PDF
Abstract
Background: In stage IV breast cancer, surgical resection of the primary tumor was traditionally performed solely to palliate symptoms such as bleeding, infection, or pain. The ongoing discussion has shown that there are many research gaps in the current literature and differences in clinical practice. Thus, this systematic review and meta-analysis was designed to evaluate how primary tumor resection (PTR) affects the overall survival (OS) of patients with stage IV breast cancer. Method: A thorough literature search was completed using different databases (PubMed, Google Scholar, Scopus, ScienceDirect, and Cochrane Library) to find papers contrasting PTR with no PTR. The quality of research articles was evaluated using the Cochrane Risk of Bias 2.0 Tool and the Newcastle-Ottawa Scale (NOS). Review Manager 5.4 was used to determine how much demographic and clinical factors contribute to heterogeneity through subgroup and meta-regression analysis. Results: Data derived from 44 observational studies (OS) and four randomized controlled trials (RCTs) including 227,889 patients were analyzed. Of all cases, 150,239 patients were included in the non-PTR group, and 70,795 patients in the PTR group (37 observational studies and 4 randomized control trials). The pooled outcomes of four RCT studies (Hazard Ratio (HR) = 1.03, 95%CI: 0.67-1.58; I2 = 88%; P < 0.0001; chi-square 24.57) favor non-PTR. While pooled outcomes of 43 observational studies showed PTR significantly improved OS (HR = 0.66, 95%CI: 0.61-0.71; I2 = 87%; P < 0.00001; chi-square 359.12). Additionally, subgroup analysis that compared PTR with non-PTR in patients with stage IV breast cancer for progression free-survival (HR = 0.89, 95%CI: 0.62-1.28; P = 0.03; I2 = 71%) and locoregional progression-free survival (LPFS) (HR = 0.33, 95%CI: 0.14-0.74; P = 0.0004; I2 = 87%) was found to be significant favoring the PTR group. Distant progression-free survival (DPFS) had a non-significant relationship (HR = 0.42, 95%CI: 0.29-0.60; P = 0.12; I2 = 53%), while overall, there was a significant relationship (HR = 0.49, 95%CI: 0.32-0.75; P < 0.00001; I2 = 90%). Subgroup analysis revealed that PTR is beneficial in patients with bone metastasis (HR = 0.83, 95%CI: 0.68-1.01; P = 0.01; I2 = 56%), with one metastatic site (HR = 0.75, 95%CI: 0.63-0.59; P = 0.006; I2 = 62%), but not in patients with positive margins (HR = 0.84, 95%CI: 0.67-1.06; P = 0.07; I2 = 61%), negative margins (HR = 0.61, 95%CI: 0.59-0.63, P = 1.00; I2 = 0%). Most of the patients in PTR and non-PTR groups belonged to white compared to other ethnic groups. Overall, observational studies were of high quality, while RCTs were of low quality. Conclusion: The current research suggests that PTR may be discussed as a possible option.
Keywords
PTR
/
primary tumor resection
/
breast cancer IV stage
/
breast cancer
/
overall survival
/
metastatic disease
Cite this article
Download citation ▾
Zacharoula Sidiropoulou, Ana Rita Martins, Patricia Amaral, Vasco Cardoso, Sofia Boligo, Vasco Fonseca.
Updated evidence of primary tumor resection in stage IV breast cancer: a systematic review and meta-analysis.
