Dr. Len's Cancer Blog

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Dr. Len's Cancer Blog

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Some Thoughts While Traveling

by Dr. Len April 27, 2007

My travels over the past several days have taken me to a number of cities to participate in various meetings and speak before several groups on the topic of cancer care and cancer prevention.

 

Although the schedule has been a bit hectic, it has provided a number of opportunities to reflect on a variety of issues that are important to me personally and may be of interest to you as well.

 

This week I spoke at the annual meeting of the Oncology Nursing Society in Las Vegas (where there is still smoking on the casino floor, by the way.  See my prior blogs for additional comments on this particular topic).

 

I gave a lecture at one of the sessions on the high costs of cancer drugs. I couldn’t avoid the opportunity to reflect with those in the audience on how far this profession has come over the past 35 years since I first began my training and practice in clinical oncology.

 

When I started my own practice in Baltimore in 1977, there was no such specific designation as an oncology nurse.

 

Certainly there were nurses who cared for cancer patients.  But when it came to medical oncology in the community hospital, there was no cadre of specially trained nurses to draw from.

 

On the hospital side, I was able to find some nurses who were interested in caring for cancer patients and recruited them to staff the fledgling unit we established in the hospital.  It took some effort to have my colleagues and others understand that the in-hospital administration of chemotherapy and the inpatient care of cancer patients in active treatment required special nursing expertise that was simply beyond the usual knowledge and practice of the typical RN.

 

The concept of cancer nursing care took hold, and the unit grew.  The nurses took pride in their work, and were compassionate in their care.  Other members of the support staff joined in, and when we made rounds we were joined by social workers, physical therapists, and dietitians among others.  Even the housekeeping staff became part of the team.

 

Back then, that type of specialization was unique in oncology circles in community care.  Now, it is standard and routine. Many of the wonderful nurses and others who are part of the cancer treatment team have no knowledge of what it was like when we started.

 

Much of cancer chemotherapy care is now provided in the office.  Again, back in the mid-1970s, there were nurses who worked in the outpatient areas of major cancer centers.  But there weren’t nurses trained to provide that same care in private oncology offices like mine.

 

So we started from scratch.  First one and soon thereafter a second nurse and then a third nurse joined my practice as we ventured into unknown territory.

 

My patients and I will forever be indebted to those wonderful people who helped get my practice off the ground.   We made an effort to establish an academic level outpatient practice, devoted to quality oncology care including participation in clinical trials through university affiliations.  My nursing colleagues made it happen.

 

We learned a lot in those early days, including how to mix the drugs and care for the patients in a community setting.

 

A lot has changed in cancer care over the past 35 years. There are now thousands of oncology nurses, many of whom are certified.

 

What has not changed is the fact that these wonderful, devoted people are so committed and so caring for our patients.

 

As I mentioned at my presentation this past Tuesday, there isn’t a forum I participate in where the focus is on cancer care where the topic of cancer nursing and its value and importance to cancer patients isn’t discussed in the most glowing terms.

 

Doctors treat and doctors prescribe.  Nurses care every day.  Their patients know their value, and are grateful for their compassion. I am grateful to have had the opportunity to share my appreciation personally with those in the audience.

 

On another topic, last week I attended the annual meeting of the American College of Physicians in San Diego.

 

During that meeting, I attended a lecture on breast cancer diagnosis and prevention offered by a professor from a medical school in Chicago.

 

What interested me about this presentation was a quick poll of the physicians in the audience to see how many of them were aware of the Gail score and used the Gail score in the routine management of their female patients.

 

The Gail score, you may recall, is one of several measures that provides information to a woman about her potential risk of developing breast cancer over the next five years and her lifetime.

 

It takes into account a number of factors, including age, family history of breast cancer, personal history of breast biopsy, and other considerations.  It is the foundation of making a recommendation to a woman that she is or is not a candidate for possible preventive treatment for breast cancer with tamoxifen or raloxifene.  These treatments have the potential of reducing the incidence of breast cancer by 50% in women who have a 5 year risk of 1.66% or greater.

 

The reality is that, despite the enthusiasm of many experts in the cancer community, this is a treatment recommendation that has not gone far in the general medical community or among women at risk.

 

The experts keep saying that the reason for the underwhelming acceptance of this prevention option is that women and their doctors fear the side effects of the drugs.

 

That may well be the case, but I don’t completely agree.  In my personal opinion, the issue is more fundamental. 

 

The sad reality is that primary care doctors (including gynecologists) simply don’t know much about assessing breast cancer risk and the options available to reduce that risk.  They simply don’t incorporate this knowledge and recommendation as part of their routine care processes.

 

If we are ever going to make progress in this area, we are going to have to rethink how we educate women and their physicians about breast cancer risk, and what options are available to reduce that risk when it is elevated.

 

Getting back to the lecture, in response to the quick poll on whether doctors knew their own Gail score and determined it for their patients, few hands went up.  Most of the attendees in this lecture were primary care internists and the response supported my own impression (which doesn’t necessarily mean I am correct).

 

How we address this issue is important, especially since the experts tell us that millions of women are candidates for medical treatment that can significantly reduce the numbers of breast cancers diagnosed in this country every year.

 

(By the way, there is now a controversy going on in the medical community regarding the funding for the next clinical trial on reducing breast cancer risk which would compare the benefits of aromatase inhibitors to raloxifene.  A major national cooperative clinical trial group designed the trial and received multiple approvals, only to have funding turned down by the National Cancer Institute at the last minute.  That matter is now receiving intense scrutiny, but the final decision has not been made.)

 

Wednesday found me in Secaucus, NJ spending some time with my Cancer Society colleagues from our Eastern Division which covers New York and New Jersey.

 

What struck me about this meeting is that there are some pretty special folks who work for the American Cancer Society and help us to achieve our mission nationwide and internationally.

 

I have the privilege of working in our national home office in Atlanta.  The group I met with Wednesday represent the people who are actually responsible “on the ground” for dealing with communities, constituents, businesses and others in their particular area of responsibility.  They are the ones who “make it happen” for patients who need services in their communities.  They are the people who have helped make Relay for Life such a success.

