Bilateral Breast and Ovarian Metastases of Signet-ring Cell Gastric Cancer: A Case Report and Literature Review

Bilateral Breast and Ovarian Metastases of Signet-ring Cell Gastric Cancer: A Case Report and Literature Review | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Bilateral Breast and Ovarian Metastases of Signet-ring Cell Gastric Cancer: A Case Report and Literature Review Qiang Li, Zhengwei Zhang, Ziyu Feng, Wan Wei, Jianhua Shi This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1886166/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Breast cancer metastasis accounts for only 0.4–2% of all breast cancer cases. Gastric cancer with breast metastases is extremely rare, while mammary and ovarian metastases from the stomach are even more uncommon. Breast metastases might be mistaken for primary cancer due to their uncommon and generic clinical and radiological symptoms, leading to ineffective and debilitating therapy. Case Presentation: We present a 43-year-old woman with bilateral multiple metastases from stomach signet-ring cell carcinoma to the breast and ovary, which is the seventh case to our knowledge. Conclusion We highlight the epidemiological, diagnostic, therapeutic, and prognostic aspects of this extremely rare disease through our case, which are critical to understand in order to avoid diagnostic errors and subsequent incorrect care. breast metastases ovarian metastases diagnosis signet-ring cell gastric cancer core needle biopsy case report Figures Figure 1 Figure 2 Figure 3 Introduction Metastatic breast cancer is rare, accounting for only 0.4 to 2% of all breast cancers [ 1 ]. Most cases involve females, with approximately 5–8% of cases involving males [ 2 , 3 ]. Extramammary breast metastases are more common in patients with hematological and cutaneous melanoma [ 4 ]. However, the lung, ovary, cervix, prostate, kidney, gastrointestinal system, liver, and head and neck regions are other possible initial tumor sites [ 1 , 2 , 4 – 7 ]. There were 73 cases of gastric cancer with breast metastasis published online up until June 2022, including 17 cases with breast and ovarian metastases and only 6 cases with bilateral breast and ovarian metastasis (Table 1 ). Reitmann et al . [ 8 ] reported one of the first cases of stomach cancer with breast metastases in 1908. Signet-ring cell histology, antral tumor location, and lymph node involvement are all standard in gastric cancer patients with breast metastases [ 4 , 9 – 13 ]. Because the symptoms of primary breast cancer and metastases are similar, distinguishing between the two is critical for determining the best treatment option. Table 1 Clinical characteristics of cases with bilateral breast matastases and ovary metastasis of GC Case Age (years) Histology Presentation Interval * (months) Other metastases Follow-up (months) IHC Country Localization Prognosis Dawson 1936[ 1 ] 25 Mucinous N/A N/A Ovaries N/A N/A Scotland Bilateral N/A Di Cosimo 2003[ 2 ] 39 Signet-ring cell Nodules 1 Ovaries, peritoneum, skin N/A N/A Italy Bilateral N/A Doval 2009[ 3 ] 34 Signet-ring cell Palpable masse N/A Ovaries 8 GCDFP-15-ER-,PR-,HER2-, CA125- India Bilateral Died Byun 2009[ 4 ] 45 Signet-ring cell Palpable masse N/A Left ovarian N/A ER-, PR-, HER2- South Korea Bilateral N/A Iesato2014[ 5 ] 41 Signet-ring cell Inflammatory N/A Ovaries 9 p53+, MUC 5AC+, HIK1083+ Japan Bilateral Died Jayi 2013[ 6 ] 32 Adenocarcinoma Nodules Concomitant Ovaries N/A CK+, CD20-, ER-,PR-,HER2- Morocco Bilateral N/A Present case 2022 41 Signet-ring cell Nodules 36 Ovaries 5 CDX-2+, HER2-, ER-, PR-, CK7+, E-cad+, MUC 5AC+ China Bilateral, multifocal Alive *The interval from the discovery of GC to the discovery of breast metastases. N/A, not available; IHC, immunohistochemistry; ER, oestrogen receptor; PR, progesterone receptor; HER2, human epidermal growth factor receptor 2 protein; CK, cytokeratin; MUC 5AC, recombinant mucin 5 subtype AC; GCDFP-15, gross cystic fluid protein 15; CDX-2, caudal-type homeobox 2; E-cad, epithelial cadherin. 1. Tachibana S, Asano M, Miya K, Hino T, Furuichi N, Misawa K. A case report of gastric cancer with breast metastasis (Jpn). J Clin Surg 1986; 41:1719–1722. 2. Di Cosimo S, Ferretti G, Fazio N, Mandalà M, Curigliano G, Bosari S, et al. Breast and ovarian metastatic localization of signet-ring cell gastric carcinoma. Annals of oncology : official journal of the European Society for Medical Oncology. 2003; 14(5):803-4. 3. Doval DC, Pande SB, Sharma JB, Khatri S, Khurana AK, Vaid AK, et al. Metastatic Signet-Ring Cell Gastric Carcinoma Masquerading as Breast Primary. Case reports in gastroenterology. 2009; 3(1):21 − 5. 4. Byun KD, Hur CY, Kim KH, Park JI, Kim KH, Kim TH, Choi CS, Choi YK. Breast and ovarian metastasis of signet-ring cell gastric cancer. Korean J Clin Oncol 2009; 5:31–35. 5. Iesato A, Oba T, Ono M, Hanamura T, Watanabe T, Ito T, et al. Breast metastases of gastric signet-ring cell carcinoma: a report of two cases and review of the literature. OncoTargets and therapy. 2015; 8:91 − 7. 6. Jayi S, Fatemi H, Laabadi K, Bouguern H, Chaara H, Laamarti A, et al. [Breast metastases of gastric adenocarcinoma associated with a pregnancy of 32 weeks of gestation: about a rare case]. The Pan African medical journal. 2013; 15:116. Case Presentation Gastroscopy revealed gastric cancer in a 41-year-old female with epigastric discomfort (Fig. 1 A). Complete gastrectomy and D2 lymph node dissection followed the procedure. Postoperative pathology showed gastric signet-ring cell carcinoma (Fig. 2 A,B). The cancer tissue invaded the gastric wall submucosa, the upper and lower incision borders and the intestinal wall, but the omentum did not show cancer tissue invasion; however, metastases was found in the lower curvature lymph nodes (14/16) and no metastases was found in the higher curvature lymph nodes (0/4). Immunohistochemistry (IHC) revealed the presence of CK20 (local +), CK18 (+), Villin (+), CDX-2 (weak +), HER-2 (human epidermal growth factor receptor-2, -), and Ki-67 (10%) (Fig. 3 A,B,C). The patient denied a family history of gastric cancer. The patient was then given eight cycles of SOX regimen chemotherapy with mild side effects (S-1 80 mg/m 2 , oxaliplatin 100 mg/m 2 ). Ultrasonography (US) and abdominal computed tomography (CT) showed multiple metastatic lesions in the bilateral pelvis three years later. The patient had stomach cancer that had spread to her pelvis (Fig. 1 B,C,D). Bilateral upper ovary arteriovenous ligation and bilateral adnexectomy were performed. On postoperative pathology, the Krukenberg tumor of the ovary was