Category Archives: Breast Cancer

New York’s Breast Density Law – TMI with TLI for Too Many Women

MOST RECENT POST ON THIS ISSUE  Dense Breasts on Mammogram. No need to be Afraid.

Once again, legislators are meddling into healthcare. This time, it’s in my own home state, where Governor Cuomo has just signed a bill requiring radiologists to notify women when their normal mammogram also shows that they have dense breasts. In such cases, the following text must be included in the lay summary mammogram report given to the patient –

“Your mammogram shows that your breast tissue is dense. Dense breast tissue is very common and is not abnormal. However, dense breast tissue can make it harder to find cancer on a mammogram and may also be associated with an increased risk of breast cancer.

This information about the result of your mammogram is given to you to raise your awareness. Use this information to talk to your doctor about your own risks for breast cancer. At that time, ask your doctor if more screening tests might be useful, based on your risk. A report of your results was sent to your physician.”

New York is the fifth state to pass a mandatory breast density notification law. As of this writing, Connecticut, Virginia, California and Texas have similar laws.

What is Breast Density ? 

Breast density is a subjective radiologic assessment of how well x-rays pass through the breast tissue. It is a surrogate for how much of the breast is composed of glandular tissue and how much is fat. The radiologist reading the mammogram classifies the breast composition as one of the following  –

  1. Almost entirely fat (<25% glandular)
  2. Scattered fibroglandular densities (25-50%)
  3. Heterogeneously dense breast tissue (51-75% glandular)
  4. Extremely dense (> 75% glandular)

For the purposes of the law, dense breasts are defined as those that are heterogeneously dense or extremely dense.

Mammographically dense breasts are extremely common, especially in younger women. According to a recent report of mammograms here in New York City, 74% of women in their 40s, 57% of women in their 50’s, 44% of women in their 60’s and 36% of women in their 70’s had dense breasts.

What We Know (and Don’t Know) About Breast Density

Increased breast density can be a risk factor for breast cancer . 

The mechanism is unknown, but it may be that breast density is just the end result of other factors that increase breast cell proliferation and activity – factors like genetics and postmenopausal hormone use.

How much of a risk? Well, it depends on what study you read and who you compare to whom. If you compare the two extremes of breast density in older women, those with extremely dense breasts have a three to five-fold higher cancer risk than those with mostly fatty breast. The risk is lower than that in those in the middle category of breast density and in younger women, though not well-defined.

The truth is, we really have no way to translate individual breast density into individual risk. Researchers are trying to see if breast density can be incorporated into current risks assessments such as the Gail Model, but at this point, breast density has not been shown to add much more than we already know about a woman’s risk from using these models.

Dense breasts can obscure a cancer on mammogram.  

This makes mammogram less reliable in women with dense breasts. Digital mammograms may be better at finding breast cancers in women with dense breasts who are also peri-menopausal or < age 50, but it is not known if this translates into better outcomes.

Additional testing with ultrasound and MRI can find cancers that mammograms miss in women with dense breasts. Unfortunately, breast ultrasound and MRI screening tests are less specific than mammograms – three times as many biopsies will be done, most of which will not be cancer.

We do not know if additional screening beyond mammograms saves lives.

It might seem to makes sense that it would, but there are no randomized trials to show this. For now, this additional screening is only recommended in women at highest risk for breast cancer based on other factors such as genetic, family and personal health history.

Why the Breast Density Law is Misguided

Our legislators have women’s best interests at heart, but unfortunately, when it comes to the practice of medicine, they really don’t know what they are doing. Allow me to explain…

1.Most women under age 60 have dense breasts.  

Three quarters of New York women in their 40’s, all of whom have just had a normal mammogram, will now be told that they may be at increased risk for breast cancer.

2. Breast density measurement is subjective. Different radiologists may give the same mammogram different ratings. Use of computerized density measurement could alleviate inter-observer variability, but there is not yet a standardized computer rating system.

3. Breast density can vary across a woman’s menstrual cycle and over her own lifetime. The same women being scanned at a different time of month or at a later year can land into a higher or lower breast density category, and may or may not get that letter above. Recent research suggests that a single breast density reading may not be the best way to predict breast cancer risk, and that the risk may be confined to those women whose breast density does not decrease with age.

4. Sonogram and/or MRI for breast cancer screening is currently not recommended based on breast density alone. Additional screening beyond mammography is only used in women at highest risk for breast cancer  – those with cancer in a first degree relative with a high risk gene mutation, a family history suggesting one of these mutations, a Gail model or other combined lifetime breast cancer risk assessment >25% or a history of chest irradiation. Even in this group, declines in morality with the additional screening have not yet been shown, and the false positive rate of this additional testing is extremely high – only 20% of abnormals are cancer  when biopsied.

There are no recommendations to use sonogram and MRI in otherwise low risk women, and none that have shown that using it based on breast density alone saves lives.

5. Additional screening adds significant costs to breast cancer screening.  For some women, this additional cost may not be covered by insurance. While Connecticut has passed a law mandating that insurers cover additional sonograms, New York State has not.

6. The law is a medico-legal nightmare.  The legislators are creating a medical standard where there is none. That however, has never stopped the lawyers.

I would expect a lot more business for radiologists doing defensive breast ultrasounds ordered by referring docs who don’t want to get sued for a missed diagnosis by a woman with dense breasts. After the first breast density law passed in Connecticut, the use of ultrasound in that state skyrocketed.  (The American College of Radiology, by the way, urges caution on breast density legislation.)

I would also expect a lot more lawsuits for missed diagnosis aimed at the referring physicians whenever dense breasts are noted on a mammogram, even if that woman had no other risks factors for breast cancer.

7. The EMR Makes This Law Unnecessary. As EMR use expands, women will be able to read their actual radiology report online. Those who want to know their density will, and the rest will not be unnecessarily alarmed.

8. The law violates the free speech of physicians. This regulation did not originate from within the medical community or the department of health. It is a lay attempt to push screening beyond what the evidence supports at this point in time, and to set a medical standard (ultrasound for every woman with dense breasts) that does not exist.

At This Point, What Can be Done?  

Short of radiologists filing a lawsuit claiming free speech violation ? (Not a bad idea I think…)

We have 180 days before the law takes effect. In that interval, I would recommend that the New York State Health department come up with some educational materials on breast density that informs rather than frightens women. They could include information about breast cancer, mammograms in general, their limitations, benefits and harms. And tell women what to do and where to go if they feel a lump or have a breast symptom.  This additional material can be included with the report so that women actually get the information they need about breast cancer screening, rather than an unexpected scare when what they thought they had just gotten was a normal mammogram.

