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Page 14 of 18 D'Angelo et al. J Cancer Metastasis Treat 2019;5:30 I http://dx.doi.org/10.20517/2394-4722.2018.86
[12]
in patients with low performance status . The surgical option must be as little invasive as possible, for
[15]
example a palliative bypass can be considered in case of outlet obstruction .

[53]
Many studies, such as the one conducted by McLemore et al. , 2005 report a lack of survival benefit from
surgical treatment; palliative surgery can be associated with a prolonged median survival in some cases, but
other factors can affect this difference such as biased patient selection for surgical palliation. In literature,
few studies show surgical resection in patients with unique localization with reported improvement in
[4]
overall survival: the study published by Taal et al. , 2000 patients with complete remission of primary breast
cancer that underwent gastric resection for solitary gastric metastasis shows a survival time of 38 months
[3]
to be compared with 14.38 months for patients who didn’t undergo resection . This can be explained
considering that for patients submitted to surgical treatment the stomach is the unique localization without
other metastasis or peritoneal carcinomatosis. In these patients the disease is not as advanced as in those
candidates for systemic therapy. Therefore enhanced survival is due to patient clinical conditions and not
strictly related to the type of treatment. In general, surgery does not offer an increase in survival but may
[53]
have role in palliation . In our study surgery was also used to perform final diagnosis; gastric biopsies were
confounding, thus authors performed gastrectomy to rule out the origin of the gastric disease [23,28,29,35,37-39,43,45] .

CDH1 mutation
As mentioned before, E-cadherin is a transmembrane glycoprotein involved in calcium-dependent
adhesion; when E-cadherin is mutated, this leads to loss of cell adhesion, cell migration and subsequently
[86]
tumorigenesis . An important gene mutation that is both associated with breast cancer and gastric cancer
is CDH1, that encodes E-cadherin. Families with CDH1 mutations have a cumulative risk of developing
hereditary diffuse gastric cancer (HDGC) of 70% and 56% in males and females, whereas female members
[87]
have a cumulative risk of 42% for lobular breast cancer by age 80 . Other gene mutations related to breast
cancer but not to gastric cancer are BRCA1, BRCA2, and TP53; both BRCA1 and TP53 are associated with
invasive ductal carcinoma, BRCA2 with both ductal and lobular carcinoma while CDH1 is only associated
[88]
with lobular breast carcinoma . CDH1 is a gene mutation that is mutually exclusive with BRCA1/2
germline mutations. Screening for CDH1 should be suggested to women who have a personal or a family
history of a combination of diffuse gastric cancer and lobular breast cancer (with at least one diagnosed
before the age of 50), bilateral lobular carcinoma diagnosed at a young age, or family history of multiple
[89]
lobular carcinomas with onset before 50 years old without gastric tumour . Sometimes diagnosis of lobular
breast cancer with early onset might be the first manifestation of HDGC; so in patients with a history of
multiple LBCs at a young age, especially with bilateral manifestation, it’s advisable to perform a test for gene
[90]
mutations . When CDH1 mutation is diagnosed, therapeutic management for the stomach and the breast
is quite different: usually prophylactic total gastrectomy is advised because of the high risk of DGC, whereas
prophylactic mastectomy is not performed, considering various genetic penetrance for LBC, but female
[86]
patients should undergo to yearly mammography and breast MRI from age 35 years onwards .

[3,4]
In conclusion, gastric metastases are a rare but not unusual site of secondarism from breast cancer . They
[5,6]
usually arise several years after diagnosis of primary tumor and sometimes this can mislead the diagnosis .
The differential diagnosis between primary gastric cancer and gastric metastasis is crucial and made possible
only by histology and immunohistological patterns. Systemic therapy is the treatment of choice because the
disease is usually not only localized to the stomach but presents other concurrent metastases [5,15,84] . Surgery
still has a role in case of complications or for definitive diagnosis when preoperative biopsy is not diriment
[85]
and there is still a suspicion for primary gastric cancer , even though this latter case is progressively
decreasing thanks to innovation in instrumental tools for diagnosis. Breast metastasis to the stomach should
be considered in any patient suspected of gastric cancer previously treated for breast carcinoma, especially if
the treated carcinoma was ILC.