Lobular Carcinoma Of Breast Research Articles

The Role of E-cadherin in the Differentiation of Ductal and Lobular Breast Carcinomas

Background: Diagnosis of certain types of breast cancer can be difficult due to similarities in their histopathological patterns. In such cases markers can be useful in confirming results. E-cadherin is one such marker. Objective: To differentiate the rate of E-cadherin immunohistochemical expression between the major histological types of breast cancer (lobular versus ductal), in addition to correlating it to the clinicopathological factors such as age of patients and grade of the tumor and explore the effectiveness of using it in distinguishing the cases with overlapping features. Patients and Methods: A total of 100 malignant breast samples (55 ductal lesions, 24 lobular lesions, and 21 uncertain types), collected during the period of 2014 – 2017 in Erbil, and were reviewed before undergoing E-cadherin immunohistochemistry (IHC) staining. The results from IHC were compared with the results from the morphological study of the samples and they were statistically analyzed in relation with clinicopathological factors. Results: The normal ductal cells had strong complete homogenous membrane E-cadherin reactivity in 85% of the ductal carcinoma cases. The complete absence of E-cadherin membrane staining occurred in all 24 cases of lobular cases. The rest of the 21 cases, showed variable degrees of staining. Conclusion: There is diagnostic usefulness in the detection of E-cadherin expression by immunohistochemistry as a tool in distinguishing ductal from lobular carcinoma.

Breast lobular carcinoma in situ associated podocytopathy

Paraneoplastic glomerular diseases are rare. While membranous nephropathy has been classically associated with solid malignancies, minimal change disease has been commonly described with hematologic malignancies. Other podocytopathies such as focal segmental glomerulosclerosis have not been classically associated with solid malignancy. In this case report, we present a case of a 52-year-old female with a diagnosis of focal segmental glomerulosclerosis associated with breast lobular carcinoma in situ. The focal segmental glomerulosclerosis diagnosis preceded the diagnosis of the breast cancer. While the proteinuria came into partial remission with conservative management, a dramatic resolution of focal segmental glomerulosclerosis was noted post-surgery and hormonal therapy for the breast cancer.

Asymptomatic solitary metastasis to the stomach from breast cancer: A case report.

Distant metastases from breast cancer are frequently found in bones, lungs and the liver. Metastasis to the stomach is rare, and its clinical presentation remains unclear. The present report describes a case of isolated gastric metastasis from breast cancer identified by contrast-enhanced computed tomography (CT). A 45-year-old female patient underwent right mastectomy and axillary lymph node dissection after preoperative chemotherapy for right invasive lobular breast carcinoma T4bN2M0, stage IIIB. Postoperative radiotherapy and endocrine therapy with tamoxifen for 5 years were performed. CT for postoperative follow-up at 52 years old revealed thickening of the stomach wall. Although the patient was asymptomatic, erosive mucosa was observed on the gastric body during gastroscopy. The gastric lesion was immunohistochemically diagnosed as metastatic luminal disease from the breast cancer. Positron emission tomography/CT revealed no abnormal accumulation suggesting metastasis to other organs. Palbociclib and fulvestrant treatment were initiated for gastric metastasis. Invasive lobular breast carcinoma results in gastrointestinal metastasis, including the stomach, more frequently than invasive ductal breast carcinoma. However, most gastric metastases occur simultaneously with systemic metastases. Solitary metastasis to the stomach without symptoms as in this case has rarely been reported. The possibility of gastric metastasis should be considered among the differential diagnoses, even in the absence of symptoms, when gastrointestinal abnormalities are seen on CT in patients with a history of breast cancer.

Abstract LB-002: ER alpha-positive human cell line xenograft models recapitulate metastatic dissemination and endocrine response of invasive lobular breast carcinoma

