Duodenal Metastasis in Triple-Negative Invasive Ductal Breast Carcinoma With Negative Mammography: A Case Report and Review of the Literature


Naila A Khan, DO1; Sonha T Nguyen, MD1; Phildrich G Teh, MD1; Vishal N Ranpura, MD2; Taruna Bhatia, MD3

Perm J 2021;25:20.244

E-pub: 07/28/2021

Breast cancer metastasis to the gastrointestinal tract is uncommon, and duodenal involvement is exceptionally rare. Those cases that do metastasize are reported to be lobular, with ductal carcinomas comprising only a small percentage of reported cases. Furthermore, these invasive carcinomas are typically estrogen receptor–, progesterone receptor–positive ± human epidermal growth factor receptor 2 malignancies. We present a unique case of a patient with duodenal metastasis as the first sign of metastatic breast cancer. The rarity of this case is highlighted by the fact that the patient had no known breast malignancy, and pathological findings revealed triple-negative invasive ductal carcinoma consistent with primary breast cancer. Diagnostic mammogram and ultrasound were negative for any lesions.


Breast cancer is the most common neoplasm in women and the second leading cause of cancer-related death in women worldwide.1 Although atypical, gastrointestinal (GI) tract metastasis of breast cancer can occur but is exceedingly rare in the small intestine. GI disturbances may be the first presenting sign of metastatic breast cancer. If diagnosis and treatment are delayed, this can result in a grim overall prognosis. GI involvement of breast malignancy is not only limited to invasive lobular carcinoma (ILC) but can also occur in invasive ductal carcinoma (IDC), which is a rare entity.2,3 Screening mammography improves mortality by facilitating early detection and treatment.4 However, its sensitivity and specificity can depend on patient age and density of breast tissue, further complicated by the possibility of imaging-negative malignancy. We report a case of a 57-year-old woman with GI metastasis as the presenting finding of triple-negative breast cancer with negative mammography.


A 57-year-old Caucasian woman presented to clinic with a 2-month history of recurrent postprandial epigastric pain with associated nausea, decreased appetite, and bloating. The patient visited the clinic multiple times and was prescribed proton pump inhibitors (pantoprazole) and antacid (sucralfate) for presumed dyspepsia, but her symptoms persisted. She denied fevers, night sweats, unexplained weight loss, melena, hematochezia, or hematuria. She reported a nontender lump on the right side of the neck for several weeks. The patient had an unremarkable screening colonoscopy 7 years earlier. In addition, routine mammogram was negative 6 months earlier. She had a history of remote tobacco use. Family history was negative for breast or ovarian cancer. Laboratory results revealed new onset of severe anemia, with a hemoglobin level of 7.0 g/dL (normal, 12.0-15.5 g/dL), a notable decline from her baseline of 14.5 g/dL 6 months prior. The patient was admitted to the hospital for further workup.

On arrival, the patient was afebrile with mild sinus tachycardia. She had conjunctival pallor and right supraclavicular lymphadenopathy (2.0 × 2.0 cm). Abdominal examination revealed diffuse tenderness without guarding or rebound. No palpable breast or axillary masses were noted. Fecal occult blood test was positive. Laboratory studies confirmed microcytic anemia (hemoglobin, 7.1 g/dL). Contrast-enhanced computed tomography (CT) scan of the abdomen and pelvis revealed bulky mesenteric and retroperitoneal adenopathy and several segments of small bowel wall thickening (Figure 1). CT scan of the thorax with contrast showed bilateral supraclavicular and extensive mediastinal and right hilar lymphadenopathy. The patient underwent urgent esophagogastroduodenoscopy, which revealed a semicircumferential, necrotic, and fragile mass in the second portion of the duodenum (Figure 2). Colonoscopy revealed diverticulosis but was otherwise unremarkable.


