Whole genome sequencing of locally advanced and metastatic breast carcinoma unravels relevant molecular signatures and novel events.

Ribociclib, a cyclin-dependent kinase (CDK) 4/6 inhibitor, is widely used in combination with endocrine therapy for advanced hormone receptor-positive breast cancer. However, drug exposure may be highly variable in older patients due to organ dysfunction and polypharmacy, raising the need for therapeutic drug monitoring (TDM). We report the case of an 88-year-old woman with metastatic lobular breast carcinoma treated with ribociclib and tamoxifen, who developed progressive renal impairment and was co-prescribed apixaban. Serial TDM demonstrated ribociclib overexposure (Cmin 1022-1318 ng/mL vs. ~ 500 ng/mL expected at steady state), associated with markedly increased plasma concentrations of tamoxifen, endoxifen, and apixaban (923 ng/mL vs. reference peak ~ 206 ng/mL). Monte Carlo simulations incorporating patient covariates confirmed that measured ribociclib concentrations exceeded predicted distributions, likely due to the accumulation of uremic toxins. TDM of CDK4/6 inhibitors provides valuable insight into drug exposure in complex geriatric oncology settings. Beyond monitoring ribociclib itself, this approach facilitates a broader discussion on individualized dosing, comedication safety, and management of organ dysfunction in elderly patients with cancer.

Echocardiographically occult nonbacterial thrombotic endocarditis with tumor cell-containing valvular vegetations in metastatic breast cancer.

Abstract Introduction Male breast cancer (MBC) is an uncommon malignancy, accounting for less than 1% of all breast cancers. Most tumors are invasive ductal carcinomas and hormone receptor-positive, often diagnosed at advanced stages due to low clinical suspicion. Although pulmonary metastases are a recognized feature of disseminated disease, malignant pleural effusion (MPE) is rarely reported in men. We describe a case of biopsy-proven metastatic MBC complicated by MPE after prolonged stability with sequential endocrine and targeted therapy, culminating in the development of MPE. Case Report An elderly man with a history of atrial fibrillation and type 2 diabetes mellitus presented with a retroareolar breast mass and nipple retraction. Imaging revealed a right breast lesion with axillary lymphadenopathy. Biopsy confirmed invasive ductal carcinoma, estrogen and progesterone receptor positive, HER2 and BRCA1/2 negative. The patient declined surgery and was started on tamoxifen, achieving metabolic response on follow-up PET-CT.After two years, disease progression was observed with a hypermetabolic pulmonary nodule. CT-guided biopsy confirmed metastatic breast carcinoma with glandular morphology, GATA3 positivity, and TTF-1 negativity, consistent with breast origin. Treatment was transitioned to fulvestrant combined with palbociclib, a CDK4/6 inhibitor. Despite hematologic toxicity necessitating dose adjustment, the patient maintained durable partial response and clinical stability.Approximately one year later, he developed progressive dyspnea and cough. Chest radiography demonstrated near-complete opacification of the left hemithorax. Thoracentesis drained over one liter of bloody exudative fluid. Cytology and immunostaining were GATA3 positive, confirming malignant pleural effusion. His course was complicated by recurrent pulmonary infections and frailty, prompting transition to hospice following multidisciplinary goals-of-care discussions. Discussion This case highlights the therapeutic complexity and evolving management of advanced MBC. Tamoxifen remains the cornerstone of treatment for hormone receptor-positive MBC and achieved durable disease control in this patient. The addition of CDK4/6 inhibition with fulvestrant reflects the expanding role of targeted therapy, which has demonstrated benefit in men despite limited trial inclusion. The subsequent development of MPE marked terminal progression, emphasizing both the limitations of systemic therapy and the importance of palliative integration. Few reports document MPE in MBC, underscoring the need to recognize pleural involvement as a late manifestation of disease.Documentation of such cases enhances understanding of MBC’s clinical course and supports continued refinement of evidence-based treatment strategies for this rare malignancy. This abstract is funded by: None