 

Their level of caring and commitment to their clients and their communities is what makes the Cancer Society mean so much to so many.

 

I feel blessed and privileged to work for an organization which is filled with people who share that commitment.  Many of my colleagues get little recognition for what they do every day. 

 

Throughout this Society, there are people who look at their daily efforts as much more than a job to pay the bills.  There is a level of commitment to a cause that is palpable, and this commitment influences everything they do. 

 

I suspect there are many people who read this blog who have been touched in some way by their efforts and also appreciate on a very personal level what it means to know there are people who care to help, and help to care.

 

A final thought as I sit in another meeting in Chicago is how to travel well and stay within some reasonable healthy limits when it comes to taking care of yourself “on the road”.

 

I suspect I am not alone in having problems with traveling for business and fitting in some personal time for eating properly, exercising, and just basically taking care of yourself.  The demands of business travel are substantial, and I find too frequently that it is difficult to stick to my own standards while I travel.

 

I find myself now packing various protein bars, liquid concoctions of different types, and even the latest addition: packaged tuna fish all intended to try to keep my personal eating habits on track.

 

At least I am trying to avoid the bad stuff, but I can tell you I am not always successful.  The temptation of the breakfast buffet is overwhelming.  The excitement of eating properly at the dinner buffet is a rare moment of meeting the challenge.

 

Traveling through the airport in search of something healthy to eat is frequently a futile exercise.  They sure don’t make it easy. 

 

To provide an example of how little it takes to make me happy these days,  I was thrilled to find a nice chef salad—with all the right stuff and not too much of the bad stuff—at a pizza outlet, of all places.

 

It is difficult enough to take care of yourself, your diet, your exercise and your basic health when you are in your own home.  Avoiding the sauces, the fries, and the extras they put on your food when your travel is a test of commitment, to say the least.

 

So to those of you who share my concerns and try to do the right things for yourself while you are moving about the country and perhaps the world, my sympathy and understanding. And, my kudos and congratulations if you are successful in keeping your commitments. 

 

It is certainly an uphill battle.

 

 

Filed Under:

Breast Cancer | Cancer Care

The New Prostate Cancer Test: A Major Advance?

by Dr. Len April 26, 2007

An article in the current issue of Urology illustrates some of the hopes and barriers related to advancing our abilities to diagnose prostate cancer accurately through screening tests, at the earliest possible time.

 

This particular article reports information about a prostate cancer protein found in the blood called EPCA-2.

 

The research, performed at Johns Hopkins in Baltimore—which is recognized as one of the leading prostate cancer treatment and research centers in the world—demonstrates that this new marker appears to be more sensitive and specific in detecting prostate cancer compared to the widely used PSA test.

 

But the question remains whether or not this is a major advance in the screening and diagnosis of prostate cancer.

 

The problem with the PSA test—which the article notes has been around and widely used for over 25 years—is that although it does detect prostate cancer through a fairly simple and routine blood test, it nonetheless is not particularly specific for prostate cancer.  That means that it frequently picks up other prostate conditions such as benign, or non-cancerous, enlargement of the gland.

 

Another issue with the PSA test is what is normal and what is abnormal in terms of the PSA level in the blood.

 

We used to say that a PSA value on the blood test that was less than 4 was OK.  More recent research suggests that even lower levels can be associated with prostate cancer.

 

When assessing a “normal” PSA, the doctor should be considering the age of the patient and the change in the PSA value over time.  This change in value is called PSA velocity.

 

What that means is that if a young man (for this discussion that would be someone in their 40s or early 50s) has a PSA of 2, that may be abnormal, while a PSA slightly over 4 in an 80 year old man may not be of much concern.

 

Or, if a man has a PSA of 0.7 one year and 2.0 the next year, his doctor should have heightened concern that prostate cancer may be present, and the man should be further evaluated—even though the PSA value is less than the “normal” 4.0 cutoff point.

 

It would be great if we had another simple test that helped solve some of these problems, and allow us to focus in on those men who actually have prostate cancer as opposed to doing further investigations and evaluations on many men who don’t have prostate cancer.

 

After all, these tests are not simple, inexpensive or painless.   They involve rectal ultrasounds, biopsies discomfort and risk, and even then they can miss a prostate cancer if the biopsy doesn’t “hit” the cancer when it is performed.

 

The researchers report in this current study that their new test is in fact more accurate in diagnosing prostate cancer, and it may also distinguish whether the prostate cancer is still in an early stage when it is confined to the prostate gland, or if it is more advanced when it has broken through the capsule that surrounds the gland.

 

The next logical question is whether this test is really as good as it seems.  And, if it is in fact a major advance, you might be asking how soon the test will be available.

 

The answer to the first question is “hopefully.”  The answer to the second question is that we don’t know.

 

Frequently when these types of papers appear in the literature, there are great claims made that the new test is a major advance and many folks get very excited about them.

 

I was recently reminded of such a circumstance when a colleague of mine asked my opinion about how to handle an inquiry from someone who contacted us, very upset that we were not promoting an early detection test for ovarian cancer called Ovacheck.  The caller apparently derided us for not promoting the test that was initially reported in a major medical journal in 2002.

 

What the caller did not know is that the FDA subsequently had questions about the accuracy of the test, and apparently other investigators had difficulty confirming that the test in fact measured the protein pattern that was supposedly diagnostic for ovarian cancer.

 

It is that type of experience that makes one very cautious in interpreting similar research reports.

 

To the credit of the authors of the current report, they have made it very clear in their article that this is simply a preliminary report of a newly discovered protein-based test.  They commented that the test itself was “tested” on highly selected patients, and was not evaluated in a typical setting where the doctor is actually screening a man for prostate cancer.

 

Establishing the value of this test, therefore, must be done in the context in which the test is going to be used.  That will mean many men who do not have prostate cancer will have the new test done side-by-side with the standard PSA test.  Then, the researchers will look at the outcomes of both tests in comparison with each other.

