Hormone Therapy Accelerates Breast Cancer Progression And Raises Risk

[News]

Postmenopausal women who take hormone therapy - estrogen plus progestin - not only have an increased risk of developing breast cancer, but also of a faster progressing one, researchers from the Los Angeles Biomedical Research Institute reveal in an article published in the peer-reviewed journal JAMA (Journal of the American Medical Association)...

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[gdpawel]

A new study links the Prempro hormone replacement treatment, which is already linked to a higher risk of breast cancer and heart disease, to a higher risk of death. The data was published in the Journal of the American Medical Association. The study followed 12,788 women since 2002, when the federally funded Women's Health Initiative study that compared HRT with placebos was halted, after it became apparent that taking hormones elevated post-menopausal women's risk of breast cancer and heart attacks. Many experts say the gradual decline in the breast cancer incidence rate in the U.S. in the succeeding years can be directly traced to the decline in use.

In the findings, there were 678 cases of invasive breast cancer, including 385 for women taking hromones and 293 with a placebo. More women who took hormones died from breast cancer (0.03% versus 0.01% per year in the placebo). That amounts to 2.6 deatrhs per 10,000 women per years versus 1.3 deaths in the placebo group. The breast cancer among those who took hormones was also more likely to be invasive.

After the Women's Health Initiative was released in 2002, HRT use plummeted and led to a drop in breast cancer rates, with about 100,000 fewer invasive tumors detected from 2002 to 2007 than expected, said lead researcher Rowan Chlebowski, chief of medical oncology at the University of California, Los Angeles, School of Medicine, told Bloomberg News. Using a 10-year mortality rate of about 20 percent, he calculates the reduction in hormone use may have prevented about 20,000 deaths.

The findings should cause doctors to cut back on long-term usage to treat hot flashes and night sweats. “I don’t think you can say that now,” Chlebowski tells the news service. “I know some people have to take it because they can’t function, but the message now is that you really should try to stop after a year or two. Women should think critically about if they need this, if their symptoms are significant and if they would persist.”

In an accompanying editorial in JAMA, Peter Bach, a physician at Memorial Sloan-Kettering Cancer Center, writes that, “given the substantial population of women who seek relief from menopausal symptoms and the large potential burden of disease that could be created if medications given to alleviate symptoms today cause cancer and other deaths tomorrow, it seems that additional randomized trials are needed specifically to determine whether lower doses or shorter durations of hormone therapy could alleviate menopausal symptoms without increasing cancer risk.”

Bach noted that the difference in mortality rates between the two groups was continuing to widen seven years after stopping the drugs, and highlighted the fact the prognosis for those women who developed cancer was worse if they had taken hormones.

He also questioned the common strategy among physicians of prescribing hormones for women during the early years of menopause with the idea of stopping them later to avoid negative health consequences. Many women want the pills to relieve symptoms like decreased libido, vaginal dryness and painful intercourse, which can be destructive of family life in the early years of "the change."

Pharmalot

[gdpawel]

Estrogen Plus Progestin and Breast Cancer Incidence and Mortality in Postmenopausal Women

Rowan T. Chlebowski, MD, PhD; Garnet L. Anderson, PhD; Margery Gass, MD; Dorothy S. Lane, MD; Aaron K. Aragaki, MS; Lewis H. Kuller, MD; JoAnn E. Manson, MD, DrPH; Marcia L. Stefanick, PhD; Judith Ockene, MD; Gloria E. Sarto, MD; Karen C. Johnson, MD, MPH; Jean Wactawski-Wende, PhD; Peter M. Ravdin, MD, PhD; Robert Schenken, MD; Susan L. Hendrix, DO; Aleksandar Rajkovic, MD, PhD; Thomas E. Rohan, PhD; Shagufta Yasmeen, MD; Ross L. Prentice, PhD; for the WHI Investigators

JAMA. 2010;304(15):1684-1692. doi:10.1001/jama.2010.1500

Context

In the Women's Health Initiative randomized, placebo-controlled trial of estrogen plus progestin, after a mean intervention time of 5.6 (SD, 1.3) years (range, 3.7-8.6 years) and a mean follow-up of 7.9 (SD, 1.4) years, breast cancer incidence was increased among women who received combined hormone therapy. Breast cancer mortality among participants in the trial has not been previously reported.

Objective

To determine the effects of therapy with estrogen plus progestin on cumulative breast cancer incidence and mortality after a total mean follow-up of 11.0 (SD, 2.7) years, through August 14, 2009.

Design, Setting, and Participants

A total of 16 608 postmenopausal women aged 50 to 79 years with no prior hysterectomy from 40 US clinical centers were randomly assigned to receive combined conjugated equine estrogens, 0.625 mg/d, plus medroxyprogesterone acetate, 2.5 mg/d, or placebo pill. After the original trial completion date (March 31, 2005), reconsent was required for continued follow-up for breast cancer incidence and was obtained from 12 788 (83%) of the surviving participants.

Main Outcome Measures

Invasive breast cancer incidence and breast cancer mortality.

Results

In intention-to-treat analyses including all randomized participants and censoring those not consenting to additional follow-up on March 31, 2005, estrogen plus progestin was associated with more invasive breast cancers compared with placebo (385 cases [0.42% per year] vs 293 cases [0.34% per year]; hazard ratio [HR], 1.25; 95% confidence interval [CI], 1.07-1.46; P = .004). Breast cancers in the estrogen-plus-progestin group were similar in histology and grade to breast cancers in the placebo group but were more likely to be node-positive (81 [23.7%] vs 43 [16.2%], respectively; HR, 1.78; 95% CI, 1.23-2.58; P = .03). There were more deaths directly attributed to breast cancer (25 deaths [0.03% per year] vs 12 deaths [0.01% per year]; HR, 1.96; 95% CI, 1.00-4.04; P = .049) as well as more deaths from all causes occurring after a breast cancer diagnosis (51 deaths [0.05% per year] vs 31 deaths [0.03% per year]; HR, 1.57; 95% CI, 1.01-2.48; P = .045) among women who received estrogen plus progestin compared with women in the placebo group.

