Neuroendocrine Carcinoma Of Breast Research Articles

Primary Large-Cell Neuroendocrine Carcinoma of the Breast.

Breast neuroendocrine carcinoma (NECB) is a rare type of breast tumor. Large-cell neuroendocrine carcinomas of the breast (LCNECB) are a special and rare histological subtype of NECB. Here, we present a case of a 59-year-old woman who was diagnosed with an LCNECB. A mass in the upper outer quadrant of the right breast was revealed via imaging. A histological examination showed the tumor cells were composed of clusters of large cells with obvious atypia that were polygonal or irregularly shaped. The patient underwent a right-breast-conserving radical surgery and sentinel lymph node biopsy (SLB). A histopathological examination revealed that the tumor of the right breast was 2.5 × 2 cm in size with vascular invasion, and the sentinel lymph node was negative. The immunohistochemical results showed that the tumor cells were diffuse and positive for chromogranin A (CgA), synaptophysin (Syn), and INSM1. The patient successfully completed chemotherapy and radiotherapy and is currently undergoing endocrine therapy.

Primary Neuroendocrine Carcinoma of Breast: Changing Paradigm

Primary Neuroendocrine Carcinoma of Breast: Changing Paradigm

Neuroendocrine Breast Carcinoma: Interesting Images of an Underdiagnosed Entity.

Breast cancer is the most common type of cancer of the female gender. A rare subtype of breast cancer is the invasive breast carcinoma (IBC) with neuroendocrine (NE) differentiation. Its incident is believed to be 0.1% to 5% of all breast cancers. We report a rare case of a 66-year old woman who presented with an isolated nodule of the left breast. The patient underwent modified radical mastectomy. Pathology revealed invasive breast carcinoma with neuroendocrine differentiation. Invasive breast carcinoma is an extremely rare group of neoplasms, the exact frequency of which cannot be determined with current data. Therefore, it is necessary for future studies to focus on the pathophysiology of this subtype of breast cancer and on the potential therapeutic approaches.

Comparison of clinical characteristics and outcomes in primary neuroendocrine breast carcinoma versus invasive ductal carcinoma.

Neuroendocrine breast carcinoma (NECB) is a rare, special histologic type of breast cancer. There are some small sample studies on the clinical outcomes of NECB patients, which are worthy of further discussion. We conducted a retrospective case-control study of clinical characteristics and outcomes among patients with primary NECB versus invasive carcinoma of no special type (NST) between November 2004 and November 2017 in the Peking Union Medical College Hospital, Beijing. NST patients were strictly matched 1:4 during the same period based on the TNM stage. Statistical comparisons were performed to determine the differences in survival between NST and NECB patients and to identify clinical factors that correlate with prognosis. A total of 121 participants affected by primary NECB were included in our analysis from November 2004 to November 2017. Elderly persons (>60 years of age) were more likely to have primary NECB than young persons (p=0.001). In addition, primary NECB patients had significantly higher odds of having tumors 2-5cm (36.5%) and >5cm (6.1%) in size than NST patients. Despite a significant difference in tumor size, the proportion of patients with lymph node metastases showed no difference between the two groups (p=0.021). In addition, the rate of patients with ER-negative tumors in the NECB group (4.2%) was significantly lower than that in the primary NST group (29.8%). Significant differences were noted in the PR-negative (13.3% versus 36.6%, P<0.001) and HER2-negative (90.5% versus 76.4%, P=0.001) expression statuses among these patients. Of 121 primary NECB patients, 11 (9.1%) experienced relapses during the follow-up period. We found that tumor size was an independent risk factor for relapse. For hormone receptors on tumor cells, ER-positive breast cancer patients had significantly lower odds of relapse than receptor-negative patients. Our data demonstrate no significant difference in mortality and relapse between the primary NECB and NST groups. The tumor size in the primary NECB group was significantly larger than that in the NST group. In addition, the absence of ER independently increased the relapse rate for breast carcinoma patients.

