Diagnosis Of Invasive Breast Cancer Research Articles

Patterns of screening and access to care in women diagnosed with breast cancer in a safety-net system.

1531 Background: Screening mammography reduces breast cancer specific mortality by allowing diagnosis at an earlier stage. Inconsistent guidelines and limitations in access to primary care are among factors that affect screening uptake. In this study, we reviewed patient characteristics, access to care, and uptake of screening mammogram (SMMG) prior to a breast cancer diagnosis at a safety-net system. Methods: Parkland Health (PH) is the safety-net system for Dallas County and is affiliated with the University of Texas Southwestern Simmons Comprehensive Cancer Center. Electronic medical records of patients with a new invasive breast cancer diagnosis between 2018 and 2019 at PH were reviewed and data on demographics and clinical presentation were collected. Patients were categorized based on SMMG uptake prior to their cancer diagnosis: never-screened, ever-screened (SMMG > 2 years prior to diagnosis) and recent-screened (SMMG within 2 years of diagnosis). Results: A total of 468 new breast cancer cases were identified (48.7% Hispanic; 32.9% Black). Of these, 12.2% were younger than 40 and 27.8% were 40-49. Payer mix included 64.7% uninsured and 34.8% Medicare/Medicaid. Half of the patients (50.6%) never had SMMG. Never-screened rate was higher among younger patients (98.2% in < 40; 53.8% in 40-49; and 39.4% in >50; p < 0.0001). Only 25.2% (118/468) of the patients had a SMMG within 2 years prior to their diagnosis. Among patients aged >40, 44.0% (181/411) were never-screened and 28.7% (118/411) were recent-screened. Screen-detection rate among patients >40 was 40.1% (165/411), of whom 22 (13.3% of screen-detects) were diagnosed with cancer on their first ever SMMG. Race/ethnicity, insurance status, and positive family history of cancer were not significantly different between never, ever, and recent-screened patients. Screening uptake correlated with nodal status, tumor size and stage at diagnosis. Patients who had a prior encounter at Parkland were more likely to have a SMMG. Patients established with Parkland primary care at diagnosis were more likely to have early-stage disease. In patients < 40, 24.6% presented with stage IV disease at diagnosis and 57.9% did not have a primary care provider. A positive family history of breast/ovarian cancer or any cancer was noted in 38.6% and 57.9% of patients < 40, respectively. Conclusions: In the cohort presented here, 27.8% of patients were between age 40-49, reflecting the impact of a gap in the guideline, which is now addressed in the most recent iteration of USPSTF guidelines. Connecting ED users to primary care, identifying higher risk individuals through family history, and increasing SMMG rate in the primary care setting are among strategies to reduce the rate of late-stage diagnosis of breast cancer, particularly among vulnerable patient populations.

Abstract PO5-09-05: Characteristics of newly diagnosed breast cancer patients at a large safety-net system: Implications for health equity and care delivery

Abstract Introduction: Despite the increased awareness and advocacy for health equity, racial and socioeconomic disparities remain prevalent among breast cancer patients. Since lack of access to care is a major barrier, safety-net systems that provide services for the uninsured/underinsured play a significant role in promoting health equity and eliminating disparities. Understanding the patient population treated within these systems, which are often resource-limited, can help develop strategies to improve care delivery and outcomes. Here, we describe characteristics of breast cancer patients treated at a large safety-net system. Methods: Parkland Health (PH) is the safety-net system for Dallas County, and is affiliated with the University of Texas Southwestern Harold C. Simmons Comprehensive Cancer Center (NCI-CCC). Electronic medical records of patients with a new invasive breast cancer diagnosis between 2018 to 2020 at PH were reviewed and data on demographics and clinical presentation were collected. Categorical data was summarized with counts and percentages and continuous data was summarized with median and interquartile range. Statistical comparisons used Chi-square test for categorical data and rank sum test for continuous data with a significance level of 0.05. Data from the National Cancer Database (NCDB) for the same period was used for comparison. Results: A total of 657 patients at PH were included in the analysis (50.2% Hispanic; 32.3% Black). Median age at diagnosis was 53 years (range 46-61), with 39.1% of patients < 50 (12.3% < 40). The majority of patients were uninsured at the time of diagnosis (67.0%). Hispanic patients were younger than others (median age 49 years (range 43-57) vs 57 (range 48-63), p < 0.01), with 51.2% < 50. Late-stage diagnosis was observed in 30.6% of patients (stage III 16.4%, stage IV 14.2%), and triple negative breast cancer (TNBC) accounted for 22.8% of cases. While the stage distribution was not statistically different between racial and ethnic subgroups (p=0.66), black patients were diagnosed with TNBC at a significantly higher rate compared to others (30.2% vs 19.3%, p < 0.01). Although a trend towards higher rate of HER2(+) disease was noted among Hispanics, this difference did not reach the level of statistical significance (22.7% vs 16.5%, p=0.06). One hundred eighty-nine patients (28.8%) were diagnosed outside PH. Compared to Black patients, Hispanic patients were more often diagnosed in the community (22.2% vs 32.4%, p=0.01). Of the 564 patients with stage I-III, 340 (60.3%) had T2-4 and 203 (36.0%) had node positive disease at diagnosis. Median time to treatment initiation (TTI) was 51 days (range 35-76) and was significantly longer in patients who were diagnosed in the community compared to those diagnosed at PH, median 63 days (range 44-96) vs 48 (range 34-70), p < 0.01. Compared to the NCDB, PH patients were younger (39.1% vs 18.4% < 50 years, p < 0.01), presented at a higher rate with late-stage disease (30.6% vs 13.2%, p < 0.01) and TNBC (22.8% vs 10.7%, p < 0.01), and had a longer median time from diagnosis to treatment initiation - 51 days (range 35-76) vs 33 (range 21-49), p < 0.01. Conclusion: Breast cancer patients at PH were significantly different from the national average, with over a third below the USPSTF recommended breast cancer screening age. The rate of late-stage diagnosis at PH was more than two-fold the national average. Lowering the screening age to 40, expansion of outreach mammography programs, improving patient navigation, and simplifying access to indigent care programs are among strategies to promote health equity. Considering the high disease burden among safety-net patients, a systematic effort to increase resources at safety-net health systems is warranted. Citation Format: Sarah Kashanian, Shifa Kanjwal, L. Steven Brown, Andrea Semlow, Mary Hodges, Robyn Cobb, Brad Walsh, Umber Dickerson, Navid Sadeghi. Characteristics of newly diagnosed breast cancer patients at a large safety-net system: Implications for health equity and care delivery [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-09-05.

