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Introduction: Despite the recent overall improvement in survival for patients with breast cancer, racial disparities in outcomes persist. While studies have demonstrated that socioeconomic factors and access to treatment play a role, differences in tumor biology may also contribute. Black women are significantly more likely to develop triple negative breast cancer (TNBC), the deadliest of the breast cancer subtypes, with more TNBC patients progressing to incurable, metastatic disease than patients with any other breast cancer subtype. Studies have demonstrated that TNBC patients who achieve a pathologic complete response (pCR), defined as no residual invasive cancer in the breast or lymph nodes after neoadjuvant chemotherapy (NAC), have improved survival. We hypothesize that rates of pCR and overall survival (OS) in patients with TNBC may differ by race/ethnicity, which may account in part for the disparities in outcomes observed. Methods: Adult female patients with stage I-III TNBC diagnosed in 2010-2019 who received NAC followed by surgery were identified from the National Cancer Database (NCDB). Race/ethnicity was defined as Hispanic (H), Non-Hispanic White (NHW), Non-Hispanic Black (NHB), Non-Hispanic Asian (NHA), and Non-Hispanic Other (NHO). pCR was defined as no invasive cancer in either the breast or axilla (ypT0/is,N0) at surgery. Logistic regression was used to estimate the association of race/ethnicity with achievement of pCR after adjustment for covariates. Unadjusted OS was estimated using the Kaplan-Meier method, and the log-rank test was used to compare groups. Cox Proportional Hazards models were used to estimate the association of race/ethnicity and achievement of pCR with OS after adjustment for covariates. Additional interaction and subgroup analyses were also conducted. Results: Of the 40,890 patients identified, 29.8% (n=12,173) demonstrated pCR after NAC. The unadjusted 5-year OS rates for those who achieved pCR were significantly higher compared to patients with no pCR (0.917, 95% CI 0.911-0.923 vs 0.667, 95% CI 0.661-0.673, log-rank p< 0.001). Hispanic patients were more likely to achieve pCR (OR 1.19, 95% CI 1.08-1.31, p=0.001), and NHB patients were less likely to achieve pCR (OR 0.89, 95% CI 0.83-0.95, p=0.001) compared to NHW, even after adjustment. Unadjusted OS was also notably lower for NHB patients compared to every other race group (5-year OS rate: NHB 0.709 vs NHW 0.746 vs NHO 0.771 vs H 0.772 vs NHA 0.816, log-rank p< 0.001); however, this difference did not persist after adjustment for patient and disease factors, including achievement of pCR. Interval from diagnosis to start of chemotherapy (OR 0.95, 95% CI 0.94-0.96, p< 0.001) and duration after chemotherapy start to surgery (OR 1.02, 95% CI 1.02-1.03, p< 0.001) were associated with the odds of achieving pCR. Overall, the effect of achieving pCR on OS did not differ by race/ethnicity (interaction p=0.10). Discussion: Achieving pCR after NAC in patients with TNBC is associated with a significant improvement in OS. Yet, rates of pCR appear to differ based on race/ethnicity, with NHB patients demonstrating significantly lower rates of pCR than NHW patients, which may contribute to the disparities in survival outcomes observed. In addition to addressing socioeconomic factors and access to treatment, further research examining whether biological differences exist based on race that influence response of TNBC to current standard therapies is essential for improving survival outcomes for this disproportionately affected patient population. Citation Format: Hannah E. Woriax, Samantha M. Thomas, Jennifer K. Plichta, Laura H. Rosenberger, Astrid Botty van de bruele, Akiko Chiba, Gayle DiLalla, Carolyn Menendez, E Shelley Hwang, Maggie L. DiNome. The effect of race on pathologic complete response rates and overall survival in patients with triple negative 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 P1-06-02.

Background: The predictive and prognostic value of the 21-gene recurrence score (RS) has emphasized the importance of tumor biology and minimized the credence of a limited (1-3 positive) nodal burden. The practice changing results of RxPonder demonstrated that post-menopausal women with 1-3 positive lymph nodes (pN1) and a RS of ≤25 did not necessarily benefit from adjuvant chemotherapy. Given that RS influences adjuvant therapy decision-making more significantly than nodal status, it is unclear whether axillary staging with sentinel lymph node biopsy (SLNB) has a continued role in the surgical care of post-menopausal patients otherwise presenting with early stage, clinically node negative (cN0) hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) invasive breast cancer. In this context, the de-escalation of axillary staging, especially in the presence of a low RS, is an area of active investigation. To help elucidate this further, we sought to estimate the association of RS with pathologic nodal stage. Methods: Using the 2004-2019 National Cancer Database (NCDB) Patient User File (2022 release), we evaluated the association of RS with the incidence of pN0, pN1 and pN2-3 disease. Only female patients diagnosed who were age 50 and older with HR+/HER2- invasive breast cancer were eligible, and only those presenting with cT1-T2N0 who underwent upfront surgery with a SLNB comprised our study population. Those with Oncotype DX testing performed with an available RS were included. Given the limitations within the dataset, age 50 and over was selected as a surrogate for post-menopausal status. Categorical variables were compared between RS groups (≤25 vs. >25) using chi-square tests and continuous variables were compared using t-tests. A logistic regression analysis was performed to estimate the association between RS (≤25 vs. >25) and nodal burden (pN2-3 vs pN0-1). Results: There were 151,447 patients with an invasive breast cancer diagnosis between 2015 and 2019 who met inclusion criteria. The average age at diagnosis was 64.1 (IQR 58-69) and almost 75% of tumors displayed ductal histology. There were 130,568 (86.2%) patients with a RS≤25 and 20,879 (13.8%) with a RS >25. On final pathology, 85.2% were pN0 and 14.8% were pN1-3. For those with a RS ≤25, 84.9% were pN0, 14.8% were pN1 and 0.3% were pN2-3. For those with a RS >25, 86.8% were pN0, 12.9% were pN1 and 0.3% were pN2-3. Overall, 14.5% demonstrated pN1 disease, of which 12.3% yielded a RS >25. Of the 461 patients with pN2-3 disease for whom RS was available, 12.4% (57 patients) had RS >25. After adjustment, RS >25 was associated with reduced incidence of pN2-3 compared to pN0-1 (OR=0.64, 95% CI 0.47-0.87, p=0.004). Conclusion: In this population of post-menopausal patients with cT1-T2N0, HR+/HER2- invasive breast cancer and an available RS, almost 86% displayed pN0 or pN1 disease in conjunction with a RS ≤25. Based on the current available literature, less than 5% of cT1-2N0 patients are thought to harbor >pN1 disease. These data add further support, suggesting that this patient population is unlikely to harbor a higher than limited nodal burden given a clinically negative axilla. Though less than 0.5% of the studied patient population demonstrated pN2-3 disease, an important caveat to make is that these patients would not have met criteria for RS, and it’s likely this low number reflects the absence of testing. Given that RS has not been validated for this higher nodal stage, we cannot make recommendations to omit axillary surgery in this cohort of patients. The data presented here provides further rationale for the two large prospective studies addressing whether SLNB could be eliminated in patients with otherwise small HR+/HER2- tumors which are currently ongoing. Table 1: Pathologic Nodal Staging Based on Recurrence Score Citation Format: Astrid Botty van den Bruele, Morgan Paul, Samantha M. Thomas, Sarah L. Sammons, Maggie L. DiNome, Jennifer K. Plichta, Akiko Chiba, Laura H. Rosenberger, E Shelley Hwang. Low 21-Gene Recurrence Score Is Not Associated with a High Axillary Nodal Burden in Post-Menopausal Women Presenting with a Clinically Negative Axilla [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 P3-05-20.