Abstract Invasive lobular breast carcinoma (ILC) is the most common special histological subtype of breast cancer, accounting for 10-15% of all cases, and characterized by the loss of adherens junctions through inactivating mutations in E-cadherin. Although currently existing genetically engineered mouse models of ILC faithfully capture its dyscohesive, single-file growth and expression of estrogen receptor alpha (ER), they do not fully recapitulate all aspects of human ILC such as unique sites of metastases and endocrine response. While recent work on human ILC cell lines has proven them useful for studying ILC in vitro, there is limited data on their growth as xenografts in mice and their fidelity as in vivo models. Using dual bioluminescent and fluorescent labeled ER-positive human ILC cell lines (MDA-MB-134, SUM44PE, MDA-MB-330, BCK4), herein we characterized their growth orthotopically and at secondary sites following spontaneous or experimental metastasis. Mammary fat pad xenografts gave rise to primary tumors with single-file infiltration and cytoplasmic translocation of p120-catenin, characteristic of human ILC. The tumor microenvironment exhibited deposition of collagen fibers and infiltration by fibroblasts and neutrophils. In this orthotopic model, we observed spontaneous metastases of most cell lines to bones, brain and ovaries, closely mirroring the clinical patterns of human ILC dissemination. In contrast, experimental metastases were only observed following intravenous or intracardiac xenografts of MDA-MB-134 cells. Interestingly, tail vein injections of this cell line lead to colonization of bones and lymph nodes but not of lungs, while intracardiac injections resulted in brain, bone and lymph node metastases. Importantly, we observed high ER expression in the primary tumors and the metastatic lesions, along with a significant response to the selective ER down-regulator fulvestrant in both the mammary fat pad and intracardiac models. Ongoing work focused on genomic and transcriptional analyses of primary tumors and metastases, as well as of cell lines isolated from these lesions, will reveal additional mechanistic insights into the biology of ILC dissemination. This is the first report of ER-positive and endocrine responsive human cell line xenografts faithfully representing unique ILC features such as ovarian metastases. These versatile models will serve as an invaluable pre-clinical platform for validating candidate ILC genetic drivers and testing novel therapeutics towards translation into the clinic. Citation Format: Nilgun Tasdemir, Laura Savariau, Julie Scott, Joseph D. Latoche, Weizhou Hou, Kyle Biery, Minji Chung, Emily A. Bossart, Sreeja Sreekumar, Daniel D. Brown, Azadeh Nasrazadani, Ye Qin, Jagmohan Hooda, Fangyuan Chen, Carlos A. Castro, Carolyn J. Anderson, Jennifer Atkinson, Peter C. Lucas, Nancy E. Davison, Adrian V. Lee, Steffi Oesterreich. ER alpha-positive human cell line xenograft models recapitulate metastatic dissemination and endocrine response of invasive lobular breast carcinoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-002.

Targetable ERBB2 mutation status is an independent marker of adverse prognosis in estrogen receptor positive, ERBB2 non-amplified primary lobular breast carcinoma: a retrospective in silico analysis of public datasets

BackgroundInvasive lobular carcinoma (ILC) accounts for 10–15% of primary breast cancers and is typically estrogen receptor alpha positive (ER+) and ERBB2 non-amplified. Somatic mutations in ERBB2/3 are emerging as a tractable mechanism underlying enhanced human epidermal growth factor 2 (HER2) activity. We tested the hypothesis that therapeutically targetable ERBB2/3 mutations in primary ILC of the breast associate with poor survival outcome in large public datasets.MethodsWe performed in silico comparison of ERBB2 non-amplified cases of ER+ stage I–III primary ILC (N = 279) and invasive ductal carcinoma (IDC, N = 1301) using METABRIC, TCGA, and MSK-IMPACT information. Activating mutations amenable to HER2-directed therapy with neratinib were identified using existing functional data from in vitro cell line and xenograft experiments. Multivariate analysis of 10-year overall survival (OS) with tumor size, grade, and lymph node status was performed using a Cox regression model. Differential gene expression analyses by ERBB2 mutation and amplification status was performed using weighted average differences and an in silico model of response to neratinib derived from breast cancer cell lines.ResultsILC tumors comprised 17.7% of all cases in the dataset but accounted for 47.1% of ERBB2-mutated cases. Mutations in ERBB2 were enriched in ILC vs. IDC cases (5.7%, N = 16 vs. 1.4%, N = 18, p < 0.0001) and clustered in the tyrosine kinase domain of HER2. ERBB3 mutations were not enriched in ILC (1.1%, N = 3 vs. 1.8%, N = 23; p = 0.604). Median OS for patients with ERBB2-mutant ILC tumors was 66 months vs. 211 months for ERBB2 wild-type (p = 0.0001), and 159 vs. 166 months (p = 0.733) for IDC tumors. Targetable ERBB2 mutational status was an independent prognostic marker of 10-year OS—but only in ILC (hazard ratio, HR = 3.7, 95% CI 1.2–11.0; p = 0.021). Findings were validated using a novel ERBB2 mutation gene enrichment score (HR for 10-year OS in ILC = 2.3, 95% CI 1.04–5.05; p = 0.040).ConclusionsTargetable ERBB2 mutations are enriched in primary ILC and their detection represents an actionable strategy with the potential to improve patient outcomes. Biomarker-led clinical trials of adjuvant HER-targeted therapy are warranted for patients with ERBB2-mutated primary ILC.