Abstract PO2-11-02: Incidence, treatment patterns and outcomes of breast cancer during the first year of the COVID pandemic: A population-based study

Abstract Background: The COVID pandemic created significant challenges in breast cancer (BC) care which were most pronounced during 2020 when screening and treatment access were reduced. The aims of this study were to evaluate and compare the incidence of BC, treatment patterns, and outcomes during the year 2020 versus the immediate pre-pandemic (2018 and 2019) period. Methods: Using data from the Surveillance, Epidemiology, and End Results (SEER) program, we calculated age-adjusted incidence rates of ductal carcinoma in situ (DCIS) and invasive BC during 2018, 2019 and 2020, with a 95% confidence interval (CI) for each. In the invasive BC cohort, we compared chemotherapy and radiation utilization by year. To account for potential misclassification of cause of death (COD) during the pandemic, we evaluated outcomes by overall survival (OS) in the invasive cohort, defined as time from BC diagnosis until death from any cause. To assess the impact of COVID, OS was truncated at 12 months from diagnosis for each year and we compared OS at 12 months for patients (pts) diagnosed with invasive BC in 2020 versus 2018 and 2019. OS was compared in a multivariable Cox model with diagnosis year 2020 as the reference. The Cox model was adjusted for age at diagnosis, race and ethnicity, sex, tumor grade, histology, stage, tumor subtype, surgery, radiation, chemotherapy, marital status, median household income, and rurality. Results: There were 37,834 DCIS diagnoses, and 199,594 invasive BC diagnoses between 2018-2020, with the distribution by year shown in the table. In 2020, the age-adjusted incidence of female DCIS decreased to 31.0 cases per 100,000, and the age-adjusted incidence of female invasive BC decreased to 166.6 cases per 100,000. As shown in the table, the incidence of male BC did not change. Among females, the relative reductions in incidence from 2019 to 2020 were: 15% for DCIS, 12% for stage I, 6% for stage II, 3% for stage III, and 2% for stage IV. Comparing 2020 to 2018-2019, we observed small absolute decreases in the proportions of pts who had surgery (2%) or radiation therapy (2.8%), and a small absolute increase in chemotherapy (1.4%) (p< 0.001 for each). These treatment changes were present across each individual stage. The table shows the 12-month OS rates for each year of diagnosis. COVID was the COD for 77 pts in 2020, 43 pts in 2019 and 0 pts in 2018. In the Cox model, there were no significant differences in the risk of death between pts diagnosed 2018 and 2020 (adjusted Hazard Ratio: 0.95; 95% CI, 0.90 – 1.01; p=0.13) or between pts diagnosed 2019 and 2020 (adjusted Hazard Ratio: 0.95; 95% CI, 0.89 – 1.01; p=0.08). Conclusions: During the first year of the pandemic, the incidence of BC decreased significantly, largely driven by a decrease in DCIS and early-stage diagnoses. Of interest, there was no stage shift observed with respect to the incidence of stage III or de novo stage IV disease, and no change in male BC incidence. We hypothesize that the observed trends are due to a reduction in screening, but this needs further study. It will be critical to evaluate future trends in cancer incidence beyond 2020, as it is possible that the reduction in early-stage diagnoses represent missed diagnoses that will be identified at a later stage in subsequent years. Finally, while there was no difference in 12-month OS by year of diagnosis, the true impact of the COVID pandemic on BC-specific outcomes will require further follow-up. Citation Format: Jose Leone, Julieta Leone, Michael Hassett, Rachel Freedman, Jorge Avila, Carlos Vallejo, Nabihah Tayob, Sara Tolaney, Nancy Lin. Incidence, treatment patterns and outcomes of breast cancer during the first year of the COVID pandemic: A population-based 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 PO2-11-02.

