Lobular Carcinoma Of Breast Research Articles

Abstract 1158: A.I.-assisted clinical data curation to determine genomic biomarkers of cancer metastasis

Abstract While progression to metastatic disease is the main cause of cancer death, little is known about the genomic mechanisms that drive metastasis. Rapidly growing clinical genomic data sets have the potential to identify genomic biomarkers of cancer metastasis, however, manual curation of clinical data is quickly emerging as a bottleneck. To overcome this challenge, we have developed a natural language processing (NLP) pipeline to identify organs affected by metastasis from radiology reports of patients with cancer. To develop our NLP models, we leveraged the AACR GENIE Biopharma Collaborative lung and colorectal cancer datasets generated in part at Memorial Sloan Kettering Cancer Center (MSK), containing curated labels of ten metastatic disease sites derived from 31,445 corresponding free-text radiology reports (2,310 patients). Using these data, we trained three machine learning models for identifying metastatic events from clinical text, using logistic regression, convolutional neural networks (CNN), and Bidirectional Encoder Representations from Transformers (BERT). We split patients into a training set (80% of patients) and validation set (20%). The BERT model yielded superior performance across evaluation metrics, with an average per metastatic disease site area under the receiver operating characteristic curve (AUC) of 0.981, average accuracy of 97.3%, macro-average precision/recall of 85.1/85.6, and micro-average precision/recall of 87.5/89.6. We applied our method to radiology reports from 52,000 patients with tumors prospectively profiled using the MSK-IMPACT clinical sequencing cohort. A comparison with the MSK-MET cohort, which contains metastatic events derived from billing codes in a subset of 25,000 patients, showed strong concordance (79.7% of metastatic events matched), with the NLP-based method identified an average of 1.4 additional metastatic sites per patient, an expected result given the incomplete nature of the billing code data. Analyzing genomic and clinical data in this cohort, we confirmed that chromosomal instability, as inferred by the fraction of genome altered (FGA), is strongly correlated with metastatic burden (defined as the number of distinct organs affected by metastases) in several tumor types, including prostate adenocarcinoma, lung adenocarcinoma and HR-positive breast ductal carcinoma, and we identified this trend in 10 additional cancer types not previously identified, including lobular HR-positive breast carcinoma and esophageal adenocarcinoma.We demonstrate that mining of electronic health records can be used to extract rich, structured clinical information. Our models, applied at scale, offer a unique resource for the investigation of the biological basis for metastatic spread. We hope our automated clinical data extractions can enable further large-scale studies of associations between genomic biomarkers and metastatic behavior. Citation Format: Anisha Luthra, Karl Pichotta, Brooke Mastrogiacomo, Samantha McCarthy, Steven Maron, Jianjiong Gao, Justin Jee, Christopher J. Fong, Nikolaus Schultz. A.I.-assisted clinical data curation to determine genomic biomarkers of cancer metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1158.

Abstract 2690: Loss of E-cadherin induces IGF1R activation revealing a targetable pathway in invasive lobular breast carcinoma

Abstract Invasive Ductal Carcinoma (IDC) and Invasive Lobular Carcinoma (ILC) are two major subtypes of breast cancer with significant differences in their histological and molecular underpinnings. ILC has a unique loss of E-cadherin (CDH1) which we have previously demonstrated as a negative regulator of the Insulin-like Growth Factor 1 receptor (IGF1R) through a comprehensive analysis of cell line models and tumor samples. We propose that loss of E-cadherin in ILC sensitizes cells to growth factor signaling and thus alters their sensitivity to growth factor signaling inhibitors. To investigate this, we used CRISPR to generate CDH1 knockout (KO) IDC cell lines (MCF7, T47D, ZR75.1) to uncover the mechanism by which E-cadherin loss activates the IGF pathway while also assessing its targetability. CDH1 KO cells exhibited anchorage independent growth in suspension culture and altered p120 catenin localization as observed in ILC tumors. Through in vitro studies, we show increased signaling sensitivity to IGF/insulin ligands and enhanced signaling duration in CDH1 KO cells. In addition, we observed a higher migratory potential of CDH1 KO cells compared to wild type (WT) cells, which was further enhanced as a chemotactic response to IGF1 or serum. Further, this phenotype could be reversed with an IGF1R inhibitor, BMS-754807. We additionally identified an increase in Collagen I haptotaxis in the CDH1 KO cells, which was also translated into a novel invasive phenotype towards serum in the T47D CDH1 KO cells. Despite no significant differences in membranous IGF1R levels between WT and CDH1 KO cells, higher ligand-receptor interaction was observed with CDH1 KO cells, demonstrating an increased ligand-receptor complex formation upon stimulation. Our results suggest that loss of CDH1 results in an increase in IGF1 receptor availability for ligand binding which in turn allows for an enhanced downstream signaling activation. Interestingly, a physical repression of E-cadherin on IGF1R could not be demonstrated, suggesting spatial changes on the membrane following E-cadherin loss may control ligand binding. Critically, increased sensitivity to IGF1R, PI3K, AKT and MEK inhibitors was observed in CDH1 KO cells suggesting that these targets should be further explored in ILC and that CDH1 loss may be exploited as a biomarker of response, or for patient stratification to inhibitors targeting these pathways. Citation Format: Ashuvinee Elangovan, Laura Savariau, Megan E. Yates, Jagmohan Hooda, Alison M. Nagle, Steffi Oesterreich, Jennifer M. Atkinson, Adrian V. Lee. Loss of E-cadherin induces IGF1R activation revealing a targetable pathway in invasive lobular breast carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2690.

