CASE REPORT article

Front. Oncol., 29 January 2025

Sec. Gastrointestinal Cancers: Colorectal Cancer

Volume 14 - 2024 | https://doi.org/10.3389/fonc.2024.1391393

Changes in hormone receptor when breast cancer metastasizes to the colon: case report and literature review

  • HL

    Huimeng Li 1

  • LY

    Liying Yang 2

  • XS

    Xiqiang Sun 3

  • ZW

    Zhuquan Wang 1

  • SQ

    Shuangwei Qin 1

  • CL

    Chengcheng Li 1

  • GL

    Gongwu Liu 3

  • FX

    Fengming Xie 1*

  • WG

    Weiwei Gao 4*

  • 1. Department 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

  • 2. Department 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

  • 3. Department 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

  • 4. Department 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

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Abstract

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

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

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

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

Figure 5

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

AuthorYearAgePrimary(breast)TreatmentTime since first diagnosis (years)Metastasis
SitePathological typesBiomarkersSiteBiomarkers
Takeuchi H (18)201238leftILCER+,PR-,HER2-Surgery, Chemotherapy, Radiation therapy, Endocrine Therapy3Stomach and ColonER+,PR-, HER2-
-
Jansen van Rensburg A (19)202174leftDCER+,PR-Surgery, Radiation therapy, Endocrine Therapy27Bone,ovary, sigmoid colonER +, PR+
E-cadherin+, GATA3+,CK20-
Sheen-Chen SM (20)200841rightIDCSimultaneousovary and omentum-
CK7+、CEA+、CK20-
Higley C (21)202074rightbreast-conserving surgery and radiation therapy, Endocrine Therapy40transverse colon.ER-、PR-、HER2-
CDX-2-、CK20-、GATA3+、E-cadherin-、PD-L1-
Khan I (22)201756rightring cell adenocarcinomaSimultaneousstomach, small intestine, and
colon
Noor A (23)202068ILCER+,PR+,HER2-Surgery, Radiation therapy, Endocrine Therapy30Bone、sigmoid colonER+、PR+、HER2-,CK7+, CK20-,CDX2-,CA19-9-
Bering J (5)202067leftILCER+,PR+,HER2-Endocrine TherapySimultaneoustransverse colonER-,PR-,HER2+
GATA3+,CK7+,CDX2-,CK20-,E-cadherin-,GCDFP-15+
Abid A (24)201359leftLCER+,PR+,HER2-Simultaneousstomach, duodenum, and colonER+、PR+
GCDFP-15+
Takedomi H (4)201976rightILCChemotherapySimultaneousdescending colon-
GCDFP-15+,mammaglobin+
Abu Zaanona MI (25)202073Endocrine TherapycolonER+,PR-,HER2-,Pancytokeratin+, GATA3 +, E-cadherin-, CDX2-,
SOX10-
Inoue H (26)202263rightChemotherapy,Endocrine Therapy15ER+,PR-,HER2+,CK7+, GATA3+, ER+, HER2+, CK20-, PR-, E-cadherin-, GCDFP15- ,caudal-related homeobox 2
Mostafa A (27)200256IDCER+,PR+Surgery, Radiation therapy, Endocrine Therapy5descending colonER-,PR--
Tsujimura K (28)201751leftILCER+,PR+SimultaneousileocecalER+,PR+,HER2-
Feng CL (29)200949rightIDC2ColonCK7+, CK20-
Kobayashi M (30)202074ILCsurgery23stomach
and colon
CAM5.2+,ER+, E-cadherin-
Théraux J (31)200869bilateralIDCSurgery, Endocrine Therapy28transverse colonER+,PR+, HER2-, CK7+, CK20-
Malhotra A (32)200971bone, transverse colon
Villa Guzmán JC (33)201758ILCER+,PR+,HER2-Surgery, Chemotherapy, Radiation therapy, Endocrine Therapy3stomachcytokeratin-19+,ER+
Gerova VA (34)201256leftILCPR+Surgery, Chemotherapy, Radiation therapy, Endocrine Therapy5stenotic, stomach
42leftER+,PR+Surgery, Chemotherapy, Radiation therapy, Endocrine Therapy7stomachER+,PR+,CK7+, E-cadherin+,S-100+, GCFP15-,CDX2-
Wang G (35)201470leftIDCE-cadherin+、34βE12-、ER+、PR+、CK19+、CK20+Surgery, Radiation therapy, Endocrine Therapy10ascending colonCK7+、E-cadherin+、34βE12-、ER+、GCDFP-15+、CK19+、CK20+