Metastatic Breast Lobular Carcinoma to Unusual Sites: A Report of Three Cases and Review of Literature

Invasive lobular carcinoma of the breast is the second most common type of invasive breast carcinoma. Invasive lobular carcinoma has an unusual pattern of metastases, which poses a diagnostic challenge for both clinicians and pathologists. We herein present three cases of breast invasive lobular carcinoma presented with metastasis to unusual sites, namely, uterus, colon and stomach. We recommend a higher index of suspicion in any case with breast cancer developing gastrointestinal tract or genital tract symptoms. J Med Cases. 2020;11(9):292-295 doi: https://doi.org/10.14740/jmc3538

Lobular to Lobule: Metastatic Breast Carcinoma to Olfactory Neuroblastoma.

Tumor-to-tumor metastasis (TTM) is a rare, but well-described phenomenon occurring in patients with multiple synchronous or metachronous primary malignancies. Olfactory neuroblastoma (ONB) is a rare malignant, neuroectodermal sinonasal tract tumor that occurs within the ethmoid sinus involving the cribriform plate. Very few cases of ONB have been documented to metastasize to other primary malignancies, but the reverse scenario is exceptional. During an evaluation for anosmia, a right nasal polyp was identified on imaging and endoscopy in a 66-year-old woman, with a polypectomy performed. Histologic examination showed classical features of a low-grade olfactory neuroblastoma, but within the tumor wereisolated epithelioid cells which were strongly pancytokeratin immunoreactive. Review of the clinical history revealed lobular breast carcinoma treated 10years earlier. Further evaluation with immunohistochemistry showed strong and diffuse nuclear estrogen and progesterone receptor reactivity, along with GATA3. These results confirmed TTM of an invasive lobular breast carcinoma to ONB. By employing a limited immunohistochemistry panel for all small round blue cell tumors that includes pancytokeratin, p40, S100 protein, SOX10, synaptophysin, desmin, CD99, and CD45, one is able to more accurately diagnose the classical tumor types, while also showing potentially unusual tumor features or exceptionally rare events like metastatic lobular breast carcinoma to ONB.

Differential Regulation and Targeting of Estrogen Receptor α Turnover in Invasive Lobular Breast Carcinoma.

Invasive lobular breast carcinoma (ILC) accounts for 10% to 15% of breast cancers diagnosed annually. Evidence suggests that some aspects of endocrine treatment response might differ between invasive ductal carcinoma (IDC) and ILC, and that patients with ILC have worse long-term survival. We analyzed The Cancer Genome Atlas dataset and observed lower levels of ESR1 mRNA (P = 0.002) and ERα protein (P = 0.038) in ER+ ILC (n = 137) compared to IDC (n = 554), and further confirmed the mRNA difference in a local UPMC cohort (ILC, n = 143; IDC, n = 877; P < 0.005). In both datasets, the correlation between ESR1 mRNA and ERα protein was weaker in ILC, suggesting differential post-transcriptional regulation of ERα. In vitro, 17β-estradiol (E2) decreased the rate of degradation and increased the half-life of ERα in ILC cell lines, whereas the opposite was observed in IDC cell lines. Further, E2 failed to induce robust ubiquitination of ERα in ILC cells. To determine the potential clinical relevance of these findings, we evaluated the effect of 2 selective estrogen receptor downregulators (SERDs), ICI 182,780 and AZD9496, on ERα turnover and cell growth. While ICI 182,780 and AZD9496 showed similar effects in IDC cells, in ILC cell lines, AZD9496 was not as effective as ICI 182,780 in decreasing ERα stability and E2-induced proliferation. Furthermore, AZD9496 exhibited partial agonist activity in growth assays in ILC cell lines. Our study provides evidence for a distinct ERα regulation by SERDs in ILC cell lines, and therefore it is important to include ILC models into preclinical and clinical testing of novel SERDs.