Abstract 956: Role of E-cadherin in progression of invasive breast lobular carcinoma

Abstract Invasive lobular carcinoma (ILC) is the second most frequently diagnosed histologic subtype of invasive breast cancer following invasive ductal carcinoma (IDC) and accounts for 15% of all cases. The hallmark of ILC is the genetic loss of E-cadherin (CDH1) causing the disruption of adherens junctions and resulting in discohesive, linear growth of ILC cells in tissues. Beyond its effects on this unique histology, there is limited data on the role of E-cadherin loss in ILC metastasis. Therefore, we generated three ILC cell lines (MDA-MB-134, SUM44PE and BCK4) with inducible E-cadherin overexpression. Using immunoblotting and immunofluorescence microscopy we confirmed E-cadherin expression, re-expression of other adherens junction proteins including α and β-catenin, and re-localization of cytoplasmic p120-catenin to the membrane. Successful cell adhesion to E-cadherin coated plates suggested formation of functional junctions. E-cadherin expression had no effect on 2D growth but did diminish cell growth in ultra-low attachment (ULA) conditions consistent with its previously described role in anoikis. We confirmed increased cell death of MM134 with E-cadherin overexpression compared to control cells when grown in ULA. Overexpression of E-cadherin failed to rescue poor migratory and invasive ability of ILC cell lines as measured by transwell assays. However, E-cadherin expression in SUM44PE lead to decreased haptotaxis to collagen I, and altered morphology from loose grape-like structure to tight sphere-like formation when embedded in collagen I.In vivo analyses revealed reduced primary tumor formation in E-cadherin-overexpression SUM44PE cells after mammary fat pad injection. Additional studies aimed at understanding E-cadherin’s effect on in vivo metastasis are ongoing.Collectively, our studies using novel cell line models will lead to an improved understanding of the hallmark loss of E-cadherin and disease mechanisms in ILC, which we hope will ultimately enable the development of more effective therapies and improve the outcome of patients with this understudied histological subtype of breast cancer. Citation Format: Laura Savariau, Nilgun Tasdemir, Ashuvinee Elangovan, Kai Ding, Pooja Sree Tallapaneni, Jagmohan Hooda, Jennifer M. Atkinson, Adrian V. Lee, Steffi Oesterreich. Role of E-cadherin in progression of invasive breast lobular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 956.

Loss of E-cadherin Induces IGF1R Activation and Reveals a Targetable Pathway in Invasive Lobular Breast Carcinoma.

Overall, this suggests that these targets require further exploration in ILC treatment and that CDH1 loss may be exploited as a biomarker of response for patient stratification.

Development of Histologically Verified Thyroid Diseases in Women Operated for Breast Cancer: A Review of the Literature and a Case Series.