Hmmm, that’s actually not a bad idea…If someone wants to pass a law that Department of Health written breast cancer screening info be given out at the time of Mammography, I’d get behind it in a second.

But telling the majority of women in their 40’s who have just had a normal mammogram that they may be at increased risk for breast cancer? That’s just wrong.

Mammograms Decline in 40-49 year Old Age Group

Since the US Preventive Service Task Force published revised guidelines recommending individualized screening schedules rather than routine annual mammograms for low to average risk women in their 40’s, the number of mammograms being done in this age group has declined.

In the year after the guidelines were published, nearly 54,000 fewer mammograms were performed on women ages 40 to 49. That represented a 5.72 percent decrease from the previous period. The authors said that the modest reductions probably reflected some public resistance to the new recommendations, in part because of conflicting guidelines from other groups that urge more frequent routine screenings.

I’m not surprised.

The study reflects what I’ve been seeing in my own practice – women in their 40’s asking “Do I really need this test?”  and “Can I wait till I am 50?”. In most cases, after confirming that a patient is not an increased risk of having concerning symptoms or exam findings, we end up compromising on an every other year schedule. This seems to be something both they and I can feel comfortable with in light of the newness of the recommendations and the current medical legal climate in the United States.  The few who have chosen to wait till 50 tend to be those who come from Europe (where mammgrams are done later than in the US) and those with prior experience, either personal or familial, of harms from mammograms.

Depo-Provera Use Does Not Raise Overall Breast Cancer Risk in Young Women

That’s the headline the media should have used when publicizing the results of a recent study comparing Depo-Provera use among women ages 20-44 with or without breast cancer. Because that’s exactly what the study’s authors found.

There was no difference in exposure to Depo-Provera among women with breast cancer compared to controls – about 11% of women in each group had ever used Depo-Provera.

Small Sub-group analysis raised a question

However, the researchers also did what is called sub-group analysis – looking at smaller and smaller groups within the breast cancer study population to see if they could find any women who might have a higher risk from Depo-Provera use, even if the overall group did not.

Before I get to those results, I need to point out that cases and controls, and Depo-Provera users and non-users had significant differences in body mass index, ethnicity, family history, age and pregnancy history – all factors related to breast cancer risk.  In addition, controls had had less mammograms than their counterparts who had breast cancer. There is also a large issue of recall bias at play in studies such as this, since we know that subjects with the disease or condition being studied tend to remember drug exposures better than controls do.

Despite these marked differences between the groups, no statistically significant difference was found between Depo-Provera use in breast cancer patients compared to controls.

BUT, when subgroup analysis was done, there was one group that showed a difference – women who had used Depo-Provera for a year or more within the past 5 years. Here’s the finding that led to the headlines –

However, recent users of DMPA (Depo-Provera) for 12 months or longer had a 2.2-fold increased risk of breast cancer (95% CI: 1.2-4.2).

That was all the media needed to hear, and they were off and running, with headlines such as “Depo-Provera shots tied to breast cancer ” and “Depo-Provera shots double breast cancer risk.” Such headlines fail to convey the overall results of the study in a way that is meaningful to anyone but the lawyers.

The Sub-Group analysis that raised concerns was conducted in less than 100 women

What the media did not tell you was that in this “large study”, the actual number of women in the sub-group that showed this statistically significant and concerning result was extremely small – only 34 controls and 36 cases had used Depo-Provera in the past 5 years. Among these, only 15 and 32 respectively had used Depo-Provera for a year or more in that time!

So there you have it – headlines based on a subgroup analysis of less than 100 women who were poorly matched to start with.

These kinds of studies raise far more questions than they answer

Subgroup analysis is a research tool to look for potential topics for further investigation or to inform questionable findings in the overall analysis. For researchers, this type of analysis can be valuable in defining areas for future larger study. But publicizing the results of a small subgroup analysis as if it were the findings of the larger group mis-represents the strength and reliability of the findings. And in this case, that publicity does nothing more that to frighten women away from using hormonal birth control.

I for one am not changing my prescribing practices around Depo-Provera based on this study. Depo-Provera remains an important contraceptive option for many women, although potential side effects (irregular bleeding, weight gain) limit its acceptability as a first line method for the majority of them.  Overall, about 3% of women who use contraception in the United States currently use Depo-Provera.

The discussion around breast cancer and current hormonal contraception is not new

The magnitude of the risk cited, and it’s relationship to current use of Depo-Provera in younger women, is similar to that which has been reported in the past in studies of oral contraceptives and breast cancer risk.  Specifically with Depo-Provera, the risk that appears in current users in some studies actually disappears with longer term use, suggesting that the mechanism may be acceleration of growth of pre-existing tumors, rather than induction of new cancers over time.

Overall, neither oral contraceptives nor Depo-Provera appear to increase lifetime risk of breast cancer. Both reduce the risk of endometrial cancers, and the pill reduces ovarian cancer risk.

Future research may elucidate better what the effect of medroxyprogesterone acetate, the drug in Depo-Provera and the one studied as hormone replacement in the Women’s Health Initiative, may be on breast cancer risk. For now, that risk has best been defined in post-menopausal women, and not in users of hormonal contraception.

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Further reading on Breast Cancer Risks and Depo-Provera

  • Depot medroxyprogesterone acetate and breast cancer. A review of current knowledge. Drug Safety Review, 1996
  • WHO Study showed similar results in subgroup analysis for current use in women under age 35.
  • WHO Memorandum on Depo-Provera and Cancer risks.
  • New Zealand study showing risk with longer term use in younger women, with same limitation of small numbers
  • Pooled Analysis of WHO and New Zealand Studies . JAMA 1995

Conflict statement – In the late 90’s, I published two studies of Depo-Provera acceptance and continuation, one of which was partially funded by small investigator-initiated grant from Upjohn that paid part of my research assistant’s salary, along with an NIH training grant.  I have no current conflicts to report.

Alternatives to Komen for Channeling You Dollars & Energy to Fight Breast Cancer

By now, you’ve heard that Susan G Komen For the Cure, which at first announced that it would withdraw its funding to Planned Parenthood for breast cancer screening programs, now appears to (but may not actually) have reversed that decision after an enormous public outcry.

Komen is not new to controversy.  Many have criticized their “pink-washing” campaign, which has promoted some very unhealthy products and brands in return for donations (Pink buckets of fried chicken? Really?…) But with this latest political move, they’ve gone too far for many of their supporters, some of whom say they will stop supporting Komen. Planned Parenthood, in the meantime, has raised record dollars since Komen’s initial announcement, topped off by a $250,000 matching grant from Michael Bloomberg.