identified as a poorly differentiated ovarian adenocarcinoma, partly signet-ring cell carcinoma (Fig. 2 C,D). IHC showed CDX-2 (3+), HER-2 (-), Ki-67 (20%), ER (estrogen receptor, -), PR (progesterone receptor, -), CK7 (3+), and CK20 (2+) (Fig. 3 D,E,F). The right breast tumor was punctured after multiple breast tumors on both sides were diagnosed simultaneously (Fig. 1 E,F,G). Pathological findings included signet-ring cells, suggesting metastatic adenocarcinoma (Fig. 2 E,F). CDX-2(3+), Her-2(-), Ki-67 (60%), ER(-), PR(-), CK7(3+), CK20(-), and E-cad (3+) were all detected by IHC (Fig. 3 G,H,I,J,K,L). The patient then received TX regimen chemotherapy for six cycles (docetaxel 60 mg/m 2 d1 + capecitabine 825 mg/m 2 bid d1-14) with mild chemotherapy side effects. Imaging evaluation during treatment showed her condition to be stable. The patient underwent a double mastectomy, and postoperative pathology showed that some cells showed a signet-ring appearance. Poorly differentiated adenocarcinoma of gastric cancer accompanied by breast metastasis was considered in both breasts, and tumor emboli were observed in the vessels. The patient's serum tumor markers CEA, CA153, CA125, and CA199 were not elevated throughout the course of the disease. Breast metastasis postoperative IHC results were comparable with those of the biopsy. According to the American Joint Committee on Cancer tumor-node-metastasis (AJCC/TNM) cancer staging system for gastric cancer, the pathological staging of this case was pT1bN3aM1. During the five months of follow-up, there was no further illness progression. The patient and her family were delighted with the course of treatment. The treatment timeline of the patient is depicted in Supplementary Fig. 1. Discussion We summarized and analyzed the clinicopathological features of 74 cases, including the present case (Table 2 ). These patients were between the ages of 22 and 72 (mean 45.02 years). The breast is a hormone-dependent organ, and fluctuations in hormone levels in women undergoing high reproductive activity [ 14 ] may explain this type of breast injury, as they did in the 43-year-old patient in our study. Furthermore, due to hormone-related factors, the biological activity of stomach cancer appears to be more aggressive in younger age patients [ 15 ]. Hormone levels in the ovaries and the mammary glands are linked to metastases and invasiveness [ 14 ]. At the same time, some pregnant patients were reported to develop metastases, confirming its link to hormones [ 16 ]. Table 2 Clinical characteristics of cases with breast metastasis of GC Characteristic Number (%) Mean ± SD or Median[Quartile] Age(years) 74(100) 45.02 ± 1.65 Gender male 2(2.70) female 60(81.08) N/A 12(16.22) Histology Scirhous 2(2.70) Mucinous 5(6.76) Anaplastic 1(1.35) Signet-ring cell 45(60.81) Adenocarcinoma 10(13.51) N/A 11(14.86) Interval(months) * premonitory sign of GC 0 synchronous sign of GC 20(27.03) delayed sign of GC 27(36.49) 12.00[4.00,31.50] N/A 27(36.49) Combined metastasis Y 47(63.51) Ovary 19(25.68) Other metastases 28(37.84) N 2(2.70) N/A 25(33.78) Site of BM L 26(35.14) R 12(16.22) Bilateral 15(20.27) N/A 21(28.38) Outcome(months) Without progression 8(10.81) 8.50[4.25,12.25] With progression 32(43.24) 6.00[2.00,9.00] N/A 34(45.95) XELOX (capecitabineþ oxaliplatin) According to the previously published cases, bilateral breast metastases made up 20.27% (15/74) of all cases, although only 9.46% (7/74) of those individuals also had ovarian metastases. Multifocal and bilateral forms of breast metastases are uncommon and can be mistaken as primary breast cancer clinically and radiologically. This palpable tumor usually occurs in the upper lateral quadrant of the breast. Typically, there are no skin or breast abnormalities. However, there have been reports of inflammatory breast cancer that present with edema and skin redness, as well as axillary lymph node metastases in more than 15% of cases [ 17 ]. This case must be distinguished histologically from primary signet-ring cell carcinoma of the breast with gastrointestinal metastases. Signet-ring cell carcinoma can either be lobular or ductal. Metastatic breast tumors must be identified to avoid unnecessary and disabling surgery, and misidentification can result in the initial tumor being ignored. The absence of lobular carcinoma in situ or initial intraductal tumor of the breast characterizes secondary breast cancer, and the tumor type is the same as the primary lesion type. After the core needle biopsy (CNB) of the breast lesions, the characteristics of signed-ring cells were observed in this case. Breast metastases were suspected because of the history of stomach cancer, which was verified by IHC. Preoperative CNB and IHC of breast lesions were particularly helpful in this case. Secondary signet-ring cell cancer of the breast is MUC-5AC positive and CK7 positive, whereas primary signet-ring cell carcinoma of the breast is estrogen receptor-positive [ 18 , 19 ]. CK20 negativity, estrogen receptor negativity, progesterone receptor negativity, HER-2 negativity, MUC-5AC positivity, and CK7 positivity distinguish primary from secondary signet-ring cell cancer of the breast in this case. A recent study suggested that GATA3 and PAX8 could be helpful as breast cancer biomarkers [ 20 , 21 ]. The current findings indicate that no single marker is particular and that its expression varies between primary and metastatic lesions, particularly in tissue biopsies [ 22 ]. Local tumor surgery and radiation therapy are not appropriate treatments for gastrogenic breast metastases [ 23 ]. The treatment should be surgical control of the local tumor combined with systemic therapy. Breast cancer metastasis from primary gastrointestinal tumors, especially gastric cancer, has a poor prognosis, with approximately 80% of patients dying one year after diagnosis [ 24 , 25 ]. The median survival for metastatic breast cancer was 8.6 months, according to Ma et al .’s study [ 9 ] on the clinicopathological characteristics and prognosis of 54 patients with gastric cancer with breast metastases (3 new cases and 51 from prior studies). The most frequent patient characteristics were age greater than 43 years, pathological type of signet-ring cell carcinoma, lymph node involvement, and early lesions in the stomach antrum. As shown in the literature, signet-ring cell carcinoma is the most common pathological type, with a maximum survival of 22 months (Table 2 ). It is interesting that signet-ring tumor cells in our patient developed in endocrine target organs. The occurrence of breast and ovarian