Secretory Carcinoma Of Breast Research Articles

Effect of screening with a pan-TRK immunohistochemistry-based algorithm on NTRK fusion detection rates.

e15135 Background: Rearrangements in the NTRK1, NTRK2, and NTRK3 genes are clinical actionable and predictive of response to TRK kinase inhibitors in solid tumors. Their detection in clinical practice is a priority, but their low prevalence (0.25-1%) poses a diagnostic challenge. In this study, we describe our immunohistochemical-based and cost-effective approach for NTRK rearrangements detection. Methods: We implemented a comprehensive NTRK testing approach at a reference center that combined clinical criteria (e.g., iodine therapy-resistant thyroid cancer); molecular biomarkers (e.g., non-small-cell lung carcinoma negative for driver alterations, colorectal carcinoma with deficient MMR and/or microsatellite instability); and histopathological criteria (identifying tumor subtypes associated with NTRK fusions, such as breast secretory carcinoma). Automated immunohistochemistry (Ventana BenchMark ULTRA IHC/ISH System) using the antibody pan-TRK (Ventana, EPR17341) was used as a screening tool. Positive results were confirmed through molecular techniques, including Next Generation Sequencing, NGS (Oncomine Focus Assay, Thermo Fisher, based on DNA and RNA) and/or FISH (NTRK3 break-apart probe, Zytovision). Results: We evaluated 172 patients (99 female/73 male), with a mean age of 52 years (SD 23.8). Eighteen (18) patients with neoplasms expressing TRK proteins were identified. Confirmatory studies using NGS identified fusions in 7 cases. In instances of poor RNA quality, FISH techniques (NTRK3) were employed, confirming the findings in an additional 3 patients. Overall prevalence of NTRK fusions was 5.8%. Histological types included the following tumor types: Thyroid carcinoma, 4 patients (one medullary and 3 papillary carcinomas, two of them in the pediatric population); soft tissue sarcomas, 3 patients (2 corresponding to infantile fibrosarcoma and a soft tissue provisional entity, "NTRK-rearranged spindle cell neoplasm”); secretory carcinoma of the breast, one patient; secretory carcinoma of the salivary gland, one patient; colorectal carcinoma, one patient, with a deficient MMR phenotype. NTRK3 gene fusions were found in 10 patients, (6 fusions with ETV6 detected by NGS and 3 detected by FISH), and NTRK1 fusion in 1 case (fusion with LMNA detected by NGS). The positive predictive value of pan-TRK immunohistochemistry as a screening tool was 0.55. Conclusions: In our experience, the comprehensive screening approach based on morphological and clinical/ molecular inclusion criteria, along with the use of immunohistochemical techniques (pan-TRK antibody), significantly enhances the detection rate of NTRK fusions (5.8% vs. 0.25-1%). Additionally, FISH provides a valuable tool in samples with poor RNA quality. This approach allows for a reduction in the impact of costly testing, such as NGS, on the healthcare system.

Abstract PO4-25-08: Secretory breast carcinoma (SBC) in an 8-year-old male: Report of an exceptionally rare case with review of clinicoradiologic and pathomolecular findings of SBC in the male pediatric population