I could go on and on about the controversy, but that’s not the point of this post, which is simply to answer the question I found myself asking – what should Komen’s former supporters do now? How can they channel their efforts to fight breast cancer if they are not going to give to Komen?

One option, of course, is to give to Planned Parenthood, The other option is to donate to one of the other charities on the front lines in the battle against breast cancer. Komen, after all, is not the only game in town.

Here are a few other places where your dollars will be put to good use fighting breast cancer. All of the following groups get high ratings from the American Institute of Philanthroy and/or Charity Navigator–

And if you’re not already donating to the fight against breast cancer? Well, maybe it’s time to start.

CNN Does a Nice Job Covering the Aftermath of the Mammogram Controversy

Kudos to CNN’s Lisa O’Neil Hill for a well-balanced and thoughtful article on the mammogram controversy. Absent from the article is hyperbole and stridency that make the medical community sound like a bunch of cats and dogs. Instead of “Them’s fightin’ words” soundbites, O’Neil Hill gives a well-written summary of all the major viewpoints on the issue.  She took the time to understand everyone’s point of view, and chose quotes that illustrate the fact that this is not a fight, but an intelligent discussion about how to maximize the benefits and diminish the harms of a less than perfect screening test for breast cancer.

“The initial recommendation from the task force caused a great deal of confusion, which was unfortunate because what I think they were trying to say is, I think, something very reasonable. The way they said it and the way it came out was very unreasonable,” said Dr. Otis W. Brawley, chief medical officer of the American Cancer Society.

“What the task force was trying to say is mammography is an imperfect screening tool and there are some harms associated with it, but there are also some benefits associated with it,” he said. “They were trying to say the benefits are not nearly as good as we would all like.”

Moyer said Brawley is on target.

“In many, many instances, our recommendation has been interpreted as a ‘don’t do it.’ That is incorrect,” she said. “It’s something that needs to be discussed on an individual basis. For some women, it will be consistent with their values to choose to have a mammogram between 40 and 50. For other women, they will choose not to, and those are both reasonable decisions.”

I strongly encourage you to read and share the article.

The Annual Mammogram – It’s What Women Want, But Is it For the Right Reasons?

Most women in their 40’s believe they should have annual mammograms, regardless of what screening regimen their doctor might recommend.

So say researchers in Massachusetts who surveyed women (primarily white, highly educated) ages 39-49 presenting for annual checkups. They gave the women a fact sheet about the new USPSTF guidelines on mammogram screening in their age group, and asked them to read one of two articles either supporting or opposing the guidelines. The researchers then asked women about their beliefs, concerns and attitudes about breast cancer and mammogram screening. Here’s what they found –

  • Women overwhelmingly want annual mammograms – Close to 90% of women surveyed felt they should have annual mammograms, regardless of what their doctor might recommend.
  • Women overestimate breast cancer risks – Eighty eight percent overestimated their lifetime risk for the disease, with the average estimate being 37%. (The correct lifetime risk for breast cancer is 12%). This is consistent with previous research on breast cancer beliefs.
  • The media may not influence women’s opinions about screening guidelines – No matter which article they read, close to 90% felt that that the (USPSTF) guideline changes were unsafe and 84% would not be comfortable delaying screening mammograms even if their doctor recommended it.
  • Friends and Family are a strong influence. Seventy six percent of women reported having a close friend or family member who had been diagnosed with breast cancer. Secondary analysis showed that 92% of those with a close friend or family member with breast cancer vs 77% of those without a close friend or family member with breast cancer felt women should continue to undergo routine mammography in their 40’s despite the new USPSTF guidelines.
  • The experience of false positive mammograms only reinforces women’s faith in mammogram screening. Ninety two percent of those with a prior false positive mammogram expressed discomfort with the USPSTF guidelines vs 79% of those who had not had a false positive mammogram.

This finding suggests that these patients were more likely to view the additional imaging and biopsies as a near miss rather than a false alarm. This is an important finding because it is in direct contrast to the conclusions drawn by the USPSTF, which cited psychological harm from false-positive results as one of the major risks of screening mammography in the fifth decade. Our findings are consistent with other research showing that women are very tolerant of false alarms if they perceive the issue being addressed as significant.

Breast cancer awareness or breast cancer misinformation?

Previous studies have shown that women not only over-estimate their personal risk for getting breast cancer, but also inflate their 10-year chances of dying from breast cancer by over 20-fold. They also wildly overestimate the efficacy of mammograms in lowering breast cancer mortality, believing it to be almost 100 times as effective as it actually is in reducing breast cancer deaths.

Who can blame women for believing they are at higher risks for breast cancer than they actually are? After all, breast cancer awareness campaigns have been among the most successful outreach programs ever created, with the pink ribbon being used at this point to market everything from jewelry to Kitchen Aid mixers. Whether these campaigns have actually had any impact in reducing deaths due to breast cancer remains a point of some debate, and there are those who credit the declines in breast cancer mortality more to new treatments than to increased uptake of mammography screening.

Have we lost women’s trust? 

With the disagreement among doctors about guidelines, the miscommunication of recommendations by the very folks writing the guidelines and the resulting confusion in the media attempting to report these guidelines, it’s no wonder women don’t trust their doctor’s recommendations and have made their own decisions about screening.

At this point, it’s probably easier to just write the mammo referrals once a year and move on. After all, the American College of Obs-Gyn agrees that women should be offered annual screening. And my medical-legal risks align nicely as well, since failure to diagnose breast cancer is one of the biggest reasons gynecologists get sued.

But it that the right thing to do?

Call me crazy, but I happen to think that an informed screening choice is still the best one.

I’m not giving up yet. My patients want to make their own decisions about mammograms, and that’s just fine with me. But I’m going to do my best to be sure that decision is not just a gut response to an inflated sense of risks, but a careful decision informed by risks as well as benefits of screening and realistic expectations about what mammograms can and can’t do to lower breast cancer mortality.

To that end, here are some great resources for getting better informed about breast cancer screening –

  • National Cancer Institute  mammogram information. NCI recommends having mammograms every 1-2 years starting at age 40
  • ACOG pamphlet on mammography – ACOG recommends that women be offered annual mammograms starting at age 40.
  • American Cancer Society information on breast cancer screening – ACS recommends having annual mammograms starting at age 40.
  • USPSTF guidelines on mammogram screening – USPSTF recommends having mammograms every 2 years from ages 50-74. The decision to start biennial screening in women under age 50 should be individualized.
  • Breast Cancer Coalition -31 myths and truths about breast cancer

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Davidson AS, Liao X, Magee BD. Attitudes of women in their forties toward the 2009 USPSTF mammogram guidelines: a randomized trial on the effects of media exposure. Am J Obstet Gynecol 2011;205:30.e1-7.

