Dataset Information

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

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.

SUBMITTER: Olivier M

PROVIDER: S-EPMC6336331 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Publications

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

Olivier Magali M Bouaoun Liacine L Villar Stephanie S Robitaille Alexis A Cahais Vincent V Heguy Adriana A Byrnes Graham G Le Calvez-Kelm Florence F Torres-Mejía Gabriela G Alvarado-Cabrero Isabel I Imani-Razavi Fazlollah Shahram FS Inés Sánchez Gloria G Jaramillo Roberto R Porras Carolina C Rodriguez Ana Cecilia AC Garmendia Maria Luisa ML Soto José Luis JL Romieu Isabelle I Porter Peggy P Guenthoer Jamie J Rinaldi Sabina S

PloS one 20190117 1

<h4>Background</h4>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.<h4>Methods</h4>Pathological tumor tissues were collected from incident cases from four LA countries. Immunohistochemistry (IHC) w ...[more]

PMID: 30653559

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Project description:Background: African American (AA) women have higher incidence of aggressive, young-onset (<40 years) breast cancers. Young- and older-onset disease may have distinct tumor biologies and etiologies; however, studies investigating age differences among AA women have been rare and generally underpowered.Methods: We examined tumor characteristics and breast cancer risk factors associated with premenopausal young (<40) vs. older (?40) AA women's breast cancer in the African American Breast Cancer Epidemiology and Risk Consortium (2,008 cases and 5,144 controls). Unconditional logistic regression models assessed heterogeneity of tumor biology and risk factor associations by age, overall, and by estrogen receptor status.Results: Premenopausal AA women <40 years had higher frequency of poorer-prognosis tumor characteristics compared with older women, including negative estrogen and progesterone receptor status, triple-negative subtype, higher grade, higher stage, and larger tumors. Adiposity (i.e., waist-to-hip ratio) and family history of breast cancer were more strongly associated with young-onset disease [case-control OR = 1.46, 95% confidence interval (CI) = 1.04-2.05; OR = 3.10, 95% CI = 2.08-4.63, respectively] compared with older-onset disease (OR = 1.11, 95% CI = 0.91-1.35; OR = 1.57, 95% CI = 1.26-1.94). Breastfeeding showed a slight inverse risk association among young women (OR = 0.70, 95% CI = 0.43-1.16). Oral contraceptive use was associated with increased risk regardless of age. Considering various cutoff points for young age (<40, <45, <50), age-related heterogeneity was greatest when <40 was used.Conclusions: Among premenopausal AA women, diagnosis before age 40 is associated with more aggressive breast tumor biology and some etiologic differences.Impact: Modifiable risk factors including breastfeeding, adiposity, and oral contraceptive use may be important targets for mitigating harms of young-onset breast cancer. Cancer Epidemiol Biomarkers Prev; 26(12); 1722-9. ©2017 AACR.

Project description:Molecular profile of breast cancer in Latin-American women was studied in five countries: Argentina, Brazil, Chile, Mexico, and Uruguay. Data about socioeconomic characteristics, risk factors, prognostic factors, and molecular subtypes were described, and the 60-month overall cumulative survival probabilities (OS) were estimated. From 2011 to 2013, 1,300 eligible Latin-American women 18 years or older, with a diagnosis of breast cancer in clinical stage II or III, and performance status ≦̸1 were invited to participate in a prospective cohort study. Face-to-face interviews were conducted, and clinical and outcome data, including death, were extracted from medical records. Unadjusted associations were evaluated by Chi-squared and Fisher's exact tests and the OS by Kaplan-Meier method. Log-rank test was used to determine differences between cumulative probability curves. Multivariable adjustment was carried out by entering potential confounders in the Cox regression model. The OS at 60 months was 83.9%. Multivariable-adjusted death hazard differences were found for women living in Argentina (2.27), Chile (1.95), and Uruguay (2.42) compared with Mexican women, for older (≥60 years) (1.84) compared with younger (≤40 years) women, for basal-like subtype (5.8), luminal B (2.43), and HER2-enriched (2.52) compared with luminal A subtype, and for tumor clinical stages IIB (1.91), IIIA (3.54), and IIIB (3.94) compared with stage IIA women. OS was associated with country of residence, PAM50 intrinsic subtype, age, and tumor stage at diagnosis. While the latter is known to be influenced by access to care, including cancer screening, timely diagnosis and treatment, including access to more effective treatment protocols, it may also influence epigenetic changes that, potentially, impact molecular subtypes. Data derived from heretofore understudied populations with unique geographic ancestry and sociocultural experiences are critical to furthering our understanding of this complexity.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

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