Abstract Secretory breast carcinoma (SBC) is a rare and distinct disease, comprising approximately 0.01% of all breast carcinomas. This is a case of an 8-year-old boy who presented with a 1.5-year history of a non-tender, slowly enlarging left subareolar mass, not associated with nipple discharge. Serologic workup revealed minimally elevated prolactin with normal-range FSH, LH, estradiol and testosterone, as well as normal-range beta-hCG, LDH and AFP. Ultrasound showed a circumscribed solid hypoechoic lesion with internal arterial vascularity, favoured to represent a sebaceous cyst. Excisional biopsy was performed, and histologic examination revealed the classic intra- and extracellular secretory material typically seen in SBC. Immunohistochemical (IHC) stains for mammaglobin, S-100 and high molecular weight keratin (CK5) were positive. ER was positive, though not strong staining, and PR and HER2 were negative. A screen for NTRK fusions with pan-TRK IHC was positive. No skin, perineural or lymphovascular invasion was identified. RNA-based NGS demonstrated ETV6-NTRK3 fusion and confirmed the diagnosis of SBC. The patient underwent mastectomy and SLNB, which showed no residual tumor and no positive lymph nodes. A full metastatic work-up was not performed and the patient did not receive neoadjuvant therapy. First described as “juvenile breast carcinoma,” SBC has since been recognized to occur across a wide age range, with most cases occurring in adults. SBC in male pediatric patients is exceptionally rare, with fewer than 20 cases reported in the literature. In this demographic, SBC is usually detected clinically as a subareolar mass not associated with nipple discharge, and appears as a well-circumscribed mass on imaging, mimicking benign entities. SBC is usually detected at a low stage, treated surgically, and follows a clinically indolent course with excellent outcomes. Positive axillary nodes have been identified in a few male children, who subsequently underwent chemo- and/or radiotherapy, with no recorded recurrences in these cases. Distant metastases are an extremely uncommon feature of SBC and have not been reported in the pediatric male population; however, due to the rarity of this diagnosis, particularly in this demographic, robust long-term follow-up data are still lacking. The name “secretory” derives from the histologic appearance of the dense eosinophilic secretory material seen in tumor lumina and bubbly material in the cytoplasm of tumor cells. Similar to the cytologic characteristics of other translocation-driven neoplasms, SBC shows minimal pleomorphism. Mitoses are absent or rare. IHC stains are typically positive for S-100 and high molecular weight keratins and negative for ER, PR, and HER2. Despite the immunophenotypic similarities to triple negative/basal-like carcinomas (TNBC/BLC) the molecular relationship between SBC and TNBC/BLC is unclear. Though initially defined by its distinctive secretions on histology, SBC is now chiefly characterized by a balanced translocation, t(12;15)(p13;q25), resulting in oncogenic ETV6-NTRK3 fusion. Recent cases have demonstrated this using a variety of molecular techniques, including FISH, RT-PCR, and in our case, RNA-based NGS. This translocation also characterizes non-breast secretory carcinomas and has been identified in several other neoplasms, including pediatric mesenchymal tumours and adult acute myeloid leukemia. The rarity of SBC, particularly in the male pediatric population, underlines the necessity of this case report. Additionally, this case highlights the importance of considering SBC as a potential diagnosis in male children presenting with a breast mass, even in the presence of benign imaging characteristics. Table 1: Clinicoradiologic and pathomolecular characteristics of SBC in pediatric males AND, axillary node dissection; CT, chemotherapy; ER, estrogen receptor; FISH, fluorescence in situ hybridization; LE, local excision; MRM, modified radical mastectomy; nd, no data; NED, no evidence of disease; NGS, next-generation sequencing; NS, nodal sampling; PA, periareolar; PR, progesterone receptor; RA, retroareolar; RM, radical mastectomy; PCR, polymerase chain reaction; RT, radiotherapy; SA, subareolar; SLNB, sentinel lymph node biopsy; SM, simple mastectomy; WLE, wide local excision *Not reported as strong staining Table 2: Immunohistochemical phenotype of secretory breast carcinoma EMA, epithelial membrane antigen; ER, estrogen receptor; PR, progesterone receptor *Not reported as strong staining Table 3: Laboratory investigations AFP, alpha fetoprotein; FSH, follicle stimulating hormone; hCG, human chorionic gonadotropin; LDH, lactate dehydrogenase; LH, luteinizing hormone Citation Format: Rebecca Brassington, Svetlana Silverman, Ioana Bratu. Secretory breast carcinoma (SBC) in an 8-year-old male: Report of an exceptionally rare case with review of clinicoradiologic and pathomolecular findings of SBC in the male pediatric population [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-25-08.

TRPS1 expression in salivary gland-type breast carcinoma and its clinical application