The metastases of breast cancer to bone marrow can mimic plasma cell neoplasia morphologically due to presence of plasma cell-like neoplastic cells and even positive staining for a carcinoma metastasis with plasma cell marker CD138/ Syndecan-1 may cause confusion in diagnosis. This case report details a 71-year-old female initially suspected of plasma cell myeloma due to hypercalcemia and multiple lytic bone lesions. However, a bone marrow biopsy revealed syndecan-1 positive metastatic lobular breast cancer mimicking a plasma cell neoplasm. Bone marrow aspirate smears and the bone marrow biopsy showed plasmacytoid cells that were strongly positive for syndecan-1, indicating metastatic lobular breast carcinoma. The overexpression of syndecan-1 was a critical marker in identifying the breast cancer cells, emphasizing the diagnostic challenges when syndecan-1 positive metastatic lobular BC presents with plasmacytoid features.

IGF-2–Mediated Non-Islet Cell Tumor Hypoglycemia in Metastatic Breast Carcinoma: A Case of Refractory Hypoglycemia Improving With Change in Systemic Therapy

The retinoblastoma protein (Rb) is a critical cell-cycle regulator, and its loss of function can lead to resistance to CDK4/6 inhibitors (CDK4/6i), which are the standard first-line treatment for estrogen receptor (ER)-positive metastatic breast carcinoma (mBC). Thus, identifying Rb-deficient mBC is crucial for optimal personalized breast cancer management. This study aimed to determine the prevalence of Rb loss by immunohistochemistry (IHC) in a cohort of ER + mBC and to assess its correlation with RB1 genetic inactivation. We analyzed Rb IHC in 50 consecutive ER-positive mBC. Histopathologic and clinical features were analyzed. p16 IHC was performed in a subset of Rb-deficient cases. Targeted next-generation tumor-normal sequencing (NGS) data using MSK-IMPACT were retrospectively analyzed in 38 mBCs. Rb loss was identified in 20% (10/50) of mBC, and was either partial (8%, 4/50) or complete (12%, 6/50). In all evaluable cases (100%, 9/9), Rb loss was associated with p16 positivity. Neuroendocrine (NE) features were observed in 40% (4/10) of mBCs with Rb loss. MSK-IMPACT data were available for six Rb-deficient cases and revealed pathogenic RB1 alterations in two (33%). None of the tumors with preserved Rb expression (80%, 40/50) showed RB1 genetic alterations or NE features. Notably, one mBC case demonstrated disease progression on CDK4/6 inhibitor therapy, accompanied by acquired Rb loss and acquisition of an NE phenotype. Rb loss in mBC can be reliably detected by Rb IHC, especially when interpreted alongside p16, offering a rapid and cost-effective means of assessing Rb status. This approach may identify Rb-deficient tumors that are missed by conventional methods, such as next-generation sequencing, and help guide personalized therapeutic strategies in patients with mBC.

Synchronous breast carcinoma and diffuse large B-cell lymphoma occurring as independent primary malignancies is exceptionally rare. Because these tumors differ markedly in histological origin, biological behavior, and treatment strategies, their coexistence can easily lead to diagnostic pitfalls and therapeutic dilemmas. Reporting such a case provides new insights into the clinical recognition and management of rare dual primaries. A 54-year-old woman presented with a painless left cervical (neck) mass. Imaging revealed a left breast lesion with multi-station lymphadenopathy (including cervical nodes), initially interpreted as metastatic breast carcinoma. Breast core biopsy confirmed HER2-overexpressing invasive ductal carcinoma with strong ER/PR positivity. Cervical (neck) lymph-node biopsy established diffuse large B-cell lymphoma (non-GCB/MCD) with TP53, MYD88, and CD79B mutations. The patient received rituximab-based therapy plus a Bruton tyrosine kinase inhibitor and underwent simple mastectomy. The breast carcinoma has remained controlled without evidence of recurrence, whereas the relapsing lymphoma ultimately determined the disease course. This case emphasizes the need for independent biopsies of suspicious lesions to avoid misclassification as metastatic disease. Management should follow a “lymphoma-first” approach with careful sequencing to balance treatments for both malignancies and to minimize overlapping toxicities. Prognosis is largely driven by the biological features of the lymphoma, particularly in high-risk molecular subtypes. A dual-track follow-up strategy, recording outcomes for each tumor separately, may improve clarity in assessing prognosis and guiding individualized care. This report underscores the importance of multidisciplinary collaboration and highlights potential directions for future research on the mechanisms and management of synchronous dual primaries.

