title: Growth fraction as a predictor of response to chemotherapy in node-negative breast cancer.
abstract: Accurate predictive markers of chemotherapeutic response in early breast cancer are still lacking. The role of tumour growth fraction as a predictor of response to chemotherapy was assessed in early breast cancer. In this study, immunohistochemical expression of MIB1 was studied in a well-characterised series of early (Stages I and II) node-negative breast carcinoma cases (n = 100) with long-term follow-up that have received adjuvant chemotherapy (cyclophosphamide/methotrexate/5-fluorouracil regimen). In addition, 728 cases who did not receive adjuvant chemotherapy were used as a control group. Increased tumour growth fraction was associated with a better response to adjuvant chemotherapy in terms of longer breast cancer specific survival and disease-free interval [hazard ratio (HR) = 0.354, 95% CI = 0.177-0.688, p = 0.003 and HR = 0.396, 95% CI = 0.205-0.768, p = 0.006, respectively]. In contrast to the control group, patients with high growth fraction tumour (>70%) showed an excellent outcome with infrequently reported events during the period of follow-up. Importantly, patients with a low growth fraction (< or =10%) showed frequent recurrences and shorter survival time with outcome comparable to those of high growth fraction who did not receive chemotherapy. Therefore, tumour growth fraction can be used to assign patients into distinct groups showing differential response to adjuvant chemotherapy. Patients with a high growth fraction appear to be ideal candidates for adjuvant chemotherapy while those with low growth fraction are less likely to benefit and are prone to the potential serious side effects of adjuvant chemotherapy.
authors.affiliation: Division of Pathology, School of Molecular Medical Sciences, University of Nottingham, Nottingham, United Kingdom.
authors.forename: Mohammed A
authors.initials: MA
authors.lastname: Aleskandarany
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Green
authors.forename: Emad A
authors.initials: EA
authors.lastname: Rakha
authors.forename: Rabab A
authors.initials: RA
authors.lastname: Mohammed
authors.forename: Somaia E
authors.initials: SE
authors.lastname: Elsheikh
authors.forename: Desmond G
authors.initials: DG
authors.lastname: Powe
authors.forename: Emma C
authors.initials: EC
authors.lastname: Paish
authors.forename: R Douglas
authors.initials: RD
authors.lastname: Macmillan
authors.forename: Steve
authors.initials: S
authors.lastname: Chan
authors.forename: Samreen I
authors.initials: SI
authors.lastname: Ahmed
authors.forename: Ian O
authors.initials: IO
authors.lastname: Ellis
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen / Q000378:metabolism*; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D019394:Ki-67 Antigen; D003520:Cyclophosphamide; D005472:Fluorouracil; D008727:Methotrexate