Metastatic infiltrating lobular breast carcinoma into the colon diagnosed by routine bowel screening in a 60-year-old woman

Breast cancer is the second most common cancer diagnosed in Australia and the most common cancer in women, with an estimated incidence of over 20,600 cases in 2022. [1]. Common sites for distant metastases are bone (59.9%), lung (47.8%), liver (40.9%) and brain (38.8%). [2]and metastases to the gastrointestinal tract, especially the colon, are uncommon. The diagnosis of colon metastases is difficult because of its rarity, and there is also a long disease-free interval between the diagnosis of breast cancer and the diagnosis of gastrointestinal metastases. [3]. We present a case of an incidental finding of colonic metastases using a fecal occult blood screening test to alert surgeons that the possibility of metastases should be considered when evaluating the patient for a positive result in patients with a history of breast cancer.

A 67-year-old woman was diagnosed with pT1a pN1 M0 infiltrating lobular carcinoma of the right breast in 2013. Out of personal preference, she underwent bilateral mastectomy and axillary clearance, followed by adjuvant chemotherapy with 5-fluorouracil, epirubicin and cyclophosphamide. She was then treated with palbociclib after failure of an aromatase inhibitor and ribociclib due to intolerance.

Seven years after her breast cancer (BC) diagnosis, she was referred for a colonoscopy when the fecal occult blood test (FOBT) showed a positive result. She was up-to-date on her bowel screening and had regular follow-up, with all follow-up examinations negative for distant metastases and local recurrence. Colonoscopy revealed melanosis coli due to previous stimulant laxative use, but no other abnormalities or lesions were seen (Fig. 1). Random biopsies were taken, which unexpectedly revealed infiltration of the lamina propria by atypical cells (Fig. 2) positive for GATA-3, consistent with metastatic BC (Fig 3) [4]. Further computed tomography (CT) and whole-body bone scan revealed no further distant metastases. The patient decided not to continue with active treatment and was referred to the palliative care team.

Random biopsy of the ascending colon

Random biopsy of the ascending colon with immunoperoxidase-GATA3 staining

BC is divided into ductal and lobular carcinoma, with the most common type being infiltrating ductal carcinoma (IDC). Lobular carcinoma (LC) accounts for approximately 10-14% of all BC [5]. A review by Xiao et al of 295,213 patients with newly diagnosed invasive BC showed that the most common sites for distant metastases at the time of diagnosis were bone (59.9%), lung (47.8%), liver (40.9%), and brain (38.8%) [2]. Metastases to the gastrointestinal tract (GIT) are uncommon in BC, and most reported cases of GIT metastases have been seen in patients with the lobular subtype, with the ductal subtype metastasizing to the GIT less frequently [5].

McLemore’s retrospective review of 12,001 cases of metastatic BC between 1985 and 2000 identified 73 patients (0.6%) with pathologic confirmation of GIT and/or peritoneal metastasis. These were most commonly seen in the infiltrating lobular carcinoma (ILC) subtype, accounting for 44 of 73 (60%) cases [3]. Only 24 of 12,001 patients (0.2%) had colon metastases (CM). In a review of 2588 patients with BC, Montagna and colleagues found that 40 patients (1.55%) had GIT metastases, with only two having CM (0.07%) [6]. Both studies show that CM is extremely rare in BC. The average interval between the diagnosis of BC and the diagnosis of GIT metastases was seven years [3]however, they did not report the mean interval time to CM detection specifically.

Tasujimura and colleagues reported a case of a 51-year-old woman with abdominal pain due to an ascending colonic mass and stenosis found on CT followed by colonoscopy [7]. Positron emission tomography-CT (PET-CT) showed enhancement in the ascending colon, mesentery, left breast, and left axilla, and left breast biopsy confirmed ILC BC. She developed progressive abdominal pain and colonic obstruction requiring emergency open ileocecal resection, and a surgical specimen confirmed metastatic ILC in the area [7]. The patient recovered well and was discharged with continued treatment with letrozole.

Similarly, Noor and colleagues reported a case of a 68-year-old woman with ILC BC who presented with symptoms of obstruction 30 years after the initial diagnosis of BC. CT confirmed circumferential narrowing and thickening in the distal sigmoid [8]and due to her history of BC, it was decided to investigate with a colonoscopy first. Colonoscopy revealed diffuse proliferation of neoplastic cells with histochemical confirmation of metastatic BC [8]. Further endoscopic examination also revealed gastric metastases. No surgical resection was performed, she continued hormone therapy and died four years later due to disease progression [8].

A key difference between these reported cases and our current case is that our patient was asymptomatic and colonic metastases were detected through FOBT screening and random biopsies, as there were no suspicious lesions to prompt biopsy. No colonic lesions or enlarged lymph nodes were seen even on recent follow-up CT. This may be due to the tendency of ILCs to infiltrate the submucosal layer of the GIT, which may appear as thickening of the smooth intestinal wall on CT alone, mimicking physiological peristalsis [9,10]. The mucosa may appear normal during a colonoscopy, suggesting that it would be falsely negative if random biopsies were not taken [10].

This case highlights that when evaluating patients with a history of BC for a positive FOBT, especially those with the ILC subtype, surgeons should be alerted to the possibility of colonic metastases; even if no malignant lesions are found at colonoscopy, random biopsies may be useful in detecting microscopic metastases because ILC metastases infiltrate the submucosa. Careful histological examination is also necessary to correctly differentiate CM from primary colon malignancy using breast cancer specificities such as GATA-3 [3]as estrogen receptor can be positive in primary colon cancers in up to 70% of cases [11].

Correctly differentiating CM from primary colonic malignancy is essential as treatment would differ. There are no guidelines for the treatment of CM from BC, however McLemore’s review of 12,001 BC patients compared median survival in patients with GI metastases and/or carcinomatosis between palliative surgery, systemic therapy such as chemotherapy, and hormonal therapy, finding that surgery did not significant increase in overall median survival compared with systemic therapy (28 months versus 26 months) [3]. In cases where BC and CM have not yet been confirmed, as in the case reported by Tasujimura [7]bowel resection may be performed. However, in patients with more advanced disease and multiple GI metastases and/or carcinomatosis, surgery should only be considered for life-threatening complications, such as bowel obstruction with threatened perforation, as surgery has not been shown to have a survival benefit; they should be treated with systemic therapy [3].

The combination of the long interval from initial BC diagnosis to presentation and the rarity of isolated colonic metastases makes the diagnosis of colonic metastases difficult and easy to miss. In addition, ILC metastases to the GIT have been reported to infiltrate the submucosa first, which may lead to false-negative colonoscopy and CT scans in search of metastatic lesions. The surgeon should carefully consider the possibility of CM when referred as a patient with a history of ILC BC and a positive FOBT. There are no specific guidelines for managing CM from BC; however, surgical resection has not been shown to improve survival in patients with GI metastases and/or carcinomatosis over chemotherapy and hormonal therapy and should only be considered for life-threatening complications.

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