Objective: To investigate the expression of TRPS1 in salivary gland-type breast carcinoma and its clinical application. Methods: A total of 30 cases of salivary gland-type breast carcinoma diagnosed from May 2015 to November 2022 at the Department of Pathology of the First Affiliated Hospital of Nanjing Medical University were collected. The expression of TRPS1 was detected by immunohistochemistry and compared with that of GATA3. TRPS1 and GATA3 expression in 24 cases of primary salivary gland carcinoma. Results: There were 10 cases of breast secretory carcinoma, aged 21-61 years (median 53.5 years), with the size ranging from 0.9-2.2 cm (median 1.6 cm), 2 of which were accompanied by axillary nodal macrometastasis. All patients were alive after 2-55 months of follow-up (median 29.5 months, mean 29.7 months). There were 20 cases of breast adenoid cystic carcinoma, aged 36-77 years (median 53.5 years), with the size ranging from 1.2-5.5 cm (median 2.5 cm), 3 of which were accompanied by axillary nodal macrometastasis. All patients were alive after 3-92 months of follow-up (median 22.5 months, mean 31.7 months), and 1 patient had lung metastasis 15 months after surgery. The medium/high expression ratio of TRPS1 in breast secretory carcinoma was 10/10, which was higher than that of GATA3 (7/10). TRPS1 was also positive in the 2 cases with lymph node metastases. The medium/high expression rate of TRPS1 in breast adenoid cystic carcinoma was 20/20, which was significantly higher than that of GATA3 (2/20). TRPS1 was highly expressed in both classic and solid subtypes, while GATA3 was only expressed in a few cases of the classic subtype. TRPS1 was also positive in 3 cases with lymph node metastases and 1 case of the pulmonary metastases. The expression level of TRPS1 was the same in 1 case before and after neoadjuvant chemotherapy. In addition, TRPS1 was positive in parotid secretory carcinoma and adenoid cystic carcinoma. The medium/high expression rate of TRPS1 in parotid secretory carcinoma (6/6) was higher than that of GATA3 (2/6), and the medium/high expression rate of TRPS1 in parotid adenoid cystic carcinoma (17/18) was higher than that of GATA3 (2/18). Conclusions: The expression of TRPS1 is highly sensitive to salivary gland-type breast carcinoma, especially in GATA3-negative solid subtype of adenoid cystic carcinoma, which plays an important role in clinical practice.

Secretory breast carcinoma: clinicopathological features and prognosis of 52 patients.

Secretory breast carcinoma is a rare histological subtype of invasive breast cancer and considered with an indolent clinical behavior. This study was conducted to analyze the clinicopathological features of patients with secretory breast carcinoma (SBC), explore the outcome, and compare the prognostic difference with invasive ductal breast carcinoma (IDC). METHODSAND MATERIALS: Patients with SBC diagnosed between 2006 and 2017 from Fudan University Shanghai Cancer Center were included in the study, excluding patients with previous malignant tumor history and incomplete clinical data or follow-up records. Peculiar clinicopathological and immunohistochemical features of the cases were fully described. Clinical data of 4979 cases of IDC were also evaluated during this period. After propensity score matching, prognostic analysis of SBCs and IDCs was calculated by Kaplan-Meier method and landmark analysis method. The data of 52 patients diagnosed with SBC were identified from the pathological files. Among them, 47 patients were women, and 5 were men. The median age of the 52 SBCs was 46years (mean, 48.1years; range, 10-80years). The tumor sizes ranged from 0.3 to 6.8cm, with a mean of 3.5cm. Eight patients (15.4%) had positive axillary lymph node involvement. The molecular classification was mostly triple-negative breast cancer (65.4%). Fluorescence in situ hybridization confirmed the presence of ETV6::NTRK3 rearrangement in 16 of 18 cases (88.9%). Furthermore, Kaplan-Meier survival analysis and landmark analysis demonstrated that there were no statistically significant differences in DFS and OS between SBC and IDC patients. Although SBCs are generally associated with a favorable prognosis, our work exhibited that the clinicopathological features of SBC were partly different from former understandings, indicating that therapeutic procedure should be prudent. Further studies are necessary to fully identify the clinical behavior and predictive markers to improvediagnosis and management in this unique subtype of breast cancer.

Secretory carcinoma of breast: No more a juvenile tumor

: Secretory breast carcinoma (SBC) is one of the rare breast neoplasm with an incidence rate of < 0.15% of all breast cancers. Previously it was described as juvenile breast carcinoma. Young children and adolescent girls are most commonly affected. It is characterized by balanced translocation t (12;15), ETV6-NTRK3 gene fusion. : A 45 -year-old female presented with palpable lump in left breast. FNAC was suggestive of mucinous carcinoma. The diagnosis of SBC was made through histopathology and Immunohistochemistry: Recent study report suggested that the disease may also occur at a later age group in contrast to the conventional thought of onset at juvenile age group. Long-term survival is good for these cases. In radiological studies of breast imaging it mimics a benign tumour Immuno-histochemistry and cytogenetic are of the tumour are the ancillary investigations for confirmation of diagnosis. : Although rare diagnosis of SBC can be confirmed by histopathological studies and IHC. It is slowly progressive but has a good prognosis.