metastases may be associated with the hormonal milieu in premenopausal patients and to the stomach cancer histotype. In reality, young women's natural physiological and hormonal milieu may impact the development of stomach cancer in specific individuals [ 14 ]. Recent studies have suggested that the action of estrogen in gastric cancer may be mediated by ER-β, notably in signet-ring cell carcinoma [ 26 , 27 ]. Based on Krukenberg's initial criteria and the possible stromal origin of signet-ring cells in the ovary, it is also believed that luteinizing hormone is involved in stromal luteinization in Krukenberg tumors. Last but not least, we believe that accurate characterization of the underlying tumor is crucial for effective treatment, notwithstanding the rarity of signet-ring cell gastric cancer metastases to the breast and ovaries. Conclusion From a clinical and radiological perspective, preoperative CNB and IHC of breast lesions can help compensate for the lack of differentiation between primary and secondary breast cancer. As a result, a comprehensive judgment must be made based on various factors, such as physical examination, imaging examination, pathological diagnosis, and tumor indicators. Abbreviations CNB: core needle biopsy; IHC: immunohistochemistry; ER: estrogen receptor; PR: progesterone receptor; HER-2: human epidermal growth factor receptor-2; AJCC: American Joint Committee on Cancer; TNM: tumor-node-metastasis; US: ultrasonography; CT: computed tomography; TX: docetaxel + capecitabine; SOX: S-1 + oxaliplatin Declarations DATA AVAILABILITY STATEMENT The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation. ETHICS STATEMENT Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article. ACKNOWLEDGMENTS The authors thank the patient for her cooperation and participation. And we would like to thank AJE (www.aje.com) for English language editing. AUTHOR CONTRIBUTIONS J-HS was in charge of designing and conducting the study. The data was gathered and examined by Z-WZ and WW. QL, Z-YF and Z-WZ wrote the main manuscript text. All authors have evaluated and given their approval for the article's submission. CONSENT Written informed consent was obtained from the patient. COMPETING INTERESTS The authors declare there are no competing interests. FUNDING No. References Lee SK, Kim WW, Kim SH, Hur SM, Kim S, Choi JH, et al. Characteristics of metastasis in the breast from extramammary malignancies. J Surg Oncol. 2010;101:137–40. Akçay MN. Metastatic disease in the breast. Breast. 2002;11:526–8. Alvarado Cabrero I, Carrera Alvarez M, Pérez Montiel D, Tavassoli FA. Metastases to the breast. Eur J Surg Oncol. 2003;29:854–5. Georgiannos SN, Chin J, Goode AW, Sheaff M. Secondary neoplasms of the breast: a survey of the 20th Century. Cancer. 2001;92:2259–66. Yeh CN, Lin CH, Chen MF. Clinical and ultrasonographic characteristics of breast metastases from extramammary malignancies. Am Surg. 2004;70:287–90. Semba R, Horimoto Y, Arakawa A, Saito M. 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Localization of estrogen receptors in gastric cancer using immunohistochemical staining of monoclonal antibody. Cancer. 1991;67:2401–6. Di Cosimo S, Ferretti G, Fazio N, Mandalà M, Curigliano G, Bosari S, et al. Breast and ovarian metastatic localization of signet-ring cell gastric carcinoma. Ann Oncol. 2003;14:803–4. Doval DC, Pande SB, Sharma JB, Khatri S, Khurana AK, Vaid AK, et al. Metastatic signet-ring cell gastric carcinoma masquerading as breast primary. Case Rep Gastroenterol. 2009;3:21–5. Byun KD, Hur CY, Kim KH, Park JI, Kim KH, Kim TH, et al. Breast and ovarian metastasis of signet-ring cell gastric cancer. Korean J Clin Oncol 2009;5:31–35. Iesato A, Oba T, Ono M, Hanamura T, Watanabe T, Ito T, et al. Breast metastases of gastric signet-ring cell carcinoma: a report of two cases and review of the literature. Onco Targets Ther. 2015;8:91–7. Jayi S, Fatemi H, Laabadi K, Bouguern H, Chaara H, Laamarti A, et al. [Breast metastases of gastric adenocarcinoma associated with a pregnancy of 32 weeks of gestation: about a rare case]. Pan Afr Med J. 2013;15:116. Additional Declarations No competing interests reported. Supplementary Files SupplimentaryFigure1Flowchart.tif Supplemental Figure 1 Timeline of data related to the case.  SupplimentaryTable2CAREchecklistEnglish2013.pdf Supplementary Table 1 CARE checklist of the case.  Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About In Review Editorial Policies Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-1886166","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":123645673,"identity":"2d9cc0b6-2104-4b1d-a36d-d6f994b2fbb4","order_by":0,"name":"Qiang Li","email":"","orcid":"","institution":"the Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Qiang","middleName":"","lastName":"Li","suffix":""},{"id":123645674,"identity":"a12db910-7bc7-420f-a799-d1f63a65c9c1","order_by":1,"name":"Zhengwei Zhang","email":"","orcid":"","institution":"the Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Zhengwei","middleName":"","lastName":"Zhang","suffix":""},{"id":123645675,"identity":"f03376c6-fba6-4813-aa16-bd41ae760c1e","order_by":2,"name":"Ziyu Feng","email":"","orcid":"","institution":"the Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Ziyu","middleName":"","lastName":"Feng","suffix":""},{"id":123645676,"identity":"f69a6d49-dfd8-4e68-b420-1f357b983f81","order_by":3,"name":"Wan Wei","email":"","orcid":"","institution":"the Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Wan","middleName":"","lastName":"Wei","suffix":""},{"id":123645677,"identity":"c638870d-44f5-4e58-8297-465ac99ccec5","order_by":4,"name":"Jianhua Shi","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAyklEQVRIiWNgGAWjYBACxmYGBmYQw4CZ+cCBDz9I08KWeHBmD5E2QbQw8Bgf5mAjRnk787PHhW129ubsPB8OM/AwyPOLHSDkMDZz45ltyYk7m3k3HC6wYDCcOTuBkBYGM2neNuYEg8NALTN4GBIMbhPUwv4NqKXe3uAwz4PDPGxEaeEB2XKYccNhHgaitZRJ85w7nrjhMJsBMJAlCPvFsP/4Nmmesmp7g/OHH3/48MNGnl+akJYGVL4EfuUgIE9YySgYBaNgFIx4AAAsMj8kE/S5wQAAAABJRU5ErkJggg==","orcid":"","institution":"the Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Jianhua","middleName":"","lastName":"Shi","suffix":""}],"badges":[],"createdAt":"2022-07-22 15:14:26","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-1886166/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-1886166/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":24512714,"identity":"8c30cd3d-db00-4b54-a91f-116750c870a1","added_by":"auto","created_at":"2022-07-29 15:09:49","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1712191,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePreoperative and postoperative imaging data. \u003c/strong\u003eA biopsy was done after a gastroscopy identified a tumor in the gastric wall \u003cstrong\u003e(A)\u003c/strong\u003e. CT shows postoperative changes of gastric cancer, pelvic and bilateral ovarian metastases (Krukenburg tumor) \u003cstrong\u003e(B-D)\u003c/strong\u003e. US \u003cstrong\u003e(E)\u003c/strong\u003e and Magnetic resonance imaging \u003cstrong\u003e(F-G)\u003c/strong\u003e show multiple lesions of the bilateral breast in 2022.