Background: The possible relationships between breast and thyroid diseases have been reported in the literature. The purpose of our study was to evaluate the occurrence of histologically verified thyroid pathologies in women who were diagnosed with breast cancer and, after mastectomy/quadrantectomy complemented by oncological treatment, were thyroidectomized based on their periodic thyroid evaluation. Patients and Methods: Our series consist of 31 women with a mean age of 62.9 ± 10.9 years (range, 45–81) treated for breast cancer (18 right-sided, 11 left-sided, and 2 bilateral), of whom 29 were thyroidectomized, since two women who developed Graves’ disease refused thyroidectomy. These 31 women belong to a cohort of 889 women who referred to the Breast Surgery Unit of our university hospital during the period January 2010 through December 2020. Results: The mean time interval between breast cancer and thyroid pathologies was 48.1 ± 23.4 months (range, 12–95). The final diagnosis at histopathology was infiltrating ductal breast carcinoma in 26 women (with 2/26 patients having bilateral carcinoma) and infiltrating lobular breast carcinoma in the other 5 women. Ten of the twenty-nine thyroidectomized women (34.5%) had a thyroid malignancy on histology: five papillary carcinomas, three papillary micro-carcinomas and two follicular carcinomas. Two of the five women with papillary carcinoma also had histological evidence of chronic lymphocytic thyroiditis/Hashimoto’s thyroiditis, which was also detected in another five women with benign thyroid diseases. Conclusions: We suggest that breast cancer survivors should be made aware of the possible increased risk of thyroid pathologies (including thyroid malignancy) so that they can undergo screening and follow-up.

Predicting Characteristics Associated with Breast Cancer Survival Using Multiple Machine Learning Approaches.

Breast cancer is one of the most commonly diagnosed female disorders globally. Numerous studies have been conducted to predict survival markers, although the majority of these analyses were conducted using simple statistical techniques. In lieu of that, this research employed machine learning approaches to develop models for identifying and visualizing relevant prognostic indications of breast cancer survival rates. A comprehensive hospital-based breast cancer dataset was collected from the National Cancer Institute's SEER Program's November 2017 update, which offers population-based cancer statistics. The dataset included female patients diagnosed between 2006 and 2010 with infiltrating duct and lobular carcinoma breast cancer (SEER primary cites recode NOS histology codes 8522/3). The dataset included nine predictor factors and one predictor variable that were linked to the patients' survival status (alive or dead). To identify important prognostic markers associated with breast cancer survival rates, prediction models were constructed using K-nearest neighbor (K-NN), decision tree (DT), gradient boosting (GB), random forest (RF), AdaBoost, logistic regression (LR), voting classifier, and support vector machine (SVM). All methods yielded close results in terms of model accuracy and calibration measures, with the lowest achieved from logistic regression (accuracy = 80.57 percent) and the greatest acquired from the random forest (accuracy = 94.64 percent). Notably, the multiple machine learning algorithms utilized in this research achieved high accuracy, suggesting that these approaches might be used as alternative prognostic tools in breast cancer survival studies, especially in the Asian area.

Loss of E-cadherin leads to Id2-dependent inhibition of cell cycle progression in metastatic lobular breast cancer

Invasive lobular breast carcinoma (ILC) is characterized by proliferative indolence and long-term latency relapses. This study aimed to identify how disseminating ILC cells control the balance between quiescence and cell cycle re-entry. In the absence of anchorage, ILC cells undergo a sustained cell cycle arrest in G0/G1 while maintaining viability. From the genes that are upregulated in anchorage independent ILC cells, we selected Inhibitor of DNA binding 2 (Id2), a mediator of cell cycle progression. Using loss-of-function experiments, we demonstrate that Id2 is essential for anchorage independent survival (anoikis resistance) in vitro and lung colonization in mice. Importantly, we find that under anchorage independent conditions, E-cadherin loss promotes expression of Id2 in multiple mouse and (organotypic) human models of ILC, an event that is caused by a direct p120-catenin/Kaiso-dependent transcriptional de-repression of the canonical Kaiso binding sequence TCCTGCNA. Conversely, stable inducible restoration of E-cadherin expression in the ILC cell line SUM44PE inhibits Id2 expression and anoikis resistance. We show evidence that Id2 accumulates in the cytosol, where it induces a sustained and CDK4/6-dependent G0/G1 cell cycle arrest through interaction with hypo-phosphorylated Rb. Finally, we find that Id2 is indeed enriched in ILC when compared to other breast cancers, and confirm cytosolic Id2 protein expression in primary ILC samples. In sum, we have linked mutational inactivation of E-cadherin to direct inhibition of cell cycle progression. Our work indicates that loss of E-cadherin and subsequent expression of Id2 drive indolence and dissemination of ILC. As such, E-cadherin and Id2 are promising candidates to stratify low and intermediate grade invasive breast cancers for the use of clinical cell cycle intervention drugs.