 Figure 1. Contrast-enhanced computed tomography scan of the abdomen and pelvis with (a) coronal view and (b) axial view revealing bulky mesenteric and retroperitoneal adenopathy with segments of small bowel wall thickening


 Figure 2. (a) Esophagogastroduodenoscopy revealing (a and b) a semicircumferential necrotic and fragile mass in the second portion of the duodenum.

Histopathologic findings from the duodenal biopsies revealed poorly differentiated, primary, triple-negative ductal breast carcinoma (Figure 3). Specifically, immunohistochemistry (IHC) staining showed positive cytokeratin 7 (CK7), GATA binding protein 3, and vimentin (Figure 4a, 4c) with negative caudal type homeobox transcription factor 2 (CDX2) and cytokeratin 20 (CK20; Figure 4b), suggestive of metastatic breast carcinoma. Furthermore, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) results were all negative (Figure 4d). Diagnostic bilateral mammogram and bilateral breast ultrasound were negative for any breast lesion (Figure 5). The cancer antigen 15-3 (CA 15-3) level was normal, at 5.0 U/mL (normal < 31.3 U/mL). During her hospital course, the patient was treated with blood transfusions and discharged home with medical and radiation oncology follow-up.


 Figure 3. Histologic staining with hematoxylin and eosin from the duodenal biopsy shows (a) invasive ductal carcinoma with mitosis (×20) and (b) malignant cells surrounded by tumor necrosis (×10).


 Figure 4. Immunohistochemical staining from the duodenal biopsy was (a) positive for cytokeratin 7 (×10), (b) negative for cytokeratin 20 and caudal type homeobox transcription factor 2 (×10), (c) positive for GATA binding protein 3 (×10), and (d) negative for estrogen, progesterone, and human epidermal growth factor receptor 2 (×10).


 Figure 5. Diagnostic mammogram of (a) right and (b) left breast revealing no evidence of malignancy.

The patient received palliative radiation therapy to the distal stomach and duodenum at a dose of 2000 cGy in 250 cGy fractions for 10 treatment sessions. She was then started on palliative chemotherapy with weekly paclitaxel. However, after 1 dose of chemotherapy, the patient returned to the emergency department with orthopnea, abdominal pain, distention, and bilateral peripheral edema. Laboratory studies revealed a hemoglobin level of 7.1 g/dL, hyponatremia of 124 mEq/L (normal, 135-145 mEq/L), hyperkalemia of 6.2 mEq/L (normal, 3.5-4.5 mEq/L), and acute renal failure with a creatinine level of 1.69 mg/dL (normal, 0.5-1.0 mg/dL). A repeat CT scan of the abdomen and pelvis showed multiple dilated loops of small bowel with air-fluid levels suggestive of small bowel obstruction. A chest radiograph demonstrated further findings of left pleural effusion. The general surgery team on consult determined no intervention was necessary, given her overall poor prognosis. The patient and her family opted for comfort measures; she went into cardiorespiratory arrest and died 2 days later.


Two million new cases of breast cancer occur globally, with a lifetime risk of 1 in 8 women in the United States.5 The disease metastasizes to the brain, lymph nodes, skin, lung, liver, and bone.2 GI tract metastasis is infrequently reported, and when present, is an indication of a poor prognosis.6 In a study of approximately 2600 patients with breast malignancy, < 1% were noted to have GI metastatic involvement.3 Furthermore, Ambroggi et al7 studied the specific metastatic sites of breast malignancy within the GI tract and found that the most common involvement is the stomach (60%), followed by the esophagus (12%), colon (11%), and rectum (7%). Breast cancer metastasis to the small intestine (8%), especially the duodenum, is very rare and usually discovered on autopsy.7-9

