Plasma DNA and DNA integrity in breast cancer patients undergoing neoadjuvant chemotherapy.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e21067-e21067
Author(s):  
Oliver J. Stoetzer ◽  
Holdenrieder Stefan ◽  
Julia Lehner ◽  
Deborah Fersching ◽  
Christoph Salat
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Patients ◽  
Metastatic Breast ◽  
Therapy Response ◽  
Response To Therapy ◽  
Dna Integrity ◽  
Healthy Controls ◽  
Breast Cancer Patients ◽  
Plasma Dna

e21067 Background: In breast cancer patients undergoing neoadjuvant chemotherapy before surgery, biomarkers for predicting the response to the therapy are highly needed. Methods: Concentrations of ALU115, ALU247 and DNA integrity were analyzed in prospectively collected plasma of 68 patients with localized breast cancer (UICC II and III), of 47 patients with metastatic breast cancer and 28 healthy women as controls. In all 68 patients with breast cancer who had completed the course of chemotherapy until surgery, DNA and tumor biomarkers CEA and CA 15-3 were evaluated concerning response to therapy (no change, NC: N=18; partial remission, PR: N=35; complete remission, CR: 15). Results: Plasma levels of ALU 115 and ALU 247 were significantly higher in patients with localized (medians 16.3 and 16.8 ng/mL) and metastasized breast cancer (22.2 and 29.8 ng/mL) than in healthy controls (1.8 and 1.9 ng/mL). However, plasma DNA integrity showed no significant differences between the diagnostic groups. AUCs in ROC curves for discrimination of localized breast cancer from healthy controls were 96% for ALU 115 and ALU 247, respectively, and 60% for DNA integrity. Concerning therapy response, pretherapeutic ALU 115, 247, and DNA integrity and also CEA and CA 15-3 were not significantly different when patients with and without remission (CR vs PR+NC and CR+PR vs NC) were compared. Conclusions: While plasma DNA levels are valuable for discrimination of breast cancer patients from controls, pretherapeutic DNA integrity provides no additive diagnostic information nor indicates response to neoadjuvant therapy.

Circulating plasma DNA and DNA integrity in breast cancer patients undergoing neoadjuvant chemotherapy

2013 ◽  
Vol 425 ◽  
pp. 206-211 ◽  
Author(s):  
Julia Lehner ◽  
Oliver J. Stötzer ◽  
Debora Fersching ◽  
Dorothea Nagel ◽  
Stefan Holdenrieder
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Patients ◽  
Dna Integrity ◽  
Breast Cancer Patients ◽  
Plasma Dna

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

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.

CDK4/6 plus aromatase inhibitor-induced alopecia in breast cancer patients.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e12537-e12537
Author(s):  
Donald Chan ◽  
Azael David Freites Martinez ◽  
Shari Beth Goldfarb ◽  
Shanu Modi ◽  
Devika Gajria ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Aromatase Inhibitor ◽  
Cancer Patients ◽  
Metastatic Breast ◽  
Response To Therapy ◽  
Emotional Impact ◽  
Breast Cancer Patients ◽  
Novel Therapy ◽  
Clinical Images ◽  
Topical Minoxidil

e12537 Background: Cyclin-dependent kinase (CDK) 4 and 6 inhibitors are a novel therapy for metastatic breast cancer, and have shown to double the risk of alopecia. This study analyzed CDK4/6 plus aromatase inhibitor-induced alopecia (CDKIA), its impact on quality of life (QoL), and response to topical dermatologic therapy. Methods: The study analyzed a retrospective cohort of breast cancer patients diagnosed with CDKIA, evaluating clinical features, QoL, and response to therapy. CDKIA was also compared with endocrine-therapy induced alopecia (EIA). Results: 39 female CDKIA patients (median age 62 years [range 34-81]) were included, and 36 (92%) had standardized clinical images. CDKIA was most commonly attributed to a CDK inhibitor and letrozole in 23 patients (59%). CDKIA was similar to androgenetic alopecia (AGA) in every patient. Compared to EIA, CDKIA took less time to develop, was more severe, was associated with diffuse alopecia more frequently, and consisted of more vellus hairs on trichoscopy (Table). The Hairdex questionnaire, an alopecia-specific QoL survey, showed that CDKIA patients experienced worse QoL than EIA patients ( P < 0.05) and were most affected emotionally ( P < 0.01). There was a moderate to significant alopecia improvement in 11 of 13 CDKIA patients (85%) after treatment with topical minoxidil. Conclusions: CDKIA was clinically similar to AGA in association with diffuse alopecia. Patients with CDKIA had a negative emotional impact on appearance-based QoL. However, topical minoxidil may improve the severity of CDKIA. Baseline characteristics of CDKIA and EIA patients. [Table: see text]

scholarly journals Analysis of the serial circulating tumor cell count during neoadjuvant chemotherapy in breast cancer patients

