Gastrointestinal metastasis from invasive lobular carcinoma following breast cancer treatment: A case report

Abstract

BACKGROUND

Metastasis of breast cancer usually affects the lungs, bones, liver, and brain. It rarely spreads to the gastrointestinal tract, and cases with similar endoscopic manifestations are even rarer. Herein, we report a 52-year-old woman presenting with metastatic lobular carcinoma involving the gastrointestinal tract four years following a left mastectomy, chemoradiotherapy, and hormone therapy for lobular carcinoma of the breast.

CASE SUMMARY

A 52-year-old woman presented with a history of invasive lobular carcinoma and experienced metastasis of breast cancer to the gastrointestinal tract. The patient underwent a left mastectomy and tumor cells were positive for estrogen receptor (ER) and progesterone receptor (PR), negative for human epidermal growth factor receptor 2 (HER2) and E-cadherin. She did not experience any local or distant recurrences for four years following the mastectomy, chemoradiotherapy, and hormone therapy. However, the patient complained of upper abdominal discomfort and was transferred to our hospital. The endoscopic examination revealed multiple crater-like ulcers scattered throughout the stomach, gastric antrum, and colorectum. Surprisingly, the histology of colorectum lesions was the same as that of gastric metastasis. Gastric tumor cells were positive for GATA-binding protein 3 (GATA3), PR, and ER, negative for HER2. The colorectum tumor cells were positive for GATA3 and ER and negative for cytokeratin 20. Based on the results of immunohistological examination, a final diagnosis of gastrointestinal metastases from breast cancer was established.

CONCLUSION

Distinguishing metastatic breast cancer from primary gastrointestinal lesions is crucial for initiating the correct treatment and enhancing the quality of life for patients.

Key Words: Breast neoplasms; Lobular carcinoma; Neoplasm metastasis; Stomach neoplasms; Colonic neoplasms; Case report

Core Tip: It is uncommon for breast cancer to spread simultaneously to the stomach and intestinal tract. We report a case of a 52-year-old woman with metastatic lobular carcinoma in the gastrointestinal tract. This case highlights the critical role of multidisciplinary collaboration. Endoscopic biopsy combined with immunohistochemistry is essential to differentiate metastatic breast cancer from primary gastrointestinal malignancies, guiding timely systemic therapy.

INTRODUCTION

Breast cancer is the most common malignant disease and the leading cause of cancer-related death in women[1]. The tissue form of breast cancer has the highest number of invasive ductal carcinoma (IDC), while invasive lobular carcinoma (ILC) accounting for 5%-15% of invasive breast cancers is the second most common subtype of breast cancer[2]. ILC can be difficult to be detected clinically and radiographically, and consequently further biopsies are necessary[3]. Histologically, ILC is made up of non-cohesive cells scattered in a single-file linear pattern in a stroma[4]. The positivity rate of estrogen receptor (ER) in ILC is 80%-95%, and that of progesterone receptor (PR) is approximately 70%, while the human epidermal growth factor receptor 2 (HER2) overexpression is rare in ILC[3]. The comprehensive treatment includes surgical treatment, hormonal therapy, radiotherapy, and chemotherapy. The mutations of germline cadherin 1 gene and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha gene and E-cadherin inactivation are considered significant in the development of lobular breast cancer[5]. The distant metastasis rate of ILC is higher, but there is no significant difference in overall survival rate compared to IDC[6]. Lobular carcinoma metastasizes to gastrointestinal tract more often than IDC[7]. However, similar endoscopic manifestations between the involved gastric and colorectal lesions are even more infrequent. Advanced patients often have a frequent recurrence and can die from the disease[8]. Our report describes a 52-year-old woman presenting with metastatic lobular carcinoma involving the gastrointestinal tract four years following a left mastectomy, chemoradiotherapy, and hormone therapy for lobular carcinoma of the breast.

CASE PRESENTATION

Chief complaints

A 52-year-old female patient was referred to our hospital with a chief complaint of upper abdominal discomfort on January 29, 2023.

