Hormone Replacement Therapy HRT Does NOT Cause Breast Cancer, New Study
Estrogen Actually Prevents Breast Cancer
by Jeffrey Dach MD
In March 2012, a new study concluded that hormone replacement (HRT) with estrogen DOES NOT INCREASE RISK for breast cancer. This report appeared in Lancet Oncology and provided data on the 11.8 year follow up on the Women’s Heath Initiative Study which was originally published in JAMA in 2004. (1-4)
The Original 2004 WHI Report – 6.8 years of Follow Up
The original WHI study (second arm) enrolled about 10,000 women after hysterectomy. Half were given placebo, and the other half were given Premarin ( a horse estrogen) Premarin is also called CEE for Conjugated Equine Estrogen.
23% Less Breast Cancer
The original report in JAMA 2004 included 6.8 years of follow up showing 23% less invasive breast cancer in the Premarin treated group (also called CEE) compared to placebo group . There were 94 breast cancer cases in the estrogen hormone group (CEE) and 124 cases of breast cancer in the placebo group.
Less Heart Disease- Less Hip Fracture
In addition, there was 9% less heart disease, and 39% less hip fracture in the estrogen hormone treated group.
Problems With Blood Clots
The Premarin pill caused increased clotting (hypercoagulable state) resulting in increased stroke and pulmonary embolus in the Premarin Pill users, which caused early termination of the study. This is one reason why topical estrogen is preferable to pill form estrogen. Topical delivery of estradiol (bioidentical estrogen) does not cause increased coagulability, does not increase risk for CVA or stroke, is safer and the preferred delivery route.
11.8 years of Follow Up on the WHI Women – Still 23% Reduction
The original WHI group of women were followed for an additional 6 years, for a total of 11.8 years of follow up, and this data was reported in Lancet Oncology by Garnet L Anderson PhD, and Rowan T Chlebowski (3,4).
Here is what they found:
After 11.8 years of follow up, the Premarin (horse estrogen) had 151 cases of invasive breast cancer and the placebo group had 199 cases. This represents a 23% reduction in breast cancer in the hormone treated group. This was statistically significant. (P=.02) See below data chart (blue circle) for Figure 5 of the JAMA article.
Estrogen Group Had 63% Reduction in Mortality From Breast Cancer
In addition, in the estrogen hormone treated group, there was a 63% per cent reduction in death from breast cancer. 16 women died from invasive breast cancer in the placebo group, compared to only 6 in the hormone treated group.
Figure 5. Data Page from JAMA Study (click on image to enlarge):
The above image courtesy of Fig 5 Data Page for the 2011 JAMA report for the estrogen only WHI second arm. All age groups had a 23 % reduction in breast cancer (blue circle).
Editorial by Howell and Cuzick
In an editorial in the same issue of Lancet Oncology, the Drs Anthony Howell and Jack Cuzick review the findings and conclude that the benefits of estrogen HRT include:
1) reduced risk of coronary artery disease and reduced risk of heart attacks
2) Reduced Risk of All Cause Mortality with improved survival numbers in the hormone treated group.
3) They advise women to avoid PremPro (the combined HRT pill ) which adds in a synthetic progestin, as the synthetic progestin IS associated with increased breast cancer.
Here is the quote fromDrs Anthony Howell and Jack Cuzick:
“Young women (50—59 years) taking oestrogen were significantly less likely to have coronary heart disease, myocardial infarction, and death from all causes, not only with respect to older women but also placebo controls of the same age. Observational and WHI studies agree on the increased risk of breast cancer with combined hormone replacement therapy (including a progestin). “…. “The WHI investigators should be congratulated for providing insight into the value of conjugated equine oestrogens and young women can be reassured of the low risks and potentially striking benefits,”
Chemical structure of Premarin (left) compared to Human Bioidentical Estrogen (right) courtesy of wikimedia commons:
Above Left Image: Equilin – Premarin (Horse estrogen CEE) Above Right Image:Human Estradiol
The NIH Should Study Human Bioidentical Estradiol and Progesterone
The WHI study showing the Estrogen reduces risk of breast cancer, reduces heart disease, reduces risk of hip fracture, and other and health benefits was done with Premarin, a horse estrogen.