Abstract PO4-02-10: Predictive Factors of Nodal Upstaging at Time of Surgery in Clinically Node Negative Patients Undergoing Neoadjuvant Chemotherapy

Abstract Introduction: Neoadjuvant chemotherapy (NAC) can be given with the intent of downstaging breast cancer or to provide prognostic information prior to any surgical intervention in both node negative (N0) and node positive patients (pts). Residual nodal disease following neoadjuvant chemotherapy generally indicates poorer overall prognosis relative to those who are node negative. Several risk factors have been postulated to predict the presence of occult lymph node metastasis: age at diagnosis, tumor size, status of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor (HER-2), and BMI. NAC has been shown to eradicate axillary lymph node metastasis in up to 40% of pts. This study aims to evaluate characteristics of clinically N0 pts who underwent NAC and were upstaged to node positive status at the time of surgery. We hope to identify patient related factors that may help predict the presence of occult nodal disease as well compare pathological complete response rate (PCR) in the breast between N0 and patients who were upstaged. Methods: Data was collected through retrospective chart review of the Stroger Cook County electronic medical records system (CERNER). Pts treated at John H. Stroger Hospital from 2017-2021 with a new diagnosis of cT2-T3 invasive breast cancer who were clinically and radiologically node negative and received NAC were included. We compared demographic data, staging information, cancer characteristics and pathologic complete response rates (PCR) in the breast between those who remained node negative and those who had positive sentinel lymph nodes at the time of surgery. Pts with prior breast cancer diagnosis and those who underwent treatments at an outside institution were excluded. Statistical analysis included 2-tailed t-test and 2-tailed fisher’s (p< 0.05). Results: A total of 98 pts were identified, 62 with complete data for analysis,11 were upstaged at the time of surgery. When comparing pts who had nodal upstaging to those that remained node negative at time of surgery there was no significant difference between average BMI (28.5), age of diagnosis (58 years). Most pts (73%) were T2 at presentation, of those with nodal upstaging at time of surgery, 20% were T3 or higher, while only 5% of those who were not upstaged at surgery were greater than T3 (NS). Upstaged pts had an average tumor size of 4.16 cm while non-upstaged on average were 2.85 cm (P< 0.01). ER positive pts (ER+) and PR positive (PR+) were more likely to have nodal upstaging post op (P< 0.0012, P< 0.0013) when compared to ER negative (ER-) and PR negative (PR-) respectively. The distribution of receptor status was significantly different between groups, the most common receptor status in upstaged patients was triple positive (63%) while triple negative was most common in non-upstaged (41%). Triple positive pts were more likely to be upstaged than those with other receptor statuses (64% vs 40%, p 0.0004). There was a 100% PCR rate in the breast among non-upstaged pts compared to 10% of upstaged patients (P< 0.0001). Among all triple negative pts, 42% had PCR, of ER-/PR-/HER2+, 60% had a PCR, ER+/HER 2 negative had a 40% PCR. Conclusion: Pts with larger presenting tumor size who are node negative at presentation and have undergone chemotherapy are more likely to have occult positive nodes at the time of surgery. ER positive pts and triple positive pts are also more likely to have occult positive nodes at time of surgery. While our sample is small, our breast PCR rate is consistent with other published literature. Further investigation confirming this with larger samples and multi-institutional investigation may help to establish these relationships and elucidate a predictive model. The optimal management of these patients is worthy of further study. Citation Format: Rangel Melissa, Julia Alexieva, Alison Coogan, Elizabeth Marcus, Julie Wecsler. Predictive Factors of Nodal Upstaging at Time of Surgery in Clinically Node Negative Patients Undergoing Neoadjuvant Chemotherapy [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 PO4-02-10.

Association between long-term use of calcium channel blockers (CCB) and the risk of breast cancer: a retrospective longitudinal observational study protocol

IntroductionCalcium channel blockers (CCB), a commonly prescribed antihypertensive (AHT) medicine, may be associated with increased risk of breast cancer. The proposed study aims to examine whether long-term CCB use is...

Concordance between freehand SPECT and conventional scintigraphy for sentinel lymph node detection in breast cancer

IntroductionFreehand SPECT can be a useful imaging technique for preoperative planning of sentinel lymph node biopsy (SLNB) as it allows localization of the sentinel node by 3D and real-time tomographic imaging and determines its depth after a few minutes of scanning.The aim of the study was to evaluate the correlation between the number of detected SNs between freehand SPECT images and lymphoscintigraphy (LS). Materials and methods100 patients with a diagnosis of invasive breast cancer and no clinical evidence of lymph node involvement prospectively underwent SLNB. The preoperative study included freehand SPECT imaging at 15min after injection and LS imaging at 25 and 60−90min after injection (early and late). The observed agreement was analyzed and a concordance study was performed between the number of SNs detected with freehand SPECT and LS. ResultsThe observed agreement in the detection of SNs between freehand SPECT and early LS was 72%; between freehand SPECT and late LS was 85%; and between early and late LS was 87%. In the concordance study, there was moderate concordance between freehand SPECT and early LS (kappa coefficient: 0.42); moderate-high concordance between freehand SPECT and late LS (kappa coefficient: 0.60); and moderate-high concordance between early and late LS (kappa coefficient: 0.70), with no significant differences between them (p-value=0.16). ConclusionFreehand SPECT showed a moderate-high concordance with conventional imaging studies and could be a valid alternative for the presurgical study of SLNB in breast cancer.