 

If the new test is in fact more accurate than PSA, then it will be a major advance.  But, we must always bear in mind that it may not show value in the subsequent “real life” evaluation. 

 

The fact is that we simply don’t know today, based on this initial report, whether or not this test is going to be better, as good as, or even worse than PSA testing when it is put into a clinical trial.

 

Another example that comes to mind—and this in no way a reflection on the quality of this particular prostate cancer research—was the media excitement that occurred in January of last year when an obscure medical journal reported on the ability of dogs to sniff breath samples and predict with a high degree of accuracy which samples came from a patient with cancer. 

 

This story even resulted in my appearing on the Today show to explain the importance of this discovery. 

 

What I said was that although this seemed interesting, it certainly wasn’t definitive.  But I couldn’t completely dismiss the report. 

 

This had not been the first report of a similar finding in a major medical journal (in another report, the dogs were able to detect bladder cancer in a urine sample).  Maybe what the dogs were detecting was an organic volatile compound that our sophisticated laboratory tests were not yet able to detect.

 

But I pointed out that the real value would only come if this could be applied to large numbers of people to detect cancer at an early stage.  That would be an entirely different type of study, and to date I have not been aware that any such research has been reported.

 

Trying to find cancer through a blood test has been an area of research interest for many years.

 

We have actually had other tests besides the PSA test that have been used in monitoring cancer patients for some time. 

 

Some of those tests include the CEA test used to monitor colorectal cancer patients, and CA-125 which has been used to monitor patients with ovarian cancer.  This latter test has also been promoted as an early detection tool for ovarian cancer, but it is not used regularly in that setting except perhaps for some women at particularly high risk.

 

So, the EPCA test reported here is new, but it is not alone.  There are many researchers seeking protein markers in the blood that may lead us to screen and diagnose cancer at the earliest possible moment.

 

I have heard experts say that within the next decade we will have methods available which will incorporate nanotechnology, and will allow us to take a drop of blood, put it on a chip, send it to the lab, and diagnose disease long before a doctor could find evidence of that disease by more standard clinical tests.

 

Other experts have reported research where they can monitor levels of a cancer-related protein called VEGF in rats, and pre-treat those animals before a cancer tumor can be clinically detected.

 

So to me, what this new report represents is an exciting opportunity that may impact medical care in the future.

 

If the clinical research which will undoubtedly follow this report produces positive results, it will certainly help us direct our attention to men who have a greater likelihood of having prostate cancer, instead of the more non-specific approaches we have today with the less sophisticated PSA test.

 

But we can’t diminish the value of the PSA test in apparently helping to reduce deaths from prostate cancer, and we still need to prove that the new test is in fact better than the older PSA test. 

 

(One needs to be careful here, because many experts are not yet convinced that the PSA test in fact has been responsible for the reduction in prostate cancer mortality.  Other very knowledgeable experts have long been of the opinion that in fact it is clear that the PSA test has been primarily responsible for the reduction in deaths from this disease that we have seen over the past decade.)

 

So, as with so many other exciting developments I have discussed in this blog, we still have a way to go to really understand how much impact this new test will actually have on the diagnosis of men with prostate cancer.

 

We are simply not there yet.

What Caused The Sudden Decline in Breast Cancer?

by Dr. Len April 18, 2007

In December 2006 I discussed a paper presented at a national breast cancer meeting in San Diego which reported that there had been a dramatic decrease in the incidence of breast cancer between 2002 and 2003.

 

At the time, the authors indicated they thought the decrease was due to the fact that women had stopped taking their hormone replacement therapy medications in 2002 in response to a warning from the Women’s Health Initiative (WHI).  This large, nationwide study reported that combined hormonal replacement therapy (HRT) with estrogen and progesterone in post-menopausal women increased a woman’s risk of developing breast cancer.

 

My response was that I wasn’t so certain that stopping HRT was the complete explanation for the observed decrease in breast cancer cases.

 

Now, with the publication of a more detailed paper in the current issue of the New England Journal of Medicine, I must admit that I am still confused as to all the factors that contributed to the decline.

 

Like any puzzle, this one may yet turn out to have many complexities that have to be solved before we get to the conclusion.

 

In doing an analysis of breast cancer cases reported in SEER registries—which monitor cancer incidence, stage and mortality in nine regions of the United States, and which are thought to reflect the incidence of cancer throughout the country—the authors of the New England Journal article found that in 2003 the incidence of breast cancer in the United States fell by 6.7% compared to 2002. 

 

The decrease in breast cancer diagnoses began in mid-2002, coincident with the publication of the major report from the Women’s Health Initiative on July 17, 2002.  The article, published in the Journal of the American Medical Association, concluded combination hormone replacement therapy increased a woman’s risk of developing breast cancer (see previous blog posting for more details of this report).

 

To bolster the case that this decrease in breast cancer cases—which appears to have leveled off in 2004 according to the SEER analysis—the authors were able to determine that the decline was present only in women age 50 and older (and therefore menopausal), and that the decline was limited to cancers which were estrogen-receptor positive (suggesting they hormones could accelerate their growth).

 

The total decrease in incidence, when comparing 2001 to 2004, was 8.6% which is certainly very dramatic.

 

Some additional important information was that the decrease was equivalent in women ages 50-69 and women age 70 and older.

 

The authors note—as also previously reported in this blog—that from 2000 to 2003 there had been a 3.2% decrease in mammography rates in this country.   They further comment that as a result of women stopping their hormone therapy, they may see their doctors less frequently and that this too could have resulted in decreased adherence to a yearly screening mammogram schedule.

 

A final consideration that they considered to explain the decline was the fact that, like prostate cancer, there may come a time when fewer breast cancers will be found since many had already been discovered through mammography and early detection.  

 

More simply, with effective screening, there should eventually be a decrease to a lower steady state incidence rate.  However, the researchers indicated they thought that this was not a likely explanation for the current observation.

