Archive for the ‘Breast Cancer’ Category

Estrogen Lowers Breast Cancer and Heart Attack Risk in Some

Wednesday, April 6th, 2011


Ron Wurzer for The New York Times Andrea LaCroix of the Fred Hutchinson Cancer Center in Seattle found that estrogen lowers breast cancer risk in some women.

In a finding that challenges the conventional wisdom about the risks of some hormones used in menopause, a major government study has found that years after using estrogen-only therapy, certain women had a markedly reduced risk of breast cancer and heart attack.

The research, part of the landmark Women’s Health Initiative study, is likely to surprise women and their doctors, who for years have heard frightening news about the risks of hormone therapy. But most of those fears are related to the use of a combination of two hormones, estrogen and progestin, which are prescribed to relieve hot flashes and other symptoms of menopause, and have been shown to increase a woman’s risk of breast cancer.

The new findings, reported Tuesday in The Journal of the American Medical Association, come from 10,739 women in the Women’s Health Initiative study who had previously had a hysterectomy, the surgical removal of the uterus. Nationwide, about one-third of women in their 50s have had a hysterectomy.

While other women in the study were taking combination hormone therapy, women without a uterus took estrogen alone or a placebo for about six years and were followed for nearly 11 years. The estrogen-only group was not given progestin, which is prescribed only to protect the uterus from the harmful effects of estrogen. Although all the women in the estrogen study stopped using the treatment in 2004, the investigators have continued to monitor their health, as is typical in large clinical trials.

The most surprising new finding relates to breast cancer. The women with hysterectomies who used estrogen alone had a 23 percent lower risk for breast cancer compared with those who had taken a placebo. This is in stark contrast to the higher risk of breast cancer shown in the estrogen-progestin part of the trial.

“The decreased risk of breast cancer in this group is something we totally didn’t expect when we started the W.H.I. hormone therapy trials,” said Andrea Z. LaCroix, the study’s lead author and a professor of epidemiology at the Fred Hutchinson Cancer Research Center in Seattle. “This study differentiates estrogen alone from estrogen and progestin in a very big way. I hope it gets across to women, because we are not reversing ourselves.”

Indeed, the investigators emphasized that the results do not change recommendations concerning combination hormone therapy for the two-thirds of menopausal women who still have a uterus. The Women’s Health Initiative data have consistently shown that the combination of estrogen and progestin raises breast cancer risk, and the treatment should be used only to relieve severe menopause symptoms, using the lowest dose for the shortest possible time.

An accompanying editorial in the journal was skeptical about the results, arguing that the design of the Women’s Health Initiative, which is skewed toward older women and stopped all forms of hormone treatment after several years of use, does not match the way doctors typically prescribe treatment to women in their 50s at the onset of menopause.

Dr. Graham Colditz, an author of the editorial and professor of surgery at Washington University School of Medicine in St. Louis, said he thought data collected from observational studies that show a higher risk of breast cancer associated with estrogen use were more reliable than the data gathered from the Women’s Health Initiative clinical trial.

“The finding doesn’t reflect how hormones are used in the U.S. at the moment,” Dr. Colditz said.

The trial has, however, been held up for years as the gold standard for medical research, and its findings linking combination hormones to breast cancer and heart problems led to significant changes in the way doctors around the world treated menopause.

A major caveat in interpreting the new estrogen data is that the study used conjugated equine estrogens, which are estrogen compounds derived from the urine of pregnant mares and marketed by Wyeth Pharmaceuticals under the brand Premarin. The brand has fallen out of favor with many women who are choosing treatments that contain estradiol, which is chemically similar to a woman’s natural estrogen. It is not known whether the benefits of estrogen shown in the Women’s Health Initiative would be replicated using a different type of estrogen.

Nobody knows why estrogen treatment alone appeared to lower breast cancer risk in the study, but one explanation may be that in menopausal women with low levels of natural estrogen, the effects of estrogen drugs induce cell death in existing tumors. Nobody is suggesting that women start using estrogen to prevent breast cancer, but the finding opens a potentially new avenue of research in the prevention of the disease.

“We need to look closely at these findings to see if we can learn more about ways to prevent breast cancer in women,” said Dr. JoAnn Manson, a Women’s Health Initiative investigator and an author of the study who is chief of preventive medicine at Brigham and Women’s Hospital in Boston.

In the estrogen-only group in the trial, use of the hormone was not associated with any significant risks or benefits pertaining to blood clots, stroke, hip fracture, colon cancer or overall death rates.

But there were surprising differences in the risks and benefits of estrogen use on heart risk when comparing the youngest and oldest women in the study. Women who were in their 50s when they first started using estrogen also had significantly fewer heart risks, including almost 50 percent fewer heart attacks, compared with those assigned to the placebo group.

The data indicate that for every 10,000 women in their 50s, those using estrogen would experience 12 fewer heart attacks, 13 fewer deaths and 18 fewer adverse events like blood clots or stroke in a given year, compared with those taking a placebo.

But the risks of estrogen use were pronounced in older women. For every 10,000 women in their 70s, using estrogen would cause 16 extra heart attacks, 19 extra deaths and 48 serious adverse events.

“The big message there is that the data look much more favorable for younger women and much riskier for older women,” said Dr. LaCroix.

Dr. Rowan Chlebowski, another author of the study and a medical oncologist at Los Angeles Biomedical Research Institute, said the findings underscore the fact that the risks and benefits of menopause hormones change depending on a woman’s health status, her age and the type of hormone used.

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.”

“When you look at the debate, people are saying hormones are good or not good – it’s been all or nothing. This calls attention to the fact that there are differences,” said Dr. Chlebowski. “I hope that separation will become clearer now.”

Breast Cancer Risk: Get the Facts then Take Action

Friday, January 28th, 2011

Ricki Pollycove, MD, MS

Your Watch Dog on Women’s Health

Shocking, fear inducing headlines scare us again today with the release of the sub-analysis from the Million Women study. The current breast cancer scare press release, “Breast Cancer Risk in Relation to the Interval Between Menopause and Starting Hormone Therapy” Valerie Beral, et al, Jan. 28, 2011, in The Journal of the National Cancer Institute. The authors give us a huge mass of data, including some non-significant trends in relative risk numbers which frighten us but are actually so small they are barely detectable differences. We need to insist on medical news providing us with absolute risk data when sharing information from clinical trials.

Crunching the numbers one arrives at a tiny absolute risk difference of 0.006 between the no-hormone therapy women and those who used HT of various types over 7.2 years in the million women study. In fact the numbers are so small that our FDA considers them very rare and not a significant individual concern. And if you are impressed by numbers, consider the average risk of breast cancer in American women, by age 80, is roughly 12.15%, [SEER data base] with rates of death from breast cancer much lower still (less than 2 % of us will die of breast cancer) as compared to the huge majority who suffer and will die from heart disease, with death rates approaching 50% in the first year after a heart attack. 267,000 women die each year from heart attacks, which kill six times as many women as breast cancer. Take a look at the information on the Women’s Heart Foundation web site and help motivate the sisterhood. [Women and heart disease facts ] .

What we need to focus on, what we can individually do a lot about, is lowering our risks for heart disease and breast cancer by attending to the factors that are known to increase or lower risk. To improve the health of women as we age let’s be proactive and do our diligence to pay attention to these quality of life lowering, death rate increasing health problems. To quote the past president of the North American Menopause Society, Cynthia Stuenkel, MD, UC San Diego School of Medicine, “…almost everything we do to care for women should be geared toward helping them live a healthier lifestyle that will ultimately lead to a healthier heart.” And the 2010 compelling review of hormones and the heart supports the role of judicious use of hormones early in the menopause if we are to make the greatest difference in keeping blood vessels healthy. [A “window of opportunity:” The reduction of coronary heart disease and total mortality with menopausal therapies is age- and time-dependent. Hodis HN, USC Keck School of Medicine, Mack WJ, Brain Res. 2010 Oct 25.] The sooner women support menopause with estrogen the lower the rates of blood vessel inflammation that cause heart disease.

