The major histological type of colon cancer is adenocarcinoma, which accounts for more than 90% of all cases [3]. Mucinous adenocarcinomas represent about 8–10% of colon cancer [5]. Signet-ring cell carcinoma is a rare separate classification, which accounts for 2–4% of mucinous carcinomas and characters by containing intracellular mucin pushing the nucleus to one side [3]. Both mucinous adenocarcinomas and signet-ring cell carcinoma represent aggressive behavior and were related to poor prognosis in patients [6, 7]. Recent research demonstrated that female and younger patients are more likely to suffer from mucinous adenocarcinoma, which is more frequently diagnosed at an advanced stage [8]. In this article, we report a case of 44-year-old Chinese woman who suffered from stage of IIIB with mucinous adenocarcinoma of colon and metastatic signet ring cell carcinoma of breast, which is consistent with the characteristics of young women prone to this disease. Covering more than 50% of the mucinous component, mucinous adenocarcinoma is composed of an extracellular mucin pool, which may contain layers, acini, cribriform sheets of malignant glands, or scattered individual signet ring cells [9]. Signet ring cell carcinoma was classified as mucinous adenocarcinoma with more than 50% signet ring cell component [10]. Due to the different proportion of signet ring cells, colon cancer contains both mucinous and signet ring cell components are occasionally confusing. That’s may explain why the pathological results of colon and breast in this case are inconsistent. Moreover, immunohistochemistry for cytokeratin 20 (CK-20) and caudal-type homeobox 2 (CDX2) can accurately identify colon adenocarcinoma origin [3]. Cytokeratin 7 (CK-7) is positive for most breast cancers, but negative for colon cancer [11]. In this case, the patient’s immunohistochemistry of the breast showed that CK-20 positive expression, CDX-2 weakly positive expression and CK-7 negative expression, which confirmed the intestinal tract origin.
Breast tumors are mostly primary cancers in women, but tumors metastasis to breast is quite rare, which account for only 0.5-3% of all breast metastasis[12]. Although literature reported some rare regions metastasis to breast, such as contralateral breast, ovary, lung, stomach, leukemia, melanoma and lymphoma, colon metastasis to breast was even more rarely[13–15]. As far as we know, there are no more than 30 cases of colon cancer metastasis to breast worldwide [12, 16, 17]. Researchers’ statistical analysis of those cases revealed that the average time form colorectal cancer diagnosis to breast metastasis was 21 months and the longest transfer time to breast was 7 years so far [12]. What's more, after the detection of breast metastasis, the average survival time is 14.9 months [16]. Only one case had a more than five-year overall survival with colon cancer metastasis to breast [16]. As shown in our case, histopathology often exhibited mucinous or signet-ring cell features for those patients [12]. It’s well-known that dissemination of clonogenic cells lead to the formation of the micrometastatic foci, which of those clonogenic cells charactered similarly with the primary tumor. By systemic circulation, lymphatic circulation or transcoelomic migration, these clonogenic cells spread [13]. However, this theory couldn’t explain the solitary metastasis of rare sites, such as breast. Baum and his colleagues proposed a hypothesis that primary cancer cells shed subcellular particles, which were taken up by wandering cells of the monocyte macrophage system and transported to distant sites. Subsequently, the genetic information in subcellular particles was transfected to the local mesenchymal cells. Thus, the expression of oncogenic sequences and the development of cancer cell phenotypes occur in usual locations [18].
Surgery is the main treatment for colon cancer, but tumors recur in 30%-50% of all cases, which usually presenting as metastasis [19]. After surgery resection, adjuvant chemotherapy is the standard treatment for patients with stage III colon cancer, which could provide a 22–32% overall survival advantage and a 30% relative risk reduction in recurrence[20]. For patients with unresectable locally advanced disease or high metastatic burden, palliative systemic chemotherapy is appropriate. And for patients with individualized local-recurrent disease may receive multimodality therapy. We have lack experience in the treatment of patients with rare site metastasis. For now, a majority of the patients with breast metastasis form colon received standardized management of their primary tumor [21]. If the patients recur with solitary nodules within the breast, surgical excision with negative margins may benefit for them [22, 23]. To slow the growth of breast metastasis, patients accepted oral capecitabine as palliative chemotherapy [12, 16]. Simple mastectomy was needed for bulky or painful tumor [14]. Avoiding surgical excision for patients with the short survival time expectancy and poor prognosis, who were more suitable for systemic chemotherapy [24, 25]. Combination capecitabine and bevacizumab may be helpful to elderly patients with breast metastasis from colon [16]. In the patients we are describing, she underwent radical surgery for stage IIIB of primary colon cancer followed by 6 cycles of XELOX adjuvant chemotherapy regimen. Unfortunately, she presented breast metastasis 14 months later. Because of the solitary nodules within the right breast, the patient underwent mastectomy with negative margins. Considering her younger age, more aggressive pathology and primary tumor, we performed XELOX chemotherapy regimen combination with bevacizumab to this patient for 8 cycles. Clinical examination after the last multimodality therapy showed as stable disease (RECIST criteria).
Breast metastasis form primary colon cancer is rare. The mechanism of this metastasis has not been fully clarified and the prognosis of this disease is poor. At present, there is no unified standard treatment for this disease. Through the sharing of this case, we hope to increase the knowledge for breast metastasis form primary colon cancer and provide an effective treatment mode for this disease.