Estrogen Receptor and Claudin-6 Might Play Vital Roles for Long-Term Prognosis in Patients With Luminal A Breast Cancer Who Underwent Neoadjuvant Chemotherapy

FRONTIERS IN ONCOLOGY(2022)

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Abstract
PurposeIt is well-known that the pathological complete response (pCR) rate in patients with luminal A cancer (LAC) is lower than those of other subtypes of breast cancer. The phenotype of cancer often alters after neoadjuvant chemotherapy (NAC) which may be related to hypoxia, and the latter might induce the drift of the estrogen receptor (ER). The phenotype drift in local advanced LAC after NAC might influence the long-term prognosis. MethodsThe oxygen concentration of cancer tissues during NAC was recorded and analyzed (n = 43). The expression of ER and claudin-6 was detected in pre- and post-NAC specimens. ResultsNAC might induce the cycling intracanceral hypoxia, and the pattern was related to NAC response. The median follow-up time was 61 months. Most of the patients (67%) with stable or increased ER and claudin-6 expression exhibited perfect prognosis (DFS = 100%, 61 months). About 20% of patients with decreased claudin-6 would undergo the poor prognosis (DFS = 22.2%, 61 months). The contrasting prognosis (100% vs. 22.2%) had nothing to do with the response of NAC in the above patients. Only 13% patients had stable claudin-6 and decreased ER, whose prognosis might relate to the response of NAC. ConclusionNAC might induce cycling intracanceral hypoxia to promote the phenotype drift in local advanced LAC, and the changes in ER and claudin-6 after NAC would determine the long-term prognosis.
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Key words
luminal A breast cancer, cycling hypoxia, estrogen receptor, claudin-6, neoadjuvant chemotherapy
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