Summary
There remains a number of unmet clinical needs in patients with breast cancer that research and development aims to address. More sensitive and specific indicators of prognosis are required to identify those patients at greatest risk for disease progression. A number of biological markers including the cyclins, circulating epithelial cells, and components of the urokinase plasminogen system have been shown to correlate with patient outcome. Genomic analysis also has the potential to predict patient response to specific agents, thus ensuring patients derive the maximum benefit from the treatment they receive. Patients who require treatment are often exposed to the undesirable toxic effects that are associated with some treatments. Liposomal and nanoparticle formulations of currently available agents have been shown to be at least as effective as their parent compounds but with improved safety and tolerability profiles. Studies into patient quality of life during therapy have highlighted the importance of early administration of an erythropoietic agent to treat chemotherapy-induced anemia. Further research in breast cancer should further optimize the treatment patients receive ensuring that patients not only live longer but also have quality survival.
Similar content being viewed by others
References
American Cancer Society: Breast Cancer Facts & Figures 2003–2004. 1–25, 2003
R Peto J Boreham M Clarke C Davies V Beral (2000) ArticleTitleUK and USA breast cancer deaths down 25% in year 2000 at ages 20–69 years Lancet 355 1822
InstitutionalAuthorNameEarly Breast Cancer Trialists’ Collaborative Group (1998) ArticleTitlePolychemotherapy for early breast cancer: an overview of the randomised trials Lancet 352 930–942
L Pusztai M Ayers J Stec GN Hortobágyi (2003) ArticleTitleClinical application of cDNA microarrays in oncology Oncologist 8 252–258
K Keyomarsi SL Tucker TA Buchholz M Callister Y Ding GN Hortobagyi I Bedrosian C Knickerbocker W Toyofuku M Lowe TW Herliczek SS Bacus (2002) ArticleTitleCyclin E and survival in patients with breast cancer N Engl J Med 347 1566–1575
JS Michaelson M Silverstein J Wyatt G Weber R Moore E Halpern DB Kopans K Hughes (2002) ArticleTitlePredicting the survival of patients with breast carcinoma using tumor size Cancer 95 713–723
JS Michaelson M Silverstein D Sgroi JA Cheongsiatmoy A Taghian S Powell K Hughes A Comegno KK Tanabe B Smith (2003) ArticleTitleThe effect of tumor size and lymph node status on breast carcinoma lethality Cancer 98 2133–2143
InstitutionalAuthorNameEarly Breast Cancer Trialists’ Collaborative Group (1998) ArticleTitleTamoxifen for early breast cancer: an overview of the randomised trials Lancet 351 1451–1467
RC Bast SuffixJr. P Ravdin DF Hayes S Bates H Fritsche SuffixJr. JM Jessup N Kemeny GY Locker RG Mennel MR Somerfield (2001) ArticleTitle2000 update of recommendations for the use of tumor markers in breast and colorectal cancer: clinical practice guidelines of the American Society of Clinical Oncology J Clin Oncol 19 1865–1878
JS Ross JA Fletcher GP Linette J Stec E Clark M Ayers WF Symmans L Pusztai KJ Bloom (2003) ArticleTitleThe Her-2/neu gene and protein in breast cancer 2003: biomarker and target of therapy Oncologist 8 307–325 Occurrence Handle10.1634/theoncologist.8-4-307 Occurrence Handle1:CAS:528:DC%2BD3sXmvFSqt74%3D Occurrence Handle12897328
DJ Slamon B Leyland-Jones S Shak H Fuchs V Paton A Bajamonde T Fleming W Eiermann J Wolter M Pegram J Baselga L Norton (2001) ArticleTitleUse of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2 N Engl J Med 344 783–792 Occurrence Handle10.1056/NEJM200103153441101 Occurrence Handle1:CAS:528:DC%2BD3MXisVGktrc%3D Occurrence Handle11248153
T Fehm A Sagalowsky E Clifford P Beitsch H Saboorian D Euhus S Meng L Morrison T Tucker N Lane BM Ghadimi K Heselmeyer-Haddad T Ried C Rao J Uhr (2002) ArticleTitleCytogenetic evidence that circulating epithelial cells in patients with carcinoma are malignant Clin Cancer Res 8 2073–2084
