Ductal carcinoma in situ of the breast: an update for the pathologist in the era of individualized risk assessment and tailored therapies

Abstract

Ductal carcinoma in situ (DCIS) is a neoplastic proliferation of mammary ductal epithelial cells confined to the ductallobular system, and a non-obligate precursor of invasive disease. While there has been a significant increase in the diagnosis of DCIS in recent years due to uptake of mammography screening, there has been little change in the rate of invasive recurrence, indicating that a large proportion of patients diagnosed with DCIS will never develop invasive disease. The main issue for clinicians is how to reliably predict the prognosis of DCIS in order to individualize patient treatment, especially as treatment ranges from surveillance only, breast-conserving surgery only, to breast-conserving surgery plus radiotherapy and/ or hormonal therapy, and mastectomy with or without radiotherapy. We conducted a semi-structured literature review to address the above issues relating to "pure" DCIS. Here we discuss the pathology of DCIS, risk factors for recurrence, biomarkers and molecular signatures, and disease management. Potential mechanisms of progression from DCIS to invasive cancer and problems faced by clinicians and pathologists in diagnosing and treating this disease are also discussed. Despite the tremendous research efforts to identify accurate risk stratification predictors of invasive recurrence and response to radiotherapy and endocrine therapy, to date there is no simple, well-validated marker or group of variables for risk estimation, particularly in the setting of adjuvant treatment after breast-conserving surgery. Thus, the standard of care to date remains breast-conserving surgery plus radiotherapy, with or without hormonal therapy. Emerging tools, such as pathologic or biologic markers, may soon change such practice. Our review also includes recent advances towards innovative treatment strategies, including targeted therapies, immune modulators, and vaccines.

Ductal Carcinoma In Situ of the Breast: An Update with Emphasis on Radiological and Morphological Features as Predictive Prognostic Factors

“…High-grade DCIS often shows comedonecrosis, when the necrotic core extends into the ductal lumen that canundergo calcifications. Necrosis is also constantly and strongly associated with ipsilateral recurrence, with the hazard ratio (HR), in general, above 2.0 [16]. Some studies demonstrated that the risk of ipsilateral recurrence is greater if DCIS with comedonecrosis is only treated with breast conserving surgery, compared to DCIS managed with mastectomy, skin-sparing mastectomy, or breast conserving surgery plus radiotherapy [16].…”

“…Zhang et al also disagreeon the role of comedonecrosis, suggesting that there is no correlation between necrosis and the risk of invasive local recurrence [15]. demonstrated that the risk of ipsilateral recurrence is greater if DCIS with comedonecrosis is only treated with breast conserving surgery, compared to DCIS managed with mastectomy, skin -sparing mastectomy, or breast conserving surgery plus radiotherapy [16]. Zhang et al also disagreeon the role of comedonecrosis, suggesting that there is no correlation between n ecrosis and the risk of invasive local recurrence [15].…”

“…Although several immunohistochemical studies have been performed on DCIS, with the aim of correlating a specific immunohistochemical profile with the risk of local recurrence (in terms of in situor invasive lesions), the results are conflicting [16]. This is true not only for each single immunomarker tested but also after classifying DCIS into molecular subtypes, similarly to what has been applied to invasive breast carcinoma [25].…”

“…The DCIS score can be used to quantify the risk within 10 years of developing a relapse, even invasive, following the diagnosis of DCIS without radiotherapy. The histopathological aspects that correlate with the score are unclear, but several studies explain that the predictive value of this score assumes greater value if correlated with age at diagnosis, tumor size, and multifocality [16].…”

Breast Mammographic Density: Stromal Implications on Breast Cancer Detection and Therapy

“…Epidemiologically, DCIS represents 20-25% of all new BC cases diagnosed [31] and this incidence is increasing as a result of an upgraded resolution of breast mammography [32]. Around 80% of the DCIS are identified by the presence of micro-calcifications and the remaining 20% by the detection of architectural deformation in mammography screening [33,34] (Figure 1B2).…”