ACOG’s New Mammogram Recommendations – Not What You Think

The American College of Obstetrics and Gynecology has issued new breast cancer screening guidelines recommending that mammography be offered annually to women beginning at age 40. This is a change from their prior recommendations for mammogram screening every 1-2 years in women ages 40-49, and annually thereafter.

The media is playing the announcement as a face off between ACOG and the United States Preventive Services Task Force (USPSTF), which initially recommended against routine annual mammograms in women in their 40’s, but later softened that statement by saying that the decision to start mammograms in the 40’s should be an individualized one.

But is it really ACOG vs USPSTF? 

Here’s the statement from ACOG’s press release–

Based on the incidence of breast cancer, the sojourn time for breast cancer growth, and the potential for reduction in breast cancer mortality, the College recommends that women aged 40 years and older be offered screening mammography annually.

Here’s that statement in context in from the ACOG practice bulletin (requires paid subscription)-

Based on the incidence of breast cancer, the sojourn time for breast cancer growth, and the potential for reduction in breast cancer mortality, the College recommends that women aged 40 years and older be offered screening mammography annually.

However, as with any screening test, women should be educated on the predictive value of the test and the potential for false-positive results and false-negative results. Women should be informed of the potential for additional imaging or biopsies that may be recommended based on screening results. The physician should work with the patient to determine the best screening strategy based on individual risk and values. In some women, biennial screening may be a more appropriate or acceptable strategy. Some average-risk women may prefer biennial screening, which maintains most of the benefits of screening while minimizing both the frequency of screening and the potential for additional testing, whereas other women prefer annual screening because it maximizes cancer detection.

Hmm…..That’s not really so different from the USPSTF guidelines, which state –

The decision to start regular, biennial screening mammography before the age of 50 years should be an individual one and take patient context into account, including the patient’s values regarding specific benefits and harms.

There is a difference, however. By starting with a statement to offer mammography annually, ACOG seems to be trying take the USPSTF recommendations for individualized screening and put some teeth into them. They are also, I think, aligning themselves with the majority of women, who favor annual screening, regardless of its potential harms. (More on this tomorrow…)

As a clinician, what I think ACOG is saying is that I should be sure I offer an annual mammogram, even if the patient and I end up making an individual decision about having screening that goes another way. It’s a strategy that assures that every woman has the opportunity to have an annual mammogram if that is what she wants, ideally after she has engaged in a discussion that takes into accounts the benefits as well as harms of screening in the context of her own risks, beliefs and concerns.

I think that’s right.

Unfortunately, ACOG’s press release says nothing about individualizing screening decisions

It’s incredible, really.

Just like the USPSTF, ACOG has written a press release and summary statement that does not exactly match it’s recommendations or place them in context. Worse still, they have placed their full recommendations behind a paid subscription firewall, assuring that few folks other than gynecologists will have access to them. This deprives the public (and many reporters and bloggers) of the opportunity to read what is an extremely well-written summary of the current state of knowledge about breast cancer screening.

ACOG has also missed a real opportunity to better inform women about the magnitude of breast cancer risk (much lower than most women think), and the limitations of mammography (much greater than most women think).

Finally, and most importantly, by leaving out any context of individualized risk assessment, benefits and harms of screening, and shared decision making, ACOG has left the simplistic misperception that anything other than an annual mammogram is bad medicine.

And that’s just not fair.

To me, or to my patients.

And, as any women who has tried to fit into a one-size fits all pair of pantyhose will tell you, it’s a set up for failed expectations and anger on all sides.

Not to mention a really bad run.

The Doctor’s Wife Has Breast Cancer

If you’ve come here looking for Peter Bach’s recent New Yorker essay on his wife’s death, it’s here. And here are my thoughts on his essay.

A Well Blog post series in the NY Times, written by Peter Bach, MD, an attending physician at Memorial Sloan-Kettering Cancer Center in NYC, chronicle’s his experiences with his wife’s diagnosis and treatment for breast cancer.

As painful as it was to read of Bach’s wife’s breast cancer diagnosis and treatment, I found reading the comments section on the first few posts to be equally difficult. The comments ranged from supportive to downright vitriolic, as patients took the opportunity to vent at doctors and a medical system that they perceive gave Bach’s wife better access to treatment than theirs. The bitterness that comes through these comments is astonishing, but should not be.

Fortunately, as the series has progressed, the bitter comments have subsided. (And Bach has a much better photo…) His most recent post on how his wife’s doc refused to spout recurrence numbers for them was quite thought (and comment) provoking.

So, Doc, why not just tell us our odds?

Ruth’s oncologist elaborated on his refusal, promising he would tell us the number just as soon as we told him what probability of recurrence would cause us to make different choices for our lives.

Neither of us had an answer.

I encourage you to spend some time reading this excellent series and discussion it has prompted. I wish Dr Bach’s wife all the best for a speedy recovery and both of them many years ahead together.

Escitalopram (Lexapro) for Treatment of Hot Flashes in Menopausal Women

In a well-done placebo controlled study published in this week’s JAMA, use of Escitalopram (Lexapro) reduced hot flashes in post-menopausal women.

Investigators enrolled 205 women, randomizing them to either Lexapro 10 mg or placebo, with instructions to increase to two pills a day if needed after 4 weeks.

Lexapro users experienced about a 60% reduction in hot flash frequency over the 8 week study. About half ended up on the larger 20 mg daily dose by study’s end. The drug’s effect was apparent at about one week of use, and it was well-tolerated.

As in almost studies of menopausal treatments, the placebo group also experienced a significant reduction in symptoms – about 40% – but the difference between placebo and drug groups was significant. Compared to placebo users, Lexapro users had a bigger rebound of symptoms when stopping their treatment, were more satisfied and more likely to want to continue study drug, another validation of the drug’s efficacy.

Add another SSRI to the List of Drugs Proven to Treat Hot Flashes

The results of this study are not surprising. This class of anti-depressant medications (SSRI’s and SNRI’s) seem to have a modest but consistently shown impact on the vasomotor symptoms of menopause. All of the SSRI’s studied to date seem to have a similar efficacy – about a 60% reduction in hot flash frequency. None work quite as well as estrogen does, but in women concerned about breast cancer risks, SSRI’s may be preferable to hormone replacement, especially if mood issues are also significant symptoms.

Unlike their use in depression, where effects may not become apparent for 6 weeks or more, SSRI’s begin to work within the first 1-2 weeks when used to treat hot flashes (and, by the way, PMS…).