E Racila D Euhus AJ Weiss C Rao J McConnell LWMM Terstappen JW Uhr (1998) ArticleTitleDetection and characterization of carcinoma␣cells in the blood Proc Natl Acad Sci USA 95 4589–4594
DF Hayes TM Walker B Singh ES Vitetta JW Uhr S Gross C Rao GV Doyle LWMM Terstappen (2002) ArticleTitleMonitoring the expression of HER-2 on circulating epithelial cells in patients with advanced breast cancer Int J Oncol 21 1111–1117
Hayes DF, Cristofanilli M, Budd GT, Ellis M, Stopeck A, Matera J, Miller MC, Doyle GV, Allard WJ, Terstappen LW: Monitoring circulating tumor cell (CTC) levels to predict rapid progression in metastatic breast cancer (MBC): a prospective, multi-institutional trial. In: 40th Annual Meeting of the American Society of Clinical Oncology, New Orleans, LO, USA June 5–8, 2004 (abstract 509)
RL Sutherland EA Musgrove (2002) ArticleTitleCyclin E and prognosis in patients with breast cancer N Engl J Med 347 1546–1547
T Lindahl G Landberg J Ahlgren H Nordgren T Norberg S Klaar L Holmberg J Bergh (2004) ArticleTitleOverexpression of cyclin E protein is associated with specific mutation types in the p53 gene and poor survival in human breast cancer Carcinogenesis 25 375–380
K Keyomarsi SL Tucker I Bedrosian (2003) ArticleTitleCyclin E is a more powerful predictor of breast cancer outcome than proliferation Nature Med 9 152
P Rudolph H Kühling P Alm M Fernö B Baldetorp H Olsson R Parwaresch (2003) ArticleTitleDifferential prognostic impact of the cyclins E and B in premenopausal and postmenopausal women with lymph node-negative breast cancer Int J Oncol 105 674–680
H Kühling P Alm H Olsson M Fernö B Baldetorp R Parwaresch P Rudolph (2003) ArticleTitleExpression of cyclins E, A, and B, and prognosis in lymph node-negative breast cancer J Pathol 199 424–431
MJ Duffy (2002) ArticleTitleUrokinase plasminogen activator and its inhibitor, PAI-1, as prognostic markers in breast cancer: from pilot to level 1 evidence studies Clin Chem 48 1194–1197
MP Look WL van Putten MJ Duffy N Harbeck IJ Christensen C Thomssen R Kates F Spyratos M Ferno S Eppenberger-Castori CG Sweep K Ulm JP Peyrat PM Martin H Magdelenat N Brunner C Duggan BW Lisboa PO Bendahl V Quillien A Daver G Ricolleau ME Meijer-van Gelder P Manders WE Fiets MA Blankenstein P Broet S Romain G Daxenbichler G Windbichler T Cufer S Borstnar W Kueng LV Beex JG Klijn N O’Higgins U Eppenberger F Janicke M Schmitt JA Foekens (2002) ArticleTitlePooled analysis of prognostic impact of urokinase-type plasminogen activator and its inhibitor PAI-1 in 8377 breast cancer patients J Natl Cancer Inst 94 116–128
Harbeck N, Kates R, Look MP, Foekens JA: Pooled analysis (n = 8,377) evaluates predictive impact of uPA and PAI-1 for response to adjuvant therapy in breast cancer. In: 40th Annual Meeting of the American Society of Clinical Oncology, New Orleans, LO, USA, June 5–8, 2004 (abstract 523)
JA Foekens HA Peters MP Look H Portengen M Schmitt MD Kramer N Brünner F Jänicke ME Meijer-van Gelder SC Henzen-Logmans WL van Putten JG Klijn (2000) ArticleTitleThe urokinase system of plasminogen activation and prognosis in 2780 breast cancer patients Cancer Res 60 636–643
LJ van’t Veer H Dai MJ van de Vijver YD He AA Hart M Mao HL Peterse K van der Kooy MJ Marton AT Witteveen GJ Schreiber RM Kerkhoven C Roberts PS Linsley R Bernards SH Friend (2002) ArticleTitleGene expression profiling predicts clinical outcome of breast cancer Nature 415 530–536 Occurrence Handle10.1038/415530a Occurrence Handle11823860
Y Wang Y Zhang A Sieuwerts F Yang D Talantov J Yu T Jatkoe E Berns J Klin D Atkins J Foekens (2003) ArticleTitleGene expression profiles and molecular markers to predict distant metastasis of early stage␣breast cancer Breast Cancer Res Treat. 82 IssueIDSuppl 1 S120
L Pusztai M Ayers FW Simmans A Damokosh K Hess V Valero E Clark JS Ross GN Hortobagyi J Stec (2003) ArticleTitleEmerging science: prospective validation of gene expression profiling-based prediction of complete pathologic response to neoadjuvant paclitaxel/FAC chemotherapy in breast cancer Proc Am Soc Clin Oncol 22 1
