Navigating diagnostic dilemmas toward precision therapy: a case report and literature review on gastric metastasis from breast cancer.

A 54-year-old female presented to our hospital in August 2022 with a history of progressively worsening pain and restricted movement in the left shoulder and elbow. Previous surgery for a presumed adhesive capsulitis of the shoulder (Feb 2022) had provided no relief. Physical examination revealed a shrunken, firm, and fixed left breast with induration of the surrounding chest wall skin. Movement of the left shoulder and elbow was severely restricted. CT scans demonstrated a left breast mass, infiltration of the left chest wall and axilla, a large left pleural effusion, and multiple osteolytic bone lesions, while the gastric wall thickness remained normal ( Figures 1A, B ). A left breast biopsy confirmed ILC, histological grade 3, with the following immunoprofile: ER (80%), PR (5%), HER2 (1+), Ki67 (30%), CK5 (–), Ecadherin (–), Calponin (–), P120 (cytoplasmic, +), P63 (–). The diagnosis was stage IV Luminal B (HER2-negative) breast cancer. Baseline tumor markers were elevated: carbohydrate antigen 125 (Ca125) at 168.6 U/ml and carbohydrate antigen 153 (Ca153) at 255 U/ml. Imaging and pathological data of the case patient: (A) Chest CT (2022-08-24) showing extensive metastatic breast cancer in the left chest wall and massive left pleural effusion; (B) Abdominal CT (2022-08-24) demonstrating normal gastric wall thickness; (C) Abdominal CT (2024-07-02) revealing significant gastric wall thickening; (D) Gastroscopy (2024-07-03) showing multiple antral ulcers (suspected malignancy)? with pyloric deformation (Borrmann type III); (E) Gastric antral mucosal biopsy (2024-07-04) indicating focal ulceration with partial epithelial dysplasia, consistent with breast cancer metastasis based on immunohistochemical results; (F) Abdominal CT (2024-11-15) demonstrating reduced gastric wall thickening compared to previous imaging. From August 2022 to February 2023, she received 7 cycles of first-line chemotherapy with Nab-paclitaxel and Capecitabine, achieving a partial response (PR). This was followed by maintenance therapy with Capecitabine, Abemaciclib, Exemestane, and Leuprorelin until April 2024. In April 2024, despite stable solid lesions, rising tumor markers (Ca125: 151.3 U/ml, Ca153: 76.55 U/ml) and increased pleural/pelvic effusions suggested progression. The regimen was switched to Capecitabine, Abemaciclib, Fulvestrant, and Leuprorelin. By July 2024, the patient reported significant upper abdominal discomfort, anorexia, bloating, and weight loss. Tumor markers surged further (Ca125: 433.3 U/ml, Ca153: 153.8 U/ml). Repeat CT showed increased effusions and new, marked thickening of the gastric wall, presenting a “linitis plastica” pattern ( Figure 1C ). We reached a crossroads in diagnosis: is it primary gastric cancer or metastatic disease? Gastroscopy revealed two irregular, depressed lesions with raised margins in the gastric antrum, involving the angle and lower body, causing deformation of the gastric antrum and pylorus ( Figure 1D ). The endoscopic impression was malignant ulcers (Borrmann type III). Histopathological examination of the biopsy showed focal ulceration with partial epithelial dysplasia. Critical IHC analysis confirmed breast cancer metastasis: ER (30%), PR (–), CerbB-2 (1+), Ki67 (40%), GATA3 (++), P120 (++), CKL (+++), p53 (10%), MUC5AC (+++, glandular epithelial positive), MUC-6 (++, intrinsic gland positive), CDX-2 (–), CMV (–), INSM-1 (–), E-Cad (–) ( Figure 1E ). A diagnosis of breast cancer with metastases to the pleura, chest wall, bone, peritoneum, and stomach was confirmed. Given the suspected endocrine resistance, third-line chemotherapy with Eribulin was initiated. After one cycle, her abdominal symptoms improved markedly. A follow-up CT in December 2024 showed reduced gastric wall thickening ( Figure 1F ) and stabilized disease, though tumor markers began to rise again.

