No one likes the side effects of chemotherapy.  But would your attitude change if you knew that the side effects may predict success with your treatment for cancer?

A study in today’s issue of Lancet Oncology describes just such a finding in women with breast cancer treated with either tamoxifen or anastrozole as part of an adjuvant (preventive) treatment clinical trial. 

Women who participated in the trial had been diagnosed and treated for primary breast cancer.  In this study, the researchers examined the records of women who then received either anastrozole or tamoxifen to prevent the breast cancer from returning.

If a woman was treated with anastrozole or tamoxifen and developed vasomotor symptoms and/or joint pain after they started their medicine, then the chances that their breast cancer would return were lower than for a woman who did not develop either symptom.

The researchers can’t explain why this happened.  They suggested it may be related to a woman’s genetic profile and how her body processed the medications, but that isn’t for certain. 

The end result was that if a woman had vasomotor (usually called menopausal) symptoms, the chance that her breast cancer would return was decreased by about 16%.  If she developed joint symptoms, the recurrence rate was reduced by about 41%.  And, if she had both symptoms occur after treatment, the odds of recurrence were decreased by about 47%.

Both anastrozole and tamoxifen decrease the effects of estrogen in post-menopausal women with breast cancer, although they work differently. 

Tamoxifen is an estrogen blocker and blocks the impact of circulating estrogen on breast cancer cells in post-menopausal women whose cancers are hormone sensitive.  Anastrozole works by decreasing the amount of estrogen circulating in the body substantially.  (You may be surprised to learn that there is estrogen in women who are post-menopausal.  For example, fat cells in post-menopausal women are a source of estrogen.  A low level source to be sure, but a source nonetheless.)

In an interesting and thought-provoking comment, the authors note that “the occurrence of certain symptoms could be the ultimate bioassay, which might be a reflection of the degree of biologically relevant estrogen suppression produced in individual women by a specific treatment.”

This isn’t the first time a biologic response has been linked to positive treatment response in cancer therapy.

Shortly after cetuximab (Erbitux) was investigated in the treatment of advanced colon cancer, researchers were commenting that patients in the waiting rooms quickly picked up on the fact that a rash on the face was associated with a better chance of response.  The same effect was subsequently noted in patients treated with Iressa (gefitinib) and Tarceva (erlotinib), which are targeted therapies used in the treatment of lung and pancreatic cancer.

Years ago, back in the mid-1970’s, when tamoxifen was first made available for the treatment of women with metastatic breast cancer, I would not infrequently have women come to my office soon after starting this new medicine (it was revolutionary at that time because it was a pill, easy to take and generally free of side effects) complaining of bone pain.  Some of these women also had significantly elevated blood calcium levels.

Imagine reassuring a woman with significant pain that—based on your limited medical experience with this new pill—this was in fact a good sign, since it had meant in many other women who had developed those same symptoms that they responded to the treatment with improvement in their breast cancer. 

I went back into the medical literature this afternoon, and actually found an article from 1978 in the Journal of the American Medical Association that described this observation, and called it a “tamoxifen flare.”  It also confirmed my recollection that these women actually did well with respect to their cancer.

So, with all of the fancy tests we have to measure the impact of the drugs we use, it turns out that symptoms such as joint pain and hot flashes in a woman with breast cancer treated with a hormone-blocking drug may actually be a good sign that the drug is working.

Sometimes, our bodies are better indicators of our conditions than our science. 

That’s actually not a new observation, but it helps remind us that with all our knowledge we can’t measure everything with a lab test or x-ray. Listening to our patients still has value.

Just because it’s “natural” and looks like it might work to prevent cancer doesn’t mean it will work to prevent cancer.

That’s the message of today’s announcement from the National Cancer Institute and the Southwest Oncology Group (which is a national research group that does clinical trials in cancer) that they are telling the over 35,000 men participating in a prostate cancer prevention trial to stop taking their pills.

The study, called “SELECT” and which was started in 2001, was based on two earlier trials that found pretty much by accident that it appeared selenium and vitamin E decreased the incidence of prostate cancer. 

Both of those studies were designed to primarily look at cancers other than prostate cancer. One, in Finland, was done to see if vitamin E reduced lung cancer incidence and the other examined the impact of selenium on the incidence of skin cancer.  In both of the studies, there was tempting data that selenium or vitamin E unexpectedly reduced the risk of prostate cancer.

But those “accidental findings” didn’t hold up in a well-designed clinical trial.  Life is not always simple in medical research.

After 7 years, the results are in: An independent review board which monitored the SELECT trial found selenium and vitamin E—either alone or in combination—did not reduce the risk of developing prostate cancer.  In fact, there was a small but not significant increase in the incidence of prostate cancer in the men taking only vitamin E and diabetes in the men taking only selenium.

The result: men are being instructed to stop their pills, but will continue to be monitored for several years.

The theories that vitamin E or selenium can reduce the risk of prostate cancer have been around for awhile.   There were many men who already believed that vitamin E and selenium could reduce the risk of prostate cancer.  But, once subjected to critical study through a randomized clinical trial—the gold standard of medical research—we find the evidence didn’t support the theories.

We have been here before with various vitamins and minerals.  And, there are those out there who have been suggesting that other vitamins and minerals can reduce cancer risk.