Concordancia entre SPECT portátil y la gammagrafía convencional para detección de ganglio centinela en cáncer de mama

IntroductionFreehand SPECT can be a useful imaging technique for preoperative planning of sentinel lymph node biopsy (SLNB) as it allows localization of the sentinel node by 3D and real-time tomographic imaging and determines its depth after a few minutes of scanning.The aim of the study was to evaluate the correlation between the number of detected SNs between freehand SPECT images and lymphoscintigraphy (LS). Materials and methodsOne hundred patients with a diagnosis of invasive breast cancer and no clinical evidence of lymph node involvement prospectively underwent SLNB. The preoperative study included freehand SPECT imaging at 15min after injection and LS imaging at 25 and 60–90min after injection (early and late). The observed agreement was analyzed and a concordance study was performed between the number of SNs detected with freehand SPECT and LS. ResultsThe observed agreement in the detection of SNs between freehand SPECT and early LS was 72%; between freehand SPECT and late LS was 85%; and between early and late LS was 87%. In the concordance study, there was moderate concordance between freehand SPECT and early LS (kappa coefficient: 0.42); moderate-high concordance between freehand SPECT and late LS (kappa coefficient: 0.60); and moderate-high concordance between early and late LS (kappa coefficient: 0.70), with no significant differences between them (p-value=0.16). ConclusionFreehand SPECT showed a moderate-high concordance with conventional imaging studies and could be a valid alternative for the presurgical study of SLNB in breast cancer.

Prognostic factors in non-metastatic HER2 'low' and HER2 'negative' breast cancer: single institute experience.

Comparison of prognosis and survival in human epidermal growth factor receptor 2 (HER2)-low and HER2-negative patients with early stage or locally advanced, hormone receptor-positive breast cancer. In aretrospective single center study, the patients with early stage or locally advanced stage, hormone receptor (HR)-positive [estrogen receptor (ER) ≥ 1% and/or progesterone receptor (PR) ≥ 1%] and HER2 negative or HER2 low invasive breast cancer diagnosis were included. Atotal of 444 patients were included in the study. Patients were divided into two groups: HER2 negative and HER2 low. There were 235 (53%) patients in the HER2 negative group and 209 (47%) patients in the HER2 low group. The HER2 low group had significantly longer 5‑year disease-free survival (DFS) than the HER2 negative group. The patients with lower Ki67 (< 20%) also had a longer 5‑year DFS. Nonmetastatic HR+/HER2 low breast cancer patients had better DFS than HR+/HER2 negative ones. The Ki67 level and HER2 low status were independent prognostic factors. Randomized clinical trials are needed in early stage HER2 low breast cancer patients.

Imaging changes and outcomes of patients undergoing active monitoring for ductal carcinoma in situ: Seven-year follow-up study

Rationale and ObjectiveTo determine the imaging changes and their associated positive predictive value (PPV) for invasive breast cancer in women undergoing active monitoring for DCIS. Materials and MethodsIn this seven-year follow-up retrospective IRB-exempted cohort study, we reviewed patients diagnosed with DCIS who elected active monitoring between 2003 to 2022 at a single academic institution. Imaging characteristics, histopathology at initial diagnosis, and subsequent follow-up were recorded. Low-risk DCIS was defined as low or intermediate grade and hormone receptor (HR) positive (estrogen and/or progesterone receptor positive) disease diagnosed in women at least 40 years of age. Progression was defined as subsequent ipsilateral invasive breast cancer diagnosis. ResultsThere were 39 patients with a median age of 58.4 years (IQR: 51.1 – 69.6 years) and a median follow-up of 4.3 years (range: 0.6-16.4 years). Nearly two thirds of patients (64%, 25/39) had stable imaging (range: 0.6-16.4 years) and remained progression-free during active monitoring. Among the remaining 14 patients (36%) there were 24 imaging findings which prompted 22 subsequent core needle biopsies (range: 1-3 biopsies per patient) and two surgical biopsies. The positive predictive value (PPV) of invasive cancer was 29% (7/24) overall and 38% (3/8) for masses, 33% (3/9) for calcifications, 17% (1/6) for non-mass enhancement, and 0% (0/1) for architectural distortion. ConclusionsOf the radiographic changes prompting an additional biopsy, development of a new mass (38%) and new calcifications (33%) had the highest PPV for invasive progression. Close imaging follow-up should be a critical component for patients undergoing monitoring for DCIS.

The accuracy of core needle biopsy in determining histological type and Scarf-Bloom-Richardson grade in invasive breast cancer

Core needle biopsy provides information not only on the histological diagnosis but also about tumor grade and different prognosis factors for breast cancer. This study was designed to determine the accuracy of percutaneous core needle biopsy (CNB) through comparative analysis of histological diagnosis and SBR tumor grade of invasive breast cancer between CNB and surgical excision specimen (SES). This was a retrospective cross-sectional study from January 2023 to July 2023. All patients with invasive breast cancer diagnosed by CNB and confirmed by surgical excision specimen (SES) examination were included in the study. Patients who received neoadjuvant chemotherapy were excluded. One twenty-three patients were assessed. All patients were female. The median age was 45 years (37 – 54). Invasive ductal carcinoma (IDC) was the major histological type of breast cancer (95.1%) followed by invasive lobular carcinoma (ILC) (4.9%). SBR grade 2 tumors accounted for 78.1% of cases. The majority of patients presented with locally advanced stage breast cancer (65.9%) or a metastatic disease (31.7%). Concordance for histological type was substantial (k= 0.79; p&amp;#60;0,001) whereas it was moderate (k= 0.45; p&amp;#60;0,001) for Scarf-Bloom-Richardson grade. Histological type on CNB correlates almost perfectly with that of the surgical excisional specimen in case of breast cancer. Nevertheless, the agreement of tumor grade between CNB and SES remains moderate, with a significant underestimation and overestimation rates.

