Introduction: Radiotherapy (RT) plays an indispensable role in postoperative breast cancer treatment. This study aimed to assess the feasibility of preoperative RT for stage III breast cancer by comparing preoperative RT with postoperative RT in terms of overall survival (OS). Methods: Based on the information in the Surveillance, Epidemiology, and End Results database from 2000 to 2018, patients with stage III breast cancer who had undergone radical surgery and RT were divided into two groups: a preoperative RT group and a postoperative RT group. OS was calculated using Kaplan-Meier analysis. The Cox proportional hazards model was used to evaluate independent factors associated with OS. Propensity score matching (PSM) was used to balance stratification factors. Results: In total, 9,605 patients were enrolled, of whom 9,456 received postoperative RT and 149 received preoperative RT. After a median follow-up of 72 months, postoperative RT was found to be superior to preoperative RT in terms of OS (p < 0.000). Compared to the postoperative RT group, the preoperative RT group showed a significantly higher risk of overall mortality without PSM in univariate (OS: hazard ratio [HR] = 1.653, 95% confidence interval [CI]: 1.288–2.123, p < 0.000) and multivariate analyses (OS: HR = 1.409, 95% CI: 1.096–1.810, p = 0.007). After PSM, the OS of the postoperative RT group was superior to the OS in the preoperative RT group (p = 0.041). Compared with the postoperative RT group, the preoperative RT group showed a significantly higher risk of overall mortality without PSM in univariate (HR = 1.312, 95% CI: 1.010–1.704, p = 0.042) and multivariate analyses (HR = 1.466, 95% CI: 1.127–1.906, p = 0.004). Conclusion: Preoperative RT does not improve OS in patients with stage III breast cancer and has a worse prognosis. Preoperative RT has not changed the existing treatment paradigm in the current therapeutic context for patients with stage III breast cancer.

Clarke M, Collins R, Darby S, Davies C, Elphinstone P, Evans V, et al. Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005;366(9503):2087–106.
Early Breast Cancer Trialists’ Collaborative Group EBCTCG; Darby S, McGale P, Correa C, Taylor C, Arriagada R, et al. Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10,801 women in 17 randomised trials. Lancet. 2011 Nov 12;378(9804):1707–16 Epub 2011 Oct 19.
Whelan TJ, Olivotto IA, Parulekar WR, Ackerman I, Chua BH, Nabid A, et al. Regional nodal irradiation in early-stage breast cancer. N Engl J Med. 2015;373(4):307–16.
EBCTCG Early Breast Cancer Trialists’ Collaborative Group; McGale P, Taylor C, Correa C, Cutter D, Duane F, et al. Effect of radiotherapy after mastectomy and axillary surgery on 10-year recurrence and 20-year breast cancer mortality: meta-analysis of individual patient data for 8,135 women in 22 randomised trials. Lancet. 2014 Jun 21;383(9935):2127–35 Epub 2014 Mar 19.
Liedtke C, Mazouni C, Hess KR, André F, Tordai A, Mejia JA, et al. Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. J Clin Oncol. 2008 Mar10;26(8):1275–81 Epub 2008 Feb 4.
Cortazar P, Zhang L, Untch M, Mehta K, Costantino JP, Wolmark N, et al. Pathological complete response and long term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet. 2014 Jul 12;384(9938):164–72 Epub 2014 Feb 14.
von Minckwitz G, Untch M, Blohmer Jens-U, Costa SD, Eidtmann H, Fasching PA, et al. Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J Clin Oncol. 2012 May 20;30(15):1796–804 Epub 2012 Apr 16.
Pazos M, Corradini S, Dian D, von Bodungen V, Ditsch N, Wuerstlein R, et al. Neoadjuvant radiotherapy followed by mastectomy and immediate breast reconstruction: an alternative treatment option for locally advanced breast cancer. Strahlenther Onkol. 2017 Apr;193(4):324–31 Epub 2017 Jan 25.
Kaidar-Person O, Vrou Offersen B, Hol S, Arenas M, Aristei C, Bourgier C, et al. ESTRO-ACROP consensus guideline for target volume delineation in the setting of postmastectomy radiation therapy after implant- based immediate reconstruction for early stage breast cancer. Radiother Oncol. 2019 Aug;137:159–66 Epub 2019 May 17.