You might ask the obvious question, “Why Did The Study Not Use Estradiol”, which is a human hormone (a bioidentical hormone)? Why use estrogen from a horse when human estradiol in available? The answer is obvious. The NIH is a branch of the government and the government is controlled by the Pharmaceutical industry which makes Premarin. We need the NIH to do studies for the benefit of the people, not the drug industry. We need to repeat the WHI study using estradiol and progesterone, and never again victimize women with the carcinogenic PremPro pill ( Premarin and Provera) which was shown to cause breast cancer and heart disease.
Bioidentical Hormones Are Safe and Do Not increase Risk of Breast Cancer
In retrospect, the Lancet Oncology findings have been known for decades. Bioidentical Hormone users are healthier and live longer than non-hormone users. Bioidentical Hormones do not cause increased breast cancer risk, and are associated with all the health benefits shown in the Women’s Health Initiative (second arm) for women using estrogen alone. Premarin is not human, but it is natural. A much more better HRT program is the combination of human bioidentical estrogen available as Bi-Est (Estradiol and Estriol), with the addition of Progesterone a human bioidentical hormone. This is the program we use in our office.
Articles with related interest:
Jeffrey Dach MD
7450 Griffin Road Suite 190
Davie, Florida 33314
Links and References:
2011 WHI Follow Up Study shows less breast cancer in homone users.
1) JAMA. 2011;305(13):1305-1314. Health Outcomes After Stopping Conjugated Equine Estrogens Among Postmenopausal Women With Prior Hysterectomy A Randomized Controlled Trial Andrea Z. LaCroix, PhD; Rowan T. Chlebowski, MD, PhD;et al for the WHI Investigators Health outcomes after conjugated equine estrogens postmenopausal women with hysterectomy LaCroix Andrea Jama 2011
Over the entire follow-up, lower breast cancer incidence in the CEE group persisted and was 0.27% compared with 0.35% in the placebo group (HR, 0.77; 95% CI, 0.62-0.95).
Original 2004 JAMA Report of Second Arm WHI
Effects of Conjugated Equine Estrogen in Postmenopausal Women With Hysterectomy The Women’s Health Initiative Randomized Controlled Trial ,The Women’s Health Initiative Steering Committee* by Garnet L. Anderson, PhD, WHI Clinical Coordinating Center, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, M3-A410, Box 19024, Seattle, WA 98109
5200 women CEE, 5200 placebo, with 7 year follow up
Cancer. Invasive breast cancer,
23% lower rate in the CEE group than in the placebo group (26 vs 33 per 10 000 person-years)
94 CEE 124 placebo and this comparison narrowly missed statistical significance (P = .06).
Results CEE vs placebo (average follow-up 6.8 years):
CHD, 0.91 (0.75-1.12) with 376 cases;
breast cancer, 0.77 (0.59-1.01) with 218 cases; (94 CEE and 124 placebo)
stroke, 1.39 (1.10-1.77) with 276 cases;
PE, 1.34 (0.87-2.06) with 85 cases;
colorectal cancer, 1.08 (0.75-1.55) with 119 cases; and
hip fracture, 0.61 (0.41-0.91) with 102 cases.
Editorial – JAMA. 2011;305(13):1354-1355.
Short-term Use of Unopposed Estrogen A Balance of Inferred Risks and Benefits by Emily S. Jungheim, MD, MSCI; Graham A. Colditz, MD, DrPH
Idiotic statement – the previously quoted studies used progestins.
