. While nearly all respondents (99%) reported treating lactating patients at least once or twice per year, 78% reported that their training was inadequate. The most frequently cited sources of lactation information were peer-to-peer informal knowledge sharing (50%) and personal experience with breastfeeding (44%). Nearly all respondents (99%) agreed that formal lactation education would benefit breast surgeons. Specific topics of interest included management of patients with complications of lactation (48%), management of lactating patients with a new diagnosis of breast cancer (47%), and counseling patients with pregnancy-associated breast cancer who desire to breastfeed (46%). The most frequently recommended educational formats included presentation at a national conference (60%), evidence-based management guidelines (58%), webinar (55%), and workshop/course (47%). Breast surgeons self-report minimal formal training in the management of benign and malignant breast disease in lactating patients and strong desire for expanded education. Development of clinical practice guidelines and additional educational content for surgeons should be considered to meet the needs of this patient population.

Rates of reoperation after breast conserving cancer surgery in Western Australia before and after publication of the SSO-ASTRO margins guideline.

A 2014 SSO-ASTRO guideline on surgical margins aimed to reduce unnecessary reoperation after breast conserving surgery (BCS). We investigate whether publication of the guideline was associated with a reduction in reoperation in Western Australia (WA). In this retrospective, population-based cohort study, cases of newly-diagnosed breast cancer were identified from the WA Cancer Registry. Linkage to the Hospital Morbidity Data Collection identified index BCS for invasive cancer between January 2009 and June 2018 (N=8059) and reoperation within 90 days. Pre-guideline (2009-2013) and post-guideline (2014-2018) reoperation proportions were compared, and temporal trends were estimated with generalised linear regression. The pre-guideline reoperation proportion was 25.8% compared with 21.7% post-guideline (difference -4.0% [95% CI -5.9, -2.2, p<0.001], odds ratio [OR] 0.80 [95% CI 0.72, 0.89, p<0.001]). Absolute reductions were similar for repeat BCS (16.3% versus 14.6%; difference -1.8% [95% CI -3.4, -0.2, p=0.03]) and conversion to mastectomy (9.4% versus 7.2%; difference -2.2% [95% CI -3.4, -1.0, p<0.001]). Over the study period, there was an annual absolute change in reoperation of -0.8% (95% CI -1.2, -0.5, p<0.001). Accounting for this linear trend, the difference in reoperation between time periods was -0.5% (95% CI -4.3, 3.3; p=0.81), reflecting a non-significant reduction in conversion to mastectomy. Comparisons of pre- versus post-guideline time periods in WA showed reductions in reoperation that were similar to international estimates; however, an annual decline in reoperation predated the guideline. Analyses that do not account for temporal trends are likely to overestimate changes in reoperation associated with the guideline.

Prognostic Significance Of FOXP3+ Tumour-Infiltrating Tregs In Egyptian Breast Cancer Patients.

To evaluate the prognostic importance of tumour-infiltrating forkhead box P3 protein + regulatory T cells in breast cancer patients. The case-control study was conducted from January 2020 to March 2021 at the Kafrelsheikh University Hospital, Egypt, and comprised individuals with newly-diagnosed breast cancer who underwent conventionalsurgery, and controls who had a fibrocystic change of the breast. The density of tumour-infiltrating forkhead box P3 protein + regulatory T cells was assessed by immunohistochemistry. Overall survival and disease free-survival were assessed. Data was analysed using SPSS 25. Of the 100 patients having mean age 44.9±9.1 years, 76(76%) had moderate/strong forkhead box P3 protein expression in tumour-infiltrating regulatory T cells, and 24(24%) with no/low expression. On follow-up, Patients with moderate/strong expression had a significantly greater rate of recurrence (p<0.05). Disease-free survival was substantially shorter in patients with moderate/strong expression compared to those with little or low expression (p=0.035). Compared to individuals with no/low expression, patients with moderate/strong expression had a greater rate of mortality, but the difference was not statistically significant (p>0.05). High density of forkhead box P3 protein + regulatory T cellsin Egyptian women with breast cancer may serve as a prognostic indicator.

