Mortality following development of breast cancer while using oestrogen or oestrogen plus progestin: a computer record-linkage study

Research and Evaluation Department, Kaiser Permanente Southern California, Pasadena, 91101, USA.
British Journal of Cancer (Impact Factor: 4.82). 09/2005; 93(4):392-8. DOI: 10.1038/sj.bjc.6602701
Source: PubMed

ABSTRACT The literature on the relationship between breast cancer mortality and postmenopausal oestrogen and combined oestrogen/progestin therapy is seemingly contradictory. This study explored survival after exposure to oestrogen or oestrogen plus progestin at or in the year prior to breast cancer diagnosis. Information on patients first diagnosed with invasive breast cancer between 1993 and 1998 was linked with outpatient pharmacy data from 1992 to 2000. Patients were classified according to use of oestrogen alone or oestrogen plus progestin at or in the year prior to diagnosis. Compared to nonusers, and adjusting for age at diagnosis, race/ethnicity, tumour size and grade, oestrogen receptor status, surgery status, and chemotherapy and hormone therapy for breast cancer treatment, oestrogen plus progestin users had lower all-cause mortality (stage I hazard ratio (HR) = 0.69, 95% confidence interval (CI)= 0.48-0.99; stage II HR = 0.53, 95% CI = 0.39-0.72) and breast cancer mortality (stage I HR = 0.52, 95% CI = 0.26-1.04; stage II HR = 0.69, 95% CI = 0.48-0.98). Oestrogen users experienced little or no survival benefit for all-cause mortality (stage I HR = 1.04, 95% CI = 0.77-1.42; stage II HR = 0.86, 95% CI = 0.65-1.14) or breast cancer mortality (stage I HR = 1.23, 95% CI 0.72-2.10; stage II HR = 1.01, 95% CI 0.72-1.41). Our findings suggest, relative to nonusers, a lower risk of death from all causes and from breast cancer in patients who were diagnosed with breast cancer while exposed to oestrogen plus progestin, but not in patients exposed to oestrogen only.

  • [Show abstract] [Hide abstract]
    ABSTRACT: The Women’s Health Initiative (WHI) has conducted two randomized, placebo-controlled clinical trials to evaluate the influence of menopausal hormone therapy on chronic disease risk. Estrogen plus progestin was evaluated in 16,608 postmenopausal women without prior hysterectomy during 5.6 years’ intervention. In that setting, combined hormone therapy use significantly increased breast cancer incidence and interfered with breast cancer detection. The breast cancers were not limited to estrogen receptor positive, favorable prognosis cancers and were identified at more advanced stage. As a result, deaths from breast cancer were significantly increased by estrogen plus progestin use. While the absolute breast cancer risk for relatively short term (2-4 years) use of combined hormone therapy is small, on a population basis a therapy which nearly doubles deaths from breast cancer requires cautious use. Estrogen alone was evaluated in 10,739 postmenopausal women with prior hysterectomy during 7.1 years’ intervention. There was an overall reduction of breast cancer incidence seen with estrogen alone use and a suggestion that the effect on risk was more pronounced in women initiating hormone therapy further from menopause. Nonetheless, women with prior hysterectomy can be assured that short duration estrogen alone use for climacteric symptom management is relatively safe. Neither estrogen plus progestin nor estrogen alone should be used for chronic disease risk reduction. The safety of duration of use on chronic disease risk longer than in the WHI clinical trials is not defined.
    04/2015; 6(2). DOI:10.1177/2042098614568300
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background In the Women's Health Initiative (WHI) randomized trial, estrogen plus progestin increased both breast cancer incidence and mortality. In contrast, most observational studies associate estrogen plus progestin with favorable prognosis breast cancers. To address differences, a cohort of WHI observational study participants with characteristics similar to the WHI clinical trial was studied.Methods We identified 41 449 postmenopausal women with no prior hysterectomy and mammogram negative within 2 years who were either not hormone users (n = 25 328) or estrogen and progestin users (n = 16 121). Multivariable-adjusted Cox proportional hazard regression was used to calculate hazard ratios (HRs) with 95% confidence intervals (CI). All statistical tests were two-sided.ResultsAfter a mean of 11.3 (SD = 3.1) years, with 2236 breast cancers, incidence was higher in estrogen plus progestin users than in nonusers (0.60% vs 0.42%, annualized rate, respectively; HR = 1.55, 95% CI = 1.41 to 1.70, P < .001). Women initiating hormone therapy closer to menopause had higher breast cancer risk with linear diminishing influence as time from menopause increased (P < .001). Survival after breast cancer, measured from diagnosis, was similar in combined hormone therapy users and nonusers (HR = 1.03, 95% CI = 0.79 to 1.35). On a population basis, there were somewhat more deaths from breast cancer, measured from cohort entry (HR = 1.32, 95% CI = 0.90 to 1.93, P = .15), and more all-cause deaths after breast cancer (HR = 1.65, 95% CI = 1.29 to 2.12, P < .001) in estrogen plus progestin users than in nonusers.Conclusions Consistent with WHI randomized trial findings, estrogen plus progestin use is associated with increased breast cancer incidence. Because prognosis after diagnosis on combined hormone therapy is similar to that of nonusers, increased breast cancer mortality can be expected.
    CancerSpectrum Knowledge Environment 03/2013; DOI:10.1093/jnci/djt043 · 15.16 Impact Factor
  • Gynécologie Obstétrique & Fertilité 01/2008; 36(1):98-103. DOI:10.1016/j.gyobfe.2007.11.008 · 0.58 Impact Factor

Full-text (2 Sources)

Available from
May 31, 2014