It can be challenging to diagnose GI metastasis secondary to primary breast carcinoma because it is uncommon and may be overlooked in the initial presentation. The clinical diagnosis can be delayed because of symptoms of nausea, vomiting, anorexia, abdominal pain, changes in stool, hemorrhage, or, less commonly, perforation; these nonspecific findings can mimic primary GI disorders and lead to underdiagnosis of breast cancer metastasis.2,6 At the time of initial diagnosis, 5% to 10% of patients with breast cancer present with metastasis – an eventual 20% to 50% will develop metastasis during their disease course.10 Furthermore, the interval between breast cancer diagnosis and GI metastasis can be variable, with a latency period of several months to decades.11,12 In our case, the patient had recurrent visits to the clinic for generalized abdominal pain, which was misdiagnosed and treated as dyspepsia. Unlike most reported cases, she had no prior diagnosis of breast malignancy and, therefore, metastatic disease had a lower index of suspicion. This cautions clinicians on the importance of obtaining a detailed medical history and formulating a broad differential. Our patient had also presented with a neck lump during her first clinic visit for which a CT scan of the neck was ordered on a routine basis; however, the patient was admitted before the scheduled outpatient scan. Expediting imaging orders in many cases may prevent an additional delay in diagnosis.

Metastatic patterns vary depending on the 2 histologic subtypes of breast cancer. ILC accounts for only 10% to 14% of all invasive breast carcinomas, whereas IDC constitutes 80% of cases.11,13,14 Interestingly, ILC more frequently metastasizes to the GI tract compared with ductal cancer and is reported in up to 64% of all lobular metastatic cases.11,13,15,16 The exact mechanism of lobular versus ductal spread remains unknown. It has been hypothesized that ILC metastasis is a result of tropism of lobular cells16,17 and loss of the cell adhesion molecule E-cadherin, which may contribute to its predilection for the GI system.18,19 Lobular metastasis may also be caused by hematogenous dissemination of malignant cells to the GI tract, given its rich blood supply or via peritoneal and lymphatic spread.20,21 In contrast, the GI metastasis of IDC is uncommon, with duodenal involvement being exceptionally rare.3,22 In a landmark article, Harris et al23 studied 76 postmortem cases of metastatic ductal carcinoma, in which only 3 had metastasized to the intestines. They also noted that lobular metastatic patterns involved tiny nodules leading to a more confluent spread, whereas ductal metastasis formed distinct nodules.

Although duodenal metastasis of primary ductal breast carcinoma is rare, it has been reported in previous studies.24-30 When small bowel involvement is present in metastatic breast cancer, the terminal ileum is a more common site of metastasis compared with the duodenum.2 The presentation in our case – small bowel obstruction as the first manifestation of metastasis to the GI tract – is documented in previous patient reports.13,26,31-33 However, each of these cases involves patients with a known diagnosis and prior treatment of breast cancer who eventually developed GI metastasis after some interval. Our case is unique in that the patient had no prior history of breast cancer, including no breast complaints or focal findings. In 1 reported case by Woo et al,34 a patient with hormone-positive ILC presented with an initial manifestation of malignancy as gastric metastasis; this patient’s screening mammography was also negative at the time of diagnosis. Further literature review demonstrated another case by Khairy et al26 of a patient with no prior history of breast cancer who first presented with small bowel obstruction, and biopsy revealed triple-positive IDC, also with negative mammography. This patient did have axillary lymphadenopathy, and a biopsy helped confirm the diagnosis. Similarly, our patient had supraclavicular lymph nodes as a late presentation of advanced disease for which biopsy was planned; however, this biopsy was not completed, given her rapid decline.