Adherence to a western dietary pattern and risk of invasive ductal and lobular breast carcinomas: a case\u2013control study

Little is known about the role of diet in the risk of invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) of the breast, the most common histological subtypes of breast cancer (BC). This is because, the majority of studies on the association of diet and the risk of BC are focused on single food items, and studies considering the overall diet in terms of dietary patterns are limited. Also, the potential heterogeneity in the impact of Western diet (WD) on histological subtypes of BC is not established. This, the age-frequency-matched case–control study included 1009 incident BC cases and 1009 healthy controls. The required data was obtained from the patients’ medical files and interviews using a previously validated researcher-designed questionnaire for collecting data on socio-economic and anthropometric statuses and a valid food frequency questionnaire (FFQ) to measure the participants’ dietary intake. We used multinomial logistic regression, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. A positive and significant association was observed between higher adherence to a WD and risk of IDC (OR comparing highest with the lowest tertile: 2.45, 95% CI 1.88, 3.17; p-trend < 0.001), whereas no significant association was observed between adherence to the WD and the risk of ILC (OR comparing highest with the lowest tertile: 1.63, 95% CI 0.63, 3.25) (p for heterogeneity = 0.03). The results of an analysis stratified by menopausal status suggested a similar pattern. We provided evidence that adherence to a WD raises the risk of IDC, but not ILC, suggesting different etiological mechanisms for IDC and ILC.

A review on the added value of whole-body MRI in metastatic lobular breast cancer.

Invasive lobular breast carcinomas (ILC) account for approximately 15% of breast cancer diagnoses. They can be difficult to diagnose both clinically and radiologically, due to their infiltrative growth pattern. The pattern of metastasis of ILC is unusual, with spread to the serosal surfaces (pleura and peritoneum), retroperitoneum and gastrointestinal (GI)/genitourinary (GU) tracts and a higher rate of leptomeningeal spread than IDC. Routine staging and response assessment with computed tomography (CT) can be undertaken quickly and measurements can be reproduced easily, but this is challenging with metastatic ILC as bone-only/bone-predominant patterns are frequently seen and assessment of the disease status is limited in these scenarios. Functional imaging such as whole-body MRI (WBMRI) allows the assessment of bone and soft tissue disease by providing functional information related to differences in cellular density between malignant and benign tissues. A number of recent studies have shown that WBMRI can detect additional sites of disease in metastatic breast cancer (MBC), resulting in a change in systemic anti-cancer therapy. Although WBMRI and fluorodeoxyglucose-positron-emission tomography-computed tomography (FDG-PET/CT) have a comparable performance in the assessment of MBC, WBMRI can be particularly valuable as a proportion of ILC are non-FDG-avid, resulting in the underestimation of the disease extent. In this review, we explore the added value of WBMRI in the evaluation of metastatic ILC and compare it with other imaging modalities such as CT and FDG-PET/CT. We also discuss the spectrum of WBMRI findings of the different metastatic sites of ILC with CT and FDG-PET/CT correlation. KEY POINTS: • ILC has an unusual pattern of spread compared to IDC, with metastases to the peritoneum, retroperitoneum and GI and GU tracts, but the bones and liver are the commonest sites. • WBMRI allows functional assessment of metastatic disease, particularly in bone-only and bone-predominant metastatic cancers such as ILC where evaluation with CT can be challenging and limited. • WBMRI can detect more sites of disease compared with CT, can reveal disease progression earlier and provides the opportunity to change ineffective systemic treatment sooner.

Application of organometallic chemistry in the formulation of a modern therapeutic drug by Ag nanoparticles green-mediated by Allium to treat the breast cancer

In the recent study, we decided to survey the capacities of metallic nanoparticles formulated by Allium monanthum (AgNPs) as a novel chemotherapeutic drug in the treatment of several types of breast cancers. Characterization of AgNPs was done by UV–Visible Spectroscopy (UV–Vis), Fourier Transformed Infrared Spectroscopy (FT‐IR), Transmission Electron Microscopy (TEM), and Field Emission Scanning Electron Microscopy (FE‐SEM). For investigating the antioxidant properties of AgNO 3 , Allium monanthum , and AgNPs, the DPPH test was used in the presence of butylated hydroxytoluene as the positive control. To survey the cytotoxicity and anti-breast cancer effects of AgNO 3 , Allium monanthum , and AgNPs, MTT assay was used on the breast adenocarcinoma (MCF7), breast carcinoma (Hs 578Bst), infiltrating ductal cell carcinoma (Hs 319.T), infiltrating lobular carcinoma of breast (UACC-3133), inflammatory carcinoma of the breast (UACC-732), and metastatic carcinoma (MDA-MB-453) cell lines. DPPH test revealed similar antioxidant potentials for Allium monanthum , AgNPs, and butylated hydroxytoluene. Silver nanoparticles had very low cell viability and anti-breast cancer properties dose-dependently against MCF7, Hs 578Bst, Hs 319.T, UACC-3133, UACC-732, and MDA-MB-453 cell lines without any cytotoxicity on the normal cell line. The best result of anti-breast cancer properties of AgNPs against the above cell lines was seen in the case of the UACC-3133 cell line. According to the above findings, the silver nanoparticles containing Allium monanthum aqueous extract can be administrated in humans for the treatment of several types of breast cancer especially breast adenocarcinoma, breast carcinoma, infiltrating ductal cell carcinoma, infiltrating lobular carcinoma of breast, inflammatory carcinoma of the breast, and metastatic carcinoma.

