Estrogen Protects Against Breast Cancer Long After Treatment

[Hopeful]

Elsevier Global Medical News. 2012 Mar 6, MA Moon

In a study of postmenopausal women who had undergone hysterectomy, the use of unopposed estrogen significantly reduced the incidence of invasive breast cancer for up to 5 years after they stopped taking the hormone, according to a report published online March 7 in the Lancet Oncology.

For study subjects who did develop breast cancer, estrogen use reduced breast-cancer mortality and all-cause mortality, Garnet L. Anderson, Ph.D., and her associates reported in an extended follow-up study of 7,645 participants in the Women's Health Initiative (WHI).

"Our findings ... provide reassurance about breast cancer safety for postmenopausal women with [a] previous hysterectomy who receive unopposed estrogen to reduce climacteric symptoms," they noted.
The WHI, a multicenter, randomized clinical trial involving more than 10,000 women, compared outcomes between those who took conjugated equine estrogen and those who took a matching placebo.

The intervention phase of the WHI was terminated early in February 2004, after a mean follow-up of 7 years. Approximately 78% of the study subjects - 3,778 who had been randomly assigned to receive estrogen and 3,867 to receive placebo - agreed to extended follow-up until August 2009, for a total median follow-up of 11.8 years.

At this final assessment, women who had taken estrogen for a median of 6 years during the intervention phase had an overall incidence of invasive breast cancer of 0.27% per year (151 cases), which was significantly lower than the 0.35% per year rate (199 cases) among women who had taken placebo, said Dr. Anderson of the Fred Hutchinson Cancer Research Center, Seattle, and her colleagues.

"The continued, postintervention effect of estrogen on breast cancer incidence is akin to that reported for other hormone-targeted drugs shown to reduce breast cancer incidence," the investigators said (Lancet Oncol. 2012 March 7 [doi:10.1016/S1470-2045(12)70075-x]).

Estrogen was associated with a reduced risk of developing infiltrating ductal carcinoma but not infiltrating lobular cancers. It also decreased the risk of human epidermal growth factor receptor 2 (HER-2)-negative tumors but not HER-2-positive tumors, and appeared to reduce the risk of small and node-negative cancers but not large (2 cm or larger) or node-positive cancers. However, these differences among tumor subtypes did not reach statistical significance.

Among the study subjects who did develop breast cancer, those in the estrogen group were significantly less likely to die of any cause (30 deaths, for a mortality of 0.046% per year) than were those in the placebo group (50 deaths, for a mortality of 0.076% per year).

Breast-cancer-specific mortality also was significantly lower in the estrogen recipients (6 deaths, for a mortality of 0.009% per year) than in the placebo recipients (16 deaths, for a mortality of 0.024% per year).

However, the number of deaths was small, limiting the strength of these associations, Dr. Anderson and her associates noted.

These protective effects appeared to be restricted to women who had a lower risk for breast cancer. They did not apply to women with a history of benign breast disease or those with a first-degree family history of breast cancer.

In subgroup analyses, estrogen's protective effects showed no interactions with patient age, body mass index, oophorectomy status, years since the onset of menopause, previous estrogen use, or the presence of vasomotor symptoms.

The WHI was limited in that it assessed "only one dose and schedule of oral conjugated equine estrogens; whether these findings apply to lower doses, other estrogen preparations, or longer durations of use is not known," the researchers noted.

In an editorial comment accompanying Dr. Anderson's report, Dr. Anthony Howell and Dr. Jack Cuzick said that these WHI results are significant though "modest."

The findings should be viewed "in the context of the update of the study in 2011 reporting the effects of estrogen on overall health. No overall difference was noted in participants' global index of health (including cardiovascular disease, thrombosis and embolism, breast and colorectal cancer, hip fracture, and death from all causes)," wrote Dr. Howell of the University Hospital of South Manchester (England) and Dr. Cuzick of Queen Mary University of London (Lancet Oncol. 2012 March 7 [doi:10.1016/S1470-2045(12)70110-9]).

However, "this null result masked an unexpected but significant interaction with age," in which younger women (aged 50-59 years) showed health improvements while older women showed health decrements, Dr. Howell and Dr. Cuzick said.

They reported no relevant financial disclosures.The WHI was supported by the National Heart, Lung, and Blood Institute; the National Institutes of Health; the Department of Health and Human Services; and Wyeth. One of Dr. Anderson's associates reported ties to AstraZeneca, Novartis, Amgen, and Pfizer. Dr. Anderson and the other investigators said they had no relevant financial disclosures.

Hopeful