 

All of these comments are well taken, appropriate and backed up by evidence.  

 

Nonetheless, the authors caution, it is still possible that this is a temporary observation and that at some time in the future, the incidence of breast cancer may once again increase.

 

Looking at the data, it is hard to ignore the relationship between the date the initial hormone study and editorial about the dangers of HRT appeared in the Journal of the American Medical Association (July 17, 2002) and the beginning of the decline in the incidence of breast cancer.

 

As reflected in the data in the current report, it is almost uncanny how the incidence of breast cancer began to decline in the third quarter of 2002, which would encompass July, August and September.

 

Although I was a skeptic that so many women stopped taking their hormones so quickly, maybe I was wrong in my assumption.

 

After all, as pointed out in the paper, 61 million prescriptions were written for hormone replacement therapy—both combination pills with estrogen and progesterone, and pills that contained only estrogen (for women who have had a hysterectomy)—in 2001, 47 million in 2002, and 21 million in 2004.

 

That implies that by 2004, only about 1in 3 women continued taking HRT compared to 2001 (this simplistic analysis doesn’t take into account the number of women who started taking HRT during that time).

 

My “resident expert” on gynecologic matters (my wife, who is a gynecologist and deals with these issues every day) indicated that these numbers reflected her own practice’s experience in terms of how long it took for the decrease in hormone use to run its course.  (That’s not very scientific, but an anecdote from time to time is acceptable in a blog like this.)

 

However, the key point here is that when the HRT paper came out, it only dealt with women who were taking a combination replacement therapy, not estrogen alone.  The recommendation to stop taking HRT was limited in that July paper and editorial to those women on the combination therapy.  A similar recommendation was not made for women on estrogen alone, since that study was ongoing at the time.

 

The current paper doesn’t tell us how many of the women who stopped their HRT therapy were taking the combination pill (the one that increased breast cancer risk) compared to those who were taking the estrogen-only medication. 

 

In fact, the estrogen-only arm of the study was continued and eventually reported that the women with a hysterectomy who took estrogen alone and were at average risk for developing breast cancer had a lower incidence of breast cancer when compared to women who took a placebo (or dummy pill).

 

In addition, the actual increased risk of developing breast cancer for women taking combination HRT compared to those taking a placebo was modest, about 8 additional cases of breast cancer each year for every 10,000 women taking the medication.

 

That amounts to about 0.8% fewer cases of breast cancer in a group of 10,00 women who theoretically were all taking combination hormonal therapy under the conditions of the WHI study (where, by the way, not every woman who was supposed to take the medication continued it for the duration of the study).

 

In 2001, the last year before HRT became suspect, the incidence of breast cancer in women age 50 and older in the 9 SEER registries was 38.3 cases/10,000 women.  This rate fell to 33.8 in 2003, which is about 12% lower over that 2 year period of time.

 

(Another note: these data—as reported on the SEER website—are incomplete and do not accurately reflect the latest information, which apparently was available to the authors but has not yet been posted on the web for public view. It takes several years for the complete data to “trickle in,” allowing for delays in reporting.)

 

When you consider that not every woman took hormone pills, and that not every woman stopped her hormone pills, and finally that not every woman was taking the combination pill, you end up with an implied impact of stopping combination hormonal therapy on the risk of getting breast cancer that is nothing short of amazing.

 

Looked at another way, one would have expected even greater declines if every woman had stopped her medication.

 

And, yet, that’s not what the data from the WHI study suggested would happen, as noted above. That information suggested that, in real life with all of the considerations just noted, there would have been a less than 0.8% decline in breast cancer incidence if, in fact, combination HRT caused the breast cancers that "disappeared."

 

(One factor not considered in this discussion is that the increase in breast cancer incidence in the WHI study started only several years after women started taking HRT.  It is plausible that if the women had continued the medication for many more years that their risk of getting breast cancer may have increased much more than that observed in the study.)

 

I will be the first to admit that I am not an epidemiologist, nor is this a scientifically rigorous discussion.

 

But this is not the first time that there has been a dramatic decrease in breast cancer incidence in the SEER registries.

 

In 1999, the incidence rate of breast cancer per 100,000 women age 50 and older in the United States was 395.  In 2000, it was 378, a decrease of 17 cases per 100,000 women, or about 4.4%. 

 

Much of this decrease appears to be due to a decrease in the incidence of breast cancer in black women age 50 and older, where the rate fell from 336 to 304.6, a decrease of 9.4%.  In 2002, however, the rate of breast cancer in black women once again went up to 330.

 

From 2002 to 2003, a significant decrease in breast cancer incidence occurred in white women age 50 and older, where the rates went from 392.3 to 352.4, or a decline of 11.2%.  (But, once again, I need to remind you that this may not be the latest, most complete set of data.)

 

When you look at the data over several years in women age 50 and older, what you begin to see is that there are fluctuations from year to year.

 

As the authors point out in their article, and as I mentioned previously here in the December blog, changing hormonal environments by the addition or withdrawal of hormones such as estrogen can influence the course of breast cancer.

 

For example, a long forgotten therapy for the treatment of pre-menopausal women with recurrent breast cancer was oophorectomy, or the removal of the ovaries.  The goal was to substantially reduce the amount of estrogen in the body.

 

Before tamoxifen, when I was in the early years of my training and practice, this procedure was routinely used with occasionally excellent results in treating these young women.

 

If my memory serves me right, I recall some of the surgeons I worked with advising pre-menopausal women who were diagnosed with primary breast cancer to consider an oophorectomy as part of their initial treatment.  This was prior to the tamoxifen era, which began in the mid-late 1970s.

 

We also know that in women who are at particularly high risk for breast cancer (carriers of the genetic abnormalities called BRCA 1 and 2), oophorectomy after completion of childbearing can decrease their risk of breast cancer.

 

In the midst of what must be to you, the readers, a bunch of confusing information, rests the real question of what is going on here.

 

Based on past experience, it is not unexpected that withdrawing a supplemental hormone pill may influence the rate of breast cancer.