Metastatic Lobular Breast Cancer Mimicking Colitis

Breast cancer is the most frequent cancer diagnosed in women in the world regardless of race or ethnicity. About 10% of invasive breast carcinomas are lobular subtype. The loss of the E-caderin expression that occurs in lobular carcinoma leads to a higher risk of metastases in membranes (meningeal, pleural, peritoneum) and gastrointestinal and/or endobronchial mucous, which may lead to several odd symptomatology. We report a 79 years old female patient with lobular breast cancer associated to CDH1 germline mutation. She was diagnosed with breast cancer in December 2016 after noticing a right-armpit nodule whose pathological examination demonstrated an immunohistochemistry profile compatible with lobular breast carcinoma metastasis and had estrogen receptors 98%, progesterone receptors &lt; 1%, ki67 25%, negative her2 score. Family history of only one paternal uncle with stomach cancer. After two lines of hormone therapy, she had disease progression and started oral chemotherapy with capecitabine. In a few weeks, the patient had refractory diarrhea. At the beginning, it was defined like colitis chemotherapy related. However, the clinical features showed necessity of further investigation. Then, she was diagnosed with CDH1 germline mutation after massive progression at gastrointestinal mucous. This case made possible to inform the family about risk of germline mutation and necessity of genetic counseling.

Hereditary Gastric and Breast Cancer Syndromes Related to CDH1 Germline Mutation: A Multidisciplinary Clinical Review.

E-cadherin (CDH1 gene) germline mutations are associated with the development of diffuse gastric cancer in the context of the so-called hereditary diffuse gastric syndrome, and with an inherited predisposition of lobular breast carcinoma. In 2019, the international gastric cancer linkage consortium revised the clinical criteria and established guidelines for the genetic screening of CDH1 germline syndromes. Nevertheless, the introduction of multigene panel testing in clinical practice has led to an increased identification of E-cadherin mutations in individuals without a positive family history of gastric or breast cancers. This observation motivated us to review and present a novel multidisciplinary clinical approach (nutritional, surgical, and image screening) for single subjects who present germline CDH1 mutations but do not fulfil the classic clinical criteria, namely those identified as—(1) incidental finding and (2) individuals with lobular breast cancer without family history of gastric cancer (GC).

Histomorphological evaluation of Breast carcinoma – A study of 15 cases

Purpose/Objective: Breast cancer occurs in any of the cells of the mammary gland and exhibits a wide scope of morphological features, different immunohistochemical profiles, and unique histopathological subtypes that have specific clinical course and outcome. This study was conducted to assess various histomorphological variants of breast carcinoma. Material and Methods: Total of fifteen cases of modified radical mastectomy specimens were prospectively assessed from January 2019 to June 2019 in pathology department of Dr B.R. Ambedkar Medical college and hospital, Bangalore. Observation: Out of 15 cases, Invasive ductal carcinoma NOS was most common variant accounting for 10 cases (66.66%) followed by 1 cases of Invasive Lobular Carcinoma breast, 1 case of Invasive micropapillary carcinoma, 1 case of Medullary carcinoma, 1 case of Metaplastic breast carcinoma. The histological grading of breast carcinoma was done on the basis of Elston – Ellis modification of Scarff - Bloom - Richardson grading system. We found that Grade 2 tumours were more common accounting to 9 cases (60%) followed by Grade 1 tumour (26.66%). Conclusion: This study emphasizes on the importance of assessment of histopathological variants of breast carcinoma in not only in establishing the final diagnosis, but also in predicting the prognosis by histological typing, staging and grading of breast carcinoma. Keywords: Breast carcinoma, MRM, Histomorphology, WHO, Staging, Grading.

Histopathologic Analysis of Signet-ring Cell Carcinoma In Situ in Patients With Hereditary Diffuse Gastric Cancer.

