Dataset Information

Phylogenetic reconstruction of breast cancer reveals two routes of metastatic dissemination associated with distinct clinical outcome.

ABSTRACT: BACKGROUND:In breast cancer (BC), axillary lymph node (ALN) involvement is one of the strongest adverse prognostic factors. However, it is unclear whether loco-regional lymph node deposits are effectively the root of secondary metastases or only an indicator of competence of the primary tumour to spread to distant organs. METHODS:Here, we investigated the evolutionary trajectories of primary tumour, ALN and distant metastasis samples from 16 estrogen-receptor (ER)-positive lymph node-positive BC patients. Low-pass whole genome sequencing was performed to infer somatic copy number aberrations and the phylogenetic profiles for all patients were obtained. FINDINGS:We show that lymph nodes and distant metastases shared a common origin in only 25% of the cases highlighting that the predominant route of metastatic dissemination is the direct seeding of tumour cells from the primary tumour to distant organs, independently of lymph node metastasis. Noticeably, patients sharing a common origin significantly have worse prognosis. INTERPRETATION:Our results shed light on the routes on which tumour cells metastasize and their role in disease progression in ER-positive BC. FUNDING:This work has received financial support from Les Amis de l'Institut Bordet, MEDIC, the Breast Cancer Research Foundation (BCRF), the Belgian Fonds National de la Recherche Scientifique (F.R.S-FNRS) and from a grant of the Région Wallonne.

SUBMITTER: Venet D

PROVIDER: S-EPMC7281848 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Phylogenetic reconstruction of breast cancer reveals two routes of metastatic dissemination associated with distinct clinical outcome.

Venet David D Fimereli Danai D Rothé Françoise F Boeckx Bram B Maetens Marion M Majjaj Samira S Rouas Ghizlane G Capra Maria M Bonizzi Giuseppina G Contaldo Federica F Galant Christine C Piccart Martine M Pruneri Giancarlo G Larsimont Denis D Lambrechts Diether D Desmedt Christine C Sotiriou Christos C

EBioMedicine 20200605

<h4>Background</h4>In breast cancer (BC), axillary lymph node (ALN) involvement is one of the strongest adverse prognostic factors. However, it is unclear whether loco-regional lymph node deposits are effectively the root of secondary metastases or only an indicator of competence of the primary tumour to spread to distant organs.<h4>Methods</h4>Here, we investigated the evolutionary trajectories of primary tumour, ALN and distant metastasis samples from 16 estrogen-receptor (ER)-positive lymph n ...[more]

PMID: 32512508

Similar Datasets

Project description:Traditional factors currently used for prognostic stratification do not always adequately predict treatment response and disease evolution in advanced breast cancer patients. Therefore, the use of blood-based markers, such as circulating tumor cells (CTCs), represents a promising complementary strategy for disease monitoring. In this retrospective study, we explored the role of CTC counts as predictors of disease evolution in breast cancer patients with limited metastatic dissemination.A total of 492 advanced breast cancer patients who had a CTC count assessed by CellSearch prior to starting a new line of systemic therapy were eligible for this analysis. Using the threshold of 5 CTCs/7.5 ml of blood, pretreatment CTC counts were correlated in the overall population with metastatic site distribution, evaluated at baseline and at the time of treatment failure, using Fisher's exact test. Time to visceral progression and time to the development of new metastatic lesions and sites were estimated in patients with nonvisceral metastases and with single-site metastatic disease, respectively, by the Kaplan-Meier method. Survival times were compared between groups according to pretreatment CTC count by logrank test.In the overall population, a pretreatment level ?5 CTCs/7.5 ml was associated with an increased baseline number of metastatic sites compared with <5 CTCs/7.5 ml (P?=?0.0077). At the time of treatment failure, patients with ?5 CTCs/7.5 ml more frequently developed new metastatic lesions and sites compared with those with <5 CTCs/7.5 ml (development of new lesions: P?=?0.0002; development of new sites: P?=?0.0031). Among patients with disease originally confined to nonvisceral sites, ?5 CTCs/7.5 ml was associated with remarkably shorter time to visceral metastases (P?=?0.0021) and overall survival (P?=?0.0006) compared with <5 CTCs/7.5 ml. In patients with single-site metastatic disease, ?5 CTCs/7.5 ml was associated with a significant reduction of the time to development of new metastatic sites (P?=?0.0051) and new lesions (P?=?0.0002) and with worse overall survival (P?=?0.0101).Our results suggest that baseline CTC counts can be used as an early predictor of metastatic potential in breast cancer patients with limited metastatic dissemination.

Dataset Information

Phylogenetic reconstruction of breast cancer reveals two routes of metastatic dissemination associated with distinct clinical outcome.

Publications

Phylogenetic reconstruction of breast cancer reveals two routes of metastatic dissemination associated with distinct clinical outcome.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets