Sometimes you are taken a bit by surprise. When that happens to me, I have learned the "surprise" may not be what it appears to be.
Yesterday’s report from the San Antonio Breast Cancer Symposium that the incidence of breast cancer fell dramatically between 2002 and 2003 was one of those surprises.
Not that we weren’t aware that the incidence of breast cancer was either leveling off—or actually decreasing—but we were surprised at the magnitude of the change.
But what has me concerned is the rush to judgment by some experts and much of the media as to the explanation for this apparent welcomed news.
They are saying that this is in fact due to one factor: the decrease in the use of hormone replacement therapy.
I do not agree. There is something going on here that just doesn't add up.
Let me say at the outset that I have no argument with the researchers who presented this abstract or the quality of their research. They are “top drawer,” and highly regarded in the research and medical communities. I do not dispute their methods or their findings as they reported them from the San Antonio Breast Cancer Symposium.
I am concerned how those findings have been reported by the media, and the implications of the various expert soundbites that may not be getting the whole story into its proper perspective.
Let’s take a moment to examine what the researchers reported, then go from there to develop a bit of historical background and updating from other sources of information.
What they did in this study was examine information that is collected by a national cancer registry that closely follows people diagnosed with cancer in a number of communities in the United States.
This registry, called SEER, is considered the premier source of information on cancer incidence and mortality in the United States. Although it only samples a small number of locations throughout this country, the information it develops is considered representative of what is happening with respect to cancer incidence and mortality throughout the nation.
The researchers looked at data collected from 1990 through the end of 2003.
We know that from 1990 through 1998 there was been an increase of 1.7% per year in the number of breast cancers diagnosed every year. From 1998 until 2003, there was actually a decrease of 1% per year.
What was striking in the research was that in 2003 alone, there was a decrease of 7% in the incidence of breast cancer in that single year.
The authors note in their abstract that this decrease appeared to begin in early 2003, and accelerated later in the year.
The decrease was most notable, according to the authors, in women in their 50’s, 60’s and 70’s (11%, 11%, 7% declines, respectively). The decline was greater in women with hormone positive tumors, compared to those diagnosed that were not hormone sensitive.
The authors concluded in their report that this significant decline in breast cancer diagnoses could be due to the publication in 2002 of a study demonstrating the risks of hormone replacement therapy (HRT). They go on to say that, as a result, many women stopped their HRT containing estrogen and progesterone.
Now a bit of history.
The use and value of HRT, whether in combinations containing estrogen and progesterone or estrogen alone, has been controversial for many years. I can recall medical school lectures on the topic as far back as 1970, when we really didn’t know all of the benefits and risks of using HRT in post-menopausal women.
Over time, the use of HRT increased, supported in no small part by studies and beliefs that these treatments were beneficial to women in many ways.
We did learn that for women who still had their uterus after menopause the use of progesterone in addition to estrogens significantly decreased the rate of uterine cancer, while women who had hysterectomies could use estrogen alone since they no longer were at risk for uterine cancer.
Enter the Women’s Health Initiative.
I don’t have space here to go into all of the details of the study, some of which have been discussed in prior blogs. Suffice to say, it was a large study of post-menopausal women that studied many aspects of aging, including the effects of HRT, diet, calcium and more.
On July 17, 2002 the Journal of the American Medical Association published an article from the Women’s Health Initiative discussing the risks and benefits of combined HRT.
The study of COMBINED hormone replacement therapy had been stopped early, because the risks of treatment with hormones exceed the risk of not taking hormones. (I would emphasize that this increased risk was limited to the combined HRT—estrogen/progesterone—arm of the study. No increased risks were found in the estrogen only arm of the trial, and that study was continued at that time.)
The decision to stop the trial resulted from assessing a combination of risks, among them the increased risk of developing breast cancer.
The study showed a significant increase in the rate of invasive breast cancers, but not an increase in the risk of non-invasive breast cancers, commonly referred to as DCIS.
In an editorial that accompanied the JAMA article, the editorialists pointed out that based on the study they would estimate that for every 10,000 women taking combined HRT, there would be an additional 8 breast cancers each year.
If we flip that estimate around, what the authors are saying that there would be 0.8% fewer breast cancers each year if women on HRT had in fact not taken those medications (recall the increased breast cancers I mentioned previously, on the order of 11% per year in some age groups. And this is for all women in that age group, including those on combined HRT, estrogen alone, and no HRT).
The authors wrote in their editorial:
“The results of this study provide strong evidence that the opposite is happening for important aspects of women's health, even if the absolute risk is low. Given these results, we recommend that clinicians stop prescribing this combination for long-term use. Primum non nocere (Latin for “first do no harm”) applies especially to preventive health care.
The WHI provides an important health answer for generations of healthy postmenopausal women to come—do not use estrogen/progestin to prevent chronic disease.” (Emphasis mine)
I still recall the uproar in the medical community about this recommendation. Plain and simple, the implication was that any woman taking combined HRT should stop it immediately.
A lot of doctors didn’t agree, and a lot of patients didn’t agree either—the evidence notwithstanding.
Over the next several years, numerous experts dissected the results of the study and made several criticisms, which were widely shared in the medical community.
Today, when it comes to combined HRT, the recommendation is “as low a dose as possible, for the shortest time possible consistent with effective control of menopausal symptoms.”