Duodenal Metastasis of Breast Cancer: A Case Report and Review of the Literature

Rationale: The usual metastases of breast cancer are mainly represented by the following organs: lymph nodes, bone, liver, lung, pleura and brain. While gastrointestinal involvement remains rare. Patient Concerns: A 67-year-old postmenopausal woman presented with abdominal pain and obstructive symptoms, she was diagnosed with duodenal metastasis of breast cancer with infiltration of the duodenal mucosa by lobular breast carcinoma. The patient had undergone the right breast mastectomy for infiltrating lobular carcinoma 6 years previously. Diagnosis: Metastatic infiltration of the duodenal mucosa by mammary lobular carcinoma was proven histologically and immunohistochemically. Lessons: The importance of thinking about metastases of the gastrointestinal tract in the presence of non-specific and vague symptoms and of clearly differentiating in this context these metastases from primary gastrointestinal tumors.

Green preparation of copper nanoparticle-loaded chitosan/alginate bio-composite: Investigation of its cytotoxicity, antioxidant and anti-human breast cancer properties

In this study, an eco-friendly and low-cost procedure for the in situ fabrication of Cu nanoparticles by using chitosan/alginate hydrogel. The prepared Cu [email protected]/Alg nanocomposite were characterized by advanced physicochemical techniques like Fourier Transformed Infrared spectroscopy (FT-IR), Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), Energy Dispersive X-ray spectroscopy (EDX) and X-ray Diffraction (XRD) study. It has been established that chitosan/alginate-capped gold nanoparticles have a spherical shape with a mean diameter from 10 to 20 nm. In the cellular and molecular part of the recent study, the treated cells with Cu [email protected]/Alg nanocomposite were assessed by MTT assay for 48 h about the cytotoxicity and anti-human breast cancer properties on normal (HUVEC) and breast cancer cell lines i.e. infiltrating lobular carcinoma of breast (UACC-3133), inflammatory carcinoma of the breast (UACC-732), and metastatic carcinoma (MDA-MB-453). In the antioxidant test, the IC50 of Cu [email protected]/Alg nanocomposite and BHT against DPPH free radicals were 344 and 193 µg/mL, respectively. The IC50 of Cu [email protected]/Alg nanocomposite were 297, 386, and 359 µg/mL against KYSE-270, OE33, and ESO26 cell lines, respectively. The viability of malignant breast cell line reduced dose-dependently in the presence of Cu [email protected]/Alg nanocomposite.

Abstract P3-04-03: The value of screening MRI in patients with high-risk breast lesions: An observational single-institution cohort study