Factors contributing to the use of preoperative MRI remain poorly understood.Data from a randomized controlled trial of stage 0-3 breast cancer patients undergoing breast conserving surgery between 2016 and 2018 were analyzed.Of the 396 patients in this trial, 32.6% had a preoperative MRI. Patient age, race, ethnicity, tumor histology, and use of neoadjuvant therapy were significant predictors of MRI use. On multivariate analysis, younger patients with invasive lobular tumors were more likely to have a preoperative MRI. Rates also varied significantly by individual surgeon (p 0.001); in particular, female surgeons (39.9% vs. 24.0% for male surgeons, p = 0.001) and those in community practice (58.9% vs. 14.2% for academic, p 0.001) were more likely to order preoperative MRI. Rates declined over the two years of the study, particularly among female surgeons.Preoperative MRI varies with patient age and tumor histology; however, there remains variability by individual surgeon.

PURPOSE: To develop optoacoustic, spectrally distinct, actively targeted gold nanoparticle–based near-infrared probes (trastuzumab [TRA], TRA-Aurelia-1, and TRA-Aurelia-2) that can be individually identifiable at multispectral optoacoustic tomography (MSOT) of human epidermal growth factor receptor 2 (HER2)–positive breast tumors. MATERIALS AND METHODS: Gold nanoparticle–based near-infrared probes (Aurelia-1 and 2) that are optoacoustically active and spectrally distinct for simultaneous MSOT imaging were synthesized and conjugated to TRA to produce TRA-Aurelia-1 and 2. Freshly resected human HER2-positive (n = 6) and HER2-negative (n = 6) triple-negative breast cancer tumors were treated with TRA-Aurelia-1 and TRA-Aurelia-2 for 2 hours and imaged with MSOT. HER2-expressing DY36T2Q cells and HER2-negative MDA-MB-231 cells were implanted orthotopically into mice (n = 5). MSOT imaging was performed 6 hours following the injection, and the Friedman test was used for analysis. RESULTS: TRA-Aurelia-1 (absorption peak, 780 nm) and TRA-Aurelia-2 (absorption peak, 720 nm) were spectrally distinct. HER2-positive human breast tumors exhibited a significant increase in optoacoustic signal following TRA-Aurelia-1 (28.8-fold) or 2 (29.5-fold) (P = .002) treatment relative to HER2-negative tumors. Treatment with TRA-Aurelia-1 and 2 increased optoacoustic signals in DY36T2Q tumors relative to those in MDA-MB-231 controls (14.8-fold, P < .001; 20.8-fold, P < .001, respectively). CONCLUSION: The study demonstrates that TRA-Aurelia 1 and 2 nanoparticles operate as a spectrally distinct HER2 breast tumor–targeted in vivo optoacoustic agent. Keywords: Molecular Imaging, Nanoparticles, Photoacoustic Imaging, Breast Cancer Supplemental material is available for this article. © RSNA, 2023

Breast tumors have their own specific microbiota, distinct from normal mammary gland tissue. Patients with breast cancer that present with locally advanced disease often undergo neoadjuvant chemotherapy to reduce tumor size prior to surgery to allow breast conservation or limit axillary lymph node dissection. The purpose of our study was to evaluate whether neoadjuvant chemotherapy modulates the tumor microbiome and the potential impact of microbes on breast cancer signaling. Using snap-frozen aseptically collected breast tumor tissue from women who underwent neoadjuvant chemotherapy (n = 15) or women with no prior therapy at time of surgery (n = 18), we performed 16S rRNA-sequencing to identify tumoral bacterial populations. We also stained breast tumor microarrays to confirm presence of identified microbiota. Using bacteria-conditioned media, we determined the effect of bacterial metabolites on breast cancer cell proliferation and doxorubicin therapy responsiveness. We show chemotherapy administration significantly increased breast tumor Pseudomonas spp. Primary breast tumors from patients who developed distant metastases displayed increased tumoral abundance of Brevundimonas and Staphylococcus. We confirmed presence of Pseudomonas in breast tumor tissue by IHC staining. Treatment of breast cancer cells with Pseudomonas aeruginosa conditioned media differentially effected proliferation in a dose-dependent manner and modulated doxorubicin-mediated cell death. Our results indicate chemotherapy shifts the breast tumor microbiome and specific microbes correlate with tumor recurrence. Further studies with a larger patient cohort may provide greater insights into the role of microbiota in therapeutic outcome and develop novel bacterial biomarkers that could predict distant metastases.Implications:Breast tumor microbiota are modified by therapy and affects molecular signaling.

Obesity influences breast tumor microbiota populations. Breast tumor 16S sequencing results were stratified based upon patient body mass index (BMI). Tumor bacterial populations from non-obese patients with a BMI of 20-27 (n=9) were compared with bacterial populations from obese patients with a BMI of 31-48 (n=8). A. Relative abundance of bacterial genera in different tumor samples is visualized by bar plots. Each bar represents a single tumor and each colored box a bacterial taxon. The height of a color box represents the relative abundance of that organism within the sample. ''Other'' represents lower abundance taxa. B. Phylum level distribution in tumors from obese and non-obese patients. Primary breast tumors from obese patients have decreased proportional abundance of Comamonadaceae (C) and Ruminococcaceae (D) family level taxa. E. Obese patients' breast tumors display elevated abundance of Enterobacteriaceae_unclassified. *p

A. Uninfected 4T1 tumor volume from mice treated 1 x weekly control diet-derived fecal transplant. B. Uninfected 4T1 tumor volume from mice treated 1 x weekly lard diet-derived fecal transplant. C. Tumor volume over time of uninfected 4T1 cells mixed with control diet-derived fecal conditioned media infected RAW 264.7 (macrophage) cells. D. Tumor volume over time of uninfected 4T1 cells mixed with lard diet-derived fecal conditioned media infected RAW 264.7 (macrophage) cells. E. Tumor proliferation as determined by Ki67 immunoreactivity. F. Gram-positive bacteria content in 4T1 breast tumors. G. LPS positive bacteria content in 4T1 tumors. H. Infiltrating tumor-associated macrophage content in 4T1 tumors was determined by F4/80 immunoreactivity. n=5-6.*p

Background Radial scars (RS) and complex sclerosing lesions (CSL) are breast radiologic findings described as small, stellate lesions causing architectural distortion. This can mimic malignancy. Core needle biopsy (CNB) is often performed. Advances in breast imaging have led to increased detection of RS/CSL. The upstage rate of RS/CSL to in situ or invasive disease is 0-40%. We sought to determine the upstaging rate of RS/CSL to in situ, invasive disease, or high-risk lesion at our institution to create excision guidelines. Methods The pathology database of a single center was searched for RS/CSL, from January 2013 to September 2020. We included CNB without malignancy or high-risk lesion (eg, atypical ductal hyperplasia). Patient demographics, indications for biopsy, imaging findings, biopsy procedure, and final pathology were collected. Results Forty-four patients were included. 52.3% had CNB for architectural distortion on mammography, 18.2% for mass, 11.4% for calcifications, 2.3% for abnormal MRI, and 15.9% for multiple reasons (eg, calcifications and mass). Most had an ultrasound: 43.2% had no abnormality and 34.1% had a mass. All CNB were vacuum assisted, 65.9% with 9-gauge needle, and averaged 10.0 cores. 77.3% were stereotactic biopsies, 13.6% ultrasound, and 6.8% MRI. 59.1% had excision after CNB. 82.1% of patients did not upstage. One patient upstaged to invasive ductal carcinoma (3.6%) and two patients to high-risk lesion (7.1%). Discussion There was low upstage rate of RS/CSL on excisional biopsy. Centers could consider close surveillance for RS/CSL on CNB. Longer follow-up in cases of deferred excision is needed to ensure oncologic safety.

