title: Menstrual cycle and timing of breast surgery in premenopausal node-positive breast cancer: results of the International Breast Cancer Study Group (IBCSG) Trial VI.
abstract: OBJECTIVE
  It has been postulated that breast cancer surgery performed during the follicular phase of the menstrual cycle is associated with poorer outcome.
  
  
  METHODS
  We tested this hypothesis by evaluating disease-free survival (DFS) for 1033 premenopausal patients who received definitive surgery either during the follicular phase (n = 358) or the luteal phase (n = 675). All patients were enrolled in a randomized trial conducted between July 1986 and April 1993. All had node positive breast cancer and randomization was stratified by estrogen receptor (ER) status. All patients received at least three cycles of adjuvant cyclophosphamide, methotrexate, and 5-fluorouracil (CMF). The median follow-up was 60 months.
  
  
  RESULTS
  Patients who underwent definitive surgery for breast cancer in the follicular phase had a slightly worse disease-free survival than those operated on during the luteal phase (five-year DFS percentage: 53% versus 58%; hazard ratio, 1.13; 95% confidence interval (CI), 0.94-1.38; P = 0.20). The effect was significantly greater for the subpopulation of 300 patients with ER-negative primaries (P = 0.02 interaction effect; five-year DFS percentages 42% vs. 59%; hazard ratio 1.60; 95% CI, 1.12-2.25; P = 0.008). The effect of timing of surgery diminished for analyses based on lesser surgical procedures, e.g., excisional biopsies. In particular, no effect of timing was observed for fine needle aspiration procedures.
  
  
  CONCLUSIONS
  Surgical procedures which are more extensive than a fine needle aspiration biopsy might be associated with worse prognosis if conducted during the follicular phase of the menstrual cycle. This phenomenon was seen predominantly for high risk breast cancer with low levels or no estrogen receptors in the primary tumor.
authors.affiliation: International Breast Cancer Study Group. European Institute of Oncology, Milan, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Goldhirsch
authors.forename: R D
authors.initials: RD
authors.lastname: Gelber
authors.forename: M
authors.initials: M
authors.lastname: Castiglione
authors.forename: A
authors.initials: A
authors.lastname: O'Neill
authors.forename: B
authors.initials: B
authors.lastname: Thürlimann
authors.forename: C M
authors.initials: CM
authors.lastname: Rudenstam
authors.forename: J
authors.initials: J
authors.lastname: Lindtner
authors.forename: J
authors.initials: J
authors.lastname: Collins
authors.forename: J
authors.initials: J
authors.lastname: Forbes
authors.forename: D
authors.initials: D
authors.lastname: Crivellari
authors.forename: A
authors.initials: A
authors.lastname: Coates
authors.forename: F
authors.initials: F
authors.lastname: Cavalli
authors.forename: E
authors.initials: E
authors.lastname: Simoncini
authors.forename: M F
authors.initials: MF
authors.lastname: Fey
authors.forename: O
authors.initials: O
authors.lastname: Pagani
authors.forename: K
authors.initials: K
authors.lastname: Price
authors.forename: H J
authors.initials: HJ
authors.lastname: Senn
mesh_terms: D001943:Breast Neoplasms / Q000401:mortality / Q000601:surgery*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008597:Menstrual Cycle; D015999:Multivariate Analysis; D017697:Premenopause; D011960:Receptors, Estrogen / Q000032:analysis; D013997:Time Factors
chemical_list: D011960:Receptors, Estrogen