Resumption or persistence of menstruation after cytotoxic chemotherapy is a prognostic factor for poor disease-free survival in premenopausal patients with early breast cancer

Ann Oncol. 2012 Sep;23(9):2283-2289. doi: 10.1093/annonc/mds006. Epub 2012 Feb 29.

Abstract

Background: We investigated the relationship between resumption or persistence of menstruation after cytotoxic chemotherapy (RM) and disease-free survival (DFS) in premenopausal patients with early breast cancer.

Methods: Medical records from 872 patients who received cytotoxic chemotherapy for stage I to III breast cancer were retrospectively reviewed.

Results: The median patient age was 41 years (range, 21-54) and the median follow-up duration was 6.2 years (range, 0.7-10.4). Six hundred ninety-two patients (79.4%) were hormone receptor (HR) positive and the majority of these received tamoxifen therapy after completing chemotherapy. The chemotherapy-induced amenorrhea (CIA) rate was 76.7% (n = 669), and 51.8% (n = 452) experienced RM during the follow-up period. One hundred twenty-one (13.9%) patients had persistent menstruation without CIA. DFS was significantly affected by younger age at diagnosis (≤35 years) (P = 0.013), tumor size > 2 cm (P < 0.001), node positivity (P < 0.001), HR negativity (P < 0.001), HER2 positivity (P = 0.010), and RM (P < 0.001). HR negativity [hazard ratio 1.7, 95% confidence interval (CI) 1.2-2.4, P = 0.006], tumor size > 2 cm (hazard ratio 2.1, 95% CI 1.4-3.0, P < 0.001), node positivity (hazard ratio 3.0, 95% CI 2.0-4.7, P < 0.001), and RM (hazard ratio 1.8, 95% CI 1.2-2.7, P = 0.004) remained significant factors for DFS on multivariate analysis.

Conclusions: A considerable proportion of premenopausal patients treated with chemotherapy experienced RM after CIA. RM was a poor prognostic factor for DFS in premenopausal patients with early breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amenorrhea / chemically induced*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / mortality
  • Breast Neoplasms / physiopathology*
  • Capecitabine
  • Cyclophosphamide / administration & dosage
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • Disease-Free Survival
  • Docetaxel
  • Doxorubicin / administration & dosage
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / analogs & derivatives
  • Humans
  • Kaplan-Meier Estimate
  • Menstrual Cycle / drug effects*
  • Methotrexate / administration & dosage
  • Middle Aged
  • Multivariate Analysis
  • Premenopause*
  • Prognosis
  • Proportional Hazards Models
  • Retrospective Studies
  • Taxoids / administration & dosage
  • Young Adult

Substances

  • Taxoids
  • Deoxycytidine
  • Docetaxel
  • Capecitabine
  • Doxorubicin
  • Cyclophosphamide
  • Fluorouracil
  • Methotrexate