Our patient received annual screening mammograms starting at 44 years of age. She had a routine mammogram just 6 months prior, which was negative, with a BI-RADS (Breast Imaging, Reporting and Data System) score of 1. Notably, diagnostic mammogram and ultrasonography revealed no evidence of malignancy after her biopsy-proven IDC in the duodenum. This illustrates an important concept of diagnostic accuracy. Although regular screening mammography is the most effective tool to reduce breast cancer-related mortality, it has its limitations. The sensitivity of screening mammograms is 85%, and specificity is approximately 96%.35 However, sensitivity is reduced to 47.8% to 64.4% in females with denser breast tissue. In a large prospective study by Barlow et al36 involving 41,427 diagnostic mammograms, it was concluded that these have higher sensitivity but lower specificity in patients with signs of breast cancer compared with screening mammography. Perhaps using a more accurate diagnostic modality like magnetic resonance imaging (MRI) in our patient scenario could have detected a breast lesion. MRIs are far more sensitive and specific than mammograms or ultrasounds in detecting small breast malignancies.37 In our patient, MRI was ordered but she clinically deteriorated before the test could be performed. Despite any evidence of breast pain, mass, or axillary adenopathy, a breast biopsy may have been another option to potentially diagnose primary carcinoma in the breast tissue. For instance, a case presentation written by Zuhair and Maron38 reports a patient with no known diagnosis of breast cancer who presented with abdominal pain and was found to have ER-positive lobular carcinoma in the GI tract. Previous mammography in this patient was notable for nonspecific findings of dense nodular parenchyma, but ILC was identified only after core biopsy of breast tissue was completed.

Differentiating metastasis from an unknown primary can be challenging, especially in a patient without a history of malignancy. Distinction can be made with analysis of morphologic patterns through histopathologic studies and IHC staining. Determining CK7 and CK20 immunophenotypes is valuable to distinguish colorectal from extraintestinal malignancies.39 The CK7+/CK20 pattern, as in our case, is highly specific for breast carcinomas.40 Caudal type homeobox transcription factor 2, a transcription factor, is a strong marker for carcinomas of intestinal origin and was negative in our patient.41 Vimentin, a structural protein, was positively expressed on our patient’s biopsy and has been associated with invasive and chemoresistant ductal carcinomas.42 Additionally, the presence of the GATA binding protein 3 is a hallmark of metastasis due to breast origin, especially triple-negative malignancies.43 To date, there are no reliable serum tests to serve as screening and diagnostic markers for breast cancer. The CA 15-3 is a common tumor marker used for prognostic purposes and to detect breast cancer recurrence, but its use is controversial.44 CA 15-3 levels may be elevated in metastatic disease and its presence is associated with poor prognosis in nonmetastatic cases.45 However, the CA 15-3 level was normal in our patient. A study conducted by Dede et al46 found that CA 15-3 levels in triple-negative breast cancer cases were significantly lower at the time of diagnosis and during metastasis compared with other forms of breast cancer. We did not analyze cancer antigen 19-9 (CA 19-9) levels, but 1 study reports elevated levels in metastatic lobular breast carcinoma to the GI tract.47

Triple-negative breast carcinomas do not express ER, PR, and HER2 receptors. They are high-grade with increased mitotic activity and poor overall prognosis. Triple-negative findings are present in 20% to 25% of all breast malignancies31; they are more frequently seen in ductal carcinomas and, thus, usually metastasize to the brain, lung, and liver.48,49 As discussed previously, GI metastasis of IDC is an overall rare phenomenon and predominantly hormonal (ER/PR) positive ± HER2.13,26,31-33 There are only a handful of case reports describing metastasis of triple-negative carcinoma to the GI tract, and these include both ILC and IDC subtypes.31,38,50,51 Geredeli et al50 report a case of lobular triple-negative carcinoma to the stomach. Another article by Baa et al48 reports a patient who presented with a breast lump and dyspepsia who was diagnosed with triple-negative IDC with stomach involvement. Only 1 case of triple-negative IDC to the small bowel, specifically the jejunum, was reported.51 Of note, all these patients had either a known previous breast cancer diagnosis or presented with focal breast findings. To our knowledge, there have been no case reports on triple-negative IDC to the duodenum, which is unique to our patient scenario (Tables 1, 2).

