DOI: https://doi.org/10.21203/rs.3.rs-1458638/v1
Background: Colon cancer is one of the most common diagnosed malignancies. Although the use of surgery, chemotherapy, radiotherapy, targeted therapy, immunotherapy and other comprehensive treatment, distant metastasis is still one of the main causes for dying of colon cancer. The common metastatic site of colon cancer is liver, lung and bone. In this article, we report a rare case of breast metastasis of signet ring cell carcinoma from the colon.
Case Presentation: A 44-year-old woman was diagnosed with colon cancer and received a radical surgery of colon cancer in 2019. Combined with postoperative pathological and CT images, a diagnosis of cT3N2M0 mucinous adenocarcinoma of colon (according to AJCC cancer staging manual, Version 8) was established. Adjuvant chemotherapy (XELOX: oxaliplatin 130 mg/m2 on day 1 plus capecitabine 1000 mg/m2 twice daily on days 1 to 14 every 3 weeks for 18 weeks) was performed followed by surgical resection. 14 months later, the patient received mastectomy for breast mass, which was diagnosed pathologically as metastasis of signet ring cell carcinoma from the colon. XELOX chemotherapy regimen (oxaliplatin 130 mg/m2 on day 1 plus capecitabine 1000 mg/m2 twice daily on days 1 to 14 every 3 weeks for 24 weeks) combined with bevacizumab (7.5mg/kg on day 1) were used after the mastectomy. The patient was stable disease according to her last examination (RECIST criteria).
Conclusion: It is rare to report a patient diagnosed with colon cancer which metastasis to breast. We hope to increase treatment experience for patients with this rare metastasis.
Colon cancer is the third most common diagnosis malignancy worldwide [1, 2]. Nowadays the main treatment methods of colon cancer include surgical resection, chemotherapy, radiotherapy, targeted therapy and immunotherapy [3]. With the help of those treatments, five-year survival rates for patients with localized or regionally disease is 90.1% and 69.2%, respectively. But the five-year survival rate is only 11.7% for patients suffered from distantly spread colon cancer [2]. Colon cancer often metastasizes to liver, lung or bone, metastasis to breast is not common [4]. In this article, we experienced a rare case of breast metastasis from colon cancer.
A 44-year-old woman was initially referred to People’s Hospital of Longyou for recurrent left abdominal obtuse pain without obvious cause. She had no surgical history or chronic diseases, such as hypertension or diabetes. She denied family genetic history and tumor history. Her performance status was normal with 37.0°C of initial body temperature, 89 beats/min of pulse rate, 20 breaths/min of breath rate and 130/79 mmHg of blood pressure. A physical examination revealed left abdominal tenderness, but there was no muscle guarding or rebound tenderness. No obvious mass was touched in the abdomen and bowel sounds were normal. An abdominal computed tomography (CT) showed feces in colon, thickening of intestinal wall at the junction of sigmoid colon and descending colon (Fig. 1A). Colonoscopy revealed colonic stenosis is sixty-centimeter away from the anus, which may on account of colonic mass or colitis (Fig. 1B). Blood tests showed that the patient's CA 724 was 11.48 U/mL (0.20–6.90). Laparoscopic radical resection was performed on August 4, 2019. Pathological examination showed as sigmoid colon cancer, which was poor differentiated mucinous adenocarcinoma with serosa invasion, vessel invasion and 4 of 10 peri-intestinal lymph nodes metastasis (Fig. 2). According to AJCC cancer staging manual (Version 8), the patient was considered as stage of IIIB with cT3N2M0. Adjuvant chemotherapy regimen of XELOX (oxaliplatin 130 mg/m2 on day 1 plus capecitabine 1000 mg/m2 twice daily on days 1 to 14 every 3 weeks for 18 weeks) was used followed by surgical resection. And the last time of the chemotherapy was in February 2020. After adjuvant chemotherapy finished, the patient was rechecked every three months. And the examination results showed that the patient’s disease was stable.