\u0026nbsp;\u003c/p\u003e","description":"","filename":"Fig1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-1886166/v1/4fb6e1e9a553ec2eed56585e.jpg"},{"id":24512717,"identity":"03959ca0-f14b-461b-93ce-2e9bacd491a2","added_by":"auto","created_at":"2022-07-29 15:09:50","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":2113796,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eHematoxylin \u0026amp; eosin–stained section.\u003c/strong\u003e \u003cstrong\u003e(A) \u003c/strong\u003egastric cancer (×100)\u003cstrong\u003e (B)\u003c/strong\u003e gastric cancer (×400)\u003cstrong\u003e (C)\u003c/strong\u003e ovarian metastases\u003cstrong\u003e \u003c/strong\u003e(×100)\u003cstrong\u003e (D) \u003c/strong\u003eovarian metastases\u003cstrong\u003e \u003c/strong\u003e(×400)\u003cstrong\u003e (E)\u003c/strong\u003e breast metastases (×100)\u003cstrong\u003e (F)\u003c/strong\u003e breast metastases (×400)\u003cstrong\u003e.\u003cspan class=\"ql-cursor\"\u003e\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Fig2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-1886166/v1/cf5969cbe70e3434381d7fff.jpg"},{"id":24512716,"identity":"0dadb372-c030-41a9-9493-6c1747d0a3ed","added_by":"auto","created_at":"2022-07-29 15:09:50","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":1762535,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eImmunohistochemical staining section. \u003c/strong\u003eCDX2 \u003cstrong\u003e(A)\u003c/strong\u003e, CK20 \u003cstrong\u003e(B)\u003c/strong\u003e and Villin \u003cstrong\u003e(C)\u003c/strong\u003e are positive in gastric cancer (×400). CDX2 \u003cstrong\u003e(D)\u003c/strong\u003e, CK20 \u003cstrong\u003e(E)\u003c/strong\u003e and CK7\u003cstrong\u003e(F)\u003c/strong\u003e are positive in ovarian metastases. CDX2 \u003cstrong\u003e(G)\u003c/strong\u003e, E-cad\u003cstrong\u003e(H)\u003c/strong\u003e, ER \u003cstrong\u003e(I)\u003c/strong\u003e, PR \u003cstrong\u003e(J)\u003c/strong\u003e, Her-2 \u003cstrong\u003e(K)\u003c/strong\u003e, MUC-5AC \u003cstrong\u003e(L) \u003c/strong\u003eare detected in breast metastases.\u003c/p\u003e","description":"","filename":"Fig3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-1886166/v1/35ffca2be3f4713ac2bc6fd2.jpg"},{"id":29534472,"identity":"13c4d4c9-bf86-4baf-a547-e8c88f31ac1c","added_by":"auto","created_at":"2022-11-26 03:59:31","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":853646,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1886166/v1/e0674318-90d2-41fd-bb64-c2f26d8e9a53.pdf"},{"id":24512718,"identity":"5c1cc807-1d06-4313-be22-b115418d94cd","added_by":"auto","created_at":"2022-07-29 15:09:50","extension":"tif","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":896638,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSupplemental Figure 1 Timeline of data related to the case.\u003cspan class=\"ql-cursor\"\u003e\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"SupplimentaryFigure1Flowchart.tif","url":"https://assets-eu.researchsquare.com/files/rs-1886166/v1/8800bad27ca0a81156247236.tif"},{"id":24512715,"identity":"06be78de-5353-4803-9441-d8f2f5ab59ce","added_by":"auto","created_at":"2022-07-29 15:09:50","extension":"pdf","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":751287,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSupplementary Table 1 CARE checklist of the case.\u003cspan class=\"ql-cursor\"\u003e\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"SupplimentaryTable2CAREchecklistEnglish2013.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1886166/v1/aaa415e88d7395a804040ca2.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Bilateral Breast and Ovarian Metastases of Signet-ring Cell Gastric Cancer: A Case Report and Literature Review","fulltext":[{"header":"Introduction","content":"\u003cp\u003eMetastatic breast cancer is rare, accounting for only 0.4 to 2% of all breast cancers [\u003cspan class=\"CitationRef\"\u003e1\u003c/span\u003e]. Most cases involve females, with approximately 5\u0026ndash;8% of cases involving males [\u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e]. Extramammary breast metastases are more common in patients with hematological and cutaneous melanoma [\u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e]. However, the lung, ovary, cervix, prostate, kidney, gastrointestinal system, liver, and head and neck regions are other possible initial tumor sites [\u003cspan class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e7\u003c/span\u003e]. There were 73 cases of gastric cancer with breast metastasis published online up until June 2022, including 17 cases with breast and ovarian metastases and only 6 cases with bilateral breast and ovarian metastasis (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). Reitmann \u003cem\u003eet al\u003c/em\u003e. [\u003cspan class=\"CitationRef\"\u003e8\u003c/span\u003e] reported one of the first cases of stomach cancer with breast metastases in 1908. Signet-ring cell histology, antral tumor location, and lymph node involvement are all standard in gastric cancer patients with breast metastases [\u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e13\u003c/span\u003e]. Because the symptoms of primary breast cancer and metastases are similar, distinguishing between the two is critical for determining the best treatment option.