Post Mastectomy Radiation Therapy Impact on Clinical Outcomes of Male Breast Cancer: A Meta-Analysis of Comparative Studies

Male breast cancer accounts for less than 1 percent of all cancer diagnoses in men. Because it is rare, it does not lend itself to large, randomized trials. In general, the approach to the treatment of early, non-metastatic male breast cancer has largely been extrapolated from female breast cancer trials though it is deemed to be a different disease. Data on early-stage post mastectomy radiation therapy (PMRT) is limited, and its benefits remain unclear. We conducted this meta-analysis to determine the impact of PMRT on recurrence patterns and survival outcomes using the available male breast cancer data. A review of the medical literature was conducted using online databases. Inclusion criteria consisted of English language, diagnosis of invasive non-metastatic male breast cancer (MBC), comparative studies of PMRT versus none, and studies that reported the incidence of local and distant recurrences as well as survival data in the compared arms. A meta-analysis using the Mantel-Haenszel method for calculating the weighted pooled relative risk (RR) under the fixed effects model was conducted. Subsequently, the heterogeneity statistic was incorporated to calculate the summary RR under the random effects model. Ten retrospective comparative studies with 3912 patients were included and analyzed. Eight studies reported survival data. Six and three studies reported local and distant recurrence incidence, respectively. PMRT did not have an impact on overall survival or distant recurrences. However, PMRT significantly lowered the RR of locoregional recurrences (RR = 0.53, 95% CI 0.31-0.92). In addition, when survival was analyzed by TNM stage and N status, PMRT was found to have a significant reduction in RR of death in stage III (RR = 0.85, 95% CI 0.75-0.97), N1 (RR = 0.77, 95% CI 0.61-0.98), and N2 (RR = 0.61, 95% CI 0.49-0.78) disease. This is the first meta-analysis to show that PMRT is associated with a lower relative risk of death in stage III MBC as well as N1 and N2 disease. It also demonstrates a significant reduction in RR of locoregional recurrences. In the absence of randomized clinical trials, it represents the most compelling data supporting the use of PMRT in this MBC patient population using MBC data.

Optimized Bayesian convolutional neural networks for invasive breast cancer diagnosis system

Deep learning (DL) has depicted unprecedented results in the diagnosis of invasive ductal carcinoma (IDC). However, most DL methods are not able to infer the uncertainty in their predictions, and are often too confident which may cause undesirable consequences. The ability of DL models to express their uncertainty in their predictions is particularly important in diagnosing diseases. Therefore, this paper proposes an uncertainty-aware approach called optimized Bayesian convolutional neural network (OBCNN) for the automated detection of IDC from histopathology images and is capable of estimating and inferring the uncertainty in its predictions. The proposed OBCNN employs an approximate Bayesian version of a pre-trained convolutional neural network (CNN) model named ResNet101V2 that is fine-tuned to the histopathology images of IDC. The Bayesian approximation is performed by adding Monte Carlo dropout (MC-dropout) to ResNet101V2 architecture. Due to the effect of MC-dropout on the obtained posterior predictive distribution (PPD), the value of MC-dropout should be chosen carefully because if the MC-dropout value is too large, the predictive distribution (PD) will be very diverse. Whereas if the MC-dropout value is very small, the PD will be very similar. Therefore, an optimization algorithm known as the slime mould algorithm is utilized to set the optimal value of the MC-dropout. During inference, the proposed OBCNN runs for T forward passes to configure the PPD. The mean, standard deviation (SD) and entropy are then calculated over the obtained PD to estimate the predictive uncertainty (PU) of the OBCNN. The proposed OBCNN achieved an accuracy of 93.83%, a precision of 96.14%, a G-mean of 93.04%, False Negative Rate of 4.72%, and False Positive Rate of 9.96 %. The proposed OBCNN has also been compared with recent related work, the comparison’s results demonstrated that OBCNN performed better in the diagnosis of IDC.

