In a re-analysis of the recently released Women’s Health Initiative study, researchers showed a trend toward an increased absolute risk for breast cancer in women aged 50 to 59 years who take combination hormone therapy for 5 years. In the plenary session talk, a model was presented that showed 94% of the women with breast cancer in the WHI study most likely had a growth of pre-existing cancer rather than new instances of de novo cancer.
Richard J. Santen, MD, professor of medicine, endocrinology and metabolism at the University of Virginia, gave the Plenary Joint Lecture at the Conjoint Meeting of the International Federation of Fertility Societies and the American Society for Reproductive Medicine and said the recently updated WHI analysis led by JoAnn Manson, MD, DrPH, should be commended for its concentration on absolute risk, rather than relative risk, but commented on the breakdown of risk per 10,000 women for 1 year of HT.
“We don’t think that’s the best way to express the risk because most women take hormone therapy for 3, 4 or 5 years,” Santen told Endocrine Today. “If you express the risk per 1 year, you may be underemphasizing the risk.”
Santen and colleagues presented data from the WHI re-analysis and looked at 5 years of HT, focusing on women aged 50 to 59 years because this cohort would be making immediate decisions about HT. Santen said the average age of the participants in the entire WHI study was 63 years, whereas the WHI re-analysis also looked at a subset ages 50-59.
The 5-year data showed a trend toward an increased risk of breast cancer of three women per 1,000 with estrogen plus progestin therapy (EPT), but a 2.5 per 1,000 risk reduction with estrogen alone. Santen postulated that the reduction with ET resulted from apoptosis in women whose breast cancer tumor had been deprived of estrogen for some time.
In addition, Santen applied a previously published model that took the doubling time of breast cancer tumors into consideration, suggesting that only 6% of cancers seen in the WHI study were de novo tumors. The others, Santen said, were most likely growths of undetected tumors present at the start of the study.
“What happens then, in the women on estrogen plus progestin, is that the tumor that’s there, rather than growing at a doubling time of 200 days, grows at a doubling time of 150 days,” Santen said. “In other words, it’s growing faster. Our model almost precisely predicts what was seen in the WHI study when we did that.”
“Hormone therapy does not cause breast cancer, it causes existing breast cancer to grow more rapidly,” he added.
With this in mind, Santen said the ideal treatment for menopause symptoms would also prevent these occult breast cancers from growing.
“The next thing is if estrogen plus a progestin has more risk associated with it than estrogen alone — that appears true for breast cancer — you’d like to have a therapy that does not include a progestin,” Santen said.
In his presentation, Santen discussed the recently approved combination therapy of conjugated estrogens and selective estrogen receptor modulator bazedoxifene (Duavee, Pfizer), which has shown promise in menopause symptom reduction. In animal studies, this combination does not stimulate the growth of breast cancer xenografts. This combination eliminates the need for a progestin and potentially may be safer with respect to breast cancer, he said.
“This has yet to be proven in clinical trials, but it makes this the potential for a very exciting way to manage menopause,” Santen said.
For more information:
Santen R. Plenary Lecture 6. Presented at: the Conjoint Meeting of the IFFS/ABRM; Oct. 12-17, 2013; Boston.
Disclosure: Santen reported a relationship with Pfizer as a paid consultant and recipient of grant funding.