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Elevated levels of extracellular vesicles are associated with therapy failure and disease progression in breast cancer patients undergoing neoadjuvant chemotherapy.

ABSTRACT: Extracellular vesicles (EVs) have been discussed as a diagnostic tool for minimal residual disease (MRD) evaluation in breast cancer (BC) in addition to the analysis of circulating tumor cells (CTCs). Therefore, we investigated circulating EV levels as surrogate markers for disease monitoring and prediction of prognosis in primary, non-metastatic, locally advanced BC patients. EVs were enriched from blood samples of BC patients before and after neoadjuvant chemotherapy (NACT) and from healthy females. EV marker expression analysis was performed and EV sizes and concentrations were determined by nanoparticle tracking analysis. The results were associated with disease status, outcome and CTC presence, evaluated by gene expression analysis after enrichment. We demonstrated that i) the EV concentration was 40-fold higher in BC patients compared to healthy females, ii) the EV concentration increased during therapy, iii) an increased EV concentration pre-NACT was associated with therapy failure and iv) an elevated EV concentration post-NACT was associated with a reduced three-year progression-free and overall survival. Of note, residual stem cell-like and/or resistant CTCs after therapy were associated with a lower EV concentration post-NACT. Our study highlights that the concentration of EVs within BC blood samples may serve as a complementary parameter reflecting the status of MRD as well as therapy and disease outcome in parallel with CTC investigation.

SUBMITTER: Konig L

PROVIDER: S-EPMC5739576 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Elevated levels of extracellular vesicles are associated with therapy failure and disease progression in breast cancer patients undergoing neoadjuvant chemotherapy.

König Lisa L Kasimir-Bauer Sabine S Bittner Ann-Kathrin AK Hoffmann Oliver O Wagner Bettina B Santos Manvailer Luis Felipe LF Kimmig Rainer R Horn Peter A PA Rebmann Vera V

Oncoimmunology 20170927 1

Extracellular vesicles (EVs) have been discussed as a diagnostic tool for minimal residual disease (MRD) evaluation in breast cancer (BC) in addition to the analysis of circulating tumor cells (CTCs). Therefore, we investigated circulating EV levels as surrogate markers for disease monitoring and prediction of prognosis in primary, non-metastatic, locally advanced BC patients. EVs were enriched from blood samples of BC patients before and after neoadjuvant chemotherapy (NACT) and from healthy fe ...[more]

PMID: 29296534

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Project description:Neoadjuvant chemotherapy (NC) is increasingly being used in patients with breast cancer, and evidence-based reports related to its independent effects on morbidity after mastectomy with immediate breast reconstruction are limited.To determine the effect of NC on 30-day postoperative morbidity in women undergoing mastectomy with or without immediate breast reconstruction.All women undergoing mastectomy with or without immediate breast reconstruction from January 1, 2005, through December 31, 2011, at university and private hospitals internationally were analyzed using the American College of Surgeons National Surgical Quality Improvement Program 2005-2011 databases. Patients who received NC were compared with those without a history of NC to estimate the relative odds of 30-day postoperative overall, systemic, and surgical site morbidity using model-wise multivariable logistic regression.Neoadjuvant chemotherapy.Thirty-day postoperative morbidity (overall, systemic, and surgical site).Of 85,851 women, 66,593 (77.6%) underwent mastectomy without breast reconstruction, with 2876 (4.3%) receiving NC; 7893 patients were excluded because of missing exposure data. The immediate breast reconstruction population included 19,258 patients (22.4%), with 820 (4.3%) receiving NC. After univariable analysis, NC was associated with a 20% lower odds of overall morbidity in the group undergoing mastectomy without breast reconstruction (odds ratio [OR], 0.80; 95% CI, 0.71-0.91) but had no significant effect in the immediate breast reconstruction group (OR, 0.98; 95% CI, 0.79-1.23). After adjustment for confounding, NC was independently associated with lower overall morbidity in the group undergoing mastectomy without breast reconstruction (OR, 0.61; 95% CI, 0.51-0.73) and the immediate tissue expander reconstruction subgroup (OR, 0.49; 95% CI, 0.30-0.84). Neoadjuvant chemotherapy was associated with decreased odds of systemic morbidity in 4 different populations: complete sample (OR, 0.59; 95% CI, 0.49-0.71), mastectomy without breast reconstruction (OR, 0.59; 95% CI, 0.48-0.72), any immediate breast reconstruction (OR, 0.57; 95% CI, 0.37-0.88), and the tissue expander subgroup (OR, 0.41; 95% CI, 0.23-0.72).Our study supports the safety of NC in women undergoing mastectomy with or without immediate breast reconstruction. Neoadjuvant chemotherapy is associated with lower overall morbidity in the patients undergoing mastectomy without breast reconstruction and in those undergoing tissue expander breast reconstruction. In addition, the odds of systemic morbidity were decreased in patients undergoing mastectomy with and without immediate breast reconstruction. The mechanisms behind the protective association of NC remain unknown and warrant further investigation.

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Elevated levels of extracellular vesicles are associated with therapy failure and disease progression in breast cancer patients undergoing neoadjuvant chemotherapy.

Publications

Elevated levels of extracellular vesicles are associated with therapy failure and disease progression in breast cancer patients undergoing neoadjuvant chemotherapy.

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