Abstract
BackgroundThe efficacy of neoadjuvant chemotherapy regimens in advanced luminal breast cancer patients is difficult to predict. Intrinsic properties of breast tumors, including altered gene expression profile and dynamic evaluation of metabolic properties of tumor cells using positron emission tomography/computed tomography (PET/CT) of tumor cells, have been identified to guide patient’s prognosis. The aim of this study is to determine if both analyses may improve the prediction of response to neoadjuvant chemotherapy in ER-positive / HER2-negative breast cancers (BCs) patients.MethodsWe used metabolic PET parameters, at diagnosis and after two cycles of chemotherapy and proliferation gene expression profile on biopsy at diagnosis, in particular, the genomic grade index (GGI) analyzed by reverse transcription and quantitative polymerase chain reaction (RT-qPCR). The pathological response was the surrogate endpoint.ResultsThe change of FDG uptake between baseline PET and interim PET after 2 cycles of neoadjuvant chemotherapy (ΔSUVmax) was highly associated with pCR (p=0.008). We also observed an ability of P53 mutated status (p=0.042), in addition to histological grade (p=0. 0004), and PR expression (p=0.01) to predict pCR in ER-positive BCs, whereas no proliferation marker predicted pCR (P=0.39 for GGI). Finally, only ΔSUVmax was significantly associated with event free survival (p=0.047).ConclusionsOur results confirm the predictive and prognostic value of tumor ΔSUVmax in ER-positive /HER2-negative advanced BCs patients. These findings can be helpful to select high-risk patients within trials investigating novel treatment strategies.
Highlights
Breast cancer (BC) is a heterogeneous disease with different phenotypes, each subtype having specific rates of response to therapy and specific prognoses [1, 2]
We observed an ability of P53 mutated status (p=0.042), in addition to histological grade (p=0. 0004), and PR expression (p=0.01) to predict pathological complete response (pCR) in ERpositive BCs, whereas no proliferation marker predicted pCR (P=0.39 for genomic grade index (GGI))
In the series of 75 luminal breast cancers, a mean of 18% [7 to 38%] cells were stained by MIB-1 antibodies using KI67 and 46/75 (64%) samples were considered as proliferative tumors, by automated counting
Summary
Breast cancer (BC) is a heterogeneous disease with different phenotypes, each subtype having specific rates of response to therapy and specific prognoses [1, 2]. Recent research and clinical trials have shown strong correlation of breast cancer responses to neoadjuvant therapies with survival and prognosis, mainly in triple negative and HER2overexpressing breast carcinoma [4]. PCR rate still varies according to treatment regimen and intrinsic subtype of tumor and is achieved in only 5-10 % of luminal breast cancer [4, 5]. The efficacy of neoadjuvant chemotherapy regimens in advanced luminal breast cancer patients is difficult to predict. The aim of this study is to determine if both analyses may improve the prediction of response to neoadjuvant chemotherapy in ER-positive / HER2-negative breast cancers (BCs) patients
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