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Abstract

Gastrointestinal tract (GIT) metastases occur in only 0.6% of metastatic breast cancer cases, with invasive lobular carcinoma being the predominant histological subtype. Synchronous GIT metastases at the time of invasive ductal carcinoma (IDC) diagnosis are exceptionally uncommon. We report a case of de novo IDC presenting with synchronous, multifocal metastases in the stomach and colon. The diagnosis was prompted by significantly elevated tumor markers and confirmed via endoscopic examination and biopsy. This case underscores the rarity of GIT metastases, particularly in IDC, and highlights the critical need for a high index of suspicion in the face of markedly elevated tumor markers, even without gastrointestinal symptoms. While contrast-enhanced computed tomography has limited sensitivity for detecting small GIT lesions, endoscopic biopsy with immunohistochemical analysis remains the gold standard for diagnosis. Accompanying this report is a systematic literature review on breast cancer metastases to the GIT.

Keywords

breast neoplasms invasive ductal carcinoma gastrointestinal metastases from breast cancer synchronous metastases

Introduction

Breast cancer remains the most prevalent malignancy among women worldwide,¹ with distant metastases (particularly to bone, lung, liver, and brain) representing the primary cause of mortality. In contrast, gastrointestinal tract (GIT) metastasis of breast cancer is clinically uncommon,² occurring predominantly in invasive lobular carcinoma (ILC). These metastases typically manifest as isolated gastrointestinal involvement years after the initial breast cancer diagnosis and treatment.^2,3 Here we present a rare case of de novo invasive ductal carcinoma (IDC) with synchronous, multifocal gastric and colonic metastases. Through a comprehensive review of current literature, we systematically analyze the epidemiological characteristics, diagnostic approaches, therapeutic strategies, and prognostic factors associated with breast cancer GIT metastases. Our objective is to enhance clinicians’ understanding of this distinctive metastatic pattern.

Case report

A 45-year-old female was admitted to our gynecology department with the chief complaints of “menorrhagia and anemia.” Her past medical history was unremarkable. Her obstetric history was recorded as 1-0-3-1 (one full-term delivery, no preterm births, three spontaneous abortions, and one living child). She had undergone one cesarean section. Her last menstrual period was 7 April 2025. Family history was significant for paternal gastric cancer and maternal lung cancer.

Initial evaluation revealed a white blood cell count of 8.2 × 10⁹/L, red blood cell count of 2.77 × 10¹²/L, hemoglobin of 65 g/L, and platelet count of 80 × 10⁹/L. Serum tumor markers showed elevated levels of Alpha-Fetoprotein (AFP) (2.59 ng/mL), Carcinoembryonic Antigen (CEA) (207 ng/mL), CA-125 (267 U/mL), CA-153 (2434 U/mL), and CA-199 (505.2 U/mL). Gynecological ultrasound demonstrated a scarred, enlarged uterus with thickened heterogeneous endometrium, uterine fibroids, and bilateral small ovarian cysts. Breast ultrasound identified an irregular mass measuring 6.0 × 5.0 cm with microcalcifications (BI-RADS 4c) in the left breast, accompanied by left axillary lymphadenopathy. Unenhanced computed tomography (CT) revealed multiple pulmonary micronodules, left axillary lymphadenopathy, and diffuse osteolytic lesions. Brain magnetic resonance imaging ruled out intracranial metastasis. Contrast-enhanced abdominal CT showed no definite gastrointestinal mass.

The patient exhibited markedly elevated serum tumor markers (CEA, CA-125, CA-153, and CA-199) while reporting no gastrointestinal symptoms such as nausea, vomiting, abdominal pain, bloating, diarrhea, constipation, or hematochezia. Endoscopy identified lesions in both the stomach and colon. Gastric examination showed three slightly elevated lesions (0.4–0.6 cm) on the greater curvature, with well-demarcated borders and yellowish discoloration under white light. Narrow-band imaging (NBI) characteristics included prominent surface vasculature, microvascular dilation, and glandular loss (Figure 1). In the colon, two discrete hemispherical translucent yellow lesions (0.3 cm) with whitish internal features were found in the transverse and descending colon; they displayed indistinct margins on NBI (Figure 2). Deep biopsies were obtained from all lesions for histopathological evaluation.

