We investigated the prevalence of anaemia (haemoglobin concentration < 12 g/dl) in 336 women with early-stage breast cancer and its association with other known prognostic factors. The median follow-up period was 60.5 months (range 9-123 months). Seventy-nine women (23.5%) had a low pre-treatment haemoglobin concentration, but anaemia was not correlated with age, tumour size, nodal status, histological grade or hormone receptor status. Univariate analysis revealed that disease-free survival and overall survival were shorter in patients with anaemia at the time of diagnosis than in patients with normal haemoglobin concentrations. Anaemia remained a significant prognostic factor for disease-free survival and overall survival in the multivariate analysis (relative risk, 1.884 and 1.785, respectively). These results suggest that pre-treatment haemoglobin concentration is an independent prognostic factor in patients with early-stage breast cancer.
MercadanteSGebbiaVMarrazzoAFilostoS: Anaemia in cancer: Pathophysiology and treatment. Cancer Treat Rev2000; 26: 303–311.
2.
GroopmanJEItriLM: Chemotherapy-induced anaemia in adults: Incidence and treatment. J Natl Cancer Inst1999; 91: 1616–1634.
3.
BronDMeulemanNMascauxC: Biological basis of anaemia. Semin Oncol2001; 28: 1–6.
4.
LudwigH: Epoetin in cancer-related anaemia. Nephrol Dial Transplant1999; 14: 85–92.
5.
LeeWRBerkeyBMarcialVFuKKCooperJSVikramB: Anaemia is associated with decreased survival and increased locoregional failure in patients with locally advanced head and neck carcinoma: A secondary analysis of RTOG 85-27. Int J Radiat Oncol Biol Phys1998; 42: 1069–1075.
6.
WagnerWHermannRHartlappJEsserEChristophBMullerMK: Prognostic value of haemoglobin concentrations in patients with advanced head and neck cancer treated with combined radio-chemotherapy and surgery. Strahlenther Onkol2000; 176: 73–80.
7.
GroganMThomasGMMelamedIWongFLPearceyRGJosephPK: The importance of haemoglobin levels during radiotherapy for carcinoma of the cervix. Cancer1999; 86: 1528–1536.
8.
CaroJJSalasMWardAGossG: Anaemia as an independent prognostic factor for survival in patients with cancer: A systemic, quantitative review. Cancer2001; 91: 2214–2221.
9.
KirshnerJHatchMHennessyDDFridmanMTannousRE: Anaemia in stage II and III breast cancer patients treated with adjuvant doxorubicin and cyclophosphamide chemotherapy. Oncologist2004; 1: 25–32.
10.
HenkeMSindlingerFIkenbergHGerdsTSchumacherM: Blood haemoglobin level and treatment outcome of early breast cancer. Strahlenther Onkol2004; 180: 45–51.
11.
HockelMSchlengerKAralBMitzeMSchafferUVaupelP: Association between tumour hypoxia and malignant progression in advanced cancer of the uterine cervix. Cancer Res1996; 56: 4509–4515.
12.
VaupelPThewsOKelleherDKHoeckelM: Oxygenation of human tumours: The Mainz experience. Strahlenther Onkol1998; 174: 6–12.
13.
HockelMVaupelP: Biological consequences of tumour hypoxia. Semin Oncol2001; 28: 36–41.
14.
ReynoldsTYRockwellSGlazerPM: Genetic instability induced by the tumour microenvironment. Cancer Res1996; 56: 5754–5757.
15.
ReiherFKIvanovichMHuangHSmithNDBouckNPCampbellSC: The role of hypoxia and p53 in the regulation of angiogenesis in bladder cancer. J Urol2001; 165: 2075–2081.
16.
YoungSDMarshallRSHillRP: Hypoxia induces DNA overreplication and enhances metastatic potential of murine tumour cells. Proc Natl Acad Sci U S A1988; 85: 9533–9537.
17.