Pseudoangiomatous stromal hyperplasia (PASH) is an uncommon, benign breast lesion often diagnosed incidentally and frequently mistaken for fibroadenoma given similar radiographic appearance. Histopathology classically reveals diffuse, dense fibrous stromal background with a complex network of spindle cells forming slit-like spaces, giving it the appearance of angiomatous proliferation. Surgical excision is generally not necessary. Here we present two unusual cases of PASH: an adolescent patient with bilateral rapid onset of symptoms, and a premenopausal patient with bilateral, diffuse, recurrent PASH. Both required mastectomy. We aim to highlight the variable nature of presentation and briefly review current management options.

Background: The microbiome consists of the totality of microorganisms (bacteria, fungi, protist, viruses, and phages) that live on and within the body. Studies implicate the gut bacterial microbiome as a risk factor for estrogen receptor-positive (ER+) breast cancer. While diet is the main contributor to the gut microbiome, medications also shift the bacterial microbiome. We currently do not know whether oral endocrine targeting therapies, such as aromatase inhibitors or tamoxifen shift the gut microbiome. Furthermore, we do not know whether gut microbiome populations can influence drug efficacy. Methods: Fecal samples from human donors were placed into ex-vivo colonic bioreactors for stabilization (n=3). Bioreactors were untreated or treated with letrozole or tamoxifen citrate for 48 hours. Samples were collected, DNA isolated, and metagenomic sequencing performed to determine direct drug-bug interactions. C57BL/6 mice were placed on a healthy control (HC; 21% kcal from fat derived from olive oil and fish oil) or a Western diet (45% kcal from fat derived from corn oil, lard, and milkfat) for 6 weeks. Mice within dietary patterns were randomized and administered control, tamoxifen (TAM; 37 ppm tamoxifen citrate), or an aromatase inhibitor (AI; 5 ppm letrozole) for 16 weeks. Metagenomics sequencing were performed on fecal DNA samples at study endpoint. Female BALB/c mice fed a HC or Western diet were injected with bone metastatic 4T1.2ER+ breast cancer cells. Mice were administered tamoxifen citrate, oral probiotics, or a combination of TAM + probiotics for 3-weeks. Tumor volume, tumor weight, and lung weight were recorded at the end of the study. Hindlimbs were analyzed for metastatic lesions. Results: Metagenomic sequencing from the ex-vivo colonic bioreactors treated with aromatase inhibitors or tamoxifen display differential shifts in several β-glucuronidase-expressing and obesity-associated bacterial species suggesting AI and selective estrogen receptor modulators have varying effects in the gut microbiome that may influence estrogen bioavailability and metabolic parameters. C57BL/6 mice on HC or Western diet treated with AI or TAM also display differences in the microbiota and phage populations with TAM elevating Lactobacillus johnsonii and letrozole increasing Lactococcus lactis bacterial proportional abundance. In the tumor-bearing model, combination of oral Lactobacillus probiotics and TAM significantly reduced tumor weight when compared with the tumor weight in control, TAM, or probiotic treated mice fed a Western diet. Combination of probiotics and TAM also prevented the development of ER+ bone metastatic lesions. Conclusions: Our study indicates oral endocrine therapies differentially affect the gut microbiome and these drug-bug interactions are sensitive to dietary-influenced baseline microbiota populations, which may influence drug efficacy and metabolic outcomes. Furthermore, our preclinical studies suggest oral probiotic supplements may enhance tamoxifen efficacy to reduce tumor growth and metastatic development. Further clinical studies are needed on this topic. Citation Format: Alana Arnone, Adam S. Wilson, Akiko Chiba, Bethany Kerr, David R. Soto-Pantoja, Alexandra Thomas, Katherine L. Cook. Endocrine-targeted therapies modify the gut microbiome affecting responsiveness in ER+ 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 P1-02-05.

Previous studies have found that bile acids influence the growth of breast cancer cells in vitro, suggesting that naturally occurring bile acids may also influence the growth of human breast cancer cells. Cholecystectomy alters modulation of bile acid metabolites, and therefore postcholecystectomy women could be at an increased risk of cancer development and recurrence. This study examined the breast cancer outcome in women who underwent cholecystectomy as compared to those with intact gallbladder. Ninety-three patients diagnosed with Stage I-III invasive mammary carcinoma in 2014 were retrospectively identified and patient demographics, treatment, and outcomes were collected and statistically analyzed. Results revealed 36% of patients who underwent cholecystectomy had recurrence compared to 25% recurrence in patients with intact gallbladders ( p = .30). Forty-six percent of cholecystectomy patients were deceased, and 23% of those with intact gallbladder were deceased ( p = .024). The effect of cholecystectomy on bile acid modulation and breast cancer recurrence requires further investigation.

Background Genetic testing is increasingly utilized in breast cancer patients; however, testing rates remain low. We aimed to evaluate the rate of genetic testing at a tertiary academic medical center utilizing a multidisciplinary clinic model including genetic counselor. Methods A single-center retrospective chart review was performed on a cohort of newly diagnosed breast cancer patients from January 2018 through February 2019. Patients were reviewed for genetic screening eligibility, consultation with a genetic counselor, and test results. Results Final analysis included 426 patients. 261 (61.3%) were found to meet National Comprehensive Cancer Network guidelines for genetic testing, of which 178 patient (68.2%) underwent testing and 32 patients (12.3%) declined testing. Of the 165 not eligible for testing, 5 patients were tested. A total of 183 patients underwent testing and 116 (63.4%) had a negative result, 17 (9.3%) were positive for at least one gene mutation and 50 (27.3%) were identified to have a variant of unknown significance (VUS). There was a positive association between those patients who met with a genetic counselor and eligibility for testing (OR 31.1, 95% CI 16.0-60.5). Conclusions Genetic testing result has become an increasingly important factor when defining optimal surgical treatment for breast cancer patients. Increasing the availability of genetic consultation for breast cancer patients can improve testing rates and patient selection.

Background The recommendation for management of intraductal papilloma has not been clearly established and its surgical excision criteria remain controversial. This study determines the institutional malignancy upstage rate of benign intraductal papillomas and identifies risk factors for upstage. Methods Retrospective review was conducted on female patients who were diagnosed with intraductal papillomas without atypia on core needle biopsy at Atrium Health Wake Forest Baptist Hospital between 1/2012 and 6/2021. Patients were excluded if there was a concomitant malignancy or atypia or deemed to be discordant with imaging. Features associated with upstage on imaging and histopathology were obtained from the electronic medical record. Results This study included 245 intraductal papillomas without atypia in 231 women (mean age, 59.1 ± 12.3 [SD] years). Approximately 31% (76/245) of the papillomas were excised, whereas 69% (169/245) of the papillomas underwent surveillance. Of the patients who underwent excisional biopsy, upstage rate for DCIS was 1.3% (1/76) and 5.3% (4/76) for atypia. All of the papillomas upstaged to DCIS or atypia had lesion size ≥10 mm on imaging. Out of the 139 intraductal papillomas that underwent radiologic surveillance, two (1.4%) developed malignancy and three (2.2%) developed atypia. Discussion The risk of upstaging of intraductal papilloma without atypia to malignancy remains extremely low. Therefore, routine surgical excision may not be necessary. While the papillomas upstaged to either malignancy or atypia have size abnormality ≥10 mm, other potential selective excision criteria should be explored to further decrease the risk of an upstage.