Journal of Cancer Metastasis and Treatment, 2023, 9: 41 DOI:10.20517/2394-4722.2023.93
| [1] |
WHO. Breast cancer. 2021. Available from: https://www.who.int/news-room/fact-sheets/detail/breast-cancer [Last accessed on 27 Dec 2023].
|
| [2] |
Wilkinson L.Understanding breast cancer as a global health concern.Br J Radiol2022;95:20211033 PMCID:PMC8822551
|
| [3] |
Khan SA,Goldstein LJ.Early local therapy for the primary site in de novo stage IV breast cancer: results of a randomized clinical trial (E2108).J Clin Oncol2022;40:978-87
|
| [4] |
Stein KD,Andrykowski MA.Physical and psychological long-term and late effects of cancer.Cancer2008;112:2577-92
|
| [5] |
Ferrell BR,Funk B,Garcia N.Quality of life in breast cancer. Part I: physical and social well-being.Cancer Nurs1997;20:398-408
|
| [6] |
Hurvitz SA,Crosby RD.Use of the metastatic breast cancer progression (MBC-P) questionnaire to assess the value of progression-free survival for women with metastatic breast cancer.Breast Cancer Res Treat2013;142:603-9 PMCID:PMC3855533
|
| [7] |
Sales CACC,Scandiuzzi D.Qualidade de vida de mulheres tratadas de câncer de mama: funcionamento social.Rev Bras Cancerol2001;47:263-72
|
| [8] |
Jiang Z,Chen J.Chinese society of clinical oncology (CSCO) breast cancer guidelines 2022.Transl Breast Cancer Res2022;3:13
|
| [9] |
NBCF. Stage 4 (IV) breast cancer. Available from: https://www.nationalbreastcancer.org/breast-cancer-stage-4/#:~:text=Although%20Stage%204%20breast%20cancer,life%20as%20a%20primary%20goal [Last accessed on 22 Dec 2023].
|
| [10] |
Carlson RW,Anderson BO.Invasive breast cancer.J Natl Compr Canc Netw2011;9:136-222
|
| [11] |
Gnerlich J,Jeffe DB,Thompson S.Patient and tumor characteristics associated with primary tumor resection in women with Stage IV breast cancer: analysis of 1988-2003 SEER data.Breast J2008;14:538-42
|
| [12] |
Asaad M,Hoskin TL.Primary tumor resection in patients with stage IV breast cancer: 10-year experience.Breast J2021;27:863-71
|
| [13] |
Shien T.Significance of primary lesion resection in Stage IV breast cancer.Jpn J Clin Oncol2017;47:381-4
|
| [14] |
Marks CE,Fayanju OM.Metastatic breast cancer: who benefits from surgery?.Am J Surg2022;223:81-93 PMCID:PMC8688223
|
| [15] |
Lane WO,Blitzblau RC.Surgical resection of the primary tumor in women with de novo stage IV breast cancer: contemporary practice patterns and survival analysis.Ann Surg2019;269:537-44 PMCID:PMC5994388
|
| [16] |
Hotton J,Leufflen L.Early locoregional breast surgery and survival in de novo metastatic breast cancer in the multicenter national ESME Cohort.Ann Surg2023;277:e153-61
|
| [17] |
Tosello G,Mota BS,Riera R.Breast surgery for metastatic breast cancer.Cochrane Database Syst Rev2018;3:CD011276 PMCID:PMC6494198
|
| [18] |
Arciero C,Gillespie T.Surgery and survival in patients with stage IV breast cancer.Breast J2019;25:644-53 PMCID:PMC6612438
|
| [19] |
Soran A,Ozbas S.A randomized controlled trial evaluating resection of the primary breast tumor in women presenting with de novo stage IV breast cancer: Turkish study (protocol MF07-01).J Clin Oncol2016;34:1005
|
| [20] |
Baum M,Hrushesky W.Does surgery unfavourably perturb the “natural history” of early breast cancer by accelerating the appearance of distant metastases?.Eur J Cancer2005;41:508-15
|
| [21] |
Coffey JC,Smith MJ,Cotter TG.Excisional surgery for cancer cure: therapy at a cost.Lancet Oncol2003;4:760-8
|
| [22] |
Patel F.Non-surgical management of metastatic breast cancer and palliative care. In Sharma SC, Mazumdar A, Kaushik R, editors. Breast cancer: comprehensive management. Singapore: Springer Nature; 2022. pp. 497-517.