Occult breast carcinoma (OBC) refers to the clinical presentation of breast carcinoma occurring in axillary lymph node(s) without a detectable primary breast cancer. Prior studies of OBC have focused on treatment regimens. We sought to study the clinical, morphologic, and immunohistochemical features of OBCs. We retrospectively identified cases of OBC treated at our center between 1996 and 2021. All patients included in the study had biopsy-proven axillary metastatic breast carcinoma and underwent MRI after a noncontributory mammogram/ultrasound. Patients with a prior history of breast carcinoma were excluded. The study included 68 patients with a median age of 56 years (range: 31 to 84y). The morphology in 55 cases (81%) was poorly-differentiated carcinoma, no special type (ductal). The remaining tumors showed lobular, micropapillary, apocrine, clear cell, and signet ring cell morphology. Thirty-nine (57.4%) OBC were hormone receptor positive, 19 (33.3%) were HER2 positive and 13 (22.8%) tumors were triple negative. Fifty (74%) patients had a breast sampling procedure while 18 (26%) did not. Thirty-four (50%) patients underwent neoadjuvant chemotherapy. Fifty-nine (87%) patients underwent axillary lymph node dissection while 9 (13%) had sentinel lymph node biopsy only. Nineteen (56%) patients achieved a complete pathologic response in the axilla. Fourteen (21%) patients developed a recurrence: 5 in the ipsilateral breast or axilla, 1 in the contralateral axilla and mediastinum, and 8 in distant metastatic sites. The median time to recurrence was 51.9 months. The final pathologic lymph node stage was the only feature found to be significantly associated with the development of recurrence.

106 Sequential Biomarker Evolution in Metastatic Breast Carcinoma: Directional Correlation of Receptor Discordance with Systemic Therapy Exposure

175 MHC Class I Loss as a Potential Predictor of Checkpoint Inhibitor Resistance in Metastatic Triple-Negative Breast Carcinoma

569 Diagnostic Specificity of the Novel Marker TRPS1 compared with Traditional Breast Specific Markers in Differentiating Metastatic Breast Carcinoma from Adrenal Neoplasms

Breast cancer is the most common malignancy among women worldwide. It typically metastasizes to the bone, lungs, and liver, while ovarian involvement is relatively uncommon. This report aims to illustrate the clinical features, diagnostic approach, and treatment strategies for this rare type of metastasis through a case study, thereby enhancing clinicians' awareness and management capabilities. A 32-year-old premenopausal woman presented with a palpable nodule in the left breast. Comprehensive diagnostic evaluation, including mammography, ultrasonography, contrast-enhanced computed tomography, and core needle biopsy, confirmed invasive ductal carcinoma, classified as Luminal A subtype (estrogen receptor/progesterone receptor-positive, human epidermal growth factor receptor 2-negative). Invasive ductal carcinoma of the left breast (pT3N3M1, stage IV) with ovarian metastasis. The patient received 6 cycles of docetaxel/doxorubicin/cyclophosphamide chemotherapy (docetaxel, doxorubicin, and cyclophosphamide), followed by left modified radical mastectomy with axillary lymph node dissection, achieving R0 resection. Laparoscopic bilateral adnexectomy was also performed for ovarian ablation. Final pathology confirmed metastatic breast carcinoma in the ovaries. The patient successfully achieved surgical tumor reduction, recovered well postoperatively, and showed no clinical evidence of disease progression. This case highlights the distinct characteristics of ovarian metastases in HR+/HER2- breast cancer and their critical importance in differential diagnosis, particularly in distinguishing them from primary gynecologic tumors. For patients with a history of breast cancer, the presence of pelvic lesions should prompt consideration of metastatic potential to guide appropriate comprehensive treatment.

