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Br J Cancer. 2014 May 13;110(10):2623-32. doi: 10.1038/bjc.2014.193. Epub 2014 Apr 22.

Breast cancer risk after radiotherapy for heritable and non-heritable retinoblastoma: a US-UK study.

Author information

  • 1Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
  • 2Department of Statistics, University of California Los Angeles, Los Angeles, CA 90095, USA.
  • 3Department of Public Health and Epidemiology, Centre for Childhood Cancer Survivor Studies, School of Health and Population Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
  • 4Ophthalmic Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA.
  • 5Department of Radiation Physics, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
  • 6Radiation Epidemiology Group, Unit 1018 INSERM, Institut Gustave Roussy, 98000 Villejuif, France.
  • 7Ophthalmic Epidemiology and Genetics Service, Tufts-New England Medical Center, Boston, MA 02111, USA.

Abstract

BACKGROUND:

Retinoblastoma is a rare childhood eye cancer caused by germline or somatic mutations in the RB1 gene. Previous studies observed elevated breast cancer risk among retinoblastoma survivors. However, there has been no research on breast cancer risk in relation to radiation (primarily scatter radiation from the primary treatment) and genetic susceptibility of retinoblastoma survivors.

METHODS:

Two groups of retinoblastoma survivors from the US and UK were selected, and breast cancer risk analysed using a case-control methodology, nesting within the respective cohorts, matching on heritability (that is to say, having bilateral retinoblastoma or being unilateral cases with at least one relative with retinoblastoma), and using exact statistical methods. There were a total of 31 cases and 77 controls.

RESULTS:

Overall there was no significant variation of breast cancer risk with dose (P>0.5). However, there was a pronounced and significant (P=0.047) increase in the risk of breast cancer with increasing radiation dose for non-heritable retinoblastoma patients and a slight and borderline significant (P=0.072) decrease in risk of breast cancer with increasing radiation dose for heritable retinoblastoma patients, implying significant (P=0.024) heterogeneity in radiation risk between the heritable and non-heritable retinoblastoma groups; this was unaffected by the blindness status. There was no significant effect of any type of alkylating-agent chemotherapy on breast cancer risk (P>0.5).

CONCLUSIONS:

There is significant radiation-related risk of breast cancer for non-heritable retinoblastoma survivors but no excess risk for heritable retinoblastoma survivors, and no significant risk overall. However, these results are based on very small numbers of cases; therefore, they must be interpreted with caution.

PMID:
24755883
PMCID:
PMC4021527
DOI:
10.1038/bjc.2014.193
[PubMed - indexed for MEDLINE]
Free PMC Article
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