This blog is no stranger to evidence based medicine.  No matter how tempting the reports of success may be, until the right trial is done you simply can’t authoritatively support an unproven theory that a vitamin or anything else can prevent cancer.

Let’s always keep that principle in mind before we start advocating that “this thing” or “that thing” prevents cancer.

Until the evidence is in, the evidence isn’t in.

Maybe occasionally there is a glimmer of truth to the saying, “I’m from Washington and I’m here to help you.” 

Today, the Social Security Administration unveiled a new initiative to make it easier for people with certain serious medical conditions to get their Social Security disability benefits promptly and with a lot less hassle.

Called “The Compassionate Allowances Initiative,” this new program is due to the efforts of the Hon. Michael Astrue, the Commissioner of Social Security, and his staff to finally bring some streamlining to a process that has been frustratingly and agonizingly slow for so many patients and their families for so many for decades. 

The American Cancer Society was honored to participate in this effort through our testimony and subsequent support as this initiative moved through the Agency.  We thank the Agency for listening to patients, their families, the Society and others. 

Now we have a program to streamline and improve the process for determining Social Security benefits.  This is truly special for those with cancer who need help at the most difficult time of their lives.

What does this program offer?

For a total of 50 conditions—including 25 specific cancers and 25 rare diseases—if a person has that condition, a decision on their eligibility for social security benefits will be made in days instead of months or years, according to a statement from the Commissioner.  In addition, the Agency also noted that this list may expand over time.

(You can find more information on the Compassionate Allowance Initiative at: www.socialsecurity.gov/compassionateallowances.)

The list of cancers covered under this program includes, among others: acute leukemia, aggressive brain cancer (astrocytoma grades 3 and 4 and glioblastoma multiforme), advanced breast cancer, esophageal cancer, pancreatic cancer and advanced lung cancer.  (The complete list is available at the same website noted above.)

I first became aware of how serious the situation was when I started my oncology practice in Baltimore in the mid 1970’s. 

Patients diagnosed with late stage cancer who had no hope of recovery or faced debilitating cancer treatment and were obviously disabled even under the very strict definitions of the Social Security disability program had to wait months for approval before they could get their benefits.

Unfortunately for some (and their families and dependents), the wait for benefits was longer than their survival.

Fast forward to more recent times and you have a Commissioner who was finally willing to take on the problem and gave his staff the opportunity to creatively address a true failing of an important safety net system. 

I know that this may not seem like a “big” news story to many of you who are fortunate to be well and able to work.  But I can tell you first hand the heartache that many patients and their families have experienced once they have been diagnosed with advanced cancer and need whatever financial help they can get.  (I wrote in greater detail about the problem in a previous blog in April, after I had testified at a hearing convened by the Commissioner in Boston.)

So, my hat is off the Social Security Administration and Commissioner Astrue for doing something to benefit our patients and their families.

There is always a lot of talk about people in Washington doing this and doing that to help us, especially during this campaign season.  Most of us dismiss those promises as part of the “same old same old” Washington line.

In my opinion, what we have here is an example of an agency that has actually reached out and done something “real” that can only serve to help those in need at one of the most distressing times in their lives.

On behalf of those who are so personally affected by this dreaded disease, thank you, thank you, thank you!!!!

Cancer and survivorship have played an unusually high-profile role in the current campaign for the Presidency.  Elizabeth Edwards and Rudy Giuliani come to mind.

Today, the Lancet—a well respected and authoritative British medical journal known among many for sometimes highlighting controversial topics to promote discussion—included a letter to the editor which concluded that Senator McCain had a 24% chance of surviving 10 years after his treatment for melanoma in 2000.

The author of the letter goes on to say that with regard to future risk, another data source suggested that the risk of dying from melanoma is constant over time, meaning that there is no expectation that the majority of deaths from melanoma occur shortly after the disease is diagnosed.  The author calculated that risk of death at essentially 12% per year for the foreseeable future of a McCain presidency. He then cut that to 6% given the Senator's negative lymph node dissection.

The letter is short, the statistics complicated, and in my personal opinion, they lead the reader to an incorrect conclusion.

I have assiduously avoided getting involved in predicting the cancer outcome of the Presidential candidates, starting with some of the questions I began receiving a couple of years ago.  But when the statistics may have an influence on a campaign and are presented in a manner that may not be consistent with the evidence, then I think it is appropriate to shine some light on the situation.

A recent article in the New York Times by Lawrence Altman, MD goes into great detail about McCain’s medical history with regard to his various melanomas which have been diagnosed since 1993.

The melanoma episode that has caused the greatest concern was in 2000, when one was diagnosed on his face.  Following removal of that lesion, which was 2.2 mm thick (an important factor in determining outlook and treatment for particular patient’s melanoma), he had a radical dissection of the lymph nodes on the left side of his neck.  That surgery showed no evidence that the cancer had spread to the lymph nodes.

Now, what do we know about Senator McCain and other patients with similar histories of melanoma and how does it compare to the information the letter writer cited in terms of anticipated survival?