Adenocarcinoma involving the skin presents a diagnostic challenge, as it may represent either a rare primary cutaneous adnexal malignancy or cutaneous metastasis from an internal primary, most commonly breast carcinoma. We report the case of a 77-year-old female with a scalp lesion excised for presumed squamous cell carcinoma (SCC), with an immunohistochemical profile raising concern for metastatic breast carcinoma. Despite a strong family history of breast cancer, comprehensive systemic investigation with various imaging modalities, tumour markers, and screening mammograph identified no primary malignancy. Surgical re-excision was performed to achieve clear margins, and final histopathology demonstrated a small residual focus of adenocarcinoma with negative margins. In the absence of an identifiable visceral primary, findings were most consistent with primary cutaneous adnexal adenocarcinoma. This case emphasises the importance of a multidisciplinary approach and supports complete surgical excision with margin clearance as definitive management when metastatic disease is excluded.

Abstract Background Breast cancer is the most frequently diagnosed malignancy among women, with invasive lobular carcinoma (ILC) comprising 15% of cases. ILC frequently harbors CDH1 mutations, resulting in the loss of E-cadherin as well as a dyscohesive growth pattern that hinders detection. Signet ring cell carcinoma of the breast, a rare but diagnostically significant variant with poor prognosis, can closely mimic primary gastric adenocarcinoma. Shared histomorphology, particularly in metastatic setting at diagnosis, predisposes to misclassification and consequent therapeutic misdirection. Case Presentation A 61-year-old woman presented to the emergency room with one-month of dysphagia, nausea, vomiting, and unintentional weight loss. Radiographic studies revealed abdominopelvic ascites, periportal lymphadenopathy, right adnexal enlargement, osseous lesions, and omental carcinomatosis. A biopsy of the gastric fundus was positive for invasive adenocarcinoma, diffuse type with signet ring features, supported by positive pan-cytokeratin AE1/AE3 staining. Further biopsy of an omental mass showed CK7 positivity and negativity for PAX8, CDX2, and CD20. Metastatic gastric adenocarcinoma was presumed, and capecitabine-oxaliplatin was commenced. Additional molecular profiling was completed, which revealed breast markers including ESR1, GATA 3, cytokeratin, and mammaglobin. A pathogenic loss of function variant in CDH1 was also detected. Further immunohistochemistry (IHC) on the omental specimen revealed ER 90%, PR 90%, and HER2 IHC 0. IHC of the omentum was also positive for GATA3, mammaglobin, and E-cadherin. These findings supported a diagnosis of metastatic lobular breast carcinoma with signet ring features. MRI breast did not identify a primary breast mass and there were no pathologic axillary lymph nodes. Following bilateral salpingo-oophorectomy, pathology for the right adnexal mass showed carcinoma of breast origin (ER 95%, PR 70% and HER2 IHC2+ and FISH negative). The treatment was switched to a first line aromatase inhibitor and CDK 4/6 inhibitor and the patient has since undergone multiple lines of therapy. Discussion Although breast cancer metastasizing to the stomach is rare—with an estimated incidence of just 0.04%—accurate diagnosis of primary origin of adenocarcinoma is vital due to the stark differences in management and outcomes. The clinical and morphological overlap between metastatic ILC with signet ring features and primary gastric carcinoma necessitates a high index of suspicion and thorough immunohistochemical analysis. ILC may metastasize in a diffuse pattern mimicking gastrointestinal malignancies and can present without an identifiable breast lesion. Literature has shown that ER, GCDFP-15, mammaglobin, and GATA3 are highly sensitive and specific for identifying breast origin, whereas CK20 and CDX2 are associated with gastrointestinal differentiation. Although not unique to breast tumors, CDH1 and PIK3CA alterations are detected in roughly 63-65% and 46% of invasive lobular carcinomas, respectively, versus only about 9.7% and 12% of gastric adenocarcinomas. Further studies are warranted to refine diagnostic algorithms that couple IHC with next-generation sequencing, clarifying when the addition of breast-specific markers is essential for definitive tumor origin assignment. Conclusion This case emphasizes the need for comprehensive diagnostic workup in atypical presentations and supports broader use of breast-specific IHC markers and molecular profiling in gastrointestinal biopsies with ambiguous or signet ring histology. Integrating markers such as ER, PR, GATA3, mammaglobin, and CDH1/PIK3CA profiling into a tiered diagnostic algorithm can prevent misclassification, facilitate timely therapy, and ultimately improve patient outcomes. Citation Format: J. Eckman, H. Jeon, S. Oh. When Signet Ring Cells Mislead: A Case of Metastatic Breast Cancer Presenting as Gastric Malignancy [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS5-06-21.