Missing Components of Receptor Status Among Women With Invasive Breast Cancer

There are well-known differences in patient outcomes and effective therapeutic options across subtypes of breast cancer (BC), defined by the status of estrogen receptor, progesterone receptor, and erb-B2 receptor tyrosine kinase 2 (ERBB2 [formerly HER2]) expression, making testing for these receptors part of the routine workup for all patients with a diagnosis of invasive BC. Despite its importance, this information is missing in some BC cases. To identify female patients with BC without record of testing for estrogen receptor, progesterone receptor, or ERBB2 status, defined as missing components of receptor status (MCRS). This cross-sectional study used data from National Cancer Institute's Surveillance, Epidemiology and End Results Program of 18 population-based registries from women with a diagnosis of invasive BC (excluding death certificate-only and autopsy cases) from January 2012 to December 2016. The final analyses were completed in February 2022. The primary outcome was MCRS. Those with MCRS were summarized by age, race, stage at diagnosis, reporting source, primary payer, and geography. Multivariable logistic regression was used to estimate adjusted odds ratios (aORs) for MCRS. Overall, 321 913 patients with invasive BC were included (1928 [1%] American Indian or Alaska Native, 28 173 [9%] Asian or Pacific Islander, 36 357 [11%] Black, and 252 447 [78%] White individuals); of these, 15 250 (4.7%) had MCRS. The multivariable model showed that the odds of MCRS were higher in women 80 years or older compared with those younger than 49 years (aOR, 1.75; 95% CI, 1.65-1.88), Black compared with White women (aOR, 1.09; 95% CI, 1.00-1.16), and those with distant stage or unknown/unstaged cancer at diagnosis compared with a local stage at diagnosis (aOR, 3.33; 95% CI, 3.17-3.50; and aOR, 19.39; 95% CI, 18.15-20.72; respectively). With hospital inpatient/outpatient or clinic as the reference group, cases reported by laboratory only, nursing/convalescent home/hospice, and a physician's office were more likely to have MCRS (aOR, 1.42; 95% CI; 1.28-1.60; aOR, 9.37; 95% CI, 6.03-14.53; and aOR, 2.32; 95% CI, 2.06-2.62; respectively). Adjusted odds of MCRS were higher for the categories of insured/no specifics and insurance status unknown compared with those who were insured. The adjusted odds of MCRS were higher in rural compared with urban areas (aOR, 1.08; 95% CI, 1.03-1.15). The results of this cross-sectional study of women with a diagnosis of invasive BC suggest that despite a standard of care recommended by all expert guidelines, there needs to be greater focus on hormone receptor and ERBB2 testing in all women with invasive BC. The results of this study may help clinicians, public health practitioners, and policymakers target affected populations to minimize or eliminate this critical health disparity and help save more lives.

Three-Dimensional Breast Cancer Model to Investigate CCL5/CCR1 Expression Mediated by Direct Contact between Breast Cancer Cells and Adipose-Derived Stromal Cells or Adipocytes.

The tumor microenvironment (TME) in breast cancer is determined by the complex crosstalk of cancer cells with adipose tissue-inherent cells such as adipose-derived stromal cells (ASCs) and adipocytes resulting from the local invasion of tumor cells in the mammary fat pad. This leads to heterotypic cellular contacts between these cell types. To adequately mimic the specific cell-to-cell interaction in an in vivo-like 3D environment, we developed a direct co-culture spheroid model using ASCs or differentiated adipocytes in combination with MDA-MB-231 or MCF-7 breast carcinoma cells. Co-spheroids were generated in a well-defined and reproducible manner in a high-throughput process. We compared the expression of the tumor-promoting chemokine CCL5 and its cognate receptors in these co-spheroids to indirect and direct standard 2D co-cultures. A marked up-regulation of CCL5 and in particular the receptor CCR1 with strict dependence on cell-cell contacts and culture dimensionality was evident. Furthermore, the impact of direct contacts between ASCs and tumor cells and the involvement of CCR1 in promoting tumor cell migration were demonstrated. Overall, these results show the importance of direct 3D co-culture models to better represent the complex tumor-stroma interaction in a tissue-like context. The unveiling of tumor-specific markers that are up-regulated upon direct cell-cell contact with neighboring stromal cells, as demonstrated in the 3D co-culture spheroids, may represent a promising strategy to find new targets for the diagnosis and treatment of invasive breast cancer.

Breast density quantitative measures and breast cancer risk among screened Black women.

Mammographic density is a strong predictor of breast cancer but only slightly increased the discriminatory ability of existing risk prediction models in previous studies with limited racial diversity. We assessed discrimination and calibration of models consisting of the Breast Cancer Risk Assessment Tool (BCRAT), Breast Imaging-Reporting and Data System density and quantitative density measures. Patients were followed up from the date of first screening mammogram until invasive breast cancer diagnosis or 5-year follow-up. Areas under the curve for White women stayed consistently around 0.59 for all models, whereas the area under the curve increased slightly from 0.60 to 0.62 when adding dense area and area percent density to the BCRAT model for Black women. All women saw underprediction in all models, with Black women having less underprediction. Adding quantitative density to the BCRAT did not statistically significantly improve prediction for White or Black women. Future studies should evaluate whether volumetric breast density improves risk prediction.

Identification of intraductal component by core-biopsy in invasive breast cancer and its impact on pCR achievement.

