There is growing evidence of a survival benefit for metastatic breast cancer patients receiving surgery of the primary tumor. We investigated whether or not adjuvant radiotherapy can improve survival.
Methods
Women diagnosed between 1988 and 2003 with metastatic, histologically confirmed unilateral primary breast cancer were selected from the SEER Program. Overall survival and specific survival were computed by the Kaplan-Meier method. Treatment hazard ratios of breast-conserving surgery or mastectomy versus no surgery, and radiotherapy versus none, were computed by Cox regression adjusting for period of diagnosis, age, marital status, race, histology, grade, and hormone receptors.
Results
Of 8761 women, radiotherapy was given to 1473 of 3905 who did not undergo surgery, to 882 of 2070 who underwent breast-conserving surgery, and to 1103 of 2786 mastectomy patients. Median overall survival was: for no surgery, 14 months; for breast-conserving surgery, 23 months; and for mastectomy, 28 months (P <0.0001). The median overall survival of radiotherapy versus none was respectively 16 vs 13 months without surgery (P = 0.0003), 28 vs 20 months for breast-conserving surgery patients (P <0.0001), and 28 vs 28 months among mastectomy patients (P = 0.895). Multivariate analysis showed relative mortality reductions of 28% by breast-conserving surgery, 42% by mastectomy, and 10% by radiotherapy. Specific survival showed comparable results.
Conclusions
Surgery and radiotherapy were associated with a significant survival advantage. We argue that local therapy should be considered even in metastatic disease. Free full text available at www.tumorionline.it
JemalA., SiegelR., WardE., HaoY., XuJ., MurrayT., ThunM.J.: Cancer statistics, 2008. CA Cancer J Clin, 58: 71–96, 2008.
2.
RiesL.A.G., MelbertD., KrapchoM., StinchcombD.G., HowladerN., HornerM.J., MariottoA., MillerB.A., FeuerE.J., AltekruseS.F., LewisD.R., EisnerM.P., ReichmanM., EdwardsB.K.: SEER Cancer Statistics Review, 1975–2005.National Cancer Institute, Bethesda, MD, 2008. Availableathttp://seer.cancer.gov/csr/-1975_2005/ (accessed 16 May 2009).
3.
KhanS.A., StewartA.K., MorrowM.: Does aggressive local therapy improve survival in metastatic breast cancer?Surgery, 132: 620–626, 2002.
4.
RapitiE., VerkooijenH.M., VlastosG., FiorettaG., Neyroud-CasparI., SappinoA.P., ChappuisP.O., BouchardyC.: Complete excision of primary breast tumor improves survival of patients with metastatic breast cancer at diagnosis. J Clin Oncol, 24: 2743–2749, 2006.
5.
BabieraG.V., RaoR., FengL., Meric-BernstamF., KuererH.M., SingletaryS.E., HuntK.K., RossM.I., GwynK.M., FeigB.W., AmesF.C., HortobagyiG.N.: Effect of primary tumor extirpation in breast cancer patients who present with stage IV disease and an intact primary tumor. Ann Surg Oncol, 13: 776–782, 2006.
6.
GnerlichJ., JeffeD.B., DeshpandeA.D., BeersC., ZanderC., MargenthalerJ.A.: Surgical removal of the primary tumor increases overall survival in patients with metastatic breast cancer: analysis of the 1988–2003 SEER data. Ann Surg Oncol, 14: 2187–2194, 2007.
7.
BlanchardD.K., ShettyP.B., HilsenbeckS.G., ElledgeR.M.: Association of surgery with improved survival in stage IV breast cancer patients. Ann Surg, 247: 732–738, 2008.
8.
FieldsR.C., JeffeD.B., TrinkausK., ZhangQ., ArthurC., AftR., DietzJ.R., EberleinT.J., GillandersW.E., MargenthalerJ.A.: 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 Oncol, 14: 3345–3351, 2007.
9.
MorroghM., ParkA., NortonL., KingT.A.: Changing indications for surgery in patients with stage IV breast cancer: a current perspective. Cancer, 112: 1445–1454, 2008.
10.
