Hypoxia-Inducible Factor-1 Alpha Expression Is Predictive of Pathological Complete Response in Patients with Breast Cancer Receiving Neoadjuvant Chemotherapy

• Published in: Cancers 2022-11, Vol.14 (21), p.5393
• Main Authors: Ramírez-Tortosa, César L, Alonso-Calderón, Rubén, Gálvez-Navas, José María, Pérez-Ramírez, Cristina, Quiles, José Luis, Sánchez-Rovira, Pedro, Jiménez-Morales, Alberto, Ramírez-Tortosa, MCarmen
• Format: Article
• Language: English
• Subjects: Anthracycline; Antigens; Biopsy; Breast cancer; Breast carcinoma; Cancer therapies; Carcinogenesis; Care and treatment; Chemotherapy; Chi-square test; Cloning; Development and progression; Epidermal growth factor receptors; Gene amplification; Health aspects; Hypoxia; Hypoxia-inducible factor 1; Hypoxia-inducible factor 1a; Immunohistochemistry; Kinases; Medical prognosis; Methods; Monoclonal antibodies; Multivariate analysis; Neoadjuvant therapy; Patient outcomes; Patients; Phenotypes; Progesterone; Progesterone receptors; Statistical analysis; Surgery; Taxanes; Transcription factors; Tumor cells; Tumors
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers14215393

To demonstrate the value of hypoxia-inducible factor-1α (HIF-1α) in predicting response in patients with breast cancer receiving standard neoadjuvant chemotherapy (NAC). Methods: Ninety-five women enrolled in two prospective studies underwent biopsies for the histopathological diagnosis of breast carcinoma before receiving NAC, based on anthracyclines and taxanes. For expression of HIF-1α, EGFR, pAKT and pMAPK, tumor samples were analyzed by immunohistochemistry in tissues microarrays. Standard statistical methods (Pearson chi-square test, Fisher exact test, Kruskal–Wallis test, Mann–Whitney test and Kaplan–Meier method) were used to study the association of HIF-1α with tumor response, survival and other clinicopathologic variables/biomarkers. Results: HIF-1α expression was positive in 35 (39.7%) cases and was significantly associated to complete pathological response (pCR) (p = 0.014). HIF-1α expression was correlated positively with tumor grade (p = 0.015) and Ki-67 expression (p = 0.001) and negativity with progesterone receptors (PR) (p = 0.04) and luminal A phenotype expression (p = 0.005). No correlation was found between HIF-1α expression and EGFR, pAKT and pMAPK. In terms of survival, HIF-1α expression was associated with a significantly shorter disease-free survival (p = 0.013), being identified as an independent prognostic factor in multivariate analysis. Conclusions: Overexpression of HIF-1α is a predictor of pCR and shorter DFS; it would be valuable to confirm these results in prospective studies.