Figure 1.

Gastric metastasis.

Figure 2.

Colonic metastasis.

Core needle biopsy of the left breast mass confirmed IDC (Figure 3) with the following immunohistochemical profile: ER (2+, 40%), PR (+, 10%), Her2 (1+), E-Cadherin (+), P63 (−), CK5/6 (−), Ki67(50%+), GATA3(+), CDX-2(−). Histopathological evaluation confirmed metastatic breast carcinoma across multiple sites: gastric biopsy demonstrated carcinoma of breast origin (CDX-2−, GATA3+, MUC6−, ER 2+, PR 1+, Her2 1+) (Figure 4), colonic biopsies showed similar immunohistochemical results (CDX-2−, GATA3 +, CEA weak+, Ki67 high, ER 2+, PR 1+, Her2 1+), and bone marrow biopsy revealed metastatic adenocarcinoma consistent with breast primary (Figure 5). Representative Hematoxylin-eosin and immunohistochemistry images are depicted in Figures 3, 4, and 5.

Figure 3.

Histopathological and immunohistochemical analysis of breast tumor (×200) (a) HE staining (b) CK5-6 (−) (c) P63 (−) (d) E-Cadherin (+) (e) GATA3 (+) (f) CDX-2 (−) (g) ER (+) (h) PR (+) (i) Her2 (1+).

Figure 4.

Histopathological and immunohistochemical analysis of gastric metastasis (×200) (a) HE staining (b) GATA3 (+) (c) CDX-2 (−) (d) ER (+) (e) PR (+) (f) Her2 (1+).

Figure 5.

Histopathological and immunohistochemical analysis of bone marrow biopsy (×200) (a) HE staining (b) CKpan (+) (c) GATA3 (+) (d) ER (+) (e) CDX2 (−).

The patient was therefore diagnosed with IDC of the left breast exhibiting synchronous metastatic involvement of the stomach, colon, bone, and bone marrow, classified as cT3NxM1, Stage IV, Luminal B subtype. Initial treatment included ovarian function suppression (OFS) combined with a CDK4/6 inhibitor (ribociclib) and an aromatase inhibitor (exemestane), with continued clinical monitoring.

Discussion

Breast cancer represents the most prevalent malignancy and the leading cause of cancer-related mortality among women worldwide.¹ Despite the broad implementation of screening programs, 3.6%–6.0% of newly diagnosed breast cancer cases still present as stage IV disease annually.² Application of novel antitumor agents has progressively improved overall survival rates; however, prolonged survival has led to an increasing incidence of metastatic recurrence in clinical settings.

Breast cancer predominantly metastasizes to regional lymph nodes, bones, lungs, liver, and brain. In contrast, GIT metastases are notably rare (clinical incidence: 0.6%; autopsy prevalence: 6%–18%).³ This marked disparity suggests substantial underdiagnosis of GIT metastases in clinical practice. This diagnostic challenge primarily arises from prolonged disease-free intervals, asymptomatic clinical courses, and nonspecific symptoms that are commonly misinterpreted as side effects of systemic cancer treatment.⁴ Current evidence suggests that Helicobacter pylori colonization, inflammatory cell infiltration, and chemokine signaling collectively establish a tumor-tropic microenvironment that facilitates GIT metastasis in breast cancer.⁵

Notably, while IDC constitutes the overwhelming majority of histological subtypes, gastrointestinal metastases arise predominantly from ILC.⁶ E-cadherin deficiency in ILC,⁷ inherent lobular cellular tropism,⁶ and GIT microenvironmental compatibility⁷ may be responsible for the difference in the metastatic patterns of the two subtypes. The specific reasons for the occurrence of gastrointestinal metastasis in IDC are currently unclear. The expression level of Ki67 is one of the indicators reflecting the proliferation ability of breast cancer cells. In this case, the Ki67 of breast cancer focus is 50%, which belongs to high expression. Therefore, we speculate that the multiple gastrointestinal metastases of IDC in this case may be related to the high level of Ki67.

