Ulcerative colitis (UC), one of the two primary forms of inflammatory bowel disease (IBD), is characterized by mucosal inflammation extending continuously from the rectum to the proximal colon (1). While the exact etiology of IBD remains incompletely understood, current evidence suggests a multifactorial pathogenesis involving molecular and cellular mechanisms, microbial factors, microbiome interactions, genetic predisposition, and immune dysregulation (2). Similar to other chronic inflammatory conditions, UC is associated with an elevated risk of malignancy. Notably, colitis-associated cancer (CAC)—colorectal cancer being the most prevalent—demonstrates risk stratification based on factors including age at diagnosis, disease duration, and disease severity (3). Given the elevated cancer risk associated with autoimmune diseases (AIDs), there has been growing attention on the long-term management of patients with pre-existing AIDs (4). Recent studies have yielded divergent findings regarding the cancer risks of different AIDs, with some conditions, such as rheumatoid arthritis (RA), potentially conferring a reduced risk rather than an increased one (5). Using breast cancer as an example, recent research has revealed that the impact of autoimmune disorders on breast cancer development extends far beyond the initially recognized association with thyroid disease, particularly the involvement of both anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-TG) antibodies (6, 7). Furthermore, mounting evidence confirms a bidirectional interplay between AIDs and cancer, wherein certain malignancies may significantly alter susceptibility to subsequent autoimmune conditions. This relationship is exemplified by a nationwide population-based cohort study (Chen et al.), which revealed that breast cancer patients showed markedly reduced incidence rates of systemic lupus erythematosus (SLE), RA, and Sjögren’s syndrome (SS) compared to matched controls (8, 9).

A 58-year-old female patient underwent sequential radical mastectomies, first on the right breast (20 September 2023) and then followed by the left breast (8 November 2023). Histopathological analysis revealed the following: Right breast: invasive ductal carcinoma (Estrogen receptor (ER) >90%, Progesterone receptor (PR) 60%, Human epidermal growth factor receptor 2 (Her2) 1+, Ki-67 10-20%), pathological stage pT2N0Mx; Left breast: predominantly ductal carcinoma in situ with focal invasive ductal carcinoma (ER <1%, PR <1%, HER2 3+, Ki-67 40%), pathological stage pT1bN0Mx ( Table 1 ). The patient initiated the AC-THP adjuvant chemotherapy regimen, completing four cycles (cyclophosphamide 0.8g d1 + doxorubicin liposome 50mg d1, Q3W). During the fifth cycle (trastuzumab 560mg d0 + pertuzumab 840mg d0 + albumin-bound paclitaxel 400mg d1), she developed acute hematochezia (approximately 10 episodes per day). Emergency endoscopy demonstrated diffuse superficial colonic ulcers ( Figure 1 ), though a biopsy was refused by the patient due to bleeding concerns. Given the result of negative stool cultures and C. difficile toxin assays, the absence of serum autoimmune antibodies ( Table 2 ), and the clinical improvement following glucocorticoid and mesalazine therapy, combined with the endoscopic findings, the patient was diagnosed with UC. Follow-up endoscopy (January 2, 2025) showed complete ulcer resolution ( Figure 2 ). The complete treatment timeline summarizing the main events is shown in Figure 3 .

Bilateral breast cancer represents a distinct and relatively uncommon form of malignant breast neoplasia, characterized by independent primary tumors originating from the ductal and/or lobular epithelium in both breasts, either synchronously or metachronously. Since Kilgore’s initial description in 1921 (10), reported cases have progressively increased, with synchronous bilateral breast cancer (SBBC) constituting ≤5% of all breast malignancies (11). UC, an idiopathic chronic inflammatory disorder of the colonic mucosa (with potential pancolonic involvement), typically manifests with relapsing-remitting hematochezia (12). We herein present a rare case of synchronous bilateral breast cancer complicated by UC. The mechanisms underlying CAC involve multiple molecular pathways that may include genetic mutations, such as TP53 gene alterations; inflammatory signaling, such as TLR4-MyD88-dependent NF-κB activation, which perpetuates a pro-inflammatory microenvironment; the prostaglandin pathway, such as COX-2-mediated PGE2 production, promoting angiogenesis and immune modulation via PI3K signaling; metabolic reprogramming, such as PI3K/AKT activation by cytokines that facilitates GLUT4 translocation, enhancing TH2 and TH17 lymphocyte metabolism; genetic regulation, such as modifications in key regulatory genes (IL23R and rs10889677 [c.*309C>A]) of the PI3K/AKT signaling pathway. These molecular alterations interact with immune components (macrophages, neutrophils, and T-regulatory cells) and cellular processes (autophagy), ultimately driving CAC development (13).

