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  • br The involved invasive margin rate in

    2020-08-24


    The involved invasive margin rate in our study is 6,7% for ‘BCS after NAC’ compared to 3,1% for ‘primary BCS’. The overall positive
    Fig. 2. Percentage of patients with invasive cT1-4M0 breast cancer and involved invasive margins who have received breast conserving surgery with or without chemotherapy upfront (2012e2016).
    margin rate in our study is 6,9% for ‘BCS after NAC’ compared to 3,3% for ‘primary BCS’. These rates are relatively low compared to other studies. In a systematic review performed by Volders et al. in which they aimed to determine surgical outcomes for BCS after NAC, involved margins ranged from 5% to 39.8% after NAC versus 13.1%e46% for primary BCS [36]. These percentages were based on ten studies describing involved margins with or without NAC, but a clear comparison between these studies was not possible due to variation in terminology and variation amongst patient groups. Because of the nationwide character of our study in which all pa-tients treated with invasive breast cancer are included, a 6,9% involved margin rate for BCS after NAC and a 3,3% involved margin rate for primary BCS is a reliable baseline for the quality of care in the Netherlands nowadays.
    An important result of this nationwide data is that BCS after NAC leads to equal surgical outcomes for cT2 and improved outcomes for cT3 invasive breast cancer compared to primary BCS. Boughey et al. already described in 2006 using data from 1998 to 2005, that NAC reduces the volume of tissue excised in patients with T2 and T3 breast cancer treated with BCS, without an increase in rates of re-excision [37]. Ever since, improvements of targeted therapies to achieve a pathologic complete response (pCR) in combination with improvements in the identification of the original tumour location have led to more BCS after NAC with less involved invasive margins and a lower re-operation rates [9e12,22].
    Our multivariable analyses detailed important prognostic fac-tors associated with a higher risk of involved invasive margins for patients who will receive BCS after NAC: lobular invasive breast cancer, an increasing clinical tumour stage and a hormone GSK 3 positive receptor status. A decreased feasibility for successful BCS has been described in the setting of lobular histology, multi-centricity and diffuse calcifications noted on preoperative mammography [38]. And, it is known that HR-positive subtypes are associated with the lowest rates of pathological complete response (pCR) [30]. Another interesting assumption made by Landscaper et al. is that cancer subtypes may have an independent association with a surgical outcome, reported that triple-negative patients not receiving NAC had the lowest reoperation rate. This result corre-lates with our findings that a positive hormone receptor status was clearly associated with involved invasive margins for cT3 tumours, with no difference between patients receiving NAC and patients 
    receiving no NAC. Because larger tumour size and higher grade are characteristics commonly reported on triple negative patients and because NAC is the standard of care for many of these patients [39], this will have contributed to the lower rate of involved margins for cT3 invasive breast cancer patients treated with NAC as seen in our study. Moreover, it supports the biologic heterogeneity of invasive breast cancer with its own approach and expected surgical outcomes.
    Unaddressed issues are recurrence rates and cosmetic out-comes for patients treated with BCS after NAC, which we were unable to investigate in this study. A strong association of improved long-term outcomes in patients with pCR compared to patients with residual invasive tumour at the time of surgery has been consistently reported by many groups [11,30,40,41]. How-ever, the surrogacy of pCR as an endpoint for long-term clinical outcome has not been established [42]. Future analyses of ran-domized trials of targeted agents in homogeneous tumour sub-types will help elucidate whether there is a significant association between pCR and long-term outcomes. Cosmetic outcomes for NAC followed by BCS have only been reported in retrospectives studies and no conclusions can be drawn yet [43,44]. Several studies do describe a lower resected volume in patients treated with neoadjuvant therapy compared to adjuvant therapy, what potentially could lead to better cosmetic outcomes and an improved quality of life. Although we did not specify resection volumes and cosmetic outcome in this study, we emphasize the fact that follow-up on this subject is necessary and of major impact in delivering quality care to patients. A poor cosmetic outcome after BCS should be avoided at any time. Work has been established to link patient reported outcome mea-surements (PROMS) to clinical data of patients treated with BCS after NAC and will eventually show the patients’ satisfaction and long term cosmetic outcomes. This information will be of great value empowering patients to be effective advocates for their health, and that they can make informed decisions in light of it.