“the reduced incidence of breast cancer persisted. This finding is inconsistent with a longstanding, corroborated body of evidence 7,8? and raises the possibility that other important factors modify documented risks and benefits of estrogen therapy among these long-term WHI participants. ”
WHI Follow Study Lancet Oncology
The Lancet Oncology, Early Online Publication, 7 March 2012
Conjugated equine oestrogen and breast cancer incidence and mortality in postmenopausal women with hysterectomy: extended follow-up of the Women’s Health Initiative randomised placebo-controlled trial
Prof Garnet L Anderson PhD, Prof Rowan T Chlebowski MD b, Aaron K Aragaki MS a, Prof Lewis H Kuller MD c, Prof JoAnn E Manson MD d, Prof Margery Gass MD e, Elizabeth Bluhm MD f, Prof Stephanie Connelly MD g, Prof F Allan Hubbell MD h, Prof Dorothy Lane MD i, Lisa Martin MD j, Prof Judith Ockene PhD k, Prof Thomas Rohan MBBS l, Prof Robert Schenken MD m, Prof Jean Wactawski-Wende PhD
Methods Between 1993 and 1998, the WHI enrolled 10,739 postmenopausal women from 40 US clinical centres into a randomised, double-masked, placebo-controlled trial. Women aged 50—79 years who had undergone hysterectomy and had expected 3-year survival and mammography clearance were randomly allocated by a computerised, permuted block algorithm, stratified by age group and centre, to receive oral conjugated equine oestrogen (0·625 mg per day; n=5310) or matched placebo (n=5429). The trial intervention was terminated early on Feb 29, 2004, because of an adverse effect on stroke.
(It is well known that oral estrogen pills cause hypercoagulable state and increased stroke risk)
Follow-up continued until planned termination (March 31, 2005). Consent was sought for extended surveillance from the 9786 living participants in active follow-up, of whom 7645 agreed. Using data from this extended follow-up (to Aug 14, 2009), we assessed long-term effects of oestrogen use on invasive breast cancer incidence, tumour characteristics, and mortality. We used Cox regression models to estimate hazard ratios (HRs) in the intention-to-treat population.
Findings: After a median follow-up of 11·8 years (IQR 9·1—12·9), the use of oestrogen for a median of 5·9 years (2·5—7·3) was associated with lower incidence of invasive breast cancer (151 cases, 0·27% per year) compared with placebo (199 cases, 0·35% per year; HR 0·77, 95% CI 0·62—0·95; p=0·02) with no difference (p=0·76) between intervention phase (0·79, 0·61—1·02) and post-intervention phase effects (0·75, 0·51—1·09).
In subgroup analyses, we noted breast cancer risk reduction with oestrogen use was concentrated in women without benign breast disease (p=0·01) or a family history of breast cancer (p=0·02).
In the oestrogen group, fewer women died from breast cancer (six deaths, 0·009% per year) compared with controls (16 deaths, 0·024% per year; HR 0·37, 95% CI 0·13—0·91; p=0·03).
Fewer women in the oestrogen group died from any cause after a breast cancer diagnosis (30 deaths, 0·046% per year) than did controls (50 deaths, 0·076%; HR 0·62, 95% CI 0·39—0·97; p=0·04).
Our findings provide reassurance for women with hysterectomy seeking relief of climacteric symptoms in terms of the effects of oestrogen use for about 5 years on breast cancer incidence and mortality. However, our data do not support use of oestrogen for breast cancer risk reduction because any noted benefit probably does not apply to populations at increased risk of such cancer.
Editorial in Lancet Oncology MArch 2012
The Lancet Oncology, Early Online Publication, 7 March 2012
Oestrogen and breast cancer: results from the WHI trial by Anthony Howell and Jack Cuzick
“Young women (50—59 years) taking oestrogen were significantly less likely to have coronary heart disease, myocardial infarction, and death from all causes, not only with respect to older women but also placebo controls of the same age. Observational and WHI studies agree on the increased risk of breast cancer with combined hormone replacement therapy (including a progestin). ”
“The WHI investigators should be congratulated for providing insight into the value of conjugated equine oestrogens and young women can be reassured of the low risks and potentially striking benefits,”
News Media – LA Times
Estrogen taken alone is linked to lower breast cancer risk by By Shari Roan, Los Angeles Times March 7, 2012
An analysis finds that women who took the hormone by itself after menopause had a reduced risk of developing breast cancer. ”’ Dr. Rowan T. Chlebowski, an investigator at the Los Angeles Biomedical Research Institute in Torrance and chief of medical oncology and hematology at Harbor-UCLA Medical Center.said : ”
Estrogen alone for the period we studied seems to be pretty safe and maybe even beneficial.” Researchers followed 7,645 women from the original group of almost 11,000 participants for almost five years to see what happened to them after stopping estrogen therapy. The study found that women who took estrogen had a 23% reduced risk of breast cancer compared with those who took a placebo. Among the women who did develop breast cancer, those who took estrogen had a 63% reduced risk of dying from the disease compared with those who took a placebo.
