Abstract
Purpose Galectin-3 (Gal-3) is a glycan-binding lectin with a debated role in cancer progression due to its various functions and patterns of expression. The current study investigates the relationship between breast cancer prognosis and secreted Gal-3. Methods Breast cancer patients with first time cancer diagnosis and no prior treatment (n = 88) were placed in either adjuvant or neoadjuvant setting based on their treatment modality. Stromal and plasma Gal-3 levels were measured in each patient at the time of diagnosis and then throughout treatment using immunohistochemistry (IHC) and ELISA, respectively. Healthy women (>18 years of age, n = 63) were used to establish baseline levels of plasma Gal-3. Patients were followed for 84 months for disease-free survival analysis. Results Enhanced levels of plasma (adjuvant) and stromal (neoadjuvant) Gal-3 were found to be markers of chemotherapy efficacy. The patients with chemotherapy-induced increase in extracellular Gal-3 had longer disease-free interval and significantly lower rate of recurrence during 84-month follow-up compared to patients with unchanged or decreased secretion. Conclusion The findings support the use of plasma Gal-3 as a marker for chemotherapy efficacy when no residual tumor is visible through imaging. Furthermore, stromal levels in any remaining tumors postchemotherapy can also be used to predict long-term prognosis in patients.
Highlights
While there have been significant advances in technology to diagnose breast cancer, accurate prognostic tools during treatment remain lacking
As levels of secreted Gal-3 in stroma and plasma of breast cancer patients were altered with varying grades, we examined if stromal Gal-3 levels change with chemotherapy and if they could be correlated to response in patients receiving adjuvant treatment following surgical removal of primary tumor
Pearson’s correlation tests show positive correlation between stromal Gal-3 levels and TUNEL reactivity in postchemotherapy samples (Supplemental fig. 3c & d; Pearson coefficient correlation = 0:730 postchemotherapy). These results propose a possible role of extracellular Gal-3 in induction of tumor apoptosis in response to chemotherapy
Summary
While there have been significant advances in technology to diagnose breast cancer, accurate prognostic tools during treatment remain lacking. A low-grade or localized tumor may be treatable with minimal chemotherapy after surgical removal (adjuvant) while a high-grade tumor may require initial aggressive chemotherapy to shrink the mass prior to surgery (neoadjuvant) [1]. Monitoring of therapy efficacy is essential, so that treatment may be continually optimized to reduce remaining cancer burden and possibility of disease relapse [2, 3]. Various measurements have been developed, including (1) size and cellularity of the primary tumor and nodal metastases [3], (2) imaging techniques such as MRI and PET/CT imaging [2, 4], and (3) circulating tumor cell DNA (ctDNA) detection [5]. Tissue-based biomarkers such as estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth
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