History of present illness

On January 9, 2023, the patient experienced epigastric discomfort without obvious triggers, which became worse after meals, without nausea, vomiting, acid reflux, heartburn, abdominal pain, diarrhea, dry stool, and blood in the stool. Her general medical history was unremarkable.

History of past illness

The patient was diagnosed with a left breast cancer four years ago. The right side of the breast and other parts of the body showed no significant abnormalities on imaging examinations. She underwent a left mastectomy and axillary dissection on January 30, 2019. The histologic type of breast cancer was ILC (pT2, N2a, M0, luminal B). In postoperative immunohistochemistry (IHC), tumor cells were positive for ER and PR, and negative for HER2 and E-cadherin. She received adjuvant chemotherapy with epirubicin and cyclophosphamide every 21 days for four cycles and paclitaxel liposomal for injection every 21 days for another four cycles, starting on March 9, 2019. In addition, she received a total of 25 times of radiotherapy beginning on September 10, 2019, and commenced hormonal therapy with an aromatase inhibitor on the same day. Four years after chemotherapy, radiation, and hormone therapy, the patient did not experience any local or distant recurrences as confirmed by chest X-ray, computed tomography (CT), and bone scanning.

Personal and family history

The patient had unremarkable familial or personal history, with no notable medical conditions or genetic predispositions.

Physical examination

On admission, physical examination revealed epigastric tenderness. No obvious rebound pain and muscle tension in abdomen.

Laboratory examinations

Routine laboratory tests showed no apparent abnormalities. Histological examination revealed poorly differentiated carcinoma with regular glandular structure formation by hematoxylin and eosin staining (Figure 1A and B). Immunohistochemical staining showed that gastric tumor cells were positive for GATA-binding protein 3 (GATA3) (Figure 1C), PR (Figure 1D), ER (Figure 1E), and negative for E-cadherin (Figure 1F), gross cystic disease fluid protein 15, and HER2 (Figure 1G). The colorectum tumor cells were positive for GATA3 (Figure 1H) and ER (Figure 1I) and negative for cytokeratin (CK) 20 and E-cadherin (Figure 1J).

Figure 1 Histopathology and immunohistochemistry findings. A: Biopsy specimens showing diffuse proliferation of poorly differentiated carcinoma cells in the gastric mucosa [hematoxylin and eosin (HE) staining, 200 ×]; B: Biopsy specimens showing diffuse proliferation of poorly differentiated carcinoma cells in the colonic lamina propria (HE staining, 200 ×); C: Gastric immunohistochemical analysis reveals diffuse expression of GATA-binding protein 3 [immunohistochemistry (IHC) for GATA-3, 200 ×]; D: Gastric immunohistochemical analysis reveals diffuse expression of progesterone receptor(IHC for progesterone receptor, 200 ×); E: Gastric immunohistochemical analysis reveals strong immunoreactivity for estrogen receptor (ER) in about 90% of the neoplastic cells (IHC for ER, 200 ×); F: Gastric immunohistochemical analysis reveals absence of E-cadherin expression (IHC for E-cadherin, 200 ×); G: Human epidermal growth factor receptor 2 (HER2) is faintly stained on the cell membranes of some gastric tumors (IHC for HER2, 200 ×); H: Immunohistochemical staining of colonic lesions shows diffuse expression of GATA-3 (IHC for GATA-3, 100 ×); I: Immunohistochemical staining of colonic lesions shows strong immunoreactivity for ER (IHC for ER, 200 ×); J: Immunohistochemical staining of colonic lesions shows absence of E-cadherin expression (IHC for E-cadherin, 200 ×).