Table 1. Summary of select cases of metastatic breast cancer to the gastrointestinal tract, highlighting the rarity of triple-negative IDC metastasis to the duodenum

Gastrointestinal metastasis of breast cancer Characteristic
Primary breast diagnosed Primary breast undiagnosed Subtype Receptor status Reference
Duodenum x   IDC HR+/HER2− 24
Duodenum x   IDC HR+/HER2− 25
Duodenum x   IDC HR+/HER2− 27
Duodenum x   IDC HR+/HER2− 29
Duodenum x   IDC HR+/HER2− 16
Duodenum   x IDC HR+/HER2+ 26
Duodenum x   ILC HR+/HER2− 52
Duodenum x   ILC HR+/HER2− 32
Duodenum   x ILC HR+/HER2− 38
Jejunum x   ILC HR−/HER2− 31
Jejunum x   IDC HR−/HER2− 51
Colon x   IDC HR+/HER2− 17
Colon x   ILC HR+/HER2− 53
Stomach x   ILC HR+/HER2− 11
Stomach x   ILC HR−/HER2− 50
Stomach x   IDC HR−/HER2− 48
Stomach   x ILC HR+/HER2− 38
Stomach   x ILC HR+/HER2− 34

HR = hormone receptor; HER2 = human epidermal growth factor receptor 2; IDC = invasive ductal carcinoma; ILC = invasive lobular carcinoma

Table 2. Case report timeline and relevant history

Date: Summaries from initial and follow-up visits Diagnostic testing Interventions
04/18/2019 Patient presented to primary care for epigastric pain and nausea for past month. No imaging ordered at this time. Dietary and lifestyle modification recommended along with trial of proton pump inhibitor (omeprazole).
04/30/2019 Patient returns for continued and worsening abdominal pain now radiating to back with no relief from proton pump inhibitor therapy. CT of the abdomen and pelvis ordered along with laboratory tests, including CBC, CMP, lipase, and Helicobacter pylori stool testing. Dietary and lifestyle modification along with addition of sucralfate. Omeprazole was switched to pantoprazole.
04/30/2019 Laboratory testing performed as an outpatient revealed acute drop in hemoglobin. Patient was called and advised to go to the ED immediately. Hemoglobin drop to 7.0 g/dL from baseline of 14 g/dL and positive fecal occult blood test. CT of the abdomen and pelvis revealed adenopathy and several segments of wall thickening. Patient was admitted to inpatient service for further workup of anemia, gastrointestinal bleeding, and abdominal pain.
05/01/2019 Gastroenterology consulted for epigastric pain and anemia. EGD and colonoscopy planned. EGD revealed necrotic and fragile semicircumferential mass found in second portion of duodenum; multiple biopsies taken. Colonoscopy was unremarkable.
05/02/2019 Patient was treated with 2 units of packed red blood cell transfusion and improvements noted in her hemoglobin.   Patient was discharged home with outpatient follow-up.
05/07/2019 Final pathological results from duodenal biopsies revealed poorly differentiated triple-negative primary breast cancer. Patient referred for urgent oncologic evaluation.  
05/08/2019 Patient seen by oncology for newly diagnosed metastatic breast cancer. Previous screening mammograms, last one in 10/2018, were negative for breast lesions. Diagnostic mammogram and ultrasound of the breasts ordered; both returned negative and without any suggestive findings. Tumor marker CA 15-3 levels were normal at 5.0 U/mL. Overall poor prognosis and plan for palliative chemotherapy. Referral to radiation oncology also placed.
05/10/2019 Patient started on course of radiation therapy to duodenum for 10 planned treatment sessions.    
05/16/2019 Patient started on chemotherapy with paclitaxel weekly planned for 6 cycles.    
05/21/2019 Patient presents to the ED with fatigue, nausea, vomiting, and worsening abdominal pain. CT of the abdomen and pelvis revealed multiple dilated loops of small bowel suggestive of obstruction. Chest x-ray revealed bilateral pleural effusions. Significant laboratory findings included hyponatremia, hyperkalemia, and acute renal injury. Patient was admitted for further evaluation and surgical consultation for abdominal findings.
05/22/2019 Patient deemed not a surgical candidate for small bowel obstruction. Patient symptomatically treated for pain and nausea. Hydration therapy initiated and electrolyte impairments monitored.   Palliative care team consulted given overall poor prognosis. Patient opted for comfort measures and died on 5/24/2019.
Relevant medical history and interventions
Medical history Hyperlipidemia, attention deficit hyperactivity disorder.
Past medical testing Screening colonoscopy in 2017 was normal. Screening mammograms biennially from 2006 to 2018 were negative.
Family history Negative for breast or ovarian cancer. Paternal grandfather with colon cancer at unknown age.
Psychosocial history Former tobacco use (21 pack-years and quit 10 y prior). Recently under a lot of stress, working 3 jobs and over 80 h per week. Divorced with 2 adult children.