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Sung-chan Gwark ◽  
Jisun Kim ◽  
Cham Han Lee ◽  
Young Hun Kim ◽  
Myoung Shin Kim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Tumor Cell ◽  
Cancer Patients ◽  
Pathologic Complete Response ◽  
Metastatic Breast ◽  
Circulating Tumor Cell ◽  
Breast Cancer Patients ◽  
Her2 Positive

Abstract We evaluated the prognostic implications of the circulating tumor cell (CTC) count in non-metastatic, HER2-negative breast cancer patients who failed to achieve pathologic complete response (pCR) after neoadjuvant chemotherapy (NCT). A total of 173, non-metastatic breast cancer patients treated with NCT were prospectively enrolled. CTCs were obtained from blood drawn pre-NCT and post-NCT using a SMART BIOPSY SYSTEM isolation kit (Cytogen Inc., Seoul, Korea) with immunofluorescence staining. Excluding 26 HER2-positive patients, Relapse-free survival (RFS) and overall survival (OS) related to the CTC count and the association of the CTC count with the treatment response to given therapy were analyzed in 147 HER2-negative patients. Among 147 HER2-negative patients, 28 relapses (19.0%) and 13 deaths (8.8%, all breast cancer-specific) were observed during a median follow-up of 37.3 months. One hundred and seven patients (72.8%) were hormone receptor-positive, and 40 patients (27.2%) had triple-negative breast cancer (TNBC). One or more CTCs were identified in 88 of the 147 patients (59.9%) before NCT and 77 of the 134 patients (52.4%) after NCT. In the entire HER2-negative patient cohort, the initial nodal status was the most significant factor influencing RFS and OS. In TNBC, 11 patients (27.5%) achieved pCR and patients that failed to achieve pCR with ≥ 5 CTCs after NCT, showed worse RFS (HR, 10.66; 95% CI, 1.80–63.07; p = 0.009) and OS (HR, 14.00; 95% CI, 1.26–155.53; p = 0.032). The patients with residual tumor and a high number of the CTCs after NCT displayed the worse outcome. These findings could provide justification to launch a future, well designed trial with longer follow-up data to obtain regulatory approval for clinical use of the assay, especially for the ER-positive, HER2-negative breast cancer subset.

Analysis of AKR1B10 levels among various groups of breast cancer patients.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14548-e14548
Author(s):  
Krishna A. Rao ◽  
Kathy Robinson ◽  
Kristin Delfino ◽  
Vivekanand Tiwari ◽  
Yun Zhu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Patients ◽  
Locally Advanced ◽  
Elevated Serum ◽  
Metastatic Breast ◽  
Oncotype Dx ◽  
Breast Cancer Patients ◽  
Serum Samples ◽  
Primary Tumors

e14548 Background: Aldo-keto reductase 1B10 (AKR1B10) is a protein that is primarily expressed in human colon and small intestine, but induced in hepatocellular carcinoma and non-small cell lung cancer. Our recent studies have revealed that AKR1B10 is overexpressed in primary, metastatic, and recurrent cancers of the breast. Methods: We recruited four cohorts of patients: Patients with breast cancer undergoing primary surgery from whom we procured breast cancer and matched normal adjacent tissue to evaluate AKR1B10 expression in primary tumors. The matched serum samples were collected before surgery and at various time points after the surgery (approximately 3 days, 7 days, and 1 month Patients with recurrent or advanced (metastatic) breast cancer. Serum samples were collected and serially monitored for up to 2years before and during metastatic therapy and correlated with RECIST measurements. Patients with locally advanced disease undergoing neoadjuvant chemotherapy. AKR1B10 serum levels were monitored during therapy and correlated with RECIST measurements. Healthy individuals with normal mammograms were recruited and submitted serum samples for AKR1B10 serum measurements. Results: AKR1B10 rapidly cleared the serum of early stage breast cancer patients with an estimated half-life of 24-30 hours. Serum AKR1B10 levels correlated strongly with tissue IHC staining and PR positivity but not with RECIST levels or Oncotype Dx scores. Neoadjuvant chemotherapy did not affect serum AKR1B10 levels. Individuals with normal mammograms displayed substantially lower levels of AKR1B10 than breast cancer patients. Patients with DCIS also displayed elevated serum AKR1B10 levels. Conclusions: AKR10 may serve as tumor marker to independently identify high risk patients whose tumors have intermediated risk Oncotype Dx scores and may also identify early breast cancers in patients with equivocal breast biopsies.

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