Huimeng Li1†Liying Yang2†Xiqiang Sun3Zhuquan Wang1Shuangwei Qin1Chengcheng Li1Gongwu Liu3Fengming Xie1*
Weiwei Gao4*- 1Department of Thyroid and Breast Surgery, Southern Central Hospital of Yunnan Province, The First People’s Hospital of Honghe State, Honghe Hospital Affiliated to Kunming Medical University, Gejiu, Yunnan, China
- 2Department of Pathology, Southern Central Hospital of Yunnan Province, The First People’s Hospital of Honghe State, Honghe Hospital Affiliated to Kunming Medical University, Gejiu, Yunnan, China
- 3Department of Hepatobiliary Surgery, Southern Central Hospital of Yunnan Province, The First People’s Hospital of Honghe State, Honghe Hospital Affiliated to Kunming Medical University, Gejiu, Yunnan, China
- 4Department of Rheumatology and Immunology, Southern Central Hospital of Yunnan Province, The First People’s Hospital of Honghe state, Honghe Hospital Affiliated to Kunming Medical University, Gejiu, Yunnan, China
The metastasis of breast cancer to the colon is a rare occurrence, especially in the presence of changes in estrogen and progesterone receptors. To date, literature has only reported two cases of invasive ductal carcinoma and two cases of invasive lobular carcinoma metastasizing to the colon with concurrent changes in hormone receptors. This report describes a 65-year-old woman with a history of left breast cancer, who presented with symptoms of bloody stools and abdominal pain. CT and colonoscopy results revealed a malignant tumor in the ascending colon, and the patient underwent surgery. Pathological results post-surgery indicated changes in hormone receptors, differing from the previous breast cancer pathology, ultimately leading to the diagnosis of breast cancer metastasis to the colon. The patient was found to have liver metastasis 14 months after right hemicolectomy, and systemic metastases in various locations were discovered at the 19-month mark.
Introduction
Breast cancer is the most common malignant tumor in women. Recurrence and distant metastasis often pose challenges in treatment. Common sites of metastasis include bones, liver, and lungs, while gastrointestinal metastases are extremely rare. Previous reports have shown that the pattern of metastasis differs between lobular carcinoma and ductal carcinoma of the breast. Gastrointestinal, gynecologic, and peritoneal metastases are more common in lobular carcinoma (1, 2). ILC (invasive lobular carcinoma) has an increased tendency to metastasize to the GI (gastrointestinal) tract compared with breast carcinomas of NST (non-special type) (40% vs. 2%) (3). We report a case of infiltrating ductal carcinoma that metastasized to the ascending colon, with changes in estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) status. To our knowledge, there have been only two similar cases reported previously.
Case presentation
A 65-year-old woman presented to our center with intermittent abdominal pain and hematochezia for several months. She had a previous diagnosis of ER- and PR-positive (Figure 1), HER2 ++ (no further testing was done) invasive ductal carcinoma of the left breast 5 years before. She underwent modified radical mastectomy for breast cancer. The pathological examination did not indicate the presence of axillary lymph node metastasis and received chemotherapy with anthracycline and cyclophosphamide, followed by taxanes. Subsequently, she received 5 years of endocrine therapy with letrozole until she presented to our center. The patient denied having smoked or consumed alcohol in the past.
Figure 1. Pathological findings of breast malignancy and colon malignancy. breast malignancy: HE staining (A); ER+ (C); PR+ (E); HER2+ (G); Ki67 15%+ (I); E-Cadherin+ (K); colon malignancy: HE staining (B); ER- (D); PR- (F); HER2- (H); Ki67 50%+ (J); E-Cadherin+ (L). HE staining: Hematoxylin-Eosin staining; ER: estrogen receptor; PR: progesterone receptor; HER2: human epidermal growth factor receptor-2; Ki67: nuclear-associated antigen Ki67.