The temporal spectrum of GIT metastasis development ranges from synchronous presentation to delayed occurrence exceeding three decades post-primary diagnosis (median interval: 6.5 years),^2,8,9 with metachronous presentations accounting for most cases.^3–9 Synchronous GIT metastasis at initial breast cancer diagnosis is exceptionally rare. In extraordinary instances, GIT symptoms may serve as the initial clinical manifestation prompting subsequent identification of breast cancer.^2,10 While gastric and colorectal sites demonstrate predilection, metastases have been reported throughout the entire gastrointestinal continuum.^3,6 However, existing literature primarily consists of case reports focusing on single GIT organ metastases, with ILC being the predominant tumor type. This case represents an exceptionally rare presentation of de novo breast IDC with synchronous multifocal metastases involving both gastric and colonic sites. Of concern, while isolated gastric metastases are uncommon (representing only 5.8% of metastatic breast cancer cases), multiorgan involvement represents the predominant pattern.² The concurrent bone metastases and bone marrow infiltration observed in this patient underscore the imperative for comprehensive systemic assessment in such clinical scenarios. As in this case, this patient’s menorrhagia and anemia were considered to be caused by the suppression of hematopoietic function caused by bone marrow infiltration of breast cancer, which then led to the reduction of red blood cells and platelets.

Our research team conducted a literature search in May 2025 for articles published over the past two decades, using the search terms “breast cancer/neoplasms” AND “gastrointestinal metastasis/metastases.” Searches were performed in PubMed (English) and CNKI and WANFANG (Chinese). The retrieved articles were comprised mainly of case reports and case series, along with several literature reviews. We also conducted further reading of key references from these publications. Articles were excluded if they addressed occult breast cancer (with no detectable primary lesion), lacked histopathological details of breast tumor, or described metachronous gastrointestinal metastases (identified during the follow-up period). As demonstrated in Table 1, presenting our compiled case data,^11–36 these findings further substantiate the aforementioned observation. However, the limitation of some literature lies in the lack of expression data for relevant indicators such as HER2 and E-cadherin, especially for GIT metastases.

Table 1.

A comprehensive review of metastatic breast cancer with synchronous gastrointestinal metastases at initial diagnosis reported in the past two decades.