Hereditary diffuse gastric cancer (HDGC) is a rare autosomal dominant syndrome associated with an increased risk of developing Laurén's diffuse-type gastric carcinoma and lobular breast carcinoma. Although signet-ring cell carcinoma (SRCC) in situ (SRCC-pTis) has been reported as a characteristic lesion in HDGC cases with CDH1 germline mutations (CDH1 pathogenic variant), and a precursor of conventional intramucosal SRCC (SRCC-pT1a), its histopathologic features and specificity have not been sufficiently clarified. Here, we examined gastrectomy samples from 6 Japanese HDGC patients with CDH1 germline mutation, belonging to 4 families, and analyzed SRCC lesions histologically and immunohistochemically. Of the 274 foci found in the 6 samples, SRCC-pT1a accounted for 225 lesions (range: 8 to 107, mean 45.7 lesions per patient), while 46 foci were of SRCC-pTis (range: 1 to 15, mean 7.67 foci per patient). All SRCC-pTis foci were observed in the fundic gland area and on the superficial side of the mucosa. Histologically, tumor cells of SRCC-pTis were found between normal foveolar epithelial cells and the basement membrane, following a typical pagetoid spread pattern. Immunohistochemically, E-cadherin expression was lost in SRCC-pTis (27/28, 96.4%) more frequently than in SRCC-pT1a (95/197, 48.2%; P<0.001). To elucidate the specificity of SRCC-pTis for HDGC, 60 samples (range: 0.12 to 1.49 m, total 28.8 m of mucosal length) from gastric cancer cases were analyzed as controls, in which no SRCC-pTis were identified. Our results indicate that SRCC-pTis is a distinct histologic feature with high specificity for HDGC cases with CDH1 germline mutations.

Triple negative lobular breast carcinoma metastatic to an ovarian fibrothecoma

ABSTRACT A postmenopausal woman with lobular breast carcinoma metastatic to a large ovarian fibrothecoma is presented. The two metastatic tumor nodules were grossly subtle and could have been overlooked in the background of the large ovarian stromal tumor. Thorough sampling of the tumor for histologic examination and supporting immunohistochemical stains were important in establishing the diagnosis. Differential diagnostic considerations are discussed.

Fecal expression of Escherichia coli lysine decarboxylase (LdcC) is downregulated in E-cadherin negative lobular breast carcinoma.

Breast cancer is characterized by oncobiosis, the abnormal composition of the microbiome in neoplastic diseases. The biosynthetic capacity of the oncobiotic flora in breast cancer is suppressed, as suggested by metagenomic studies. The microbiome synthesizes a set of cytostatic and antimetastatic metabolites that are downregulated in breast cancer, including cadaverine, a microbiome metabolite with cytostatic properties. We set out to assess how the protein expression of constitutive lysine decarboxylase (LdcC), a key enzyme for cadaverine production, changes in the feces of human breast cancer patients (n = 35). We found that the fecal expression of Escherichia coli LdcC is downregulated in lobular cases as compared to invasive carcinoma of no special type (NST) cases. Lobular breast carcinoma is characterized by low or absent expression of E-cadherin. Fecal E. coli LdcC protein expression is downregulated in E-cadherin negative breast cancer cases as compared to positive ones. Receiver operating characteristic (ROC) analysis of LdcC expression in lobular and NST cases revealed that fecal E. coli LdcC protein expression might have predictive values. These data suggest that the oncobiotic transformation of the microbiome indeed leads to the downregulation of the production of cytostatic and antimetastatic metabolites. In E-cadherin negative lobular carcinoma that has a higher potential for metastasis formation, the protein levels of enzymes producing antimetastatic metabolites are downregulated. This finding represents a new route that renders lobular cases permissive for metastasis formation. Furthermore, our findings underline the role of oncobiosis in regulating metastasis formation in breast cancer.

Metastasis of lobular breast carcinoma in the bowel

Metastasis of lobular breast carcinoma in the bowel

Human epidermal growth factor receptor 2 positive rates in invasive lobular breast carcinoma: The Singapore experience.