Abstract Background: The value of screening MRI in women with a history of breast atypical hyperplasia (AH) or lobular carcinoma in situ (LCIS), collectively termed high-risk lesions (HRL), remains unclear. In our high-risk clinic, we recommend annual mammograms (MMG) and consideration of annual breast MRI, with an emphasis on shared decision-making between patients and providers regarding MRI. Here we report cancer detection rates and outcomes by screening strategy.Methods: Patients with personal history of an HRL evaluated in the Brigham and Women’s Hospital high-risk clinic between 2015-2020 were identified from a prospective database. We excluded those whose HRL upgraded to malignancy at excision, or with a known pathogenic variant in a breast cancer gene. Patient characteristics associated with MRI use were compared with univariable and multivariable logistic regression. Kaplan Meier methods, univariable and multivariable Cox proportional hazards models were used to compare breast cancer detection and biopsy rates during follow-up.Results: Among 914 eligible patients with an HRL, 716 (78%) with at least two clinical visits were included for analysis. Screening MRI was used in 147 (21%) patients; 54% had 1 MRI, 29% had 2 MRIs, and 17% had 3-5 MRIs. Those receiving MRI were significantly younger and more likely to be white, premenopausal, have extremely dense breasts on MMG, normal body mass index, a family member age&amp;lt;50 with breast cancer, LCIS (vs. AH), and higher lifetime breast cancer risk by the Tyrer Cuzick model (all p&amp;lt;0.02). Chemoprevention (CP) was used in 276 (39%) patients and was more common in those receiving MRI (48% vs. 36%, p&amp;lt;0.01). In multivariable analysis, age (OR 0.96, p=0.02), white race (OR 2.98, p&amp;lt;0.01), LCIS (OR 1.72, p=0.03) and CP use (OR 1.68, p=0.01) remained significantly associated with MRI use, with a trend seen for extremely dense breasts (OR 1.6, p=0.07).At a median follow-up of 21 months (IQR: 11-35), 12 (1.7%) patients developed breast cancer, 4 receiving screening MRI and 8 not receiving MRI. The 3-year rate of breast cancer detection was 2.6% (95%CI: 0.8-8.0%) in those with MRI and 2.0% (95%CI: 0.9-5.4%) in those without MRI (p=0.53). Adjusting for age, LCIS vs. AH and CP use, MRI screening was not associated with increased likelihood of cancer detection (HR 1.35, p=0.64). Patients having MRI screening were significantly more likely to require a biopsy during surveillance; 3-year biopsy rates were 24.0% vs. 8.5% (p&amp;lt;0.01).Of the 12 cancers, 3 were DCIS and 8 invasive carcinomas, all clinically node negative, hormone receptor positive and AJCC pathologic prognostic stage 0-I. The remaining 1 cancer was an angiosarcoma. Most of the invasive carcinomas were &amp;lt;2cm (7/8 [88%], median 1.2cm), grade 1-2 (7/8 [88%]), HER2 negative (7/8 [88%]) and pathologic node negative (5/7 [71%] with sentinel node biopsy performed). Of the 4 cancers in those receiving MRI, 50% were visible on MMG. The 2 mammographically occult lesions were 6mm and 2cm MR-detected masses, corresponding to a pT1aN0 invasive tubular carcinoma and a 1.5cm angiosarcoma, respectively.Conclusions: In our high-risk clinic, MRI use was selective, most commonly in women who were younger, white, had LCIS and/or extreme breast density. CP is routinely recommended, yet uptake rates were higher in those receiving MRI, suggesting patient interest in preventative health measures likely also played a role in MRI use. Among patients with an HRL, the 3-year cancer detection rate was 2%, with no difference in rates between those undergoing screening MRI vs. annual MMG alone. However, MRI was associated with a threefold increased risk of breast biopsy. All cancers detected were early stage and clinically node negative. While longer follow-up is needed, the value of MRI screening in patients with HRL appears to be low. Citation Format: Alison Laws, Fisher Katlin, Marybeth Hans, Mary Graichen, Olga Kantor, Christina Minami, Brittany Bychkovsky, Lydia Pace, Rochelle Scheib, Judy Garber, Tari King. The value of screening MRI in patients with high-risk breast lesions: An observational single-institution cohort study [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-04-03.

Abstract P1-05-03: Integrating spatial transcriptomics and high-resolution morphological annotation to investigate tumor heterogeneity and PAM50 molecular subtyping in lobular breast cancer

