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

SIMPLE SUMMARY: Standard neoadjuvant chemotherapy, based on taxanes and anthracyclines, makes conservative treatment of breast cancer possible and it allows for the evaluation of the tumor response in terms of achieving pathological complete response. Whereas hypoxia participates in carcinogenesis, resulting in less differenced tumor cells and poorer prognosis, HIF-1α could be predictive of the tumor response to treatment. Nonetheless, very few studies have evaluated the predictive value of HIF-1α in breast cancer in patients receiving neoadjuvant chemotherapy. ABSTRACT: 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.