Internal Medicine News
Estrogen Protects Against Breast Cancer Long After Treatment By: MARY ANN MOON, Internal Medicine News Digital Network |
7) (link removed)
Estrogen-only HRT continues to protect women against breast cancer long after they have stopped March 6, 2012 in Cancer
Women who use the oestrogen-only form of hormone replacement therapy (HRT) appear less likely to develop breast cancer in the longer term, according to new research published Online First in The Lancet Oncology. A follow-up study of over 7500 women from the Women’s Health Initiative (WHI) trial who took oestrogen for about 6 years and then stopped has found that they are over 20% less likely to develop breast cancer and remain significantly less likely to die from the disease than those who never used HRT, a period of nearly 5 years after stopping treatment.
New York Times
Estrogen Lowers Breast Cancer and Heart Attack Risk in Some By TARA PARKER-POPE April 5, 2011,
Dr. Chlebowski previously led research that showed cancer risks associated with combination hormone therapy, but he says the new data on estrogen alone show that in certain women, estrogen use to relieve menopausal symptoms is a “good choice.”
Estrogen pills reduce breast cancer risk in study of menopausal women By CBS News Staff “Estrogen on its own appears to be safe,” said Dr. Anthony Howell, professor of medical oncology at the University of Manchester, who co-authored a commentary in the same issue.
My Response to New York Times Article by Tara Pope by Suzanne Somers 4/6/2011
This is my response to Tara Pope’s article yesterday in the New York Times. I have no idea if they will print my letter but I thought you’d like my perspective. Her article follows my response. Ms. Pope ignores the existence of biodidentical hormone replacement therapy.
11) Estrogen Lowers Breast Cancer Risk In Some Women By MARIA CHENG 03/ 6/12
Estrogen-Only Therapy May Reduce Breast Cancer Risk TUESDAY March 6, 2012 — Some women who take estrogen-only hormone replacement therapy to stave off hot flashes, night sweats and other symptoms of menopause may be at lower risk for developing breast cancer down the road, a news study says.
Study: Estrogen treatment may protect against breast cancer Posted on: March 8, 2012, by Nina Sparano, DENVER — Estrogen, a hormone known to fuel breast cancer, may actually protect against the disease. According to a new study women taking Hormone Replacement Therapy (HRT) are more than 20-percent less likely to develop breast cancer and had a reduced risk of dying from the disease.
More than 7,600 women taking HRT were studied. Women who took estrogen-only for six years and then stopped taking the hormone showed the reduced risk. The new study, published in the journal Lancet Oncology, provides the strongest evidence yet that estrogen alone not only lowers breast cancer risk for a sustained time for some women but curbs the chances of dying from the disease.
13) Broken link removed
Breast cancer risk reduced by estrogen-only hormone replacement therapy By Rachael Rettner, MyHealthNewsDailyTue, Mar 06 2012
Friday, March 9, 2012 Estrogen therapy helps reduce breast cancer risk in some patients Dr Susan Love
16) blog.dslrf.org/?p=497 Estrogen and Breast Cancer: It’s Complicated! The conventional wisdom is that estrogen causes breast cancer.
Estrogen After Hysterectomy Lowers Cancer Risk? Experts Say the Decision to Use Hormone Replacement Is a Still Complicated One By Brenda Goodman, MA WebMD Health News
Compared to women taking a placebo, women who took estrogen had a 23% reduced risk of invasive breast cancer. That means 151 women got breast cancer in the estrogen group compared to 199 women assigned to the placebo. Women taking estrogen also had a 63% reduced risk of dying from breast cancer compared to women on the placebo. Overall, there were six deaths in the estrogen group compared to 16 in the placebo group.
studies which show that estrogen causes breast cancer (????) They included progestin use which DOES CAUSE breast cancer….