Management of Neuroendocrine Breast Carcinoma (NEBC): Review of Literature.

Extra pulmonary high-grade poorly differentiated neuroendocrine carcinomas (EP-NECs) are rare tumors that usually arise in the gastrointestinal and genitourinary tracts. Primary neuroendocrine carcinoma of the breast (NEBC) is extremely rare, representing less than 0.1% of all breast cancers and less than 1% of neuroendocrine neoplasms. Consequently, they can be misdiagnosed as other types of breast cancer, however, proper immunohistochemical (IHC) studies can assist with making the correct diagnosis. Management of NEBC can be challenging given the paucity of evidence-based literature and should not routinely follow the therapeutic guidelines of other breast cancers. In this article, we review the current literature regarding the management of NEBC.

Neuroendocrine Breast Carcinoma: a Case Series

Neuroendocrine breast carcinoma (NEBC) is histologically a rare type of invasive breast cancer. It constitutes only 0.2–0.5% of all invasive breast cancers. In this case series, we are presenting five cases having primary neuroendocrine breast cancers that had been reported at a high-volume cancer centre in Pakistan. In this study, neuroendocrine breast cancer patients at Shaukat Khanum Memorial Cancer Hospital and Research Centre Peshawar were evaluated. We had retrospectively collected information on demographic characteristics of our patients, physical examination, radiological findings, surgical procedures with their outcomes, histopathological and immuno-histochemical characteristics, systemic adjuvant/neoadjuvant therapy and follow-up.

High frequency of alternative splicing variants of the oncogene Focal Adhesion Kinase in neuroendocrine tumors of the pancreas and breast.

The characteristic genetic abnormality of neuroendocrine neoplasms (NENs), a heterogeneous group of tumors found in various organs, remains to be identified. Here, based on the analysis of the splicing variants of an oncogene Focal Adhesion Kinase (FAK) in The Cancer Genome Atlas datasets that contain 9193 patients of 33 cancer subtypes, we found that Box 6/Box 7-containing FAK variants (FAK6/7) were observed in 7 (87.5%) of 8 pancreatic neuroendocrine carcinomas and 20 (11.76%) of 170 pancreatic ductal adenocarcinomas (PDACs). We tested FAK variants in 157 tumor samples collected from Chinese patients with pancreatic tumors, and found that FAK6/7 was positive in 34 (75.6%) of 45 pancreatic NENs, 19 (47.5%) of 40 pancreatic solid pseudopapillary neoplasms, and 2 (2.9%) of 69 PDACs. We further tested FAK splicing variants in breast neuroendocrine carcinoma (BrNECs), and found that FAK6/7 was positive in 14 (93.3%) of 15 BrNECs but 0 in 23 non-NEC breast cancers. We explored the underlying mechanisms and found that a splicing factor serine/arginine repetitive matrix protein 4 (SRRM4) was overexpressed in FAK6/7-positive pancreatic tumors and breast tumors, which promoted the formation of FAK6/7 in cells. These results suggested that FAK6/7 could be a biomarker of NENs and represent a potential therapeutic target for these orphan diseases.

Differences in clinical characteristics and prognosis between breast neuroendocrine carcinoma and breast invasive ductal carcinoma: A multicentre population-based study from China.

We constructed a multicentre cohort in China to analyse the differences in clinical characteristics, treatment strategies and prognoses between breast neuroendocrine carcinoma (NEC) and invasive ductal carcinoma (IDC) of the breast. All patients with early-stage breast cancer who attended three hospitals in Beijing from 2000 to 2018 were included in the study. We used propensity score matching to make a 1:3 match between NEC and IDC. After propensity score matching, 153 patients with IDC and 51 patients with NEC were analysed. Multivariate Cox regression showed that compared to patients with IDC, patients with NEC had a worse disease-free survival (HR=2.94, 95% CI: 1.69-5.12, p < 0.001). NEC patients have a worse disease-free survival than IDC patients.

