Good Science, Bad Conclusions

Sometimes you are taken a bit by surprise. When that happens to me, I have learned the real "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 welcome news.

They are saying that this is due to a single 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.

The researchers who presented this abstract are "top drawer," and highly regarded in the research and medical communities. I do not dispute their methods or their findings.

I am concerned about how those findings have been reported by the media, and the implications of the various expert sound bites that may not be putting the whole story into its proper perspective.

Let's take a moment to examine what the researchers reported. The researchers looked at data collected from 1990 through the end of 2003 on breast cancer incidence. We know that from 1990 through 1998 there has been an increase of 1.7 percent per year in the number of breast cancer cases diagnosed. From 1998 until 2003, there was actually a decrease averaging 1 percent per year.

What was striking in the research was that in 2003 alone, there was a decrease of 7 percent 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 50s, 60s and 70s (11 percent, 11 percent and 7 percent declines, respectively) and in women with hormone-positive tumors. The authors conclude that the decline could be due to the 2002 publication of a study demonstrating the risks of hormone replacement therapy (HRT) that led many women to stop HRT involving estrogen and progesterone.

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."

But there is another wrinkle in the picture that hasn't been considered in this discussion.

When my colleagues here at the American Cancer Society reviewed similar data this past summer, they were concerned that the news was not altogether good, and that the drop might have something to so with mammography use having stabilized and perhaps decreased.

In a report in the medical journal Cancer Epidemiology Biomarkers and Prevention, researchers point out that we may actually be diagnosing fewer cancers, explaining at least some of the drop (about one-third of it).

So what does all of this mean? I, for one, have a real concern that what we may be seeing is not necessarily a rosy scenario.

Please do 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 diagnosis, which in turn means a poorer outcome.

Here are my concerns:

We were already seeing a slight decrease in the number of breast cancers year to year before the 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 the decrease. Examples could be fewer mammograms in general and in particular for the increasing number of uninsured or under-insured 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 percent 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 attended several of their meetings and 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 to 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 18, 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 that there is indeed some positive benefit from the decreased emphasis on combination HRT, which years from now will 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 percent of breast cancers in some of the post-menopausal women have suddenly disappeared or 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 receiving mammograms.

We recommend that a woman at average risk aged 40 and over should have a mammogram and clinical breast examinations annually.

If you are a post-menopausal women who either stopped taking hormones or never took hormones, please do not delude yourself into thinking that 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 make for your health.

Dr. Len Lichtenfeld is deputy chief medical officer of the American Cancer Society. Read a longer version of this commentary, as well as comments on other ongoing cancer news, at his blog.

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