Epidemiological studies have shown that patients with a history of LCIS are as likely as those diagnosed with DCIS to eventually develop invasive breast cancer (relative risk, ~10 times that for age-matched controls) (Rosen et al., 1980; Rosen, 1981). Unlike DCIS, the risk associated with LCIS is bilateral, suggesting that LCIS may be a marker for rather than a precursor of invasive breast cancer. Furthermore, LCIS is often multifocal and bilateral, suggesting that it may arise in response to a carcinogenic “field defect.” Recent studies have unequivocally demonstrated that LCIS shares identical genetic defects with invasive cancer in the same breast (Lu et al., 1998; Nayar et al., 1997), consistent with the notion that LCIS may be both a marker for and a direct precursor to invasive tumors. LCIS is present in about 5 percent of breast biopsy specimens. It is almost always clinically occult and is encountered as an incidental finding in breasts biopsied for some other reason. Surgery is not considered an option for patients with LCIS because of its multifocal nature, and there is no universally agreed upon approach to the management of LCIS because it is not a true malignancy. In the recent chemoprevention trial conducted by the National Surgical Adjuvant Breast and Bowel Project, a history of LCIS was one of the enrollment criteria. There was a 50 percent reduction in the incidence of invasive breast cancer in the LCIS group receiving tamoxifen compared with the incidence in the group receiving a placebo, suggesting that tamoxifen may be reasonable therapy for patients with LCIS (Fisher et al., 1998a).
Increasing the ability to identify DCIS and LCIS raises important questions in regard to breast cancer screening. What are clinicians looking for, and what should they do when they find it? The biology of these small lesions and how to treat them are not as well studied, and research has been possible only since it became possible to detect them, so clarity about optimal treatment will take many years to develop.
Sharyl J. Nass, I. Craig Henderson, and Joyce C. Lashof
Committee on Technologies for the Early Detection of Breast Cancer
National Cancer Policy Board INSTITUTE OF MEDICINE and Division of Earth and Life Studies
NATIONAL RESEARCH COUNCIL