- Among women with prior hysterectomy, 238 cases of breast cancer (annualised rate, 0.30%) developed in those taking CEE versus 296 (annualised rate 0.37%) in those taking placebo (HR=0.78, 95%CI 0.65‒0.93; P=0.005). Furthermore, women taking CEE had a significantly lower breast cancer mortality, with 30 deaths (annualised mortality rate 0.031%) among those taking CEE versus 46 deaths (annualised mortality rate 0.046%) among those taking placebo (HR=0.60, 95%CI 0.37‒0.97; P=0.04).
- Among women with an intact uterus, 585 cases of breast cancer (annualised rate, 0.45%) developed in those taking CEE plus MPA versus 447 cases (annualised rate 0.36%) in those taking placebo (HR=1.28, 95%CI 1.13‒1.45; P<0.001). There was, however, no significant difference in breast cancer mortality between the groups, with 71 deaths among women taking CEE plus MPA (annualised mortality rate 0.045%) versus 53 deaths among those taking placebo (annualised mortality rate 0.035%) (HR=1.35, 95%CI 0.94‒1.95; P=0.11).
20-year WHI follow-up study finds oestrogen selectively protects against breast cancer in women who have undergone hysterectomy

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This analysis has overlooked the totality of the WHI breast cancer findings. In 2010, researchers – 8 years post-trial cessation – did report a significant doubling in BC mortality with E+P (HR 1.96). That this increase in mortality is not sustained 18 years later makes perfect sense because these women have been off hormones for so long now, even if incidence is still higher. The E-alone data, however, should be approached with caution. Breast cancer prevention trials have not shown lower mortality rates with either tamoxifen or AIs. WHI was not a BC prevention trial. Also, Chlebowski originally reported in the (planned) 2016 post-trial followup that not only was the reduced breast cancer incidence seen with E-alone not sustained, but the HR had shifted in the opposite direction (1.17). It just doesn’t seem prudent to be telling women that estrogen, categorically, prevents breast cancer. No one knows why WHI found a lower risk, but it’s either due to an adherence issue (>60% became noncompliant prior to study termination) or a Premarin issue (which may be behaving more like a SERM in women with hysterectomy vs. estradiol). Additionally, this new analysis is confounded by the fact that it is years beyond the original blinded, controlled setting. Might those who received E-alone actually be doing more to protect their health in light of the trial’s findings? In other words, knowing that they had taken a drug for many years that raises stroke and dementia risk might have prompted a more health conscious mindset.