TY - JOUR
T1 - The association of mammographic density with risk of contralateral breast cancer and change in density with treatment in the WECARE study
AU - WECARE Study Collaborative Group
AU - Knight, Julia A.
AU - Blackmore, Kristina M.
AU - Fan, Jing
AU - Malone, Kathleen E.
AU - John, Esther M.
AU - Lynch, Charles F.
AU - Vachon, Celine M.
AU - Bernstein, Leslie
AU - Brooks, Jennifer D.
AU - Reiner, Anne S.
AU - Liang, Xiaolin
AU - Woods, Meghan
AU - Bernstein, Jonine L.
AU - Capanu, Marinela
AU - Orlow, Irene
AU - Robson, Mark
AU - Boice, John D.
AU - Brooks, Jennifer
AU - Concannon, Patrick
AU - Conti, Dave V.
AU - Duggan, David
AU - Elena, Joanne W.
AU - Haile, Robert W.
AU - Mellemkjær, Lene
AU - Olsen, Jørgen H.
AU - Seminara, Daniela
AU - Shore, Roy E.
AU - Stovall, Marilyn
AU - Stram, Daniel O.
AU - Tischkowitz, Marc
AU - Thomas, Duncan C.
AU - Blackmore, Kristina
AU - Diep, Anh T.
AU - Goldstein, Judy
AU - Harris, Irene
AU - Langballe, Rikke
AU - O'Brien, Cecilia
AU - Smith, Susan
AU - Weathers, Rita
AU - West, Michele
N1 - Publisher Copyright:
© 2018 The Author(s).
PY - 2018/3/22
Y1 - 2018/3/22
N2 - Background: Mammographic density (MD) is an established predictor of risk of a first breast cancer, but the relationship of MD to contralateral breast cancer (CBC) risk is not clear, including the roles of age, mammogram timing, and change with treatment. Multivariable prediction models for CBC risk are needed and MD could contribute to these. Methods: We conducted a case-control study of MD and CBC risk in phase II of the WECARE study where cases had a CBC diagnosed ≥ 2 years after first diagnosis at age <55 years and controls had unilateral breast cancer (UBC) with similar follow-up time. We retrieved film mammograms of the unaffected breast from two time points, prior to/at the time of the first diagnosis (253 CBC cases, 269 UBC controls) and ≥ 6 months up to 48 months following the first diagnosis (333 CBC cases, 377 UBC controls). Mammograms were digitized and percent MD (%MD) was measured using the thresholding program Cumulus. Odds ratios (OR) and 95% confidence intervals (CI) for association between %MD and CBC, adjusted for age, treatment, and other factors related to CBC, were estimated using logistic regression. Linear regression was used to estimate the association between treatment modality and change in %MD in 467 women with mammograms at both time points. Results: For %MD assessed following diagnosis, there was a statistically significant trend of increasing CBC with increasing %MD (p = 0.03). Lower density (<25%) was associated with reduced risk of CBC compared to 25 to < 50% density (OR 0.69, 95% CI 0.49, 0.98). Similar, but weaker, associations were noted for %MD measurements prior to/at diagnosis. The relationship appeared strongest in women aged < 45 years and non-existent in women aged 50 to 54 years. A decrease of ≥ 10% in %MD between first and second mammogram was associated marginally with reduced risk of CBC (OR 0.63, 95% CI 0.40, 1.01) compared to change of <10%. Both tamoxifen and chemotherapy were associated with statistically significant 3% decreases in %MD (p < 0.01). Conclusions: Post-diagnosis measures of %MD may be useful to include in CBC risk prediction models with consideration of age at diagnosis. Chemotherapy is associated with reductions in %MD, similar to tamoxifen.
AB - Background: Mammographic density (MD) is an established predictor of risk of a first breast cancer, but the relationship of MD to contralateral breast cancer (CBC) risk is not clear, including the roles of age, mammogram timing, and change with treatment. Multivariable prediction models for CBC risk are needed and MD could contribute to these. Methods: We conducted a case-control study of MD and CBC risk in phase II of the WECARE study where cases had a CBC diagnosed ≥ 2 years after first diagnosis at age <55 years and controls had unilateral breast cancer (UBC) with similar follow-up time. We retrieved film mammograms of the unaffected breast from two time points, prior to/at the time of the first diagnosis (253 CBC cases, 269 UBC controls) and ≥ 6 months up to 48 months following the first diagnosis (333 CBC cases, 377 UBC controls). Mammograms were digitized and percent MD (%MD) was measured using the thresholding program Cumulus. Odds ratios (OR) and 95% confidence intervals (CI) for association between %MD and CBC, adjusted for age, treatment, and other factors related to CBC, were estimated using logistic regression. Linear regression was used to estimate the association between treatment modality and change in %MD in 467 women with mammograms at both time points. Results: For %MD assessed following diagnosis, there was a statistically significant trend of increasing CBC with increasing %MD (p = 0.03). Lower density (<25%) was associated with reduced risk of CBC compared to 25 to < 50% density (OR 0.69, 95% CI 0.49, 0.98). Similar, but weaker, associations were noted for %MD measurements prior to/at diagnosis. The relationship appeared strongest in women aged < 45 years and non-existent in women aged 50 to 54 years. A decrease of ≥ 10% in %MD between first and second mammogram was associated marginally with reduced risk of CBC (OR 0.63, 95% CI 0.40, 1.01) compared to change of <10%. Both tamoxifen and chemotherapy were associated with statistically significant 3% decreases in %MD (p < 0.01). Conclusions: Post-diagnosis measures of %MD may be useful to include in CBC risk prediction models with consideration of age at diagnosis. Chemotherapy is associated with reductions in %MD, similar to tamoxifen.
KW - Breast cancer treatment
KW - Contralateral breast cancer
KW - Mammographic density
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U2 - 10.1186/s13058-018-0948-4
DO - 10.1186/s13058-018-0948-4
M3 - Article
C2 - 29566728
AN - SCOPUS:85044278641
SN - 1465-5411
VL - 20
JO - Breast Cancer Research
JF - Breast Cancer Research
IS - 1
M1 - 23
ER -