Abstract and Introduction
Abstract
Introduction Mammographic density is a strong risk factor for breast cancer, but it is unknown whether density at first breast cancer diagnosis and changes during follow-up influences risk of non-simultaneous contralateral breast cancer (CBC).
Methods We collected mammograms for CBC-patients (cases, N = 211) and unilateral breast cancer patients (controls, N = 211), individually matched on age and calendar period of first breast cancer diagnosis, type of adjuvant therapy and length of follow-up (mean follow-up time: 8.25 years). The odds of CBC as a function of changes of density during follow-up were investigated using conditional logistic regression, adjusting for non-dense area at diagnosis.
Results Patients who experienced ≥10% absolute decrease in percent density had a 55% decreased odds of CBC (OR = 0.45 95% CI: 0.24 to 0.84) relative to patients who had little or no change in density from baseline to first follow-up mammogram (mean = 1.6 (SD = 0.6) years after diagnosis), whereas among those who experienced an absolute increase in percent density we could not detect any effect on the odds of CBC (OR = 0.83 95% CI: 0.24 to 2.87).
Conclusion Decrease of mammographic density within the first two years after first diagnosis is associated with a significantly reduced risk of CBC, this potential new risk predictor can thus contribute to decision-making in follow-up strategies and treatment.
Introduction
Mammographic density is one of the strongest risk factors for breast cancer; a meta-analysis of 14,000 cases and 226,000 non-cases showed that the women with >75% mammographic density have almost five times the risk of breast cancer compared to women in the lowest density group (<5%). Mammographic density has also been shown to be important for breast cancer recurrence and survival. Several hormonal factors affect mammographic density and changes of density have been shown to be associated with pharmacological therapies, such as hormone replacement therapy and tamoxifen.
Despite the well-known and strong association between mammographic density and unilateral breast cancer, the effect of mammographic density on the risk of a second primary breast cancer in the opposite breast, contralateral breast cancer (CBC), has to our knowledge not been investigated before. Breast cancer patients have approximately double the risk of CBC, compared to healthy women's risk of breast cancer and this increased risk does not seem to decline with time after first diagnosis. This translates into 10 to 15% of all breast cancer patients being diagnosed with CBC within 20 years of initial diagnosis. When investigating hormonal risk factors for unilateral breast cancer no association with risk of CBC has been identified. Trends of breast cancer incidence and breast cancer mortality indicate that CBC will be a greater clinical challenge in the future, since the population at risk of CBC is increasing. Since CBC also has a far less well characterized risk profile and considerably worse prognosis than unilateral breast cancer, new tools for prediction of CBC would be of great clinical importance.
The question of whether decreasing mammographic density is associated with a decreased future risk of breast cancer, or not, has been investigated in several observational studies. Two showed an association and one did not. The question was also examined in a randomized trial of tamoxifen among healthy women at high risk of breast cancer, for which the estimated association was more pronounced among the tamoxifen treated, although the association (albeit non-statistically significant) was also seen among the women who received placebo. If this association were also present among breast cancer patients, for the risk of CBC, this would have important clinical implications for follow-up care. The aim of this matched nested case-control study was, therefore, to assess whether change of mammographic density after the first breast cancer diagnosis predicts a change in risk of CBC.