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Page 6 of 18 D'Angelo et al. J Cancer Metastasis Treat 2019;5:30 I http://dx.doi.org/10.20517/2394-4722.2018.86

also show positivity for other receptors, such as CK7, CK18, GCDFP-15 and CEA, which are reported in five
articles, and they are negative for CK20 and CDX2,which are usually expressed in intestinal cells, and also
negative for E-cadherin and HER2, indicating a probable lobular breast cancer origin.

Therapy/Surgery/Palliation
Ten articles reported that the main therapy for gastric metastasis from breast origin is systemic therapy,
either chemotherapy or hormonal therapy; surgery is reserved only in case of complications or emergency,
such as bleeding, perforation or obstruction. In this latter case, a more conservative approach is advised
and three articles suggest to perform a simple bypass instead of a gastrectomy. Endoscopy can prove very
useful and must be considered before surgical approach in case of obstruction and bleeding to put stents
or to perform dilatation; also bleeding can be managed conservatively either with endoscopic hemostatic
procedures or by embolization radiologists.

Survival
Only two articles mentioned overall survival and they are approximately concordant, with Jones reporting a
survival of 28 months, and Aurello reporting 2 years.

Part 2. Case reports
We also performed a review of the literature focusing on case reports of gastric metastasis from breast cancer
from January 1st 2013 to October 31st 2018 because we wanted to update the aforementioned reviews with
the latest current clinical practice present worldwide. We found 36 reports for a total of 69 patients. Data
were not reported entirely in all the case reports, so we analyzed and compared only mentioned data. All the
[43]
patients were females except one male . The median age of the patients was 58 years, with a range from 33
to 86 years. For the case reports that reported the age of the patients, 34 (59%) patients were > 55 years old,
whereas 14 (41%) were < 55 years.

Breast tumor/receptor
The most common histological type of breast cancer was ILC (invasive lobular cancer), that was found in 42
cases (63%); other histological type of breast tumor were IDC (invasive ductal cancer) in 16 (24%), mixed in
[30]
2 (4%), and tubular in 6 cases (9%). In one case breast tumor was not found at instrumental research after
the diagnosis of gastric metastasis. Breast cancer tumor had ER positive in 34 (92%) cases and negative in
3 (8%); PgR was positive in 29 (80%) and negative in 7 (20%), and HER2 was negative in 21 (75%) cases and
positive in 7 (25%). The most common receptor status is ER+/PgR+/HER2-.

Disease free survival
Usually gastric metastases from breast tumor occur several years after primary cancer; 54 (83%) patients had
metachronous disease, whereas only 10 (17%) had synchronous tumors.

Time of presentation of gastric metastasis from primary breast cancer varies from 0.5 months to 20 years
later, with a median time of 61 months (about 5 years). This explains the difficulty to reconduct the gastric
disease to breast tumor, because in many cases there was a long time between the manifestations of the two
disease.

Symptoms
Gastric metastasis mostly presented with non specific symptoms in 45 cases, such as epigastric pain (28),
nausea and/or vomiting (14), dyspepsia (3), dysphagia (3), anorexia (5), weight loss (12), hematemesis or
melena (13), anemia (3). Five patients [24,37,49] were totally asymptomatic, and diagnosis of gastric metastasis
[37]
in these cases was incidental during exams in follow up. In one case elevated CEA and CA15-3 rose
suspiciously for metastasis and then PET scan confirmed gastric localization.