Le ScodanR., StevensD., BrainE., FloirasJ.L., Cohen-SolalC., De LaL.B., Tubiana-HulinM., YacoubS., GutierrezM., AliD., GardnerM., MoissonP., VilletteS., LereboursF., MunckJ.N., LabibA.: Breast cancer with synchronous metastases: survival impact of exclusive locoregional radiotherapy. J Clin Oncol, 27: 1375–1381, 2009.
11.
National Cancer Institute.Surveillance, Epidemiology, and End Results (SEER) Program (www.seer.cancer.gov) Public-Use Data (1973–2003), National Cancer Institute, DCCPS, Surveillance Research Program, Cancer Statistics Branch, released April 2006, based on the November 2005 submission. Available at http://seer.cancer.gov (accessed 28 May 2006).
12.
KaplanE., MeierP.: Nonparametric estimation from incomplete observations. J Am Stat Assoc, 53: 457–481, 1958.
13.
PetoR., PikeM.C., ArmitageP., BreslowN.E., CoxD.R., HowardS.V., MantelN., McPhersonK., PetoJ., SmithP.G.: Design and analysis of randomized clinical trials requiring prolonged observation of each patient. II. analysis and examples. Br J Cancer, 35: 1–39, 1977.
14.
TherneauT.M., GrambschP.M.: Modeling survival data: extending the Cox model.Springer-Verlag, New York, 2000.
15.
VenablesW.N., RipleyB.D.: modern applied statistics with S. Fourth Edition.Springer-Verlag, New York, 2002.
16.
Vinh-HungV., TruongP.T., JanniW., NguyenN.P., VlastosG., CserniG., RoyceM.E., WoodwardW.A., PromishD., TaiP., SoeteG., Balmer-MajnoS., CutuliB., StormeG., BouchardyC.: The effect of adjuvant radiotherapy on mortality differs according to primary tumor location in women with node-positive breast cancer. Strahlenther Onkol, 185: 161–168, 2009.
17.
HortobagyiG.N.: Treatment of breast cancer. N Engl J Med, 339: 974–984, 1998.
18.
Bernard-MartyC., CardosoF., PiccartM.J.: Facts and controversies in systemic treatment of metastatic breast cancer. Oncologist, 9: 617–632, 2004.
19.
HortobagyiG.N.: Multidisciplinary management of advanced primary and metastatic breast cancer. Cancer, 74: 416–423, 1994.
20.
CarmichaelA.R., AndersonE.D., ChettyU., DixonJ.M.: Does local surgery have a role in the management of stage IV breast cancer?Eur J Surg Oncol, 29: 17–19, 2003.
21.
GennariR., AudisioR.A.: Surgical removal of the breast primary for patients presenting with metastases - Where to go?Cancer Treat Rev, 35: 391–396, 2009.
22.
RuiterkampJ., ErnstM.F., van de Poll-FranseL.V., BosschaK., Tjan-HeijnenV.C., VoogdA.C.: Surgical resection of the primary tumour is associated with improved survival in patients with distant metastatic breast cancer at diagnosis. Eur J Surg Oncol, 35: 1146–1151, 2009.
23.
CadyB., NathanN.R., MichaelsonJ.S., GolshanM., SmithB.L.: Matched pair analyses of stage IV breast cancer with or without resection of primary breast site. Ann Surg Oncol, 15: 3384–3395, 2008.
24.
HazardH.W., GorlaS.R., ScholtensD., KielK., GradisharW.J., KhanS.A.: Surgical resection of the primary tumor, chest wall control, and survival in women with metastatic breast cancer. Cancer, 113: 2011–2019, 2008.
25.
LeungA.M., VuH.N., NguyenK.A., ThackerL.R., BearH.D.: Effects of surgical excision on survival of patients with stage IV breast cancer. J Surg Res, [Epub ahead of print], 2009.
26.
NeumanH.B., MorroghM., GonenM., Van ZeeK.J., MorrowM., KingT.A.: Do patients with stage IV breast cancer and intact primary benefit from local control of the breast as a component of multimodality therapy? Abstract 206. Breast Cancer Symposium, September 5–7, 2008. Available at http://www.asco.org/ (accessed 30 September 2008).
