# A gastric and pleural metastasis of occult breast lobular cancer in an elderly female and radiomics assisted analysis of a rare metastasis

**Authors:** Yuxin Xie, Qitao Gou, Wenjun Wu, Shuang Zhao, Libo Yang, Qiheng Gou

PMC · DOI: 10.3389/fonc.2026.1703374 · Frontiers in Oncology · 2026-02-06

## TL;DR

This paper describes a rare case of hidden breast cancer that spread to the stomach and pleura in an elderly woman, using radiomics and immunohistochemistry to track the disease and treatment response.

## Contribution

The paper presents the first reported case of occult breast lobular carcinoma with concurrent gastric and pleural metastases, analyzed using radiomic and immunohistochemical methods.

## Key findings

- Immunohistochemistry showed consistent ER/PR/HER2 profiles across metastatic sites but negative expression of S100, SALL4, Syn, CDX2, and CgA in gastric lesions.
- Radiomic analysis revealed tumor brightness peaking pre-treatment and significant attenuation post-treatment, with increased ngtdm_Strength indicating altered tumor vascularity.
- The patient survived 24 months after receiving two lines of treatment, highlighting the potential of combined IHC and radiomic analysis in managing rare metastases.

## Abstract

Metastatic breast cancer involving the gastrointestinal tract is rare, particularly in lobular carcinoma, often emerging later in disease progression. Occult primary breast tumors are exceptionally uncommon. This study reports the first case of occult breast lobular carcinoma (OBLC) with concurrent gastric and pleural metastases in a 65-year-old female.

A multidisciplinary diagnostic approach integrated histopathological and radiomic analyses. Immunohistochemical (IHC) profiles of axillary lymph node and gastric lesions were compared. Chest enhanced computed tomography (CT)-based radiomics quantified tumor texture features across five time points (T1-T5: pre- and post-treatment). The patient received aromatase inhibitors (AIs) combined with CDK4/6i as first-line treatment and chemotherapy as second-line treatment.

Immunohistochemistry confirmed consistent biomarker expression across metastatic sites, including ER positive, PR negative, HER2 negative and GATA3 positive. However, S100, SALL4, Syn, CDX2 and CgA were all expressed negatively in gastric metastatic lesions. Radiomics revealed progressive tumor brightness peaking at T3 (pre-treatment), followed by significant attenuation post-treatment (T4-T5). The ngtdm_Strength parameter increased markedly at T4-T5, compared to T1-T3, reflecting altered tumor vascularity after therapy. After two lines of treatment, the patient has survived for 24 months.

This case highlights OBLC’s diagnostic complexity and underscores the role of radiomics in tracking metastatic evolution. Coordinated IHC and CT-based texture analysis aided lesion characterization and treatment monitoring for managing gastric metastases in OBLC.

## Linked entities

- **Proteins:** EREG (epiregulin), PGR (progesterone receptor), ERBB2 (erb-b2 receptor tyrosine kinase 2), GATA3 (GATA binding protein 3), S100A1 (S100 calcium binding protein A1), SALL4 (spalt like transcription factor 4), FYN (FYN proto-oncogene, Src family tyrosine kinase), CDX2 (caudal type homeobox 2), CGA (glycoprotein hormones, alpha polypeptide)
- **Diseases:** breast cancer (MONDO:0004989), lobular carcinoma (MONDO:0000552)