The Lancet letter says, “McCain’s melanoma fell into the higher-risk categories identified in that study: the tumour was 2.2 mm thick, placing it into the second highest risk category (T3); McCain was older than 60 years at diagnosis; he is male; and his lesion was not on an extremity.  As a result, using the prognostic model, his predicted 10-year survival at the time of diagnosis was only 24%.”

I went back and read the article the writer used as a reference.  It was published in the Annals of Internal Medicine, a highly regarded medical journal, in 1996.  It was written by very well-qualified experts in the field of melanoma.

The researchers examined the records of 488 patients who had no evidence of spread of their melanoma at the time of diagnosis.  They followed the patients for 10 to 20.5 years after surgery.  Then, they looked at various characteristics of the melanomas to link survival time with these characteristics.

From this research they found four factors were useful in creating a model to predict survival at 10 years: the thickness of the melanoma, the site of the primary cancer, the age of the patient and the patient’s sex.

In considering Senator McCain, who was over 60 at the time of his diagnosis in 2000, the 10 year predicted survival looking forward from the time he was diagnosed was indeed 24%.

However—and this is an important however—this is a “single point” type of observation. Namely, has the patient died of the disease at 10 years, or are they still living?

The authors of the paper wrote at the time, “The 10-year interval was chosen because death from melanoma beyond 10 years is uncommon.”

Obviously, Senator McCain is still very much alive and kicking.  So what does that mean in terms of the 24% odds?  What about the future?

The author of the Lancet letter cites another paper to estimate Senator McCain’s future risk of death from melanoma. 

He writes, “With regard to future risk, Kolmel and colleagues have shown that for male patients with thickness T3 melanoma the increased mortality associated with such tumours is relatively constant and remains so for 15 years from diagnosis.”

Yes, but…

The paper referred to does have a chart that shows a relatively flat line for annual recurrence, implying that recurrence is equally distributed over a 15 year time period.

However—and this is difficult to understand—the percentage risk of recurrence is a percentage of a declining population of patients who have not already recurred.

In simpler terms, if you have 100 patients in year one, and 15% recur then the next year you have 15% recurrence rate in only 85 patients, and so on.  So the rate may be constant, but the number of patients (and consequently the number that will recur) is declining over time.

The author also missed the survival curve which clearly shows that an overwhelming number of deaths from “T3” melanomas in this German study occurred before 96 months, which is where the Senator fits into this graph.

In fact, when you measure the risk of death from melanoma from about 96 months to about 146 months (the length of time from the election to the completion of a first term in relation to Senator McCain’s diagnosis in 2000), another graph shows a decline in survival of a couple of percentage points over that same 4+ year time frame. 

And this is old data, which doesn’t include treatment advances, doesn’t consider the absence of regional lymph node surgery, and doesn’t include the fact that within this study over several time periods the survival of patients with the same characteristics improved significantly.

And there are more data sources.

SEER, which is a nationwide cancer registry supported by organizations including the National Cancer Institute and the Centers for Disease Control and Prevention shows clearly that most deaths from melanoma in white males diagnosed between the ages of 65 and 74 and measured over 16 years from 1988 through 2004 occur early after diagnosis. Few deaths occurred many years after diagnosis (although this includes “all comers” with varying melanoma characteristics). The actual survival percentage for this group is 87.30% at 8 years and 87.01% at 10 years.

Finally, another paper published in the journal Cancer in 2002 looked at the relationship between sex, location of the melanoma, thickness, and the presence or absence of ulceration.

Assuming a non-ulcerated lesion on the face in a male between 2 and 3 mm thick, the cured fraction is between 35.8 and 44.5%, the median survival is between 5.4 and 6.1 years, the assumed percentage cured at 10 years is between 70 and 74%.

However, the authors make a very interesting, important and what is at first glance illogical statement: it is the patients with thin melanomas (the Senator’s was considered a thicker melanoma) that have the higher percentage of late recurrences.  For patients with thicker lesions, although still at some risk of recurrence, most of the recurrences in that group occur closer to the time of initial diagnosis.

So, if you have a less favorable melanoma, the longer you live the more likely you are to do well.  It is a situation of what I call “diminishing probabilities” that your disease will recur.

This same paper also points out that “As survival increases, the prognosis tends to equalize among patients with thick lesions and patients with thin lesions.”  The authors continue their comments to support the observation that the longer a patient with melanoma survives, the percentage expectation of further survival also continues to increase.

In simpler words, with melanoma and a relatively poor prognostic outlook, the longer you live, the more likely you are to have been cured of this disease.

I could go on with more statistics, but I think you get the point.

Cancer of any type is an unwelcome and dangerous disease. It is a fact of our lives.

Senator McCain has had several melanomas, one of which in particular was of concern.  Because of that concern, the surgeons did extensive surgery at the time of diagnosis and found no evidence of lymph node involvement.  That factor isn’t even included in any of these statistics, and what evidence we do have suggests that puts him in an even more favorable category.

But what the data does not support, in my opinion, is a statement that he has a 6 or 12% chance of dying every year.  That is simply not borne out by the evidence.

To make such a statement in a major medical journal at this time in the campaign raises concerns for me and others.  Not that the question is not legitimate—it is.  But the timing is suspect and the chance to set the record straight is limited.

I expect higher standards from our respected medical journals.  These types of political intercessions have occurred in the past with other highly regarded research publications, but I will defer that discussion for another day.

