Context: Breast cancer is the most common malignancy in women. Noninvasive biomarkers are needed for its early diagnosis and/or prognosis.
Objective: The aim of this case-control study was the comparison of serum activins, follistatins, and members of the IGF family levels in women with benign vs malignant breast neoplasms vs apparently healthy controls.
Design and patients: Women with breast benign (n = 100) or malignant tumors (n = 145) and disease-free controls (n = 100) were recruited. Women with breast cancer were subsequently subdivided into recently diagnosed/treatment-naive (n = 112) and chemotherapy-treated (n = 33). Anthropometric, demographic, biochemical, and histological data were recorded.
Setting: A breast cancer clinic in Thessaloniki, Greece.
Main outcome measures: Serum levels of activin A, activin B, follistatin, follistatin-like (FSTL)-3, total IGF-1, total and intact insulin-like growth factor binding protein (IGFBP)-4 and pregnancy-associated plasma protein-A (PAPP-A) were measured with highly specific ELISA kits.
Results: In adjusted comparisons, substantial differences in FSTL-3, total and intact IGFBP-4, PAPP-A, and total IGF-1 were observed between groups. In logistic regression analysis, primarily total IGFBP-4 levels were independently associated with the overall presence of breast malignancy. FSTL-3 was the only variable that could distinguish between a benign vs malignant breast mass. In linear regression analysis, FSTL-3 was independently associated with tumor size.
Conclusions: We showed that members of the IGF-1/IGFBP-4/PAPP-A axis and FSTL-3 may serve as surrogate markers in breast cancer. Future mechanistic and longitudinal studies and/or clinical trials are needed to explore the efficacy of these molecules as noninvasive biomarkers and their possible therapeutic potential in breast cancer.