The patient underwent left modified radical mastectomy and right mastectomy with sentinel lymph node biopsy in May 2017. Pathology revealed invasive carcinoma in the left breast (NST, grade 2, size 3.5×2.5×2.3cm) with extensive lymph node involvement (9/14 axillary nodes and 2/6 sentinel nodes positive). Immunohistochemistry (IHC) revealed estrogen receptor (ER) positivity (90%), low Ki-67(11%), and HER2-negative status. The right breast showed low-grade DCIS with clear margins. Postoperative treatment included dose-dense chemotherapy (EC regimen followed by paclitaxel), chest wall radiotherapy, and endocrine therapy (anastrozole with goserelin). The patient initially achieved disease control with this approach.

In May 2019, bone metastasis was detected (Table 1). Despite continued endocrine therapy, progressive disease was noted, with chest wall and lymph node metastases observed in 2021. Biopsy of recurrent lesions revealed reduced ER expression (30%) and maintained HER2-negative status. Treatment was changed to exemestane plus palbociclib with goserelin. Further progression occurred with the development of pleural and pericardial effusions in 2022-2023. Cytology confirmed metastatic breast cancer with complete loss of hormone receptor expression and increased Ki-67 (60-80%). Endocrine therapy was discontinued in October 2022 due to the progression to ER-negative disease. The patient received salvage chemotherapy with docetaxel plus capecitabine (6 cycles), followed by maintenance capecitabine from February 2023.

In August 2024, seven years after initial diagnosis, the patient presented with changes in bowel habits and abdominal distention. CT imaging revealed rectal wall thickening (Figure 1), and colonoscopy revealed mucosal changes with stenosis 12 cm from the anal verge (Figure 2). Biopsy confirmed metastatic breast cancer with immunohistochemistry showing (-1 slice) P53 (mutant type), CK (+), INSM1 (-), Ki67 (50%). (-2 slices) P53 (mutant type), Rb (+), CK (+), CD56 (-), Syn (-), СgА (-), GATA3 (+), CDX2 (-), ER (-), PR (-), Her-2 (1+), GCDFP15 (-), Ki67 50%, SSTR2 (-), INSM1 (-). These findings confirmed that the rectal lesion was a metastasis from the primary breast cancer.

The patient currently has widespread metastatic disease involving multiple sites including bones, lymph nodes, pleura, pericardium, and rectum (Figure 3). An intestinal stent was placed to relieve obstruction.

October 2024, the patient’s pericardial effusion has also worsened. After drainage, dyspnea improved slightly. The patient’s general condition remains poor. Our outpatient department recommends intensifying supportive symptomatic treatment. If the patient’s general condition improves, subsequent treatment options may include erlotinib, chemotherapy, or ADC drugs. The patient’s family has requested discharge to seek palliative care.

While systemic metastasis of breast cancer (BC) predominantly involves the bones, lungs, liver, and brain, gastrointestinal (GI) tract involvement remains uncommon. A recent comprehensive review revealed that intestinal metastases from BC are detected in less than 5% of patients (3). Maekawa et al. reported that, in a cohort of 980 metastatic BC patients, only 0.5% exhibited GI tract metastases, with rectal involvement being particularly rare (7). Other cohort and case series studies report similarly low incidence rates (8, 9). These data emphasize the rarity of GI metastasis, particularly rectal involvement, which can contribute to underdiagnosis, especially when the clinical presentation is non-specific.

The clinical symptoms of GI metastasis from BC—such as bowel obstruction, changes in bowel habits, or nonspecific abdominal discomfort—often overlap with those of primary GI malignancies (10, 11). Given these diagnostic challenges, histopathology alone may be insufficient. Immunohistochemical (IHC) profiling is critical for accurate diagnosis. In several reported cases, IHC markers like GATA3 and GCDFP-15, combined with the absence of intestinal markers such as CDX2 or CK20, were pivotal in confirming the breast cancer origin (8, 10). Furthermore, as metastatic breast cancer often undergoes clonal evolution, comparing the IHC profiles of the metastatic site with the original primary tumor is essential for tailoring subsequent therapy (7, 8, 12). This underscores the necessity for a high index of suspicion and a comprehensive IHC evaluation, particularly for markers such as GATA3, which are crucial for confirming breast cancer metastasis (13, 14). Notably, the presence of GI metastases is generally indicative of advanced systemic disease, associated with a poor prognosis (15).

A review focused on lower GI tract metastases (including the colon, rectum, and small bowel) highlights that, while rare, such cases have been increasingly reported (3, 12). Although invasive lobular carcinoma (ILC) has traditionally been associated with a higher propensity for GI metastasis due to its diffuse growth and loss of E-cadherin, our case demonstrates that invasive ductal carcinoma (IDC) can also metastasize to the GI tract (8, 11, 16). This finding is crucial, as it underscores that clinicians should remain vigilant for GI/rectal metastasis in IDC cases as well. The latency between the initial breast cancer diagnosis and the appearance of GI metastasis can span several years, with some case reports documenting a 5–10-year gap (10, 17).

GI metastases from BC typically signal advanced systemic disease and are associated with a poor prognosis. Median survival following the detection of GI metastasis is often limited, with some series reporting a median survival of approximately one year (3, 10, 11) Given the systemic nature of the disease, systemic therapy remains the cornerstone of treatment. Endoscopic or surgical interventions, such as stent placement, are generally reserved for palliative purposes, particularly in cases of obstruction, bleeding, or severe symptoms (3, 8, 11). Although most data are derived from retrospective case series and reports, these findings emphasize the importance of individualized treatment plans based on receptor status, patient performance status, symptoms, and previous therapies (8).

In hormone receptor-positive (HR+) metastatic breast cancer, acquired resistance to endocrine therapy is frequently driven by mutations in ESR1 (18, 19). ESR1 mutations are recognized as a major mechanism of resistance in metastatic disease, particularly in HR+/HER2– breast cancer. The introduction of CDK4/6 inhibitors (CDK4/6i) has significantly improved the standard of care for this subtype; however, resistance eventually develops (20, 21). Studies on CDK4/6i resistance have identified several molecular alterations, including dysregulation of cell cycle regulators (e.g., RB1 loss, activation of the Cyclin E–CDK2 axis), reactivation of alternative mitogenic pathways (such as PI3K/AKT/mTOR), and possible epigenetic reprogramming (22). These alterations contribute to a shift toward estrogen-independent, more aggressive tumor clones (23–26).

In the case of our patient, the evolution from ER-positive IDC to ER-negative metastatic disease may have selected for subclones with increased invasive capacity, survival advantage, and the ability to colonize uncommon sites like the rectum. While direct evidence linking these molecular changes to rectal tropism is lacking, the convergence of receptor loss, cell-cycle deregulation, and therapy resistance provides a plausible biological explanation for the observed metastatic pattern. Once hormone receptor expression is lost, endocrine therapy becomes ineffective, and systemic chemotherapy remains the primary treatment option. Additionally, as our understanding of resistance mechanisms advances, novel therapeutic strategies targeting downstream pathways (e.g., PI3K/mTOR inhibitors) may offer new treatment avenues for future cases (20, 23). In the context of GI obstruction due to metastatic lesions, local palliative interventions, such as stent placement, are crucial for symptomatic relief and maintaining quality of life. A multidisciplinary approach, involving oncologists, gastroenterologists, and surgeons, is essential for managing such complex metastatic disease.