Gastric Metastasis with Lobular Phenotype from a Primary Invasive Ductal Breast Carcinoma: A Case Report

Abstract

Introduction

Breast cancer is a leading cause of cancer-related mortality in women, with common metastatic sites including bone, lung, liver, and brain. Metastasis to the gastrointestinal tract, particularly the stomach, is a rare occurrence, with a reported clinical incidence of 0.2–0.7%. Its nonspecific symptomatology and heterogeneous endoscopic presentation often lead to diagnostic confusion with primary gastric cancer or benign conditions.

Case Presentation

We report the case of a 51-year-old woman with a history of stage IIIC invasive ductal breast cancer, treated 9 years prior with multimodal therapy. She presented with a 6-month history of severe abdominal pain, significant weight loss (15 kg), vomiting, and diarrhea, initially managed as a Helicobacter pylori-associated gastric ulcer without improvement. Upper endoscopy revealed a large, raised-margined ulcer. Biopsy and immunohistochemical analysis were pivotal, showing a profile positive for CK7, GATA3, and estrogen receptors and negative for E-cadherin, confirming metastatic breast carcinoma. Staging CT scans showed no other metastatic disease. The patient was initiated on systemic hormonal therapy with an aromatase inhibitor combined with a CDK4/6 inhibitor.

Conclusion

This case underscores that gastric metastasis should be considered in breast cancer survivors presenting with persistent upper GI symptoms, even many years after initial remission. It highlights the critical role of immunohistochemistry in achieving a correct diagnosis, which is essential for guiding appropriate systemic therapy and avoiding unnecessary surgical intervention. A multidisciplinary approach is paramount for managing this rare manifestation of advanced breast cancer.

Introduction

Annually, nearly two million new cases of breast cancer are diagnosed globally. In high-income nations, approximately 6% of breast cancer patients present with metastatic disease at diagnosis, and a further 20–30% will subsequently develop metastatic breast cancer [1]. The most common sites of metastasis include soft tissues, the brain, liver, and lungs, while involvement of the gastrointestinal (GI) tract remains uncommon.

Invasive lobular carcinoma (ILC) has a higher propensity to metastasize to the GI tract compared to invasive breast carcinoma of no special type [2]. Specifically, the incidence of gastric metastases from breast cancer has been estimated by follow-up and autopsy studies to be between 0.2% and 0.7% [3].

Gastric metastases from breast cancer typically occur years after the initial diagnosis. The diagnostic process is notably challenging due to nonspecific and varied clinical presentations, which can range from asymptomatic patients to those with severe GI complications [4, 5]. Furthermore, a predisposition for developing both breast and gastric cancer has been observed in patients with CDH1 and BRCA2 genetic mutations [6, 7]. Although novel immunohistochemical markers are improving diagnostic accuracy, distinguishing a primary gastric cancer from metastatic breast cancer based solely on clinical, endoscopic, or pathological criteria remains difficult [8].

Case Presentation

A 51-year-old Arab female with a history of breast cancer presented with a 6-month history of severe abdominal pain, a 15 kg weight loss, vomiting, and diarrhea. Her oncological history was significant: she had undergone a left radical mastectomy with axillary lymph node dissection 9 years prior for a locally advanced (stage IIIC) tumor. The primary tumor was invasive ductal carcinoma (IDC) grade 2 with a focal ductal carcinoma in situ component (pT2, N16/21, M0), with lymphovascular invasion and tumor deposits in peritumoral fat, but surgical margins were clear. Estrogen receptors (ERs) were positive in 70% of tumor cells, progesterone receptors (PRs) in 30%, and HER2 was negative. Her adjuvant treatment included four cycles of AC (cyclophosphamide and doxorubicin), 12 weeks of paclitaxel, and radiotherapy, followed by hormonal therapy. This consisted of 4 years of tamoxifen and subsequently 3 years of letrozole. She completed 8 years of recurrence-free follow-up and discontinued hormonal therapy in early 2024.

