Abstract IA020: After DCIS surgery, what next? The prevention of future breast events

Abstract

Abstract Following surgical resection of DCIS, the next priority is to prevent future occurrence of invasive breast cancer (IBR). The probability of this can range from 1.5% annually to 0.2% annually, depending on age at diagnosis and a number of lesion and treatment related factors. Large clinical trials over three decades have demonstrated the efficacy of both breast radiotherapy (RT) and endocrine therapy (ET) in the prevention of subsequent IBR and DCIS (ipsilateral only for RT and contralateral as well for ET). Of these, RT is more widely used and accepted than ET, which has low uptake due concerns regarding adverse effects, and prevents only hormone receptor positive breast cancer; and. For women and their physicians, decisions regarding use of one, both, or neither of these modalities must consider both the benefits and the burdens of each. Recently updated 10-year results of RTOG 9804 show that even for low-risk DCIS, the 15-year cumulative incidence of new events was more than halved by the use of RT (7.1% versus 15.1%, P = .0007; HR = 0.36; 95% CI, 0.20 to 0.66). On multivariable analysis, only radiotherapy and tamoxifen use (HR = 0.45; 95% CI, 0.25 to 0.78; P = .0047) were associated with reduced IBR rates. Radiotherapy decisions have been aided recently by molecular assays which provide good prognostic stratification, and potentially also predictive information regarding RT benefits; these are entering clinical practice although further refinement and validation is needed. Medical therapy protects both breasts against further events, but Improvements are clearly needed, to extend the range of preventive efficacy to hormone insensitive disease, and to improve the tolerability of existing therapies. The value of identifying new agents that are effective and tolerable in the DCIS setting where the population is healthy, with long life expectancy, will likely be extendable to the larger high risk population. Therefore, DCIS provides an excellent opportunity to test new approaches to breast cancer prevention. Recent innovative attempts to improve medical therapy have focused on increasing the tolerability of known effective agents through dosing modifications (low dose tamoxifen and intermittent exemestane), and alternate delivery approaches (transdermal 4-hydroxytamoxifen). Encouraging data regarding neoadjuvant therapy has been reported from a 6-month treatment with letrozole. Strategies targeting HER-2 (expressed in a high frequency of DCIS lesions) include a trial of radiosensitization with trastuzumab, a window trial of lapatinib, and several vaccine-based approaches. Presurgical window trials have been initiated with interventions that range from palbociclib intralesional pembrolizumab. The search for new strategies that will prevent additional breast events in women diagnosed with DCIS continues will be complemented by work on improving acceptance and adherence to proven interventions. Together, these efforts will benefit the broader population of women at increased risk of breast cancer. Citation Format: Seema A. Khan. After DCIS surgery, what next? The prevention of future breast events [abstract]. In: Proceedings of the AACR Special Conference on Rethinking DCIS: An Opportunity for Prevention?; 2022 Sep 8-11; Philadelphia, PA. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_1): Abstract nr IA020.