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D'Angelo et al. J Cancer Metastasis Treat 2019;5:30 I http://dx.doi.org/10.20517/2394-4722.2018.86 Page 7 of 18

Endoscopy
At endoscopy the most common presentation was linitis plastica, present in 21 cases (37%), whereas ulcers
were found in 16 cases (28%). In three of these latter cases [27,28,41] the first presentation was perforation, which
resulted in elevated morbidity and mortality. Polips or nodules were present in 4 patients (7%).

Gastric tumor/receptor
Histological study of gastric metastasis showed in the majority of cases adenocarcinoma with signet ring
cells. In six (9%) patients initial gastric biopsies suspected a primary gastric cancer so they were submitted to
surgical treatment; only after histological study of the specimen it was clear that they were metastases from
breast cancer and not primary tumor of the stomach.

Immunohistotype is essential to diagnose and differentiate primary gastric cancer from metastatic tumor;
the mainly studied receptors were ER, that was positive in 50 (91%) cases and negative in 5 (9%); PgR, positive
in 28 (61%) cases, and negative in 18 (39%); HER2 negative in 25 (70%) and positive in 11 (30%); CK7 positive
in 21 (91%) and negative in 2 (9%) cases; CK20 negative in 20 (95%) and positive in only 1 case (5%); CDX2
negative in 7 cases (100%); GCDFP-15 positive in 9 (75%) and negative in 3 cases (25%); GATA-3 positive in
4 cases, Mammoglobine positive in 6 cases (86%) and negative in 1 (14%); E-cadherin positive in 3 (37%) and
negative in 5 cases (63%).

In 45 cases immunohystological study of the biopsies from gastric lesions or gastric wall were taken before
starting any treatment; considering patients who underwent gastrectomy, nine [23,26,27,28,35,42,43,45] were taken
after surgical treatment whereas three [23,28,43] were done before, but authors decided to perform surgery
because they suspected primary gastric cancer or they couldn’t exclude it.

In two patients [22,43] immunohistological pattern of gastric metastasis was different from the one of primary
[40]
breast cancer; in one patient pattern changed during treatment history, passing to a luminal A type and
then to a triple negative.

Other metastasis
Gastric metastasis is usually part of a systemic disease and presents with other localization of malignant
cells; considering all case reports, 56 patients (81%) presented with other metastases at time of diagnosis.

Therapy
The preferred treatment is systemic therapy, as chemotherapy, endocrine therapy or a combination of both
of them; 41 of the patients were subjected to chemotherapy with or without hormonal therapy. Combination
of surgery and chemotherapy was used in 10 patients [23,28,29,35,37-39,41,43,45] ; two of them [28,29] were submitted to
neoadjuvant chemotherapy followed by surgery in the belief of a primary gastric cancer. Surgical treatment
alone was chosen in 7 [26,27,42] patients, with three [27,42] of them in an emergency setting for bleeding and
perforation. Endoscopic stenting for obstruction was used successfully in 2 patients [19,22] .

Survival
Median overall survival was 24 months, in line with data given by current literature. In some papers survival
at follow up was the only data cited, and the media of these data was 28 months. Patients submitted to
chemotherapy had an OS of 23 months; patients subjected to surgical treatment alone had an OS of 45 months.
Those subjected to surgery plus chemotherapy had an OS of 91 months. We must consider the fact that for
this latter group only two patients were considered and that they had stomach as the only site of metastasis.
However, due to the paucity of number of cases considered, this data can be misleading.

Part 3. Comparison between reviews and case reports
The final results from the review and the case reports show that the breast cancer that is responsible for most
of the metastasis is the lobular type (83% vs. 63%). Both summaries report that the time of presentation of