Abstract P3-05-07: Primary neuroendocrine carcinoma of the breast: A case series by WHO classfication in 2019

Abstract Introduction Neuroendocrine tumours (NET) are thought to arise from cells throughout the diffuse endocrine system and can occur almost everywhere in the body. Most NETs arise from the gastrointestinal tract, lung, thymus, and pancreas. Primary neuroendocrine carcinoma (NEC) of the breast is a rare and under-recognized subtype, accounting for less than 1% of breast carcinomas. Only a few small studies and case reports have been reported and there are no clear diagnostic criteria and established treatment options. World Health Organization (WHO) classification of tumor series’ fifth edition was published in 2019 and adopted ‘Neuroendocrine neoplasm (NEN)’ as a term encompassing all tumour classes with predominant neuroendocrine differentiation. NENs of the breast are classified into invasive ductal carcinoma (IDC) with neuroendocrine differentiation (NED), NET, and NEC of small cell or large cell types. Thus we aim to report pathologic reviews and treatment outcomes of patients with NENs of the breast at a single center. Methods We retrospectively screened the medical record of 34,370 patients diagnosed with breast cancer from 2007 to 2022 by Corporate Data Warehouse (CDW) and revealed there were 22 patients diagnosed with primary breast NEN. The pathologist reviewed the pathology slides and reclassified the diagnosis according to the WHO classification of tumor series’ fifth edition. Clinical characteristics, treatment modalities, and therapeutic outcomes were reviewed retrospectively. Results We reviewed pathology slides of 22 patients with histologically proven diagnoses of primary breast NEN from 2007 to 2022. We found only 8 patients meet the criteria of primary breast NEC (large cell 2, small cell 6), 3 patients with NET, and 3 patients with IDC with NED. We excluded 8 patients who did not fulfill the criteria of NEN. The median age of NEN was 48.5 years (range, 31-70) and 6 patients (42.9%) were postmenopausal women. The median follow-up duration was 25.3 months (Interquartile range(IQR), 15.0-54.7). All patients underwent surgery, 3 patients underwent a mastectomy and 11 patients underwent breast-conserving surgery (BCS) with a curative aim. Five patients had lymph node metastasis. There was no expression of the human epidermal growth factor receptor 2 (HER2) in all 14 cases. Hormone receptor expression was shown in 4 of NECs (50%) and all NETs or IDC with NED patients. Patients with primary breast NEC had a median recurrence-free period (RFP) of 14.6 months (95% confidence interval (CI), 11.0-18.2) and median overall survival (OS) of 52.1 months (95% CI, 0.0-120.0). Patients with NET or IDC with NED had an overall favorable outcome, none of the patients died and only one patient with IDC with NED experienced disease progression. The median PFS and OS were not reached in NET or IDC with NED subgroups. Conclusion NETs are rare tumours with a wide range of clinical presentations according to the site of involvement. Primary breast NENs are extremely rare and there are no specific guidelines for treatment. NENs are often underdiagnosed, as neuroendocrine markers are not routinely tested in breast cancer. In this retrospective single-center study, the incidence of primary breast NENs was 0.04% (14 of 34,370 patients) and primary breast NEC was associated with poor prognosis compared with breast NET or IDC with NED. Identifying innovative treatment strategies is needed to overcome poor outcomes of primary breast NEC. Citation Format: Young Kyung Jeon, Ji-Yeon Kim, Jin Seok Ahn, Young Hyunk Im, Kyue-Hee Choi, Sun Young Jeong, Yeji Jung, Jae Yeon Jang, Daeho Choi, Joohyun Hong, Hyo Jung Kim, Soo Youn Cho, Yeon H. Park. Primary neuroendocrine carcinoma of the breast: A case series by WHO classfication in 2019 [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 P3-05-07.