BACKGROUNDInvasive lobular carcinomas (ILC) form 5%-10% of breast cancer and rarely show overexpression of human epidermal growth factor receptor 2 (HER2).AIMTo describe the prevalence and prognostic factors of HER2 positive (HER2+) ILC in an Asian population.METHODSA retrospective review of patients with ILC seen between January 1985 and March 2018 at various SingHealth medical institutions was conducted. Demographic and clinical data were collected from medical records. We examined clinicopathological characteristics and survival in relation to HER2 status.RESULTSA total of 864 patients were included. Prevalence of HER2 positivity was 10.1% (87 patients). Compared with HER2 negative (HER2-) ILC, HER2+ ILC was associated with a higher proportion of estrogen receptor negative (24.4% vs 5.9%, P < 0.001), progesterone receptor negative (PR-) (40.2% vs 24%, P = 0.002) and grade 3 tumours (Grade 3, 29.0% vs 10.2%, P < 0.001). Overall survival rate was poorer in patients with HER2+ compared to HER2- ILC (56.7% vs 72.9% alive at 10 years; hazard ratio 1.87, 95% confidence interval: 1.21-2.90, P = 0.004). Based on multivariate analysis, negative prognostic factors for overall survival included HER2 positivity, PR negativity, older age, Indian ethnicity and higher tumour stage.CONCLUSIONPrevalence of HER2+ ILC was 10.1%. HER2+ ILC was more likely to have poorer prognostic features such as estrogen receptor negative, PR- and higher tumour grade, and have a poorer survival.

SAT-222 Aggressive Phenotype Pheochromocytoma Associated with NF-1 and BRCA Mutation

IntroductionPheochromocytomas are catecholamine-secreting tumors of the adrenal medulla that occur sporadically or with familial association. Familial predilection occurs in those with multiple endocrine neoplasia type 2, von Hippel-Lindau disease, and neurofibromatosis Type 1 (NF-1). To date, more than 21 gene mutations have been identified that are involved in the development of pheochromocytomas. However, co-existence of two different mutations such as NF-1 and BRCA gene mutations with pheochromocytoma has not been well described.Clinical CaseA 40 year-old woman with NF-1 and recently diagnosed left breast invasive ductal carcinoma, estrogen positive, progesterone positive, HER-2 negative BRCA2 positive breast cancer and right breast lobular carcinoma in situ underwent staging CT scan. A 2.7 cm left adrenal incidentaloma with heterogeneous texture and 69–100 HU was discovered. Symptom review revealed chronic headaches and increasing frequency of anxiousness and irritability. She had no personal or family history of hypertension. Laboratory analysis showed elevated catecholamine levels included plasma normetanephrine of 2.8 nmol/L (normal <0.9), metanephrine of 0.9 nmol/L (normal <0.5), 24 hour urine metanephrine 498 mcg/24 hr (normal <180) and 24 hour urine normetanephrine of 1,152 mcg/24 hr (normal <451). Findings were consistent with adrenal pheochromocytoma.She was immediately started on phenoxybenzamine and encouraged to increase fluid intake to expand intravascular volume before surgery. She underwent laparoscopic left partial adrenalectomy fourteen days later. Surgical pathology revealed a 3.0 cm pheochromocytoma in a background of nodular hyperplasia of the medulla, described as an aggressive tumor phenotype based on morphological features.ConclusionsIt has been estimated that 1.5–14% of adrenal incidentalomas are pheochromocytomas. While only 3% of NF-1 patients have pheochromocytomas, 20–50% of NF-1 patients with concurrent hypertension have underlying chromaffin tumors. This association is significant when compared to the pheochromocytoma incidence of 0.1% in all hypertensive individuals. Interestingly, germline mutations of BRCA-1 associated protein-1 gene have been reported in patients with paragangliomas, therefore it may be plausible to consider interactions between NF-1 and breast cancer BRCA-2 gene mutations, resulting in an unusual and more aggressive pheochromocytoma phenotype, even when detected at an early stage, as in this case. It is also important to recognize and adequately treat pheochromocytoma prior to having surgery to avoid possible intraoperative hypertensive crisis, a concept that was underscored in this particular case when the patient was relatively asymptomatic and entirely normotensive preoperatively.

