SAN ANTONIO — Women who are treated for ductal carcinoma in situ are threefold more likely to develop invasive breast cancer in the other breast if their breasts are mammographically dense, Dr. E. Shelley Hwang said at a breast cancer symposium sponsored by the Cancer Therapy and Research Center.
The clinical implication of this new observation is that women undergoing treatment for ductal carcinoma in situ (DCIS) are particularly likely to benefit from preventive strategies aimed at contralateral breast risk reduction—such as adjuvant systemic hormone therapy with tamoxifen—if they have high breast density, according to Dr. Hwang of the University of California, San Francisco.
DCIS affects roughly 60,000 women per year in the United States. It is treated aggressively because it is considered a precursor to invasive breast cancer. Today, roughly one-third of women with DCIS receive lumpectomy without radiation, 38% get lumpectomy with radiotherapy, and 28% undergo mastectomy. Of women with DCIS, 10%–15% progress to invasive cancer in 10 years. However, the overall prognosis for women treated for DCIS is excellent, with a long-term breast cancer-specific mortality of 1%.
The search is on for easily monitored risk factors for cases of DCIS that are likely to progress to invasive disease. Breast density, which can be categorized simply and reproducibly via the widely used four-level American College of Radiology Breast Imaging Reporting and Data System (BIRADS) of mammographic classification, seemed like a promising candidate.
Twin studies indicate breast density has a heritable component that explains 60% of individual variation; exposure to endogenous and exogenous hormones also plays an important role.
To examine the relationship between breast density and invasive recurrence risk following local therapy for DCIS, Dr. Hwang studied 3,274 women diagnosed with DCIS as a result of screening mammography conducted at a National Cancer Institute Breast Cancer Screening Consortium site. They were followed for a mean of 42 months following lumpectomy plus adjuvant radiotherapy or lumpectomy alone. During that time, there were 133 invasive recurrences.
The 83 ipsilateral invasive cancers were split roughly evenly between women with low breast density as evidenced by their BIRADS score of 1 or 2 and women who had BIRADS scores of 3 or 4. Thus, ipsilateral invasive recurrence was independent of breast density.
In contrast, three-quarters of all contralateral invasive cancers occurred in women who had BIRADS scores of 3 or 4. In a Cox proportional hazard analysis adjusted for age and the use of radiotherapy, women with high breast density were 3.1 times more likely to develop contralateral invasive cancer than were those with BIRADS scores of 1 or 2. This increased risk remained stable over time, contradicting the notion that a masking phenomenon was at work.
The increased risk of contralateral invasive recurrence in DCIS patients with high breast density was present regardless of whether the women received adjuvant radiation. Patients with BIRADS scores of 3 or 4 who received radiotherapy were 3.6 times more likely to experience contralateral invasive cancer than were those with BIRADS scores of 1 or 2.
Similarly, women who did not receive radiotherapy were 2.7-fold more likely to develop contralateral invasive cancer if they had high breast density compared with low breast density.
However, the risk of ipsilateral invasive cancer was essentially the same regardless of whether a patient did or did not receive radiation, and regardless of how dense her breasts were.
Dr. Hwang's study was supported by the National Institutes of Health.
Women with high breast density were 3.1 times more likely to develop contralateral invasive cancer. DR. HWANG