Genetic factors related to mammographic density might also be associated with familial risk of breast cancer. To
determine whether the association of mammographic density with breast cancer
risk differed by family history of breast cancer (FHBC) in women of white and
Asian ancestry, we analyzed data from four case-control studies conducted in
the United States and in Japan. To standardize mammographic density assessment,
a single observer re-read all mammograms using one type of interactive
thresholding software. Logistic regression was applied to estimate odds ratios
(OR) while adjusting for known confounders. The study population included 1699 breast cancer cases
and 2422 controls, 45% of whom were white (N=1849) and 40% Asian (N=1633),
primarily Japanese. Overall, 12% of participants reported a FHBC with a lower proportion in
Japan (5%) than California (13%), Hawaii (14%), and Minnesota (14%). FHBC was
significantly associated with breast cancer risk in the adjusted model (OR=1.51;
95%CI: 1.24-1.84). The interaction terms of percent density (per 10%) with FHBC (p=0.03) and ethnicity
(p=0.01) were statistically significant. The OR associated with a 10% increase
in PD was higher for women with a FHBC (OR=1.30; 95%CI: 1.13-1.49)
than for those without (OR=1.14; 1.09-1.20). After stratification by ethnicity,
this pattern was also apparent in whites and Asians with ORs of 1.45 (95%CI:
1.17-1.80) vs. 1.22 (95%CI: 1.14-1.32) and 1.24 (95%CI: 0.97-1.58) vs. 1.09
(95%CI: 1.00-1.19). Results were similar for dense area (per 10 cm2,
square-root transformed) although
the interaction term was borderline (p=0.10). The respective risk estimates for women with and
without a FHBC were (OR=2.12;
95%CI: 1.47-3.06) and (OR=1.51;
95%CI: 1.33-1.71). In
conclusion, women with a FHBC have a higher risk than women without. Also,
white women have a higher risk than Asian women. These findings support the hypothesis
that FHBC and ethnicity modify breast cancer risk attributable to mammographic
density.