For the present, we need to understand what the evidence shows as opposed to turning it inappropriately into a tool for a momentary political advantage.

+++++++++++

I know that I am writing this particular blog about a difficult and potentially sensitive subject. 

I want to affirm for the record that I am not a vocal supporter of either candidate, and have made no contributions to either candidate, either party or any campaign-related committee or organization in support of anyone’s Presidential campaign.  In addition, our organization and our employees are prohibited from engaging in any political activity related to our work for the American Cancer Society.

Finally, the opinions and comments contained in this blog are mine and mine alone and do not represent the position of the American Cancer Society on this matter.

Recently I wrote a blog about the effectiveness—or lack thereof--of some of the newer tests and treatments that are being marketed to cancer doctors and their patients.

An article in the current issue of the New England Journal, however, is a step in a better direction, namely a test that appears to help guide us to use our expensive (and effective) targeted therapies for patients who will benefit from them the most.

The test, which measures a change in a gene called K-ras in patients with colorectal cancer, appears to be able to predict which patients with advanced disease have the most chance of benefitting from a drug called cetuximab, which is commonly known as Erbitux.

In the clinical trial reported by researchers from Australia and Canada (and including authors from one of the drug companies that markets cetuximab), patients with advanced colorectal cancer who had failed standard chemotherapy for their disease and for whom no further treatments were available were randomly assigned to receive either cetuximab or no further treatment (best supportive care) for their disease. 

Those treated with cetuximab continued their medication until the cancer progressed or they could not tolerate the therapy any longer.

The researchers subsequently examined samples of the patients’ cancers to find out whether or not they had a mutation in the K-ras gene.  They then looked at whether or not the gene was changed (mutated) in the tumor specimens and whether or not that influenced the effectiveness of the treatment.

They found that a little over 4 out of 10 patients in both groups did indeed have such a mutation.   Six out of 10 did not.

Now, what follows is a bit confusing, so bear with me and read this carefully:

• If a patient had the K-ras mutation, they survived about 4.5 months whether they were treated or if they only received supportive care.

• If they did not have the K-ras mutation, then they survived 9.6 months if they were treated with cetuximab and only 4.8 months if they were provided only supportive care and no chemotherapy.

So, patients who did not have the mutation benefitted significantly and doubled their survival time if they were in the group that received cetuximab.  It was not a good sign if the mutation was present.

The researchers also looked at the response rates and quality of life scores.  Those patients without the mutation who received cetuximab did better on both measures compared to the other patients in the study.

This study very clearly shows that the researchers have identified a genetic marker that predicts—but does not assure—success for the majority of advanced colorectal patients who do not have the K-ras mutation.

Why is this study so meaningful and important?

We have struggled for some time to come up with tests that might predict success for various drugs used in cancer treatment.  Cancer drugs have always been expensive, but the new targeted therapies have set the bar for treatment costs so high that some patients are probably forgoing using them because of that cost.

It would be a big step forward in the rational use of medicines for cancer treatment if we could be more targeted in using our targeted therapies. 

Looking forward, my sense is that we will one day in the future be able to routinely screen cancer specimens to determine which targeted therapies have the best chance of helping our patients.  This will be a major advance in the growing field of “personalized medicine.”

This isn’t the first time we have had such a test for a cancer.

HER-2 is another genetic marker which predicts a more aggressive form of breast cancer.  HER-s also has opened the door for effective treatments that have considerably improved the outlook and survival of women with breast cancer where this marker is found on specialized testing.

I should also point out that a genetic marker has previously been touted for predicting the effectiveness of cetuximab in the treatment of colorectal cancer.

As noted in an editorial which accompanies the current report, when cetuximab was first approved by the FDA, the FDA included a requirement that another marker—EGFR—be measured and present in the cancer before the drug could be used.  That recommendation was based on the rationale that cetuximab targeted EGFR receptors in colorectal cancer.

Unfortunately, it became quickly apparent that the presence or absence of EGFR in a colon cancer specimen in fact did not predict response, and doctors quickly ignored the FDA requirement.

This time, the situation appears to be different.  This current research report shows that if K-ras is mutated, it essentially means a patient with colorectal cancer will not respond to the drug, and other treatments would be more appropriate.

Other researchers have also presented similar findings, but with a slightly different twist.

An abstract presented at last June’s American Society of Clinical Oncology meeting in Chicago found similar results, although in that study cetuximab was used as a “first line” treatment for colorectal cancer along with chemotherapy, not at a time when no further treatment options were available or when it was the only treatment offered to the patient.

One more observation on the New England Journal study: this is a research study that would likely never have been done in the United States.

We have a tendency in this country to always think there is one more treatment that will save a life, even when that opportunity is almost nil by any rational measure.

In this study, the patients were either treated or not treated.  The doctors and the patients accepted the fact that a patient could be randomly assigned to “best supportive care,” which means no chemotherapy, and no radiation therapy.  For those patients, it meant keeping them as comfortable as possible during the last months of their lives.

At the same time, it is this same study which very clearly shows us the way to more effectively use our treatments in the best interests of our patients and their families.  Those who consented to participate in this clinical trial were willing to accept the reality of their circumstance, and participate in a clinical trial which starkly presented them their options, one of which was certain to end with their death.