D87. Breast Conservation Therapy in The Augmented Woman

PURPOSE: Annually, approximately 37,500 augmented women will develop breast cancer. Augmented women are often counseled to remove their implants if they plan to receive breast conservation therapy (BCT=lumpectomy + radiotherapy), for fear of an elevated complication rate and aesthetic dissatisfaction if the augmentation is maintained. We hypothesized that the complication and revision rates will be similar amongst augmented women who receive BCT with or without explantation. METHODS: A retrospective chart review was performed to identify all women who presented with a breast augmentation and a new diagnosis of breast cancer from 2016-2022. Women who opted to have a mastectomy were excluded. The primary outcomes were complication rate and revision rate. RESULTS: 160 women were included and the mean follow up was 2.9 years. All women received a lumpectomy and adjuvant radiotherapy. Fifty-nine women received an explantation combined with lumpectomy; 101 opted to maintain their augmentation. Amongst the 101 women who maintained augmentation, 34% kept their current implants and 66% underwent an implant exchange coincident with their lumpectomy. The overall complication and revision rates were 13% and 27%, respectively. There was no difference in the complication rate (8% vs. 15.8%: p=0.1) or revision rate (26.3% vs. 26.9%; p=1) between explanted and augmented women undergoing BCT. Multivariate logistic regression identified that an implant was not an independent predictor for complications (OR=2.4,95% CI.57-8.7;p=0.24) whereas surgical site infection was an independent predictor for revision (OR=10.2, 95% CI 1.4-75.5;p=0.02). CONCLUSION: Breast augmentation is not a contraindication to BCT.

Comprehensive Reconstructive Care for Patients of All Gender Identities After Cancer of the Breast.

Breast cancer can affect anyone; therefore, it affects people of all gender identities. Reconstructive options after breast cancer must then address the needs of all people. Our institution is unique in its provision of both high-level comprehensive breast and gender affirmation care. In our practice, patients have expressed gender diverse identities during their breast cancer reconstructive journey. In these cases, goals have deviated from traditional breast restoration, gravitating toward gender-affirming mastectomy, or results often seen with "top surgery." We present a framework for the administration of breast cancer care and discussions of reconstruction from a lens of gender inclusivity. Breast cancer is a diagnosis that has been gendered, resulting in the erasure and exclusion of reconstructive needs for people affected by breast cancer that are not cisgender women. This is illustrated through the case of a nonbinary individual seen in breast cancer clinic for multifocal ductal carcinoma in situ. Our standard review of options of "going flat," implant-based reconstruction, and autologous reconstruction led to initial confusion given their early exploration of gender identity co-occurring with a new diagnosis of breast cancer. These scenarios can be challenging when viewed solely from the perspective of a breast reconstructive surgeon or a gender-affirming surgeon alone. Both perspectives are often needed. Our gender-affirming and breast reconstructive teams have discussed methods to identify patients who require more robust discussion of gender identity and reconstructive options in the setting of breast cancer, such as chest masculinization. By adding gender-affirming surgeons to the list of providers available to counsel breast cancer patients, we may be able to better provide early education on all reconstructive options and appropriately address the needs of transgender and gender diverse people affected by breast cancer.

Abstract P4-07-46: The Out-of-Pocket Cost of Breast Cancer Care in Nigeria: A Prospective Analysis