CA 15-3 = cancer antigen 15-3; CBC= complete blood count; CMP = comprehensive metabolic panel; CT = computed tomography; ED = emergency department; EDG = esophagogastroduodenoscopy.

Treatment of triple-negative metastatic breast carcinoma usually involves palliative systemic chemotherapy, immunotherapy combined with chemotherapy, or targeted treatment with poly (ADP-ribose) polymerase inhibitors. Radiotherapy is reserved for palliation to provide symptomatic relief. In select cases, surgery can be considered for refractory bleeding, obstruction, or intestinal perforation.11,16 In a retrospective study conducted by Taal et al,11 of 51 patients with GI involvement from breast carcinoma, only 6 were treated surgically, all of them for palliative reasons and relief of obstructive symptoms. Mourra et al6 found that no patient survived beyond 5 years, even with surgery, and there was no significant improvement in survival compared with those without surgical management. Our patient died within 3 months of diagnosis. Duodenal metastasis of primary breast carcinoma has a dismal prognosis, and the overall median survival in patients with GI metastasis from breast malignancy is 28 months.16 Although GI involvement is not common in metastatic triple-negative breast cancer, it must be considered to prevent delay in diagnosis and improve patient outcomes.


Breast cancer rarely metastasizes to the GI tract, especially the small intestine. This pattern of metastatic spread is not limited to ILC and is possible with IDCs. In these rare cases, the indolent symptoms can cause a delay in diagnosis and treatment of the aggressive cancer. Differentiating metastasis from an unknown primary can be challenging; we rely on detailed pathological analysis including immunohistochemical staining as important diagnostic tools. These collective findings belie the shortcomings of screening mammography, because imaging-negative breast malignancy may exist. Our case illustrates unusual findings of small bowel metastasis as the initial manifestation of triple-negative ductal carcinoma in a patient with no prior history of breast malignancy.

Disclosure Statement

The author(s) have no conflicts of interest to disclose.


CA 15-3 = cancer antigen 15-3; CA 19-9 = cancer antigen 19-9; CDX2 = caudal type homeobox transcription factor 2; CK7 = cytokeratin 7; CK20 = cytokeratin 20; CT = computed tomography; EGD = esophagogastroduodenoscopy; ER = estrogen receptor; GATA3 = GATA binding protein 3; GI = gastrointestinal; HER2 = human epidermal growth factor receptor 2; IDC = invasive ductal carcinoma; IHC = immunohistochemistry; ILC = invasive lobular carcinoma; MRI = magnetic resonance imaging; PR = progesterone receptor

Author Affiliations

1Department of Internal Medicine, University of California Riverside, Riverside, CA

2Department of Hematology and Oncology, Kaiser Permanente, Riverside, CA

3Department of Gastroenterology, Kaiser Permanente, Riverside, CA

Corresponding Author

Naila A Khan, DO (naila.ahmad.khan@gmail.com)

Author Contributions

Naila A Khan, DO, participated in the critical review, drafting, literature research, and submission of the final manuscript. Sonha T Nguyen, MD, and Phildrich G Teh, MD, participated in the literature research and drafting of the final manuscript. Vishal N Ranpura, MD, and Taruna Bhatia, MD, participated in direct patient care and editing of manuscript. All authors have given final approval to the manuscript.


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Keywords: breast cancer metastasis, duodenal metastasis, invasive ductal carcinoma, negative mammogram, triple negative


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