Patient-reported symptoms and quality of life during treatment with tamoxifen or raloxifene for breast cancer prevention: the NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 trial

JAMA. 2006 Jun 21;295(23):2742-51. doi: 10.1001/jama.295.23.joc60075. Epub 2006 Jun 5.

Abstract

Context: Tamoxifen has been approved for breast cancer risk reduction in high-risk women, but how raloxifene compares with tamoxifen is unknown.

Objective: To compare the differences in patient-reported outcomes, quality of life [QOL], and symptoms in Study of Tamoxifen and Raloxifene (STAR) participants by treatment assignment.

Design, setting, participants, and interventions: STAR was a double-blind, randomized phase 3 prevention trial designed to evaluate the relative efficacy of raloxifene vs tamoxifen in reducing the incidence of invasive breast cancer in high-risk postmenopausal women. Between July 1, 1999, and November 4, 2004, 19,747 participants were enrolled at centers throughout North America, with a median potential follow-up time of 4.6 years (range, 1.2-6.5 years). Patient-reported symptoms were collected from all participants using a 36-item symptom checklist. Quality of life was measured with the Medical Outcomes Study Short-Form Health Survey (SF-36), the Center for Epidemiologic Studies-Depression (CES-D), and the Medical Outcomes Study Sexual Activity Questionnaire in a substudy of 1983 participants, median potential follow-up 5.4 years (range, 4.6-6.0 years). Questionnaires were administered before treatment, every 6 months for 60 months and at 72 months.

Main outcome measures: Primary QOL end points were the SF-36 physical (PCS) and mental (MCS) component summaries.

Results: Among women in the QOL analysis, mean PCS, MCS, and CES-D scores worsened modestly over the study's 60 months, with no significant difference between the tamoxifen (n = 973) and raloxifene (n = 1010) groups (P>.2). Sexual function was slightly better for participants assigned to tamoxifen (age-adjusted repeated measure odds ratio, 1.22%; 95% CI, 1.01-1.46). Of the women in the symptom assessment analyses, the 9769 in the raloxifene group reported greater mean symptom severity over 60 months of assessments than the 9743 in the tamoxifen group for musculoskeletal problems (1.15 vs 1.10, P = .002), dyspareunia (0.78 vs 0.68, P<.001), and weight gain (0.82 vs 0.76, P<.001). Women in the tamoxifen group reported greater mean symptom severity for gynecological problems (0.29 vs 0.19, P<.001), vasomotor symptoms (0.96 vs 0.85, P<.001), leg cramps (1.10 vs 0.91, P<.001), and bladder control symptoms (0.88 vs 0.73, P<.001).

Conclusions: No significant differences existed between the tamoxifen and raloxifene groups in patient-reported outcomes for physical health, mental health, and depression, although the tamoxifen group reported better sexual function. Although mean symptom severity was low among these postmenopausal women, those in the tamoxifen group reported more gynecological problems, vasomotor symptoms, leg cramps, and bladder control problems, whereas women in the raloxifene group reported more musculoskeletal problems, dyspareunia, and weight gain.

Trial registration: clinicaltrials.gov Identifier: NCT00003906.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Breast Neoplasms / prevention & control*
  • Double-Blind Method
  • Female
  • Humans
  • Middle Aged
  • Postmenopause
  • Quality of Life*
  • Raloxifene Hydrochloride / adverse effects
  • Raloxifene Hydrochloride / therapeutic use*
  • Selective Estrogen Receptor Modulators / adverse effects
  • Selective Estrogen Receptor Modulators / therapeutic use*
  • Tamoxifen / adverse effects
  • Tamoxifen / therapeutic use*

Substances

  • Selective Estrogen Receptor Modulators
  • Tamoxifen
  • Raloxifene Hydrochloride

Associated data

  • ClinicalTrials.gov/NCT00003906