Breast cancer is a leading cause of cancer-related morbidity and mortality in women worldwide. While it commonly metastasizes to bone, lung, liver, and brain, gastrointestinal involvement is uncommon, with gastric metastasis occurring in approximately 0.04%-0.3% of clinical cases ( 1 , 2 ). However, autopsy studies suggest a much higher incidence (4-35%) ( 3 ), indicating that GMBC is significantly underdiagnosed ante-mortem. The clinical dilemma is twofold. First, symptoms of GMBC—such as epigastric pain, bloating, and nausea—are non-specific and can be easily attributed to adverse effects of chemotherapy or targeted agents ( 4 ). Second, both radiological and endoscopic appearances of GMBC can be indistinguishable from those of primary gastric cancer, especially Borrmann type III/IV or linitis plastica ( 5 ). This frequently leads to diagnostic delay or misdiagnosis, which can adversely impact patient outcomes. The average time from primary breast cancer diagnosis to the detection of gastric metastasis is 5–8 years, and most patients have concurrent metastases at other sites at the time of gastric diagnosis ( 6 ). Invasive lobular carcinoma (ILC) has the tendency to metastasize to the stomach more often compared to invasive breast carcinoma of no special type ( 7 ). Here, we report a case of GMBC in a patient with Luminal B breast cancer, highlighting the diagnostic challenges encountered and the pivotal role of immunohistochemistry in reaching the correct diagnosis. More importantly, we observed a notable change in the hormone receptor status of the gastric metastasis compared to the primary tumor. Through a contemporary literature review and analysis of this case, we seek to move beyond mere description and provide a clinically actionable framework for the diagnosis and management of this elusive condition, with a special focus on the implications of tumor phenotype evolution.

This case and our literature synthesis illuminate the complex landscape of GMBC. We identify three critical areas that shape patient outcomes: diagnostic challenges, tumor evolution, and therapeutic decision-making. In our patient’s case, the suspicion of a second primary malignancy are emblematic of the diagnostic odyssey in GMBC. The symptoms are non-specific, and CT findings, while suggestive, are not definitive. The endoscopic appearance can be deceptive, often mimicking advanced primary gastric cancer ( 39 ). To counter these pitfalls, we propose a structured diagnostic algorithm ( Figure 2 ) for any breast cancer patient, particularly those with ILC, who develop new or persistent upper GI symptoms: Proposed diagnostic and therapeutic algorithm for suspected GMBC. ①Initial assessment: Correlate symptoms with tumor marker trends (e.g., Ca15-3, Ca125) and review recent CT imaging for subtle gastric wall changes or effusions. ②Imaging findings: a. If CT is unequivocal for gastric pathology, proceed to gastroscopy with deep and multiple biopsies. b. If CT is negative/non-diagnostic but clinical suspicion remains high (e.g., rising markers, persistent symptoms), proceed to gastroscopy. ③Pathological confirmation: Insist on a comprehensive IHC panel. A core panel should include ER, PR, HER2, GATA3, GCFDF15+, Mammaglobin,CK7, CK20, etc. ( 40 – 44 ) This combination is highly effective in distinguishing breast origin (e.g., GATA3+/ER+/CK7+/CK20-) from primary gastric cancer (e.g., typically GATA3-/ER-/CK7+/CK20+) ( 45 ). ④Handling discordant results: If clinical/radiological suspicion persists despite a negative superficial biopsy, pursue endoscopic ultrasound (EUS)-guided fine-needle biopsy to sample the submucosa and muscularis propria, where tumor cells often reside ( 5 , 22 ). A pivotal finding in our case was the change in the hormone receptor profile between the primary tumor (ER 80%, PR 5%) and the gastric metastasis (ER 30%, PR 0%). This phenomenon, observed in several cases from our review, underscores the concept of clonal evolution under therapeutic pressure. Treatment selectively eradicates therapy-sensitive clones, allowing resistant, potentially less-differentiated clones to proliferate at metastatic sites. This finding mandates a paradigm shift in management. Re-biopsy of accessible metastatic sites at the time of progression is not optional but essential. It provides real-time biological data that can explain treatment resistance and guide subsequent therapy. A patient whose metastasis has lost ER expression is unlikely to benefit from further endocrine manipulation alone and may require a switch to chemotherapy. GMBC is a systemic disease, and management should be guided by the molecular subtype of the metastasis and the overall disease burden ( Figure 2 ). ①Systemic therapy first: For most patients, especially those with multi-organ involvement, systemic therapy is the mainstay. For HR+ disease, endocrine therapy combined with CDK4/6 inhibitors remains the preferred option if the metastasis remains HR-positive ( 46 , 47 ). For confirmed endocrine-resistant disease, chemotherapy (e.g., Eribulin, Capecitabine) is indicated. ②The role of local therapy: Surgery is generally reserved for palliation of complications like obstruction, bleeding, or perforation ( 37 ). However, for the highly selected patient with oligometastatic disease—where the stomach is the sole or dominant site of progression and the primary is controlled—curative-intent gastrectomy may be considered and has been associated with extended survival in some series ( 3 ). Endoscopic stenting is a less invasive alternative for managing gastric outlet obstruction ( 10 ).