The gorilla in the room is heart disease, with breast cancer a challenging threat to lowered quality of life, but not the death threat of cardiovascular disease. As much as breast cancer is prominent in our consciousness and circles of women friends, it is an infrequent cause of death. And there is something that we, individually and as a population of women at every age, can do to lower risk. To quote Howell A and Harvie M, “It seems likely that part of the marked increase in the incidence of breast cancer is related to increases in dietary calorie intake and reduction in exercise over the past century.” [Should lifestyle modifications be promoted to prevent breast cancer?] Same contributors to heart disease rates increasing. So the best thing we can do is to modify our lifestyles as younger women, avoiding obesity, lowering rates of breast cancer as well as significantly decreasing the heavy toll of heart disease.
Get the facts and cure your fears. We can live optimally healthy lives as active, engaged women. But we need to commit to healthy levels of activity, lowered fat nutrition, upping the fresh fruits and veggies and not smoking cigarettes, of course.

Hormone Breast Cancer Fear

Monday, November 1st, 2010

Many healthcare professionals have been asking for the opinions and/or responses of menopause experts to the recent JAMA article.

My comments echo those of my colleague, Dr. Alan Altman, as well as those of Wulf Utian, MD, founder and long-time executive director of the North American Menopause Society who recently stepped down from that post after 30 years.

  1. This is from the same WHI Study (2002) with one drug, Prempro, in one dose only, given to women average age 63.5 years with a body mass index (BMI) of 28.5 (significantly overweight) when the study began, age 68.5 years with the increased BMI of 30 upon its conclusion 5 years later (obese, a significant increase in risk for breast cancer). The wrong drug, in the wrong doses, to the wrong women. Yet misleadingly presented as if the results applied to the newly menopausal symptomatic women, which they do not.
  2. This study has absolutely NO impact on you if you are not taking Prempro! That means none of my patients are represented in this study.
  3. As the WHI has previously shown years ago, and repeated in this study, there is a very small increase in the risk of occurrence of breast cancer when taking Prempro, which as of late did not reach statistical significance (important detail to understand). This small increase was not seen in the Premarin (estrogen-only) part of the study. In fact, in the Premarin-only part of the study, regardless of their age, the women who were greater than 80% compliant with their use of the drug… meaning they took their dose as they were supposed to… had a statistically significant 23% decreased risk of breast cancer!
  4. This emphasizes once again that something about the progestin used in Prempro, called MPA, helped cause the small increase in breast cancer not seen in the Premarin-only arm. This has been shown in many other studies over the past 30 years:
    • estrogen alone = no increase in breast cancer risk, likely small decrease in risk
    • estrogen plus MPA = small increase in breast cancer risk (8/10,000 women years of getting diagnosed, 1/10,000 excess breast cancer death attributed to PremPro with 11 years of use shown in this current data set)

    This is another small but important reason why most clinicians do not use MPA (Provera brand name) any longer, and haven’t for some time (due to slightly adverse effects on risk markers for heart disease and a slight increase in breast cancer as well).

    Natural progesterone (brand name Prometrium) has NOT been shown to elevate risk for breast cancer when used with estrogen.