I don’t know what the future holds in terms of targeted therapies and determining their effectiveness for treating certain types of cancers.  But I do know that the commitment of these patients, their families and their physicians to participating in this research has shown many more patients, families and doctors the way to better care at a time when difficult decisions must be made.

We are in their debt.  They have truly advanced the science of cancer treatment.

Presidential elections aren’t the only things that interest pollsters. 

You may not know this, but periodic nationwide surveys done by respected government and private organizations have a substantial influence on how we assess the success of our health care system and how we direct our financial resources to address real or perceived problems.

But I have a longstanding bias that some of these surveys don’t reflect the state of affairs in the United States when it comes to accurately determining how many people in this country actually do what they tell the pollsters they do when it comes to cancer screening.

A research article in published in March 2008 in Oncology Nursing Forum, written by two of my colleagues at the American Cancer Society’s Behavioral Research Center confirms my suspicion: at least in a part of the African American community served by federally qualified community health centers, what the patients tell the pollsters doesn’t fit with what the medical records reveal.

The researchers interviewed African American women who attended these health centers, whose primary mission is to provide medical care to underserved populations. For the most part, the  women in this study were economically disadvantaged.

The researchers asked a number of questions about whether or not the women had recent or past cancer screenings.  Then, the researchers examined the medical records to see if there was actual documentation that the women had in fact had the recommended screenings and how that checked out with the responses they gave in the interviews.

With regard to mammography to detect early breast cancer, for example, 77% of the women who should have had a screening mammogram said they in fact had one sometime in their lives.  The chart showed that only 40% had in fact had a mammogram at some time as noted in the medical record.  29% said they had a mammogram within the past year, and 29% said they had a screening mammogram within the past two to five years.  The actual numbers were 9% and 26%, respectively.

Similar findings were reported for clinical breast examination and two of the three intervals questioned regarding pap smears.  The numbers were too small to draw particular conclusions regarding fecal occult blood testing.

This is no trivial matter.

For example, there is data from the Centers for Disease Control and Prevention regarding the number of African American women who have had a screening mammogram.  Many of us rely on that data for our discussions, presentations and planning.

That data—which is among the best available on the topic--says that 49.9% of African American women age 40 and older have had a mammogram within the past year, and 64.9% have had one in the past two years.

But other studies that have reported on the frequency of screening mammography in African American women tell a different story.  Past studies have shown that a significant number of African American women who develop breast cancer all too frequently haven’t had a recent mammogram, the telephone poll results notwithstanding.

The same situation exists with cigarette smoking.

When you look at the data available for smoking among African American youth, the numbers are the lowest for any ethnic group.  In fact, the most recent information shows about 11% of African American youths have smoked within the past 30 days.  But when you look at smoking in African American adults, the numbers are much higher.  Since most adult smokers start when they are young, there is something in these numbers that has not made sense to me for a long time.

Unfortunately, I think the difference isn’t that we are doing a much better job of stopping smoking among African American children than we are among others. I think the surveys aren’t catching the right information.

I will share with you that not all of my colleagues share my concerns about the accuracy of the available information on screening for various cancers.  They tell me essentially that the data is the data.

My concern is that the “data” is what drives a lot of decision-making by various organizations and governments when it comes to directing money to programs to increase cancer screening.  High compliance suggests we are doing a great job, so less money is needed.  If the numbers were low, then that would highlight a significant need that would require more funding.

I recently had a conversation with a researcher who happens to be interested in this very issue.  She told me that my concerns were valid.  People will tell the pollster on the phone what they think the pollster wants to hear, rather than admit they haven’t had screening.  Or, they may misunderstand what screening is and what it is not.  She also commented that the discrepancies are much less when the interviews are done face to face.

We do not do a great job in this country of getting people screened for the early detection of cancer, especially for cancers where we know screening makes a difference such as in breast and cervical cancer.

We need reliable data sources that tell us whether or not we are reaching those populations who are historically underserved, and suffer accordingly when their cancer is detected at a later stage when treatments are more difficult, and successful outcomes less certain.

This particular study does have some limitations as noted by the authors, but it lends credence to my concern that we aren’t getting the information we really need to help us address the very real issues we have in delivering adequate, comprehensive and effective health care in some of our communities.

Until we recognize and deal with this reality, we may continue to reward ourselves for a job well done when in fact the job isn’t getting done at all.

Do you really believe that red wine—and only red wine among the alcoholic beverages—really reduces the risk of lung cancer?

Last week’s research report that smokers who drink red wine had a substantially decreased risk of developing lung cancer drew such a conclusion.  And the media climbed right on the bandwagon.

But I am not so certain that we can reasonably make that connection, and would suggest that until the data is replicated with an even larger study we should be cautious in suggesting that smokers should suddenly switch their adult beverage of choice to red wine from what I suspect is the more typical beer, bourbon and scotch.

The study as reported in the current issue of Cancer Epidemiology, Biomarkers and Prevention did say that their data showed “moderate red wine consumption” was related to a lower level risk for lung cancer.  Drink more red wine and you had a much lower incidence of lung cancer if you ever smoked cigarettes.  The same effects were not seen with other alcoholic beverages, including white wine.