Secretory Carcinoma of Breast: A Population-Based Study.

In this study, it was aimed to evaluate the characteristic features and survival of secretory carcinoma of the breast (SCB), which is one of the rare malignant tumors of the breast. Data of patients with histopathological diagnosis of SCB between 2010 and 2019 were extracted from the SEER database. These patients were evaluated in terms of age, race, molecular subtype, grade, estrogen receptor (ER), progesterone receptor (PR), HER2 receptor, TNM stage, surgical status, chemotherapy and radiotherapy treatment. Overall survival (OS) and breast cancer-specific survival (BCSS) of the whole population and subgroups [in terms of surgery procedure (mastectomy/breast-conserving surgery), and hormone receptor status (positive/negative)] were analyzed. 70 patients were included in the study. The mean age was 57years (range 2-82). 32.9% of the patients were diagnosed under the age of 50. 97.1% of the patients were female; 2.9% were male. The vast majority of patients were white race (81.4%). Although the rates of localization were higher in the upper outer quadrant (31.4%), centrally located tumors (18.5%) were also quite common. The most frequently detected molecular subtype was hormone positive/HER2 negative. All patients were non-metastatic, 81.4% of patients did not have lymph node metastases, and most of the patients were stage IA. Median follow-up was 37months (range 0-118months). Considering all patients, OS was 76.3%, 5-year OS was 91.8%, and BCSS was 88%, 5-year BCSS was 97.8%. There was no statistically significant difference in OS and BCSS according to subgroups (P > .01). SCB, a rare histopathologic type, has high OS and BCSS rates.

Nuclear staining for pan-Trk by immunohistochemistry is highly specific for secretory carcinoma of breast: pan-Trk in various subtypes of breast carcinoma

AimsSecretory carcinoma of breast (SCB) typically harbours ETV6-NTRK3 gene fusion. Pan-Trk immunohistochemistry analysis (IHC) has been shown to be sensitive for SCB diagnosis. However, weak focal pan-Trk nuclear staining was...

Mammary analogue secretory carcinoma (MASC) of parotid gland- A case report

Mammary analogue secretory carcinoma is a rare salivary gland carcinoma which shares morphologic and immunohistochemical features with the secretory carcinoma of breast and was first proposed by Skalova in 2010 with translocation of (q13; q25), t (12; 15), subsequently giving ETV6-NTRK3 gene rearrangement. Usually, it is a benign tumor that affects the parotid gland, with slight predilection for males. The present article report a case of secretory carcinoma of right parotid gland with special emphasis on histological feature and immunohistochemistry for diagnostic purpose and its management. Differential diagnosis includes AciCC, ADC-NOS and MEC. In a review by Chiosa et al (2012) in 337 cases of salivary gland malignancy included AciCC, ADC-NOS, MEC, LGCC, non-ITAC, signet ring adenocarcinoma, PLGA and most common malignancy reclassified as MASC were AciCC (11/89), ADC-NOS (14/37), MEC (1/165). Management for MASC includes surgical excision of the lesion (either superficial or total parotidectomy) for local, less aggressive disease like for low-grade malignant salivary gland neoplasms. For more invasive, metastatic disease and positive margins- neck dissection, radiotherapy and chemotherapy are reserved. There is no standard multidisciplinary treatment protocol established due to scarcity of this disease.

Secretory breast cancer in a boy: A case report with genetic analysis using next-generation sequencing and literature review

Rationale: Male secretory breast cancer is a rare, low-grade carcinoma, especially in boys. Due to its rarity, not much is known about this disease. Patient concerns: A 5-year-old boy presented with a 1.4 cm painless mass in the right breast. Diagnoses: Ultrasonography could not distinguish whether the breast tumor was benign or malignant. After a biopsy of the lumpectomy specimen, it was diagnosed to be secretory breast carcinoma. Interventions: The patient underwent a modified radical mastectomy for his right breast. No postoperative chemotherapy or radiotherapy was performed. Next-generation sequencing of 211 cancer-related genes was detected, and the results revealed an ETV6-NTRK3 translocation and a PDGFRB c.2632A > G mutation. None of the most commonly altered molecules in male aggressive breast cancer (such as BRCA1-2, TP53, RAD51C, and RAD51D mutations) has been identified. Outcomes: The patient was still free from local recurrence or metastases at 6-month follow-up. Lessons: The genomic profile of male pediatric SCB is relatively simple, no other known driver genes have been found except for the ETV6-NTRK3 fusion. Our report will improve our understanding of secretory breast cancer.