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab2\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eClinical characteristics of cases with bilateral breast matastases and ovary metastasis of GC\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eCase\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eAge (years)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eHistology\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003ePresentation\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eInterval\u003csup\u003e*\u003c/sup\u003e (months)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eOther metastases\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eFollow-up (months)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eIHC\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eCountry\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eLocalization\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003ePrognosis\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDawson 1936[\u003cspan class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e25\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMucinous\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eN/A\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eN/A\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eOvaries\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eN/A\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eN/A\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eScotland\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBilateral\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eN/A\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDi Cosimo 2003[\u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e39\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSignet-ring cell\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNodules\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eOvaries, peritoneum, skin\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eN/A\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eN/A\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eItaly\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBilateral\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eN/A\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDoval 2009[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e34\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSignet-ring cell\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePalpable masse\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eN/A\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eOvaries\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eGCDFP-15-ER-,PR-,HER2-, CA125-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eIndia\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBilateral\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDied\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eByun 2009[\u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e45\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSignet-ring cell\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePalpable masse\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eN/A\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLeft ovarian\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eN/A\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eER-, PR-, HER2-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSouth Korea\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBilateral\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eN/A\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eIesato2014[\u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e41\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSignet-ring cell\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eInflammatory\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eN/A\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eOvaries\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e9\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ep53+, MUC 5AC+,\u003c/p\u003e\n\u003cp\u003eHIK1083+\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eJapan\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBilateral\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDied\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eJayi 2013[\u003cspan class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e32\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAdenocarcinoma\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNodules\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eConcomitant\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eOvaries\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eN/A\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCK+, CD20-,\u003c/p\u003e\n\u003cp\u003eER-,PR-,HER2-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMorocco\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBilateral\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eN/A\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePresent case 2022\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e41\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSignet-ring cell\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNodules\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e36\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eOvaries\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCDX-2+,\u003c/p\u003e\n\u003cp\u003eHER2-, ER-, PR-,\u003c/p\u003e\n\u003cp\u003eCK7+, E-cad+,\u003c/p\u003e\n\u003cp\u003eMUC 5AC+\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eChina\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBilateral, multifocal\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAlive\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003ctfoot\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"11\"\u003e*The interval from the discovery of GC to the discovery of breast metastases.\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"11\"\u003eN/A, not available; IHC, immunohistochemistry; ER, oestrogen receptor; PR, progesterone receptor; HER2, human epidermal growth factor receptor 2 protein; CK, cytokeratin; MUC 5AC, recombinant mucin 5 subtype AC; GCDFP-15, gross cystic fluid protein 15; CDX-2, caudal-type homeobox 2; E-cad, epithelial cadherin.\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"11\"\u003e1. Tachibana S, Asano M, Miya K, Hino T, Furuichi N, Misawa K. A case report of gastric cancer with breast metastasis (Jpn). J Clin Surg 1986; 41:1719\u0026ndash;1722.\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"11\"\u003e2. Di Cosimo S, Ferretti G, Fazio N, Mandal\u0026agrave; M, Curigliano G, Bosari S, et al. Breast and ovarian metastatic localization of signet-ring cell gastric carcinoma. Annals of oncology : official journal of the European Society for Medical Oncology. 2003; 14(5):803-4.\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"11\"\u003e3. Doval DC, Pande SB, Sharma JB, Khatri S, Khurana AK, Vaid AK, et al. Metastatic Signet-Ring Cell Gastric Carcinoma Masquerading as Breast Primary. Case reports in gastroenterology. 2009; 3(1):21\u0026thinsp;\u0026minus;\u0026thinsp;5.\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"11\"\u003e4. Byun KD, Hur CY, Kim KH, Park JI, Kim KH, Kim TH, Choi CS, Choi YK. Breast and ovarian metastasis of signet-ring cell gastric cancer. Korean J Clin Oncol 2009; 5:31\u0026ndash;35.