I am not faulting the researchers for the work they did.  In fact, it was a large study of over 84,000 men in California and the methods they used were very appropriate. The study was well done.

But when I was asked to take a look at the article by a reporter for a national news service, I did note some statistics that gave me a moment’s pause.  That, combined with my past experience with reports on the health benefits of red wine, suggests to me that we can’t be too quick to say that red wine is good for you if you smoke.

My comments, as correctly quoted in the news report, were essentially that this was interesting research but that it needed to be confirmed.  In addition, I also noted that increased wine consumption can be associated with an increased risk of other cancers, including breast cancer and head and neck cancer.

When I reviewed the article in the medical journal, I noted that there in fact was a significant reduction in lung cancer for red wine drinkers who were “ever smokers.”  Those reductions, by the statistics, were impressive, up to a decrease of 61% if you drank one or more glasses of red wine a day. 

But then I also noted that when the statistics were more carefully examined, the range of possible percentages of the effect of red wine ran from a reduction of as much as 84% to an increase of as much as 78%.

Without getting too complicated on the statistics, the reality was that for each level of red wine consumption, there was a wide range of possible answers (what we call the “confidence interval”) that might have shown up on different analyses of the data in other studies or at different times.  The level of certainty was not great that these marked reductions were in fact the “right” answer.

The reason for this is that—despite looking at tens of thousands of men—you would still have to look at thousands more before getting the level of statistical definition that would narrow these confidence intervals and make the statistics more reliable.

When the researchers did an additional analysis, where they looked at the “trend” of the data, the numbers in combination led to the conclusions that they reported in their article, namely that the trend of the data suggested that there was indeed a relationship.

It is important to keep in mind that this type of research is complicated, and so are the statistical analyses.  I even asked my statistics colleagues at work to take a look at the numbers, and they essentially came to the same conclusion. 

The other question is that although the researchers looked a number of related factors and tried to eliminate them as the cause for the “red wine effect,” I am still concerned that there could have been some other unidentified factor they may not have measured.

This may sound corny, but I just don’t know a lot of smokers who choose red wine as their “alcohol of choice”.  Those that do could have other lifestyle habits that separate them from their beer/bourbon/scotch drinking buddies that could theoretically explain the observation in the study.

I have been through the “red wine experience” in the past.  I can’t remember the exact time frame, but as best I recall it was in the early 1990’s when there was research touting the health benefits of red wine.  Even CBS’ 60 Minutes got into the act, suggesting that red wine consumption may be beneficial, citing the experience of the French who consume larger quantities of red wine without the level of anticipated ill effects.

Since that time, there has been persistent interest in the health potential of red wine—or one of its ingredients—and the possibility that it may be associated with increased longevity.

(I have to laugh a bit at my memories of the red wine story.  While in practice as a general internist back in the early 1990’s, an elderly lady—I think she was about 82 years young—who was in reasonably good health came into my office for her regular visit clutching a paper bag.  In the bag was a slightly used bottle of red wine.  She had seen the television report on red wine, and although she had been a teetotaler before that, she went out and bought herself a bottle of wine and started drinking small amounts. 

When she asked me if this was good for her, I advised her that I thought she had been doing fine without the wine.  No real objection, mind you, but I wouldn’t recommend to her that she take up this new habit for her health.

At which point, in all seriousness, she turned to me and asked if I thought the wine store would give her money back, since I—her doctors--didn’t think she really didn’t need the wine after all.)

The bottom line: the research is well done, but I don’t have the confidence that I would like to have in the conclusion that red wine drinking reduces your risk of lung cancer if you are or have been a smoker.  Any claims along that line should be viewed cautiously.

As the authors correctly concluded in their report:

“We observed an inverse association between red wine intake and risk of lung cancer among ever-smokers, which suggests further research into the lung cancer chemopreventive agents that occur in abundance in red wine.  These findings, however, should be confirmed in future epidemiologic studies that separately examine the effect of red wine from other alcoholic beverages.”

To which I say, “Cheers!”

We are now aware of where the excesses of the financial system have led us.  But I am also becoming increasingly concerned about excesses that I am seeing in claims regarding cancer research, diagnostics and treatment.

I have talked frequently about what I call the “hope and hype” cycle that was so prevalent when I started my oncology career back in the early 1970’s.  Lots of promises were made about miracles just around the corner, and unfortunately I was left to explain to patients and their families that these were more the fabric of dreams than based on solid expectations.

Fast forward to the past several years, and I have been unashamedly optimistic about where we are headed in cancer research and treatment.  We have made true progress, and the future from my vantage point is rich with potential, as we translate that progress into true advances which will reduce the burden and suffering from cancer.

I am now seeing situations where claims are being made that to me are reminiscent of that “hope and hype cycle” which was so prevalent back in the 1970’s and 80’s.

Last week’s blog on a genetically based breast cancer risk assessment test may be one example. 

The test is promoted as a risk stratification approach to women concerned about breast cancer.  However, some knowledgeable people have concerns about the statistical validity of the test and how relevant it is to clinical practice.  The test has never been subjected to a clinical trial or published in a peer reviewed medical journal.  The chorus of experts who had reservations about the test included some of the world’s leading breast cancer genetic researchers.