Secretory Carcinoma of Salivary Glands: A Case Series and Review of Literature.

Mammary analogue of secretory carcinoma is a recently described entity in WHO 2017 classification of head and neck tumours. It resembles secretory carcinoma of breast. It usually affects the salivary glands and has an indolent behaviour. We reviewed five cases of Mammary analogue of secretory carcinoma in our institute and compared our results with existing literature. All the patients underwent surgical resections and appropriate adjuvant treatment. Immunohistochemistry is an alternative cost effective tool as compared to genetic testing to differentiate secretory carcinoma from its mimickers. Surgery with adequate margins followed by adjuvant therapy is the treatment of choice.

Abstract P5-02-13: TRK inhibitor in a patient with metastatic triple negative breast cancer and NTRK fusions identified via cell-free DNA analysis

Abstract Introduction: Tissue-agnostic indications for targeted therapies are expanding options for patients with advanced solid tumors. The FDA approvals of the PD-1 inhibitor pembrolizumab and the TRK inhibitors larotrectinib and entrectinib provide rationale for next generation sequencing (NGS) in effectively all advanced solid tumor patients, as findings may indicate targeted therapy even in disease that may seem otherwise refractory. Here, we present the case of a post-menopausal woman with metastatic triple negative breast cancer (TNBC) who had disease progression on multiple lines of therapy prior to the identification of two actionable NTRK mutations, identified via cell-free DNA (cfDNA) and tissue-based NGS. She was subsequently started on the TRK inhibitor larotrectinib and had a marked clinical response. Case Presentation: A 64-year-old woman presented with metastatic TNBC five years after being treated for a localized breast cancer. The cancer rapidly progressed through 4 lines of therapy in the metastatic setting, including immunotherapy [atezolizumab/nab-paclitaxel (progression after 5 months)], antibody-drug conjugate-based therapy [sacituzumab govitecan (progression after 2 months)], and chemotherapy [gemcitabine/carboplatin (progression after 3 months), eribulin (progression after 2 months)]. Her CA 15-3 had also been consistently increasing to a peak of 206 IU/mL. Germline genetic testing was negative. Ultimately, NGS evaluation of cfDNA via an 83-gene assay (Guardant Health, Inc.) identified two NTRK3 fusions: an ETV6-NTRK3 fusion [mutant allele fraction (MAF) = 10.9%] associated with the rare secretory breast carcinoma, and CRTC3-NTRK3 (MAF = 3.2%), a fusion partner previously undescribed in breast cancer. Liver biopsy was sent for whole exome sequencing and RNA-seq analysis (BostonGene, Inc), which provided orthogonal confirmation of both the ETV6-NTRK3 and CRTC3-NTRK3 fusions. Review of the tumor pathology showed invasive ductal carcinoma with secretory features; this pathology and the ETV6-NTRK3 fusion were consistent with a diagnosis of secretory breast carcinoma. She was started on the TRK inhibitor larotrectinib, and she had a significant clinical and radiographic response after only two months of therapy. Recheck of her CA 15-3 showed a decrease to 48 IU/mL, the lowest level in our records. Repeat cfDNA testing showed a decrease of the ETV6-NTRK3 fusion to MAF 0.40% and the CRTC3-NTRK3 fusion to MAF 0.07%. The patient took larotrectinib for 7 months with good disease control. Unfortunately, unrelated to her therapy, she had experienced multiple fractures secondary to her existing osseous metastases, and these led to significant morbidity. She and her family elected to transition to comfort measures, after which she passed away. Discussion: In the presented case, the identification of NTRK fusions by plasma-based genotyping resulted in matched selection of genotype-directed therapy, and this otherwise refractory TNBC exhibited marked response to targeted therapy. While TNBC had historically been considered a subtype of breast cancer without targetable options, the expanding roles of NGS testing and targeted therapies are changing the paradigm. The actionability of rare genomic events such as NTRK fusions makes identifying them critical for individual patients, particularly in heterogeneous diseases such as TNBC. Tissue-agnostic targeted therapies now give reason for NGS testing in most solid tumors, as reflected in updated consensus guidelines. This case demonstrates the significant potential benefits of NGS testing in advanced and refractory cancers. Citation Format: Jennifer C. Keenan, Arielle J. Medford, Lauren J. Oshry, Baris Boyraz, Charles S. Dai, Lesli A. Kiedrowski, Sofia Menshikova, Anna Butusova, Tasos Gogakos, Rachel Occhiogrosso, Phoebe Ryan, Jochen Lennerz, Laura M. Spring, Beverly Moy, Leif Ellisen, Aditya Bardia. TRK inhibitor in a patient with metastatic triple negative breast cancer and NTRK fusions identified via cell-free DNA analysis. [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 P5-02-13.

