Novel secretome-to-transcriptome integrated or secreto-transcriptomic approach to reveal liquid biopsy biomarkers for predicting individualized prognosis of breast cancer patients

Breast cancer is the most commonly diagnosed cancer in women worldwide. Approximately, 70 % of breast cancer patients express hormone receptors (HR) (Luminal subtype). Adjuvant endocrine treatments are the standard of care in HR+/HER2- breast cancer. Over time, about 50% of those patients develop endocrine resistance and metastatic breast cancer. Cyclin-dependent kinase inhibitors (CDKi) in combination with an aromatase inhibitor or fulvestrant have demonstrated superior efficacy increasing progression-free survival, with a safe toxicity profile, in HR+/HER2- metastatic breast cancer patients. CDKi blocks kinases 4/6 ATP-binding domain preventing G1/S cell cycle transition. Despite this, not all patients respond to CDKi and those who respond, finally develop resistance to combination therapy. Different studies, in tumour tissue or cell lines, have tried to elucidate the mechanisms underlying this progression, but there are still no conclusive data. In the last few years, liquid biopsy has contributed relevant information to this knowledge. Liquid biopsy can be performed in real-time, non-invasively and be repeated whenever needed. Circulating tumour material are potential prognostic markers in metastatic luminal breast cancer to determine patient prognosis, monitor disease and treatment selection. The objective of this review is to outline the different studies carried out in HR+ metastatic breast cancer patients treated with CDKi plus endocrine therapy using liquid biopsy approaches looking for possible resistance mechanisms.

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Multimodal liquid biopsy for early monitoring and outcome prediction of chemotherapy in metastatic breast cancer

npj Breast Cancer ◽

10.1038/s41523-021-00319-4 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Amanda Bortolini Silveira ◽

François-Clément Bidard ◽

Marie-Laure Tanguy ◽

Elodie Girard ◽

Olivier Trédan ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Cancer Patients ◽

Liquid Biopsy ◽

Simultaneous Detection ◽

Metastatic Breast ◽

Circulating Tumor Dna ◽

Breast Cancer Patients ◽

Targeted Next Generation Sequencing ◽

Patient Prognosis

AbstractCirculating tumor cells (CTCs) and circulating tumor DNA (ctDNA) are two cancer-derived blood biomarkers that inform on patient prognosis and treatment efficacy in breast cancer. We prospectively evaluated the clinical validity of quantifying both CTCs (CellSearch) and ctDNA (targeted next-generation sequencing). Their combined value as prognostic and early monitoring markers was assessed in 198 HER2-negative metastatic breast cancer patients. All patients were included in the prospective multicenter UCBG study COMET (NCT01745757) and treated by first-line chemotherapy with weekly paclitaxel and bevacizumab. Blood samples were obtained at baseline and before the second cycle of chemotherapy. At baseline, CTCs and ctDNA were respectively detected in 72 and 74% of patients and were moderately correlated (Kendall’s τ = 0.3). Only 26 (13%) patients had neither detectable ctDNA nor CTCs. Variants were most frequently observed in TP53 and PIK3CA genes. KMT2C/MLL3 variants detected in ctDNA were significantly associated with a lower CTC count, while the opposite trend was seen with GATA3 alterations. Both CTC and ctDNA levels at baseline and after four weeks of treatment were correlated with survival. For progression-free and overall survival, the best multivariate prognostic model included tumor subtype (triple negative vs other), grade (grade 3 vs other), ctDNA variant allele frequency (VAF) at baseline (per 10% increase), and CTC count at four weeks (≥5CTC/7.5 mL). Overall, this study demonstrates that CTCs and ctDNA have nonoverlapping detection profiles and complementary prognostic values in metastatic breast cancer patients. A comprehensive liquid-biopsy approach may involve simultaneous detection of ctDNA and CTCs.