Introduction The COVID-19 pandemic has impacted many areas of health care and had a significant impact on care delivery, including breast cancer. Methods To better understand the changes to detection and treatment of breast cancer at our institution, we analyzed mammogram rates (screening and diagnostic) and breast cancer operations in 2019-2020. Mammography rates were calculated using county level census data for eligible women (Z-test). For breast cancer staging, a stage severity score was analyzed with a Mann-Whitney U-test (two-tail, P < .05) with proportions derived from WFBH operative volume quarterly reports. Results: Data revealed a relative decline from 2019 to 2020 in breast cancer screening. Screening mammograms decreased by 44% or 1558 fewer screening mammograms (Z = 4.75, P < .00001) and by 21% or 771 fewer for diagnostic mammograms (Z = 2.16, P = .03). With regards to breast cancer operations, we did not identify a statistically significant difference in number of new breast cancer operations at WFBH with 340 cases in 2020 as compared to 384 cases in 2019 ( P = .9905). We compared a breast cancer severity score (weighted by stage at time of operation), which did not reveal statistically significant difference in clinical stage of breast cancer at time of operation ( P = .71, U = 28). Conclusion Mammography was impacted more than breast surgery cases by the COVID-19 pandemic. More data needs to be collected to evaluate future morbidity and mortality related to breast cancer operations and persistent disparities related to delay in breast cancer care due to COVID-19.

Background: Several published studies demonstrate that bile acid metabolites may influence the growth of breast cancer cells in vitro. Our group has shown reduced plasma concentrations of cholic acid and chenodeoxycholic acid (primary bile acids) and deoxycholic acid and lithocholic acid (secondary bile acids) in breast cancer patients that later on develop tumor recurrence. Cholecystectomy reduces the circulating bile acid pool. In patients with prior cholecystectomy, changes in bile acid metabolites may contribute to breast cancer tumorigenesis and recurrence. This study investigates our institutional rate of cholecystectomy in women diagnosed with breast cancer and its impact on breast cancer recurrence. Methods: A retrospective review of patients with an invasive breast cancer diagnosis between 2014-2015 was conducted. Demographics, preoperative variables, surgical history and clinical outcome data was collected. 5-year disease-free survival (DFS) was compared using a Log-rank (Mantel-Cox) test. Results: The study included 264 patients with mean age of 60.9. Most were Caucasian (83.5%). The majority were diagnosed at Stage II or lower (80.3%) and had hormone receptor positive, HER2 negative breast cancer (72.9%). Approximately 22.7% of patients had prior cholecystectomy surgery. The only statistically significant heterogeneity in demographic data between patients with and without cholecystectomy was body mass index (BMI). Patients with cholecystectomy had a mean BMI of 33.3, versus 29.1 in patients with intact gallbladders. The 5-year DFS in breast cancer patients with cholecystectomy was 91.6%, versus 97.1% in patients with intact gallbladders (p=0.06). Conclusion: Women with breast cancer who had a history of cholecystectomy had increased rates of breast cancer recurrence over a 5-year period compared to women with breast cancer with intact gallbladders. Although this result was not statistically significant, a trend was seen. Future study of a larger patient sample size sample may lead to a statistical significant difference. The statistically significant difference in BMI between the two patient groups is likely a confounding factor, given increased BMI is a known risk factor for developing cholecystitis and breast cancer. This data supports existing in vitro studies that bile acids may influence the growth of breast cancer cells. There may be utility in closer follow-up of women with breast cancer and a history of cholecystectomy given the increased rate of breast cancer recurrence in this population. Citation Format: Isheeta Madeka, Rohin Gawdi, Katherine L Cook, Akiko Chiba. Impact of Cholecystectomy in Breast Cancer Recurrence [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS6-59.

BACKGROUND: It is known that breast cancer subtype (e.g., luminal vs. triple negative (TN)) can affect response to systemic therapy and prognosis; however, it is less well-understood whether these subtypes affect margin status and should therefore alter surgical management. METHODS: Data from two randomized trials evaluating cavity shave margins (CSM) on margin status in patients undergoing partial mastectomy (PM) were used for this analysis. The data were restricted to patients who had invasive carcinoma present in the PM specimen, and in whom data for all three receptors (ER, PR and HER-2) were known. Patients were classified as luminal if they were ER and/or PR+, HER-2 enriched if they were ER and PR negative but HER-2 positive, and TN if they were negative for all three receptors. We evaluated the impact of subtype on the margin status at the time the surgeon had completed their standard PM, prior to randomization to CSM vs. no CSM. Non-parametric statistical analyses were performed using SPSS Version 26. RESULTS: 350 patients were included in this cohort for analysis. The median patient age was 64 (range; 32-94 years) and the median invasive tumor size was 1.2 cm (range; 0.6-8.0 cm). 326 (93.1%) were luminal type, 22 (6.3%) were triple negative, and 2 (0.6%) were HER-2 enriched. Subtype was significantly correlated with race (black patients were more likely to have TN disease than white patients, 22.2% vs. 3.8%, p=0.001), palpability (TN tumors were more likely to be palpable than luminal cancers 54.5% vs. 29.8%, p=0.007) and grade (78.9% of TN cancers were high grade vs. 13.5% of luminal cancers p0.05 for all). While patients with TN and HER-2 enriched tumors were more likely to receive neoadjuvant therapy, this did not reach statistical significance (p=0.117). Surgeons were no more likely to take selective margins on the basis of molecular subtype (p=0.413). In this cohort, the overall positive margin rate was 33.7%. This did not vary based on molecular subtype (positive margin rate: 33.7% for patients with luminal tumors vs. 36.4% for those with TN tumors, p=0.425). On multivariate regression controlling for molecular subtype, race, grade and palpability, the only factor which predicted positive margin status was grade (p=0.005), with high grade tumors being significantly more likely to have a positive margin than low grade tumors, independent of other factors (OR=3.503, 95% CI: 1.638-7.494, p=0.001). CONCLUSION: While molecular subtype correlates with race, tumor grade and palpability, it does not predict margin status. Therefore, molecular subtype should not, independent of other factors, influence surgical decision-making. Citation Format: Andrew Fenton, Elisabeth Dupont, Theodore Tsangaris, Carlos Garcia-Cantu, Marissa Howard-McNatt, Akiko Chiba, Adam Berger, Edward Levine, Jennifer Gass, Kristalyn Gallagher, Sharon Lum, Ricardo Martinez, Alliric Willis, Sonali Pandya, Eric Brown, Amanda Mendiola, Mary Murray, Naveenraj Solomon, Maheswari Senthil, David Ollila, David Edmonson, Melissa Lazar, Jukes Namm, Fangyong Li, Meghan Butler, Noreen McGowan, Maria Herrera, Yoana Avitan, Brian Yoder, Laura Walters, Tara McPartland, Victor Haddad, Hongwei Ma, Ming Xie, Anees Chagpar. Does breast cancer subtype impact margin status in patients undergoing partial mastectomy? [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-15.