Imaging examinations

Abdominal dynamic contrast-enhanced CT did not reveal gastrointestinal related lesions. An upper gastrointestinal endoscopy revealed multiple crater-like ulcers scattered throughout the gastric body and antrum (Figure 2A and B). And a lower gastrointestinal endoscopy demonstrated numerous crater-like ulcers in the colorectum (Figure 2C-G). Narrow band imaging (NBI) displayed abnormal microvessels in the ulcer edges (Figure 2H and I), which is more common in malignant lesions. Due to multiple and conspicuous lesions, a biopsy was performed as a precaution.

Figure 2 Endoscopic images of gastric and rectum lesions. A and B: Endoscopic views of gastric antrum showing multiple crater-like ulcers; C-G: Endoscopic views of rectum showing multiple crater-like ulcers; H and I: Magnified narrow-band images of the lesions showing abnormal microvessels.

FINAL DIAGNOSIS

Based on the patient’s past medical history, endoscopic findings, and histological and immunohistochemical examination results, a final diagnosis of gastrointestinal metastases of ILC of the breast was established.

TREATMENT

The patient underwent left mastectomy, 8 cycles of chemotherapy, and 25 sessions of radiotherapy. She is currently on adjuvant toremifene therapy.

OUTCOME AND FOLLOW-UP

In February 2023, the patient was diagnosed with gastrointestinal metastasis from breast cancer by gastrointestinal endoscopy. Considering the progression of the disease, the patient's treatment with toremifene was discontinued. On February 14, 2023, the patient continued to receive combination therapy with letrozole and palbociclib. In May 2023, the patient's re-examination with gastrointestinal endoscopy suggested that the crater-like ulcers were improved (Figure 3). To achieve medical castration, the patient received a subcutaneous injection of goserelin acetate. To achieve more complete castration, the patient underwent laparoscopic bilateral salpingo-oophorectomy under general anesthesia on December 21, 2023. Histopathological examination of the bilateral ovaries and fallopian tubes revealed poorly differentiated adenocarcinoma. Combined with the patient's medical history and histopathological results, metastatic breast cancer is the most likely diagnosis. Follow-up endoscopy in August 2024 revealed scattered patchy areas of mucosal hyperplasia are observed in the gastric mucosa, accompanied by focal erosive changes, and the patient showed signs of disease progression (Figure 4). The patient received dual-agent therapy consisting of fulvestrant in combination with abemaciclib beginning August 26, 2024. The patient was readmitted in December 2024 due to abdominal distension. Dynamic contrast-enhanced abdominopelvic CT demonstrates patchy nodular thickening of the greater omentum with peritoneal effusion, highly suggestive of peritoneal carcinomatosis. On December 23, 2024, the patient initiated oral chemotherapy with capecitabine and vinorelbine. Dynamic contrast-enhanced lower abdominal CT on February 19, 2025 revealed peritoneal involvement. A therapeutic paracentesis with pigtail catheter placement was performed under ultrasound guidance on March 27, 2025 for ascites drainage. By histopathological examination, malignant tumor cells were found in the patient's ascites. Tumor cells were positive for ER and PR, and negative for HER2 by immunohistochemical staining. Based on comprehensive evaluation, the findings were consistent with peritoneal metastasis from breast cancer. The patient underwent intraperitoneal cisplatin perfusion therapy on April 1, 2025.

Figure 3 Endoscopic images of gastric and rectum lesions after four months of combination therapy with letrozole and palbociclib. A and B: The gastric mucosa exhibits scattered congestive and erosive lesions, with slightly depressed surfaces covered by small amounts of brownish blood crust; C and D: Multiple patchy erosions are noted in the rectosigmoid junction and rectal mucosa.

Figure 4 Endoscopic images of upper and lower gastrointestinal tract one and a half years after the detection of gastrointestinal lesions. A and B: Scattered patchy areas of mucosal hyperplasia are observed in the gastric mucosa, accompanied by focal erosive changes; C and D: The intestinal mucosa appears normal without evidence of pathological lesions.