Ho AY, Patel N, Ohri N, Morrow M, Mehrara BJ, Disa JJ, et al. Bilateral implant reconstruction does not affect the quality of postmastectomy radiation therapy. Med.Dosim. 2014 Mar 01;39(1):18–22.
Bartelink H. The changing landscape in radiotherapy for breast cancer: lessons from long term follow-up in some European breast cancer trials. Radiother Oncol. 2016 Dec;121(3):348–56 Epub 2016 Nov 24.
Recht A, Come SE, Henderson IC, Gelman RS, Silver B, Hayes DF, et al. The sequencing of chemotherapy and radiation therapy after conservative surgery for early-stage breast cancer. N Engl J Med. 1996 May 23;334(21):1356–61.
Mladenovic J, Susnjar S, Tanic M, Jankovic R, Karadzic K, Gavrilovic D, et al. Tumor response and patient outcome after preoperative radiotherapy in locally advanced non-inflammatory breast cancer patients. J BUON. 2017 Mar–Apr;22(2):325–33.
Vasmel JE, Vreuls CPH, Manson QF, Charaghvandi RK, van Gorp J, van Leeuwen AMG, et al. Tumor-infiltrating lymphocytes in low-risk patients with breast cancer treated with single dose preoperative partial breast irradiation. Int J Radiat Oncol Biol Phys. 2021 Apr 1;109(5):1325–31 Epub 2020 Dec 15.
Poggio F, Lambertini M, de Azambuja E. Controversis in oncology: surgery of the primary tumour in patients presenting with de novo metastatic breast cancer: to do or not to do?ESMO Open. 2018 Jan 27;3(1):e000324.
Cardoso F, Paluch-Shimon S, Senkus E, Curigliano G, Aapro MS, André F, et al. 5th ESO-ESMO international consensus guidelines for advanced breast cancer (ABC 5). Ann Oncol. 2020 Dec;31(12):1623–49 Epub 2020 Sep 23.
Finkelstein SE, Timmerman R, McBride WH, Schaue D, Hoffe SE, Mantz CA, et al. The confluence of stereotactic ablative radiotherapy and tumor immunology. Clin Dev Immunol. 2011;2011:439752.
Poleszczuk JT, Luddy KA, Prokopiou S, Robertson-Tessi M, Moros EG, Fishman M, et al. Abscopal benefits of localized radiotherapy depend on activated T-cell trafficking and distribution between metastatic lesions. Cancer Res. 2016 Mar.1;76(5):1009–18.
Burnette B, Weichselbaum RR. Radiation as an immune modulator seminars in radiation oncology. Semin Radiat Oncol. 2013 Oct;23(4):273–80.
Formenti SC, Demaria S. Radiation therapy to convert the tumor into an in situ vaccine. Int J Radiat Oncol Biol Phys. 2012;84(4):879–80.
Deng Y, Li H, Zheng Y, Zhai Z, Wang M, Lin S, et al. Impact of preoperative vs. Postoperative radiotherapy on overall survival of locally advanced breast cancer patients. Front Oncol. 2021 Nov 23;11:779185.
Zhang Y, Xu Z, Chen H, Sun X, Zhang Z. Survival comparison between postoperative and preoperative radiotherapy for stage I–III non-inflammatory breast cancer. Sci Rep. 2022;12(1):14288.
Poleszczuk J, Luddy K, Chen L, Lee JK, Harrison LB, Czerniecki BJ, et al. Neoadjuvant radiotherapy of early-stage breast cancer and long-term disease-free survival. Breast Cancer Res. 2017 Jun 30;19(1):75.
Palta M, Yoo S, Adamson JD, Prosnitz LR, Horton JK. Preoperative single fraction partial breast radiotherapy for early-stage breast cancer. Int J Radiat Oncol Biol Phys. 2012;82(1):37–42.