Conclusions

Estrogen plus progestin was associated with greater breast cancer incidence, and the cancers are more commonly node-positive. Breast cancer mortality also appears to be increased with combined use of estrogen plus progestin.

Trial Registration clinicaltrials.gov Identifier: NCT00000611

Author Affiliations: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California (Dr Chlebowski); Fred Hutchinson Cancer Research Center, Seattle, Washington (Drs Anderson and Prentice and Mr Aragaki); University of Cincinnati, Cincinnati, Ohio (Dr Gass); State University of New York at Stony Brook (Dr Lane); University of Pittsburgh, Pittsburgh, Pennsylvania (Dr Kuller); Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts (Dr Manson); Stanford Prevention Research Center, Stanford, California (Dr Stefanick); University of Massachusetts/ Fallon Clinic, Worcester (Dr Ockene); University of Wisconsin, Madison (Dr Sarto); University of Tennessee Health Science Center, Memphis (Dr Johnson); University at Buffalo, Buffalo, New York (Dr Wactawski-Wende); Cancer Therapy and Research Center (Dr Ravdin) and University of Texas Health Science Center (Dr Schenken), San Antonio; Wayne State School of Medicine and Hurtzel Hosptial, Detroit, Michigan (Dr Hendrix); Baylor College of Medicine, Houston, Texas (Dr Rajkovic); Albert Einstein College of Medicine, New York, New York (Dr Rohan); and University of California at Davis, Sacramento (Dr Yasmeen).

[gdpawel]

It is being said by some, what is being (erroneously) disseminated in the media is the following message: “Not only does prolonged use of hormone replacement therapy raise the risk of breast cancer, new research finds, but it also ups the risk for more severe forms of the disease and increases a woman’s chances of dying.”

This most recent Women's Health Initiative paper only looks at (1) breast cancer mortality and (2) all cause mortality after a diagnosis of breast cancer. It does not report all cause mortality. Therefore, it cannot be stated that HRT “increases a woman’s chances of dying.”

Risks and benefits must be individualized. Thin post menopausal women, with physically active lifestyles, non-hyperdense breasts, low to negligible alcohol consumption, lack of family history, negative mammograms, low fat diets, no tobacco use, low risk of coronary artery disease, and severe osteopenia are at high risk for high lethality hip fractures, but at low risk for breast cancer, lung cancer, and thromboembolic disorders. Might not the risk benefit ratio of lower dose, transdermal HRT be favorable?

The use of HRT is attributed not only to breast cancer. The risk of non-small cell lung cancer was cited as a possible complication of HRT. But the "absolute" magnitude of risk was very small and was not close to being significant in the case of never smokers.

Oestrogen plus progestin and lung cancer in postmenopausal women (Women's Health Initiative trial): a post-hoc analysis of a randomised controlled trial

Journal of Midwifery & Women's Health Volume 374, Issue 9697, Pages 1243-1251 (10 October 2009)

Background

In the post-intervention period of the Women's Health Initiative (WHI) trial, women assigned to treatment with oestrogen plus progestin had a higher risk of cancer than did those assigned to placebo. Results also suggested that the combined hormone therapy might increase mortality from lung cancer. To assess whether such an association exists, we undertook a post-hoc analysis of lung cancers diagnosed in the trial over the entire follow-up period.

Methods

The WHI study was a randomised, double-blind, placebo-controlled trial undertaken in 40 centres in the USA. 16608 postmenopausal women aged 50–79 years with an intact uterus were randomly assigned by a computerised, stratified, permuted block algorithm to receive a once-daily tablet of 0·625 mg conjugated equine oestrogen plus 2·5 mg medroxyprogesterone acetate (n=8506) or matching placebo (n=8102). We assessed incidence and mortality rates for all lung cancer, small-cell lung cancer, and non-small-cell lung cancer by use of data from treatment and post-intervention follow-up periods. Analysis was by intention to treat.

Findings

After a mean of 5·6 years (SD 1·3) of treatment and 2·4 years (0·4) of additional follow-up, 109 women in the combined hormone therapy group had been diagnosed with lung cancer compared with 85 in the placebo group (incidence per year 0·16% vs 0·13%; hazard ratio [HR] 1·23, 95% CI 0·92–1·63, p=0·16). 96 women assigned to combined therapy had non-small-cell lung cancer compared with 72 assigned to placebo (0·14% vs 0·11%; HR 1·28, 0·94–1·73, p=0·12). More women died from lung cancer in the combined hormone therapy group than in the placebo group (73 vs 40 deaths; 0·11% vs 0·06%; HR 1·71, 1·16–2·52, p=0·01), mainly as a result of a higher number of deaths from non-small-cell lung cancer in the combined therapy group (62 vs 31 deaths; 0·09% vs 0·05%; HR 1·87, 1·22–2·88, p=0·004). Incidence and mortality rates of small-cell lung cancer were similar between groups.

Interpretation

Although treatment with oestrogen plus progestin in postmenopausal women did not increase incidence of lung cancer, it increased the number of deaths from lung cancer, in particular deaths from non-small-cell lung cancer. These findings should be incorporated into risk–benefit discussions with women considering combined hormone therapy, especially those with a high risk of lung cancer.

Funding

National Heart, Lung and Blood Institute, National Institutes of Health.