DISCUSSION

The most frequent metastatic sites of breast cancer are the bones, lungs, liver, and brain[9]. It's rare for breast cancer to spread to the gastrointestinal tract, but in autopsies related to breast cancer, it has been reported to occur in about 6%-18% of cases[10]. ILC of the breast is more likely to spread to the gastrointestinal tract than IDC, possibly related to deletion of a protein called E-cadherin[7,10]. E-cadherin is a master regulator contributing to adherence junctions between epithelial cells and has an impact on suppressing tumorigenesis. Some studies have confirmed that the absence of E-cadherin expression has an important connection with the development of lobular lesions[11]. The stomach is the most common site for breast cancer to metastasize in the gastrointestinal tract, accounting for about 60% of cases[12], while colorectal metastasis from breast cancer is less common. Simultaneous metastasis to both the stomach and colorectum is even rarer and is typically reported as individual case studies. The present case is a 52-year-old female patient presenting with metastatic lobular carcinoma involving the gastrointestinal tract. We suggest that doctors performing endoscopy should be vigilant against simultaneous scattered ulcer-like lesions in the gastrointestinal tract. Distinguishing the benign and malignant nature of ulcer lesions is essential. And if the lesions are malignant, it is important to determine whether the tumor is primary or secondary.

We retrieved a case of a 78-year-old woman with gastric metastasis from ILC found a decade after breast cancer surgery[13]. We also retrieved a case of a 40-year-old woman with gastric metastasis from grade 2 ILC two years following chemotherapy, radiation therapy, and conservative surgery of the right breast and the ipsilateral axillary[14]. Unlike previous reports of isolated gastric metastasis, our case had synchronous gastric and colorectal involvements, suggesting a more aggressive metastatic pattern potentially linked to E-cadherin loss. This is a rare case indicating simultaneous metastasis of breast cancer to the gastrointestinal tract with similar endoscopic findings of multiple ulcer-like lesions.

Patients with gastrointestinal metastasis of breast cancer may not show any symptoms, or their symptoms may be nonspecific. They might experience dyspepsia, loss of appetite, nausea, vomiting, and abdominal pain[15]. These symptoms can be similar to the side effects of radiotherapy and chemotherapy, as well as those of primary gastrointestinal tumors, making the diagnosis of secondary neoplasm of digestive tract more challenging. Currently, there is no regular gastrointestinal examination for breast cancer patients, leading to delays in diagnosis.

In gastrointestinal endoscopic examinations, we suggest to pay special attention to the following points. Firstly, gastrointestinal lesions often appear as crater-like ulcers when viewed under the endoscope. It is worth noting that these ulcer-like lesions can be either benign or malignant. They can be distinguished based on the characteristics of the ulcer's edge and bottom, the appearance of the base, the shape of gastric movements, and the size and location of the ulcer[16]. Secondly, technologies like high-resolution micro endoscopes, NBI, and magnifying gastroscopes help differentiate between different ulcer properties. When dealing with definite malignant ulcer cases, it's essential to distinguish between primary carcinoma and secondary carcinoma. Adenocarcinoma accounts for over 95% of primary gastric cancers. Among these, the intestinal type, which often forms distinct tumor masses, is composed of highly differentiated tumor cells arranged in tubular or glandular structures, with scattered goblet cells present. The diffuse type, characterized by cells with signet-ring or non-signet-ring morphology, typically exhibits infiltrative growth patterns with diffuse invasion of the gastric wall[17]. Intestinal metastasis of breast cancer is typically diffuse and similar to primary diffuse cancer. Gastric metastases are often described as parietal nodules, polypoid masses, or ulcerated lesions[18]. Thus endoscopic findings are not specific, which can lead to misdiagnosis as primary gastrointestinal tumors.