JC Chang EC Wooten A Tsimelzon SG Hilsenbeck MC Gutierrez R Elledge S Mohsin CK Osborne GC Chamness DC Allred P O’Connell (2003) ArticleTitleGene expression profiling for the prediction of therapeutic response to docetaxel in patients with breast cancer Lancet 362 362–369
F Cardoso (2003) ArticleTitleMicroarray technology and its effect on breast cancer (re)classification and prediction of outcome Breast Cancer Res 5 303–304
Paik S, Shak S, Tang G, Kim C, Baker J, Cronin M, Baehner R, Walker M, Watson D, Park T, Bryant J, Wolmark N: Multi-gene RT-PCR assay for predicting recurrence in node negative breast cancer patients – NSABP studies B-20 and B-14. In: 26th Annual San Antonio Breast Cancer Symposium, San Antonio, TX, USA, December 3–6, 2003 (abstract 16)
Esteva FJ, Sahin AA, Coombes K, Baker J, Cronin M, Walker M, Watson D, Cristofanilli M, Shak S, Hortobagyi GN: Multi-gene RT-PCR assay for predicting recurrence in node negative breast cancer patients - M. D. Anderson Clinical Validation Study. In: 26th Annual San Antonio Breast Cancer Symposium, San Antonio, TX, USA, December 3–6, 2003 (abstract 17)
JR Less MC Posner Y Boucher D Borochovitz N Wolmark RK Jain (1992) ArticleTitleInterstitial hypertension in human breast and colorectal tumors Cancer Res 52 6371–6374
SD Nathanson L Nelson (1994) ArticleTitleInterstitial fluid pressure in breast cancer, benign breast conditions, and breast parenchyma Ann Surg Oncol 1 333–338
NK Ibrahim N Desai S Legha P Soon-Shiong RL Theriault E Rivera B Esmaeli SE Ring A Bedikian GN Hortobagyi JA Ellerhorst (2002) ArticleTitlePhase I and pharmacokinetic study of ABI-007, a cremophor-free, protein-stabilized, nanoparticle formulation of paclitaxel Clin Cancer Res 8 1038–1044 Occurrence Handle1:CAS:528:DC%2BD38XksVSqurg%3D Occurrence Handle12006516
N Desai Z Yao V Trieu P Soon-Shiong D Dykes P Noker (2003) ArticleTitleEvidence of greater tumor and red cell partitioning and superior antitumor activity of cremophor free nanoparticle paclitaxel (ABI-007) compared to taxol Proc Am Soc Clin Oncol 22 156
Desai N, Yao Z, Soon-Shiong P, Dykes D, Noker P: Evidence of a novel transporter mechanism for a Cremaphor-free, protein-engineered Paclitaxel (ABI-007) and enhanced in vivo antitumor activity in an MX-1 human breast tumor xenograft model. In: 25th Annual San Antonio Breast Cancer Symposium, San Antonio, TX, USA, December 11–14, 2002 (poster 524)
O’Shaughnessy J, Tjulandin S, Davidson N, Shaw H, Desai N, Hawkins MJ, Gradishar WJ: ABI-007 (ABRAXANETM), a nanoparticle albumin-bound (nab) paclitaxel demonstrates superior efficacy vs. taxol in MBC: a phase III trial. In: 26th Annual San Antonio Breast Cancer Symposium, San Antonio, TX, USA, December 3–6, 2003 (abstract 44)
T Safra (2003) ArticleTitleCardiac safety of liposomal anthracyclines Oncologist 8 IssueIDSuppl 2 17–24
M Theodoulou C Hudis (2004) ArticleTitleCardiac profiles of liposomal anthracyclines: greater cardiac safety versus conventional doxorubicin? Cancer 100 2052–2063
E Rivera (2003) ArticleTitleLiposomal anthracyclines in metastatic breast cancer: clinical update Oncologist 8 IssueIDSuppl 2 3–9
L Harris G Batist R Belt D Rovira R Navari N Azarnia L Welles E Winer (2002) ArticleTitleLiposome-encapsulated doxorubicin compared with conventional doxorubicin in a randomized multicenter trial as first-line therapy of metastatic breast carcinoma Cancer 94 25–36 Occurrence Handle10.1002/cncr.10201 Occurrence Handle1:CAS:528:DC%2BD38XlslKgsw%3D%3D Occurrence Handle11815957
G Batist G Ramakrishnan CS Rao A Chandrasekharan J Gutheil T Guthrie P Shah A Khojasteh MK Nair K Hoelzer K Tkaczuk YC Park LW Lee (2001) ArticleTitleReduced cardiotoxicity and preserved antitumor efficacy of liposome-encapsulated doxorubicin and cyclophosphamide compared with conventional doxorubicin and cyclophosphamide in a randomized, multicenter trial of metastatic breast cancer J Clin Oncol 19 1444–1454 Occurrence Handle1:CAS:528:DC%2BD3MXit1ertLg%3D Occurrence Handle11230490