 

It is hard to ignore the timing of the 2002 JAMA article and the resulting decrease in the number of breast cancers diagnosed in 2002 through 2004.

 

The problem in this “immediate decrease” scenario is that we know breast cancer takes many years to become detectable on a mammogram, and even more years to become palpable during a clinical examination. 

 

It is unlikely that a cancer present in the breast suddenly disappears immediately or within months after hormones are stopped.  That just doesn’t make sense.  But that is one implication of this report.

 

A more likely scenario is that stopping hormones influenced the diagnoses of breast cancer in this situation, but are not responsible for causing most of the breast cancers that would have been expected between 2002 and 2004 and were not diagnosed.

 

We do know that hormones such as estrogen can influence the growth of breast cancer tumors.  Perhaps there is some decrease in the size of a breast cancer after combination hormone therapy was stopped.  But the likelihood of it going away completely, or simply stop growing forever, is biologically remote.

 

What else could explain this decrease in breast cancer incidence?

 

A factor which may play a role is the documented decrease in mammography rates.  If you don’t look for a breast cancer, you won’t find it.

 

Maybe women are less likely to visit their doctors since they no longer have to get their prescriptions.  If they don’t visit their doctors, they won’t hear the recommendation to get their annual mammogram.

 

Perhaps, as one reader pointed out in a comment on this blog, now that women are no longer taking hormones they mistakenly believe their risk of breast cancer has gone way, way down.

 

Or perhaps this is a statistical fluke, which we have seen before in these same registries—although not necessarily to the same degree—in years past, when HRT was not the major highlighted cause.

 

Maybe it is all of the above.

 

My sense is that in fact the decrease in the use of combination hormone therapy did contribute to this decline in breast cancer diagnoses, but does not account for the entire picture.  The decline is simply too much too fast for me to believe that stopping combination HRT is the sole cause for this observation.

 

I also noted that this decline occurred equally in “younger” post-menopausal women and “older” post-menopausal women. 

 

My sense is that the use of hormone replacement therapy was less frequent in women over 70 than in women in their 50s and 60s.  That said, given the fact that rate of breast cancer is higher in women in their 70s when compared to younger women (the major risk factor for breast cancer, after all, is getting older), it may be that even a slight decrease in the number of 70+ year old women taking HRT may show a large impact in reducing the rate of breast cancer detection in that age group.

 

Even if stopping HRT explains almost all of this decline, it still could well be a temporary situation.  If that is the case, once the cancers regain their footing we will see them grow once again.  And that means we will see an increase in the numbers of diagnosed breast cancers in the years ahead.

 

If the decline in mammography has any role in this observation (and I believe it does) and if women aren’t going to their doctors for their regular check-ups (which may be the case) then we are headed for a serious problem in the not-too-distant future.

 

A recent report gives rise to further concern. 

 

Once the WHI study was released, there was a storm of criticism from the gynecology community regarding the data analysis and the fact that the participants in the study were generally older post-menopausal women, and not those who are starting to have menopausal symptoms.

 

When the data was recently reanalyzed for younger post-menopausal women, the investigators found that when HRT was started closer to  the onset of menopause, the risk of cardiovascular disease was reduced.  Risk of stroke, however, was still elevated.  (Breast cancer risk was not part of the new analysis.)

 

What that means is that we may find more women willing to start HRT to treat menopausal symptoms soon after they enter menopause than has been the case for the past several years.  That, in turn, might further blur our understanding of what is happening as we analyze breast cancer data in the years ahead. 

 

(The basic advice remains that women should use these medications for symptomatic treatment only, at the lowest dose for the shortest time possible.)

 

As I said at the beginning, the good news here is that the incidence of breast cancer is declining.

 

But the answer to the puzzle eludes us.  We may have some of it solved, but there are those among us who believe the rest of story remains to be written.

 

 

 

 

 

 

 

Senator Fred Thompson and Indolent Lymphoma

by Dr. Len April 11, 2007

News today that Presidential candidate and former United States Senator has been treated for indolent lymphoma adds to the visibility and impact of cancer diagnoses and treatment in the current Presidential campaign.

 

First, we wish Senator Thompson well in his journey with his illness.  He is another example of how people with cancer continue to live their lives with vigor and expectations. 

 

As with the recent announcements from Elizabeth Edwards and Tony Snow, we once again see someone who is determined to move forward with life despite their illness, just as millions of people surviving cancer do every day in this country.

 

The American Cancer Society estimates there will be 63,190 cases of non-Hodgkin lymphoma diagnosed in the United States in 2007.  An estimated 18,660 people will die from this disease.  The International Lymphoma Classification Project estimates that about 22 percent of lymphomas are of the follicular variety, the one most likely associated with Senator Thompson’s illness.

 

Not all non-Hodgkin lymphomas are the same.  Some are more aggressive, some less so.  Some can be treated for cure; others are less responsive.  In one particular paradox, treatments for the less aggressive lymphomas are less likely to result in cures.  That said, these lymphomas are usually associated with long survivals.

 

Many patients who are diagnosed with this lymphoma have no symptoms and are otherwise healthy.  This is one of the situations where doctors frequently advise no treatment for the disease.

 

Some patients, such as the Senator, opt for treatment for various reasons, including personal choice, or perhaps because they have decided to participate in a clinical trial.

 

No matter the choice of no treatment or treatment, it is clear that initial treatments in this disease should be the least compromising and toxic as possible, in order to preserve the most serious treatments for possible use in the future when they may be most needed.

 

This type of approach is indeed consistent with the usual natural course of the disease and accounts for the use of the term “indolent” in describing the Senator’s current situation.

 

Our thoughts and prayers go out to the Senator, and we applaud him for making his situation known to the public. 

 

By doing that, we once again are reminded of the ubiquity of cancer in our lives.

 

Because of our investments in research and better understanding of how to treat cancer, we know that cancer patients now have the opportunities to look forward to vigorous, involved, and committed lives.