Cho DH (36)201146bilateralIDCER+,PR+,HER2-Surgery, Chemotherapy, Radiation therapy, Endocrine Therapy2terminal
ileum
ER+,PR-,HER2+,
Algethami NE (37)202247bilateralILCER+,PR+,HER2-Surgery, Radiation therapy, Endocrine Therapy4rectumER+、HER2+、Pan-cytokeratin +
Zhou XC (38)201254rightIDCER+,PR+,P53+,
HER2-
Surgery, Chemotherapy, Radiation therapy, Endocrine Therapy8sigmoid colonCDX2-, Villin-, TTF-1-, -CK20-, HER2-, ER- ,PR-,
CK7+,p53+
Andriola V (39)201463leftIDC,LCSurgery, Chemotherapy, Radiation therapy, Endocrine Therapy23colon and terminal
ileum
CK19+, GCFDP-15+,HER2+
Motos-Micó J (40)201469rightILCSurgery, Chemotherapy18sigmoid colonER-,PR-,HER2-,CK7+
Abdallah H (41)202059rightILCER+,PR+,HER2-Simultaneousendometrium, myometrium, fibroid and cervixCK7+,GATA3+,ER+,PR+, desmin-, CD10-, actin- ,Caldesmon-
66rightILCCK+,ER+,PR+,HER2-SimultaneousColonCK7+,GATA-3+,ER+,CK20-,CDX2-
53rightILCSimultaneousintestine, omentum, and peritoneal wall, bilateral ovarian, stomachCK7+、GATA-3+,ER+,E-cadherin+,CK20-,CDX2-
Michalopoulos A (42)200455leftIDCSurgery, Chemotherapy4transverse
colon
CK7+,milk-fat globule protein+,
57leftILCSurgery, Chemotherapy, Radiation therapy10transverse
colon
CK7+,milk-fat globule protein+, CEA+,ER+, weakly positive for cytokeratin 20 and Breast II.
Schellenberg AE (43)201869leftIDCE-cadherin+,ER+,PR+,HER2+Surgery, Chemotherapy, Radiation therapy, Endocrine Therapy2rectosigmoidCK-7+, E-cadherin+, GCDFP+, mammoglobin+,ER+,PR+,CK-20-,CDX-2--
Matsuda I (44)201262leftILCSurgery24ascending colon and rectumCK7+,ER+,CK20-,E-cadherin-
Koleilat I (45)201054rightIDCSurgery, Chemotherapy, Radiation therapy, Endocrine Therapy13colonER+,PR+,HER2-
Mistrangelo M (46)201180leftILCSurgery, Endocrine Therapy25sigmoid colon
Razzetta F (47)201177bilateralILC(left),IDC(right)Simultaneousright, transverse and left colonER+,PR-
Cervi G (48)200159ILCSurgery8rectumER+,PR+
Amin AA (49)201161rightILCSurgery, Endocrine Therapy17rectumCK 20-,ER+,CK7+,PR+
López Deogracias M (6)200967leftILCER+,PR+Surgery15rectumER-,PR-,CK20-,CDX2-
Law WL (50)200349leftIDCER+Surgery, Endocrine Therapy5descending
colon
ER+
Samra B (51)201964colon,right sacral iliacCK-7+,GATA-3+,ER+,MOC31+,CK-20-,CD-X2-,PR-,PAX-8-,SOX-10-,CD4-5,chromogranin-, synaptophysin-, TTF-1-
Kim HW (52)201446rightmetaplasticER-,PR-,HER2-Surgery, Chemotherapy, Radiation therapy2sigmoid colonCK20-,CK5/6-,ER-,PR-,HER2-,CK7+
Signorelli C (53)200562rightILCSurgery12right chest wall, colonER+,PR+,P53-,HER2-
Gizzi G (54)201572ER+,PR+Surgery, Chemotherapy, Radiation therapy, Endocrine Therapy11sigmoid colonCK7+,GATA3+, ER+,PR+,HER2-
Dhar S (55)200375leftER+Surgery6sigmoid colonER+,CK7+,CK20-
Maekawa H (56)201252rightIDCER+,PR+Surgery, Chemotherapy, Radiation therapy, Endocrine Therapy16ascending colon
Koufopoulos N (57)201887Colonic serosaCK-20-,CDX-2-,CK7-,r GATA-3+, mammaglogin+,ER+,PR+, E-cadherin-, Chromogranin-,synaptophysin-
Critchley AC (58)201162IDCSurgery, Chemotherapy, Radiation therapy, Endocrine Therapy8stomach, ascending colonER+,PR+,HER2-,CK7+,CK20-
Kachi A (59)201958leftILCSurgery, Chemotherapy, Radiation therapy, Endocrine Therapy6sigmoid colon, appendix, and ovaries.ER+,PR+
Blachman-Braun R (60)201873bilateralSurgery, Chemotherapy,15colonER+,PR-,HER2-
Jia J (61)202367rightIDCER+,PR+,HER2-Surgery, Chemotherapy, Endocrine Therapy10Appendix, colonGATA-3+,GCDFP-15+,ER+,PR+,HER2+, E-cadherin+,p120+,CK7+,CK20-,SATB-2-,Villin-,syn-,CgA-,CD56-
Arif FZ (62)202365bilateralIDCtriple-negative (left), HER2+(right)descending colon

