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    内容提示: Viewpoints and debateLess is more. Breast conservation might be even better thanmastectomy in early breast cancer patientsOreste D. Gentilinia , * , Maria-Joao Cardoso b , Philip Poortmans ca San Raffaele University and Research Hospital, Milano, Italyb Breast Unit, Champalimaud Foundation, Lisbon, Portugalc Department of Radiation Oncology, Institut Curie, Paris, Francea r t i c l e i n f oArticle history:Received 14 April 2017Accepted 10 June 2017Available online 20 June 2017a b s t r a c tDuring the rec...

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    Viewpoints and debateLess is more. Breast conservation might be even better thanmastectomy in early breast cancer patientsOreste D. Gentilinia , * , Maria-Joao Cardoso b , Philip Poortmans ca San Raffaele University and Research Hospital, Milano, Italyb Breast Unit, Champalimaud Foundation, Lisbon, Portugalc Department of Radiation Oncology, Institut Curie, Paris, Francea r t i c l e i n f oArticle history:Received 14 April 2017Accepted 10 June 2017Available online 20 June 2017a b s t r a c tDuring the recent years an increase of mastectomy rates in early breast cancer patients has beenobserved. Nevertheless, several large population-based studies reported a possible improved outcomeafter breast conserving therapy compared to radical surgery, after all the adjustments. We herebysummarize our opinion on this topic suggesting that these robust and consistent data might challengethe statement that breast conserving therapy is merely not inferior to radical surgery.© 2017 Elsevier Ltd. All rights reserved.1. Historical versus contemporary data and the non-inferiority conceptDecades have passed since the publication of the milestonepapers which changed the life of women with early breast cancer[1,2]. Randomized trials demonstrated the non-inferiority ofbreast-conserving therapy (BCT) compared to mastectomy as theincrease of local recurrences (LR) in patients receiving BCT wasdeemed acceptable with similar overall survival (OS) and a clearlyimproved quality of life. Since then, we thought that LR of earlystage breast cancer after BCT does not affect survival. In otherwords, the excess of LR or second primary tumours reported in thehistorical trials was, albeit statistically signif i cant, so limited that itdid not have the power to translate into a statistically signif i cant orclinically relevant survival effect [3].In the meantime, the management of breast cancer patients hasdramatically improved. The pivotal BCT trials were carried outwhen adjuvant treatments were not routinely administered to allhigh-risk patients and not tailored to disease biology. Preoperativeassessment was poorer, genetic predisposition was still unknownand RT was less advanced with more side effects. In those years, therisk of LR was estimated to be around 1% per year translating into10% at 10 years. As expected, taking into account the describedimprovements, morerecentstudies showan impressive decreaseinLR ratesbeing just 2% at 10years [4].This lead tothequestion,if BCTwas not inferior to mastectomy in terms of OS despite a statisticallysignif i cant excess in local events, what happens if LR reaches thelowest conceivable rate?2. Is anything new going on here?In 2015 and in 2016 several authors suggested that somethingmight have changed over time. Agarwal et al. [5] reported on132.000 patients with early stage breast cancer from the SEERdatabase. Patients with tumours up to 4 cm and 0 to 3 positivenodes were divided according to the type of local treatment (BCT,mastectomy alone, mastectomy þ RT). Disease specif i c survival wasbetter in the BCTcohort, which was conf i rmed in subgroup analysesbased on tumour size and lymph node involvement. Vila et al. [6]carried out a meta-analysis on more than 22.000 women evalu-ating the effect of the type of surgery on OS in patients youngerthan 40 years whose LR rate is known to be higher than in oldercounterparts. A 10% borderline statistically signif i cant reduction inmortality was found in women who underwent BCT compared tomastectomy. Interestingly, the larger survival advantage occurredin node positive patients. The analyses of the National CancerDatabase Registry by Chen et al. and of the Norwegian CancerRegistry by Hartmann-Johnsen et al., both comparing BCT andmastectomy, reached the same conclusion [7,8]. The NetherlandsCancer Registry analyses conf i rms the aforementioned conclusion,even after adjusting for confounding variables. Remarkably, BCTsignif i cantly improved 10-year distant DFS in a separate cohort ofpatients with T1N0 disease [9,10]. Certainly, all these reports* Corresponding author. San Raffaele Scientif i c and Research Hospital, ViaOlgettina 60, 20132, Milano, Italy.E-mail address: gentilini.oreste@hsr.it (O.D. Gentilini).Contents lists available at ScienceDirectThe Breastjournal homepage: www.elsevier.com/brsthttp://dx.doi.org/10.1016/j.breast.2017.06.0040960-9776/© 2017 Elsevier Ltd. All rights reserved.The Breast 35 (2017) 32e33 concern retrospective analyses eeven with data gathered in aprospective way- and might thereby be biased by confoundingfactors. However, the number of patients included is very high andstatistical analysis was adjusted for all available confounding vari-ables (Table 1). Overall, these data can be considered