During the 6 months leading to her current presentation, she was treated for a Helicobacter pylori infection with a concomitant gastric ulcer, but her symptoms showed no improvement. Due to this treatment failure, a repeat endoscopy was advised. Upper endoscopy revealed a large, raised-margined ulcer extending from the gastroesophageal junction to the antrum, with induration of the greater curvature. A lower GI endoscopy identified severe agitation of the sigmoid colon.

A CT scan of the abdomen and chest showed no evidence of local breast recurrence or axillary masses (Fig. 1–2). The pulmonary parenchyma, heart, liver, pancreas, spleen, and kidneys were all unremarkable. However, the scan revealed dilation of intestinal loops in the pelvis with fluid-gas levels and associated mesenteric fat infiltration.

Fig. 1.

CT scan.

Fig. 2.

CT scan.

Biopsies taken from the gastric ulcer were sent for pathological examination, which established the diagnosis of metastatic carcinoma of breast origin (Fig. 3–7). Histology showed a grade 2 tumor with a discohesive growth pattern. Immunohistochemical staining was positive for CK7 and GATA3, and strongly positive for ERs (90% of tumor cells, 3+), while PRs were negative. HER2 was equivocal (2+), but chromogenic in situ hybridization was negative for HER2/neu gene amplification. The Ki67 proliferation index was low (5%). Loss of E-cadherin expression confirmed lobular differentiation. Notably, the primary breast tumor was originally classified as IDC; however, the E-cadherin-negative, discohesive morphology of the metastasis is characteristic of lobular carcinoma, potentially reflecting clonal evolution or a mixed ductal-lobular primary that was not sampled. The patient had no evidence of organ failure, other metastatic sites, or visceral crisis. The treatment plan consisted of an aromatase inhibitor (letrozole or anastrozole) combined with a CDK4/6 inhibitor, and the patient was placed under close observation.

Fig. 3.

Estrogen receptors.

Fig. 7.

GATA3.

Fig. 4.

CK7.

Fig. 5.

Gastric metastasis.

Fig. 6.

E-cadherin.

Discussion

Breast cancer remains the most frequently diagnosed malignancy in women and is the second leading cause of cancer-related mortality, surpassed only by lung cancer [9]. While breast cancer commonly metastasizes to sites such as soft tissue, brain, liver, bones, and lungs, involvement of the GI tract is a relatively rare occurrence. ILC metastasizes to the GI tract more frequently than invasive breast carcinoma of no special type [2]. McLemore et al. [10] reported that of 12,001 patients with metastatic breast cancer, only 0.34% developed GI metastases. The clinical incidence of gastric metastasis is estimated to be between 0.2% and 0.7%, though autopsy studies suggest a higher, previously undetected prevalence ranging from 0.8% to 18% [3]. Within the GI tract, the stomach is the most common site of metastasis (60%), followed by the esophagus (12%), colon (11%), small intestine (8%), rectum (7%), oropharynx (1%), and anus (1%) [11].

Patients with gastric metastases typically present with nonspecific GI symptoms such as anorexia, dysphagia, early satiety, epigastric pain, melena, nausea, and vomiting [3]. The largest case series to date (n = 78) on this condition identified abdominal pain as the most common symptom (75.6%), a finding consistent with the present case, in which the patient suffered from severe abdominal pain, recurrent vomiting, diarrhea, and significant weight loss of 15 kg over 7 months [3]. A more recent series further emphasizes that gastric metastases from breast cancer, particularly of lobular subtype, often present with nonspecific symptoms and can be mistaken for primary gastric disorders, delaying diagnosis [12]. This case underscores the variable clinical presentation of gastric metastases and highlights the diagnostic challenge, as these symptoms are often mistakenly attributed to chemotherapy side effects, even in patients who have undergone comprehensive treatment, including surgery, chemotherapy, and hormonal therapy.

Diagnosis primarily relies on endoscopy and biopsy, with a typical interval of 5–7 years between the initial breast cancer diagnosis and the detection of gastric metastasis [13]. The diagnostic process is complicated by the heterogeneity of endoscopic appearances, which can manifest as localized tumor deposition (18%), diffuse infiltration resembling linitis plastica (57%–73%), or external compression (25%) [14]. Diffuse infiltration, or the linitis plastica type, is a representative pattern of gastric metastasis from breast cancer [15].