Lancet. 1997 Oct 11;350(9084):1047-59.
Collaborative Group on Hormonal Factors in Breast Cancer .
Breast cancer and hormone replacement therapy: collaborative reanalysis of data from 51 epidemiological studies of 52,705 women with breast cancer and 108,411 women without breast cancer. Lancet. 1997;350(9084):1047–1059. (They used HRT which included synthetic progestins)
19) Steinberg, Karen K., et al. ” A meta-analysis of the effect of estrogen replacement therapy on the risk of breast cancer.” Jama 265.15 (1991): 1985-1990. The increase in risk was largely due to results of studies that included premenopausal women or women using estradiol (with or without progestin), studies for which the estimated relative risk was 2.2 (CI, 1.4 to 3.4) after 15 years. (Again progestins were included)
Million Women Study
Breast Cancer Risk in Relation to the Interval Between Menopause and Starting Hormone Therapy by Valerie Beral, Gillian Reeves, Diana Bull, Jane Green and for the Million Women Study JNCI J Natl Cancer Inst (2011) 103 (4): 296-305.
Among current users of estrogen-only formulations, there was little or no increase in risk if use began 5 years or more after menopause (RR = 1.05, Breast cancer risk was statistically significantly increased in users of estrogen-only hormonal therapy if use began before or less than 5 years after menopause (RR = 1.43, 95% CI = 1.35 to 1.51, P < .001), whereas if such use began 5 years or more after menopause, breast cancer risk was not increased (RR = 1.05, 95% CI = 0.89 to 1.24, P = .6). among current users of estrogen–progestin formulations (RR = 1.53 )
WHI First ARM – PREMPRO
Estrogen (premarin) plus Progestin (Provera –PremPro DOES CAUSE BREAST CANCER
21) JAMA. 2003;289(24):3243-3253 Influence of Estrogen Plus Progestin on Breast Cancer and Mammography in Healthy Postmenopausal Women – The Women’s Health Initiative Randomized Trial by Rowan T. Chlebowski, MD, PhD; et al for the WHI Investigators Influence of Estrogen Plus Progestin on Breast Cancer in Postmenopausal Womens Health Initiative Chlebowski Rowan T Jama 2003
Main Outcome Measures Breast cancer number and characteristics, and frequency of abnormal mammograms by estrogen plus progestin exposure.
Results In intent-to-treat analyses, estrogen plus progestin increased total (245 vs 185 cases; hazard ratio [HR], 1.24; weighted P<.001) and invasive (199 vs 150 cases; HR, 1.24; weighted P = .003) breast cancers compared with placebo.
The invasive breast cancers diagnosed in the estrogen plus progestin group were similar in histology and grade but were larger (mean [SD], 1.7 cm [1.1] vs 1.5 cm [0.9], respectively; P = .04) and were at more advanced stage (regional/metastatic 25.4% vs 16.0%, respectively; P = .04) compared with those diagnosed in the placebo group.
After 1 year, the percentage of women with abnormal mammograms was substantially greater in the estrogen plus progestin group (716 [9.4%] of 7656) compared with placebo group (398 [5.4%] of 7310; P<.001), a pattern which continued for the study duration.
Conclusions Relatively short-term combined estrogen plus progestin use increases incident breast cancers, which are diagnosed at a more advanced stage compared with placebo use, and also substantially increases the percentage of women with abnormal mammograms. These results suggest estrogen plus progestin may stimulate breast cancer growth and hinder breast cancer diagnosis.
2010 SABCS Interview with Rowan T. Chlebowski, M.D., Ph.D. discusses WHI Data
laura esserman breast cancer video sept 2011 mammography screening how can it help and what are its limitations. key is cancer biology. Beast cancer is not one disease
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