e12554 Background: Core biopsy is considered to be a highly accurate method of gaining a preoperative histological diagnosis of invasive breast cancer (IBC). Intraductal component (IC) is often an accompanying element of IBC. Due to the growing interest in the use of minimally invasive interventions in IBC treatment, in particular vacuum-aspiration biopsy, the accurate determination of the presence of an IC before surgery becomes crucial, since the presence of IC is an exclusion criterion in many trials. Methods: We retrospectively analyzed data from 505 patients treated in 2020-2022 for whom information about diagnostic core biopsy and postoperative histology were available with an indication of IC presence. 274 patients received neoadjuvant systemic therapy (NST) and we assessed the role of IC in achieving pCR in this subgroup. Results: In the overall population (505 pts), intraductal component was found in 167 (33.1%) pts by core-biopsy and in 294 (58.2%) pts on postoperative histology. For the overall population, sensitivity was 44.56% (95% CI 38.79 to 50.44%), specificity was 82.94% (95% CI 77.17to 87.75%), positive predictive value was 78.44% (95% CI 72.47 to 83.42%), negative predictive value was 51.78% (95% CI 48.79 to 54.75%) and false negative rate was 55.4%. The presence of an intraductal component was significantly associated with the status of receptors on the surface of tumor according to core-biopsy (HR+/HER2- = 123 from 347 pts, HER2+ = 32 from 84 pts, HR-/HER2- = 15 from 74 pts. p=0.003) and according to postoperative histology with exception of patients achieved pCR (HR+/HER2- = 66 from 102 pts, HER2+ = 9 from 18 pts, HR-/HER2- = 12 from 33 pts. p=0.014). In the population without NST (231 pts), intraductal component was found in 85 (36.7%) pts by core-biopsy and in 188 (81.4%) pts on postoperative histology. For this population, sensitivity was 44.15% (95% CI 36.93 to 51.56%), specificity was 95.56% (95% CI 84.85 to 99.46%), positive predictive value was 97.65% (95% CI 91.38 to 99.39%), negative predictive value was 29.05% (95% CI 26.22 to 32.06%) and false negative rate was 55.8%. In the population which underwent NST (274 pts), intraductal component was found in 81 (29.6%) pts by core-biopsy and in 106 (38.8%) pts on postoperative histology. For this population, sensitivity was 45.28% (95% CI 35.59 to 55.25%), specificity was 79.76% (95% CI 72.88 to 85.56%), positive predictive value was 58.54% (95% CI 49.47 to 67.06%), negative predictive value was 69.79% (95% CI 65.66 to 73.63%) and false negative rate was 53.7%. pCR rate was 44.3% (121 pts). Presence of intraductal component in core-biopsy specimen did not significantly impact pCR achievement (p=0.374). Conclusions: Core-biopsy is not very effective tool in diagnosis of intraductal component preoperatively. pCR achievement is not dependent on presence of IC in core-biopsy specimen. Presence of IC is significantly associated with receptor status of the tumor.

The somatic mutation profile of breast cancer in Uganda.

582 Background: Breast cancer, the most common cancer in sub-Saharan Africa (SSA), is characterized by poor survival compared with resource-rich regions. A variety of factors are responsible for this disparity and include late stage at presentation, limited diagnostic and therapeutic options, and potentially biologically more aggressive disease. The application of next generation sequencing to cancer specimens in resource-rich regions has identified new molecular mechanisms. However, such molecular testing has generally not been applied to tumors from SSA where the aggressive nature and younger age of women with breast cancer argues for the potential for novel pathogenic mechanisms. Here, we describe the somatic mutation profile of breast cancer in Uganda. Methods: We enrolled 100 consecutive women with a new diagnosis of invasive breast cancer at the Uganda Cancer Institute (UCI) in Kampala - the primary cancer center of Uganda and neighboring countries. Histopathologic classification was performed at the UCI and revaluated in a blinded fashion at the Fred Hutchinson Cancer Center (Seattle, WA). Demographic and clinical data were obtained. A biopsy specimen of the tumor tissue was obtained, snap frozen, processed using standard protocols to obtain DNA, and sequenced using the clinically-validated UW-OncoPlex assay, identifying all classes of variants and mutations. Results: We analyzed data from 100 women with a histologically-confirmed diagnosis of breast cancer between the ages of 35 and 65 - the vast majority of whom presented with either stage 3 or stage 4 (92%). All 100 tumor specimens were successfully sequenced, with, 96 (96%) demonstrating somatic mutations. The most commonly altered gene was TP53, with mutations in 65% of patients, with identified variant classes including truncations (18), missense (19), and copy loss (33). PIK3CA mutations were identified in 36% of patients, while copy gain or amplification were identified in MYC (50%), CCND1 (31%), FGFR1 (26%). EGFR (9%), and ERRB2 (24%). Nearly half of the women had either a mutation in BRCA1 (24%) or BRCA2 (24%); 6 (6%) of the tumors expressed mutations in both BRCA1 and BRCA2. Conclusions: We identified a diverse landscape of somatic mutations - the prevalence of BRCA1, BRCA2, and PIK3CA mutations are considerably higher than in other documented populations. A better understanding of the mutational profile can provide biological insights, inform prognosis, and serve as a predictive biomarker. As mutations in BRCA1/2 and PIK3CA can potentially be treated with targeted therapies (e.g. PARP inhibitor, PI3K inhibitor), such data can inform policymakers, allow for inclusion of these therapeutics in the formulary and in the WHO Model List of Essential Medicines, and reduce health disparities. Notably, all cases were successfully sequenced, with 96% of cases demonstrated somatic mutations, even without employing specific enrichment strategies commonly used in high-income countries.

PAVING the path to wellness: Lifestyle medicine to improve outcomes in breast cancer survivors.

