Format

Send to

Choose Destination
Eur J Cancer. 2019 Jul;116:199-206. doi: 10.1016/j.ejca.2019.05.005. Epub 2019 Jun 15.

Reproductive factors associated with breast cancer risk in Li-Fraumeni syndrome.

Author information

1
Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, 9609, Medical Center Drive, MSC 9772, Bethesda, 20892, USA. Electronic address: payal.khincha@nih.gov.
2
Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, 9609, Medical Center Drive, MSC 9772, Bethesda, 20892, USA.
3
Office of the Director, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, 9609, Medical Center Drive, MSC 9772, Bethesda, 20892, USA.
4
Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, 9609, Medical Center Drive, MSC 9772, Bethesda, 20892, USA.
5
Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, 9609, Medical Center Drive, MSC 9772, Bethesda, 20892, USA; Centro de Oncologia, Hospital Sirio-Libanes, Rua Dona Adma Jafet, 115- Bela Vista, Sao Paulo, Brazil.

Abstract

Li-Fraumeni syndrome (LFS) is a rare autosomal dominant cancer predisposition syndrome with exceptionally high lifetime cancer risks, caused primarily by germline TP53 variants. Early-onset breast cancer is the most common cancer in women with LFS. Associations between female reproductive factors and breast cancer risk have been widely studied in the general population and BRCA1/2 mutation carriers but not in LFS. We evaluated whether reproductive factors are associated with breast cancer in LFS. Questionnaire data were collected for 152 women with confirmed germline TP53 variants enrolled in the National Cancer Institute's LFS study (NCT01443468); of which, 85 had breast cancer, confirmed by pathology/medical reports. Fisher's exact test and Cox proportional hazards were used to calculate the effect of reproductive factors on breast cancer risk. Lifetime breastfeeding for at least 7 months was associated with lower breast cancer risk (hazard ratio [HR] 0.57, p = 0.05). Parity did not independently change breast cancer risk (HR 1.08, p = 0.8) but suggested an increased risk with older age at first live birth (HR 2.14, p = 0.05). Age at menarche (HR 1.09, p = 0.24) and use of oral contraceptives (HR 0.88; p = 0.7) did not significantly affect breast cancer risk. In this first study of reproductive factors and breast cancer in women with LFS, breastfeeding was observed to be protective against breast cancer risk, especially with at least 7 months of lifetime breastfeeding. Older age at first live birth was suggested to slightly increase breast cancer risk. Larger prospective studies of reproductive factors are warranted in women with LFS before making definitive clinical recommendations.

KEYWORDS:

Breast cancer; Breastfeeding; Li-Fraumeni syndrome; Reproductive; TP53

PMID:
31212162
DOI:
10.1016/j.ejca.2019.05.005

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center