Abstract Background Liquid biopsy enables minimally invasive cancer monitoring through blood circulating tumor DNA (ctDNA) sequencing. We analyzed ctDNA sequencing data of 127 blood samples from 27 patients with hormone receptor positive (HR+) metastatic invasive lobular breast carcinoma (ILC) and 10 patients with HR+ no special type/invasive ductal carcinoma (NST/IDC) from the UPMC Hillman Cancer Center APOLLO biobank collection. In APOLLO collection, patients’ blood is collected at each disease progression, enabling longitudinal analysis of ctDNA dynamics. In this study, we focused on longitudinal analysis of ctDNA dynamics in patients with ILC. Methods We analyzed 31 longitudinal NST samples (2-6 per patient, median 3) and 96 ILC samples (2-7 per patient, median 3). DNA was extracted from plasma and sequenced using shallow whole genome sequencing, with a mean coverage of 0.21x. We used ichorCNA to determine the tumor fraction (TFx) of samples, and used CNVkit to annotate gene level copy number variation (CNV) and filtered with a list of genes that have most frequent copy number aberration in breast cancer. GISTIC2.0 was applied to compare chromosomal segment aberration of ILC and NST cases. Gene level CNVs were collapsed to each patient, and continuity index (1 - [number of transition/maximum possible transitions]) was applied to measure the longitudinal consistency of gene CNVs. Results Patients with ILC had a median overall survival of 43 months (range 6-124 months) with a median of 5 treatment lines (range 2-11). IchorCNA analysis showed 85 samples (91.4%) had TFx >3% (mean TFx 12.5%). Tumor fraction fluctuates across time, and shows correlation with the patient treatment scheme. Patient-level analysis demonstrated predominant copy number gains (copy number ≥3) versus losses (copy number <2). MDM4, ELF3, IKBKE and IL10 were the four most gained genes across 88% of patients for each gene. ESR1 was amplified in 40% and ERBB2 in 32% of patients. The top copy number loss gene was ZFHX3 (68% of patients), followed by TP53, MAP2K4 and NCOR1 (totaling 64% of patients). We compared ILC cases to NST/IDC cases in genomic CNV. We discovered a chromosome 11q13.3 amplicon enriched in ILC cases. This region showed preferential gain in genes CCND1, FGF3, FGF4, and FGF19, suggesting a potential ILC oncogenesis driver locus. Additional ILC and NST/IDC samples are being prepared for sequencing to validate these findings. Conclusions This study demonstrates the dynamics of ctDNA in metastatic ILC, which can be used to infer tumor evolution in concordance with treatment scheme. ILC-enriched chromosomal signatures may suggest potential unique oncogenic drivers. We are also developing a transformer-based model to predict gene expression pattern via genomic copy number changes using public databases, and fine-tune it with in-house metastatic breast cancer sequencing dataset. We will validate the model with liquid biopsy sequencing data and paired tumor sequencing data to identify robust predictors that can stratify patients’ prognosis. Our study highlights the potential clinical utility for ctDNA-based cancer monitoring to advance precision oncology in metastatic breast cancer. Citation Format: D. Liu, R. Kumar, J. Hooda, A. C. Chang, L. Miller, M. Rosenzweig, J. M. Atkinson, A. Stalnaker, V. Gao, S. Oesterreich, A. V. Lee, M. Balic, J. Foldi. Longitudinal genomic profiling of circulating tumor DNA in metastatic invasive lobular (ILC) and no special type (NST) breast cancer [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS1-10-16.