## Full-text entities

- **Genes:** TTF1 (transcription termination factor 1) [NCBI Gene 7270] {aka TTF-1, TTF-I}, PMS2 (PMS1 homolog 2, mismatch repair system component) [NCBI Gene 5395] {aka HNPCC4, LYNCH4, MLH4, MMRCS4, PMS-2, PMSL2}, CMPK1 (cytidine/uridine monophosphate kinase 1) [NCBI Gene 51727] {aka CK, CMK, CMPK, UMK, UMP-CMPK, UMPK}, MUC1 (mucin 1, cell surface associated) [NCBI Gene 4582] {aka ADMCKD, ADMCKD1, ADTKD2, CA 15-3, CD227, Ca15-3}, CDH1 (cadherin 1) [NCBI Gene 999] {aka Arc-1, BCDS1, CD324, CDHE, ECAD, LCAM}, MSH6 (mutS homolog 6) [NCBI Gene 2956] {aka GTBP, GTMBP, HNPCC5, HSAP, LYNCH5, MMRCS3}, ADA (adenosine deaminase) [NCBI Gene 100] {aka ADA1}, CHGA (chromogranin A) [NCBI Gene 1113] {aka CGA, PHE5, PHES}, NKX2-1 (NK2 homeobox 1) [NCBI Gene 7080] {aka BCH, BHC, NK-2, NKX2.1, NKX2A, NMTC1}, SATB2 (SATB homeobox 2) [NCBI Gene 23314] {aka C2DELq32q33, DEL2Q32Q33, GLSS}, ESR1 (estrogen receptor 1) [NCBI Gene 2099] {aka ER, ESR, ESRA, ESTRR, Era, NR3A1}, IS1 (Adolescent idiopathic scoliosis) [NCBI Gene 260402] {aka AIS, AIS1}, SALL4 (spalt like transcription factor 4) [NCBI Gene 57167] {aka DRRS, HSAL4, IVIC, ZNF797}, TP63 (tumor protein p63) [NCBI Gene 8626] {aka AIS, B(p51A), B(p51B), EEC3, KET, LMS}, S100A1 (S100 calcium binding protein A1) [NCBI Gene 6271] {aka S100, S100-alpha, S100A}, PAX8 (paired box 8) [NCBI Gene 7849] {aka PAX-8}, CTNNB1 (catenin beta 1) [NCBI Gene 1499] {aka CTNNB, EVR7, MRD19, NEDSDV, armadillo}, SYP (synaptophysin) [NCBI Gene 6855] {aka MRX96, MRXSYP, XLID96}, ALB (albumin) [NCBI Gene 213] {aka FDAHT, HSA, PRO0883, PRO0903, PRO1341}, SYNM (synemin) [NCBI Gene 23336] {aka DMN, SYN}, ERBB2 (erb-b2 receptor tyrosine kinase 2) [NCBI Gene 2064] {aka CD340, HER-2, HER-2/neu, HER2, MLN 19, MLN-19}, MSH2 (mutS homolog 2) [NCBI Gene 4436] {aka COCA1, FCC1, HNPCC, HNPCC1, LCFS2, LYNCH1}, MLH1 (mutL homolog 1) [NCBI Gene 4292] {aka COCA2, FCC2, HNPCC, HNPCC2, LYNCH2, MLH-1}, KRT20 (keratin 20) [NCBI Gene 54474] {aka CD20, CK-20, CK20, K20, KRT21}, KRT7 (keratin 7) [NCBI Gene 3855] {aka CK7, K2C7, K7, SCL}, CEACAM5 (CEA cell adhesion molecule 5) [NCBI Gene 1048] {aka CD66e, CEA}, WT1 (WT1 transcription factor) [NCBI Gene 7490] {aka AWT1, GUD, NPHS4, WAGR, WIT-2, WT-1}, EREG (epiregulin) [NCBI Gene 2069] {aka EPR, ER, Ep}, S100B (S100 calcium binding protein B) [NCBI Gene 6285] {aka NEF, S100, S100-B, S100beta}, GATA3 (GATA binding protein 3) [NCBI Gene 2625] {aka HDR, HDRS}, NR4A1 (nuclear receptor subfamily 4 group A member 1) [NCBI Gene 3164] {aka GFRP1, HMR, N10, NAK-1, NGFIB, NP10}, PGR (progesterone receptor) [NCBI Gene 5241] {aka NR3C3, PR}, CDX2 (caudal type homeobox 2) [NCBI Gene 1045] {aka CDX-3, CDX2/AS, CDX3}, PIP (prolactin induced protein) [NCBI Gene 5304] {aka BRST-2, GCDFP-15, GCDFP15, GPIP4}, CTNND1 (catenin delta 1) [NCBI Gene 1500] {aka BCDS2, CAS, CTNND, P120CAS, P120CTN, p120}
- **Diseases:** IDC (MESH:D044584), gastric (MESH:D013272), axillary lymph node metastases (MESH:D008207), breast cancer (MESH:D001943), primary malignancies (MESH:D001932), gastric signet-ring cell carcinoma (MESH:D018279), hypertension (MESH:D006973), breast lesions (MESH:D061325), DFSP (MESH:D018223), gastric metastases (MESH:D009362), dysphagia (MESH:D003680), nodal (MESH:D013611), cough (MESH:D003371), weight loss (MESH:D015431), ILC (MESH:D018275), congestion (MESH:D002311), thrombocytopenia (MESH:D013921), GI (MESH:D005767), carcinomatous peritonitis (MESH:D010538), fatigue (MESH:D005221), diarrhea (MESH:D003967), lymphadenopathy (MESH:D008206), pleural effusion (MESH:D010996), Gastric Adenocarcinoma (MESH:D013274), osteolytic lesions (MESH:D030981), MPE (MESH:D016066), abdominal pain (MESH:D015746), poorly differentiated adenocarcinoma of the digestive system (MESH:D004067), edema (MESH:D004487), schizophrenia (MESH:D012559), pleural lesions (MESH:D010995), shortness of breath (MESH:D004417), Cancer (MESH:D009369), adenocarcinoma (MESH:D000230)
- **Chemicals:** denosumab (MESH:D000069448), cisplatin (MESH:D002945), CDK4/6i (-), capecitabine (MESH:D000069287), abemaciclib (MESH:C000590451), bevacizumab (MESH:D000068258), exemestane (MESH:C056516), paclitaxel (MESH:D017239)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

23 references — full list in the complete paper: https://tomesphere.com/paper/PMC12920235/full.md

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Source: https://tomesphere.com/paper/PMC12920235