title: Age of menopause among women who remain premenopausal following treatment for early breast cancer: long-term results from International Breast Cancer Study Group Trials V and VI.
abstract: BACKGROUND
  The likelihood of premature menopause has not been thoroughly explored in women who remain premenopausal after adjuvant chemotherapy for breast cancer.
  
  
  METHODS
  We used data from the International Breast Cancer Study Group (IBCSG) Trials V and VI. Trial V enrolled 1407 eligible premenopausal women randomised to no systemic therapy (No CT) or 1 cycle of perioperative CMF-based chemotherapy (PeCT) if node negative, and 6 cycles of CMF-based chemotherapy postoperatively (CMFx6) or 1 cycle perioperative CMF-based chemotherapy plus CMFx6 postoperatively (CMFx7) if node positive. From Trial VI (a 2x2 factorial designed study of 3 versus 6 initial cycles of CMF and a reintroduction of three additional courses of CMF), we included 375 women randomised to receive only six initial cycles of CMF (CMFx6).
  
  
  RESULTS
  We excluded women who reported no menses during 12-24 months after randomisation (N=934), hysterectomy (N=16) or bilateral oophorectomy (N=8), or missing menses data (N=57), creating a cohort of 767 women; 540 women had been randomised to PeCT or no CT, 227 randomised to CMFx6 or 7. A Cox proportional hazards model revealed that CMFx6 or 7 (HR=2.03, p<0.0001) and temporary amenorrhea (HR=1.96, p<0.0001) were associated with premature menopause.
  
  
  CONCLUSIONS
  Women who remain premenopausal after 6 or 7 cycles of CMF-based chemotherapy have a higher likelihood of going through menopause at an earlier age than women who received little or no chemotherapy. Temporary cessation of menses appears to be a marker for earlier onset of menopause. These findings may assist women and clinicians when making treatment and reproductive decisions after a diagnosis of breast cancer.
authors.affiliation: Dana-Farber Cancer Institute, Boston, MA 02115, USA. ahpartridge@partners.org
authors.forename: Ann
authors.initials: A
authors.lastname: Partridge
authors.forename: Shari
authors.initials: S
authors.lastname: Gelber
authors.forename: Richard D
authors.initials: RD
authors.lastname: Gelber
authors.forename: Monica
authors.initials: M
authors.lastname: Castiglione-Gertsch
authors.forename: Aron
authors.initials: A
authors.lastname: Goldhirsch
authors.forename: Eric
authors.initials: E
authors.lastname: Winer
mesh_terms: D000328:Adult; D000367:Age Factors; D000568:Amenorrhea / Q000139:chemically induced*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000188:drug therapy*; D015331:Cohort Studies; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008593:Menopause / Q000187:drug effects*; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D016016:Proportional Hazards Models
chemical_list: D003520:Cyclophosphamide; D005472:Fluorouracil; D008727:Methotrexate