One advantage of citalopram is that, unlike some SSRI”s ( Paxil and Prozac),  it does not appear to impair the efficacy of tamoxifen. These other drugs interfere with the conversion of Tamoxifen to its active metabolites. Effexor is probably the safest to use with Tamoxifen, and has similar efficacy against hot flashes.  Other SSRIs that are considered safer than Paxil and Prozac are Zoloft and Celexa.  Since hot flashes are a side effect of Tamoxifen use, it’s nice to have yet another option to treat them.   (In order of interference with tamoxifen, from highest to lowest interference, the SSRIs are Paxil, Prozac, Zoloft, Celexa, and Effexor. Maybe I’ll do a post on this later…)

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1/19/11 Note – I updated and clarified the SSRI Tamoxifen interaction data for those interested.

HRT and Breast Cancer Deaths – Just in Case You Weren’t Listening the First Time…

A new analysis of long term data from the Women’s Health Initiative confirms what we already knew the first time around – Use of combination hormone replacement (HRT*) is associated with a small, but real, risk of breast cancer. This new 11- year follow up data carries that knowledge out to its not unexpected conclusion – namely, that some (although not most) breast cancers can be fatal, and therefore the the use of HRT can increase breast cancer mortality.

While it may seem a bit of a “Duh”, this study was, in fact, necessary to quell the WHI critics who continued to argue that the breast cancers caused by HRT were somehow less aggressive than those occurring off HRT. (They are not.) It was also a wake up call for many women who were continuing to use HRT and thinking that somehow its risks did not apply to them. A fair number of these women appear to be coming off of HRT, at least in my practice. Others are staying the course and accepting the risks as they have been defined. Either of which is fine with me.

The spin going on around this study – both for and against HRT use – is tremendous and ultimately confusing to women.  The pro-HRT crowd (some of whom have relationships to Pharma) is using language like “The increased risk from using HRT for 5 years is the same as if your menopause occurred 5 years later”, which is technically true but so what?  The bioidentical hormone crowd (usually also selling the same) are using the study to further hype how their regimens are safer than the evil Big Pharma products – based on no data. Which leaves the rest of us to try to find ways to help our patients understand the risks, place them into perspective for themselves and make a decision about how and if to treat their menopausal symptoms.

While the breast cancer risks associated with HRT use appear to be quite real, for a individual woman, they are not that large. Here’s how I explain the risks to my patients –

There will be 7 extra cases of breast cancer and 1.3 additional breast cancer deaths for every 10,000 women per year who use HRT. Said another way, if you use HRT for 20 years, your risk of getting breast cancer will be increased by 1.4 % and your chance of dying from breast cancer will be increased by about a quarter of a percent. If you use HRT for less than 20 years, we can cut those numbers down accordingly.**

If you don’t already know it, I do have my own set of rules for prescribing HRT. This new data has not changed them.

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* HRT means estrogen and progesterone taken together, as opposed to ERT, or estrogen alone. In the WHI, ERT use was actually associated with a lower rate of breast cancer, a finding unique to this study that begs for replication before we can bless ERT as breast-safe.

** The formula I used for cumulative risk is CR = 1 – e-IR*t ,where CR = cumulative risk, IR is the annual incidence and t is the number of years (in this case 20). If any statistician types reading this can confirm my methodology or numbers I’d appreciate it.

Graph above from JAMA. 2010;304(15):1684-1692.

Can the NBCC End Breast Cancer by 2020?

They think  so.

The National Breast Cancer Coalition (NBCC) is setting a deadline: End breast cancer by 2020. Breast Cancer Deadline 2020. It is time.

Taking a “just do it” approach, the NBCC has decided that by setting a deadline, they can make it happen.

In setting this ambitious goal, the NBCC criticizes the incremental advances in oncologic research that may take a drug to market but not actually impact long term survival from cancer or prevent it in the first place. (For example, Avastin, which is making billions for its manufacturer while not saving a single life from breast cancer to date.)

Researchers and the media often celebrate small accomplishments. We have been conditioned to believe that a drug that may extend life a few months is a breakthrough, that a 2% reduction in mortality is promising, that tumor regression or stabilization are cause for celebration, even though at that point there is no way to determine if anyone’s life was actually prolonged. We have settled for these limited, incremental changes along with the platitude “early detection saves lives” for too long.

While not doubting the integrity, sincerity and dedication of researchers, the NBCC appears to have lost patience with the system that creates and supports them and the industries that benefit from their discoveries.

More than 40 years and billions of dollars have not ended breast cancer. It has, however, created a robust cancer industry that thrives on raising awareness and producing drugs, screening devices and genetic tests. It has also created an academic system that generates hundreds of thousands of articles about breast cancer and builds careers for thousands. Although there is no doubt individual researchers sincerely want to end breast cancer, every system is perfectly designed to achieve the results it gets. The current system is perfectly designed to be lucrative, cautious and incremental.

They appear to be looking for an “outside the box” approach to breast cancer prevention and treatment that bypasses the conventional research and pharmaceutical industrial complex, and focuses solely on the eradication of breast cancer in a decade.

Their first initiative is the development of a breast cancer vaccine.

As our first project in the campaign we are currently working with a diverse group of stakeholders to create a five-year strategic plan to catalyze the development of a preventive breast cancer vaccine that could revolutionize breast cancer prevention.

My take

While I sympathize with the NBCC’s frustration with the research and pharmaceutical infrastructure, and with the lack of significant progress towards a cure for breast cancer, this 10 year goal is looking a bit pie in the sky to me.

They make comparisons with the eradication of polio. But they forget that we knew what caused polio – a single virus. We don’t even know yet what causes breast cancer –  so developing a vaccine against it seems premature. Even if we were to develop a vaccine, the long lead time to development of breast cancer mandates much longer than a 5-10 year project to prove efficacy. And let’s not forget subject safety – we can’t throw caution to the winds here, folks, or we risk losing even more lives to the race for the cure.

They recall John F Kennedy’s race to the moon – a goal that was clearly defined and visible in the night time sky to any child, and the path to which could practically be drawn with one’s hand. But the multi-factorial nature of breast cancer means that there are dozens of moons, in solar systems we cannot even see, with hundreds of possible paths to get there, and thousands of dead ends on the way.

We just may not be close enough to get there in 10 years.

I am reminded…

The NBCC ultimatum reminds me of two women I know who gave their longtime live-in boyfriends a deadline of New Year’s Eve to propose or get out.  That first one gave her ultimatum over 25 year ago, and it worked – they are still married today. The other gave hers just last year, and well, you can guess the outcome – he moved out.

While a 10 year deadline may have worked years ago – when science was simpler and the problems less complex –  such an approach may be a bit outdated today. After all, we have pretty much tackled the simple stuff and are on to the complicated things like cancer, drug resistant infections, HIV and the multi-factorial problems of hypertension, obesity and dementia.