More recently, another WHI report appeared indicating that, except for women at high risk, women who take estrogen alone for menopausal symptoms (that would be women who have had a hysterectomy) are not at increased risk of breast cancer, except if they have a family history. (You can read more about that paper in a past blog on this site.)
But there is another wrinkle in the picture that hasn’t been considered in this discussion.
My colleagues here at the American Cancer Society have been concerned for while that something unfavorable is happening with mammography.
We have been aware for several years that the number of radiologists who specialize in mammography has been decreasing, and that there are places in the United States where women have difficulty getting access to mammography.
In addition, with increasing numbers of women who are uninsured or underinsured, there has always been a much lower rate of mammography compliance.
Further, women are becoming complacent about getting their mammograms on an annual basis.
The result of all of this is that mammography rates have stabilized and perhaps been decreasing for any and all of the above factors.
The rate of mammography in this country has been good but not great, and there was already a considerable room for improvement.
Today, we must be concerned that the numbers of mammograms are actually decreasing.
Which brings me to my next point, and something that has been pointed out by my Cancer Society colleagues in their discussions on this topic: If mammography use has reached a peak and is now decreasing, we may actually be diagnosing fewer cancers when they can be most effectively treated. If you don’t get a mammogram, you don’t diagnose a cancer.
So what does all of this mean?
Here is my “take” on the situation highlighted by yesterday’s report. I can’t say it is based on detailed modeling or other great science, but it does reflect a real concern that what we may be seeing is not necessarily a rosy scenario.
Please to not misunderstand or misinterpret my motives when I make these comments. If we are actually seeing a dramatic decrease in the number of breast cancers, and it is real, then that is terrific news.
But if there are other explanations for this story, we may let our complacency drift into a much more serious situation a couple of years down the road resulting in an increase in the diagnosis of breast cancer, coupled with later stage of diagnosis which in turn means a poorer outcome.
Here are my concerns:
We were already seeing a slight decrease in the number of cancers year to year before the WHI study. This could be due to lifestyle changes or some other unknown factor, but when you consider that this country doesn’t appear to be getting healthier, that raises the concern that there may have been some other explanation for that decrease. Examples could be fewer mammograms in general and in particularly for the increasing number of uninsured or underinsured women, or perhaps because of decreased access to mammogram facilities.
The next consideration is that the paper in JAMA was published in July of 2002. The authors of the current abstract report that there was a 6% decline in the incidence of breast cancer, especially in post-menopausal women, in the first half of 2003.
I have been a doctor and around medicine a long time. I have never seen a circumstance where a journal publishes an article and there is an immediate adherence to the recommendation and an immediate effect six months later. That simply doesn’t happen.
The more likely scenario is that the article is read and publicized, it is reviewed by practicing physicians and their patients, and over time there is a gradual decrease in the use of the “offending” medication resulting in a benefit some years down the road.
Based on my personal observations, (my wife is a gynecologist, and as a result I have the opportunity to attend several of their meetings. I have listened to a lot of talks on this issue.) gynecologists by and large did withdraw many of their patients from combined HRT over time, but certainly they did not call their patients on the phone and say, “Stop your hormones immediately.”
Then there is the biology of the disease itself.
It takes many, many years for a breast cancer to develop and become identified on a mammogram, and years more for it to become palpable in the breast in most circumstances.
Even if every woman stopped taking their hormone pills on July 18th, there would still be many breast cancers that were already present in some stage of development.
I don’t think those cancers disappeared in the next six or twelve months. That simply defies rational thought.
What I suspect may have happened is that withdrawal of hormone therapy in some way affected the growth of those cancers, but they didn’t go away.
We do know that changes in the hormonal milieu can affect breast cancer progression.
Years ago, we used to do oophorectomies in young women with breast cancer, and saw dramatic results.
We also used to use estrogen to treat breast cancer, again with remarkable results.
We would even see improvements in some women with breast cancer who had been taking estrogens for the treatment of their breast cancer, when their disease progressed and we stopped their estrogens. Some of these women actually had regression of their disease when estrogens were withdrawn.
One of my professors at the University of Pennsylvania commented regularly that changing the hormonal environment—whether by addition or subtraction—was key to understanding the treatment of breast cancer.
Of course today we have medications that effectively treat breast cancer by blocking estrogens or significantly reducing the amount of estrogen in the body.
Unfortunately, I am going to have to take a wait and see attitude about what is going on here as a result of these new reports. I don’t believe we have the explanation in hand as to why the incidence of breast cancer dropped so dramatically in 2003.
I suspect that what we are seeing is a combination of factors, including fewer women getting mammograms which in turn means fewer breast cancers are being diagnosed.
I suspect there is indeed some positive benefit from the decreased emphasis on combination HRT, which years from now will in fact contribute to a true decline in the incidence of breast cancer.
I do not believe the sudden drop in breast cancer incidence is because 11% of breast cancers in some of the post-menopausal women have suddenly disappeared and no longer exist.
Which brings me to my concluding comments:
The greatest tragedy here is if women and their doctors become complacent about ordering and getting mammograms.
We recommend that a woman at average risk age 40 and over have a mammogram and clinical breast examination annually.
If you are a post-menopausal women who either stopped taking hormones or never took hormones, please not delude yourself into thinking you don’t need a mammogram.
If my contrarian viewpoint is correct, and that discontinuation of HRT simply slowed down the growth of breast cancers that already existed, then not getting a mammogram every year could be the worst decision you could make for your health.
