title: Impact of baseline BMI and weight change in CCTG adjuvant breast cancer trials.
abstract: BACKGROUND
  We hypothesized that increased baseline BMI and BMI change would negatively impact clinical outcomes with adjuvant breast cancer systemic therapy.
  
  
  METHODS
  Data from chemotherapy trials MA.5 and MA.21; endocrine therapy MA.12, MA.14 and MA.27; and trastuzumab HERA/MA.24 were analyzed. The primary objective was to examine the effect of BMI change on breast cancer-free interval (BCFI) landmarked at 5 years; secondary objectives included BMI changes at 1 and 3 years; BMI changes on disease-specific survival (DSS) and overall survival (OS); and effects of baseline BMI. Stratified analyses included trial therapy and composite trial stratification factors.
  
  
  RESULTS
  In pre-/peri-/early post-menopausal chemotherapy trials (N = 2793), baseline BMI did not impact any endpoint and increased BMI from baseline did not significantly affect BCFI (P = 0.85) after 5 years although it was associated with worse BCFI (P = 0.03) and DSS (P = 0.07) after 1 year. BMI increase by 3 and 5 years was associated with better DSS (P = 0.01; 0.01) and OS (P = 0.003; 0.05). In pre-menopausal endocrine therapy trial MA.12 (N = 672), patients with higher baseline BMI had worse BCFI (P = 0.02) after 1 year, worse DSS (P = 0.05; 0.004) after 1 and 5 years and worse OS (P = 0.01) after 5 years. Increased BMI did not impact BCFI (P = 0.90) after 5 years, although it was associated with worse BCFI (P = 0.01) after 1 year. In post-menopausal endocrine therapy trials MA.14 and MA.27 (N = 8236), baseline BMI did not significantly impact outcome for any endpoint. BMI change did not impact BCFI or DSS after 1 or 3 years, although a mean increased BMI of 0.3 was associated with better OS (P = 0.02) after 1 year. With the administration of trastuzumab (N = 1395) baseline BMI and BMI change did not significantly impact outcomes.
  
  
  CONCLUSIONS
  Higher baseline BMI and BMI increases negatively affected outcomes only in pre-/peri-/early post-menopausal trial patients. Otherwise, BMI increases similar to those expected in healthy women either did not impact outcome or were associated with better outcomes.
  CAN-NCIC-MA5; National Cancer Institute (NCI)-V90-0027; MA.12-NCT00002542; MA.14-NCT00002864; MA.21-NCT00014222; HERA, NCT00045032;CAN-NCIC-MA24; MA-27-NCT00066573.
authors.affiliation: Department of Medical Oncology, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva and Tel-Aviv University, Tel Aviv, Israel.
authors.forename: R
authors.initials: R
authors.lastname: Yerushalmi
authors.affiliation: Canadian Cancer Trials Group (CCTG; Formerly, NCIC Clinical Trials Group), Queen's University, Kingston, Canada.
authors.forename: B
authors.initials: B
authors.lastname: Dong
authors.affiliation: Canadian Cancer Trials Group (CCTG; Formerly, NCIC Clinical Trials Group), Queen's University, Kingston, Canada.
authors.forename: J W
authors.initials: JW
authors.lastname: Chapman
authors.affiliation: Massachusetts General Hospital Cancer Center, Boston, USA.
authors.forename: P E
authors.initials: PE
authors.lastname: Goss
authors.affiliation: Department of Medical Oncology, Jewish General Hospital, McGill University, Montreal.
authors.forename: M N
authors.initials: MN
authors.lastname: Pollak
authors.affiliation: Department of Medical Oncology, Saint John Regional Hospital, Saint John.
authors.forename: M J
authors.initials: MJ
authors.lastname: Burnell
authors.affiliation: Department of Oncology, McMaster University, Juravinski Cancer Center, Hamilton, Ontario.
authors.forename: M N
authors.initials: MN
authors.lastname: Levine
authors.affiliation: Department of Medical Oncology, Tom Baker Cancer Centre, Alberta Health Services and University of Calgary, Calgary.
authors.forename: V H C
authors.initials: VHC
authors.lastname: Bramwell
authors.affiliation: Department of Medical Oncology, Sunnybrook Odette Cancer Centre and the University of Toronto, Toronto, Canada.
authors.forename: K I
authors.initials: KI
authors.lastname: Pritchard
authors.affiliation: Department of Oncology, Juravinski Cancer Center, McMaster University, Hamilton, Ontario.
authors.forename: T J
authors.initials: TJ
authors.lastname: Whelan
authors.affiliation: Department of Oncology, Mayo Clinic, Rochester, USA.
authors.forename: J N
authors.initials: JN
authors.lastname: Ingle
authors.affiliation: Canadian Cancer Trials Group (CCTG; Formerly, NCIC Clinical Trials Group), Queen's University, Kingston, Canada.
authors.forename: L E
authors.initials: LE
authors.lastname: Shepherd
authors.affiliation: Canadian Cancer Trials Group (CCTG; Formerly, NCIC Clinical Trials Group), Queen's University, Kingston, Canada.
authors.forename: W R
authors.initials: WR
authors.lastname: Parulekar
authors.affiliation: Canadian Cancer Trials Group (CCTG; Formerly, NCIC Clinical Trials Group), Queen's University, Kingston, Canada.
authors.forename: L
authors.initials: L
authors.lastname: Han
authors.affiliation: Canadian Cancer Trials Group (CCTG; Formerly, NCIC Clinical Trials Group), Queen's University, Kingston, Canada.
authors.forename: K
authors.initials: K
authors.lastname: Ding
authors.affiliation: Department of Medical Oncology, British Columbia Cancer Agency, Vancouver, Canada.
authors.forename: K A
authors.initials: KA
authors.lastname: Gelmon
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D015992:Body Mass Index; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D047648:Perimenopause; D017698:Postmenopause; D017697:Premenopause; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D015430:Weight Gain
chemical_list: D000970:Antineoplastic Agents
keywords: BMI; disease specific survival; overall survival; triple negative; weight change