**Background:** Breast cancer is the world's most prevalent cancer, with approximately 2.3 million women diagnosed and 685,000 deaths globally through 2020. In the US, an estimated 287,850 new cases represent 15% of all new cancer cases. Approximately 90% of breast cancer incidence is sporadic, while 5–10% is hereditary, with BRCA1 and BRCA2 mutations increasing risk by 20–75% for carriers between ages 40 and 70. Pancreatic cancer, while less prevalent as the 12th most common cancer worldwide, is among the most lethal, with an estimated 89,248 people living with the disease in the US in 2019 and a 5-year survival rate of only 11.5%, compared to subtype-dependent breast cancer survival rates up to 91%. Both cancers share endocrine regulation and inflammatory mechanisms. This review systematically examined clinical trial data from 2015–2022 to identify inflammation-associated biomarkers with clinical utility in both cancers, with the goal of translating breast cancer knowledge to improve pancreatic cancer outcomes.
**Methods:** A systematic search strategy was developed through the Health Sciences Library at the University of North Carolina at Chapel Hill using PubMed MeSH terms. Three separate searches were conducted for pancreatic cancer, female breast cancer, and male breast cancer. The PubMed search yielded 2,084 results for pancreatic cancer, 7,786 for female breast cancer, and 488 for male breast cancer, plus 6 articles added manually. After filtration by publication year (2015–2022) and study design (randomized controlled trials or clinical trials only), 105 papers (23 pancreatic, 82 breast) were uploaded to Covidence for screening. After removing duplicates and full-text review, 73 articles (19 pancreatic, 54 breast) were included. Inclusion criteria required human studies focusing on cancer-related inflammatory/immune biomarkers. Exclusion criteria included publication before 2015, non-clinical trial designs, animal studies, and lack of cancer-related inflammation biomarker information.
**Key Results:** IL-6 was the most frequently measured biomarker in both cancers. In breast cancer, IL-6 levels decreased with interventions including exercise, San Huang decoction, Mindfulness-Based Stress Reduction, and the CCR2 inhibitor propagermanium, while some studies showed increases following chemotherapy. In pancreatic cancer, seven of 19 studies measured IL-6, with most showing lower levels indicating better outcomes. TNF-α was the second most common inflammatory cytokine in breast cancer, with six of ten studies showing lower levels indicating better prognosis. IL-8 showed consistent results across both cancers: five pancreatic cancer studies and three breast cancer studies all found lower IL-8 levels associated with better survival. The IL-6/IL-8 ratio emerged as important in both cancers—a ratio greater than 2.0 induced MCF-7 breast cancer cell proliferation, while chemoimmunotherapy-induced decreases in the ratio improved pancreatic cancer outcomes. CD4+ and CD8+ T cells were more frequently mentioned in pancreatic cancer studies than breast cancer, with higher levels generally indicating better outcomes. IDO-1 appeared in one study per cancer type, with both showing lower levels associated with better disease outcomes. Natural killer cells showed consistent results: increased levels indicated better immunity and outcomes in both cancers. C-reactive protein results were mixed: in breast cancer, adjuvant radiotherapy and synbiotic supplementation reduced CRP, while in pancreatic cancer, patients with liver metastases had higher CRP. VEGF showed contrasting patterns—increased in breast cancer patients treated with Sapylin (promoting wound healing) but increased with Pelareorep treatment in pancreatic cancer (indicating immunosuppression).
**Clinical Implications:** This review demonstrates substantial overlap in clinically relevant inflammatory biomarkers between breast and pancreatic cancers, supporting the premise that breast cancer research can inform pancreatic cancer strategies. The consistent finding that lower IL-6 and IL-8 levels predict better survival in both cancers suggests these markers could serve as universal prognostic tools. The IL-6/IL-8 ratio may be particularly valuable as a dual-cancer biomarker. Biomarkers currently validated only in breast cancer—including leptin, the adiponectin/leptin ratio, matrix metalloproteinases (MMP-2, MMP-9, MMP-1), and CCL2—warrant investigation in pancreatic cancer. The authors specifically highlight that CCL2 inhibition, which showed efficacy in breast cancer using propagermanium, deserves further study in pancreatic cancer after a CCR2 inhibitor trial showed limited efficacy. Given pancreatic cancer's late-stage diagnosis and 11.5% 5-year survival rate, identifying inflammatory biomarkers for earlier detection is critical. The review also notes that BRCA gene mutations, long established in hereditary breast cancer, are increasingly recognized in pancreatic cancer risk, suggesting that BRCA-targeted therapies like Olaparib could be explored for pancreatic cancer. Additionally, estrogen's opposing effects in these cancers (promoting breast cancer growth but inhibiting pancreatic cancer cell growth in experimental studies) highlight the need for cancer-specific therapeutic approaches.