e24053 Background: Lifestyle medicine emphasizes the role of 6 pillars in preventing chronic disease and improving health: nutrition, physical activity, sleep, stress management, social connection, and avoiding risky substance use. While most oncologists are aware of the role of these factors in reducing risk of recurrence and improving outcomes, there are numerous barriers to addressing these lifestyle factors during clinic visits. The PAVING the Path to Wellness for Breast Cancer Survivors program (PAVING) is a 12-week lifestyle medicine group intervention designed to deliver lifestyle medicine guidelines and practices to cancer survivors in a supportive setting. This study assessed short-term impacts of PAVING on behavioral and psychological outcomes. Methods: 101 women who completed PAVING since 2019 were invited to complete a survey. Inclusion criteria were primary oncology treatment at Massachusetts General Hospital, age &gt; 22, diagnosis of invasive breast cancer (Stages I-III) within past 5 years, ECOG score 0-1, and English fluency. 16 enrolled in the study, 13 of whom fully completed the survey. The REDCap survey included the REAP-S and EHQ nutrition scales, IPAQ-SQ physical activity measure, COPE Inventory for coping skills, Psychological Wellbeing Scale, PROMIS-QOL scale, and ratings of the impact of the program on well-being. Statistical analysis was completed in SPSS. Results: The participants, N = 16, were women above the age of 22 with a primary diagnosis of breast cancer. Analysis found while ASCO recommends a minimum of 150 min/week of moderate-vigorous exercise, PAVING participants achieved a median of 255 min/week (120 to 420). A Spearman’s rank correlation found a significant positive relationship between fruit intake and self-rated dietary improvement due to PAVING, r(13) = .764, p = .002. A significant positive relationship also existed between PAVING-attributed emotional well-being improvements and general mental health, r(13) = .615, p = .025. Participants strongly agreed PAVING improved their confidence in their ability to cope (M = 1.9, SD = .76) and set goals (M = 1.92, SD = .862). Participants agreed their quality of life (QOL) improved since completing PAVING (M = 2, SD = .816); QOL ratings (M = 1.69, SD = .751) reflect very good-to-excellent QOL in the average PAVING participant. Conclusions: PAVING Participants report positive lifestyle practices, many attributed to the program, supporting further investigation of this program for patients with cancer. Mental well-being, QOL, and fruit intake were all positively correlated with self-rated growth resulting from PAVING. Participants exceeded guidelines for physical activity, which has been shown to reduce risk of breast cancer recurrence. PAVING is an effective lifestyle-medicine intervention for breast cancer survivors, and expansion will enable a broader population to improve outcomes following diagnosis and treatment.

Adolescent Physical Activity and Breast Cancer Risk in Young Women: Findings From the ProF-SC Study

Study Purpose: The incidence of breast cancer (BC) in young women under age 40 years has increased substantially over time, underscoring the need for a better understanding of early life modifiers of risk. We examined the association of recreational physical activity (RPA) with BC risk before age 40 years, focusing on RPA during the adolescent window of susceptibility. Methods: We used data from the ProF-SC Study, which is enriched for young women at increased risk for BC. We conducted an ambidirectional cohort analysis that included women, aged ≤ 55 years at baseline, who were enrolled within 5 years of their first primary BC diagnosis or had no history of BC at baseline (n = 14,865). Women reported by baseline questionnaire their average levels of moderate and strenuous RPA during adolescence (12–17 years), which we converted to total metabolic equivalents per week (METs-per-week) and categorized into quartiles after adjusting for baseline age. We conducted attained age analyses until 40 years using multivariable Cox proportional hazards regression models adjusted for baseline sociodemographic and lifestyle factors. Follow-up started at age 18 years and ended at age at first invasive BC diagnosis, last follow-up, or 40 years, whichever came first. Results: There were 1,646 BC diagnoses before age 40 during 30,5594 person-years of follow-up. Being in the highest vs. lowest quartile of adolescent RPA was significantly associated with a 16% reduced risk of BC until age 40 before adjustment for baseline RPA (HR = 0.84, 95% CI = 0.73–0.97). This association was attenuated and no longer statistically significant after adjustment for baseline RPA (HR = 0.89, 95% CI = 0.77–1.04). We identified a statistically significant multiplicative interaction between adolescent and baseline RPA (interaction P value = 0.03). A one standard deviation increase in METs-per-week of baseline RPA was associated with a 5% reduced BC risk for women in the 10th percentile of adolescent RPA (HR = 0.95, 95% CI = 0.90–1.00) and an 11% reduced risk in the 90th percentile (HR = 0.89, 95% CI = 0.84–0.95). Conclusions: These findings suggest that adolescent physical activity might reduce breast cancer risk in young women and underscore the importance of maintain or increasing RPA levels across the lifecourse.

Vitamin D and Calcium Supplement Use and High-Risk Breast Cancer: A Case-Control Study among BRCA1 and BRCA2 Mutation Carriers.

The role of vitamin D and calcium use in the development of breast cancer among women in the general population is not clear. Furthermore, whether vitamin D and calcium supplement use are associated with breast cancer in high-risk populations has not been evaluated. Thus, we evaluated the association between vitamin D and/or calcium supplement use and breast cancer among women with a pathogenic variant (mutation) in BRCA1 or BRCA2. BRCA mutation carriers enrolled in a longitudinal study were invited to complete a supplemental questionnaire on lifetime supplement use. Cases included women with a prevalent diagnosis of invasive breast cancer, and controls had no history of breast cancer. Vitamin D and calcium use were categorized as never/ever use, and as tertiles of supplement intake (total average daily supplement use). Unconditional logistic regression was used to estimate the odds ratio (OR) and 95% confidence intervals (CIs) of breast cancer. This study included 134 breast cancer cases and 276 controls. Women who used vitamin D-containing supplements had 46% lower odds of having breast cancer compared to those who never used supplements (OR 0.54; 95% CI 0.31, 0.91; p = 0.02). Increasing vitamin D and calcium supplement intake was inversely associated with the odds of having breast cancer (p-trend = 0.04). Findings were suggestively stronger among BRCA1 mutation carriers; however, analyses were limited by small strata. These findings suggest a potential inverse association between vitamin D and calcium supplementation and BRCA breast cancer. Additional studies are warranted to confirm these findings and accurately inform clinical care guidelines.