Using the keywords “breast cancer” “gastric metastasis” and “metastases to the stomach”, we collected a total of 35 cases of breast cancer with gastric metastasis from 2019 to 2024 from databases such as PubMed and Wiley ( Table 1 ) ( 4 , 6 , 8 – 38 ). Among these cases, 34 were female and 1 was male. The average age at breast cancer diagnosis was 59.76 years, and the average age at gastric metastasis diagnosis was 65.56 years. The average interval between breast cancer diagnosis and gastric metastasis was 5.60 years. In 6 cases (17.14%), breast cancer and gastric metastasis occurred simultaneously. The primary tumor was invasive lobular carcinoma in 20 cases (57.14%), invasive ductal carcinoma (IDC) in 11 cases (31.43%), and mixed-type carcinoma in 1 case (2.86%). Among the primary tumors, 21 cases (60%) were hormone receptor (HR)-positive, 4 cases (11.43%) were triple-negative, and 3 cases (5.71%) showed HER2 protein expression. Among the gastric metastases, 23 cases (65.71%) were HR-positive, 3 cases (8.57%) were triple-negative, and 3 cases (8.57%) showed HER2 protein expression. Further immunohistochemical analysis of gastric metastases revealed GATA3 positivity in 25 cases (71.43%), CK7 (Cytokeratin 7) positivity in 13 cases (37.14%), GCFDF15 (grosscystic disease fluid protein 15) positivity in 9 cases (25.71%), and Mammaglobin positivity in 5 cases (14.29%). The most common symptoms of gastric metastasis were abdominal pain or discomfort (19 cases, 54.29%), nausea or vomiting (7 cases, 20%), melena or hematochezia (7 cases, 20%), weight loss (6 cases, 17.14%), and decreased appetite (4 cases, 11.43%). In 5 cases (14.29%), patients were asymptomatic. CT findings primarily showed localized or diffuse gastric wall thickening (13 cases, 37.14%). Some patients presented with gastric outlet obstruction and proximal gastric dilation (2 cases, 5.71%), while 2 cases (5.71%) showed no significant abnormalities on CT. The entire stomach (10 cases, 28.57%), gastric body (9 cases, 25.71%), gastric antrum (7 cases, 20%), gastric fundus (5 cases, 14.29%), and cardia (5 cases, 14.29%) were commonly involved under endoscopy. The layers of the gastric wall most frequently involved were the lamina propria (11 cases, 31.43%), mucosal layer (7 cases, 20%), submucosal layer (5 cases, 14.29%), muscular layer (2 cases, 5.71%), and serosal layer (2 cases, 5.71%). In addition to gastric metastasis, almost all cases were accompanied by metastases to other organs, commonly including bone (14 cases, 40%), lymph nodes (9 cases, 25.71%), intestines (6 cases, 17.14%), peritoneum or omentum (6 cases, 17.14%), lung (6 cases, 17.14%), and liver (4 cases, 11.43%). The time from the detection of gastric metastasis to death ranged from a few weeks to 5 years. Summary of 35 cases of breast cancer with gastric metastasis (2019–2024). ND, not described. Key findings with clinical implications: ①Symptoms: Abdominal pain/discomfort (54.29%) was the most common symptom, but 14.29% of patients were asymptomatic. ②Imaging: CT most frequently showed gastric wall thickening (37.14%), but was normal in 5.71% of cases, underscoring its limited sensitivity. ③IHC profile: GATA3 was the most valuable positive marker (71.43% of tested cases), while loss of Ecadherin was a common finding in ILC metastases. A combination of immunohistochemical markers (e.g., ER+/GATA3+/GCFDF15+/CK7+/CK20-) was highly suggestive of breast origin. ④Therapeutic response: Endocrine therapy, often combined with CDK4/6 inhibitors, was a cornerstone of treatment for HR-positive cases and was associated with prolonged survival in several reports. ⑤Clinical course: The time from GMBC diagnosis to death varied widely, from weeks to over 5 years, highlighting the heterogeneous biology of the disease and the impact of effective systemic therapy.

GMBC is a diagnostic chameleon that demands vigilance. Our case and review highlight that overcoming this challenge requires a proactive and structured diagnostic approach, centered on endoscopy and definitive IHC profiling. Furthermore, the potential for phenotypic evolution between primary and metastatic sites makes re-biopsy a critical component of personalized cancer care, directly influencing therapeutic decisions. By integrating these principles—high clinical suspicion, rigorous pathological confirmation, and treatment tailored to the metastatic phenotype—clinicians can improve diagnostic accuracy and optimize outcomes for patients facing this complex manifestation of advanced breast cancer.