Predictive Value of Immune Genomic Signatures from Breast Cancer Cohorts Containing Data for Both Response to Neoadjuvant Chemotherapy and Prognosis after Surgery

Abstract BackgroundPrevious studies of immune-related gene signatures (IGSs) in breast cancer have attempted to predict the response to chemotherapy or prognosis and were performed using different patient cohorts. The purpose of this study was to evaluate the predictive functions of various IGSs using the same patient cohort that included data for response to chemotherapy as well as the prognosis after surgery.MethodsWe applied five previously described IGS models in a public dataset of 508 breast cancer patients treated with neoadjuvant chemotherapy. The prognostic and predictive values of each model were evaluated, and their correlations were compared.ResultsWe observed a high proportion of expression concordance among the IGS models (r: 0.56-1). Higher gene expression scores of IGSs were detected in aggressive breast cancer subtypes (basal and HER2-enriched) (P < 0.001). Four of the five IGSs could predict chemotherapy responses and two could predict 5-year relapse-free survival in cases with hormone receptor-positive (HR+) tumors. However, the models showed no significant differences in their predictive abilities for hormone receptor-negative (HR-) tumors.ConclusionsIGSs are, to some extent, useful for predicting prognosis and chemotherapy response; moreover, they show substantial agreement for specific breast cancer subtypes. However, it is necessary to identify more compelling biomarkers for both prognosis and response to chemotherapy in HR- and HER2+ cases.

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Association between the nucleosome footprint of plasma DNA and neoadjuvant chemotherapy response for breast cancer

npj Breast Cancer ◽

10.1038/s41523-021-00237-5 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Xu Yang ◽

Geng-Xi Cai ◽

Bo-Wei Han ◽

Zhi-Wei Guo ◽

Ying-Song Wu ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Neoadjuvant Chemotherapy ◽

Cancer Patients ◽

Cell Receptor ◽

Chemotherapy Response ◽

Breast Cancer Patients ◽

Plasma Dna ◽

Transcription Start Sites ◽

Response To Chemotherapy

AbstractGene expression signatures have been used to predict the outcome of chemotherapy for breast cancer. The nucleosome footprint of cell-free DNA (cfDNA) carries gene expression information of the original tissues and thus may be used to predict the response to chemotherapy. Here we carried out the nucleosome positioning on cfDNA from 85 breast cancer patients and 85 healthy individuals and two cancer cell lines T-47D and MDA-MB-231 using low-coverage whole-genome sequencing (LCWGS) method. The patients showed distinct nucleosome footprints at Transcription Start Sites (TSSs) compared with normal donors. In order to identify the footprints of cfDNA corresponding with the responses to neoadjuvant chemotherapy in patients, we mapped on nucleosome positions on cfDNA of patients with different responses: responders (pretreatment, n = 28; post-1 cycle, post-3/4 cycles, and post-8 cycles of treatment, n = 12) and nonresponders (pretreatment, n = 10; post-1 cycle, post-3/4 cycles, and post-8 cycles of treatment, n = 10). The coverage depth near TSSs in plasma cfDNA differed significantly between responders and nonresponders at pretreatment, and also after neoadjuvant chemotherapy treatment cycles. We identified 232 TSSs with differential footprints at pretreatment and 321 after treatment and found enrichment in Gene Ontology terms such as cell growth inhibition, tumor suppressor, necrotic cell death, acute inflammatory response, T cell receptor signaling pathway, and positive regulation of vascular endothelial growth factor production. These results suggest that cfDNA nucleosome footprints may be used to predict the efficacy of neoadjuvant chemotherapy for breast cancer patients and thus may provide help in decision making for individual patients.

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Impact of Nuclear Oestrogen Receptor Beta Expression in Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy

Geburtshilfe und Frauenheilkunde ◽

10.1055/a-0987-9898 ◽

2019 ◽

Vol 79 (10) ◽

pp. 1110-1117

Author(s):

Florian Heitz ◽

Sherko Kümmel ◽

Bianca Lederer ◽

Christine Solbach ◽

Knut Engels ◽

...

