Abstract
Breast cancer is the most common malignancy in women and the main cause of cancer death in the UK. Gastrointestinal (GI) tract metastasis and carcinomatosis from primary breast cancer are rare but breast cancer is the second most common primary malignancy to metastasise to the GI tract after malignant melanoma. The metastatic patterns of invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) have been shown to differ considerably. Liver, lung and brain metastases are more common in IDC. Most series report a greater prediliction for lobular carcinoma to metastasise to the GI tract, gynaecological organs or peritoneum.
The presentation of GI metastasis due to breast cancer is typically vague and the clinical, radiological, endoscopic and histopathologic findings are often difficult to distinguish from primary gastric carcinoma. Such a patient is more likely to present to a luminal surgeon or gastroenterologist than a breast surgeon. Therefore a high index of clinical suspicion with early endoscopy in those with non-specific symptoms and a past history of breast cancer, particularly ILC, are recommended.
It is imperative to differentiate between metastatic breast cancer and primary gastric carcinoma as treatment strategies differ hugely. Therefore, correlation of endoscopic biopsy histology with the primary breast cancer histology is essential. Treatment modalities are limited to appropriate systemic therapy, which may have a palliative effect in up to 50%. Surgical intervention is nearly always limited to palliative bypass only. Prognosis is consistent with the median survival of all women with metastatic disease secondary to breast cancer.
Keywords: Breast cancer, Lobular, Metastasis
Breast cancer is the most common malignancy in women and the main cause of cancer death in the UK. Gastrointestinal (GI) tract metastasis and carcinomatosis from primary breast cancer are rare but breast cancer is the second most common primary malignancy to metastasise to the GI tract after malignant melanoma.1 The metastatic patterns of invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) have been shown to differ considerably. Liver, lung and brain metastases are more common in IDC. Most series report a greater prediliction for lobular carcinoma to metastasise to the GI tract, gynaecological organs or peritoneum.2,3
Case history
We present a 62-year old woman who was diagnosed with metastatic carcinoma of the stomach. Eight years earlier she had been treated for a grade 2 ILC that was oestrogen receptor positive with 8 of 9 axillary lymph nodes positive for metastatic disease. She underwent mastectomy and level 2 axillary clearance, followed by adjuvant chemotherapy (epirubicin/cyclophosphamide/methotrexate/fluorouracil), adjuvant chest wall and supraclavicular radiotherapy and adjuvant hormonal therapy with 5 years of tamoxifen followed by 3 years of letrozole. There was no relevant family history.
The patient had presented to the gastroenterologist with loose stools, normocytic anaemia and slight weight loss. Upper GI endoscopy showed an area of raised mucosa in the lower stomach, which was biopsied. Histology demonstrated metastatic invasive lobular cancer that was oestrogen/ progesterone receptor positive, HER2 negative, CK7 positive and CK20 negative. Computed tomography (CT) confirmed prominent gastric mucosa in the gastric body. In addition, marked wall thickening of the ascending colon raised the suspicion of further metastatic spread. Initial colonoscopy was inconclusive. Repeat colonoscopy demonstrated poorly differentiated carcinoma consistent with metastatic infiltrating cancer. The CT positron emission tomography and isotope bone scans both failed to demonstrate any definite evidence of disease recurrence.
The patient underwent six cycles of docetaxel chemotherapy and subsequently started anastrozole. A repeat CT scan of the abdomen suggested progressive disease, prompting further chemotherapy with capecitabine. Due to poor renal function, this was changed to a limited 10-week course of epirubicin. The patient is currently taking exemestane and remains asymptomatic.
Discussion
Gastric metastases have been recognised in 6% of cases of breast carcinoma and autopsy series have reported frequencies of 8% to 35%.3,4 Furthermore, GI metastases occur much more commonly with ILC than IDC of the breast.
During a study period of 15 years reported by the Mayo Clinic in 2005, 41 (0.34%) of 12,001 patients with metastatic breast cancer had pathologic confirmation of GI tract metastasis with a mean interval since diagnosis of 7 years. Of these 41 patients, 25 (61%) of the primary breast cancers were confirmed as ILC. The incidence of ILC in newly diagnosed breast cancer patients at the same institution during the same period was 1,516 (12%) of 12,550 cases, highlighting the predominance of ILC over IDC in breast cancer metastasis to the GI tract (p<0.001).5
The reasons for the differing metastatic patterns between ILC and IDC are poorly understood. The loss of expression of E-cadherin in ILC, a molecule responsible for cell-to-cell adhesion, is one possible explanation.6 ILC differs from IDC in its histology and mammographic appearance as well as the pattern of metastatic spread. In ILC, malignant cells tend to surround the mammary ducts and lobules in single file, often creating a targetoid appearance, without forming glandular aggregates.7 This difference in histological behaviour may contribute to an alternative pattern of metastasis.8
The diagnosis of GI metastases secondary to breast cancer can be difficult for several reasons. These include a potentially long disease-free interval, diverse and non-specific symptoms at presentation, challenging histopathology and the relative unlikelihood compared to another diagnosis.4 Diagnosis requires a high index of clinical suspicion. Most reported cases of gastric metastases from ILC have been observed in patients with disseminated disease.3 Isolated intestinal obstruction due to metastases without disseminated disease is very unusual.
Accurate histopathological diagnosis is critical as the treatment options for primary gastric carcinoma and metastatic ILC are vastly different and comparison with the primary breast carcinoma specimen is essential.
Endoscopic biopsy findings are normal in up to 50% of patients, perhaps because tumour growth is likely to be submucosal and focal. Endoscopic biopsies from metastatic IDC are more likely to be positive (90%) than those from ILC (64%).9
The radiological appearances on ultrasound and CT of linitis plastica due to metastatic breast carcinoma are quite similar to those of primary gastric carcinoma.3,9
Evidence regarding treatment outcomes is lacking. Gastrectomy would be considered for primary gastric carcinoma whereas systemic therapy would be indicated for metastatic ILC. Most patients are treated with systemic chemotherapy or hormonal therapy. Few receive radiotherapy and surgical palliation is reserved for those with obstruction or mass effect.
Summary
GI tract metastases and carcinomatosis from primary breast carcinoma are rare but are more common in the case of ILC than IDC. The presentation of GI metastasis due to breast cancer is typically vague and difficult to distinguish from primary gastric carcinoma. Patients are more likely to present to a luminal surgeon or gastroenterologist than a breast surgeon and a high index of clinical suspicion is required in those with non-specific symptoms and a past history of breast cancer, particularly ILC. Early endoscopy, possibly repeated with further biopsies, is recommended.
It is imperative to differentiate between metastatic breast cancer and primary gastric carcinoma as treatment strategies differ hugely. Treatment is likely to be palliative only and prognosis is consistent with the median survival of all women with metastatic disease secondary to breast cancer (24–36 months).3,10
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