229 - A rare case of breast neuroendocrine carcinoma

229 - A rare case of breast neuroendocrine carcinoma

A high-quality model for predicting the prognosis of breast neuroendocrine carcinoma to help clinicians decide on appropriate treatment methods: A population-based analysis

BackgroundBreast neuroendocrine carcinoma (NEC) is a rare malignancy with unclear treatment options and prognoses. This study aimed to construct a high-quality model to predict overall survival (OS) and breast cancer-specific survival (BCSS) and help clinicians choose appropriate breast NEC treatments. Patients and methodsA total of 378 patients with breast NEC and 349,736 patients with breast invasive ductal carcinoma (IDC) were enrolled in the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2018. Propensity score matching (PSM) was performed to balance the clinical baseline. Prognostic factors determined by multivariate Cox analysis were included in the nomogram. C-index and calibration curves were used to verify the performance of the nomogram. ResultsNomograms were constructed for the breast NEC and breast IDC groups after PSM. The C–index of the nomograms ranged from 0.834 to 0.880 in the internal validation and 0.818–0.876 in the external validation, indicating that the nomogram had good discrimination. The risk stratification system showed that patients with breast NEC had worse prognoses than those with breast IDC in the low-risk and intermediate-risk groups but had a similar prognosis that those in the high-risk group. Moreover, patients with breast NEC may have a better prognosis when undergoing surgery plus chemotherapy than when undergoing surgery alone or chemotherapy alone. ConclusionsWe established nomograms with a risk stratification system to predict OS and BCSS in patients with breast NEC. This model could help clinicians evaluate prognosis and provide individualized treatment recommendations for patients with breast NEC.

Prognostic factors of primary neuroendocrine breast cancer: A population‐based study

BackgroundPrimary neuroendocrine breast carcinomas (NEBCs) are an extremely rare and underrecognized subtype of mammalian carcinoma. The prognostic factors for NEBCs remain controversial.MethodsIn this multicenter retrospective study, the prognostic factors for patients with primary NEBCs who underwent surgery and had a pathologically confirmed diagnosis of neuroendocrine carcinoma in China and the United States were examined. The endpoints were disease‐free survival (DFS) and overall survival (OS).ResultsA total of 51 Chinese patients and 98 US patients were included. In the Chinese cohort, tumor grade and Ki‐67 levels were prognostic factors for DFS in univariate analysis (hazard ratio [HR] = 5.11 [1.67–15.60], p = 0.004; HR = 57.70 [6.36–523.40], p < 0.001, respectively) and multivariate analysis (HR = 100.52 [1.33–7570.21], p = 0.037; HR = 31.47 [1.05–945.82], p = 0.047, respectively). In the US cohort, age was an important prognostic factor for OS in univariate analysis (HR = 1.09 [1.04–1.15], p = 0.001). The random effects model for the combined cohorts revealed age and positive expression of estrogen receptor (ER) as potential prognostic factors for OS (HR = 1.08 [1.01–1.14], p = 0.015; HR = 0.10 [0.02–0.44], p = 0.003, respectively).ConclusionsTumor grade and Ki‐67 levels are important prognostic factors for DFS of patients with primary NEBCs. Age and ER status are important prognostic factors for OS of patients with primary NEBCs.

Utility of KI-67 as a prognostic biomarker in pulmonary neuroendocrine neoplasms: a systematic review and meta-analysis

ObjectivesKi-67, a marker of cellular proliferation, is associated with prognosis across a wide range of tumours, including gastroenteropancreatic neuroendocrine neoplasms (NENs), lymphoma, urothelial tumours and breast carcinomas. Its omission from...