Breast primary neuroendocrine tumors (BNETs) are rare, making up less than 1% of all breast carcinoma diagnosis. Their detection relies on physical exams and mammography. Diagnosis of primary BNET requires findings of no other source of neuroendocrine tumor (eg, pancreatic, lung, and appendix). Histopathologically, they typically stain positive for chromogranin A and/or synaptophysin, as do most neuroendocrine tumors. Currently, there are no agreed upon and standardized treatment protocols as it is a rare diagnosis. Treatment protocols are often built on anecdotal evidence and small case reports and series. Here we discuss a case of BNET in a 51-year-old female and discuss commonly encountered treatment protocols.

Background Molecular subtype in invasive breast cancer guides systemic therapy. It is unknown whether molecular subtype should also be considered to tailor surgical therapy. The present investigation was designed to evaluate whether breast cancer subtype impacted surgical margins in patients with invasive breast cancer stage I through III undergoing breast-conserving therapy. Methods Data from 2 randomized trials evaluating cavity shave margins (CSM) on margin status in patients undergoing partial mastectomy (PM) were used for this analysis. Patients were included if invasive carcinoma was present in the PM specimen and data for all 3 receptors (ER, PR, and HER2) were known. Patients were classified as luminal if they were ER and/or PR positive; HER2 enriched if they were ER and PR negative but HER2 positive; and TN if they were negative for all 3 receptors. The impact of subtype on the margin status was evaluated at completion of standard PM, prior to randomization to CSM versus no CSM. Non-parametric statistical analyses were performed using SPSS Version 26. Results Molecular subtype was significantly correlated with race ( P = .011), palpability ( P = .007), and grade ( P < .001). Subtype did not correlate with Hispanic ethnicity ( P = .760) or lymphovascular invasion ( P = .756). In this cohort, the overall positive margin rate was 33.7%. This did not vary based on molecular subtype (positive margin rate 33.7% for patients with luminal tumors vs 36.4% for those with TN tumors, P = .425). Discussion Molecular subtype does not predict margin status. Therefore, molecular subtype should not, independent of other factors, influence surgical decision-making.

This study investigated consecutive fluctuations in serum activities of bone-specific alkaline phosphatase (ALP) isoenzyme 3 (ALP3) in 11 clinically healthy Holstein heifers during the first 18 months of life. ALP3 activities at the first sampling time point after weaning (3 months) were significantly lower than those at multiple time points during the pre-weaning period. Those activities increased from a minimum at 3 months to a peak at 6 months during the post-weaning period. In the anthropometric data, daily body weight and wither height gains appeared to be below the public data at 4 months and 4-5 months, respectively. The data suggested that serum ALP3 activity can be used to monitor skeletal growth of heifers at weaning.

Background: Patients who achieve a pathological complete response (pCR- defined as no invasive cancer) after neoadjuvant chemotherapy (NAC) for breast cancer (BC) have improved outcomes, but there is still controversy about the significance of residual ductal carcinoma in situ (DCIS) on local recurrence rate (LRR). The I-SPY 2 TRIAL is an adaptive neoadjuvant platform trial evaluating novel experimental regimens in comparison to standard chemotherapy in women with high-risk breast cancer. The purpose of this study is to determine if residual DCIS after NAC in early BC affects LRR in patients with or without residual invasive disease in the I-SPY 2 TRIAL. Methods: 933 I-SPY 2 patients with residual cancer burden (RCB) and follow-up data were included in this analysis. Residual DCIS was defined as any carcinoma in situ > 0% on RCB evaluation. Local recurrence was defined as recurrence in breast, chest wall or locoregional nodes and/or skin and subcutaneous tissue. We stratified our cohort into four groups: those without residual invasive disease (defined as RCB0) ± residual DCIS, and those with residual invasive disease (RCB>0) ± residual DCIS. We estimated LRR within each group using the Kaplan Meier method; and used Cox proportional hazards models to assess LRR differences between groups, with: patients with no residual disease (invasive or in situ) as reference group. Results: Among 933 patients assessed, median follow up time was 3.9 years. RCB 0 status was achieved in 337 patients (36%). Of these, 267 (29%) had no residual DCIS, which represents our reference group, and 70 (7%) had residual DCIS. Among 596 (64%) patients who had RCB>0, 296 (32%) had residual DCIS. For patients with RCB0 without DCIS and RCB0 with DCIS, the LRR at 3 years were similar: 2% vs 3% respectively (Hazard ratio: 1.29 [0.26-6.39]). Results were also similar in the RCB>0 group, with a LRR of 10% at 3 years in those without residual DCIS, and 11% in those with residual DCIS. Both RCB>0 groups had significantly higher LRR when compared to the patients with RCB0 without DCIS (Hazard ratio: 5.25 [2.20-12.5]) and HR 5.85 [2.47-13.9] respectively). Conclusion: There was no association between residual DCIS and LRR after neoadjuvant chemotherapy, regardless of resolution of invasive disease. Further work is needed to determine whether residual DCIS should drive locoregional therapy decisions after neoadjuvant chemotherapy for invasive breast cancer. Citation Format: Marie Osdoit, Christina Yau, W. Fraser Symmans, Judy C. Boughey, Smita M. Asare, Ron Balassanian, Jodi M. Carter, Yunn-Yi Chen, Kimberly Cole, Laila Khazai, Molly Klein, Dina Kokh, Gregor Krings, Sunati Sahoo, Gretchen Ahrendt, Akiko Chiba, Cheryl Ewing, Constantine Godellas, Nora Jaskowiak, Brigid Killelea, Helen Krontiras, Rachael Lancaster, Julie Lang, M. Catherine Lee, Arpana Naik, Roshni Rao, Julia Tchou, Shannon Tierney, Eleni Tousimis, Tod Tuttle, Anne Wallace, I-SPY 2 TRIAL Consortium, Bev Parker, Laura J. Esserman, Rita A. Mukhtar. The impact of residual ductal carcinoma in situ on breast cancer recurrence in the neoadjuvant I-SPY2 TRIAL [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-08-16.