Then there was a recent report from a public company regarding their prostate cancer vaccine currently in a clinical trial. 

The purpose of the trial is to determine if the vaccine prolongs the lives of men with advanced prostate cancer.  An “interim analysis” was undertaken by the company’s data safety monitoring committee watching over the trial.  The company said that if the results of the trial stay on course, then the committee predicted when the trial concludes it will show that the vaccine is effective in reducing deaths from advanced prostate cancer.

This certainly would ordinarily be welcome news, but this particular vaccine and questions about its effectiveness have kindled intense public debate in the past. 

Usually, results of clinical trials are presented only when the trial is completed and the data is “unblinded,” frequently at a major scientific meeting such as the annual meeting of the American Society of Clinical Oncology.

Until that time, the only people who should have access to the results are the monitoring committee, and they usually closely guard the results of the trial—not release them in a press release. These committees usually only make public pronouncements when a trial shows overwhelming benefit for a particular treatment, or shows that the new treatment is causing harm, or there remains no possibility the new treatment will show benefit over the control group in the trial.

I don’t know what to make of a statement about the “possibility of success”, but past experience has taught me that until you have the end results, predicting what may or may not happen is fraught with problems. 

(By the way, the statistics quoted in the press release did not show that the drug was effective at this time from a statistical standpoint.  The hope is that with more time, the number will in fact become statistically significant. )

When I was in training, we used to see a lot of clinical trial data reported that was based on statistical estimates of what the future would hold.  The data using the estimates would be published, new treatments would be proclaimed effective and we were off to the races. 

Unfortunately, as the trials continued to grind on, we found not infrequently that the predictions of the future did not hold up in the real world. 

Experience frequently trumped statistical predictions and models (sound familiar?). 

It was those events that have made many of us much more cautious in how we approach the statistical analysis and predictability of clinical trials, and prevent us from claiming a result until the final data are in and thoroughly analyzed.

Then there are the increasing numbers of other types of genetic tests that are coming to market.

There are several tests available which are supposed to help women and their doctors determine the risk that their breast cancer will recur after primary treatment and help them decide whether or not to pursue adjuvant chemotherapy after their surgery and radiation therapy. 

The problem here is that these tests have never been looked at prospectively in a clinical trial.  Those trials are now underway, and until they are concluded we won’t know the full impact—or possibly lack of impact—of these tests in something close to real world decision making. 

In other words, do these tests really make a difference when they suggest that a woman is or is not likely to benefit from adjuvant chemotherapy?

That isn’t stopping doctors from ordering these tests with or without the patients’ permission.

I heard recently from a colleague about a friend with breast cancer, whose surgeon had ordered one of these breast cancer tests without her knowledge.  It was after her surgery that she was told the doctor had ordered the test.  Then, the patient asked the obvious question: what will this test mean in terms of my treatment?  Will it make a real difference in what I do?

I was asked a couple of weeks ago to comment by a reporter on another genetic test that is being promoted to help doctors determine the origin of cancers where the pathologist looks at the tissue under the microscope and can’t say for sure where the cancer started (such as the lung, pancreas or ovary).

The developers of the test were able to demonstrate in hundreds of known cancers that the test would accurately identify the source of the cancer.  But they only tested a handful of “unknown primary cancers,” which is the “target use” of the test. And of those unknown cancers that were tested, the test may have helped identify the source of the cancer in some of the cases.  But the researchers hadn’t demonstrated that the test made a meaningful difference in the patients’ treatment or outcome.

The FDA has approved this test, but I suspect they looked only at whether or not the test worked as described, instead of asking the same questions it asks of the drugs it evaluates, namely is it effective in treating the disease and (usually) prolonging survival?  Does it make a real difference in the real world?

I could go on with my list, but I suspect you get the point of this discussion.

We have made great progress in cancer research and treatment.  That progress has been painstakingly slow at times, but we have seen successes that provide us with a reasonable sense of certainty that our advances work as claimed.

When we start having a slew of “early press releases,” or have tests promoted in the marketplace that have not been subject to the rigors of a clinical trial to demonstrate that they make a real difference in the lives of our patients, then we run the risk of “running the bill” at a time when we can least afford to do so. 

We may be approaching a time when we may have too much information that can confuse our treatment decisions, as opposed to clarifying them.

We need to have an eye towards making certain that we get our cancer diagnostics and treatments “right.”  We need to have some degree of certainty that when we spend thousands of dollars for a test or a treatment that it makes a real difference in the lives of our patients.

If we don’t do that, then we run the risk of overdiagnosing, overtreating, overspending, and quite frankly wasting peoples’ hard earned money. 

We all deserve better.

I want to bring to your attention a correction which may be minor, but nonetheless important if you are considering getting the breast cancer genetic/prediction test discussed in my blog on October 8.

I noted in the blog that the cost of the test was $625.  My statement was based on a press release issued by the company.  I have the statement in my hand, and the price is clearly $625.

When the Washington Post reported on the test, it said the cost was $1,625.  Obviously, this is considerably greater than I wrote in my blog.

A loyal reader brought to my attention today that the link I provided in my blog to the company's website says the cost is $1625.  