Abstract Background: Breast cancer is the most commonly diagnosed malignancy in women and the second leading cause of cancer death. While bone, lung, liver, and regional lymph nodes are frequent sites of metastasis, laryngeal involvement is exceedingly rare, accounting for <1% of all laryngeal tumors, with breast cancer representing an uncommon primary source. Diagnosis can be challenging when laryngeal lesions present as the sole clinical manifestation of recurrence. Case Presentation: A 79-year-old woman with history of hormone receptor-positive, HER2-negative, high-risk luminal breast cancer (stage IIB) diagnosed in 2015, previously treated with mastectomy, adjuvant chemotherapy (docetaxel/cyclophosphamide), and seven years of endocrine therapy, presented with progressive hoarseness and a 10-pound unintentional weight loss over four months. She denied dysphagia, decreased appetite, recent infections, neck trauma, surgery, or tobacco and alcohol use. On physical examination, the larynx was midline with mild left-sided tenderness, but no palpable cervical or supraclavicular lymphadenopathy. Flexible laryngoscopy revealed left vocal cord swelling, reduced mobility and fullness of the left aryepiglottic fold. Computed tomography (CT) revealed a left laryngeal mass destroying the thyroid cartilage, associated left level II lymphadenopathy, and lytic bone lesions in the right sixth rib and T11 vertebra, concerning for metastatic disease. Biopsy of the laryngeal lesion confirmed poorly differentiated carcinoma, which was strongly estrogen receptor-positive (100%), moderately progesterone receptor-positive (30%), HER2-negative, high Ki-67 (30%). Immunohistochemistry supported metastatic breast carcinoma. Positron emission tomography-CT showed intense FDG uptake in the laryngeal mass (SUVmax 15.1) and multiple skeletal metastases, without visceral involvement. Intensity-modulated radiation therapy was administered to the larynx for local control and symptom palliation. Antiestrogen therapy with letrozole was initiated, with plans to add a CDK 4/6 inhibitor after the completion of radiation. Given her diffuse bony disease, she was started on monthly denosumab, with radiation planned for symptomatic bony lesions. Discussion: Laryngeal metastasis from breast cancer is exceedingly rare and carries a poor prognosis, typically signaling disseminated disease. Laryngeal involvement usually presents with nonspecific symptoms such as dysphonia, chronic cough, dysphagia, or stridor, which are often misattributed to benign conditions or primary laryngeal cancer, leading to diagnostic delays. Hormone receptor status is a key determinant of prognosis and mortality in metastatic breast cancer, including rare sites like the larynx. ER-positive metastatic disease is associated with longer median survival, whereas triple-negative breast cancer has the poorest prognosis and highest mortality. Notably, receptor status can change between the primary tumor and metastatic sites; thus, biopsy and reassessment of receptor status in metastatic lesions is recommended, as it may impact both prognosis and therapeutic options. Management remains multidisciplinary, with systemic endocrine therapy preferred for hormone receptor-positive disease and localized radiotherapy for symptom control. Conclusion: Laryngeal metastasis from breast cancer, though rare, should be considered in patients presenting with persistent hoarseness or other unexplained laryngeal symptoms. Improved survival among breast cancer patients has increased the risk of metastasis to uncommon sites, underscoring the importance of vigilant follow-up and a high index of suspicion for atypical presentations. Timely diagnosis and individualized therapy are essential to optimize outcomes and maintain quality of life. Citation Format: D. Samat, S. Iqbal, M. Haas, N. Leasure, S. Singh. A Rare Case of Breast Cancer Recurrence Presenting as Laryngeal Metastasis [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS5-06-05.