|
| [23] |
Zafir-Lavie I,Goltsman H.Successful intracranial delivery of trastuzumab by gene-therapy for treatment of HER2-positive breast cancer brain metastases.J Control Release2018;291:80-9
|
| [24] |
Ye F,Li Y.Advancements in clinical aspects of targeted therapy and immunotherapy in breast cancer.Mol Cancer2023;22:105 PMCID:PMC10324146
|
| [25] |
Fallowfield L,Travado L.Gaps in care and support for patients with advanced breast cancer: a report from the advanced breast cancer global alliance.JCO Glob Oncol2021;7:976-84 PMCID:PMC8457864
|
| [26] |
Page MJ,McKenzie JE.Introduction to preferred reporting items for systematic reviews and meta-analyses 2020 and implications for research synthesis methodologists.Res Synth Methods2022;13:156-63
|
| [27] |
Guyot P,Ouwens MJ.Enhanced secondary analysis of survival data: reconstructing the data from published Kaplan-Meier survival curves.BMC Med Res Methodol2012;12:9 PMCID:PMC3313891
|
| [28] |
Begg CB.Operating characteristics of a rank correlation test for publication bias.Biometrics1994;50:1088-101
|
| [29] |
Badwe R,Nair N.Locoregional treatment versus no treatment of the primary tumour in metastatic breast cancer: an open-label randomised controlled trial.Lancet Oncol2015;16:1380-8
|
| [30] |
Fitzal F,Knauer M.Impact of breast surgery in primary metastasized breast cancer: outcomes of the prospective randomized phase III ABCSG-28 posytive trial.Ann Surg2019;269:1163-9
|
| [31] |
Soran A,Ozbas S.Randomized trial comparing resection of primary tumor with no surgery in stage IV breast cancer at presentation: protocol MF07-01.Ann Surg Oncol2018;25:3141-9
|
| [32] |
Khan SA,Morrow M.Does aggressive local therapy improve survival in metastatic breast cancer?.Surgery2002;132:620-6; discussion 626-7
|
| [33] |
Rapiti E,Vlastos G.Complete excision of primary breast tumor improves survival of patients with metastatic breast cancer at diagnosis.J Clin Oncol2006;24:2743-9
|
| [34] |
Babiera GV,Feng L.Effect of primary tumor extirpation in breast cancer patients who present with stage IV disease and an intact primary tumor.Ann Surg Oncol2006;13:776-82
|
| [35] |
Fields RC,Trinkaus K.Surgical resection of the primary tumor is associated with increased long-term survival in patients with stage IV breast cancer after controlling for site of metastasis.Ann Surg Oncol2007;14:3345-51
|
| [36] |
Blanchard DK,Hilsenbeck SG.Association of surgery with improved survival in stage IV breast cancer patients.Ann Surg2008;247:732-8
|
| [37] |
Cady B,Michaelson JS,Smith BL.Matched pair analyses of stage IV breast cancer with or without resection of primary breast site.Ann Surg Oncol2008;15:3384-95
|
| [38] |
Hazard HW,Scholtens D,Gradishar WJ.Surgical resection of the primary tumor, chest wall control, and survival in women with metastatic breast cancer.Cancer2008;113:2011-9
|
| [39] |
Ahn S,Min J.Impact of primary site surgical resection on survival in stage IV breast Cancer.Cancer Res2010;13:90-5
|
| [40] |
McGuire KP,Rodriguez A,Cox CE.Factors associated with improved outcome after surgery in metastatic breast cancer patients.Am J Surg2009;198:511-5
|
| [41] |
Ruiterkamp J,van de Poll-Franse LV,Tjan-Heijnen VC.Surgical resection of the primary tumour is associated with improved survival in patients with distant metastatic breast cancer at diagnosis.Eur J Surg Oncol2009;35:1146-51
|
| [42] |