If we knew how to do it, we would have done it by now.

All of this could change, by the way

A deadline would work, by the way, if we were to find a single necessary cause for all breast cancers – in the same way  we now know that the HPV virus causes cervical cancer.

If this were to happen, then yes, we could eradicate breast cancer – maybe not in 10 years,  but certainly in my children’s lifetime.

That same potential now exists to eradicate cervical cancer – if we could develop a vaccine that targets all the cervical cancer causing strains. Instead, we are vaccinating girls right and left with a vaccine that will certainly prevent some cervical cancers, but will never eradicate cervical cancer because it does not target the entire range of viral strains that cause cervical cancer.  It has, however, brought millions of dollars to the pharmaceutical companies that have developed it.

In this sense, I share the frustration of the members of the NBCC, who see profit-driven goals impeding the long term goal of disease eradication.

So I guess I’ll just wish them all the best in their efforts.

And send them a check.

Prophylactic Oophorectomy in BRCA Carriers Reduces Mortality

Removal of the ovaries (oophorectomy) in women who carry harmful BRCA mutations prevents both ovarian and breast cancer, and reduces overall mortality.

In a landmark study published last week in JAMA, researchers followed 2343 women with BRCA1 and BRCA2 mutations for a mean of 3-6 years (range 0.5-27 yrs), and compared cancer and mortality outcomes between those who had risk-reducing surgery (172 had mastectomy and 993 had removal of the ovaries) and those who chose not to have surgery. Those who did not have surgery were offered aggressive surveillance for breast cancer (annual mammography and breast MRI) and ovarian cancer (ultrasound and Ca125 testing every 4-12 months).

In women who underwent risk-reducing salpingo-oophorectomy, 1.1% were subsequently diagnosed with ovarian cancer (ie, primary peritoneal cancer), 11.4% were subsequently diagnosed with breast cancer, and 3.1% subsequently died of any cause. In women who did not undergo risk-reducing salpingo-oophorectomy, 5.8% were subsequently diagnosed with ovarian cancer, 19.2% with breast cancer, and 9.8% subsequently died from any cause.

Ovarian cancer risks were higher in BRCA 1 (7-8%) than BRCA2 carriers (3%) who kept their ovaries. No BRCA2 carriers who had their ovaries removed got peritoneal cancer during the follow up. (This is consistent with prior literature on these mutations and ovarian cancer risks.) Nine women who had their ovaries removed had small occult ovarian cancers diagnosed in the removed ovaries.

Prophylactic oophorectomy was also protective against primary breast cancer, cutting the risk in half – from 22% to 11%. In women who had prior breast cancer, oophorectomy reduced the odds of a second breast cancer from 14% to 11%.

Prophylactic oophorectomy appears to be more effective in BRCA2 than BRCA1 carriers – there were no breast or ovarian cancer-related deaths in BRCA 2carriers who had their ovaries removed.  The surgery appeared to be of equal value in women over and over age 50.

While prophylactic mastectomy indeed reduced the risk of acquiring breast cancer (no women who had the surgery got breast cancer), it did not impact mortality.

Bottom Line

Women who carry harmful BRCA mutations have a markedly increased cancer risk ; 15-40% will develop ovarian cancer in their lifetime (compared to about 1% of the general population) and 6-% will develop breast cancer (compared to 12% of the general population of women).

While we can offer BRCA mutation carriers effective screening for breast cancer (mammogram, sonogram and MRI), we do not have an equally effective screening tool for ovarian cancer. Even the much touted ultrasound and Ca125 tests have not been shown to reduce mortality from ovarian cancer. In this study, in fact, women were offered sonograms and Ca125 testing, and although we do not know to what extent they actually availed themselves of the surveillance, it clearly did not offer them the same protection against ovarian cancer as oophorectomy.

The protective effect of oophorectomy in carriers of harmful BRCA mutations stands in marked contrast to oophorectomy in women at average risk of ovarian cancer, which has been shown to actually increase mortality when performed in women under age 65.

What are the risk factors for having a harmful BRCA mutation?

About 2% of women have risk facotrs for BRCA 1 and 2 mutations. According to the NCI, these are –

For women who are not of Ashkenazi Jewish descent :

  • two first-degree relatives (mother, daughter, or sister) diagnosed with breast cancer, one of whom was diagnosed at age 50 or younger;
  • three or more first-degree or second-degree (grandmother or aunt) relatives diagnosed with breast cancer regardless of their age at diagnosis;
  • a combination of first- and second-degree relatives diagnosed with breast cancer and ovarian cancer (one cancer type per person);
  • a first-degree relative with cancer diagnosed in both breasts (bilateral breast cancer);
  • a combination of two or more first- or second-degree relatives diagnosed with ovarian cancer regardless of age at diagnosis;
  • a first- or second-degree relative diagnosed with both breast and ovarian cancer regardless of age at diagnosis; and
  • breast cancer diagnosed in a male relative.

For women of Ashkenazi Jewish descent –

  • any first-degree relative diagnosed with breast or ovarian cancer; and
  • two second-degree relatives on the same side of the family diagnosed with breast or ovarian cancer.

Women who have none of these family history patterns have a low probability of having a harmful BRCA1 or BRCA2 mutation.

How I Will Use these Study Results

I encourage women with suggestive family histories to see a genetic counselor to discuss BRCA testing. Despite making many such referrals,  I find most women don’t follow through.  “Why should I want to know?” they ask.  “What would I do differently if I had the BRCA gene other than worry?”

It’s an important question that deserves an answer. So I tell them –

We would offer prophylactic oophorectomy. That’s because we have no good screening that has been proven to reduce ovarian cancer mortality. But if we remove the ovaries, we can significantly reduce the odds of getting both ovarian and breast cancer.  With this new study, I can now tell these women that this cancer risk reduction also translates to a significant reduction in mortality. And give them some numbers to chew on as they think about what, if anything, they want to do.

The decision to proceed to oophorectomy is never undertaken lightly. Which is why BRCA testing is helpful – it may allow us to avoid surgery in women who test negative for harmful mutations. It is also why we offer oophorectomy at too young an age and certainly not until childbearing is completed in women who do carry harmful mutations. Sometime in the 40’s seems about the right age for oophorectomy in BRCA mutation carriers. The surgery can usually be done laparoscopically, with same day discharge in many cases.

The price we pay for oophorectomy, of course, is menopause. Menopause that we may not want to treat with estrogen because of your predisposition to breast cancer. However, there are non-hormonal ooptions for hot flashes that can be effective. And here it can get complicated, as some patients decide to have a hysterectomy as well as an oophorectomy, so that they can take unopposed estrogen, which (at least in the WHI) is not associated with an increased risk for breast cancer. (Not unreasonable thinking, in my opinion…) But these are just some of the things you’ll want to think about before considering prophylactic oophorectomy.

