Opportunities for molecular epidemiological research on ductal carcinoma in-situ and breast carcinogenesis: Interdisciplinary approaches

Abstract

Most invasive breast cancers arise from ductal carcinoma in-situ (DCIS), a non-obligate precursor of invasive breast cancer. Given that the natural history of individual DCIS lesions is unpredictable, many women with DCIS receive extensive treatments, which may include surgery, radiation and endocrine therapy, even though many of these lesions may have limited potential to progress to invasion and metastasize. In contrast to valid concerns about over-treatment, the fact that invasive breast cancers outnumber DCIS lesions by more than three-to-one, suggests that many cancer precursors (particularly DCIS, but LCIS also) progress to invasion prior to detection. Thus, DCIS poses a dual problem of over diagnosis among some women and failure of early detection among others. These concerns are heightened by the multi-fold increase in rates of DCIS in conjunction with widespread use of mammographic screening and access to outpatient radiologically-guided biopsies. Accordingly, methods are needed to both specifically detect and identify DCIS lesions with potential to progress to invasive cancer and to discover techniques to triage and conservatively manage indolent cases of DCIS.

Comparison of Mammographic Density Assessed as Volumes and Areas among Women Undergoing Diagnostic Image-Guided Breast Biopsy

“…Evaluation of the contralateral breast mitigated concerns that density estimates were influenced by so-called “field effects” related to the suspicious lesions. On the other hand, these field effects – if apparent in the mammogram – may serve as a useful clinical indicator of underlying pathology (43). Prior studies have reported that high-risk lesions tend to occur in regions of the breast that are mammographically dense (44, 45), suggesting that localized density measures may prove to be informative with respect to risk prediction.…”

Screening Mammography

“…This need is particularly problematic for ductal carcinoma in situ (51), but it also applies to diagnoses of localized ''invasive'' carcinoma. Surgical oncologists at the Netherlands Cancer Institute (52) and others (53) are evaluating gene signatures for this purpose and have already been able to sort out patients with an ''ultralow-risk.''…”

The hallmarks of premalignant conditions: a molecular basis for cancer prevention

“…These individuals are a key group for whom interventions and monitoring are achievable. However, as discussed earlier, in the absence of a complete understanding of the natural history of the condition and knowledge of which premalignant lesions will progress to malignancy, it will be difficult to know for whom interventions are necessary and thus it will be important to conservatively manage such cases [60,179]. Furthermore, these individuals remain in a high-risk category, even following removal or regression of the premalignant condition.…”