Shien T,Shimizu C.Primary tumor resection improves the survival of younger patients with metastatic breast cancer.Oncol Rep2009;21:827-32
|
| [43] |
Leung AM,Nguyen KA,Bear HD.Effects of surgical excision on survival of patients with stage IV breast cancer.J Surg Res2010;161:83-8
|
| [44] |
Neuman HB,Gonen M,Morrow M.Stage IV breast cancer in the era of targeted therapy: does surgery of the primary tumor matter?.Cancer2010;116:1226-33 PMCID:PMC4505547
|
| [45] |
Pathy NB,Taib NA,Yip CH.Impact of breast surgery on survival in women presenting with metastatic breast cancer.Br J Surg2011;98:1566-72
|
| [46] |
Pérez-Fidalgo JA,Caballero A.Removal of primary tumor improves survival in metastatic breast cancer. Does timing of surgery influence outcomes?.Breast2011;20:548-54
|
| [47] |
Rashaan ZM,Portielje JE.Surgery in metastatic breast cancer: patients with a favorable profile seem to have the most benefit from surgery.Eur J Surg Oncol2012;38:52-6
|
| [48] |
Lang JE,Mitchell MP.Primary tumor extirpation in breast cancer patients who present with stage IV disease is associated with improved survival.Ann Surg Oncol2013;20:1893-9 PMCID:PMC4353581
|
| [49] |
Akay CL,Chisholm GB.Primary tumor resection as a component of multimodality treatment may improve local control and survival in patients with stage IV inflammatory breast cancer.Cancer2014;120:1319-28 PMCID:PMC4278570
|
| [50] |
Anula JJ,Machuca Chiriboga P,Dueñas Rodríguez B.Tratamiento quirúrgico del tumor primario en pacientes con cáncer de mama en estadio IV. [Surgical treatment of the primary tumor in stage IV breast cancer].Cir Esp2015;93:375-80
|
| [51] |
Rhu J,Kil WH,Nam SJ.Surgery of primary tumour has survival benefit in metastatic breast cancer with single-organ metastasis, especially bone.ANZ J Surg2015;85:240-4
|
| [52] |
Quinn EM,O’Meara S.Is there a role for locoregional surgery in stage IV breast cancer?.Breast2015;24:32-7
|
| [53] |
Thomas A,Chrischilles EA.Initial surgery and survival in stage IV breast cancer in the United States, 1988-2011.JAMA Surg2016;151:424-31 PMCID:PMC5844269
|
| [54] |
Kolben T,Himsl I.Local resection of primary tumor in upfront stage IV breast cancer.Breast Care2016;11:411-7 PMCID:PMC5290443
|
| [55] |
Xie Y,Luo C.Surgery of the primary tumor improves survival in women with stage IV breast cancer in Southwest China: a retrospective analysis.Medicine2017;96:e7048 PMCID:PMC5459728
|
| [56] |
Muzaffar M,Vohra N.Impact of primary tumor surgery in stage IV male breast cancer.Clin Breast Cancer2017;17:e143-9
|
| [57] |
Yoo TK,Kim SJ.Identifying long-term survivors among metastatic breast cancer patients undergoing primary tumor surgery.Breast Cancer Res Treat2017;165:109-18
|
| [58] |
Barinoff J,Schneeweiss A.Primary metastatic breast cancer in the era of targeted therapy - prognostic impact and the role of breast tumour surgery.Eur J Cancer2017;83:116-24
|
| [59] |
Choi SH,Choi J.Locoregional treatment of the primary tumor in patients with de novo stage IV breast cancer: a radiation oncologist’s perspective.Clin Breast Cancer2018;18:e167-78
|
| [60] |
Desille-Gbaguidi H,Body G.Survival impact of primary site surgery on metastatic breast cancer patients at diagnosis.J Gynecol Obstet Hum Reprod2019;48:171-7
|
| [61] |
Lim SM,Park HS.Effect of primary tumor resection on overall survival in patients with stage IV breast cancer.Breast J2019;25:908-15
|
| [62] |