Case reports of breast carcinomas with colonic metastases.

ILC, Invasive lobular carcinoma; IDC, Invasive ductal carcinoma; DC, ductal carcinoma; LC, lobular carcinoma; ER, estrogen receptor; PR, progesterone receptor; HER2, human epidermal growth factor receptor-2; CK7, Cytokeratin 7; CK20, Cytokeratin 20; GATA3, GATA 3 binding protein. CEA, Carcinoembryonic antigen; CDX2, caudal-related homeobox transcription factor 2; GCDFP, Gross cystic disease fluid protein; CAM5.2, cytokeratin CAM5.2; S-100, closely related, small, acidic Ca2+-binding proteins; 34βE12, cytokeratin 34βE12; P53, tumour suppressor gene p53; PAX-8, a nephric cell lineage transcription factor; SOX-10, SRY-related HMG-box 10; CD45, receptor-like protein tyrosine phosphatase; TTF-1, Thyroid transcription factor 1; CK5/6, cytokeratin 5/6; p120, p120-catenin; SATB-2, special AT-rich sequence-binding protein 2; syn, Synuclein; CgA, Chlorogenic acid; CD56, Neural cell adhesion molecule; SOX10, transcription factors SOX10.

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 (710). 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.

Statements

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

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

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Summary

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

Volume

14 - 2024

Edited by

Daniel Reis Waisberg, Hospital das Clinicas da Faculdade de Medicina da USP (HC-FMUSP), Brazil

Reviewed by

Nektarios I. Koufopoulos, University General Hospital Attikon, Greece

Hanen Bouaziz, Salah Azaiez Institute, Tunisia

Updates

Copyright

*Correspondence: Weiwei Gao, ; Fengming Xie,

†These authors have contributed equally to this work

Disclaimer

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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