In any event, whether the price is $625 or $1,625, I can't find many of my colleagues who think that it really has much value.  Not to mention their considerable concern about how the company has confused various types of risks regarding breast cancer, ending up with a number that my experts don't think has value or meaning.

Bottom line, if you are considering getting this test, it is our recommendation that you be fully informed as to its value, whether that is the value of the cost or the value of the information.

We are entering exciting times when it comes to the impact of genetics on the diagnosis and treatment of cancer. 

However, my colleagues’ discussions over the past 24 hours about a new test that claims to predict a woman’s risk of breast cancer have me thinking these exciting times may be more like the Old Wild West where “anything goes” than some meaningful movement forward in our battle against cancer.

The stated goal of the test is to enable a woman to predict her lifetime risk of getting cancer.  The accompanying material from the company liberally quotes the American Cancer Society and the American Society of Clinical Oncology as references to support the value of the test.

The company says that this test—which is an analysis of genetic code obtained from cells that are either swabbed from the mouth or taken with a blood sample and then analyzed in the company’s laboratory—measures seven genetic changes that “contribute to the incidence of an estimated 60 per cent of all breast cancer cases.”

The test is based on “studies published in major peer-reviewed journals and involving nearly 100,000 breast cancer patients and healthy volunteers, principally of European descent.”  The company presents several recently published journal articles and their own proprietary unpublished data as support for the science behind the test.

If you do this test (which costs $1625; please see correction posted 10/10/08), you will receive a calculated estimate of your risk of developing breast cancer.  This estimate apparently is obtained by multiplying the increased risk values found in the research studies for the particular genetic changes. 

The problem is, no one to our knowledge has ever shown that multiplying all of these newly discovered genetic risk factors together really gets you to a number that has real meaning. 

Why should we be concerned about this?

There is a lot we know about breast cancer risk, and there is a lot we don’t know.

There are genetic tests widely available in this country which measure a change in the genes of certain women called BRCA 1 and BRCA 2.  These genes, when present, do predict for certain women that they have a very high risk of developing breast and/or ovarian cancer during their lifetimes. For the vast majority of women, however, we don’t have any specific genetic tests to pinpoint their individual risk. 

In general, we are left to rely on other factors such as family history, age of menarche, age at first pregnancy, prior breast biopsies, and similar information to give us a gauge of their risk.

Once we know their risk of breast cancer, we can recommend strategies to reduce that risk.  For women who are BRCA positive, that includes preventive mastectomies and oophorectomies, for example.  For other women, it could mean treatment with tamoxifen or raloxifene.

Along comes this new genetic test making certain claims, and we start to wonder what does it mean?

First, you should know that the test has not been approved by the Food and Drug Administration, according to the company's consent form for the test. 

Actually, for laboratory tests, that is not unusual since a single laboratory that develops a test is allowed to market it without FDA approval.  However, the FDA is particularly concerned about the burgeoning numbers of genetic tests, how they are performed, and whether they in fact produce the types of results they claim under this so-called “home brew” exemption.

In addition, for this particular test, there are several states that do not allow it according to the informed consent provided by the company.  Those states include California, Maryland, New York, and Pennsylvania.

Most importantly, according to my American Cancer Society colleagues, they are not aware of any research that has looked directly at this particular test as a forward-looking assessment of the risk of an individual woman developing breast cancer.  They don’t know whether or not it really measures the risk it is supposed to measure.  Doing such studies takes time, and costs money (which may be in short supply for this company according to public documents).

Simply stated, this lab has taken advantage of published research, said that they can measure the presence or absence of a particular genetic change in a woman’s DNA as reported in that research, multiplied the risk factors together, and come up with a number.

Whether or not that particular approach translates into real life risk, in the opinion of my colleagues, is uncertain.

And, there is no published data on the test as to whether or not the test itself accurately measures these genetic changes.

But what concerns us the most is the link between our guideline recommendations for MRI breast cancer screening and the test’s promotional materials.

The American Cancer Society and its advisors have not evaluated this test, nor are our guideline recommendations regarding preventive treatment or breast cancer screening with MRI based on the results of this test.  It is not appropriate to link the results of this test with any recommendation from the American Cancer Society.

Our guideline recommendations are based on what we call “clinical factors” related to risk, not this particular test.  In our opinion, to cross-link this test with our guidelines is not appropriate in the absence of validated clinical research.

I could go on about our concerns, but you would probably become even more confused that you are already.  Even I have difficulty trying to sort out the data and the recommendations made by the company’s promotional literature.  When my colleagues start to talk about the blurring of relative and absolute risk even my eyes start to glaze over.

I would emphasize that the American Cancer Society encourages research and development of biomarker tests for breast and other cancers.  It is our recommendation that these tests must be studied carefully before being offered to the public.  They should undergo validation studies and demonstrate their value in the clinic. 

We don’t see the evidence that that is the case in this particular situation.

Like I said, we hold out great hope for the role of genetics in the diagnosis and treatment of cancer.  We know that the future holds great promise for these types of tests.

The question for today, however, is whether some of these tests that are coming to market really advance our cause in the fight to reduce deaths from cancer in a meaningful, evidence-based and scientifically accurate way.

For now, with respect to this particular test, our opinion is—unfortunately—not a positive one.