Baseline incidence of invasive breast cancers in non-HRT users is 32/1000 between ages 50 and 65 years. Baseline incidence of endometrial cancers in non-HRT users is 5/1000 between ages 50 and 64 years.
The excess risk of breast cancer with long-term use (10 years) of 19/1000 EPT and 5/1000 for ET alone can be compared with the excess risk of endometrial cancer after 10 years use of ET alone of 10/1000. Ten years of EPT is estimated to result in no increased risk of endometrial cancer.
Since the Million Women study shows a greater risk of breast cancer with combined EPT, women and their physicians will need to weigh the possibility that the increased risk of breast cancer caused by the addition of a progestogen is greater than the risk of endometrial cancer with estrogen only. If this is correct, the logical conclusion may be that women should be advised to take estrogen alone for hormonal therapy, even if they have a uterus and that screening be instituted for endometrial cancer. This possibility would need extensive discussion before making a general recommendation. Other options include using progestogen delivery systems that allow a local progestogen effect at the uterus.
Because this is an observational study, it has potential for error. According to Utian and colleagues6, the major weakness is that the study took only a snapshot of hormone therapy use at the time of entry into the study, when women had their every third year mammogram. No further information was obtained about changes in hormones, route, dose, or discontinuation.
In conclusion, the Million Women Study serves as a large observational study that confirms the WHI findings of a small increase in absolute risk of breast cancer with EPT therapy, and confirms prior observational studies of a smaller increase in absolute risk of breast cancer with ET. These findings are important to convey to women making decisions about initiation or continuation of hormone therapy. The findings do not change current recommendations to use hormones primarily for menopausal symptom relief, vulvovaginal atrophy, and quality of life issues in symptomatic menopausal women with natural, premature, or surgically induced menopause.
They support current recommendations from the North American Menopause Society (NAMS)7, American College of Obstetrics and Gynecology (ACOG),8 and the Food and Drug Administration (FDA)9,10 to use the lowest, most effective dose for the shortest period of time.