Similarities in the pathologies of autoimmune diseases and cancers can be traced back at least 30 years. Autoimmune diseases result from the breakdown of peripheral immune tolerance, specifically, the disruption of the delicate balance between immune tolerance and immune activation. This equilibrium is normally maintained by specialized cell subsets, such as regulatory T cells (Tregs) and B cells (Bregs), macrophages, fibroblasts, and myeloid-derived suppressor cells (MDSCs) (14). When this balance is disturbed, it leads to pathological immune overactivation. While the recruitment of tolerogenic immune cell subsets and evasion of immune surveillance are recognized as the hallmarks of cancer, often termed “cancer tolerance”, malignant cells achieve this through multiple mechanisms. These include the expression of immune checkpoint proteins, impaired antigen presentation, epithelial-to-mesenchymal transition (EMT), and dysregulated RNA editing. A very important part of this complex network is the microbiome, as both the microbiome and its metabolites can exert pro-tumor function, and a gut microbiota imbalance can cause gastrointestinal cancers or IBD (15). Inflammatory cytokines and growth factors mediate cell proliferation, and proteinases, especially the collagenase, matrix metalloproteinase-1 (MMP-1), contribute to disease progression by remodeling the extracellular matrix and modulating the microenvironment (16). Chronic inflammation caused by autoimmune diseases or the anti-rheumatic therapies and oncogenic virus infections, such as human papillomavirus, hepatitis B and C viruses, and Epstein–Barr virus, which are difficult to treat, may contribute to the development and progression of cancer (8). Autoimmuity-induced chronic inflammation and tissue damage may produce inflammatory mediators, such as TNF-α, interleukin (IL)-6, tumor growth factor (TGF)-β, and IL-10, leading to the failure of Treg-mediated immune tolerance and stimulating the development of malignant tumors through various mechanisms such as DNA damage, inactivation of tumor-suppressor genes, triggering of angiogenesis, and enhancing invasiveness (17).

Conversely, anti-tumor immune responses may cross-react with self-tissues, leading to the development of autoimmunity (6). Previous studies indicate that patients with pre-existing autoimmune diseases often exhibit shortened survival, primarily attributable to the direct or indirect immune-related adverse events (irAEs) induced by anti-tumor therapies such as chemotherapy, radiation therapy, and, notably, the accumulated application of immune checkpoint inhibitor in the management of advanced tumors (18), leading to the flare-up or onset of autoimmune diseases (8, 19, 20). Numerous chemotherapeutic agents have been implicated in the development of autoimmune-like manifestations, especially bleomycin, gemcitabine, carboplatin, and paclitaxel have been associated with scleroderma-like syndromes and Raynaud’s phenomenon (21). Aromatase inhibitors (AIs), a mainstay of hormone receptor-positive breast cancer treatment, frequently induce arthralgias (22). Radiotherapy targeting the head and neck regions can induce xerostomia that clinically resembles primary Sjögren’s syndrome. Emerging evidence suggests that approximately 50% of breast cancer patients may develop radiation-induced cutaneous fibrosis at treatment sites, though current studies remain limited by small cohort sizes and methodological constraints (23). In patients with SLE, low levels of transforming growth factor-beta 1 (TGF-β1) correlate with increased disease severity. Therefore, radiotherapy-induced TGF-β release may have therapeutic potential in SLE by compensating for this deficiency (24). ICIs induce uncontrolled T-cell activation, resulting in systemic inflammatory syndromes that may involve multiple organ systems. These irAEs can manifest as autoimmune-like pathologies affecting the skin, endocrine, gastrointestinal, cardiovascular, pulmonary, and neurological systems (25, 26). The patient in this case report received multiple chemotherapy, targeted, and endocrine therapies. While treatment-induced colitis has not been previously reported with these specific regimens, the potential for immune-related adverse events, including autoimmune-like manifestations such as colitis, cannot be ruled out.

Breast cancer and autoimmune diseases represent two prevalent conditions that threaten women’s health, with growing evidence suggesting their complex bidirectional relationship. This case highlights the co-occurrence of breast cancer and UC, offering several important insights. While colorectal cancer remains the predominant malignancy associated with UC, this case suggests the potential oncogenic effects of UC beyond the colon. The patient’s diverse therapeutic regimens (chemotherapy, targeted agents, and endocrine therapy) may have contributed to UC development, consistent with established evidence linking anticancer treatments and autoimmune-like manifestations. However, there is also a limitation as the exact causal relationship between breast cancer and UC in this case remains undetermined. This also calls for clinical vigilance regarding autoimmune manifestations in cancer patients and the requirement for large-cohort studies to elucidate the disease-disease interactions and treatment-related autoimmune effects to provide guidelines for oncologists, immunologists, and gastroenterologists to optimize care for patients with overlapping cancer and autoimmune diseases.