Both of the patients in this report were initially diagnosed with an apparent primary gastric cancer. Ultimately this diagnosis was revised to metastatic breast cancer, but only after surgery had been performed in patient 1. The incidence of breast cancer metastasis to the stomach in long term follow up and post mortem studies has been estimated at 2–18% [3
]. This may occur many years after the diagnosis of the primary breast lesion and, in 90 – 94% of patients, there will be concurrent sites of breast cancer metastasis [6
]. Patient 2 had been treated for recurrent breast cancer prior to her presentation with a gastric tumour.
The clinical presentation of a breast cancer metastasis to the stomach is often indistinguishable from primary gastric cancer, as seen in the two patients in this report. Common symptoms include dyspepsia, anorexia, epigastric pain, early satiety, vomiting and bleeding. The most common pattern of breast cancer metastasis to the stomach is a linitis plastica with diffuse infiltration of the submucosa and muscularis propria; less commonly, discrete nodules or external compression may occur [7
]. Madeya and Borsch reported that 73% of patients with gastric metastases had diffuse intramural infiltration imitating linitis plastica [12
]. Diffuse infiltration of the stomach is characteristic of metastases from invasive lobular carcinoma: Taal et al reported that 83% of patients with gastric metastasis had lobular breast carcinoma as the primary pathology [6
]. Patient 1 had a linitis plastica type pattern whereas patient 2 had a discrete proximal gastric lesion.
A high index of suspicion for metastatic breast cancer should be maintained when a patient develops gastric pathology with a history of breast cancer. Endoscopic, radiological and histological evaluation is essential to discriminate between primary gastric cancer and breast cancer metastasis to the stomach. Macroscopic endoscopic findings are usually unhelpful in identifying the underlying pathology. Since metastatic gastric infiltration is frequently limited to the submucosa and seromuscular layer, endoscopic evaluation may be normal in 50% of cases or only show discrete mucosal abnormalities indistinguishable from other tumours or benign disease [13
]. Radiological findings on computed tomography or barium studies include encasement of the whole stomach as seen in linitis plastica, multiple lesions of the stomach or extrinsic lesions of the gastric wall [4
]. Deep and extensive biopsies should be performed at endoscopy. Their histology should be compared with the primary breast cancer pathology as the histologic picture may be similar. However, lobular carcinoma of the breast may produce a signet ring morphology which can be confused with a primary signet ring or diffuse-type gastric adenocarcinoma [7
]. Both of the patients in this study had been previously treated for lobular breast cancer.
Detailed immunohistochemical analysis may be the only consistent method for differentiating between metastatic and primary gastric carcinoma. Although oestrogen and progesterone receptor positivity in the gastric biopsies suggest breast cancer metastasis to the stomach, it is worth noting that oestrogen and progesterone receptor positivity have been reported in 32% and 12% of patients with primary gastric cancer [14
]. However, these findings are based upon studies using first-generation antibodies against Oestrogen receptor β (ERβ) which are no longer used in standard practice. Taal et al investigated whether immunohistochemical detection with second-generation antibodies against Oestrogen receptor α (ERα) can be used to diagnose gastric metastasis of breast carcinoma [15
]. In their study none of the primary gastric carcinomas expressed ERα. Moreover, no cases with an ER- primary breast carcinoma and an ERα+ carcinoma in a gastric biopsy specimen were found. Therefore they concluded that ERα expression can be reliably used to diagnose gastric metastasis of breast carcinoma. They also investigated if the expression pattern of E-cadherin could be of help in the differential diagnosis of primary gastric cancer versus metastatic breast carcinoma. In their study absence of E-cadherin staining was significantly related to metastatic breast carcinoma. It appears that the absence of E-cadherin expression in an adenocarcinoma in a gastric biopsy should raise the possibility of metastatic breast carcinoma and ERα positivity can be reliably used to diagnose gastric metastasis of breast carcinoma.
The absence of positive oestrogen and progesterone receptors in patient 1's gastric biopsies led to the initial assumption that this was a primary gastric cancer. Positive monoclonal staining with GCDFP-15 (gross cystic disease fluid protein-15) has been found to be a sensitive (55–76%) and specific (95–100%) marker to correctly identify a malignant lesion as metastatic breast carcinoma [5
]. This marker is a monoclonal antibody of gross cystic disease fluid protein-15 (GCDFP-15) which is detected in macroscopic breast cyst fluid and in the plasma of patients with breast cancer [22
]. There is an excellent correlation between GCDFP-15 positivity and the origin of a metastatic breast adenocarcinoma [17
]. Wick demonstrated reactivity for GCDFP-15 in 76 of 105 breast carcinomas (72%) [16
]. The diagnosis of metastatic breast cancer in patient 1 was eventually confirmed on the basis of GCDFP immunohistochemistry.
In common with other sites of metastatic breast cancer, breast cancer metastasis to the stomach should be treated systemically [7
]. The choice of systemic treatment is based upon presenting symptoms, age, general performance status, receptor status and previous systemic treatments. The response rate to chemotherapy and hormonal therapy varies: the median survival in two small series of patients receiving systemic treatment for breast cancer metastasis to the stomach and gastrointestinal tract varied between 10 and 28 months [6
]. In a series of 51 patients with gastric metastases from the breast, hormonal therapy (27%) was performed almost as frequently as chemotherapy (33%) [7
]. The options for hormonal therapy included tamoxifen, oophorectomy or progesterone as first-line treatment, and aminogluthetimide, androgens or prednisolone as second line treatment. New anti-hormonal drugs also include aromatase inhibitors and GNRH analogues in pre-menopausal patients. Although combination cyclophosphamide, methotrexate and 5-fluorouracil (CMF) tends not to be used in the metastatic setting, new anti-neoplastic drugs are now available and include taxanes, capecitabine and trastzumab if c-erbB2 is positive.
One study has shown that a partial remission with a clear palliative effect can be obtained in only 46% of patients receiving systemic therapy with no obvious difference in response rates between hormonal treatment and chemotherapy. It is worth noting that symptomatic treatments alone such as acid reduction could only be performed in 20% of the patients in this study due to their poor general condition or extensive prior treatment [7
]. McLemore et al reported a median overall survival after diagnosis of 28 months in 73 patients with breast cancer metastasis to the gastrointestinal tract [24
]: whilst advanced age at diagnosis and gastric metastasis had a negative effect on survival, treatment with systemic chemotherapy or tamoxifen had a positive effect on survival. It is worth noting that there is a low response rate to chemotherapy in invasive lobular carcinoma patients which must be must taken into consideration when choosing the most appropriate treatment [25
The complications of breast cancer metastasis to the stomach can be managed in a similar manner to primary gastric cancer: endoluminal stents can be used for gastric outlet obstruction; bleeding may be controlled by endoscopic or endovascular therapy [26
]. Although surgical resection has been considered in selected patients, the role of surgery is usually limited as the gastric metastasis reflects systemic disease [6
]. Palliative surgery has not been shown to affect overall survival [24
]. Surgery should be limited to palliative bypass in those patients where less invasive measures fail to palliate their gastric outlet obstruction.