Abstract Introduction A major barrier to timely breast cancer diagnosis and care in Nigeria is attributable to the out-of-pocket cost of accessing healthcare services, despite the presence of a National Health Insurance Scheme (NHIS). Excessive out-of-pocket payments are often associated with a catastrophic health care expenditure (CHE). Despite the rising incidence of breast cancer in Nigeria, there is a paucity of economic data on the cost of care and the impact healthcare expenditure may have on a household. This study provides a comprehensive, prospective analysis of out-of-pocket spending for breast cancer care at a single tertiary care institution in South West Nigeria. Methods Consecutive patients undergoing curative intent surgery for a new diagnosis of breast cancer at Obafemi Awolowo University Teaching Hospital (OAUTH) between August 2019-April 2022 were approached for enrolment. A novel, context specific questionnaire was developed for this study and administered by trained personnel. The questionnaire was delivered to patients and caregivers during hospital admission and again during six-month follow-up. Participants were asked to estimate monthly household income and expenditures. Out-of-pocket direct and indirect expenses for breast cancer diagnosis and care were elicited. Where feasible, hospital accounting records and individual receipts were used to minimize recall bias. Sequelae of the out-of-pocket costs were also elicited, such as the use of debt financing and important forgone expenditures, such as childhood education. Capacity-to-pay was calculated for each household from the provided data as the sum of annual non-food expenditures. A CHE was defined as an aggregate healthcare expenditure that exceeded 40% of a household’s capacity-to-pay. All monetary figures were collected in the local currency (Naira) and converted to USD using the Nigerian Central Bank conversion rate of 415.83N to 1USD. Research ethics board approval was obtained for this study from OAUTH. Results Data were collected from 57 eligible patients with a mean age of 49.8 years (SD 12). The median household size was five (range 1-10) and the majority (75.4%) had completed at least secondary education. Seventy four percent (73.6%) of patients had ≥ Stage III disease at presentation and 89.5% received systemic chemotherapy. Only seven percent (4/received adjuvant radiotherapy. The mean annual capacity-to-pay for the cohort was $2,840.8 ($2,913.6). The mean cost of care, including direct and indirect expenditure was $3,379.7 (SD $3032.2). Excluding indirect costs, such as the cost of travel and self-reported lost income, the mean cost of direct expenditures associated with diagnosis and treatment was $1,705.3 (SD $1,236.6). Out of the 57 patients enrolled in the study 52 (91.2%) experienced a CHE as a result of their breast cancer treatment. As a result, 56% of households had to borrow money and seven percent withdrew children from school. Sixty-three percent of patients had no form of health insurance. Conclusions Over 90% of breast cancer patients at a tertiary care facility in Nigeria experience a CHE as a result of out-of-pocket costs associated with accessing care. This limits access to costly evidence-based adjuncts (i.e. radiotherapy) and has a negative impact on the wellbeing of the broader household. There is a need for national and global initiatives to ensure financial protection from the cost of breast cancer care. Citation Format: Funmilola Wuraola, Chloe Blackman, Israel Adeyemi Owoade, Adeoluwa Oluwaseyi Adeleye, Peter Kingham, Olusegun Alatise, Gregory Knapp. The Out-of-Pocket Cost of Breast Cancer Care in Nigeria: A Prospective Analysis [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-07-46.

Abstract P1-05-26: A blood-based lipid panel for personalized risk assessment of breast cancer

Abstract Background: The metabolic syndrome characterized in part by obesity, hyperinsulinemia, and insulin resistance is associated with increased risk of breast cancer. However there remains a need to establish a circulating biomarker metabolic profile indicative of increased risk of breast cancer. In the current study, we performed a comprehensive metabolomics screen to identify biomarkers indicative of increased risk of breast cancer. Methods: Unbiased metabolomics profiling was conducted on an initial Development Set of plasmas collected from 353 newly-diagnosed breast cancer cases and 141 controls. A deep learning neural network with 3 layers each containing 32 nodes based on 11 individual lipids corresponding to discrete lipid subclasses was built for risk prediction of breast cancer. The model was validated in an independent Test Set consisting of 79 breast cancer cases and 163 controls. Using a nested case:control matched design, we evaluated the performance of the model among body mass index (BMI) strata (≥ 30 or &amp;lt; 30kg/m2). Results: An 11-marker lipid biomarker panel encompassing lipid subclasses with known pro-inflammatory and tumor promoting roles yielded an AUC of 0.75 (95% CI: 0.70-0.79) for distinguishing breast cancer cases from controls in the Development Set. Predictive performance of the lipid panel was comparable when stratifying cases into hormone-receptor (HR) positive, HER2-positive/HR negative, and triple-negative breast cancer subtypes. The biomarker panel had an AUC of 0.74 (95% CI: 0.68-0.81) in the independent Test Set. The predictive performance of the panel was most pronounced among obese subjects (BMI ≥ 30) with an AUC of 0.81 (95% CI: 0.71-0.91) in the Test Set. Conclusions: The lipid-based biomarker panel has utility for identifying women with ‘metabolic obesity’ who are at increased risk of breast cancer and would benefit from tailored screening. Citation Format: Johannes Fahrmann, Ehsan Irajizad, Jody Vykoukal, Angelica Gutierrez Barrera, Jennifer Dennison, Ranran Wu, Banu K. Arun, Abenaa Brewster, Samir Hanash. A blood-based lipid panel for personalized risk assessment of breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-05-26.