27.
RaoR., FengL., KuererH.M., SingletaryS.E., BedrosianI., HuntK.K., RossM.I., HortobagyiG.N., FeigB.W., AmesF.C., BabieraG.V.: Timing of surgical intervention for the intact primary in stage IV breast cancer patients. Ann Surg Oncol, 15: 1696–1702, 2008.
28.
BaffordA.C., BursteinH.J., BarkleyC.R., SmithB.L., LipsitzS., IglehartJ.D., WinerE.P., GolshanM.: Breast surgery in stage IV breast cancer: impact of staging and patient selection on overall survival. Breast Cancer Res Treat, 115: 7–12, 2009.
29.
ShienT., KinoshitaT., ShimizuC., HojoT., TairaN., DoiharaH., Kashi-TanakaS.: Primary tumor resection improves the survival of younger patients with metastatic breast cancer. Oncol Rep, 21: 827–832, 2009.
30.
MorrowM., GoldsteinL.: Surgery of the primary tumor in metastatic breast cancer: closing the barn door after the horse has bolted?J Clin Oncol, 24: 2694–2696, 2006.
31.
FisherB.: Laboratory and clinical research in breast cancer – a personal adventure: the David A. Karnofsky memorial lecture. Cancer Res, 40: 3863–3874, 1980.
32.
VerschraegenC., Vinh-HungV., CserniG., GordonR., RoyceM.E., VlastosG., TaiP., StormeG.: Modeling the effect of tumor size in early breast cancer. Ann Surg, 241: 309–318, 2005.
33.
VerschraegenC., Vinh-HungV.: Effects of radiotherapy and surgery for early breast cancer. Lancet, 367: 1654–1655, 2006.
34.
KyndiM., OvergaardM., NielsenH.M., SorensenF.B., KnudsenH., OvergaardJ.: High local recurrence risk is not associated with large survival reduction after postmastectomy radiotherapy in high-risk breast cancer: a subgroup analysis of DBCG 82 b&c. Radiother Oncol, 90: 74–79, 2009.
35.
Vinh-HungV., VerschraegenC., PromishD.I., CserniG., Van de SteeneJ., TaiP., VlastosG., VoordeckersM., StormeG., RoyceM.: Ratios of involved nodes in early breast cancer. Breast Cancer Res, 6: R680–R688, 2004.
36.
AsireA., LylesB., CiceroB.J., PercyC., CunninghamJ., RiesL., HormJ., ShambaughE., KruseM.A., Van HoltenV., YoungJ.: The SEER program code manual.National Cancer Institute, 1988. Available at http://seer.cancer.gov/manuals/historic/codeman_1988.pdf (accessed 18 September 2007).
37.
GradisharW.J., BellonJ.R., GaddM.A., D'AlessandroH.A., BraatenK.: Case records of the Massachusetts General Hospital. Case 30–2008. A 47-year-old woman with a mass in the breast and a solitary lesion in the spine. N Engl J Med, 359: 1382–1391, 2008.
38.
Vinh-HungV., VerschraegenC., The Breast Conserving Surgery Project: Breast-conserving surgery with or without radiotherapy: pooled-analysis for risks of ipsilateral breast tumor recurrence and mortality. J Natl Cancer Inst, 96: 115–121, 2004.
39.
Early Breast Cancer Trialists’ Collaborative Group (EBCTCG): 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, 366: 2087–2106, 2005.
40.
SoranA., OzbasS., KelseyS.F., GulluogluB.M.: Randomized trial comparing locoregional resection of primary tumor with no surgery in stage IV breast cancer at the presentation (Protocol MF07–01): A study of Turkish Federation of the National Societies for Breast Diseases. Breast J, 15: 399–403, 2009.
41.
BadweR.A., HawaldarR.W., KhareA., NadkarniM., JalaliR., ParmarV.: Role of local-regional treatment in metastatic breast cancer at presentation: A randomized trial. Abstract 250. Breast Cancer Symposium, September 5–7, 2008. Available at http://www.asco.org/ (accessed 30 September 2008).
