Clinical Trials for Ductal Carcinoma In Situ of the Breast

Abstract

Ductal carcinoma in situ (DCIS) of the breast is a non-obligatory precursor to invasive breast carcinoma, with a variable natural history and biological potential for progression to invasive disease. Over the past 30 years, clinical trials have applied the therapeutic principles used for invasive carcinoma to treat DCIS (surgery, with or without breast radiotherapy, and post-operative endocrine therapy), with excellent survival outcomes, and in-breast recurrence rates that range from 0.5 to 1% annually. However, half of such recurrences are again in-situ lesions, and intensive therapy is likely not necessary for all patients. Current clinical research is focused on a better characterization of the potential of individual lesions to progress to invasive disease, and to identify women who would do well with lesser treatment. Three ongoing trials in the United States and Europe randomize women to active surveillance (with or without endocrine therapy) versus usual treatment with surgery and radiotherapy. The use of pre-operative endocrine therapy has been evaluated in a recently completed trial of letrozole use in postmenopausal women with DCIS; and in on-going trials of tamoxifen, used either orally, or as a 4-hydroxytamoxifen gel formulation for application to the breast skin. This review summaries the major past and current clinical trials of DCIS, and the likely trajectories of DCIS management in the near future.

Ductal carcinoma in situ: current and future management for the surgeon and non-surgeon: a narrative review

“…Approximately 70-80% of DCIS patients can be managed with wide excision (21). Candidates for wide excision are those who can achieve an oncological resection in an acceptable cosmetic manner (22).…”

“…A plasmid vaccine called WOKVAC is also being studied (21). It targets antigens from three proteins that are overexpressed in pre-invasive and high-risk breast lesions that are associated with progression to invasive breast cancer: insulin like growth factor receptors 1 and 2 and HER2.…”

Old Receptor, New Tricks—The Ever-Expanding Universe of Aryl Hydrocarbon Receptor Functions. Report from the 4th AHR Meeting, 29–31 August 2018 in Paris, France

“…Even so, the breadth of AHR activity and the context (organ, ligand)-specific effects suggests caution when using AHR agonists or antagonists because of the potential on-target side effects. Two general sets of results mitigate against the argument that AHR modulators would adversely affect normal tissue in the disease setting: (1) A similar or perhaps greater level of concern was exhibited for many now-proven effective therapeutics that target over-expressed or over-active molecules, e.g., Letrozole, an aromatase inhibitor used to treat hormone-driven cancers [ 24 , 25 ], Bortezomib, a proteasome inhibitor used to treat multiple myeloma [ 26 , 27 ] and most kinase inhibitors used for several types of cancers; (2) To date, no “show stopper” side effects have been seen with AHR modulators in vivo. For example, Mary Walker (University of New Mexico, USA) showed work done together with scientists from Teva Pharmaceuticals, Netanya, Israel.…”

The management of women with ductal carcinoma in situ of the breast in Australia and New Zealand between 2007 and 2016

“…Concerns about overtreatment of DCIS have led to the establishment of several trials of treatment de-escalation for low-risk DCIS 4,5,11 to investigate active monitoring as an alternative to surgery. 5,6,13 In current clinical practice, however, surgery remains the mainstay of clinical management of DCIS, pending results of the deescalation trials. Furthermore, in contrast to invasive breast cancer, surgical guidance for treatment of DCIS is limited or lacking and as such it is unclear to what extent variation in surgical practice may exist currently in Australia and NZ.…”