The patient went to People’s Hospital of Longyou because of breast tenderness in April 2020. Physical examination revealed a mass of 3.2× 2.0 cm on inner upper quadrant of the right breast. Ultrasonography showed an irregular mass of 33× 23 mm in the right breast with unclear boundary (Fig. 3A). Breast biopsy displayed that the mass was an invasive lobular carcinoma. Therefore, the patient was performed a modified radical mastectomy on April 11, 2020. The postoperative immunohistochemistry of the mass showed as the following: ER, PR, HER-2 resulted negative; CK-pan, CK-20, CEA, Ki-67 resulted positive; P120, CDX-2 resulted weakly positive; E-cad, CK-7 resulted negative. Pathological examination demonstrated that the mass was a metastatic signet ring cell carcinoma, which came from the intestinal tract. Tumor tissue invaded the para-mammary adipose tissue. And the cancer tissue was discovered in the vessel (Fig. 3B). For further treatment, the patient went to our hospital. Positron emission tomography computed tomography (PET/CT) exhibited strip soft tissue density signal in the surgical area with a prosthesis implantation. The maximum standardized uptake (SUVmax) of 18F-FDG was 5.3, which was considered as the postoperative changes of breast (Fig. 4A). After the radical resection of colon cancer, 18F-FDG was increased at the anastomotic site and distal intestine with a SUVmax valued to 4.4. Tracer distribution was enhanced at transverse colon, splenic flexure of colon, rectum. SUVmax of 18F-FDG was 6.6, which was considered as physiological metabolism and may complicate with intestinal polyps (Fig. 4B). Hysteromyoma also could be seen on the image (Fig. 4B). Adjuvant chemotherapy based on 130 mg/m2 oxaliplatin on day 1 plus 1000 mg/m2 capecitabine twice daily on days 1 to 14 and combined with 7.5mg/kg bevacizumab on day 1 every 21 days for 8 cycles were used for this patient. The last re-examination showed that the patient was stable disease (RECIST criteria).
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.
Our report represented a rare case of breast metastasis form primary colon cancer. We provided an effective treatment regimen which combined surgery, chemotherapy and target therapy. We will continue to follow up the prognosis of patients.
XELOX: Oxaliplatin 130 mg/m2 on day 1 plus capecitabine 1000 mg/m2 twice daily on days 1 to 14 every 3 weeks for 18 weeks
mg: milligram
kg: Kilogram
m2: square meter
mm: millimeter
CT: Computed tomography
CA 724: Carbohydrate antigen 724
AJCC: American Joint Committee on Cancer
CK-pan: Cytokeratin-pan
CK-20: Cytokeratin-20
CK-7: Cytokeratin-7
CEA: Carcinoembryonic antigen
Ki-67: marker of proliferation Ki-67
P120: p120 catenin
CDX-2: Caudal-type homeobox protein 2
E-cad: E-cadherin
PET/CT: Positron emission tomography computed tomography
SUVmax: Maximum standardized uptake
18F-FDG: 18Fluorine-fluorodeoxyglucose
RECIST: Response Evaluation Criteriain in Solid Tumors
Ethics approval and consent to participate
Not Applicable
Consent for publication
The patient has already been assigned for informed consent and agreed to the publication of the case and clinical images for medical education purposes. A copy of the written consent is available for review from the Editor-in-Chief of this journal.
Availability of data and material
All information about the patient came from oncology center, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College. All data generated or analysed during this study are included in this published article.
Competing interests
The authors declare that there are no competing interests associated with the manuscript.
Funding
This study was supported in part by grants from the Medical Science and Technology Project of Zhejiang Province (Grant number: 2022KY537)
Authors' contributions
Xiao Wang made treatment plan and treated patient. Yanwei Lu collected patient data and was a major contributor in writing the manuscript. All authors read and approved the final manuscript.
Acknowledgements
Not Applicable.