\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"11\"\u003e5. Iesato A, Oba T, Ono M, Hanamura T, Watanabe T, Ito T, et al. Breast metastases of gastric signet-ring cell carcinoma: a report of two cases and review of the literature. OncoTargets and therapy. 2015; 8:91\u0026thinsp;\u0026minus;\u0026thinsp;7.\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"11\"\u003e6. Jayi S, Fatemi H, Laabadi K, Bouguern H, Chaara H, Laamarti A, et al. [Breast metastases of gastric adenocarcinoma associated with a pregnancy of 32 weeks of gestation: about a rare case]. The Pan African medical journal. 2013; 15:116.\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tfoot\u003e\n\u003c/table\u003e\n\u003c/div\u003e"},{"header":"Case Presentation","content":"\u003cp\u003eGastroscopy revealed gastric cancer in a 41-year-old female with epigastric discomfort (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003eA). Complete gastrectomy and D2 lymph node dissection followed the procedure. Postoperative pathology showed gastric signet-ring cell carcinoma (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eA,B). The cancer tissue invaded the gastric wall submucosa, the upper and lower incision borders and the intestinal wall, but the omentum did not show cancer tissue invasion; however, metastases was found in the lower curvature lymph nodes (14/16) and no metastases was found in the higher curvature lymph nodes (0/4). Immunohistochemistry (IHC) revealed the presence of CK20 (local +), CK18 (+), Villin (+), CDX-2 (weak +), HER-2 (human epidermal growth factor receptor-2, -), and Ki-67 (10%) (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003eA,B,C). The patient denied a family history of gastric cancer. The patient was then given eight cycles of SOX regimen chemotherapy with mild side effects (S-1 80 mg/m\u003csup\u003e2\u003c/sup\u003e, oxaliplatin 100 mg/m\u003csup\u003e2\u003c/sup\u003e).\u003c/p\u003e\n\u003cp\u003eUltrasonography (US) and abdominal computed tomography (CT) showed multiple metastatic lesions in the bilateral pelvis three years later. The patient had stomach cancer that had spread to her pelvis (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003eB,C,D). Bilateral upper ovary arteriovenous ligation and bilateral adnexectomy were performed. On postoperative pathology, the Krukenberg tumor of the ovary was identified as a poorly differentiated ovarian adenocarcinoma, partly signet-ring cell carcinoma (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eC,D). IHC showed CDX-2 (3+), HER-2 (-), Ki-67 (20%), ER (estrogen receptor, -), PR (progesterone receptor, -), CK7 (3+), and CK20 (2+) (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003eD,E,F). The right breast tumor was punctured after multiple breast tumors on both sides were diagnosed simultaneously (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003eE,F,G). Pathological findings included signet-ring cells, suggesting metastatic adenocarcinoma (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eE,F). CDX-2(3+), Her-2(-), Ki-67 (60%), ER(-), PR(-), CK7(3+), CK20(-), and E-cad (3+) were all detected by IHC (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003eG,H,I,J,K,L). The patient then received TX regimen chemotherapy for six cycles (docetaxel 60 mg/m\u003csup\u003e2\u003c/sup\u003e d1\u0026thinsp;+\u0026thinsp;capecitabine 825 mg/m\u003csup\u003e2\u003c/sup\u003e bid d1-14) with mild chemotherapy side effects. Imaging evaluation during treatment showed her condition to be stable.\u003c/p\u003e\n\u003cp\u003eThe patient underwent a double mastectomy, and postoperative pathology showed that some cells showed a signet-ring appearance. Poorly differentiated adenocarcinoma of gastric cancer accompanied by breast metastasis was considered in both breasts, and tumor emboli were observed in the vessels. The patient's serum tumor markers CEA, CA153, CA125, and CA199 were not elevated throughout the course of the disease. Breast metastasis postoperative IHC results were comparable with those of the biopsy. According to the American Joint Committee on Cancer tumor-node-metastasis (AJCC/TNM) cancer staging system for gastric cancer, the pathological staging of this case was pT1bN3aM1. During the five months of follow-up, there was no further illness progression. The patient and her family were delighted with the course of treatment. The treatment timeline of the patient is depicted in Supplementary Fig.\u0026nbsp;1.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eWe summarized and analyzed the clinicopathological features of 74 cases, including the present case (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). These patients were between the ages of 22 and 72 (mean 45.02 years). The breast is a hormone-dependent organ, and fluctuations in hormone levels in women undergoing high reproductive activity [\u003cspan class=\"CitationRef\"\u003e14\u003c/span\u003e] may explain this type of breast injury, as they did in the 43-year-old patient in our study. Furthermore, due to hormone-related factors, the biological activity of stomach cancer appears to be more aggressive in younger age patients [\u003cspan class=\"CitationRef\"\u003e15\u003c/span\u003e]. Hormone levels in the ovaries and the mammary glands are linked to metastases and invasiveness [\u003cspan class=\"CitationRef\"\u003e14\u003c/span\u003e]. At the same time, some pregnant patients were reported to develop metastases, confirming its link to hormones [\u003cspan class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003ctable border=\"1\" id=\"Tab4\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eClinical characteristics of cases with breast metastasis of GC\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCharacteristic\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eNumber (%)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD or Median[Quartile]\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge(years)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e74(100)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e45.02\u0026thinsp;\u0026plusmn;\u0026thinsp;1.65\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eGender\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003emale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2(2.70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003efemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e60(81.08)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12(16.22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eHistology\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eScirhous\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2(2.70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMucinous\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5(6.76)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAnaplastic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1(1.35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSignet-ring