 

I want to add an additional comment about survival statistics in this disease, since it will inevitably come up in many of the news reports regarding the Senator's illness.

 

If you go to the American Cancer Society Cancer Facts and Figures 2007, you will see a statistic that the five year survival for non-Hodgkin lymphoma is about 63%.

 

As was the case with Elizabeth Edwards, this number has no meaning in Senator Thompson's situation.

 

The published five year survival number is a compilation of data of all types of lymphomas, from the most indolent to the most aggressive.  As noted above, follicular lymphomas comprise about 22% of that number, so their impact on survival statistics is modest.

 

Senator Thompson, based on the information released today, has an excellent outlook given the type of lymphoma he has and the apparent characteristics of that lymphoma at the time of his diagnosis.

 

I am reminded of a young lady I treated when I first started my practice in Baltimore.  She was a hospital employee and one of my first patients.  She was very special to those who worked with me in my practice (as were many of our patients), and was always grateful for the life she was granted.

 

This young lady had a follicular lymphoma.  We treated it occasionally with mild chemotherapy and she did well.   When I left my oncology practice about 12 years after I first saw her, she was still doing well, working everyday, enjoying her life, and committed in her faith.

 

A small piece of paper she handed me on day remains on my desk blotter to this very day.  When I become frustrated or distraught, I still look at that note she gave me many years ago.  It says, "Thanks to you I am doing fine."

 

I must admit that I cannot take the credit for her success.  I was able to make cautious treatment decisions because that is what her illness warranted.

 

My hope and that of many others is that Senator Thompson will also do fine, just like my patient in Baltimore (who, by the way, was the rule and not the exception).

 

No matter where we stand in the political spectrum, we are all enriched by our diversity whether it be our cultural differences or our political opinions.

 

These fine people who are in the policitical limelight share a common illness but do not share political viewpoints. 

 

Together they represent the spectrum of our politics, our culture, and now the commonality of our lives.

 

We wish them--and all of the cancer survivors who share the same experience of their illnesses--the very best that life can offer.

Mammograms Still Count For Women In Their 40s

by Dr. Len April 04, 2007

I returned from vacation this past Monday to a slew of headlines and media commentary about newly released guidelines from the American College of Physicians suggesting that women in their 40’s should reconsider the routine recommendation for screening mammograms in that age group.

 

The headlines were very specific, such as “Benefits of Mammography For Women In 40s Challenged” (Washington Post) and “Mammograms Under 50 Optional for Many Women: Group” (Reuters).

 

A press release from the College noted that the guidelines were evidence-based and advised women to become part of the decision making process.  The risks of mammography included “false-positive results, possible treatment for lesions that would not have become clinically significant, and radiation exposure.”

 

I have waded through the three articles and an editorial that comprised the report in the current issue of the Annals of Internal Medicine, and I am wondering if the media—and some of the experts who have been quoted—have actually read the articles. 

 

On top of that, I doubt that many have taken the time to actually look at the data in the United States, which has shown a clear decline in mortality from breast cancer in women in their 40’s since the early 1990’s.

 

Let me note at the outset that I have what some may say is a conflict of interest in writing this particular blog. 

 

First, and foremost, I am (obviously) employed by the American Cancer Society.  What you probably do not know is that I manage the department in the Society that is responsible for developing our various guidelines on the prevention and early detection of cancer.

 

I am also very active—and proudly so—in the American College of Physicians, the organization that authored this guideline (although I had no role whatsoever in the publication or review of this guideline).

 

Let’s try to take a look at these articles and see what they say.

 

First, there is an article on the long-term effects on women who have a false-positive mammogram.

 

This issue has always been of serious concern to those who have studied the pluses and the minuses of screening for breast cancer.  In fact, it is a matter of serious concern when discussing screening for any cancer where early detection has been effective, including prostate, cervical and colorectal cancer.

 

Very important in this discussion is the definition of a “false-positive” result.  It can be as simple as having someone come back for more x-ray views of the breast after a screening mammogram.  It can be as complicated as recommending a breast biopsy of a suspicious breast lesion which turns out to be negative.

 

The article is too long for me to summarize here, but when I read it I was struck by the fact that the authors, after having set out the potential issues surrounding a false-positive mammogram, really couldn’t substantiate a significant, large negative impact on women who had a false-positive mammogram.

 

The results of the various studies they reviewed were mixed, and sometimes contradictory.  Some theories were advanced, but no overwhelming evidence that false-positive mammograms were serious detriments to the health and well-being of most women.

 

The authors conclude, “Some women with false-positive results on mammography may have differences in whether they return for mammography, occurrence of breast self-examinations, and levels of anxiety compared with women with normal results.  Future research should examine how false-positive results on mammography affect other outcomes, such as trust and health care use.”

 

The editors’ interpretation of this article said, “False-positive mammograms may have persistent small effects on some women’s psychological well-being and behavior.”

 

To me, there are no earth-shattering findings here.  It is about what one would expect, and is not really different from what patients deal with whenever the doctor suspects something may be wrong, and that supposition turns out (fortunately) to be incorrect.

 

The next article in this series was a systematic review of the scientific literature regarding screening mammography in women 40-49 years of age.

 

The authors note that “breast cancer is one of the most common causes of death for women in their 40s…Of the 44,000 women who die of breast cancer each year, less than one-fifth received their diagnoses between the ages of 40 and 49 years.”

 

They also note that “more than 98% of women will not develop breast cancer between 40 and 50 years of age.”

 

If one follows that logic, we should make clear that for women age 50 and over, 90% will never develop the disease.  And, by the way, the highest incidence of breast cancer occurs in women who are over 70 years of age.

 

There is never a “good” time to be diagnosed with breast cancer.  But for women in their 40’s who are diagnosed with this disease, the potential years of life lost are substantial.  That is many, many years as a mother, sister, daughter, wife and friend.

 

So, while the numbers may be smaller, the impact may be much greater.

 

The authors of this paper also noted that they were going to limit their analysis to the benefits and risks of screening mammography in women age 40-49. 

