Molecular signature of response to preoperative radiotherapy in locally advanced breast cancer

Tanić, Miljana; Krivokuća, Ana; Čavić, Milena; Mladenovic, Jasmina; Karapandžić, Vesna Plešinac; Beck, Stephan; Radulović, Siniša; Šušnjar, Snežana; Janković, Radmila

doi:10.1186/s13014-018-1129-4

Cited by 18 publications

(23 citation statements)

References 42 publications

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“…Only one study that correlates MMPs and TIMPs with RT was found on the GEO database (GSE101920). 34 This study shows the gene expression profile in BC biopsies taken both prior to RT, and after RT and radical mastectomy. Due to the limited number of matched samples (n = 5) obtained, the study was continued by focusing on the analysis of pre-RT biopsies only.…”

Section: Geo Databasementioning

confidence: 92%

Matrix metalloproteases and TIMPs as prognostic biomarkers in breast cancer patients treated with radiotherapy: A pilot study

Olivares-Urbano

Griñán‐Lisón

Zurita

et al. 2019

J Cellular Molecular Medi

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Breast cancer (BC) is the most common tumour in women and one of the most important causes of cancer death worldwide. Radiation therapy (RT) is widely used for BC treatment. Some proteins have been identified as prognostic factors for BC (Ki67, p53, E‐cadherin, HER2). In the last years, it has been shown that variations in the expression of MMPs and TIMPs may contribute to the development of BC. The aim of this pilot work was to study the effects of RT on different MMPs (‐1, ‐2, ‐3, ‐7, ‐8, ‐9, ‐10, ‐12 and ‐13) and TIMPs (‐1 to ‐4), as well as their relationship with other variables related to patient characteristics and tumour biology. A group of 20 BC patients treated with RT were recruited. MMP and TIMP serum levels were analysed by immunoassay before, during and after RT. Our pilot study showed a slight increase in the levels of most MMP and TIMP with RT. However, RT produced a significantly decrease in TIMP‐1 and TIMP‐3 levels. Significant correlations were found between MMP‐3 and TIMP‐4 levels, and some of the variables studied related to patient characteristics and tumour biology. Moreover, MMP‐9 and TIMP‐3 levels could be predictive of RT toxicity. For this reason, MMP‐3, MMP‐9, TIMP‐3 and TIMP‐4 could be used as potential prognostic and predictive biomarkers for BC patients treated with RT.

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Section: Geo Databasementioning

confidence: 92%

Matrix metalloproteases and TIMPs as prognostic biomarkers in breast cancer patients treated with radiotherapy: A pilot study

Olivares-Urbano

Griñán‐Lisón

Zurita

et al. 2019

J Cellular Molecular Medi

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“…The standard treatment of locally advanced breast cancer (LABC) is almost always multimodal and involves systemic therapy with chemotherapy (CT) and/or hormone therapy (HT), surgery and RT 4 5. Systemic therapy is usually the first approach, however, more than a third of patients may not respond as expected 6 7. When inoperability criteria prevails, RT should be used for tumour downstaging.…”

Section: Introductionmentioning

confidence: 99%

Neoadjuvant radiotherapy in the approach of locally advanced breast cancer

et al. 2020

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BackgroundApproximately 4% of European patients are diagnosed with locally advanced breast cancer (LABC), a clinical condition commonly associated with poorer prognosis. Systemic therapy is the recommended initial treatment and when inoperability criteria prevails, radiotherapy (RT) should be used for tumour downstaging. This study intends to evaluate the impact of neoadjuvant radiotherapy (NART) in the treatment of inoperable LABC.MethodsA retrospective study of female patients, submitted to the NART between January 2014 and December 2018 at our institution. The evaluation of pathological response (pR) was made based on Pinder criteria. Primary endpoint: pR. Secondary endpoints: overall survival (OS) and progression-free survival (PFS). OS and PFS were calculated using the Kaplan-Meier method. Differences between groups were compared using Student’s t-test, ANOVA (Analysis of variance) and χ2 test. The statistical analyses were performed using Stata (V.13).ResultsA total of 76 patients were included, 18% with breast complete response. The 5 years OS was 54% and PFS was 61%. Subgroup analysis showed that pR >90% is correlated with a better OS (p=0.004). Basal-like intrinsic subtype is correlated with worse OS and PFS (p<0.05). No relation was found between response and age, intrinsic subtype, treatment performed and clinical T stage.ConclusionOur study confirms that NART is an effective downsizing treatment in inoperable LABC, allowing for a surgical resection regardless of the systemic treatment performed. Response to NART is independent of the intrinsic subtype and pR >90% is correlated with a better OS. Prospective studies to explore predictive response biomarkers are necessary in order to improve patient selection and optimisation of the treatment.

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“…Previous studies have generated an RSS base on the intrinsic radiosensitivity in BRCA by the integration of post-radiation clonogenic survival data with gene expression data [11,[24][25][26]. To demonstrate whether immune infiltration level has predictive ability for RT outcomes, we developed a Radiosensitivity Signature (RSS) in BRCA ( Figure 5).…”

Section: Brca Radiosensitivity Signature Based On Immune Infiltrationmentioning

confidence: 99%

“…Finally, Gene Ontology (GO) analyses were employed to define key molecular biomarkers governing response to radiation in rectal cancer [9]. However, all these studies were based on the intrinsic radiation response of tumor cells and the effects of the TME on this response were ignored [10,11].…”

Section: Introductionmentioning

confidence: 99%

“…Each picture corresponds to a different type of cancer BRCA (B), CESC (C-F), GBM(G), HNSC (H, I), LGG (J), THCA (K-P).2.1.4. BRCA radiosensitivity signature based on immune infiltrationPrevious studies have generated an RSS base on the intrinsic radiosensitivity in BRCA by the integration of post-radiation clonogenic survival data with gene expression data[11,[24][25][26]. To…”

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confidence: 99%

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Pan-Cancer Analysis of Radiotherapy Benefits and Immune Infiltration in Multiple Human Cancers

Wen

Gao

Chen

et al. 2020

Cancers

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Response to radiotherapy (RT) in cancers varies widely among patients. Therefore, it is very important to predict who will benefit from RT before clinical treatment. Consideration of the immune tumor microenvironment (TME) could provide novel insight into tumor treatment options. In this study, we investigated the link between immune infiltration status and clinical RT outcome in order to identify certain leukocyte subsets that could potentially influence the clinical RT benefit across cancers. By integrally analyzing the TCGA data across seven cancers, we identified complex associations between immune infiltration and patients RT outcomes. Besides, immune cells showed large differences in their populations in various cancers, and the most abundant cells were resting memory CD4 T cells. Additionally, the proportion of activated CD4 memory T cells and activated mast cells, albeit at low number, were closely related to RT overall survival in multiple cancers. Furthermore, a prognostic model for RT outcomes was established with good performance based on the immune infiltration status. Summarized, immune infiltration was found to be of significant clinical relevance to RT outcomes. These findings may help to shed light on the impact of tumor-associated immune cell infiltration on cancer RT outcomes, and identify biomarkers and therapeutic targets.

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Molecular signature of response to preoperative radiotherapy in locally advanced breast cancer

Cited by 18 publications

References 42 publications

Matrix metalloproteases and TIMPs as prognostic biomarkers in breast cancer patients treated with radiotherapy: A pilot study

Matrix metalloproteases and TIMPs as prognostic biomarkers in breast cancer patients treated with radiotherapy: A pilot study

Neoadjuvant radiotherapy in the approach of locally advanced breast cancer

Pan-Cancer Analysis of Radiotherapy Benefits and Immune Infiltration in Multiple Human Cancers

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