I don’t push prophylactic mastectomy, although it is certainly an option for BRCA carriers. This study makes this feel even more reasonable, because while mastectomy certainly prevented breast cancer, it did not significantly reduce mortality from breast cancer. I suspect that is because we’re pretty darned good at screening for breast cancer, and have very effective treatments. But some women will choose mastectomy regardless.

For women with suggestive family histories who choose either not ot know their BRCA status, or who opt for surveillance only, I encourage enrollment in a clinical trial of new screening methods for ovarian cancer. For those who don’t do this, I will do ca125 and sonograms, simply for the lack of anything else better to do.

One of these days, we’ll hopefully have an effective screening test for ovarian cancer. But until then, prophylactic oophorectomy remains an important option for women at increased risk for ovarian and breast cancer due to harmful BRCA mutations.

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NCI Fact Sheet on BRCA mutation testing

NCI Bulletin on this research study

Paroxetine (Paxil) Impairs Tamoxifen Benefits in Breast Cancer

An important Canadian study has shown that the use of paroxetine (Paxil) in breast cancer patients taking tamoxifen is associated with an increased risk of death from breast cancer. These findings, which were published this week in the British Medical Journal, add to a growing body of evidence that certain (but not all) SSRI antidepressants neutralize tamoxifen’s beneficial effects in treating breast cancer by interfering with it’s metabolism.

First, a few things about the study –

  • The study was done using a combination of pharmacy records, cancer registry records, hospital databases and death certificates in seniors, the age group for whom this data were readily available.
  • The study included women taking both tamoxifen and an SSRI between 1993 and 2005.
  • The median age was 74 years old (range 70-79 years)
  • We know nothing about the stage of breast cancer in these patients
  • By the end of the 2.8 year follow up, 44% of the participants had died from any cause (not surprising given the age of the study cohort), including 15% in whom breast cancer was listed as one of the causes of death.
  • No comparisons were done among women taking tamoxifen only. The researchers compared women taking different SSRI’s to one another, and within each SSRI group, compared different duration of uses as a way to measure the effect of the potential interaction.

What the researchers found

Use of Paxil was associated with an increase in deaths from both breast cancer and other causes during the follow-up period. (See PowerPoint graph ). The increase in risk was higher with longer overlapping use of Paxil with tamoxifen, and ranged from 25% to 91% increase as time on the two drugs together increased, meaning that the risk was almost double with longest use in the study. All of these results were statistically significant. (For those who know statistics, that’s a relative risk of 1.24 to 1.91 and the 95% confidence intervals did not include 1).

In more meaningful layman’s terms, there will be 1 additional breast cancer death for every 20 women taking Paxil and Tamoxifen together 41% of the time (the average in the study). If Paxil is taken the entire time tamoxifen is used, there will be 1 additional death for every 7 women treated with both drugs.

What is additionally interesting about these numbers, according to the study’s researcher Dr. David Juurlink (who graciously agreed to speak to me today), is that 7 is the number of women need to treat with Tamoxifen to prevent one breast cancer death. So, Paxil essentially is neutralizing the tamoxifen effect.

The Results are Biologically Plausible

In order to be effective, tamoxifen must be converted in the body to its active metabolites, the most potent of which is 4-hydroxy-N-desmethyltamoxifen or endoxifen. The conversion of tamoxifen to endoxifen is catalyzed by an enzyme called CYP2D6. SSRI antidepressants interfere with CPY2D6 to varying degrees, with Paxil being the most potent of the SSRI’s in this regard . (So potent that they actually call it “suicide inhibition”.) Thus, use of Paxil makes tamoxifen less effective, attenuating the survival advantage imparted by tamoxifen use.

(Note – Not all women are inherently able to optimally metabolize tamoxifen to its active metabolites, and research suggests that so called slow metabolizers of tamoxifen may have worse breast cancer outcomes. Genotyping for CYP2D6 variation may prove to be a useful genetic marker for tailoring of cancer treatment in this group.)
Another expected finding of the study was that women taking Venlafaxine (Effexor) had a reduced risk of breast cancer deaths. Venlafaxine is used to treat the hot flashes associated with tamoxifen use, and women who have hot flashes while using tamoxifen may have better survival, probably because the hot flashes are a good sign that the Tamoxifen is being activated to Endoxifen. So this group would be selected to have better survival from the start, and the use of a weak CYP2D6 inhibitor doesn’t appear to impede this survival advantage within the study group.

What was unexpected in the study results was that fluoxetine (Prozac), another known potent inhibitor of CYP2D6, was not associated with an increase death risk compared to the other less potent CYP2D6 inhibitors. The researchers warn, however, that this may be due to the relatively small numbers of women on this drug in their population. “We want to be careful that this study is not used to bless the use of fluoxetine in tamoxifen users”, says Dr Juurlink.

A few more notes on study design

Given the robustness of the data sets they had, which appear to include both cancer registry and hospital records, it’s a shame that the researchers did not have information on breast cancer stage, an important potential confounding factor. It’s a limitation of the study that they acknowledge in the paper.

I also found it odd that the researchers chose only to compare the SSRI’s to one another, without having a control group of tamoxifen users not taking an SSRI. Juurelink explained that this was a deliberate choice, to avoid potential unknown variables that would affect mortality and be associated with the need to use antidepressants.

Importance of Drug-Drug Interactions

We were first clued in to the potential interactions between SSRI’s and tamoxifen in 2005, when a landmark paper was published in JNCI on the pharmacologic interactions of these two classes of drugs. Since them, several other pharmacologic studies have confirmed the interactions and clarified which SSRI’s are problematic and which are not, and concomitant use of the more potent PYP2D6 inhibitors has decreased. In 2009, a paper presented at the American Society of Clinical Oncology reported that women who used a potent or moderate CYP2D6- inhibiting SSRI (paroxetine, fluoxetine or serttraline) in conjunction with tamoxifen had a two-fold increase in breast cancer recurrence compared to use of weakly-inhibiting SSRI’s (citalopran, escitalopram and fluvoxamine). This BMJ study is the first to report an increase in breast cancer mortality resulting from these interactions.

Enormous credit goes to those who first suspected this interaction between SSRI’s and Tamoxifen, did the excellent research to confirm it, and then went the extra mile to help identify which SSRI’s are safe to use with tamoxifen and which are best to avoid. Treatment of depression in cancer patients can be critical to both their physical as well as emotional recovery, and it’s important that we continue to have options that are effective for depression without interfering with cancer treatment.
What should you do if you are on an SSRI and Tamoxifen?