Immunohistochemical staining is critical for distinguishing metastatic breast cancer from a primary gastric malignancy. Key markers include ERs, PRs, HER2, and GATA3. Positivity for GATA3 and ER strongly suggests metastatic breast cancer, as these are typically negative in primary gastric tumors. Furthermore, E-cadherin and cytoplasmic P120 are used to differentiate between ILC and IDC. A profile of E-cadherin negativity combined with cytoplasmic P120 positivity is highly indicative of ILC, a subtype found in approximately 90% of gastric metastases from breast cancer and associated with a diffuse growth pattern that facilitates dissemination [15]. In the present case, the immunohistochemical profile (CK7+, GATA3+, E-cadherin−, ER + 3, PR−, HER2 +2 [chromogenic in situ hybridization-negative], Ki67 5% low) confirmed the diagnosis of metastatic ILC. Of note, the primary breast tumor was originally classified as IDC with positive ER/PR and negative HER2. The loss of E-cadherin and lobular morphology in the gastric metastasis represents a rare histologic discordance between primary and metastatic sites, which may be explained by clonal evolution, selection of a pre-existing lobular subclone, or sampling limitations of the primary tumor. Such discordance has been described in the literature and underscores the value of re-biopsying metastatic lesions to guide therapy [16].

Data guiding the treatment of gastric metastases from breast cancer are limited. Management primarily involves systemic therapy tailored to the tumor’s receptor status, with most patients receiving chemotherapy, endocrine therapy, or a combination; radiotherapy is rarely employed [11, 17]. In this case, the treatment plan consisted of an aromatase inhibitor (letrozole or anastrozole) combined with a CDK4/6 inhibitor. A CT scan revealed no other metastatic sites, and the patient was placed under close observation.

The prognosis following a diagnosis of gastric metastasis is generally poor, with a median survival ranging from 10 to 28 months, which is further reduced in patients with multi-organ involvement [3]. This case illustrates the diagnostic complexities and therapeutic considerations for this rare but serious manifestation of advanced breast cancer.

Conclusion

This case exemplifies the diagnostic and therapeutic challenges posed by gastric metastases from breast cancer, a rare but consequential event in the disease’s progression. It underscores that even years after successful initial treatment, nonspecific GI symptoms in a breast cancer survivor warrant a high index of suspicion. The critical role of immunohistochemistry – particularly markers like GATA3, ER, and E-cadherin – is paramount in distinguishing metastatic disease from a primary gastric malignancy, thereby guiding appropriate, targeted systemic therapy rather than surgical intervention. Furthermore, the discordance between the original ductal primary tumor and the lobular phenotype of the gastric metastasis highlights that metastatic lesions should be biopsied and immunophenotyped whenever feasible, as receptor status and histology can evolve. While the prognosis remains guarded, accurate diagnosis enables the implementation of tailored treatment strategies, highlighting the necessity of a multidisciplinary approach to manage this complex manifestation of advanced breast cancer.

Statement of Ethics

Ethical approval is not required for this study in accordance with local or national guidelines. This retrospective review of patient data did not require ethical approval in accordance with local/national guidelines. The CARE Checklist has been completed by the authors for this case report, attached as online supplementary material. Written informed consent was obtained from the patient’s next of kin for publication of the details of their medical case and any accompanying images.

Conflict of Interest Statement

The authors have no conflicts of interest to declare.

Funding Sources

This study was not supported by any sponsor or funder.

Author Contributions

Nisreen Khazeam: planned and performed the work leading to the report, reviewed successive versions, and participated in their revisions. Leen Khouri: participated in writing the report and approved the final version. Modar Alajlani: wrote and reviewed successive versions, participated in their revisions, and approved the final version. Ahmad Al-Bitar: wrote and reviewed successive versions, participated in their revisions, and approved the final version.

Funding Statement

This study was not supported by any sponsor or funder.

Data Availability Statement

All data generated or analyzed during this study are included in this article. Further inquiries can be directed to the corresponding author.