Sikov WM, Berry DA, Perou CM, Singh B, Cirrincione CT, Tolaney SM, et al. Impact of the addition of carboplatin and/or bevacizumab to neoadjuvant once-per-week paclitaxel followed by dose-dense doxorubicin and cyclophosphamide on pathologic complete response rates in stage II to III triple-negative breast cancer: CALGB 40603 (alliance). J Clin Oncol. 2015 Jan 1;33(1):13–21 Epub 2014 Aug 4.
Schmid P, Cortes J, Pusztai L, McArthur H, Kümmel S, Bergh J, et al. Pembrolizumab for early triple-negative breast cancer. N Engl J Med. 2020 Feb 27;382(9):810–21.
Schneeweiss A, Chia S, Hickish T, Harvey, V, Eniu, A, Hegg, R, et al. Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol. 2013;24(9):2278–84.
van Ramshorst MS, van der Voort A, van Werkhoven ED, Mandjes IA, Kemper I, Dezentjé VO, et al. Neoadjuvant chemotherapy with or without anthracyclines in the presence of dual HER2 blockade for HER2-positive breast cancer (TRAIN-2): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2018 Dec;19(12):1630–40 Epub 2018 Nov 6.
Johnston SRD, Harbeck N, Hegg R, Toi M, Martin M, Shao ZM, et al. Abemaciclib combined with endocrine therapy for the adjuvant treatment of HR+, HER2-node-positive, high-risk, early breast cancer (monarch E). J Clin Oncol. 2020 Dec 1;38(34):3987–98. Epub 2020 Sep 20.
Wang X, Wang SS, Huang H, Cai L, Zhao L, Peng RJ, et al. Effect of capecitabine maintenance therapy using lower dosage and higher frequency vs observation on disease- free survival among patients with early-stage triple-negative breast cancer who had received standard treatment: the SYSUCC- 001 randomized clinical trial. JAMA. 2021 Jan 5;325(1):50–8.
Masuda N, Lee SJ, Ohtani S, Im YH, Lee ES, Yokota I, et al. Adjuvant capecitabine for breast cancer after preoperative chemotherapy. N Engl J Med. 2017 Jun 1;376(22):2147–59.
Tutt ANJ, Garber JE, Kaufman B, Viale G, Fumagalli D, Rastogi P, et al. Adjuvant olaparib for patients with BRCA1- or BRCA2-mutated breast cancer. N Engl J Med. 2021 Jun 24;384(25):2394–405.
von Minckwitz G, Huang CS, Mano MS, Loibl S, Mamounas EP, Untch M, et al. Trastuzumab emtansine for residual invasive HER2-positive breast cancer. N Engl J Med. 2019 Feb 14;380(7):617–28.
Caudle AS, Gonzalez-Angulo AM, Hunt KK, Pusztai L, Kuerer HM, Mittendorf EA, et al. Impact of progression during neoadjuvant chemotherapy on surgical management of breast cancer. Ann Surg. 2011Apr;18(4):932–8.
Nozawa K, Takatsuka D, Endo Y, Horisawa N, Ozaki Y, Kataoka A, et al. Impact of tumor progression on survival during neoadjuvant chemotherapy in breast cancer: a cohort study. Anticancer Res. 2022 Jul;42(7):3735–42.
Riet FG, Fayard F, Arriagada R, Santos MA, Bourgier C, Ferchiou M, et al. Preoperative radiotherapy in breast cancer patients: 32 years of follow-up. Eur J Cancer. 2017 May;76:45–51 Epub 2017 Mar 6.
Montero A, Ciérvide R. Preoperative radio (chemo) therapy in breast cancer: time to switch the perspective?Curr Oncol. 2022 Dec 12;29(12):9767–87.
Thiruchelvam PTR, Leff DR, Godden AR, Cleator S, Wood SH, Kirby AM, et al. Primary radiotherapy and deep inferior epigastric perforator flap reconstruction for patients with breast cancer (PRADA): a multicentre, prospective, non-randomised, feasibility study. Lancet Oncol. 2022 May;23(5):682–90 Epub 2022 Apr 7.
Tanić M, Krivokuća A, Čavić M, Mladenović J, Plesinac Karapandžić V, Beck S, et al. Molecular signature of response to preoperative radiotherapy in locally advanced breast cancer. Radiat Oncol. 2018 Oct 1;13(1):193.
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