Does mainstream BRCA testing affect surgical decision-making in newly-diagnosed breast cancer patients?

BackgroundGermline pathogenic variants mutations) in the BRCA1 and BRCA2 genes cause an increased risk of breast cancer and ovarian cancer. Mainstream cancer genetic testing (MCG) was introduced for breast cancer patients in our unit in 2013. Non-geneticist clinicians have been trained to offer genetic testing during initial treatment planning. We assessed the impact of timely test results on surgical decision-making. MethodsWomen who had undergone mainstream genetic testing for breast cancer between September 2013 and September 2018 were identified from a prospective database. Surgical data were collected retrospectively. Results580 eligible women had mainstream genetic testing. For 474 this was their first breast cancer diagnosis. The median age was 46 years (interquartile range (IQR) 38–57). The indications were: age ≤45 years for 233 (49%); triple negative disease for 192 women (40.5%); bilateral breast cancer age <60 for 39 (8%) and other for 72 (14%) women. The median time for test initiation to result was 18 days (IQR 15-21). 302 (64% received results before surgery. 88% of those found to have a BRCA mutation before surgery opted for bilateral mastectomy (compared to 5% with BRCA wild type). An additional 106 patients had a new diagnosis on a background of previous treatment. Of these all with a pathogenic variant chose bilateral mastectomy. ConclusionTimely BRCA gene testing influences surgeons’ and patients’ choice of surgery. It reassures women with a negative result and allows those with a positive result to take an active decision about the management of their future risk.

Abstract 10979: Long Term Risk of Coronary Artery Disease in Breast Cancer and Lymphoma Patients After Chemotherapy Plus Radiation Treatment vs Chemotherapy Only

Introduction: patients exposed to chest, breast or mediastinal RT, may present with accelerated atherosclerosis and CAD due to diffuse micro and macrovascular fibrosis. However, CAD risk has not been well established in a community-based study. Aims: Describe CAD risk in patients treated with chemotherapy with and without RT and evaluate the cumulative incidence of CAD (coronary revascularization, MI and abnormal stress test and coronary angiogram). Methods: From 1985-2010, we identified 744 patients with a new diagnosis of breast cancer or lymphoma, using the Rochester Epidemiology Project (REP) who received chemotherapy with or without RT. CAD risk was assessed by a proportional hazards model for time to event. RT was treated as a time dependent co-variable, with index date being chemotherapy start date, significance was considered as a p&lt;.05. Characteristics were evaluated by a multivariable Cox model to consider RT and time censoring. Results: 744 patients treated with chemotherapy were identified, of these 488 (65.6%) had breast cancer, 256 (34.4%) lymphoma, and 367 (49%) also received RT. The mean total RT dose was 5.5 ± 1.2 (Gy) for those that had CAD and 5.4 (Gy) ± 1.1 for non-CAD patients, p=0.4. The cumulative incidence of CAD events (accounting for death as a competing risk) at 5 and 10 years of follow-up was 1.9% (CI 1.14-3.2) and 3.06% (CI 2.01-4.7), respectively p&lt;.05 figure1. Baseline differences between those receiving RT or not, were not significant for DM and HTN; however, males and ages 70-79 were less likely to receive RT, table1. In a multivariable model, there was no difference in the CAD outcomes between those with and without RT, HR= 1.21 [0.48-3.06] p=.69, after adjusting for age, gender, DM, and HTN and those &lt;49 y/o had a lower risk of CAD. Table2 Conclusion: In this REP retrospective cohort study, the risk of developing a CAD event was similar between chemotherapy plus RT and chemotherapy only regimens, even after considering gender, age, HTN and DM.