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Liquid biopsy using the nanotube-CTC-chip: capture of invasive CTCs with high purity using preferential adherence in breast cancer patients

Lab on a Chip ◽

10.1039/c9lc00274j ◽

2019 ◽

Vol 19 (11) ◽

pp. 1899-1915 ◽

Cited By ~ 17

Author(s):

Masoud S. Loeian ◽

Sadegh Mehdi Aghaei ◽

Farzaneh Farhadi ◽

Veeresh Rai ◽

Hong Wei Yang ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

High Purity ◽

Peripheral Blood ◽

Liquid Biopsy ◽

Breast Cancer Patients ◽

Multiple Phenotypes

We report the development of the nanotube-CTC-chip for isolation of circulating tumor cells of multiple phenotypes from peripheral blood.

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79P Liquid biopsy-based detection of PIK3Ca mutations in HR positive metastastic breast cancer patients

Annals of Oncology ◽

10.1016/j.annonc.2020.03.213 ◽

2020 ◽

Vol 31 ◽

pp. S41

Author(s):

C. Suppan ◽

Q. Zhou ◽

R. Graf ◽

V. Klocker ◽

A. Terbuch ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Liquid Biopsy ◽

Breast Cancer Patients ◽

Pik3ca Mutations

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Abstract PS2-24: Dynamics of a multi-parametric liquid biopsy, including CTCs, EVs, and cfDNA, during therapy in metastatic breast cancer patients provide useful insights for therapy management

10.1158/1538-7445.sabcs20-ps2-24 ◽

2021 ◽

Author(s):

Sabine Kasimir-Bauer ◽

Markus Storbeck ◽

Peter Hahn ◽

Siegfried Hauch ◽

Markus Sprenger-Haussels ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Cancer Patients ◽

Liquid Biopsy ◽

Metastatic Breast ◽

Breast Cancer Patients ◽

Therapy Management

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Sensitive and robust liquid biopsy-based detection of PIK3CA mutations in hormone-receptor-positive metastatic breast cancer patients

British Journal of Cancer ◽

10.1038/s41416-021-01601-9 ◽

2021 ◽

Author(s):

Christoph Suppan ◽

Ricarda Graf ◽

Stephan Jahn ◽

Qing Zhou ◽

Eva Valentina Klocker ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Cancer Patients ◽

Hormone Receptor ◽

Liquid Biopsy ◽

Metastatic Breast ◽

Breast Cancer Patients ◽

Pik3ca Mutations ◽

Hormone Receptor Positive

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Circulating tumor cells detection in tumor draining vein of breast cancer patients

Scientific Reports ◽

10.1038/s41598-019-54839-y ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 2

Author(s):

Masaya Hattori ◽

Hayao Nakanishi ◽

Mayumi Yoshimura ◽

Madoka Iwase ◽

Akiyo Yoshimura ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Liquid Biopsy ◽

Perioperative Period ◽

Complete Response ◽

Axillary Lymph ◽

Breast Cancer Patients ◽

Alternative Sources

AbstractCirculating tumor cells (CTCs) in tumor draining vein blood (DB) are potential sources for liquid biopsy. However, the identification of CTCs in DB of breast cancer has not been attempted. In this study, we investigated the feasibility of CTC detection in DB of breast cancer patients using a newly developed filtration-based microfluidic CTC detection device. Samples of peripheral vein blood (PB) and DB drawn from the lateral thoracic vein of the resected breast tissue were collected during the perioperative period. We investigated 41 breast cancer patients who underwent breast surgery with axillary lymph node dissection. DB was successfully collected in 36 patients (87.8%), with a mean amount of 0.85 ml. CTCs were detected in 58.3% of PB samples and 80.6% of DB samples. DB had significant higher number of CTCs compared with PB (p < 0.001). CTCs were detected in 75.0% of DB samples and 50.0% of PB samples from patients achieving pathological complete response after neoadjuvant chemotherapy. These results suggest that abundant CTCs are released into the DB of breast cancer patients, indicating that CTCs in DB would be alternative sources for liquid biopsy and potential indicators for monitoring of treatment response and prognosis in breast cancer patients.

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