  5. The increase in the risk of death from breast cancer while taking Prempro compared to placebo, in this newest report, was one woman per 10,000 women per year…a level described as “extremely rare” by the FDA.
  6. Every study adds a piece to the big picture. The big picture emerges over time, with all ages of women, body types and life styles to create a deeper understanding of benefits and risks; the real associations or outcomes over time. Unfortunately, the media treats each piece as a compelling new revelation, creating confusion and potential for panic. In discussing this study, there has been little media attempt to put it into context so women can better understand the whole picture of risk vs. benefit of taking this drug or any other Hormone Therapy (HT) for menopause. Benefits of HT, shown in WHI and many other studies prior to as well as since WHI, in the appropriate women using the appropriate doses of the appropriate HT begun at the appropriate time, include a decreased risk of heart attack (by far the biggest killer of women each year), diabetes, osteoporotic fracture, colon cancer, and the risk of dying from any cause at all (total mortality). These potential benefits are above and beyond the symptom relief of hot flashes, joint pains, night sweats, sleep disorders, palpitations, headaches, low mood, low libido, vaginal dryness and pain with intercourse commonly associated with menopause. A watermelon sized benefit, a watermelon seed sized risk when prescribed appropriately.
  7. Within this context of risk vs. benefit, as with any medication or drug, a woman can properly discuss her own individual situation with her doctor or nurse practitioner and make educated decisions without the fear and panic that come from sensationalized news reports and media coverage.
  8. There is a growing body of data demonstrating that the use of non-oral estrogen, via patch, gel, or vaginal ring, is safer to use than estrogen pills by mouth, taking away the risk of blood clots, and stroke from blood clots, seen with the pills used in WHI, as well as other benefits.
  9. Talk with your clinician when time allows and remain confident that this “new” Prempro story is likely not to be of any meaningful significance to you. Your quality of life is very important and should be carefully addressed at all stages of your life. Over 50 years of excellent observational data on newly menopausal women in the US, Canada, Great Britain and Europe, billions of women years of use, are not invalidated by this or any other study.

Wulf Utian response

What is it about the WHI writing team that they can take data that they agree is not statistically significant, then reach the unjustified conclusion that with hormones as used in the WHI study, “breast cancer mortality also appears to be increased with combined use of estrogen plus progestin,” and finally through their lead author and others advise women that HT is really dangerous?

So what are the facts?

As with the initial publications, this longer follow up approximately 7 years after the original WHI EPT trial termination in July 2002, confirms a slight increase in incidence of breast cancer in women on combined continuous estrogen plus progestin therapy compared to placebo. Again, as in the first reports, there was a greater incidence of node positive cancers. The original reports confirmed no increase in overall all-cause mortality, but did not report separately on breast cancer deaths. At first blush, this paper would seem to be one leading to more banner headlines against use of postmenopausal hormone therapy, reporting that “breast cancer mortality also appears to be increased with combined use of estrogen plus progestin.” However, one needs to read the paper carefully. There were 25 deaths in the HT group and 12 deaths with the placebo. The HR (hazard ratio) was 1.96 which is almost a doubling of the relative risk (I can just see the headlines – HT doubles risk of dying in postmenopausal women). But the CI (confidence interval) was 1.00-4.04. This wide spread includes 1.00 which makes the difference NOT statistically significant. Hence their statement in their conclusions that mortality “APPEARS to be increased.” For this reason it is totally appropriate to look at the absolute risk. This turns out to be 2.6 vs. 1.3 deaths per 10,000 women per year. By the WHO CIOMS classification, even if this was statistically significant, the increased risk would be classified as extremely rare.

So what do I take away from this? Firstly, the combined continuous use of estrogen plus progestin (at least the products used in the WHI) have an adverse effect on the breast, slightly increasing both the incidence of BC and possibly the chance of dying from it. While this increased risk is rare, it is mandatory on health providers to try “to do no harm” (Hippocratic oath). Fortunately, the good news is that the same WHI investigators just reported at the Asia-Pacific Menopause Society meeting in Sydney that estrogen when administered alone appears to have the opposite effect. That is, they apparently reported that the E alone group had a lower incidence of BC and mortality from BC compared to placebo. I await that publication with interest (but where and when will WHI publish good news?).

Secondly, the NIH and their WHI Writing Group should finally come out with a revised “Global Health Index” targeted specifically at the 50-59 year old group of women because they are the most likely to suffer from severe hot flashes and be prescribed hormones. If benefit on heart, bone, colon, diabetes, and possibly brain is taken into account, the balance of benefit to risk is likely to be quite different from all their previous looks at that score.

