De novo metastatic breast cancer (dnMBC) is diagnosed when breast cancer has spread at presentation and accounts for 5–10% of cases. The benefit of postoperative radiotherapy (PORT) after primary tumor surgery in this setting remains uncertain.
Methods:
We conducted a review and meta-analysis of observational studies published between 2013 and 2024. Two databases (PubMed and Embase) were searched and the review followed PRISMA 2020 guidelines. The aim was to evaluate whether PORT improves overall survival (OS) in dnMBC patients undergoing surgery. The PICOTS framework was applied. Studies were eligible if they compared surgery with or without PORT. OS was analyzed at three and five years as a binary outcome. The study was not registered prospectively.
Results:
Five studies were included qualitatively; three were eligible for quantitative synthesis (N=8,557). PORT was associated with improved OS at three years (OR=0.62; 95% CI: 0.56–0.68) and five years (OR=0.65; 95% CI: 0.60–0.71). Benefits were most evident in patients with bone-only metastases and luminal A tumors. No consistent survival advantage was seen in HER2+ or triple-negative disease.
Conclusions:
PORT may offer a survival advantage for selected dnMBC patients undergoing surgery. Further prospective studies are needed to confirm these findings and define optimal candidates.
TaoLChuLWangLI, et al. Occurrence and outcome of de novo metastatic breast cancer by subtype in a large, diverse population. Cancer Causes Control2016; 27: 1127–1138.
2.
DailyKDouglasERomittiPA, et al. (2021) Epidemiology of de novo metastatic breast cancer. Clinical Breast Cancer2021; 21: 302–308.
3.
CortesiLTossACirilliC, et al. Twenty-years experience with de novo metastatic breast cancer: De novo metastatic breast cancer. Int J Cancer2015; 137: 1417–1426.
4.
SundquistMBrudinLTejlerG.Improved survival in metastatic breast cancer 1985–2016. Breast2017; 31: 46–50.
5.
GrindaTAntoineAJacotW, et al. Evolution of overall survival and receipt of new therapies by subtype among 20 446 metastatic breast cancer patients in the 2008-2017 ESME cohort. ESMO Open2021; 6: 100114.
6.
EngLGDawoodSSopikV, et al. Ten-year survival in women with primary stage IV breast cancer. Breast Cancer Res Treat2016; 160: 145–152.
7.
HarrisEBarryMKellMR.Meta-analysis to determine if surgical resection of the primary tumour in the setting of stage IV breast cancer impacts on survival. Ann Surg Oncol2013; 20: 2828–2834.
8.
HeadonHWazirUKasemA, et al. Surgical treatment of the primary tumour improves the overall survival in patients with metastatic breast cancer: A systematic review and meta-analysis. Mol Clin Oncol2016; 4: 863–867.
9.
PetrelliFBarniS.Surgery of primary tumors in stage IV breast cancer: an updated meta-analysis of published studies with meta-regression. Med Oncol2012; 29: 3282–3290.
10.
XiaoWZouYZhengS, et al. Primary tumor resection in stage IV breast cancer: A systematic review and meta-analysis. Eur J Surg Oncol2018; 44: 1504–1512.
11.
BadweRHawaldarRNairN, et al. Locoregional treatment versus no treatment of the primary tumour in metastatic breast cancer: an open-label randomised controlled trial. Lancet Oncol2015; 16: 1380–1388.
12.
FitzalFBjelic-RadisicVKnauerM, et al. Impact of breast surgery in primary metastasized breast cancer: outcomes of the prospective randomized phase III ABCSG-28 POSYTIVE Trial. Ann Surg2019; 269: 1163–1169.
13.
ShienTHaraFAogiK, et al. Primary tumour resection plus systemic therapy versus systemic therapy alone in metastatic breast cancer (JCOG1017, PRIM-BC): a randomised clinical trial. Br J Cancer2025; 133: 625–632.
14.
SoranAOzmenVOzbasS, et al. Primary surgery with systemic therapy in patients with de novo stage IV breast cancer: 10-year Follow-up; Protocol MF07-01 Randomized Clinical Trial. J Am Coll Surg2021; 233: 742-751e5.
15.
KhanSAZhaoFGoldsteinLJ, et al. Early local therapy for the primary site in de novo stage IV breast cancer: results of a randomized clinical trial (E2108). JCO2022; 40: 978–987.
16.
SoranAOzmenVOzbasS, et al. Randomized trial comparing resection of primary tumor with no surgery in stage IV breast cancer at presentation: Protocol MF07-01. Ann Surg Oncol2018; 25: 3141–3149.
17.
Abo-ToukN.The benefit of locoregional surgical intervention in metastatic breast cancer at initial presentation. CRJ2016; 4: 32.
18.
GennariAAndréFBarriosCH, et al. ESMO Clinical Practice Guideline for the diagnosis, staging and treatment of patients with metastatic breast cancer. Ann Oncol2021; 32: 1475–1495.
