Gastric Metastasis 5 Years after Primary Invasive Lobular Adenocarcinoma of the Breast

Abstract

Breast cancers metastasize most commonly to the bone, brain, liver, and lungs, but rarely to the gastrointestinal tract. Although metastatic breast carcinomas in the stomach can be confused with primary gastric cancers due to their nonspecific presentation and rare incidence, it is important to differentiate the two since the treatment is different. Clinical suspicion is imperative for a prompt endoscopic evaluation and a definitive diagnosis that will lead to appropriate treatment. Therefore, it is important for clinicians to be aware of the possibility of gastric metastasis of breast cancers, especially in those with a history of invasive lobular breast carcinoma and a new onset of gastrointestinal symptoms.

Introduction

Although widespread adoption of screening mammography and advances in treatment have reduced its mortality in the western world, breast cancer remains the second most common cause of cancer death in women in the USA and the most prevalent cancer among women with an increasing incidence [1, 2]. Breast cancer can be classified according to its histologic type and additionally by the expression of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor-2 (HER-2) receptor, which affects treatment options and prognosis. Gene expression studies allow for further molecular classification of breast cancer into subtypes: (1) luminal subtypes (type A and type B) that are the most common subtypes of breast cancer and comprise the majority of ER-positive breast cancers; (2) HER-2-enriched subtypes that are often ER- and PR-negative; (3) basal subtypes that are mostly comprised of triple-negative breast cancers [3, 4]. Breast cancer subtypes are also associated with distinct metastatic patterns [5].

Bone, brain, liver, and lungs are the most common sites of breast cancer metastasis. Metastasis to the gastrointestinal tract is, however, uncommon, with a reported incidence of 0.3%–18%, varying upon studies [3, 6–8]. The mean time interval from primary breast cancer diagnosis to gastric metastasis is reported to be around 5–7 years [3, 6, 8].

Among the types of breast cancer, invasive lobular carcinomas are more likely to metastasize to the stomach and often present as diffuse linitis plastica-like infiltration [9, 10]. Here, we report a case of gastric metastasis discovered during endoscopy in a patient with a history of metachronous bilateral invasive lobular breast cancer treated five and two years ago, respectively. Gastric metastasis of breast cancer was diagnosed by immunohistochemical analysis. The CARE Checklist has been completed by the authors for this case report, attached as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000528506).

Case Report

A 72-year-old female presented to the gastroenterology clinic for evaluation of her abdominal bloating, chronic constipation, and intermittent episodes of painless hematochezia, described as bright red blood on wiping after defecation, over a period of 2–3 months. Her past medical history is significant for bilateral breast cancer, gastroesophageal reflux disease treated with proton pump inhibitor, colonic adenomatous polyp, and hypertension. Five years ago, she was diagnosed with invasive lobular carcinoma of her right breast (stage pT3 pN3a, ER positive 80–85%, PR positive 35–45%, HER-2 negative). She underwent right mastectomy, adjuvant chemotherapy, as well as radiation therapy and was started on an aromatase inhibitor. Three years after her initial diagnosis of breast cancer, she was subsequently found to have invasive lobular carcinoma involving her left breast (stage pT1c pN1a, ER 100% positive, PR, and HER-2 negative). She underwent left mastectomy and completed adjuvant chemotherapy and radiation therapy. Her past surgical history included a cesarean section many years ago followed by hysterectomy and bilateral mastectomy. She has a family history of breast cancer in two of her maternal aunts. She denies any history of smoking, alcohol, or recreational drug use.

Physical examination of the gastrointestinal system was unremarkable, with a soft, nontender abdomen and no visceromegaly. The remainder of the physical exam was normal. Laboratory test results at the time of our initial evaluation were unremarkable except for elevated Ca 27.29 level and shown in Table 1.

Table 1.

Laboratory findings

Labs	Value	Reference range
White blood cell	6.2	4.8–10.8 K/μL
Hemoglobin	13.2	12.0–16.0 g/dL
Hematocrit	39.7	42.0–51.0%
Platelet	314	150–400 K/μL
Sodium	138	135–145 mEq/L
Potassium	5.0	3.5–5.0 mEq/L
Chloride	99	98–108 mEq/L
Bicarbonate	28	24–30 mEq/L
Glucose	95	70–120 mg/dL
Blood urea nitrogen	14.0	6–20 mg/dL
Creatinine	0.7	0.5–1.5 mg/dL
Calcium	9.6	8.5–10.5 mg/dL
Total protein	6.8	5.8–8.3 g/L
Albumin	4.6	3.2–4.6 g/dL
Bilirubin, total	0.3	0.2–1.1 mg/dL
Alkaline phosphatase	98	43–160 unit/L
Aspartate aminotransferase	19	9–36 unit/L
Alanine aminotransferase	14	5–40 unit/L
Cancer antigen, breast Ca 15-3	17	≤25 U/mL
Cancer antigen, Ca 27.29	137.0	<38 U/mL
BRCA ½	Negative

A colonoscopy was performed for the evaluation of hematochezia, which showed two hyperplastic polyps, diverticulosis, as well as internal and external hemorrhoids. An esophagogastroduodenoscopy (EGD) was performed due to abdominal bloating and revealed a fungating mass and friable diffuse infiltrative lesions with gastric fold thickening in the gastric body. The mass was partially circumferential and occupied about two-thirds of the luminal circumference of the stomach (shown in Fig. 1). Biopsy of the gastric mass showed infiltrating poorly differentiated adenocarcinoma (shown in Fig. 2). Immunohistochemical staining revealed CK7 and GATA3 (+), GCDFP15 focally (+), CK20 and Mammaglobin (−), findings favoring metastatic breast carcinoma (shown in Fig. 2). Further staining studies revealed estrogen receptor positive (>95%, strong intensity), progesterone receptor negative, and HER-2 negative (shown in Fig. 3). Genomic profiling of the tumor cells reported a PIK3CA mutation. The patient is following with oncology for management of her bilateral breast cancer with metastasis to the stomach and is currently receiving treatment with alpelisib-fulvestrant.