Abstract Background: Invasive lobular breast carcinoma (ILC) represents 5 to 15% of all invasive breast cancers (BCs). Here, we aim to investigate inter- and intra-tumor heterogeneity in terms of microenvironment composition, PAM50 molecular classification and proliferation (genomic grade index [GGI]) by combining spatial transcriptomics (ST) and accurate morphological annotation. Methods: Spatial RNA sequencing (Visium - 10X Genomics) was performed on frozen tumor samples from 15 primary estrogen receptor positive, HER2-negative ILC patients with long-term follow up. Hematoxylin/eosin slides were morphologically annotated integrating manual and machine learning-based approaches reaching single-cell resolution (QuPath software). The relative histomorphological categories (HC) composition of each spot across the ST slide was computed as percentage of pixels, while the level of proximity of different HC was evaluated computing the proportion of co-occurring HC at each spot. The PAM50 subtypes (AIMS R package) and GGI were computed on spots containing at least 40% of tumor (merging all the spots belonging to each sample [pseudo-bulk] for PAM50, while calculating mean and standard deviation [SD] across spots for GGI). PAM50 was also computed on the pseudo-bulk of the whole set of spots per sample. Wilcoxon and Spearman rank tests were used to compare continuous variables and assess correlations. Results: Out of 15 tumors, 7 were T2 or T3, 6 were node positive at diagnosis and 14 were grade 2. Four patients experienced disease relapse. Morphological annotation revealed that an average (per patient) of 20.3% (5.6-46.7%), 65.9% (45.5-83.5%) and 6.5% (0.0-27.1%) of the spots corresponded to tumor, stroma and fat tissue respectively. Larger tumors (T2-3 vs T1) presented a higher proportion of fat tissue and tumor cells, although these differences did not reach statistical significance. The levels and spatial variability of proliferation, measured using GGI, were higher in T2-3 compared to T1 tumors (p = 0.072 and 0.040, respectively). Of note, higher spatial variability of proliferation was also associated with node-positive tumors (p = 0.066). By computing the PAM50 classification using the pseudo-bulk, 9 samples were classified as luminal A, 1 as luminal B and 5 as normal-like. Of interest, when focusing on the tumor enriched spots, 60% of the samples previously classified as normal-like were re-classified as luminal A. Samples from patients who relapsed showed a higher fraction of fat tissue at the level of the whole slide (14.4% vs 3.5%; p = 0.018), with an increased co-localization of fat tissue and tumor cells at the spot level as well as higher proliferation values, although not significant. Conclusions: High proportion of fat tissue together with higher co-localization of fat tissue with tumor cells are associated with poor outcome in ILC. Higher spatial variability of proliferation is associated with larger tumors, lymph node positivity and recurrence. The proportion of stroma and fat tissue affected substantially the PAM50 classification of the tumors. Further validation is needed. Citation Format: Matteo Serra, Laetitia Collet, Mattia Rediti, Frédéric Lifrange, David Venet, Xiaoxiao Wang, Delphine Vincent, Ghizlane Rouas, Danai Fimereli, David Gacquer, Andrea Joaquin Garcia, Isabelle Veys, Ligia Craciun, Denis Larsimont, Miikka Vikkula, François Duhoux, Françoise Rothé, Christos Sotiriou. Integrating spatial transcriptomics and high-resolution morphological annotation to investigate tumor heterogeneity and PAM50 molecular subtyping in lobular breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-05-03.

The association between migraine and breast cancer risk: A systematic review and meta-analysis.

BackgroundMigraines is likely to play a protective role in the risk of breast cancer. Some studies have shown that there is an inverse relationship between migraine and breast cancer, and some studies have not found an association; therefore, results from previous studies have been inconclusive and we conducted a meta-analysis to evaluate association between migraine and breast cancer.MethodsPubMed, EMBASE, Scopus and Web of Science were searched to identify studies on the association between migraine and breast cancer from January 1, 2000 through March 12, 2021. The pooled relative risk (RR) and the 95% confidence intervals (CI) was used to measure this relationship by assuming a random effects meta-analytic model.ResultsA total of 10 studies were included. Our study revealed that there was statistically significant inverse relationship between migraine and breast cancer in case-control studies 0.68 [95% CI: 0.56, 0.82], but no significant relationship was found in cohort studies 0.98 [95% CI: 0.91, 1.06]. Also, migraine reduced the risk of ductal carcinoma 0.84 [95% CI: 0.73, 0.96], and lobular carcinoma 0.83 [95% CI: 0.73, 0.96]. With respect to ER_PR status no association between migraine and breast cancer was found. We found no evidence of publication bias.ConclusionOur analysis demonstrated a statistically significantly inverse relationship between migraine and total risk of breast cancer only in case-control studies. In summary, cohort studies do not support an inverse association between migraine and incident breast cancer. While in case-control studies, migraine has an inverse association with ductal carcinoma and lobular carcinoma of breast.

De novo metastatic lobular breast carcinoma: A population-based study from SEER database

PurposePatients with metastatic lobular breast carcinoma constitute a heterogeneous group with distinguishing features. Our aim was to describe the features and survival of them, and further subdivide them into subcategories for prognostic stratification and treatment planning. Patients and methodsPatients with de novo metastatic breast cancer from 2010 to 2018 were identified using the SEER database. Multivariate logistic regression analysis was conducted to calculate odds ratios. The within-pair difference was minimized by propensity score matching. Multiple comparisons based on Cox proportional hazards model were performed to investigate the interactions of M1 subcategory and treatment modality on survival. ResultsA total of 1,675 patients with de novo metastatic lobular breast carcinoma were identified, they were more likely to have HR+/HER2- subtype, low histologic grade, low T/N stage, fewer metastatic sites, but worse prognosis compared with patients with metastatic ductular breast carcinoma. The M1 stage was subdivided into 3 subcategories with significantly different prognoses. The benefits of primary tumor surgery were more pronounced in M1a/b disease, whereas the benefits of chemotherapy increased with the progression of metastatic disease. ConclusionPatients with metastatic lobular breast carcinoma have unique clinicopathological characteristics and metastatic patterns. M1 subcategory assists prognosis stratification and treatment planning for such patients.