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Hormone Receptor ◽

Oestrogen Receptor ◽

Multivariate Analyses ◽

Complete Response ◽

Breast Cancer Patients ◽

Hormone Receptor Positive ◽

The Impact ◽

Receptor Beta

Abstract Introduction Oestrogen receptor beta (ER-β) is abundantly expressed in breast cancer (BC), but its impact on neoadjuvant chemotherapy outcome is unknown. Patients and Methods Patients treated in the neoadjuvant GeparTrio trial with available tissue for immunohistochemical analyses were included. Nuclear ER-β expression was correlated with clinico-pathologic characteristics. The impact of its expression on pathological complete response (pCR [ypT0/ypN0]) and survival was determined. Results Samples of 570 patients were available. Low nuclear ER-β expression (IRS < 9) was observed in 48.4% of hormone receptor positive and 58.6% of hormone receptor negative tumours. Low nuclear ER-β expression was associated with higher pCR rates compared to high nuclear ER-β expression (16.1% vs. 4.7%, p = 0.026). Low ER-β expression was no independent predictor of pCR in multivariate analyses. Disease-free and overall survival were not statistically different between patients with high and low nuclear ER-β expression. Triple-negative BCs showed low nuclear ER-β expression in 57.7%, and pCR rates were 27.1% and 0% (p = 0.23) in low and high ER-β expressing tumours, respectively. Conclusion Low ER-β expression is associated with improved pCR rates in univariate analyses. However multivariate analyses and survival analyses do not indicate an impact of ER-β on survival in patients undergoing neoadjuvant chemotherapy. Further examination of ER-β as predictor for endocrine therapy might be of value.

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Factors Influencing Decision-Making for or against Adjuvant and Neoadjuvant Chemotherapy in Postmenopausal Hormone Receptor-Positive Breast Cancer Patients in the EvAluate-TM Study

Breast Care ◽

10.1159/000452468 ◽

2016 ◽

Vol 11 (5) ◽

pp. 315-322 ◽

Cited By ~ 2

Author(s):

Paul Gaß ◽

Peter A. Fasching ◽

Tanja Fehm ◽

Johann de Waal ◽

Mahdi Rezai ◽

...

Keyword(s):

Breast Cancer ◽

Decision Making ◽

Neoadjuvant Chemotherapy ◽

Neoadjuvant Therapy ◽

Hormone Receptor ◽

Patient Population ◽

Breast Cancer Patients ◽

Research Issues ◽

Hormone Receptor Positive ◽

Positive Breast Cancer

Background: Decision-making for or against neoadjuvant or adjuvant chemotherapy in postmenopausal patients with hormone receptor-positive breast cancer does not follow any clear guidelines, and some patients may unnecessarily undergo chemotherapy and be exposed to the associated toxicity. The aim of this study was to identify the patient population for whom this issue may bear relevance. Methods: Patients being treated with letrozole in the prospective multicenter noninterventional EvAluate-TM study were recruited. The percentage of patients receiving chemotherapy and factors associated with chemotherapy administration were identified. Results: In all, 3,924 (37.4%) patients received chemotherapy before treatment with letrozole. Of these, 293 (20%) underwent neoadjuvant therapy. Younger age was predictive for both adjuvant and neoadjuvant therapy. Overall, decisions in favor of administering chemotherapy are more likely to be made in patients with a higher body mass index (BMI), and neoadjuvant chemotherapy is administered at a higher rate in women with a lower BMI. Concomitant medication influenced the overall decision-making regarding chemotherapy, irrespective of whether it was given on a neoadjuvant or adjuvant basis. Conclusion: There is an ongoing debate as to whether all of the many patients who receive chemotherapy actually benefit from it. Neoadjuvant chemotherapy is frequently administered in this patient population, and this should encourage further research to resolve current clinical and research issues.

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