Trigo J, Climent MA, Lluch A, Gascon P, Hornedo J, Gil M, Cirera L, Guillem V, Regueiro P, Baselga J: Liposomal doxorubicin Myocet® in combination with Herceptin® and paclitaxel is active and well tolerated in patients with HER2-positive locally advanced or metastatic breast cancer: a phase II study. In: 26th Annual San Antonio Breast Cancer Symposium, San Antonio, TX, USA, December 3–6, 2003 (abstract 351)
M O’Brien N Wigler M Inbar R Rosso E Grischke A Santoro R Catane DG Kieback P Tomczak SP Ackland F Orlandi L Mellars L Alland C Tendler (2004) ArticleTitleReduced cardiotoxicity and comparable efficacy in a phase 3 trial of pegylated liposomal doxorubicin HCl (CAELYXTM/Doxil®) versus conventional doxorubicin for first-line treatment of metastatic breast cancer Ann Oncol 15 440–449
AM Keller RG Mennel VA Georgoulias J-M Nabholtz A Erazo A Lluch CL Vogel M Kaufmann G von Minckwitz IC Henderson L Mellars L Alland C Tendler (2004) ArticleTitleRandomized phase III trial of pegylated liposomal doxorubicin versus vinorelbine or mitomycin C plus vinblastine in women with taxane-refractory advanced breast cancer J Clin Oncol 22 3893–3901
Fulfaro F, Valerio MR, Badalamenti G, Arcara C, Cicero G, Intrivici C, Crosta A, Sciortino C, Russo A, Gebbia N: Weekly paclitaxel (T) and pegylated liposomal doxorubicin (PLD) as first line treatment in metastatic breast cancer (MBC) patients. J Clin Oncol 22(14S): 2004 (abstract 704)
Guastalla JP, Hardy-Bessard AC, Geay JF, Cure H, Ray-Coquard I, Paraiso D, Pujade-Lauraine E: Phase I study of pegylated liposomal doxorubicin (CA) and docetaxel (T) bimonthly in the first-line treatment of metastatic breast cancer (MBC): the CAT regimen. J Clin Oncol 22(14S): 2004 (abstract 818)
A Alexopoulos MV Karamouzis H Stavrinides A Ardavanis K Kandilis J Stavrakakis C Georganta G Rigatos (2004) ArticleTitlePhase II study of pegylated liposomal doxorubicin (Caelyx®) and docetaxel as first-line treatment in metastatic breast cancer Ann Oncol 15 891–895
Fabi A, Papaldo P, Ciccarese M, Salesi N, Lorusso V, Ferretti G, Carlini P, Sacchi I, Cecere F, Cognetti F: Pegylated liposomal doxorubicin (PLD) and gemcitabine (G) in metastatic breast cancer (MBC) patients: a phase II study. J Clin Oncol 22(14S): 2004 (abstract 813)
Chia SK, Clemons M, Martin L-A, Rodgers A, Gelmon K, Pond GR, Panasci L: A multi-centre phase II trial of pegylated liposomal doxorubicin and trastuzumab in HER-2 over-expressing metastatic breast cancer. J Clin Oncol 22(14S): 2004 (abstract 630)
AC Wolff M Bonetti JA Sparano M Wang NE Davidson (2003) ArticleTitleCardiac safety of trastuzumab (H) in combination with pegylated liposomal doxorubicin (D) and docetaxel (T) in HER2-positive metastatic breast cancer (MBC): preliminary results of the Eastern Cooperative Oncology Group trial E3198 Proc Am Soc Clin Oncol 22 18
GP Amorino H Lee GE Holburn CB Paschal SK Hercules Y Shyr RP Steffen H Choy (2001) ArticleTitleEnhancement of tumor oxygenation and radiation response by the allosteric effector of hemoglobin, RSR13 Radiat Res 156 294–300
Suh J, Stea BD, Kresl JJ, Nabid A, Fortin A, Mercier J, Pinter T, Monnier A, Henke M, Holz JB, Boyd A, Craig M, Cagnoni PJ, Shaw E: Results from a subgroup analysis of patients with metastatic breast cancer (MBC) in a phase 3, randomized, open-label, comparative study of standard whole brain radiation therapy (WBRT) with supplemental oxygen, with or without RSR13, in patients with brain metastases. In: 26th Annual San Antonio Breast Cancer Symposium, San Antonio, TX, USA, December 3–6, 2003 (abstract 175)
L Del Mastro M Venturini (1998) ArticleTitleStrategies for the use of epoetin alfa in breast cancer patients Oncologist 3 314–318
J Chang F Couture (2003) ArticleTitleOnce weekly epoetin alfa maintains hemoglobin, improves quality of life and reduces transfusion in breast cancer patients receiving chemotherapy Proc Am Soc Clin Oncol 22 727
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Gradishar, W.J. The future of breast cancer: the role of prognostic factors. Breast Cancer Res Treat 89 (Suppl 1), S17–S26 (2005). https://doi.org/10.1007/s10549-005-0144-y
Issue Date:
DOI: https://doi.org/10.1007/s10549-005-0144-y