During colonoscopy, a mass was found in the ascending colon (Figure 2). Biopsy results confirmed metastasis of breast cancer to the colon, which was negative for ER, PR, and HER2. However, no local lesions or enlarged lymph nodes were detected in the contralateral breast, chest wall, or axilla through ultrasound, magnetic resonance imaging, and clinical palpation.
Figure 2. Colonoscopy revealed a mass of ascending colon.
After receiving a transfusion of six units of red blood cells to correct anemia, the patient underwent a right hemicolectomy. Intraoperatively, it was observed that the tumor had invaded the right renal fascia. Two lymph node metastases were found on pathological examination after palliative surgery for colonic malignancy. The postoperative pathological examination confirmed the colonoscopy biopsy findings. Further immunohistochemical staining revealed positive results for Cytokeratin 7 (CK7), negative results for Cytokeratin 20 (CK20), and positive results for GATA 3 binding protein (GATA3) and E-Cadherin (Figure 3).
Figure 3. Immunohistochemical staining results of colonic malignancies. CK7+, CK20-, GATA3+. CK7: Cytokeratin 7; CK20: Cytokeratin 20; GATA3: GATA 3 binding protein.
Considering the rarity of this case, we sought opinions from pathologists in different centers to confirm the diagnosis. After considering the majority of expert opinions, it was confirmed as breast cancer metastasis to the colon. The patient was prescribed oral capecitabine at a dosage of 650-mg/m2 twice daily for chemotherapy treatment.
Follow-up imaging studies performed 6 months after the operation did not show any tumor metastasis or recurrence. However, the patient discontinued medication due to severe hand–foot syndrome. In a 14-month postoperative computed tomography (CT) scan, a solitary nodule was detected in the liver, indicating a metastatic lesion (Figure 4). The patient refused intravenous chemotherapy and opted for a second course of oral capecitabine treatment. Nineteen months after surgery, multiple metastases were discovered, including the liver, abdominal lymph nodes, adrenal glands, thoracolumbar spine, lungs, and mediastinal lymph nodes, accompanied by widespread cancer-related pain. The patient declined medication treatment. During the entire follow-up, no local recurrence of breast malignancy or new tumors of the opposite breast were found. The patient was lost to follow-up at 20 months after right hemicolectomy. Treatment and follow-up are organized into a timeline (Figure 5).
Figure 4. Computedtomography (CT) scan, a solitary nodule was detected in the liver, indicating a metastatic lesion.
Figure 5. Timeline depicting the treatment and follow-up of the patient.
Discussion
Breast cancer metastases to the gastrointestinal tract is extremely rare. Previous reports have shown that the most common sites of metastases in breast cancer are the bones, lungs, liver, and brain, while gastrointestinal metastases, especially to the colon, is very rare. The incidence of breast cancer metastases to the gastrointestinal tract, particularly to the colon, is estimated to be around 1%, with a rate of approximately 0.1% specifically for metastases to the colon (4). The patterns of metastases differ between lobular carcinoma and ductal carcinoma of the breast, with gastrointestinal metastases being more common in lobular carcinoma (1, 2). In this case, it was the ductal carcinoma of the breast that had colon metastases.
Due to the final diagnosis of breast cancer metastasis to the colon with receptor changes, this case presents significant challenges in terms of diagnosis and treatment. We performed a search in the PubMed database and gathered relevant literature, as detailed in Table 1. Our findings reveal the fourth documented case of ductal carcinoma of breast metastasizing to the colon, accompanied by changes in receptor status. Additionally, there have been two cases where receptor changes were observed when lobular carcinoma metastasized to the colon (5, 6).
Table 1. Case reports of breast carcinomas with colonic metastases.