Lopez-Tarruella S,Pollan M.Survival impact of primary tumor resection in de novo metastatic breast cancer patients (GEICAM/El Alamo Registry).Sci Rep2019;9:20081 PMCID:PMC6934456
|
| [63] |
Wang K,Li ZY.Metastatic pattern discriminates survival benefit of primary surgery for de novo stage IV breast cancer: a real-world observational study.Eur J Surg Oncol2019;45:1364-72
|
| [64] |
Mudgway R,Lin AC,Garberoglio CA.The impact of primary tumor surgery on survival in HER2 positive stage IV breast cancer patients in the current era of targeted therapy.Ann Surg Oncol2020;27:2711-20
|
| [65] |
Si Y,Hu N.Primary tumor surgery for patients with de novo stage IV breast cancer can decrease local symptoms and improve quality of life.Ann Surg Oncol2020;27:1025-33 PMCID:PMC7060161
|
| [66] |
Yao N,Liu T.Primary tumor removal improves the prognosis in patients with stage IV breast cancer: a population-based study (cohort study).Int J Surg2020;83:109-14
|
| [67] |
Bilani N,Liang H,Nahleh Z.Effect of surgery at primary and metastatic sites in patients with stage IV breast cancer.Clin Breast Cancer2021;21:170-80
|
| [68] |
Bilani N,Singh Jabbal I.Survival benefit of a combined surgical approach in patients with metastatic breast cancer.J Surg Oncol2021;124:1235-41
|
| [69] |
Çöpelci Y,Dinç B,Gündüz Ş.Effects of primary tumor resection on metastatic breast cancer survival and the predictive power of neutrophil: lymphocyte ratio on prognosis.Eur J Breast Health2021;17:322-7 PMCID:PMC8496121
|
| [70] |
Huang Z,Qin Q,Wei C.Impact of primary site surgery on survival of patients with de novo stage IV breast cancer.Cancer Manag Res2021;13:319-27 PMCID:PMC7811446
|
| [71] |
Xie N,Tang Y.Impact of surgical management of primary tumors in stage IV breast cancer patients: a retrospective observational study based on SEER database.BMJ Open2022;12:e054135 PMCID:PMC8808454
|
| [72] |
Dominici L,Hughes M.Surgery of the primary tumor does not improve survival in stage IV breast cancer.Breast Cancer Res Treat2011;129:459-65 PMCID:PMC3382105
|
| [73] |
Wang W,Liu J,Zhang P.130P locoregional treatment in de novo stage IV breast cancer: a retrospective study of the Chinese population.Ann Oncol2016;27:ix39
|
| [74] |
Kim MY,Acharyya S.Tumor self-seeding by circulating cancer cells.Cell2009;139:1315-26 PMCID:PMC2810531
|
| [75] |
Petrelli F.Surgery of primary tumors in stage IV breast cancer: an updated meta-analysis of published studies with meta-regression.Med Oncol2012;29:3282-90
|
| [76] |
Harris E,Kell MR.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;20:2828-34
|
| [77] |
Xiao W,Zheng S.Primary tumor resection in stage IV breast cancer: a systematic review and meta-analysis.Eur J Surg Oncol2018;44:1504-12
|
| [78] |
Mohanty SS,Padhy RN.Role of hormone receptors and HER2 as prospective molecular markers for breast cancer: an update.Genes Dis2022;9:648-58 PMCID:PMC9243349
|
| [79] |
Winokur T. Molecular markers in breast cancer: current practice and future possibilities. Springer Science & Business Media. 2007. Available from: https://link.springer.com/chapter/10.1007/0-387-32025-3_5 [Last accessed on 27 Dec 2023].
|
| [80] |
Cianfrocca M.Prognostic and predictive factors in early-stage breast cancer.Oncologist2004;9:606-16
|
| [81] |
Saez RA,Clark GM.Prognostic factors in breast cancer.Semin Surg Oncol1989;5:102-10
|
| [82] |
Ball AB,Fish S.Radical axillary dissection in the staging and treatment of breast cancer.Ann R Coll Surg Engl1992;74:126-9 PMCID:PMC2497538
|