Background: Triple negative breast cancer (TNBC), unlike other breast cancer subtypes, lacks a specific targetable receptor. As such tumor specific delivery, which can limit off-target effects of anti-neoplastic therapies, has been an unmet clinical need in treating this aggressive breast cancer subtype. To address this need, we exploited the tumor hallmark of an acidic microenvironment and developed a pH targeted nanoparticle by conjugation of the V3 pH specific peptide on a wormhole pore mesoporous silica nanoparticles (V3-RUBY) and assessed the ability of V3-RUBY to specifically release cargo in ex vivo patient samples and in orthotopically implanted TNBC tumors as detect by multispectral optoacoustic imaging technology (MSOT). Methods: The silica nanoparticles with wormhole pore architecture were synthesized by sol-gel chemistry and characterized by transmission electron microscopy (TEM), zeta potential, and dynamic light scattering (DLS). The surface base particle was crosslinked with a gatekeeper molecule, chitosan. Further targeting of the particle using V3 pHLIP (low insertion peptide), resulted in the V3-RUBY nanoparticle which allows for pH-sensitive cargo release. The particle was loaded with imaging dye to assess tumor specificity. Fresh ex vivo TNBC patient tumor tissues were resected and rapidly treated with V3-RUBY containing propodium iodide (PI) to evaluate tumor uptake of V3-RUBY and cargo release within the tumor cells, as measured by the red fluorescence of PI when bound to nucleic acids. (PI independently cannot cross cell membranes.) In vivo, female athymic mice were implanted with MDA-MB-468 breast cancer cells by the mammary fat pad injection. Once the tumor reached 3mm in size, athymic mice were intravenously injected with V3-RUBY nanoparticles carrying IR780 infrared imaging dye and were imaged with MSOT inVision 512TF. Results: The RUBY nanoparticle with wormhole pores was 27 nm diameter. The dual targeting approach of a nanoparticle with V3 targeting peptide and chitosan demonstrated pH specificity around tumor pH. In ex vivo patient TNBC samples, V3-RUBY demonstrated active targeting and dye release at pH 6.8, which approximated the pH measured at surgical tumor removal, in 10 fresh patient samples compared to pH 7.4 controls (p Conclusion: The tumor-specific release of payload by V3-RUBY suggests the potential of a pH specific target in TNBC, with such a nanoparticle holding promise to deliver both diagnostic and therapeutic cargo directly to the tumor and limit off-target toxicity. Future translation of these technologies could have promise in TNBC, as well as other high-grade breast cancer subtypes and expand treatment options in this challenging area of oncology. TablePatientBreast Cancer SubtypeTumor GradePathologic StagePI Uptake (a.u.) pH 6.8PI Uptake (a.u.) 7.41TNBC3ypT3N3a33.20.82TNBC3ypT2N038.41.53TNBC3ypT4bN1a36.81.74TNBC3T1bN022.40.85TNBC2T1cN021.80.86TNBC2ypT0N021.50.67TNBC3ypT1aN2a22.00.48TNBC3ypT4dN239.52.19TNBC3T2N2a31.52.210TNBC3T2N1a32.21.8 Citation Format: Alexandra Thomas, Akiko Chiba, Abhilash Samykutty, Molly W. McNally, Lacey R. McNally. Tumor specific cargo release in ex vivo patient samples and murine models of triple negative breast cancer by a pH-targeted nanoparticle: V3-RUBY [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-06-04.

Breast tumors have their own specific microbiota, distinct from normal mammary gland tissue. Patients with breast cancer that present with locally advanced disease often undergo neoadjuvant chemotherapy to reduce tumor size prior to surgery to allow breast conservation or limit axillary lymph node dissection. The purpose of our study was to evaluate whether neoadjuvant chemotherapy modulates the tumor microbiome and the potential impact of microbes on breast cancer signaling. Using snap-frozen aseptically collected breast tumor tissue from women who underwent neoadjuvant chemotherapy (n = 15) or women with no prior therapy at time of surgery (n = 18), we performed 16S rRNA-sequencing to identify tumoral bacterial populations. We also stained breast tumor microarrays to confirm presence of identified microbiota. Using bacteria-conditioned media, we determined the effect of bacterial metabolites on breast cancer cell proliferation and doxorubicin therapy responsiveness. We show chemotherapy administration significantly increased breast tumor Pseudomonas spp. Primary breast tumors from patients who developed distant metastases displayed increased tumoral abundance of Brevundimonas and Staphylococcus. We confirmed presence of Pseudomonas in breast tumor tissue by IHC staining. Treatment of breast cancer cells with Pseudomonas aeruginosa conditioned media differentially effected proliferation in a dose-dependent manner and modulated doxorubicin-mediated cell death. Our results indicate chemotherapy shifts the breast tumor microbiome and specific microbes correlate with tumor recurrence. Further studies with a larger patient cohort may provide greater insights into the role of microbiota in therapeutic outcome and develop novel bacterial biomarkers that could predict distant metastases. Implications: Breast tumor microbiota are modified by therapy and affects molecular signaling.

The purpose of this study was to elucidate the colostral and foal serum immunoglobulin G (IgG) concentration values in heavy draft horses in Japan and to examine the effects of peripartum mare condition on colostral immunity. Colostrum was obtained 1 hr after foaling (pre-suckling; n=178). Blood was collected from the jugular vein of the foals (n=147) at 24 to 48 hr after birth. The foaling statuses of 73 mares were recorded. The average colostral IgG concentration was 10,540 ± 3,190 mg/dl (median=10,928; range 1,434−17,514 mg/dl). The average serum IgG concentration obtained from neonatal foals 24 to 48 hr after birth was 1,750 ± 919 mg/dl (median=1,890; range 0−3,510 mg/dl). Although colostral IgG did not differ between the normal foaling mare (n=59) and dystocial mare (n=14), foal serum IgG was lower in foals born in dystocia than in foals in normal foaling (P

De-escalation of breast cancer treatment aims to reduce patient and financial toxicity without compromising outcomes. Level I evidence and National Comprehensive Cancer Network guidelines support omission of adjuvant radiation in patients aged70 y with hormone-sensitive, pT1N0M0 invasive breast cancer treated with endocrine therapy. We evaluated radiation use in patients eligible for guideline concordant omission of radiation.Subgroup analysis of patients eligible for radiation omission from two pooled randomized controlled trials, which included stage 0-III breast cancer patients undergoing breast conserving surgery, was performed to evaluate factors associated with radiation use.Of 631 patients, 47 (7.4%) met radiation omission criteria and were treated by 14 surgeons at eight institutions. The mean age was 75.3 (standard deviation + 4.4) y. Majority of patients identified as White (n = 46; 97.9%) and non-Hispanic (n = 44; 93.6%). The mean tumor size was 1.0 cm; 37 patients (88.1%) had ductal, 4 patients (9.5%) had lobular, and 17 patients (40.5%) had low-grade disease. Among patients eligible for radiation omission, 34 (72.3%) patients received adjuvant radiation. Those who received radiation were significantly younger than those who did not (74 y, interquartile range = 4 y, versus 78 y, interquartile range = 11 y, P = 0.03). There was no difference in radiation use based on size (P = 0.4), histology (P = 0.5), grade (P = 0.7), race (P = 1), ethnicity (P = 0.6), institution (P = 0.1), gender of the surgeon (P = 0.7), or surgeon (P = 0.1).Fewer than 10% of patients undergoing breast conservation met criteria for radiation omission. Nearly three-quarters received radiation therapy with younger age being a driver of radiation use, suggesting ample opportunity for de-escalation, particularly among younger eligible patients.

Breast cancer is the second most common malignancy affecting pregnant women. Ductal carcinoma in situ (DCIS) during pregnancy has not been well described with limited literature addressing the optimal treatment options. This is important topic as the incidence of pregnancy-associated breast cancer (PABC) has been increasing. In the United States, 1 in 3000 pregnancies are complicated by breast cancer diagnosis. Most DCIS are screen detected as most patients are asymptomatic. Since routine screening mammogram is not recommended during pregnancy, diagnosis of DCIS without invasive disease is uncommon diagnosis. Although PABC is reported to account for 0.2-3.8% of all newly diagnosed breast cancer, it has not been defined between the diagnosis of DCIS or invasive breast cancer making true incidence of DCIS in pregnancy difficult to report. This review summarizes multidisciplinary recommendations for optimal treatment for DCIS diagnosed during pregnancy.

