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Page 8 of 18                        D'Angelo et al. J Cancer Metastasis Treat 2019;5:30  I  http://dx.doi.org/10.20517/2394-4722.2018.86

               gastric metastasis is very variable, and ranges from few months to many years (20 years vs. 30 years), and
               that median disease free survival is 5 years.


               Symptoms related to gastric metastasis are reported in both studies as non specific, such as epigastric or
               abdominal pain, nausea or vomiting, dysphagia, dyspepsia, anorexia, weight loss, and bleeding that may
               manifest as hematemesis, or melena or anemia. Interestingly, in five patients [24,37,49]  of case reports there were
               no symptoms and diagnosis of gastric metastasis was based on other signs, such as elevated serum markers
               or incidental findings at instrumental routine follow up.


               Regarding endoscopic findings, the principal pattern is linitis plastica in both studies; reviews say that in
               30%-50% of cases endoscopic findings are negative, but this aspect is not present in the majority of case
               reports.

               The most common histological pattern found in gastric metastasis is adenocarcinoma with signet ring
               cells; this pattern can be confused with primary gastric cancer, as said in the reviews; indeed in three
               case reports [37-39]  preoperative findings showed this pattern on gastric biopsies and surgical treatment was
               performed.

               Immunohistochemistry is mainly based on expression of ER and PgR. They are reported as positive in
               reviews, and, in the case reports, 50 (91%) tumors had ER positive and 28 (61%) had PgR positive; other
               receptors are HER2 and E-cadherin, whose absence is related to lobular cancer (negative in reviews, in case
               reports 25 (70%) tumor had HER2- and 5 (63%) had E-cadherin-); positivity for CK7, GCDFP-15 and MGB
               and absence of CK20 and CDX2 are also related to breast cancer origin. Systemic therapy is the treatment
               of choice in the reviews and even in case reports (used in 41 patients). Surgery is usually performed in
               case of complications such as perforation or bleeding; in three cases patients were submitted to emergency
                                                                  [42]
                             [28]
               laparotomy, two  for perforation and septic shock and one  for bleeding and hemorrhagic shock. Main
                                                                                          [41]
               surgical intervention is gastrectomy (performed in 13 patients), whereas in one patient  only raffia and
               biopsy were performed in the setting of a perforation. Bypass, that is considered the best option according
               to reviews, was not even considered in case reports. Indeed obstruction can be managed conservatively by
               endoscopic stenting as mentioned in reviews, and this was performed in two patients [19,22] . No embolization
               was performed in case reports. Median overall survival is similar (about 2 years) in the two summaries.
               Unfortunately reviews didn’t subdivide OS by type of treatment.


               DISCUSSION
               Breast cancer is the most common malignancy in women and the leading cause of cancer-related death in
               female gender. Global incidence increased about 3.1% every year in the past 30 years, with an increase of the
               number of cases in Middle East, south Asia, southeast Asia, and central Latin America, and also mortality
                                             [1]
               increased at an annual rate of 1.8% . Malignant proliferation may arise from ductal or lobular ephitelium:
               the most frequent is the ductal type that includes 75%-82% of all cases [4,52,53] . Other less frequent types are
               lobular carcinoma (4%-10% of all cases), phylloides, or tubular cancer.

               Metastases are possible either in ductal and lobular carcinoma, but they may develop in different organs:
               ductal carcinoma metastatizes more frequently to the lung, the brain and the liver, whereas lobular cancer
                                                                                                 [2,3]
               tends to metastatize to the gastrointestinal (GI) tract, gynecologic organs, peritoneum and bones . Breast
               cancer, melanoma and lung cancer, represent the most frequent malignancies metastatizing to GI tract [15,16,53] :
               the common sites of GI metastasis from breast tumor are colon and rectum (45%), stomach (28%), small
                                              [53]
               intestine (19%), and esophagus (8%) . Median overall survival of patients with gastric metastasis ranges
                                 [53]
               from 24 to 36 months .
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