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PLoS One. 2019 Jan 17;14(1):e0210372. doi: 10.1371/journal.pone.0210372. eCollection 2019.

Molecular features of premenopausal breast cancers in Latin American women: Pilot results from the PRECAMA study.

Author information

1
Section of Mechanisms of Carcinogenesis, International Agency for Research on Cancer, Lyon, France.
2
Section of Environment and Radiation, International Agency for Research on Cancer, Lyon, France.
3
Department of Pathology and Genome Technology Center, New York University Langone Medical Center, New York, United States of America.
4
Genetic Cancer Susceptibility Group, International Agency for Research on Cancer, Lyon, France.
5
Center for Population Health Research, National Institute of Public Health, Cuernavaca, Mexico.
6
Department of Pathology, Hospital de Oncología, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico.
7
Department of Pathology, UMAE Hospital de Gineco Obstetricia No. 4 "Luis Castelazo Ayala", Instituto Mexicano del Seguro Social, Mexico City, Mexico.
8
Group Infection and Cancer, School of Medicine, University of Antioquia, Medellín, Colombia.
9
Hemato Oncologos, Cali, Colombia.
10
Agencia Costarricense de Investigaciones Biomédicas (ACIB)-Fundación INCIENSA, Costa Rica.
11
Instituto de Nutrición y de Tecnología de los Alimentos, Santiago, Chile.
12
National Institute of Cancer, Santiago, Chile.
13
Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France.
14
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, United States of America.
15
Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, United States of America.

Abstract

BACKGROUND:

In Latin America (LA), there is a high incidence rate of breast cancer (BC) in premenopausal women, and the genomic features of these BC remain unknown. Here, we aim to characterize the molecular features of BC in young LA women within the framework of the PRECAMA study, a multicenter population-based case-control study of BC in premenopausal women.

METHODS:

Pathological tumor tissues were collected from incident cases from four LA countries. Immunohistochemistry (IHC) was performed centrally for ER, PR, HER2, Ki67, EGFR, CK5/6, and p53 protein markers. Targeted deep sequencing was done on genomic DNA extracted from formalin-fixed, paraffin-embedded tumor tissues and their paired blood samples to screen for somatic mutations in eight genes frequently mutated in BC. A subset of samples was analyzed by exome sequencing to identify somatic mutational signatures.

RESULTS:

The majority of cases were positive for ER or PR (168/233; 72%), and 21% were triple-negative (TN), mainly of basal type. Most tumors were positive for Ki67 (189/233; 81%). In 126 sequenced cases, TP53 and PIK3CA were the most frequently mutated genes (32.5% and 21.4%, respectively), followed by AKT1 (9.5%). TP53 mutations were more frequent in HER2-enriched and TN IHC subtypes, whereas PIK3CA/AKT1 mutations were more frequent in ER-positive tumors, as expected. Interestingly, a higher proportion of G:C>T:A mutations was observed in TP53 in PRECAMA cases compared with TCGA and METABRIC BC series (27% vs 14%). Exome-wide mutational patterns in 10 TN cases revealed alterations in signal transduction pathways and major contributions of mutational signatures caused by altered DNA repair pathways.

CONCLUSIONS:

These pilot results on PRECAMA tumors give a preview of the molecular features of premenopausal BC in LA. Although the overall mutation burden was as expected from data in other populations, mutational patterns observed in TP53 and exome-wide suggested possible differences in mutagenic processes giving rise to these tumors compared with other populations. Further -omics analyses of a larger number of cases in the near future will enable the investigation of relationships between these molecular features and risk factors.

PMID:
30653559
PMCID:
PMC6336331
DOI:
10.1371/journal.pone.0210372
[Indexed for MEDLINE]
Free PMC Article

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