Background We sought to determine factors affecting time to surgery (TTS) to identify potential modifiable factors to improve timeliness of care. Methods Patients with clinical stage 0-3 breast cancer undergoing partial mastectomy in 2 clinical trials, conducted in ten centers across the US, were analyzed. No preoperative workup was mandated by the study; those receiving neoadjuvant therapy were excluded. Results The median TTS among the 583 patients in this cohort was 34 days (range: 1-289). Patient age, race, tumor palpability, and genomic subtype did not influence timeliness of care defined as TTS ≤30 days. Hispanic patients less likely to have a TTS ≤30 days ( P = .001). There was significant variation in TTS by surgeon ( P < .001); those practicing in an academic center more likely to have TTS ≤30 days than those in a community setting (55.1% vs 19.3%, P < .001). Patients who had a preoperative ultrasound had a similar TTS to those who did not (TTS ≤30 days 41.9% vs 51.9%, respectively, P = .109), but those who had a preoperative MRI had a significantly increased TTS (TTS ≤30 days 25.0% vs 50.9%, P < .001). On multivariate analysis, patient ethnicity was no longer significantly associated with TTS ≤30 ( P = .150). Rather, use of MRI (OR: .438; 95% CI: .287-.668, P < .001) and community practice type (OR: .324; 95% CI: .194-.541, P < .001) remained independent predictors of lower likelihood of TTS ≤30 days. Conclusions Preoperative MRI significantly increases time to surgery; surgeons should consider this in deciding on its use.

Background The American College of Surgeons Oncology Group Z1071 trial in 2013 demonstrated the fesability of sentinel lymph node biopsy in clinically node-positive patients following neoadjuvant chemotherapy. The goal of this study was to determine the continued impact of this study on our practice pattern. Materials and Methods This is a retrospective review of institutional changes in the management of axillary nodal disease following the publication of Z1071. Patients with clinically node-positive disease that completed neoadjuvant chemotherapy between 2014 and 2020 were included. The Cocoran-Armitage trend test was used to analyze change in categorical variables over time, and the Spearman’s rank coefficient was used to analyze two-ranked variables. Results A cohort of 102 patients were included in the study and demonstrated that the number of sentinel lymph node biopsies to evaluate axillary disease increased over time. Additionally, the number of biopsies of suspicious nodes, and the use of marker clips on the biopsied nodes increased over time. Conclusion Our institution has continued to incorporate the result from Z1071 in our practice patterns.

We performed a standing hand-assisted laparoscopic ovariectomy in a draft mare that presented with high serum anti-Müllerian hormone (AMH) level and had an enlarged single cystic ovary. Histopathological examination revealed no tumor cell proliferation in the ovary, but the presence of a large ovarian cyst was confirmed. In the diagnosis of abnormal ovaries in mares, a comprehensive assessment should be performed, including the monitoring of ovarian morphology and biomarkers over time, to determine the disease prognosis and treatment plan. The case of this mare with a nonneoplastic abnormal ovary and increased serum AMH level was rare. We suggest that standing hand-assisted laparoscopic ovariectomy is useful for the removal of large ovaries in draft mares.

Background There are several techniques for localization of non-palpable breast tumors, but comparisons of these techniques in terms of margin positivity and volume of tissue resected are lacking. Methods Between 2011-2013 and 2016-2018, 2 randomized controlled trials involving 10 centers across the United States accrued 631 patients with stage 0-3 breast cancer, all of whom underwent breast conserving surgery. Of these, 522 had residual non-palpable tumors for which localization was required. The localization technique was left to the discretion of the individual surgeon. We compared margin positivity and volume of tissue resected between various localization techniques. Results The majority of the patients (n = 465; 89.1%) had wire localization (WL), 50 (9.6%) had radioactive seed (RS) localization, and 7 (1.3%) had Savi Scout (SS) localization. On bivariate analysis, there was no difference in terms of margin positivity (37.8% vs. 28.0% vs. 28.6%, P = .339) nor re-excision rates (13.3% vs. 12.0% vs. 14.3%, P = .961) for the WL, RS, and SS groups, respectively. Further, the volume of tissue removed was not significantly different between the 3 groups (71.9 cm3 vs. 55.8 cm3 vs. 86.6 cm3 for the WL, RS, and SS groups, respectively, P = .340). On multivariate analysis, margin status was affected by tumor size (OR = 1.336; 95% CI: 1.148-1.554, PConclusions While there are a number of methods for tumor localization, choice of technique does not seem to influence volume of tissue resected nor margin status.

Background The management of flat epithelial atypia (FEA) on core needle biopsy remains controversial. The upstaging rates after surgical excision are variable. In this study, we seek to determine the upstaging rate of FEA at our institution. Methods Patients with a diagnosis of FEA were identified from the institution’s pathology database from 2009 to 2018. Patients were included in the study if FEA alone, without atypia or cancer, was identified on core needle biopsy. Patient demographics, imaging, management, and pathology characteristics were obtained. Statistical analysis performed using IBM SPSS 26.0 (Armonk, NY, USA). Results FEA was diagnosed on core needle biopsy in 235 patients from 2009 to December 2018. Forty-eight patients met the inclusion criteria. The majority of patients presented with calcifications on mammogram (n = 21, 64%) with the remainder as masses (n = 6, 18%) or architectural distortion (n = 6, 18%). Of those, 15 (31%) patients declined surgical excision, of which none developed cancer over a mean follow-up of 4.4 years. Of the 33 (69%) patients undergoing excisional biopsy, 17 (52%) confirmed FEA, 11 (33%) had benign findings, and 3 (9%) demonstrated atypical ductal hyperplasia on final pathology. One (3%) case revealed ductal carcinoma in situ (DCIS) and 1 (3%) was upgraded to invasive cancer for an overall upstaging rate of 4% (2/48). After a mean follow-up of 3.4 years, none of the excisional biopsy patients developed invasive breast cancer. Adjuvant therapy was used in the cases of DCIS and invasive cancer; however, chemoprevention with raloxifene or tamoxifen was not chosen by any of the remaining patients. Conclusion In our cohort, expectant management of FEA alone appears to be a safe option as our upstaging rate to DCIS or invasive cancer for FEA diagnosed on core biopsy was only 4%. Our study suggests that close follow-up is a safe and feasible option for pure FEA without a radiographic discordance found on core biopsy.

At the intersection of the newly emerging fields of optoacoustic imaging and theranostic nanomedicine, promising clinical progress can be made in dismal prognosis of ovarian cancer. An acidic pH targeted wormhole mesoporous silica nanoparticle (V7-RUBY) was developed to serve as a novel tumor specific theranostic nanoparticle detectable using multispectral optoacoustic tomographic (MSOT) imaging. We report the synthesis of a small, < 40 nm, biocompatible asymmetric wormhole pore mesoporous silica core particle that has both large loading capacity and favorable release kinetics combined with tumor-specific targeting and gatekeeping. V7-RUBY exploits the acidic tumor microenvironment for tumor-specific targeting and tumor-specific release. In vitro, treatment with V7-RUBY containing either paclitaxel or carboplatin resulted in increased cell death at pH 6.6 in comparison to drug alone (p10X higher than in the kidney using both multispectral optoacoustic tomography (MSOT) imaging with secondary confirmation using near infrared fluorescence imaging (p

Summary: Recent identification of a mammary gland-specific microbiome led to studies investigating bacteria populations in breast cancer. Malignant breast tumors have lower Lactobacillus abundance compared with benign lesions, implicating Lactobacillus as a negative regulator of breast cancer. Diet is a main determinant of gut microbial diversity. Whether diet affects breast microbiome populations is unknown. In a non-human primate model, we found that consumption of a Western or Mediterranean diet modulated mammary gland microbiota and metabolite profiles. Mediterranean diet consumption led to increased mammary gland Lactobacillus abundance compared with Western diet-fed monkeys. Moreover, mammary glands from Mediterranean diet-fed monkeys had higher levels of bile acid metabolites and increased bacterial-processed bioactive compounds. These data suggest that diet directly influences microbiome populations outside the intestinal tract in distal sites such as the mammary gland. Our study demonstrates that diet affects the mammary gland microbiome, establishing an alternative mechanistic pathway for breast cancer prevention. : Using a non-human primate model of women’s health, Shively et al. demonstrate that diet plays a critical role in determining microbiota populations in tissues outside the gut, such as the mammary gland. These microbial populations modulate localized bile acid and bacterial-modified metabolites to potentially influence anticancer signaling pathways. Keywords: breast, mammary gland, diet, microbiome, bile acid, hippurate, oxidative stress

BACKGROUND We examined the impact of cavity shave margins (CSMs) on margin status in patients with pure ductal carcinoma in situ (DCIS) undergoing partial mastectomy (PM). METHODS One hundred and nine patients from 2 multicenter, randomized controlled trials were identified with pure DCIS (no invasive cancer). Surgeons performed their best PM, with specimen radiography and resection of selective margins per surgeon discretion. Patients were then randomized to have CSM resected or not. A positive margin was defined as

Advances in breast cancer research have made breast cancer a treatable disease. However, there is a population of women who present with large, advanced, or sometimes neglected breast cancers who can prove difficult to treat. These women often require multiple modality treatment including chemotherapy, surgery, and radiation. The purpose of our study is to examine the treatment and outcomes on women with large, locally advanced breast cancers (LABCs). We identified 8 individuals who presented with LABCs requiring extensive treatment. Patients with inflammatory or metastatic cancer at the time of presentation were excluded. These patients’ charts were reviewed and analyzed. Patient demographics, hormone receptor status, stage, types of treatment, presence of metastasis, survival, and presence of barriers for seeking treatment sooner were identified. The median age at presentation was 65 years old. The patients were equally African American and Caucasian. All patients presented with T4 or stage 3 tumors involving the skin and/or pectoralis muscle. Half of the patients were found to have triple-negative (estrogen receptor, progesterone receptor, Her-2/neu negative) tumors. 87% of the patients received chemotherapy; 1 refused. All 8 patients, either neoadjuvantly or adjuvantly, underwent a modified radical or radical mastectomy. Skin graft or flap coverage was necessary in half of the patients. Postmastectomy radiation was received in 87% of the patients; 1 patient refused the treatment. Half of the patients developed metastatic disease. Thirty-seven percent of the patients have since died with a median survival of 44 months. Reasons for delay in seeking care were monetary or social barriers. Many of the patients finally sought care via the emergency room due to symptoms they could no longer ignore. Women who present with LABC require complex multidisciplinary treatment consisting of chemotherapy, surgery, and radiation treatments. Many of these patients faced economic and social challenges to accessing care. Better access to care and more prompt connection to breast surgeons are required to assist this patient population.

Obesity and poor diet often go hand-in-hand, altering metabolic signaling and thereby impacting breast cancer risk and outcomes. We have recently demonstrated that dietary patterns modulate mammary microbiota populations. An important and largely open question is whether the microbiome of the gut and mammary gland mediates the dietary effects on breast cancer. To address this, we performed fecal transplants between mice on control or high-fat diets (HFD) and recorded mammary tumor outcomes in a chemical carcinogenesis model. HFD induced protumorigenic effects, which could be mimicked in animals fed a control diet by transplanting HFD-derived microbiota. Fecal transplants altered both the gut and mammary tumor microbiota populations, suggesting a link between the gut and breast microbiomes. HFD increased serum levels of bacterial lipopolysaccharide (LPS), and control diet–derived fecal transplant reduced LPS bioavailability in HFD-fed animals. In vitro models of the normal breast epithelium showed that LPS disrupts tight junctions (TJ) and compromises epithelial permeability. In mice, HFD or fecal transplant from animals on HFD reduced expression of TJ-associated genes in the gut and mammary gland. Furthermore, infecting breast cancer cells with an HFD-derived microbiome increased proliferation, implicating tumor-associated bacteria in cancer signaling. In a double-blind placebo-controlled clinical trial of patients with breast cancer administered fish oil supplements before primary tumor resection, dietary intervention modulated the microbiota in tumors and normal breast tissue. This study demonstrates a link between the gut and breast that mediates the effect of diet on cancer. Significance: This study demonstrates that diet shifts the microbiome in the gut and the breast tumor microenvironment to affect tumorigenesis, and oral dietary interventions can modulate the tumor microbiota in patients with breast cancer.

Background Current treatment guidelines for ductal carcinoma in situ (DCIS) treated with mastectomy recommend sentinel lymph node biopsy (SLNB). In the modern era, there is a trend toward minimizing invasive staging and treatment of the axilla. In this study, we seek to determine the role of SLNB in patients undergoing mastectomy for the treatment of DCIS. Methods Patients undergoing mastectomy were identified from our institution’s SLNB database from 2012 to 2016. Patients were included if core needle biopsy demonstrated DCIS. Patient demographics, tumor characteristics, and pathologic variables were abstracted. Results Of 187 patients undergoing mastectomy with SLNB from 2012 to 2016 for DCIS or invasive ductal carcinoma, 39 (21%) were diagnosed with DCIS on core biopsy. Mean age was 57 years. 70% were Caucasian, 18% were African American, 8% were Asian, and the remaining 5% were unknown. One patient (3%) had positive nodes on SLNB and underwent axillary lymph node dissection. Of those with DCIS on core biopsy, 14 (36%) were upstaged to invasive disease on final surgical pathology, including the patient with positive SLNB. Of the remaining 25 (64%) patients with DCIS on final pathology, 0 (0%) had SLNB positivity. Conclusion Only 3% of patients with DCIS undergoing mastectomy were found to have SLN metastases. However, a significant number of patients (36%) were upstaged due to invasive cancer. Although limited by a small sample size, our results suggest that SLNB should still be recommended to patients undergoing mastectomy for DCIS on core needle biopsy due to the high rate of upstage rate to invasive disease.

Autonomic nervous function evaluated by heart rate variability (HRV) and blood characteristics were compared between Holstein Friesian cows that developed postpartum fever (PF; n = 5) and clinically healthy (CH; n = 6) puerperal cows in this case-control study. A cow was defined as having PF when its rectal temperature rose to ≥39.5°C between 1 and 3 days postpartum. We recorded electrocardiograms during this period using a Holter-type electrocardiograph and applied power spectral analysis of HRV. Comparisons between the groups were analyzed byttest or Mann-WhitneyUtest, and the relationship between rectal temperature and each parameter was analyzed using multiple regression analysis. Heart rate was higher in PF cows than in CH cows (Mean ± SE, 103.3 ± 2.7 vs. 91.5 ± 1.7 bpm). This result suggested that PF cows had a relatively dominant sympathetic nervous function. Total (44,472 ± 2,301 vs. 55,373 ± 1,997 ms) and low frequency power (24.5 ± 3.8 vs. 39.9 ± 5.3 ms) were lower in PF cows than in CH cows. These findings were possibly caused by a reduction in autonomic nervous function. The total white blood cell count (54.3 ± 5.1 vs. 84.5 ± 6.4 ×102/μL) and the serum magnesium (2.1 ± 0.1 vs. 2.4 ± 0.1 mg/dL) and iron (81.5 ± 8.0 vs. 134.4 ± 9.1 μg/dL) concentrations were lower and the serum amyloid A concentration (277 ± 33 vs. 149 ± 21 μg/mL) was higher in PF cows than in CH cows. These results imply that more inflammation was present in PF cows than in CH cows. Multiple regression analysis showed that both of low frequency power and concentration of serum iron were associated with rectal temperature. We found differences in changes in hematologic results, biochemical findings, and HRV patterns between PF cows and CH cows.