cell\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e45(60.81)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAdenocarcinoma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10(13.51)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11(14.86)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eInterval(months)\u003c/strong\u003e\u003csup\u003e\u003cstrong\u003e*\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003epremonitory sign of GC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003esynchronous sign of GC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e20(27.03)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003edelayed sign of GC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e27(36.49)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12.00[4.00,31.50]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e27(36.49)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eCombined metastasis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eY\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e47(63.51)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOvary\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19(25.68)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOther metastases\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28(37.84)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2(2.70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e25(33.78)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eSite of BM\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26(35.14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12(16.22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBilateral\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15(20.27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21(28.38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eOutcome(months)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWithout progression\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8(10.81)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.50[4.25,12.25]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWith progression\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e32(43.24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.00[2.00,9.00]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34(45.95)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\"\u003eXELOX (capecitabine\u0026thorn; oxaliplatin)\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003c/div\u003e\n\u003cp\u003eAccording to the previously published cases, bilateral breast metastases made up 20.27% (15/74) of all cases, although only 9.46% (7/74) of those individuals also had ovarian metastases. Multifocal and bilateral forms of breast metastases are uncommon and can be mistaken as primary breast cancer clinically and radiologically. This palpable tumor usually occurs in the upper lateral quadrant of the breast. Typically, there are no skin or breast abnormalities. However, there have been reports of inflammatory breast cancer that present with edema and skin redness, as well as axillary lymph node metastases in more than 15% of cases [\u003cspan class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e\n\u003cp\u003eThis case must be distinguished histologically from primary signet-ring cell carcinoma of the breast with gastrointestinal metastases. Signet-ring cell carcinoma can either be lobular or ductal. Metastatic breast tumors must be identified to avoid unnecessary and disabling surgery, and misidentification can result in the initial tumor being ignored. The absence of lobular carcinoma in situ or initial intraductal tumor of the breast characterizes secondary breast cancer, and the tumor type is the same as the primary lesion type. After the core needle biopsy (CNB) of the breast lesions, the characteristics of signed-ring cells were observed in this case. Breast metastases were suspected because of the history of stomach cancer, which was verified by IHC. Preoperative CNB and IHC of breast lesions were particularly helpful in this case. Secondary signet-ring cell cancer of the breast is MUC-5AC positive and CK7 positive, whereas primary signet-ring cell carcinoma of the breast is estrogen receptor-positive [\u003cspan class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e19\u003c/span\u003e]. CK20 negativity, estrogen receptor negativity, progesterone receptor negativity, HER-2 negativity, MUC-5AC positivity, and CK7 positivity distinguish primary from secondary signet-ring cell cancer of the breast in this case. A recent study suggested that GATA3 and PAX8 could be helpful as breast cancer biomarkers [\u003cspan class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e21\u003c/span\u003e]. The current findings indicate that no single marker is particular and that its expression varies between primary and metastatic lesions, particularly in tissue biopsies [\u003cspan class=\"CitationRef\"\u003e22\u003c/span\u003e].\u003c/p\u003e\n\u003cp\u003eLocal tumor surgery and radiation therapy are not appropriate treatments for gastrogenic breast metastases [\u003cspan class=\"CitationRef\"\u003e23\u003c/span\u003e]. The treatment should be surgical control of the local tumor combined with systemic therapy. Breast cancer metastasis from primary gastrointestinal tumors, especially gastric cancer, has a poor prognosis, with approximately 80% of patients dying one year after diagnosis [\u003cspan class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e25\u003c/span\u003e]. The median survival for metastatic breast cancer was 8.6 months, according to Ma \u003cem\u003eet al\u003c/em\u003e.