NEUROENDOCRINE BREAST TUMOUR: A CHALLENGING ENTITY

NEUROENDOCRINE BREAST TUMOUR: A CHALLENGING ENTITY TUMOR NEUROENDOCRINO DE MAMA: UNA ENTIDAD DESAFIANTE Neuroendocrine breast carcinoma is a rare type of breast cancer with neuroendocrine differentiation which is found in around 2-5% of all invasive breast carcinomas. In most cases it is a challenge to get to the right diagnosis due to the sporadic number of cases and the need for special immunochemistry techniques, which are not routinely used. Due to the rare number of cases, it is difficult to update guidelines so that the correct diagnosis and treatment is decided. Our purpose is to present a clinical case in order to emphasize the importance of having this diagnosis in mind when breast cancer is found.

Primary neuroendocrine breast carcinoma: A rare case report

Primary neuroendocrine breast carcinoma: A rare case report

Neuroendocrine carcinoma of the breast: a case report

Neuroendocrine breast carcinomas represent a rare subtype of breast cancer. Their definition, prevalence and prognosis remain controversial in the literature. Regarding the presentation, there are no differences from other breast carcinomas and clinical syndromes related to hormone production are extremely rare. Refinement of the classification of neuroendocrine neoplasms of the breast is needed in order to improve the reproducibility of their diagnostic criteria and to define their clinical significance. This article presents the case of a 44-year-old female patient diagnosed with invasive breast carcinoma with neuroendocrine features, according to the 2012 World Health Organization (WHO) definition, with focus on presentation, clinical manifestations, diagnostic approach and differential diagnosis.

S2960 Incidental Diagnosis of a Rare Metastatic Neuroendocrine Breast Cancer During Routine Screening Mammogram Which Eventually Revealed Primary Small Intestine Carcinoid Tumor

Introduction: Neuroendocrine neoplasms (NENs), defined as epithelial neoplasms with predominant neuroendocrine differentiation, typically occur in the pancreas, tubular gastrointestinal tract, or lung with or without secretory syndromes. Neuroendocrine breast carcinoma (NEBC) is a rare tumor which accounts for 1-2% of all invasive breast carcinoma. When NENs are found on a biopsy of a breast nodule it is considered either primary NEBC or metastatic if another primary organ is discovered. NEBC usually presents as a breast lump on exam without neuroendocrine symptoms. Therefore, making a diagnosis of NEBC prior to biopsy is difficult. We present a case of an incidentaloma discovered on routine mammography that turned out to be NEBC on biopsy and further evaluation discovered an asymptomatic primary small bowel NEN, thus confirming the breast as metastatic NEBC. Case Description/Methods: A routine mammogram in 60 yo. female revealed an abnormal 4 mm solid nodule in the right breast. A core needle biopsy found a low grade, well differentiated NEN, with positive staining for synaptophysin and chromogranin. She felt well and denied any symptoms. Medical history was notable for immune hepatitis with liver cirrhosis managed by her hepatologist. An abdominal MRI/MRCP revealed thickening in the small bowel wall consistent with a primary carcinoid tumor and demonstrated hepatic surface metastases. Plasma and 24 hr. urine 5 HIAA and chromogranin A plasma levels were normal. A lumpectomy was performed and therapy with lanreotide i.m. monthly injections begun. At 6 months follow-up, she remains asymptomatic, with stable disease. Discussion: Metastasis to the breast from a primary NEN is infrequently reported in the literature. If discovered in a patient without a history of known primary NEN in another organ, imaging is warranted to seek asymptomatic and non-secreting tumors elsewhere, as in the GI tract of our patient. No proven effective chemotherapy or RT for either primary or metastatic NEBC exists. No proven effective chemotherapy regimen exists for NENs, but therapy with long-acting somatostatin analogs are the preferred first-line option for NENs associated with several hormonal syndromes as well as for growth control in well-differentiated unresectable or metastatic gastroenteropancreatic NENs as in our case.