BottiniABerrutiABrizziMPBersigaAGeneraliDAlleviG: Pretreatment haemoglobin levels significantly predict the tumour response to primary chemotherapy in human breast cancer. Br J Cancer2003; 89: 977–982.
18.
HockelMSchlengerKHockelS: Association between tumour hypoxia and malignant progression: The clinical evidence in cancer of the uterine cervix. In: Tumour Hypoxia (VaupelPKelleherDK, eds). Stuttgart: Wissenschaftliche Verlagsgesellschaft1999; pp 65–74.
19.
VaupelPMayerABriestSHockelM: Oxygenation gain factor: A novel parameter characterizing the association between haemoglobin level and the oxygenation status of breast cancers. Cancer Res2003; 63: 7634–7637.
20.
RiceGCHoyCSchimkeRT: Transient hypoxia enhances the frequency of dihydrofolate reductase gene amplification in Chinese hamster ovary cells. Proc Natl Acad Sci U S A1986; 83: 5978–5982.
21.
RussoCAWeberTKVolpeCMStolerDLPetrelliNJRodriguez-BigasM: An anoxia inducible endonuclease and enhanced DNA breakage as contributors to genomic instability in cancer. Cancer Res1995; 55: 1122–1128.
22.
HockelMSchlengerKHockelSVaupelP: Hypoxic cervical cancers with low apoptotic index are highly aggressive. Cancer Res1999; 59: 4525–4528.
23.
ShweikiDItinASofferDKeshetE: Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis. Nature1992; 359: 843–845.
24.
WilsonREKengPCSutherlandRM: Drug resistance in Chinese hamster ovary cells during recovery from severe hypoxia. J Natl Cancer Inst1989; 81: 1235–1240.
25.
MatternJKallinowskiFHerfarthCVolmM: Association of resistance-related protein expression with poor vascularization and low levels of oxygen in human rectal cancer. Int J Cancer1996; 67: 20–23.
26.
HartmannAKunzMKostlinSGillitzerRToksoyABrockerEB: Hypoxia-induced upregulation of angiogenin in human malignant melanoma. Cancer Res1999; 59: 1578–1583.
27.
GrahamCHForsdikeJFitzgeraldCJMacdonald-GoodfellowS: Hypoxia-mediated stimulation of carcinoma cell invasiveness via upregulation of urokinase receptor expression. Int J Cancer1999; 80: 617–623.
28.
DunstJPigorschSHansgenGHintnerILautenschlagerCBeckerA: Low haemoglobin is associated with increased serum levels of vascular endothelial growth factor (VEGF) in cancer patients. Does anaemia stimulate angiogenesis?Strahlenther Onkol1999; 175: 93–96.
29.
GraeberTGOsmanianCJacksTHousmanDEKochCJLoweSW: Hypoxia-mediated selection of cells with diminished apoptotic potential in solid tumours. Nature1996; 379: 88–91.
30.
GatenbyRAKesslerHBRosenblumJSLoiaLRMoldofskyPJHartzWH: Oxygen distribution in squamous cell carcinoma metastases and its relationship to outcome of radiation therapy. Int J Radiat Oncol Biol Phys1988; 14: 831–838.
31.
HasanNMAdamsGEJoinerMCMarshallJFHartIR: Hypoxia facilitates tumour cell detachment by reducing expression of surface adhesion molecules and adhesion to extracellular matrices without loss of cell viability. Br J Cancer1998; 77: 1799–1805.
32.
HallEJ: 1The oxygen effect and reoxygenation. In: Radiobiology for the radiologist, 4th edn (HallE, ed). Philadelphia, PA: Lippincott, Williams & Wilkins1994; pp 133–152.
33.
SchrijversDHighleyMDe BruynEVan OosteromATVermorkenJB: Role of red blood cells in pharmacokinetics of chemotherapeutic agents. Anticancer Drugs1999; 10: 147–153.