The endoscopic examination followed by multiple and deep biopsies will drastically improve diagnostic accuracy. Moreover, IHC can help distinguish between primary cancers and breast cancer metastasis. GATA3 expression has a diagnostic sensitivity above 90% in primary breast cancers. If CK7 is strongly expressed, it often represents breast metastasis[19]. CK20 is negative in almost all breast cancers and positive in gastrointestinal neoplasms, thus its existence often proves that the lesion tissue is a primary gastrointestinal tumor. A definitive diagnosis is essential for formulating the correct treatment plans. Metastatic breast cancer is generally an incurable disease. In patients diagnosed with gastrointestinal metastasis, systemic therapy is recommended, which is typically palliative. The prognosis of these patients is better than that of patients with primary gastric cancer[20].

Despite differential diagnosis between primary and metastatic gastric carcinoma, additional factors were considered during the diagnosis of this case. Distinguishing between peptic ulcers and malignant ulcerations should be the diagnostic priority. The pathognomonic symptom of peptic ulcer disease is rhythmic epigastric pain with distinct chronobiological patterns: Gastric ulcer pain typically exacerbates 15-30 minpostprandially, while duodenal ulcer pain characteristically ameliorates with food intake[21]. Endoscopically, peptic ulcers typically present as well-circumscribed round or oval lesions with smooth, clean bases and regular margins[21]. In contrast, malignant ulcers demonstrate irregular, heaped-up borders, frequently associated with exophytic masses and convergence of distorted mucosal folds toward the ulcer bed[22]. Gastric ulcers typically occur in the lesser curvature side of the antrum, and duodenal ulcers are most commonly located in the duodenal bulb[21]. Malignant gastric ulcers exhibit a predilection for the gastric body and are characteristically larger in diameter compared to their benign counterparts[22]. Crohn's disease represents another benign pathology requiring exclusion in the differential diagnosis. The clinical presentation of Crohn's disease encompasses right lower quadrant abdominal pain, involuntary weight loss, chronic non-bloody diarrhea, and complications including enteric fistulae and intra-abdominal abscess formation. Crohn's disease is pathognomonically characterized by longitudinal ulcerations that may involve any segment of the gastrointestinal tract, accompanied by distinctive cobblestone mucosa and non-caseating granulomas on histopathology[23]. Jejunoileal neuroendocrine tumors (NETs) represent a distinct subtype of gastrointestinal neuroendocrine neoplasms characterized by frequent multifocality[24]. Endoscopic findings of Jejunoileal NETs are sometimes similar to this case. However, it has the characteristics of NETs, which is helpful for further differential diagnosis. Carcinoid syndrome is a specific manifestation of NETs, including episodic flushing, watery diarrhea, and wheezing[25]. Monomorphic round cells with abundant eosinophilic cytoplasm and salt and pepper chromatin with rate mitotic figures may be seen in NETs. IHC is positive for cytokeratins, chromogranin A, synaptophysin, somatostatin receptors, and various hormonal receptors in functional tumors[26]. Additionally, the presence of multiple intestinal tract ulcers can be a feature of ischemic enteritis. Multiple ulcers with varied morphologies–including geographic, linear, and coin-like configurations–were observed in the intestinal tract. In contrast, ischemic enteritis results from acute insufficiency of mesenteric arterial blood flow. Computed tomographic angiography is valuable for differential diagnosis[27]. Chronic nonspecific multiple ulcers of the small intestine (CNSU) predominantly affect the ileum, typically presenting with over 20 ulcerative lesions. Gross examination reveals well-demarcated ulcers with shallow, flat bases, exhibiting linear, tall triangular, or geographic configurations. Histopathological evaluation of CNSU demonstrated ulcerations confined to the submucosal layer, associated with mild chronic inflammatory infiltrates[28]. Based on the patient's history of breast carcinoma, endoscopic characteristics, and immunohistochemical profile of the tumor, we conclusively diagnosed the gastrointestinal ulcerative lesions as metastatic breast cancer to the gastrointestinal tract.

CONCLUSION

It is uncommon for breast cancer to spread simultaneously to the stomach and intestinal tract. Endoscopic biopsy combined with IHC is essential to differentiate metastatic breast cancer from primary gastrointestinal malignancies, greatly improving diagnostic accuracy.