Clinicopathological features and genomic profiles of a group of secretory breast carcinomas in which progressive cases have more complex genomic features

BackgroundSecretory breast carcinoma (SBC) is a rare malignant breast neoplasm with distinct histological features, including solid, microcystic, tubular, and rarely papillary structures, traditionally characterized by a t (12;15) (p13:q25) translocation, which usually leads to ETV6-NTRK3 fusion, suggesting an early event in tumorigenesis. Due to the rarity of this disease, very few genome sequencing studies have been performed on a series of cases, especially progressive cases.MethodsSeven lesions from 5 patients diagnosed at the Third Affiliated Hospital of Soochow University from 2007 to 2021 were included. Clinicopathological features and prognosis/survival data were collected. Next-generation DNA sequencing was performed on six of the seven lesions.ResultsIn total, 3/7 (42.9%) lesions demonstrated estrogen receptor (ER) expression, including weak, moderate to strong staining, and no lesion demonstrated progesterone receptor (PR) expression. There were no cases of human epidermal growth factor (HER2) overexpression, and the Ki-67 index was low. S-100 and pan-TRK protein were diffusely positively expressed in all cases. All lesions were characterized by a t(12;15) (p13:q25) translocation, leading to ETV6-NTRK3 fusion confirmed by fluorescence in situ hybridization (FISH). The sequencing results showed that ETV6-NTRK3 fusion was the main driver of early tumorigenesis, while SBC with invasive biological behavior had more complex genomic variation in which TERT promoter mutation was detected.ConclusionsImmunohistochemical staining of a biomarker panel, including ER, PR, HER2, Ki-67, S-100 and pan-TRK, can be used as an auxiliary diagnostic tool, and FISH detection can be used as a diagnostic tool. ETV6-NTRK3 gene fusion involving multiple sites may drive tumorigenesis, while mutations in the TERT promoter region may be a factor driving tumor progression.

Rare case of metastatic secretary carcinoma presenting as an abscess

Secretory Breast Carcinoma (SBC) is a rare and distinct type of breast cancer which accounts for less than 0.2% of all breast cancers. The modern breast imager should be aware of this rare entity as it can sometimes masquerade as a breast abscess as in the present case

176. Secretory Cell Carcinoma: A case report of a rare salivary neoplasm

Secretory cell carcinoma of the salivary gland is a rare malignant neoplasm, described as a new entity in the 2017 WHO classification of head and neck tumours. It was previously synonymous with ‘mammary analogue secretory carcinoma’ due to the morphological, genetic and histological similarities to breast secretory carcinoma. Despite the risk of local recurrence and distant metastases it is reported to have a favourable prognosis.

Advancement of secretory breast carcinoma: a narrative review.