 

Why, you might ask?  Why did they deliberately choose not to examine the question of whether or not mammograms in this age group saved lives?

 

The answer: “Currently, 8 published metanalyses discuss the effect of mammography screening in women 40-49 years of age on breast cancer mortality rates.  All but 1 demonstrate a reduction in mortality rates from screening mammography.”

 

The researchers go on to comment about the quality of various mammography screening trials, and as has been noted by many authors previously, there are pros and cons to many of those trials.

 

They do note that the reduction in death rates from a screening mammography program takes several years to occur.  That means that the benefit women see in reducing deaths from breast cancer in their 50s begins with screening in their 40s.

 

The article states, “Although the precise contributions of screening in women 40-49 years of age and screening after a woman turned 50 years of age are difficult to determine, several analyses suggest that the most benefit is attributable to screening when women are between 40 and 49 years of age.”

 

The authors conclude, “In summary, the body of evidence indicates that women who undergo screening mammography between 40 and 49 years of age are less likely to die of breast cancer than women who do not undergo screening mammography, although the magnitude of the effect is smaller than that among women 50 years of age or older.”

 

Again, to me, no surprise here either.  Their conclusion is reasonably straight forward.

 

The study goes on to discuss a number of other issues, including whether screening actually results in less disfiguring or less aggressive treatment, and the risks of mammography including radiation induced cancer (no conclusive evidence that mammography increases the risk of cancer), overdiagnosis of cancers that would never cause a problem for a woman during her lifetime (a known fact), false positive test results (They do occur.  This study says, “Overall, these studies found that false-positive mammograms were associated with a small increase in generalized anxiety and depression during the evaluation period, which resolved quickly after the evaluation was completed.”),   false reassurance that a negative mammogram might lead a woman to delay seeking medical attention for a newly found lump in the breast (in one study it did, in the other it wasn’t clear), and pain from having a mammogram (well known, and frequently discussed by women who have had a mammogram).”

 

The article goes on to note that women who have a family history of breast cancer are more likely to have a breast cancer detected by screening.  Again, no surprise here either.

 

What was surprising to me was the failure to note that most cases of breast cancer—including women in their 40s—are what we call “sporadic,” that is they occur in women who do not have a strong family history of the disease.

 

The study also mentions the Gail model as a measure of a woman’s risk for developing breast cancer.  But (and this is an important “but” as you will see later in the paper) the authors also note that this model of breast cancer risk—which is widely used by experts in this field, along with other models—is better at predicting the risk of breast cancer in a population of women as opposed to an individual woman.

 

Despite all of this discussion, this paper concludes that women in their 40s who undergo mammography “will increase their risks of undergoing unnecessary procedures, breast cancer-related anxiety, discomfort that the time of screening and exposure to low-dose radiation.”

 

But a reading of the data in the article does not necessarily support these conclusions, as you can see from the quotes provided.  Perhaps the most salient comment of this paper is regarding the risk of false positive results in younger women because of their generally higher rate of dense breast tissue.  Most experts agree that that is a problem.

 

Many of these issues are also applicable to older women as well.

 

But here is what I think is the most disconcerting statement in the article:

 

“Given this difference (in risks and benefits for screening mammograms in women between 40 and 49), a woman 40-49 years of age who had a lower-than-average risk for breast cancer and higher-than-average concerns about false-positive results might reasonably delay screening.  Measuring risks and benefits accurately enough to identify these women remains a challenge.” (Emphasis mine)

 

I would suggest you read that last sentence very carefully.  As you will see below, if you are a woman between the ages of 40 and 49, you are going to be told in these guidelines to understand the risks and benefits of mammography before you make your decision.

 

That, in and of itself, is not a bad thing.  You should always understand the risks and benefits of any medical procedure.

 

The danger here is that you are being told you can “reasonably delay screening” based on a risk assessment that is, according to the article itself, imperfect.  In addition, the experts don’t have the data to tell you what you should do based on that risk assessment.

 

In other words, right is the “right” level of risk where you should be concerned?

 

Now, for a discussion of the guideline itself.

 

The guideline makes 4 distinct recommendations:

 

1) In women 40-49 years of age, clinicians should periodically perform individualized assessment of risk for breast cancer to help guide decisions about screening mammography.

 

That would be ok, up to the point about making a recommendation for screening mammography.

 

Women should know their risk of breast cancer.  There are preventive strategies and additional tests that might be useful if a woman is at high risk, especially if she is in her 40s.  The reality is that today doctors and patients do not discuss this.  Too little time, and frankly too little knowledge.  This has been a known problem for many years, especially now that we have medications which can reduce the risk of breast cancer in some women at high risk.

 

But to determine whether or not to get a mammogram?  The guideline is absolutely silent on what the authors consider an “acceptable” risk to recommend a mammogram.

 

Once again, they point out the limitations of the Gail model as it applies to an individual woman.

 

I am not aware of any study that has looked at a risk-based model to back up this recommendation.  In short, there is no evidence to support the conclusion that this is an effective breast cancer screening strategy

 

The practical implication is that this information without evidence-based guidance leaves both you and your doctor without any basis for a recommendation whether you should have a mammogram, in accordance with these guidelines.

 

 

2) Clinicians should inform women 40 to 49 years of age about the potential benefits and harms of screening mammography.

 

Not a bad idea.  There are benefits and harms to this procedure.  There are benefits and harms associated with every screening procedure.  You should know the answers.

 

3) For women 40-49 years of age, clinicians should base screening mammography decisions on benefits and harms of screening, as well as on a woman’s preferences and breast cancer risk profile.

 

Here, the authors advise women and their doctors that “women who are at substantially lower-than-average risk for breast cancer or who are concerned about potential risks of mammography may derive a less-than-average benefit from screening mammography.”

 

It is true that women who have lower than average risk may have a less than average benefit from mammography, if only we could accurately measure that risk.  But, once again, that doesn’t mean you won’t get breast cancer since most women who develop breast cancer don’t have many risk factors.