19.
GradisharWJMoranMSAbrahamJ, et al. Breast Cancer, Version 3.2024, NCCN Clinical Practice Guidelines in Oncology. J Nat Comp Cancer Network2024; 22: 331–357.
20.
Le ScodanRGhannamYKirovaY, et al. Radiation therapy of the primary tumour and oligometastatic sites in patients with breast cancer with synchronous metastases: A literature review. Cancer/Radiothérapie2014; 28: 3–14.
21.
SpeersCPierceLJ.Postoperative radiotherapy after breast-conserving surgery for early-stage breast cancer: a review. JAMA Oncol2016; 2: 1075.
22.
HalyardMBrownLMutterR.Benefits, risks, and safety of external beam radiation therapy for breast cancer. IJWH2015; 449.
23.
LoCK-LMertzDLoebM. Newcastle-Ottawa Scale: comparing reviewers’ to authors’ assessments. BMC Med Res Methodol2014; 14: 45.
24.
Pons-TostivintEKirovaYLusqueA, et al. Radiation therapy to the primary tumor for de novo metastatic breast cancer and overall survival in a retrospective multicenter cohort analysis. Radiother Oncol2020; 145: 109–116.
25.
WangJYangSZhouP, et al. Additional radiotherapy to breast-conserving surgery is an optional treatment for de novo stage IV breast cancer: A population-based analysis. Cancer Med2021; 10: 1634–1643.
26.
KimYJKimY-JKimYB, et al. Effect of postoperative radiotherapy after primary tumor resection in de novo stage IV breast cancer: a multicenter retrospective study (KROG 19-02). Cancer Res Treat2022; 54: 478–487.
27.
MiyashitaMBalogunOBOlopadeOI, et al. The optimization of postoperative radiotherapy in de novo stage IV breast cancer: evidence from real-world data to personalize treatment decisions. Sci Rep2023; 13: 2880.
28.
ZhangJLuoSQiuZ, et al. Impact of postoperative radiotherapy on survival of patients with de novo stage IV breast cancer: a population-based study from the SEER Database. Front Oncol2021; 11: 625628.
29.
NguyenATShiaoSLMcArthurHL.Advances in combining radiation and immunotherapy in breast cancer. Clin Breast Cancer2021; 21: 143–152.
30.
FormentiSCDemariaS.Local control by radiotherapy: is that all there is?Breast Cancer Res2008; 10: 215.
31.
EstevaFJHubbard-LuceyVMTangJ, et al. Immunotherapy and targeted therapy combinations in metastatic breast cancer. Lancet Oncol2019; 20: e175–e186.
32.
PilonesKKoelwynGEmersonR, et al. Abstract 2856: Unique changes in the TCR repertoire of tumor-infiltrating lymphocytes underlie the synergy of radiotherapy with CTLA-4 blockade. Cancer Res2015; 75: 2856–2856.
33.
SoranADoganLIsikA, et al. The effect of primary surgery in patients with de novo stage IV breast cancer with bone metastasis only (Protocol BOMET MF 14-01): A multi-center, prospective registry study. Ann Surg Oncol2021; 28: 5048–5057.
34.
BitencourtARossi SaccarelliCMorrisEA, et al. Regional lymph node involvement among patients with de novo metastatic breast cancer. JAMA Netw Open2020; 3: e2018790.
35.
JiLSongGXiaoM, et al. Subdivision of M1 category and prognostic stage for de novo metastatic breast cancer to enhance prognostic prediction and guide the selection of locoregional therapy. Thoracic Cancer2024; 15: 2193–2205.
36.
PlichtaJKThomasSMHayesDF, et al. Novel prognostic staging system for patients with de novo metastatic breast cancer. JCO2023; 41: 2546–2560.
37.
LiuBLiuHLiuM.Aggressive local therapy for de novo metastatic breast cancer: Challenges and updates (Review). Oncol Rep2023; 50: 163.
38.
AgostinettoECuriglianoGPiccartM.Emerging treatments in HER2-positive advanced breast cancer: Keep raising the bar. Cell Rep Med2024; 5: 101575.
39.
TarantinoPCuriglianoGParsonsHA, et al. Aiming at a tailored cure for ERBB2 -positive metastatic breast cancer: a review. JAMA Oncol2022; 8: 629.
40.
DebienVAgostinettoEBruzzoneM, et al (2024) The impact of initial tumor response on survival outcomes of patients with HER2-positive advanced breast cancer treated with docetaxel, trastuzumab, and pertuzumab: an exploratory analysis of the CLEOPATRA Trial. Clin Breast Cancer2024; 24: 421-430.e3.
41.
SoranASoyderAOzbasS, et al. The role of loco-regional treatment in long-term quality of life in de novo stage IV breast cancer patients: protocol MF07-01Q. Supp Care Cancer2021; 29: 3823–3830.
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