Gastrointestinal metastatic breast cancer unmasked by anticoagulation

BackgroundCancer is a leading cause of provoked venous thromboembolism (VTE) and requires use of anticoagulation. As the incidence of lobular breast carcinoma increases, more breast cancer patients experience gastrointestinal metastatic disease which often manifests with gastrointestinal bleeding. Herein we discuss the challenges associated with the diagnosis and management of breast cancer metastatic to the GI tract revealed by need for anticoagulation due to concurrent cancer-associated VTE. CaseA 72 year old woman with a past medical history of ER+ PR+ HER2- Stage IIIa left lobular breast carcinoma previously treated with neoadjuvant chemotherapy, bilateral mastectomies and radiation followed by adjuvant hormonal therapy with letrozole. After 2 years of adjuvant hormonal therapy, she was diagnosed with unprovoked VTE. She was started on rivaroxaban for indefinite anticoagulation. After 5 months she presented with complaints of melena and weakness and a hemoglobin of 7.1 g/dL and platelets of 110 x 109/L. Esophagoduodenoscopy was performed which showed acute gastritis with random gastric biopsies noted to be positive for metastatic lobular breast carcinoma. Due to GI bleeding, rivaroxaban was held, however the patient developed an acute proximal right femoral vein VTE. A second trial of anticoagulation with heparin did not reveal continued bleeding, so she was discharged on apixaban. Unfortunately, despite starting chemotherapy with ibrance and faslodex she developed worsening melena resulting in the need to the place an IVC filter and cessation of anticoagulation. DiscussionAs lobular breast cancer can spread along serosal surfaces, new onset of GI bleeding in patients with history of lobular breast cancer should increase suspicion for GI metastatic disease. Use of anticoagulation may unmask bleeding in such patients. The increased risk of GI bleeding in cancer patients must be considered when selecting anticoagulation for the management of cancer-associated VTE. Management of cancer associated thrombosis is complex and hemostasis strategies for of mucosal bleeding from metastatic lobular breast cancer may require tailored approaches that compensate for the malignant cause. Furthermore, a thorough assessment of platelet counts and other coagulation factors should be considered as a minority of patients with metastatic disease can present with consumptive coagulopathy.

PBX1 is a valuable prognostic biomarker for patients with breast cancer.

Pre-B-cell leukemia transcription factor (PBX) proteins have important roles in the development of numerous organs. To date, four members of the PBX family have been identified to be involved in human cancer but little is known about their expression patterns and precise functions in breast cancer (BC) progression. The aim of the present study was to determine whether they have the potential to be prognostic biomarkers in patients with BC. The expression patterns of PBXs were evaluated using Oncomine, Cancer Cell Line Encyclopedia and Gene expression-based Outcome for Breast cancer Online algorithm analyses. The prognostic value of PBX1 was determined by Kaplan-Meier plotter analysis. It was observed that, among all PBX family members, only PBX1 was significantly upregulated in BC vs. normal tissues. Meta-analysis in the Oncomine database revealed that PBX1 was significantly upregulated in invasive breast carcinoma stroma, ductal breast carcinoma, invasive lobular breast carcinoma, invasive mixed breast carcinoma and male breast carcinoma compared with normal tissues. In addition, PBX1 was significantly correlated with forkhead box protein A1. Subtype analysis indicated that PBX1 overexpression was associated with luminal-like and hormone receptor-sensitive subtypes. In the survival analysis, a high expression level of PBX1 was associated with poor prognosis of patients with estrogen receptor (ER)-positive, luminal A and luminal B subtypes of BC. The results of the present study indicate that PBX1 may serve as a specific biomarker and essential prognostic factor for ER-positive, luminal A and luminal B subtypes of BC.

Metastatic Anal Lesion of Primary Lobular Breast Carcinoma- An Insidious, Rare and Subclinical Progression: Case Report and Review of the Literature

Gastrointestinal metastasis from primary breast carcinoma is very uncommon, with less than 1% of breast carcinomas metastasize to the gastrointestinal tract but anorectal involvement is even rarer. These metastatic lesions can lead to diagnostic challenge for clinicians as they can mimic primary colo-rectal cancer due to the lack of diagnostic signs. The increase of patient survival could lead to an unusual late resumption of metastatic disease, often for a long-time occult. Nowadays, an almost completely absent literature is unable to suggest diagnostic pathways capable of predicting this type of disease evolution. We present the case of a 76-year old woman who underwent treatment for an infiltrative lobular carcinoma of the breast who developed metastasis of the anal canal 11- years later. A literature review was performed.