 

As to the other risks of the procedure itself, there is nothing—absolutely nothing—to suggest that if you are concerned about the pain of the procedure or a false positive result that those concerns are going to reduce your risk of getting the disease.

 

4) We recommend further research on the net benefits and harms of breast cancer screening modalities for women 40-49 years of age.

 

Again, this seems somewhat common sense.

 

Recent reports on the use of MRI in the screening of women at high risk (and with increased breast density) address some of these concerns, and pending research on the use of ultrasound will provide additional helpful information.

 

Ultimately, we need to develop even better methods of diagnosing breast cancer earlier.

 

The authors state that they agree that the data show a reduction in mortality, but there remains a statistical possibility that the benefit may not be much in this age group. 

 

Respectfully, I would note that others disagree.

 

Highly regarded organizations including the American Cancer Society, The American College of Obstetrics and Gynecology, and the United States Preventive Services Task

Force all recommend screening mammography for women ages 40-49.

 

The reality is that much of the research that forms the basis of these articles was performed many years ago, and no longer reflects current state of the art practice.

 

And, unfortunately, the research on which these guidelines are based cannot take into account the role of our current medical legal system as it influences the recommendations that doctors make about follow-up studies if they see anything suspicious on a mammogram. 

 

And they don’t take into account the access to care issues and availability of radiologists who dedicate their practice to mammography which in turn influences the quality of the interpretation of mammograms.

 

The final comment by the authors of the guideline?

 

“Assessment of an individual woman’s risk for breast cancer is important because the balance of harms and benefits will shift to net benefit as a woman’s baseline risk for breast cancer increases, all other factors being equal.  For many women, the potential reduction in risk for death due to breast cancer associated with screening mammography will outweigh other considerations.”

 

How your doctor is supposed to interpret that statement and make a rational recommendation to you as a woman seeking advice is, regrettably, not obvious to me.

 

The editorial which accompanied these articles echoes some of the same comments I made previously.

 

Here are some examples:

 

“To implement the ACP guideline in clinical practice requires negotiating major challenges.  First, the guideline recommends individualized assessment of breast cancer risk, yet the science of predicting breast cancer risk is extremely inexact.  Current tools to quantify risk (such as the Gail model) can distinguish among large groups of women with different levels of risk, but they do not help to distinguish an individual woman who will develop breast cancer from a woman who will not.  While such factors such as family history of breast cancer, breast density, and genetic mutations may help identify women at increased risk, most women with diagnosed breast cancer have none of these risk factors.”

 

“Outpatient encounters are typically too brief for an adequate assessment of individual risk or for a complete discussion of the benefits and potential harms of mammography.  Moreover, numerical literacy is often insufficient for meaningful communication of risk.”

 

Having delved into these articles and these discussions, I found myself asking what to me was the logical question: 

 

“If experts have had these raging discussions about the potential benefits and risks of screening mammography in women between 40 and 49 years of age, what does the data show?”

 

After all, mammography has been around for a while.  We should know whether or not it works.

 

Maybe that is a simplistic question, and maybe I am just not smart enough to be able to accurately interpret the numbers.  But let me take a stab at answering the question.

 

The SEER database has information on the incidence and mortality of cancer in this country, beginning in the 1970s.

 

According to SEER, the mortality rates from breast cancer in women between age 0 and 49 from 1994 to 2003 declined an average of 3.4% a year (white women fared better than black women, for reasons that have been discussed many times in other blog postings).

 

During this same time frame, the incidence of breast cancer declined by 0.13% per year.

 

Obviously, deaths declined much more than new cases.

 

Five year survival for women ages “0” to 44 was 75% in 1975-79; it was 85.1% in 1995-2002.

 

Five year survival for women ages 45-54 in 1975-79 was 76.6%.  In 1995-2002, it was 88.9%.

 

I don’t think this happened by chance, and I don’t think it happened by luck. Research has shown that mammography and improved treatments have contributed to this decline.

 

But my (honest) bias is that mammography has played a significant role in the decline of breast cancer deaths in this population of women at risk.

 

I remember the days before mammography.  We diagnosed “early” breast cancer that wasn’t early.  We diagnosed breast cancer that, in 1969, involved the axillary lymph nodes 40-50% of the time, and cancers diagnosed less than 2 centimeters in size were the exception and not the rule.

 

Mammography has changed much of that terrible scenario.

 

When expert organizations make pronouncements to the public, the public is looking for agreement and consistency.  They are looking for clarity of recommendations.  They want to know what they should do.

 

When we fail to deliver precise messages, we fail those who look to us for guidance.

 

When I reviewed these papers, as I have attempted to outline above, I tried to make some sense out of what we know, what we don’t know, what is different, and what is the basis of the difference.  I tried to seek some personal level of clarity that would help me understand the reasoning behind the headlines.

 

I didn’t find that clarity, and I didn’t find that guidance.  And, if I didn’t find it, I have difficulty believing the doctors in this country, much less the women who rely on them, will find it.

 

Perhaps worst of all, I don’t think the media found it.  And they write the headlines that will be remembered.

 

We are already seeing a decline in mammography in this country.  As I have noted previously, in my opinion, this may explain part of the decrease in the number of breast cancers being diagnosed in the United States.  If you don’t look for it, you won’t find it.

 

I don’t know for sure how all of this is going to turn out, but I have written previously that there is a possibility that several years from now we will start to see the fallout from this decline in mammograms. We will start to see an increase in the number of cancers diagnosed at a more advanced stage, and possibly an increase in deaths from this disease.

 

One of the factors I believe may be responsible for this turn of events is the confusing messaging that has been created as a result of certain studies.

 

I can only hope that the events of this week don’t add to that confusion, and provide some women an excuse not to do what needs to be done when it comes to their health.

About Dr. Len

Dr. Len

J. Leonard Lichtenfeld, MD, MACP - Dr. Lichtenfeld is Deputy Chief Medical Officer for the national office of the American Cancer Society.

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