Secretory breast carcinoma (SBC) is a rare breast malignancy. Most available studies on SBC are case reports or small case series, and the few large-sample studies available lack critical information due to database limitations. To improve the understanding of SBC and provide a reference for clinical practice, we systematically reviewed the demographic, clinical, pathologic, and genetic characteristics of SBC, as well as its treatment and prognosis. We conducted a PubMed search with the keywords "secretory breast carcinoma" or "juvenile breast carcinoma". Relevant English-language publications published from January 1966 to February 2022 were screened manually at 3 levels-title, abstract, and full text-to identify the articles that presented the demographic, clinical, pathologic, and genetic characteristics of SBC, as well as its treatment and prognosis. SBC lacks specific clinical manifestations and has typical pathological and molecular characteristics, including intracellular and extracellular eosinophilic secretions, immune spectrum similar to hormone receptor-positive tumors, and the ETV6-NTRK3 fusion gene. Surgery remains the primary treatment for SBC. Postoperative radiotherapy is recommended by most researchers for adult SBC but not for pediatric patients. The evidence of chemotherapy and endocrine therapy is insufficient, and targeted therapy of the ETV6-NTRK3 fusion gene shows a good response. Most patients with SBC have a good prognosis except for a few patients who experience distant metastases. Future studies will be focused on the molecular characteristics of those patients with SBC who have a poor prognosis. The development of histopathology and molecular genetics has promoted the progress of the clinical diagnosis of SBC. The purpose of this review is to serve as a guide for the better clinical treatment of SBC, particularly in the areas of disease identification and prognosis classification for patients.

A Parotid Gland Mammary Analogue Secretory Carcinoma in a 4-Year-Old Boy: Case Report and Literature Review

Background: Mammary analogue secretory carcinoma (MASC) is characterized by similar histologic, immunohistochemical, and molecular features with breast secretory carcinoma. MASC usually occurs in adults. Case report: A 4-year-old boy presented with a right infra-auricular mass. Features of the tumor include solid, tubular, and papillary growth patterns, with homogenous eosinophilic secretions inside microcystic structures. Immunohistochemical stains showed strong, diffuse staining for CK7, S100, pan-TRK protein. P63 was positive in a peripheral pattern. Fluorescence in situ hybridization (FISH) analysis showed the characteristic ETV6-NTRK3 gene fusion. Conclusion: Typical histological, immunohistochemical, and molecular features are present in MASC occurring early in childhood.

Secretory Carcinoma of the Breast Mimicking Invasive Ductal Carcinoma: A Case Report

Patient: Female, 40-year-old Final Diagnosis: Secretory breast carcinoma Symptoms: Breast mass Medication:— Clinical Procedure: — Specialty: Oncology Objective: Rare disease Background:Secretory breast carcinoma (SBC), an extremely rare malignancy, is related to a chromosomal translocation which leads to an ETV6-NTRK3 fusion mutation. SBC is characterized by eosinophilic secretions and is usually triple-negative, with a small number of patients demonstrating ER-positivity of the tumors. Diagnosis can be challenging and requires genomic testing for confirmation.Case Report:A 40-year-old woman presented with a breast mass found on mammography. She underwent an ultrasound-guided biopsy of the tumor. Initial pathology evaluation revealed features consistent with invasive ductal carcinoma. The immunochemistry report described an ER-positive, PR-negative, and HER2-negative tumor. The specimen was sent for oncotype scoring, which was not performed due to the specimen not meeting the criteria for invasive ductal carcinoma and displaying pathological features of SBC. A fluorescent in situ hybridization (FISH) study revealed ETV6 translocation, consistent with the diagnosis of SBC. The patient underwent lumpectomy followed by adjuvant radiotherapy and endocrine therapy. She remains in complete remission 3 years after treatment.Conclusions:Accurately diagnosing SBC is of extreme importance as it has an indolent clinical course, but has a favorable prognosis if detected early. Due to nonspecific imaging findings, pathology evaluation with immunohistochemical staining followed by genomic testing is required. Our case highlights the challenges associated with SBC diagnosis requiring genomic testing due to equivocal pathological findings, along with increasing incidence of SBT in adults. There are no established guidelines for SBC management. The mainstay of treatment is partial or total mastectomy. Data on the benefits of adjuvant endocrine therapy, chemotherapy, and radiotherapy are inconclusive.

Mammary analog secretory carcinoma in adults: A systematic review.

