Breast Density and the Risk of Breast Cancer

Among all other risk factors, breast density is the most important predictor of breast cancer risk. Increase in breast cancer risk from lowest to highest breast density category is on the order of fivefold depending on the age of the patient, with greater relative risk in older women.1,2Mammographic density, when added to the factors used in the classic Gail model for predicting breast cancer risk, increase the power of prediction and thus is independent of several other risk factors.

Recent studies have demonstrated that in areas of breast density there is a higher level of aromatase than nondense areas suggesting that the increased risk is due to in situ production of estrogen in the dense tissue of the breast.3Exogenous estrogens increase and antiestrogens reduce breast density. As evidence of the biological import of breast density, only those individuals with a reduction of greater than 10% with tamoxifen experienced prevention of breast cancer.4

Prior to menopause the mature breast undergoes cyclic changes during the menstrual cycle. Estrogen increases cell proliferation and progesterone enhances this effect. During the follicular phase (estrogen only), cell proliferation increases and is further enhanced during the luteal phase (when high levels of both estrogen and progesterone are produced). On the mammogram these cyclic changes are reflected by greater breast density during the luteal phase than during the follicular phase (when only estrogen is produced). Increased proliferation with progesterone would be expected to increase both the initiation and promotion of breast cancer. With the reduction of estrogen and progesterone levels after menopause, the cyclic proliferative process becomes quiescent. The mammographic appearance of the breasts becomes increasingly radiolucent. By age 70 to 79 years only 30% of women have 50% or greater breast density.5

Breast DensityHigher levels of breast density are fairly common since 50% of women between the ages of 40 and 49 years and 30% of women aged 70-79 have breasts that are at least 50% dense. If breast density is a risk factor and this risk factor is fairly common, breast cancer attributable to increased breast density could potentially account for a significant percentage of total breast cancer cases.5Several studies have shown that the attributable risk from increased breast density was 28 to 30% for 50% or greater breast density and 40 to 44% for any breast density.1,5In comparison, less than 5% of breast cancers are attributable to breast cancer gene (BRCA1 and BRCA2) mutations.

 

  1. Boyd, N. F., Byng, J. W., Jong, R. A., et al. Quantitative classification of mammographic densities and breast cancer risk: results from the Canadian National Breast Screening Study. Journal of the National Cancer Institute. 1995; 87(9):670-675.
  2. Harvey, J. A., Bovbjerg, V. E. Quantitative assessment of mammographic breast density: relationship with breast cancer risk. Radiology; 2004; 230(1):29-41.
  3. Vachon, C. M., Sasano, H., Ghosh, K., et al. Aromatase immunoreactivity is increased in mammographicly dense regions of the breast. Breast Cancer Researchand Treatment. 2011; 125(1):243-252.
  4. Cuzick, J., Warwick, J., Pinney, E., et al. Tamoxifen induced reduction in mammographic density and breast cancer risk reduction: a nested case-control study. Journal of the National Cancer Institute. 2011; 103(9): 744-752.
  5. Stomper, P., C., DiSouza, D., J., DiNitto, P., A. Analysis of parenchymal density on mammograms of 1353 women 25-79 years old. American Journal of Roentgenol. 1996; 167:1261-1265.