title: Relation between chemotherapy dose, oestrogen receptor expression, and body-mass index.
abstract: Clinicians often reduce chemotherapy doses when treating obese patients because of concerns about overdosing. We assessed dose-response according to body-mass index (BMI) and oestrogen receptor (ER) expression of the primary tumour in premenopausal patients with node-positive breast cancer treated with classical CMF (cyclophosphamide, methotrexate, and 5-fluorouracil). Obese patients were significantly more likely to receive a lower chemotherapy dose (<85% of expected dose) for the first course than were those with normal or intermediate BMI (39%vs 16%, p<0.0001). For obese patients and for the total population, reducing the dose of chemotherapy was associated with a significantly worse outcome for the ER-negative cohort (total population hazards ratio 85%vs <85% 0.68 [95% CI 0.54-0.86] for disease free survival; 0.72 [0.56-0.94] for overall survival) but not for the ER-positive cohort (1.16 [0.97-1.40] for disease-free survival; 1.16 [0.94-1.44] for overall survival) [interaction p values=0.0001 for disease-free survival and 0.0019 for overall survival]. Our findings suggest that for women with ER-absent or ER-low tumours, reduction in chemotherapy dose should be avoided.
authors.affiliation: European Institute of Oncology, Milan, Italy. marco.colleoni@ieo.it
authors.forename: Marco
authors.initials: M
authors.lastname: Colleoni
authors.forename: Sigui
authors.initials: S
authors.lastname: Li
authors.forename: Richard D
authors.initials: RD
authors.lastname: Gelber
authors.forename: Karen N
authors.initials: KN
authors.lastname: Price
authors.forename: Alan S
authors.initials: AS
authors.lastname: Coates
authors.forename: Monica
authors.initials: M
authors.lastname: Castiglione-Gertsch
authors.forename: Aron
authors.initials: A
authors.lastname: Goldhirsch
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D015992:Body Mass Index; D001943:Breast Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008727:Methotrexate / Q000008:administration & dosage; D009765:Obesity / Q000150:complications; D017697:Premenopause; D016032:Randomized Controlled Trials as Topic; D011960:Receptors, Estrogen / Q000032:analysis*; D015996:Survival Rate
chemical_list: D011960:Receptors, Estrogen; D003520:Cyclophosphamide; D005472:Fluorouracil; D008727:Methotrexate