e18076 Background: Mammary analog secretory carcinoma (MASC) is a rare malignant salivary gland tumor of the head and neck region that was first described by Skálová et al. in 2010. It histologically mimics breast secretory carcinoma and parotid acinic cell carcinoma, and characterized by ETV6-NTRK3 fusion gene. This review aims to investigate the clinicopathologic features, treatment, and outcomes of MASC in adults. Methods: PubMed search for MASC adults (18+ years) from data inception through 2021, pooled with a case from our institution. Kaplan-Meier analysis was used to plot survival curves. Results: Of the 254 included cases, female:male ratio 1.02:1 with a mean age at diagnosis (±SD, range) of 50.1 (±16.7, 18–86) years. In terms of location, 143 (56.3%) occurred in the parotid gland, 21 (8.3%) in the submandibular gland, 21 (8.3%) in the lip, 15 (5.9%) in the thyroid gland–all (100%) had a component of classical type papillary carcinoma, 15 (5.9%) were cutaneous, 13 (5.1%) in the buccal mucosa, 12 (4.7%) split between hard and soft palate, 4 (1.6%) in the nasal mucosa, 2 (0.8%) in the lung, and remaining 8 (3.1%) each in the conjunctiva, tongue, minor salivary gland, submaxillary gland, maxillary sinus, ethmoid sinus, upper esophagus, and mandible. Patients mostly presented with swelling or growing mass in 95.4% (out of which, 93.3% were painless), followed by a painful ulcer in 1.8%. Median tumor size was 1.9 cm (range 0.3cm–8.5cm). Median duration of symptoms at time of presentation was 12 (range 1-360) months. Tumors were T1 (49.7%), T2 (23.9%), T3 (20.3%), and T4 (6.1%), N0 (81.9%), N1 (10.7%), N2 (7.4%), M0 (97.4%), and M1 (2.6%). Most patients (70.7%) presented as early stage (I or II) which was associated with a high survival probability based on a log-rank test (p-value: 0.0007). All patients had surgical resection, mostly combined with neck dissection (ND) in11.4%, radiation (RT) in 7.8%, ND+RT in 4.7%, ND with platinum-based chemoradiation in 1.0%, and one case reported use of Crizotinib followed by Entrectinib with disease progression at 4.5 and 7 months, respectively. Among patients with reported outcomes, 92.2% were alive with a median follow-up of 26 (range 1-228) months, and 7.8% deceased with a median time-to-death of 29 (range 1-107) months. Eleven (4.3%) reported a high-grade MASC and 18.5% of patients lived for over five years after their diagnosis. Conclusions: Early stage was a notable predictor of higher survival probability in MASC patients. Its rarity, heterogeneity of clinical behaviors, and variable outcomes make it even more challenging. This review serves as real-world evidence to further our understanding of this rare entity and shed light on prospective clinical trial design.

Secretory carcinoma of the breast- A rare case report

Secretory carcinoma of breast represent a rare subtype of carcinoma breast with a incidence of less than 0.15%. Though initially thought to be limited to children. Later it was recognised that it may occur in adult as well. It has an indolent course and carries favourable prognosis. It is a slow growing tumour and it is associated with good long-term survival. Breast imaging usually mimics a benign tumour. Immunohistochemistry and cytogenetic analysis of tumour are crucial for confirmation of SBC. Currently there is no established guidelines regarding the best treatment strategy for patients with SBC. BCS with sentinel nodes biopsy is at present the first choice treatment. Further research for identification of the specific gene mutation may pave for targeted molecular therapies for this disease.

Neurotrophic receptor tyrosine kinase family members in secretory and non-secretory breast carcinomas.

BACKGROUNDBreast cancer is the most common female cancer and a major cause of morbidity and mortality. Progress in breast cancer therapeutics has been attained with the introduction of targeted therapies for specific sub-sets. However, other subsets lack targeted interventions and thus there is persisting need for identification and characterization of molecular targets in order to advance breast cancer therapeutics.AIMTo analyze the role of lesions in neurotrophic receptor tyrosine kinase (NTRK) genes in breast cancers.METHODSAnalysis of publicly available genomic breast cancer datasets was performed for identification and characterization of cases with fusions and other molecular abnormalities involving NTRK1, NTRK2 and NTRK3 genes.RESULTSNTRK fusions are present in a small number of breast cancers at the extensive GENIE project data set which contains more than 10000 breast cancers. These cases are not identified as secretory in the database, suggesting that the histologic characterization is not always evident. In the breast cancer The Cancer Genome Atlas (TCGA) cohort the more common molecular lesion in NTRK genes is amplification of NTRK1 observed in 7.9% of breast cancers.CONCLUSIONNeurotrophin receptors molecular lesions other than fusions are observed more often than fusions. However, currently available NTRK inhibitors are effective mainly for fusion lesions. Amplifications of NTRK1, being more frequent in breast cancers, could be a viable therapeutic target if inhibitors efficacious for them become available.