The conclusion is therefore that at least the progestin (MPA – medroxyprogesterone acetate) used in the WHI study is not beneficial to the breast and may cause harm. Other studies appear to indicate that alternate progestins or progesterone used in lower doses and intermittently may be safer, but there are no other studies of the size of the WHI and never likely to be.

Bottom line is that after all the hullabaloo over the past 9 years since the initial termination of the HT arm of the WHI, estrogen turns out to be quite safe, the MPA has a cloud of suspicion, and the future recommendation is for careful assessment on an individual basis for every women transiting menopause to determine health status, future risk for disease, and a decision based on a clear indication whether hormones are truly needed and recommended in her situation. If the affirmative, then current knowledge should be used to determine what dose, type, and route of administration should be used.

The WHI has succeeded finally in showing that postmenopausal hormone therapy has clear risks and rewards. The risks are rare, and it is up to every women for herself to decide based on a transparent explanation to her about the facts.

May I conclude that there is no better source for her to get these facts in a clear and unbiased way than from the NAMS website at

NAMS response

Letter to Editor in response to Kantrowitz and Wingert (Newsweek 3/1/2010)

Tuesday, March 9th, 2010

As a women’s health physician, breast cancer advocate and author, it’s time we get solid information that encourages hormonal harmony, and doesn’t fan the flames of ill founded fear. Kantrowitz and Wingert offer us an erroneous cancer scare, an old theory recycled, contributing nothing of value. Women are victims of scare campaigns about breast cancer which are doing us harm. As noted in their article, invasive breast cancer rates started dropping in 1999, thanks to more regular mammogram screening, and other factors, some known and others undiscovered. This observed decrease was more than 3 years before women bolted from their hormone replacement therapy (HRT) due to exaggerated (and now we know, wrong) reports about breast cancer rates and estrogen use in menopause. To their detriment women have continued to decrease hormone use annually since the 2002 WHI reports, yet breast cancer rates have not continued to decrease. And in Holland (one of many examples) similar decreases in hormone use are not associated with any decrease in breast cancer incidence. Not exactly a validated hunch.

In fact the 2007 data from the Women’s Health Initiative, the WHI (the largest American study of thousands of menopausal women on PremPro® or Premarin® alone compared to placebo) when analyzed and corrected to reflect disease occurrence in those women who actually took the study pills, revealed no significant difference in rates of breast cancer between the women who took Premarin© and those who took the dummy pills. After 7+ years of taking estrogen-alone, estrogen users had 17% less breast cancer compared to women who took a sugar pill. And these estrogen-alone users wisely continue to take their pills to a much greater degree than the women on the combination therapy, PremPro and others like it. These confident women continuing on their estrogen contribute to the lower rates of breast cancer documented.

And what about the statistic that everyone agrees with? Cancer specialists, radiologists and primary care docs all know that women who are diagnosed with breast cancer while taking estrogen fair a lot better. This is a very significant effect when you look at death rates from breast cancer. Since 2000 most studies of women on estrogen show they have a lower risk of being diagnosed with breast cancer, especially if those with a uterus use bioidentical progesterone along with it. This is the most important information we have today if we are to decrease suffering with this all too common disease.

It is time we got it straight about estrogen NOT being the bad guy when it comes to breast cancer. In addition to lowering breast cancer death rates, estrogen has many positive preventive effects when begun for symptom relief during early menopause. Early estrogen therapy lowers the risks of heart disease, osteoporosis, colon cancer and dementia, as well as lowering breast cancer deaths. These are big benefits that are left out of the fear-engendering mis-information that keeps getting recycled. Taken correctly, estrogen offers a watermelon size benefit and a watermelon seed size risk.

Yours sincerely,
Ricki Pollycove, MD, MS
Author, “The Pocket Idiot’s Guide to Bioidentical Hormones,” 2010, Alpha Press
Founding Director for Breast Health CPMC Breast Center