CLINICAL IMAGE Lung carcinoma mimicking breast cancer 1 Computed tomography identified an infiltrative mass in the right upper lobe (31 mm 74 mm), pleural effusion, as well as multiple bone metastases, multiple liver metastases, adrenal and renal lesions, and skeletal metastases.Mammography and breast ultrasound showed bilateral irregular, well -defined, hypoechogenic breast nodules (14-19 mm; Breast Imaging Reporting and Data System, 4c).Such lesions can mimic primary BC, including triple -negative phenotypes, which is why tissue diagnosis with immunohistochemistry is the golden standard. 4FIGURE 1A-1F shows the diagnostic imaging performed.Liver biopsy demonstrated adenocarcinoma-CK7+, TTF1+, HER2-, and Ki67 of approximately 42%-consistent with pulmonary origin.Breast biopsies in both cases showed adenocarcinoma metastatis immunoprofile: CK7+/TTF1+/ER-/ PR-/HER2-/GATA3-/GCDFP-/ mammaglobin-.The result supported lung origin rather than primary breast carcinoma.Microscopic images of histology samples are presented in FIGURE 1G and1H.Key features that can distinguish between metastatic and primary breast carcinoma include: absence of an in -situ component, multiplicity / bilaterality, and a lack of breast markers, such as ER/ PR/HER2/GATA3/GCDFP/mammaglobin, with positive lung markers (TTF -1).The treatment proposed by a multidisciplinary board included stereotactic radiotherapy for brain metastases, brachytherapy for ocular metastasis, and systemic therapy (chemotherapy or immunotherapy) pending molecular testing (programmed cell death ligand 1 and next generation sequencing).The patient remained clinically stable and was discharged with follow -up scheduled for oncology, ophthalmology, radiotherapy, and palliative care.The therapy consisted of paclitaxel, gemcitabine, and radiotherapy of the brain.The treatment followed current standards of care. 5etastatic breast disease originating from lung cancer is a rare clinical condition, even rarer

Inflammatory breast cancer (IBC) is a highly metastatic breast carcinoma, frequently characterized by estrogen receptor alpha (ERα) negativity and limited treatment options. Our previous research showed that the second ER subtype, ERβ, is associated with reduced metastasis in IBC patients and xenografts. We linked its anti-metastatic function to the inhibition of actin-based cell migration and Rho GTPase signaling. In this study, we employed a genomics approach to fully delineate the signaling underlying the anti-metastatic activity of ERβ. By cross-examining responsive mRNAs and miRNAs against chromatin binding sites in IBC cells with agonist-activated transfected and endogenous ERβ, we identified key regulatory binding motifs, direct targets, and associated biological functions. Our findings implicate pathways in development, metabolism and tumor microenvironment in the anti-metastatic action of ERβ. Clinical dataset analysis associates downstream factors with patient outcomes, indicating new molecules with therapeutic potential and highlighting the relevance of tumor repressive ERβ signaling in breast cancer.

We report a rare case of salivary duct carcinoma (SDC) in a 67-year-old male who presented with a rapidly enlarging, ill-defined left upper neck mass, accompanied by both cervical and axillary lymphadenopathy. Initial punch biopsy of the neck mass suggested metastatic breast carcinoma. However, ultrasound-guided fine-needle aspiration (US-FNA) and comprehensive immunohistochemical analysis, in conjunction with radiologic findings, confirmed the diagnosis of SDC. This case highlights the diagnostic challenges of SDC and reinforces the pivotal role of US-FNA cytology in establishing a definitive diagnosis while minimizing invasive procedures.