In this case, there was a mismatch between the receptors in the primary breast lesion and the colon metastases. Incompatible receptors between the primary and secondary lesions of breast cancer have been reported, with frequencies of alterations in ER, PR, and HER2 being approximately 16.4%–32.4%, 30.9%–37.78%, and 10.2%–14.5%, respectively (7–10). Emilia Montagna reported in 2017 that approximately 82% of breast cancer metastases in the gastrointestinal tract have positive hormone receptor expression (11). In the dozens of case reports we have collected, the majority of patients were found to be hormone receptor positive. Among these patients, most did not exhibit any changes in the hormone receptor status. Previous reports have indicated that the instability of hormone receptors in breast cancer is associated with a poorer prognosis (12, 13), Women whose ER-positive primary tumors transform into ER-negative tumors experience a significant 48% increase in the risk of death (7). In this case report, liver metastases were found at 14 months after surgery, and multiple metastases throughout the body were found at 19 months with subsequent rapid disease progression.
CK7, CK20, and GATA3 are commonly used in pathology for tumor diagnosis and classification. These markers can provide information about the type and origin of the tumor. CK7 was expressed in 89%–98% of non-specified breast cancers (14). Most gastrointestinal, pancreaticobiliary, and ovarian mucinous adenocarcinomas are CK20 positivity, in adenocarcinoma, positivity of CK20 strongly indicates a non-breast origin, and CK7−/CK20+ immunoprofile strongly suggests colorectal origin (15). Based on previous research reports, CK7+/CK20 should be considered indicative of a tumor originating from the breast. GATA3 is also thought to be often positive in primary breast disease (16, 17). It was based on the immunohistochemical staining results of CK7 positive, CK20 negative, and GATA3 positive, combined with the opinions of multicenter pathologists, showing that the case was finally diagnosed as breast cancer with colon metastasis. Even though this case is very rare, we should still pay attention to the occurrence of colon metastasis in the diagnosis and treatment of breast cancer.
Conclusions
This case serves as a reminder to clinicians that they should consider rare sites of metastases and different receptor expression patterns in breast cancer patients in order to make more accurate treatment decisions. However, further research is needed to explore the mechanisms of this metastatic pattern and related treatment strategies.
Data availability statement
The datasets presented in this article are not readily available due to participant privacy. Requests to access the datasets should be directed to the corresponding authors.
Ethics statement
The studies involving humans were approved by Ethics Review Committee of Southern Central Hospital of Yunnan Province. The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.
Author contributions
HL: Investigation, Resources, Writing – original draft, Writing – review & editing. LY: Investigation, Writing – original draft. XS: Investigation, Writing – original draft. GL: Investigation, Writing – original draft. WG: Resources, Writing – original draft. FM: Writing – review & editing. ZW: Writing – review & editing. SQ: Writing – review & editing. CL: Writing – review & editing.
Funding
The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The present study was supported by the Scientific Research Project of Southern Central Hospital of Yunnan Province (grant no.KY202401).
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Publisher’s note
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Keywords: colon metastasis, progesterone receptor, estrogen receptor, non-specific types of breast cancer, breast cancer
Citation: Li H, Yang L, Sun X, Wang Z, Qin S, Li C, Liu G, Xie F and Gao W (2025) Changes in hormone receptor when breast cancer metastasizes to the colon: case report and literature review. Front. Oncol. 14:1391393. doi: 10.3389/fonc.2024.1391393
Received: 22 April 2024; Accepted: 27 December 2024;
Published: 29 January 2025.
Edited by:
Daniel Reis Waisberg, Hospital das Clinicas da Faculdade de Medicina da USP (HC-FMUSP), BrazilReviewed by:
Nektarios I. Koufopoulos, University General Hospital Attikon, GreeceHanen Bouaziz, Salah Azaiez Institute, Tunisia
Copyright © 2025 Li, Yang, Sun, Wang, Qin, Li, Liu, Xie and Gao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Weiwei Gao, d2Vpd2VpX2dhbzIwMjNAMTYzLmNvbQ==; Fengming Xie, ZmVuZ21pbmdfeGllQDE2My5jb20=
†These authors have contributed equally to this work