Ductal Carcinoma In Situ - Quo Vadis?

Abstract

The introduction of mammographic screening in the early 1980's was associated, in the three following decades, with a dramatic increase in the detection of ductal carcinoma in situ (DCIS), pathology rarely detected before, on surgical specimen, at the periphery of an invasive cancer (1,2,3). It is estimated that in the United States the incidence of DCIS, each year, varies between 18 to 25% of the total number of newly diagnosed breast cancers (4,5). Ductal carcinoma in situ belongs, genetically and pathomorphologically, to a heterogenous group of preinvasive neoplastic lesions characterized by clonal proliferation of malignant cells limited to the lumen of breast ducts. It has not a known natural history and its phenotypical spectrum is wide, varying from a slowly evolving disease to a fast growing one, invading the surrounding stroma and even metastasizing to distant sites (6). In the absence of reliable prognostic markers, most of patients are submitted to invasive treatments consisting mainly in surgery, alone or associated with radiation and endocrine therapy (7). Molecular subtyping has improved the understanding of breast cancer biology and its possibilities for evolution and have provided the tools to design a more personalized treatment (8). In the absence of reliable molecular markers clinical management of patients with DCIS is based on patient's option and tumor characteristics. Based on the knowledge of today, DCIS could be used to exemplify the notions of overdiagnosis and overtreatment. The final goal of the treatment of DCIS is to prevent invasive breast cancer recurrence. Mortality rate associated with DCIS is very low, being estimated at 1-2 % at 10 years, while patients with DCIS treated by wide local excision with or without radiation may have a local recurrence rate of 5 to 30% and half of these present as an invasive cancer. Today's clinicians are not able to predict the risk of progression for a DCIS diagnosed by biopsy, but neither the risk of local recurrence, as an invasive cancer, of DCIS treated by conservative surgery with or without radiation (9). Progression to invasive cancer is difficult to be predicted as the disease is highly heterogenous. Because of these uncertainties, it is highly important to carefully inform the patient and engage her in the treatment decision process (10). There is a trend for de-escalation of treatment for DCIS. A study comparing two groups of patients with pure DCIS was conducted: one with standard care and the other under active surveillance (11). The main outcome was the probability to die from breast cancer at 10 years after the diagnosis. The mortality risk from breast cancer is higher for younger women, than the older ones, under active surveillance. Women over the age of 70 years, have many comorbidities that could induce the risk of dying, regardless of DCIS treatment decision. This study suggested that active surveillance could be a reasonable option for certain category of patients. This attitude is not without risks. A patient with DCIS on core needle biopsy could hide an invasive cancer in 25% of cases (12). Today, there are four randomized control trials of active surveillance offered to patients with low-grade DCIS: LORD (LOw Risk DCIS), COMET (Comparison of Operative to Monitoring and Endocrine Therapy), LORIS (LOw RISk DCIS) and LORETTA (10,13-16). Non-surgical approaches are of two types: active surveillance alone or associated with hormone therapy. There are some differences between the trials. While in LORD and LORIS trials the study arms are represented by active surveillance only, hormone therapy is an option in COMET trial and mandatory in the single arm trial LORETTA. The aim of these studies is to examine the safety and the effectiveness of active surveillance compared with surgical management for low-risk DCIS. The results of these trials are awaited with great interest. Patients with ductal carcinoma in situ need special counseling. To talk about "a good" cancer or even no cancer and to recommend as treatment a mastectomy is highly confusing. The language used by all members of the team must be unitary, removing the anxiety and helping patients to make the best decision. This special issue is a great opportunity to have the opinions of highly respected international specialists in the field for a comprehensive review of DCIS of the breast.