at least ashypothesis-generating and challenge the statement that BCT ismerely “not inferior” to mastectomy.With this in mind we wonder about the reasons explaining thisapparently strange phenomenon of a limited procedure being su-perior to a more radical surgery. The impact of RT is the mostobvious one. The concept of RTas local treatment having a systemiceffect seems now easier to understand after the overview on theimpact of postoperative RT [11]. Secondly, we might also speculateon a possibly depressed immune response after more extensivesurgery. Indeed, the complex relationship between surgical trauma,RT, medical treatment and immune response is largely unknown.Since Fisher challenged the Halstedian principle of superradicalexcision to control the disease with the systemic theory, we sus-pected that mastectomy would not be the solution to beat breastcancer as surgery is aimed at removing macroscopical disease andnot microscopical foci. Therefore, in this scenario, more extensivesurgery is not expected to improve the cure rate but eventually mayeven harm more. The “less is more” concept perfectly f i ts here.It is probably unconceivable to design a trial aimed at demon-strating these hypotheses. However, the consistent data from theselarge population-based studies should be favourably acknowledgedand digested by physicians f i rst along with the very low contem-porary LR rate after BCT. The number of patients receiving mas-tectomy is, in our opinion, still too high and should be reduced byless emotional and more rational decisions. Sometimes patientsdemand a mastectomy, driven by fear and the desire of getting ridof the disease while ignoring all this new information. It isimportant to inform them properly that, in most cases, breastcancer can be cured maybe even better without the need to beseparated from of their breasts.References[1] Veronesi U1, Cascinelli N, Mariani L, Greco M, Saccozzi R, Luini A, et al.Twenty-year follow-up of a randomized study comparing breast-conservingsurgery with radical mastectomy for early breast cancer. N Engl J Med 2002Oct 17;347(16):1227e32.[2] Fisher B, Anderson S, Bryant J, Margolese RG, Deutsch M, Fisher ER, et al.Twenty-year follow-up of a randomized trial comparing total mastectomy,lumpectomy, and lumpectomy plus irradiation for the treatment of invasivebreast cancer. N Engl J Med 2002;347:1233e41.[3] Chen Y, Jiang L, Gao B, Cheng ZY, Jin J, Yang KH. Survival and disease-freebenef i ts with mastectomy versus breast conservation therapy for earlybreast cancer: a meta-analysis. Breast Cancer Res Treat 2016;157(3):517e25.[4] Poortmans PM, Arenas M, Livi L. Over-irradiation. Breast 2017 Feb;31:295e302.[5] Agarwal S, Pappas L, Neumayer L, Kokeny K, Agarwal J. Effect of breast con-servation therapy vs mastectomy on disease-specif i c survival for early-stagebreast cancer. JAMA Surg 2014;149(3):267e74.[6] Vila J, Gandini S, Gentilini O. Overall survival according to type of surgery inyoung (</¼40 years) early breast cancer patients: a systematic meta-analysiscomparing breast-conserving surgery versus mastectomy. Breast 2015;24(3):175e81.[7] Chen K, Liu J, Zhu L, Su F, Song E, Jacobs LK. Comparative effectiveness study ofbreast-conserving surgery and mastectomy in the general population: a NCDBanalysis. Oncotarget 2015;6(37):40127e40.[8] Hartmann-Johnsen OJ, Karesen R, Schlichting E, Nygard JF. Survival is betterafter breast conserving therapy than mastectomy for early stage breast can-cer: a registry-based follow-up study of Norwegian women primary operatedbetween 1998 and 2008. Ann Surg Oncol 2015;22(12):3836e45.[9] Van Maaren MC, de Munck L, de Bock GH, Jobsen JJ, van Dalen T, Linn SC, et al.10 year survival after breast-conserving surgery plus radiotherapy comparedwith mastectomy in early breast cancer in The Netherlands: a population-based study. Lancet Oncol 2016;17(8):1158.[10] Lagendijk M, van Maaren MC, Saadatmand S, Strobbe LJA, Poortmans P,Koppert LB, et al., editors. 4LBA e breast conserving therapy and mastectomyrevisited: breast cancer-specif i c survival and the inf l uence of prognostic fac-tors in 129,692 patients. ECCO 2017-European Cancer Conference; 2017[Amsterdam].[11] EBCTCG (Early Breast Cancer Trialists' Collaborative Group), McGale P,Taylor C, Correa C, Cutter D, Duane F, Ewertz M. Effect of radiotherapy aftermastectomy and axillary surgery on 10-year recurrence and 20-year breastcancer mortality: meta-analysis of individual patient data for 8135 women in22 randomised trials. Lancet 2014;383(9935):2127e35.Table 1Recent data comparing BCS þ RT to Mastectomy.Author (ref number), year Study Period Data source Inclusion criteria N. of patients OutcomeMeasureResultsBCSþRT M MþRTAgarwal [5], 2014 1998e2008 SEER database T?4cmN0-1132.149 5y BCSS10y BCSS9794949090%83%Hartman-Johnsen [5], 2015 1998e2008 Norway Cancer Registry T1-2N0-113.015 5yOS10yOS5y BCSS10yBCSS9586979380848882eChen [6], 2015 2004e2011 National Cancer Database T1-2N1-3160.880 5y OS8y OS93.286.583.572.38370.4Lagendijk, Van Maaren [9,10],2016, 20171999e2012 Netherlands Cancer Registry T1-2N0-2129.692 11.7y OS and BCSS(1999-2005 cohort)OS:HR 0.74BCSS: HR 0.72HR 1 e6y OS and BCSS(2006-2012 cohort)OS: HR 0.67BCSS: HR 0.75HR 1BCSS¼Breast Cancer-Specif i c Survival M ¼ Mastectomy.O.D. Gentilini et al. / The Breast 35 (2017) 32e33 33

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