Response to “Estrogen Plus Progestin and Breast Cancer
Incidence and Mortality in Postmenopausal Women”, JAMA, October,
2010
(brought to you by Bellevue
Pharmacy, a ProjectAWARE sponsor)
This follow-up study continues the evaluation of breast
cancer outcomes in patients that participated in the Women’s Health
Initiative (WHI) trial that took place 1993 to 2002. The WHI trial
was stopped when risks were found to exceed benefits, including
the increased risk of breast cancer in patients treated with PremPro,
a manufactured, non-bioidentical estrogen and progestin combination
when compared to patients treated with placebo.
Results from the follow-up study:
- Over the 8 year follow-up period, breast cancers were reported
in both groups: the PremPro treatment group (6,545 participants)
reported 385 cases of invasive breast cancers compared to 293
cases in the placebo group (6,243 participants)
- Breast cancers in the PremPro treatment group were more commonly
diagnosed in an advanced stage with more lymph node involvement
compared to the placebo treatment group
- Twice as many woman diagnosed with breast cancer in PremPro
treatment group died during the follow-up period compared to placebo
treatment group (2.6 deaths per 10,000 patients vs 1.3 deaths
per 10,000 patients)
Considerations:
- The follow-up study targeted use of PremPro, a manufactured
prescription hormone therapy of conjugated equine/horse estrogens
and medroxyprogesterone, not a customized prescription compound
of bioidentical estradiol and progesterone
- The study only evaluated long-term continuous use of hormone
therapy
- Dosing or route of hormones was not evaluated
Conclusion:
The findings of this study are significant to us as clinicians
who recommend hormone therapy for treatment of menopausal symptoms.
Previous studies like the PEPI and HERS II trials have shown that
medroxyprogesterone decreased the heart saving benefit of estrogen
and also increased the risk of breast cancer. With the results of
the estrogen (Premarin) arm of the WHI study showing no increased
incidence of breast cancer, at least over the first 7 years of treatment,
combined with the results of this WHI follow-up trial, suggests
that it may be the progestin, medroxyprogesterone that increases
the risk of breast cancer.
Armed with the results of this study and others, it strengthens
the position that hormone therapy should be targeted to the individual
patient based on medical history and risk profile. Hormone therapy
in the form of human identical hormones, commonly referred to as
bioidentical hormones and not “me too” hormones that are not identical
to endogenous hormones should be the hallmark of hormone treatment.
Other important considerations are the timing of hormone dosing
(cyclic vs continuous therapy) and the route of hormone therapy.
Several clinical studies suggest cyclic progesterone halts the growth
of breast cancer cells. Additionally, transdermal (and sublingual)
dosing limits first-pass liver metabolism, which can result in high
estrone levels, often associated with higher risks of cancer. Additionally,
this liver process elevates creatinine reactive protein (CRP) and
other pro-inflammatory markers. Of course, cancer is an inflammatory
process.
Due to the potential increased risk of breast cancer with hormone
therapy, women should conduct regular breast self-exams, maintain
regular physician exams and mammograms.
For questions and further information, contact Bellevue
Pharmacy.

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