Fig. 1.

EGD findings showing a fungating mass (a), friable diffuse infiltrative lesions with gastric fold thickening in the gastric body (b), suggestive of malignancy.

Fig. 2.

Biopsy of the gastric body lesion showing an infiltrating poorly differentiated adenocarcinoma. Immunohistochemical staining revealing CK7 (+), GATA3 (+), GCDFP15 focally (+), CK20 (−), and mammaglobin (−).

Fig. 3.

Immunohistochemical staining positive for estrogen receptor (>95%, strong intensity), negative for progesterone receptor, and HER-2 overexpression.

Discussion

Gastric metastasis of breast cancer is uncommon, with only several case reports and case series reported in the literature. Invasive lobular carcinoma was the most common type of primary breast cancer in those with gastric metastasis, and therefore, the majority of tumors were positive for hormonal receptors (ER 92.3%–94%, PR 68.3%–76.9%) with low expression of HER-2 (0%–5.9%) [3, 8–11]. Patients can present with various gastrointestinal symptoms such as anorexia, abdominal pain, nausea, vomiting, bleeding, bloating, and early satiety, but can also be asymptomatic [3, 6, 8, 9]. The clinical symptoms of metastatic breast carcinoma to the stomach are often similar to those of primary gastric malignancies, and endoscopic investigation with biopsy and immunohistochemistry analysis is essential to distinguish primary from metastatic disease [8, 10, 12]. Endoscopic findings can vary from a discolored mucosal lesion with a speculated edge, polypoid lesions with or without ulceration, diffuse infiltrative lesion with spontaneous bleeding and fold thickening, to deep ulcerative lesion with exudate and bleeding. Lesions can be located anywhere from the fundus to the antrum [3]. Solitary lesions were more commonly observed than multiple lesions [3, 13]. Taal et al. [9] retrospectively reviewed the endoscopic findings of 51 patients with gastric metastases of breast carcinomas, which revealed 3 patterns: diffuse linitis plastica-like infiltration in 57%, localized lesions in 18%, external compression at the cardia or pylorus in 25% of cases [9].

However, it is difficult to differentiate primary from secondary gastric cancer solely based on gross endoscopic findings, and further histological examination is required. Since gastric metastases are mostly localized to the submucosal and seromuscular layers, endoscopic evaluation can be normal in 50% of cases, and a tissue biopsy of deeper gastric layers may be required for an accurate diagnosis [6]. Immunohistochemistry analysis is crucial to differentiate primary gastric carcinomas from gastric metastasis of breast carcinomas. Positive staining of ER, PR, gross cystic disease fluid protein-15 (GCDFP15), and cytokeratin (CK) 5/6 are highly specific for metastatic breast carcinomas, while primary gastric carcinomas are more likely to stain positive for CK20, mucin glycoprotein antigens (MUC2, MUC5AC, and MUC6), monoclonal antibody DAS-1, and caudal-type homeobox transcription factor CDX2 [14]. Furthermore, adenocarcinoma with co-expression of CK7, GATA-binding protein 3 (GATA3), and ER is highly specific for metastatic carcinoma of breast origin [15].

Systemic chemotherapy, hormone therapy, or combined therapy are the preferred treatment options for gastric metastases of breast cancer, with a response rate of 30%–50%. Although there have been limited reports of prolonged survival with gastric resection of a solitary gastric metastasis following complete remission of primary breast cancer, surgical treatment is generally not recommended as a primary treatment option. Surgical treatment can be used for palliative purposes or to treat complications such as obstruction and gastric wall perforation [6, 8, 9, 16]. Studies show a median survival of 10–28 months from the detection of gastric metastases and a 2-year survival rate of 23%–53% [9, 11, 16].

Conclusion

Although gastric metastasis of breast carcinoma is rare, clinicians may encounter such patients as the prevalence of breast cancer is increasing with more screening and advanced treatment. Therefore, physicians should be aware of such possibility and have a high index of suspicion, especially in patients with a history of invasive lobular carcinomas complaining of gastrointestinal symptoms. Endoscopic investigation with biopsy involving deeper layers of the stomach is important to obtain a proper sample for the diagnosis. Since primary gastric carcinoma and gastric metastasis of breast cancers are treated differently, it is important to further differentiate the two, which can be done effectively by immunohistochemical staining in collaboration with a pathologist.

Statement of Ethics

All procedures were performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. The case report was reviewed, and the need for approval was waived by the Institutional Review Board of BronxCare Health System. Written informed consent was obtained from the patient for publication of this case report and any accompanying images.

Conflict of Interest Statement

The authors have no conflicts of interest to declare.

Funding Sources

The authors received no funding for this research.

Author Contributions

Dongmin Shin, Haozhe Sun, and Nikhitha Mantri searched the literature, wrote, and revised the manuscript. Harish Patel revised and approved the final manuscript, and Harish Patel is the article guarantor.

Funding Statement

The authors received no funding for this research.

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.