\u0026rsquo;s study [\u003cspan class=\"CitationRef\"\u003e9\u003c/span\u003e] on the clinicopathological characteristics and prognosis of 54 patients with gastric cancer with breast metastases (3 new cases and 51 from prior studies). The most frequent patient characteristics were age greater than 43 years, pathological type of signet-ring cell carcinoma, lymph node involvement, and early lesions in the stomach antrum. As shown in the literature, signet-ring cell carcinoma is the most common pathological type, with a maximum survival of 22 months (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003eIt is interesting that signet-ring tumor cells in our patient developed in endocrine target organs. The occurrence of breast and ovarian metastases may be associated with the hormonal milieu in premenopausal patients and to the stomach cancer histotype. In reality, young women\u0026apos;s natural physiological and hormonal milieu may impact the development of stomach cancer in specific individuals [\u003cspan class=\"CitationRef\"\u003e14\u003c/span\u003e]. Recent studies have suggested that the action of estrogen in gastric cancer may be mediated by ER-\u0026beta;, notably in signet-ring cell carcinoma [\u003cspan class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e27\u003c/span\u003e]. Based on Krukenberg\u0026apos;s initial criteria and the possible stromal origin of signet-ring cells in the ovary, it is also believed that luteinizing hormone is involved in stromal luteinization in Krukenberg tumors. Last but not least, we believe that accurate characterization of the underlying tumor is crucial for effective treatment, notwithstanding the rarity of signet-ring cell gastric cancer metastases to the breast and ovaries.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eFrom a clinical and radiological perspective, preoperative CNB and IHC of breast lesions can help compensate for the lack of differentiation between primary and secondary breast cancer. As a result, a comprehensive judgment must be made based on various factors, such as physical examination, imaging examination, pathological diagnosis, and tumor indicators.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eCNB: core needle biopsy; IHC: immunohistochemistry; ER: estrogen receptor; PR: progesterone receptor; HER-2: human epidermal growth factor receptor-2; AJCC: American Joint Committee on Cancer; TNM: tumor-node-metastasis; US: ultrasonography; CT: computed tomography; TX: docetaxel + capecitabine; SOX: S-1 + oxaliplatin\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eDATA AVAILABILITY STATEMENT\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eETHICS STATEMENT\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eACKNOWLEDGMENTS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors thank the patient for her cooperation and participation. And we would like to thank AJE (www.aje.com) for English language editing.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAUTHOR CONTRIBUTIONS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eJ-HS was in charge of designing and conducting the study. The data was gathered and examined by Z-WZ and WW. QL, Z-YF and Z-WZ wrote the main manuscript text. All authors have evaluated and given their approval for the article\u0026apos;s submission.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCONSENT\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the patient.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCOMPETING INTERESTS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare there are no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFUNDING\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eLee SK, Kim WW, Kim SH, Hur SM, Kim S, Choi JH, et al. Characteristics of metastasis in the breast from extramammary malignancies. J Surg Oncol. 2010;101:137\u0026ndash;40.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAk\u0026ccedil;ay MN. Metastatic disease in the breast. 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Gastric signet-ring adenocarcinoma presenting with breast metastasis. World J Gastroenterol. 2006;12:2958\u0026ndash;61.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMerino MJ, Livolsi VA. Signet ring carcinoma of the female breast: a clinicopathologic analysis of 24 cases. Cancer. 1981;48:1830\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEspinosa I, Gallardo A, D'Angelo E, Mozos A, Lerma E, Prat J. Simultaneous carcinomas of the breast and ovary: utility of Pax-8, WT-1, and GATA3 for distinguishing independent primary tumors from metastases. Int J Gynecol Pathol. 2015;34:257\u0026ndash;65.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTempfer CB, El Fizazi N, Ergonenc H, Solass W. Metastasis of ovarian cancer to the breast: A report of two cases and a review of the literature. 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[Breast metastases of gastric adenocarcinoma associated with a pregnancy of 32 weeks of gestation: about a rare case]. Pan Afr Med J. 2013;15:116.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"breast metastases, ovarian metastases, diagnosis, signet-ring cell gastric cancer, core needle biopsy, case report","lastPublishedDoi":"10.21203/rs.3.rs-1886166/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1886166/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eBreast cancer metastasis accounts for only 0.4\u0026ndash;2% of all breast cancer cases. Gastric cancer with breast metastases is extremely rare, while mammary and ovarian metastases from the stomach are even more uncommon. Breast metastases might be mistaken for primary cancer due to their uncommon and generic clinical and radiological symptoms, leading to ineffective and debilitating therapy.\u003c/p\u003e\u003ch2\u003eCase Presentation:\u003c/h2\u003e \u003cp\u003eWe present a 43-year-old woman with bilateral multiple metastases from stomach signet-ring cell carcinoma to the breast and ovary, which is the seventh case to our knowledge.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eWe highlight the epidemiological, diagnostic, therapeutic, and prognostic aspects of this extremely rare disease through our case, which are critical to understand in order to avoid diagnostic errors and subsequent incorrect care.\u003c/p\u003e","manuscriptTitle":"Bilateral Breast and Ovarian Metastases of Signet-ring Cell Gastric Cancer: A Case Report and Literature Review","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-07-29 15:09:48","doi":"10.21203/rs.3.rs-1886166/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"d7e3e700-5ac9-4c9d-8075-4957843909b1","owner":[],"postedDate":"July 29th, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2022-11-26T03:59:19+00:00","versionOfRecord":[],"versionCreatedAt":"2022-07-29 15:09:48","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-1886166","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1886166","identity":"rs-1886166","version":["v1"]},"buildId":"re_ckhLnmML6MCF96OHNJ","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}