Anti-breast carcinoma effects of green synthesized nickel nanoparticles from Alhagi ‎sparsifolia leaf aqueous extract: A pre-clinical trial study ‎

IntroductionMany nanoparticles have pharmacological and biochemical properties, including antioxidant and anti-‎inflammatory properties, which appear to be involved in anticarcinogenic and antimutagenic activities. In the recent study, nickel nanoparticles were green-synthesized using the Alhagi sparsifolia leaf aqueous ‎extract. ‎Material and methodsThe synthesized Ni nanoparticles‎ were characterized by analytical techniques including SEM, UV-Vis., and FT-‎IR. The nanoparticles were formed in a spherical shape in the average size of 16.19 nm. ‎ResultsIn the antioxidant test, the IC50 of Ni nanoparticles‎ and BHT against DPPH free radicals were 316 and 231 ‎‎µg/mL, respectively. In the cellular and molecular part of the recent study, the treated cells with Ni ‎nanoparticles‎ were assessed by MTT assay for 48h about the cytotoxicity and anti-human breast cancer ‎properties on normal (HUVEC) and breast cancer cell lines i.e. lobular carcinoma of breast (UACC-3133), ‎inflammatory carcinoma of the breast (UACC-732), and metastatic carcinoma (MDA-MB-453). The viability of ‎malignant breast cell line reduced dose-dependently in the presence of Ni nanoparticles‎. The IC50 of Ni ‎nanoparticles‎ were 477, 548, and 605 µg/mL against lobular carcinoma of breast (UACC-3133), inflammatory ‎carcinoma of the breast (UACC-732), and metastatic carcinoma (MDA-MB-453) cell lines, respectively. ‎ConclusionsAfter clinical study, nickel nanoparticles containing Alhagi sparsifolia leaf aqueous extract may be used to ‎formulate a new chemotherapeutic drug or supplement to treat the several types of human breast cancer. ‎

Incidental solitary gallbladder metastasis from lobular breast carcinoma: a case report

Incidental solitary gallbladder metastasis from lobular breast carcinoma: a case report

Axillary Adenocarcinoma Mimicking Apocrine Carcinoma or Invasive Lobular Carcinoma of the Accessory Breast in a Male—A Case Report—

Axillary Adenocarcinoma Mimicking Apocrine Carcinoma or Invasive Lobular Carcinoma of the Accessory Breast in a Male—A Case Report—

Atypical Breast CarcinomaA Series of Six Cases

Breast cancer comprises 10.4% of all cancer among women world and it the second most common type of cancer. Increased public awareness and screening have led to earlier diagnosis at different stages. Surgical resection can be done earlier and complete cure of the disease can be achieved. As a result survival rates for breast cancer in young women have improved significantly. Six unusual type of breast carcinoma, presented to the Surgery Outpatient Department were referred to Pathology Department for further investigations. Patient age and sex, clinical characteristics of the tumour, the duration of the lesion, the size, radiological investigation, Fine Needle Aspiration Cytology (FNAC), trucut biopsy and histopathological examination were noted. Immunohistochemical examination also done in all the cases. Out of the six cases of breast carcinoma, one was the mucinous carcinoma of breast, two invasive papillary breast carcinoma, one apocrine carcinoma, one invasive Pleomorphic Lobular Carcinoma (PLC) of breast and one was fibromatosis like metaplastic carcinoma of breast. All the patients were female except, a 71-year-old male who presented with invasive papillary carcinoma. All the female patients were presented at postmenopausal age group. After careful examination of the cytology and histopathological slides the final diagnosis was made which helped the clinician for further treatment. Rare breast cancers do not differ from other types of breast cancer in their presentation. But they vary by treatment regimens and outcomes. So, proper diagnosis with imaging, FNAC, trucut biopsy and histopathological examination is a combined tool for proper diagnosis and treatment.