Case no.	Studies	Age (Year)	Primary breast cancer	Tumor size (cm)	Metastasis site of GIT	Other metastasis site	ER		PR		HER2		E-cadherin		Outcomes/Follow-up
Case no.	Studies	Age (Year)	Primary breast cancer	Tumor size (cm)	Metastasis site of GIT	Other metastasis site	Breast	GIT	Breast	GIT	Breast	GIT	Breast	GIT	Outcomes/Follow-up
1	Haberstich 2005¹¹	78	IDC	NR	rectum	–	+	+	+	+	NR	NR	NR	+	Alive at 22 months
2	Sato 2007¹²	62	ILC	diffuse lesions	duodenum	bone	–	–	–	–	–	–	–	–	Alive at 18 months
3	Vennapusa 2010¹³	61	ILC	2.0	stomach	bone	+	NR	NR	NR	NR	NR	NR	NR	NR
4	Arrangoiz 2011¹⁴	70	ILC	7.4	stomach, duodenum, rectum	bone, peritoneum	+	+	–	rectum –/ stomach +	–	rectum –/ stomach NR	NR	NR	Alive at 12 months
5	Carcoforo 2012¹⁵	73	ILC	0.5	colon	omentum, peritoneum, pelvic cavity	+	NR	+	NR	–	NR	NR	NR	Died at 12 months
6	Ambroggi 2012¹⁶	40	IDC	NR	rectum	–	+	+	+	–	–	–	NR	NR	Alive at 49 months
7	Koike 2014¹⁷	54	ILC	NR	stomach	bone	+	+	+	+	–	NR	NR	NR	Died at 60 months
8	Koike 2014¹⁷	54	IDC	NR	stomach	bone	+	+	+	+	NR	NR	NR	NR	Died at 27 months
9	Kayılıoğlu 2014¹⁸	52	ILC	1.2	stomach	NR	+	+	+	+	NR	NR	–	NR	Alive at 12 months
10	Molino 2014¹⁹	68	ILC	2.5	duodenal ampulla	–	+	+	+	NR	–	NR	NR	NR	Alive at 12 months
11	Zuhair 2015²⁰	47	ILC	0.8	stomach, duodenum	–	NR	+	NR	–	NR	–	NR	NR	Alive at 36 months
12	Dória 2015²¹	66	ILC	4.0	stomach	liver, peritoneum	+	+	+	NR	–	NR	–	–	NR
13	Soobrah 2015²²	42	ILC	3.0	appendix	orbit, peritoneum	+	+	+	+	–	–	NR	NR	NR
14	Xu 2017²³	73	ILC	1.2	stomach	bone, lung, pleura, skin	+	stomach +/ skin +	+	stomach +/ skin +	+	NR	NR	stomach NR/ skin –	Alive at 13 months
15	Khan 2017²⁴	56	ILC	NR	stomach, small intestine, colon	bone, pancreas, urinary bladder	NR	NR	NR	NR	NR	NR	NR	NR	Died after diagnosis
16	Martins 2019²⁵	43	ILC	NR	stomach, colon	orbit	+	NR	–	NR	NR	NR	NR	NR	NR
17	Hong 2019²⁶	65	ILC	NR	stomach	NR	+	+	–	NR	–	–	NR	NR	NR
18	Hong 2019²⁶	45	IDC	NR	stomach	NR	+	+	+	+	–	–	NR	NR	NR
19	Zengel 2022¹⁰	65	ILC	1.6	stomach, colon	bone	+	+	+	–	–	NR	–	NR	NR
20	Namikawa 2023²⁷	68	ILC	NR	stomach	bone	+	+	NR	NR	NR	NR	–	NR	Alive at 9 months
21	Sun 2023²	58	ILC	2.1	stomach	bone	+	+	–	–	–	NR	–	NR	NR
22	Otsuka 2023²⁸	70	ILC	1.9	colon	bone	+	+	+	–	–	NR	NR	NR	Died at 4 months
23	Otsuka 2023²⁸	80	ILC	1.4	colon	peritoneum	+	+	+	NR	–	NR	NR	–	Died at 14 months
24	Ayadi 2024²⁹	53	ILC	NR	stomach	peritoneum, bone	+	NR	NR	NR	–	NR	NR	NR	Died at 5 months
25	Cheng 2024³⁰	52	ILC	NR	stomach	bone	+	+	+	+	–	–	NR	NR	NR
26	Lu 2013³¹	41	ILC	2.9	ileum	bone	+	+	+	+	–	NR	NR	NR	Alive at 6 months
27	Liu 2014³²	59	ILC	4.0	stomach	–	+	+	+	+	–	NR	–	–	NR
28	Jiang 2017³³	42	ILC	3.7	colon	pancreas, spleen	+	+	+	–	–	NR	NR	NR	NR
29	Liu 2021³⁴	60	ILC	2.1	stomach	NR	+	+	+	+	–	–	–	–	Died at 20 months
30	Ge 2021³⁵	72	ILC	NR	colon	NR	+	+	–	–	–	NR	NR	NR	NR
31	Zhao 2022³⁶	69	IDC	3.0	colon	uterus	–	–	–	–	–	–	NR	NR	NR

GIT metastases may present with varied clinical manifestations, ranging from asymptomatic courses to nonspecific symptoms (e.g. abdominal discomfort, nausea) or severe complications (e.g. luminal obstruction, hemorrhage).⁶ Current diagnostic approaches incorporate surveillance endoscopy,³ endoscopic evaluation prompted by elevated tumor markers,^4,6 and emergent surgical interventions for acute complications.² Given these considerations, ongoing oncological surveillance remains crucial for breast cancer patients, especially those with ILC histology or emerging GIT symptoms. Notably, our case demonstrates that profound tumor marker elevation may indicate GIT metastasis even in asymptomatic patients, necessitating endoscopic evaluation. Thus, in breast cancer patients, elevated gastrointestinal tumor markers – despite the absence of specific digestive symptoms – should raise clinical suspicion for GIT metastasis.

