Breast (Dec 2020)

A case-control study of the joint effect of reproductive factors and radiation treatment for first breast cancer and risk of contralateral breast cancer in the WECARE study

  • Jennifer D. Brooks,
  • John D. Boice, Jr.,
  • Roy E. Shore,
  • Anne S. Reiner,
  • Susan A. Smith,
  • Leslie Bernstein,
  • Julia A. Knight,
  • Charles F. Lynch,
  • Esther M. John,
  • Kathleen E. Malone,
  • Lene Mellemkjaer,
  • Rikke Langballe,
  • Xiaolin Liang,
  • Meghan Woods,
  • Marc Tischkowitz,
  • Patrick Concannon,
  • Daniel O. Stram,
  • Jonine L. Bernstein

Journal volume & issue
Vol. 54
pp. 62 – 69

Abstract

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Objective: To examined the impact of reproductive factors on the relationship between radiation treatment (RT) for a first breast cancer and risk of contralateral breast cancer (CBC). Methods: The Women’s Environmental Cancer and Radiation Epidemiology (WECARE) Study is a multi-center, population-based case-control study where cases are women with asynchronous CBC (N = 1521) and controls are women with unilateral breast cancer (N = 2211). Rate ratios (RR) and 95% confidence intervals (CI) were estimated using conditional logistic regression to assess the independent and joint effects of RT (ever/never and location-specific stray radiation dose to the contralateral breast [0, >0-<1Gy, ≥1Gy]) and reproductive factors (e.g., parity). Results: Nulliparous women treated with RT (≥1Gy dose) were at increased risk of CBC compared with nulliparous women not treated with RT, although this relationship did not reach statistical significance (RR = 1.34, 95% CI 0.87, 2.07). Women treated with RT who had an interval pregnancy (i.e., pregnancy after first diagnosis and before second diagnosis [in cases]/reference date [in controls]) had an increased risk of CBC compared with those who had an interval pregnancy with no RT (RR = 4.60, 95% CI 1.16, 18.28). This was most apparent for women with higher radiation doses to the contralateral breast. Conclusion: Among young female survivors of breast cancer, we found some evidence suggesting that having an interval pregnancy could increase a woman’s risk of CBC following RT for a first breast cancer. While sampling variability precludes strong interpretations, these findings suggest a role for pregnancy and hormonal factors in radiation-associated CBC.

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