Radioembolization Outside of the Liver

AbstractTransarterial radioembolization (TARE) with yttrium-90 microspheres has emerged as an effective therapy for the treatment of both primary and metastatic hepatic lesions. It has been studied most extensively in hepatocellular carcinoma (HCC) and metastatic colorectal lesions (mCRC). The clinical success of TARE in HCC and mCRC has led to further investigation of expanding treatment to other malignancies involving the liver such as neuroendocrine carcinoma, uveal melanoma, and breast carcinoma, among others. Furthermore, interest in applications of TARE outside of the liver is emerging and small initial studies have been performed primarily in animal models to assess the effects of TARE on other organs such as the brain, stomach, spleen, kidney, and lungs. This review summarizes existing literature on the use of TARE outside of the liver.

Neuroendocrine Differentiated Breast Cancer Cases: A Retrospective Analysis and Literature Review.

Objectives:Neuroendocrine breast carcinoma (NEBC) is a rare subgroup of breast cancer, which makes up 2–5% of all invasive breast cancers. The aim of this retrospective analysis is to present and analyze our own data of primary NEBCs.Methods:We retrospectively analyzed clinical, pathological, and radiological characteristics of 36 patients diagnosed with neuroendocrine differentiated breast cancer between 2008 and 2019 compared to that of 925 patients with invasive ductal carcinoma (IDC/NOS) along with a literature review.Results:In this study, 36 patients with neuroendocrine differentiated breast carcinoma and 961 patients with (IDC/NOS), as the comparison group, were identified between 2008 and 2019. In NEBC patients, seven were premenopausal and 29 postmenopausal. Patients whose ultrasound (USG), magnetic resonance, and mammographic (MMG) images available in our hospital, high-density masses were detected in the MMG with irregular (77%), microlobulated (80%) and spiculated margins (63%), unaccompanied by asymmetry and structural distortion. Calcifications were less common than invasive breast cancer, present only in four patients (17%). When NEBC were compared to ductal carcinomas (n=925), NEBC were more often human epidermal growth factor receptor 2 negative (p=0.039), estrogen receptor positive (p=0.05), progesterone receptor positive (0.03), and the NEBC patients were older (p=0.02). Age, grade, metastatic status, lymph node number, and molecular type were identified as prognostic factors that significantly affect survival in both groups (p<0.05).Conclusion:NEBC is a subtype that is both histopathologically and radiologically distinct from other breast cancer subtypes, and neuroendocrine differentiation may be an important predictive marker in the future.

Rare presentation of metastasized primary neuroendocrine breast carcinoma to the right colon and literature review of primary neuroendocrine breast carcinoma metastasized to other organs of the body: case report

Primary neuroendocrine breast tumors account for less than 0.1% of all breast cancers, hence, unique in nature. This paper aims to report a 56 years old female, known case of primary neuroendocrine breast cancer with a metastatic right colonic neuro-endocrine tumor. The article also aims to review and acclaim the literature regarding primary breast neuroendocrine tumors metastasized to other parts of the body. The patient presented complaining of a breast mass, ulceration, and discharge, which was rapidly progressing. Examination revealed a right breast mass with skin erythema and impending ulceration and right axillary lymph nodes fixed with palpable supra-clavicular lymph nodes. Ultrasound-guided biopsy of right breast mass and axilla disclosed a large cell neuroendocrine carcinoma. CT abdomen and chest revealed metastases to the ascending colon. The patient was treated with palliative radiotherapy along with multiple cycles of chemotherapy for the primary breast cancer. She also underwent a laparoscopic-assisted right hemicolectomy with complete mesocolic excision and primary anastomosis for the metastatic colon cancer. The paper compares the reported case to other similar cases using the framework of an analysis based on age of the patient, primary breast cancer location, method of detection, presence of neuroendocrine markers, primary cancer presentation, metastases symptoms, and location and treatment approach. In conclusion, metastasized primary neuroendocrine breast cancer is a very rare presentation. Incidence and prevalence maybe influenced by age, primary breast cancer location, and presence of neuroendocrine markers. Prognosis may also be a product of metastatic location, associated symptoms and treatment approaches.