The majority of patients with metastatic breast cancer develop elevated levels of CA-153 (most prevalent), CEA, and CA-125,³⁷ and Luminal breast cancers exhibit the highest incidence of tumor marker elevation among all molecular subtypes.^37,38 Of clinical significance, increased CA-153 and CEA levels demonstrate strong correlations with visceral involvement and multiorgan metastatic disease.^38–40 Mounting evidence supports the role of tumor markers as important prognostic indicators in metastatic breast cancer,³⁷ with CA-153 levels demonstrating a particularly strong inverse correlation with progression-free survival.^38,39 This Luminal subtype case exhibited pan-tumor marker elevation, with profound increases in CA-153 and CEA levels. Confirmatory examinations substantiated the previously reported association with multiorgan metastases, indicating an aggressive disease phenotype.

Therapeutic standardization remains elusive for breast cancer GIT metastases. Personalized systemic therapy based on molecular subtypes, mainly chemotherapy and endocrine therapy, has been shown to improve survival and quality of life.² Surgical intervention is generally restricted to palliative indications, such as managing gastrointestinal obstruction or hemorrhage, with no proven survival advantage.⁶ Emerging evidence documents tumor regression with palbociclib-anastrozole combination therapy in hormone receptor-positive cases.⁷ In accordance with advanced breast cancer guidelines, our patient received OFS combined with CDK4/6 inhibition and aromatase inhibitor therapy, and the therapeutic response is under close monitoring. While the literature reports a median survival of 24–36 months for breast cancer patients with GIT metastases,² it should be noted that 84% of these cases involved metachronous rather than synchronous metastases. Our patient presented with gastric, colonic, osseous, and bone marrow metastases synchronous with the diagnosis of breast cancer (de novo stage IV), likely indicating worse outcomes.

Conclusion

This report describes a rare case of de novo breast IDC presenting with synchronous gastric and colonic metastases detected by endoscopy due to elevated tumor markers, despite the absence of digestive symptoms. Our comprehensive literature review synthesizes current knowledge on the epidemiology, diagnostic challenges, therapeutic strategies, and prognosis of breast cancer GIT metastases. This case highlights that although GIT metastases are rare in breast cancer, particularly in IDC, clinicians should maintain a high index of suspicion, especially when encountering significantly elevated or progressively increasing serum tumor markers. Contrast-enhanced CT has limited sensitivity for detecting small GIT metastatic lesions, whereas endoscopic biopsy with immunohistochemical analysis remains the diagnostic gold standard.

Footnotes

ORCID iDs

Linbo Zhu

Pengfei Li

Ethical considerations

Ethics committee approval was not required according to the declaration of the Ethics Committee of Beilun District People’s Hospital.

Consent to participate

We obtained written informed consent from the patient reported in this study.

Consent for publication

All authors have agreed to publish this paper.

Author contributions

L.B.Z. drafted this manuscript. J.Q.L., L.Y.Y., T.F.L., P.B.Z., and P.F.L. were involved in the acquisition of data and preparing the figures. Y.H. conceived of the study and revised the manuscript. All authors read and approved the final manuscript.

Funding

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by grants from the medical and health research project of Zhejiang province, China (No.2025KY1456, 2020KY140) and Beilun health technology project of Ningbo, Zhejiang, China (No. 2024BLWSYB001)

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Data availability statement

All data and materials are freely available upon request. For further information, please contact Dr. Yun Hong (1312014@zju.edu.cn), who is responsible for the dataset.

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Multiple gastrointestinal metastases in de novo invasive ductal carcinoma of the breast: A case report and literature review

Abstract

Keywords

Introduction

Case report

Discussion

Conclusion

Footnotes

ORCID iDs

Ethical considerations

Consent to participate

Consent for publication

Author contributions

Funding

Declaration of conflicting interests

Data availability statement

References