First of all, DO NOT suddenly stop your SSRI, since severe withdrawal symptoms can occur. DO talk to your doctor about which SSRI medication you are taking. If it is paroxetine or fluoxetine, it is recommended that you try to change to an SSRI that is a less potent or non-inhibitor of tamoxifen metabolism.
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Kelly, C., Juurlink, D., Gomes, T., Duong-Hua, M., Pritchard, K., Austin, P., & Paszat, L. (2010). Selective serotonin reuptake inhibitors and breast cancer mortality in women receiving tamoxifen: a population based cohort study BMJ, 340 (feb08 1) DOI: 10.1136/bmj.c693

Photo licensed from Istockphoto.com

Pink Glove Dance

I’ve been too busy to blog yet about the new mammo and cervical cancer recommendations, but promise that I will very soon. In the meantime, enjoy this video made by employees of the Providence St Vincent Health System in Portland, Oregon to raise breast cancer awareness.(Thanks to Carrie for forwarding it to me)

Drugs for Cancer Prevention – NY Times Misses the Point

In yet another article addressing the war on cancer, The New York Times today tackles cancer prevention, focusing on alternative and mainstream Pharma products marketed to reduce the risk for cancer.

While author Gina Kolata seems to have done her homework when it comes to the failure of alternative medicine to prevent cancer, she has missed the story completely when it comes to telling why the medical profession and patients may have failed to embrace Big Pharma’s push to use their drugs to prevent breast and prostate cancer. Of course, that’s not surprising since almost exclusively, the experts she interviewed were those who conducted the clinical trials of these drugs.

Since I’m not a urologist, I’m not going to comment on the use of finasteride to prevent prostate cancer, except to point out that the one expert quoted in favor of its use has served as a consultant to Merck and AstraZeneca, both of whom make the drug, while the other works for Astra Zeneca.

So let’s talk about tamoxifen and raloxifene, two drugs that are approved for the prevention of breast cancer.

Tamoxifen and Raloxifene

The maker of Evista (raloxifene) is targeting both docs and women, urging them to calculate their lifetime risk for breast cancer and consider taking the drug if that risk for breast cancer is increased. Since raloxifene is also approved for treatment of osteoporosis, the drug makers are selling it as a two for one.

Both tamoxifen and raloxifene cut the risk for breast cancer in half among high risk women who use the drug for 5 years. Tamoxifen also prevents DCIS and LCIS in addition to invasive cancer, while raloxifene does not reduce these risks.

But, Tamoxifen can cause uterine cancers. The risk is low, about 1 in 500, but includes uterine sarcomas, a particularly aggressive tumor, and may persist even after the drug is discontinued. There is no screening for uterine cancer in tamoxifen users – ultrasound is useless, since the endometrium very frequently appears abnormal even if there is no cancer. We docs are left telling women just to tell us if they blee

Now, for women who are taking tamoxifen for treatment of breast cancer, the risk for uterine cancer is almost always outweighed by the benefits in terms of cancer treatment. But for woman who have never had (and may never get) a breast cancer, the uterine cancer risk is a deal breaker, especially when she asks what I can do to screen her and I tell her “nothing”. I can quantify it for her – look, your risk for breast cancer will be reduced from 20% to 10%, I might say – and your risk for uterine cancer increased by less than one percent.

Okay, I’m interested, she might say. So tell me – Are there any other risks?

Yes, I’ll say.

Both raloxifene and tamoxifen carry an increased risk of thromboembolism. According to the package insert for Evista (raloxifene), DVT occurred in 1 out of every 100 women using the drug for an average of 2.6 yrs, over twice the rate for placebo users. Fatal stroke risk was about 1.5 times higher in Evista compared to placebo users, though that risk was concentrated in postmenopausal women at increased risk. Unfortunately, nowhere in the marketing materials for Evista is there a risk calculator that helps me or my patients assess their personal risk for these complications from the drug.

So, I’ll fudge it. Now my risk calculation for this patient looks something like this – Breast cancer, lowered from 20% to 10%. Uterine cancer, increased by 0.2%, but no screening. Blood clot risk = 1%. Fatal stroke risk = 0.3% over 5 yrs if you have risk factors, miniscule if you don’t.

Okay, she’ll ask me. How is it going to make me feel?

Probably fine, I say, but there are some side effects that might bother you, the most common of which is hot flashes in about 10% of users. Some women experience joint pains and leg cramps as well. These symptoms can occasionally be severe, although only about 1% of users stopped the drug because of hot flashes in the clinical trials. And most women will notice an increase in vaginal mucus that, as a gynecologist, I don’t have concerns about. Not uncommonly, my patient will have had a friend who has experienced a bothersome side effects from taking Tamoxifen. That’s usually the kiss of death for any drug – a girlfriend with a side effect…

And oh yeah, there’s also the increased risk for cataracts with Tamoxifen, but not raloxifene.

Now, if a woman has osteoporosis, I can add that to the plus side of the balance scale for raloxifene use. Now I’ve got to do her risk for fracture based on her bone density and talk to her about the other options she may have to treat her osteoporosis as well.

Is anyone really wondering why we docs and our patients haven’t jumped onto Big Pharma’s cancer prevention bandwagon? We’re asking patients to balance competing statistical risks for conditions she may never get, in return for a benefit she may never need.

I do prescribe raloxifene it for treatment of osteoporosis, and if there is a strong family history of breast cancer, I may even try to steer my osteoporotic patients who are not at increased risk for clots towards using it. However, it is the rare patient who chooses this drug over a bisphosphonate such as Fosamax and Actonel when I inform her of the risks and benefits of both these classes of drugs. Even patients with strong family histories of breast cancer just don’t want the potential side effects of a drug in return for a reduced risks for a cancer they may never get.

Hello – Birth Control Pills?

Kolata completely misses out on the fact that millions of women are already taking a pill that reduces their risk for cancer – the birth control pill. It cuts ovarian cancer by up to 80% and endometrial cancer by almost half.

Like Tamoxifen and Raloxifene, the pill carries an increased risk of blood clots, a trade off many women are willing to make in return for prevention of pregnancy, which itself carries an even higher risk of clotting. Not to mention the benefits the pill can confer for women with menstrual disorders such as dysmenorrhea, menorrhagia, endometriosis and its efficacy in treating acne and even PMS. For most healthy young women, the balance of benefits and risks of pill use is favorable, even before considering the cancer prevention aspects of the p

For the record, I inform each and very patient who starts estrogen containing birth control that there is an increased risks of clots. I quantify it for them, tell them that it is a real risk and give them strategies they can use to minimize these risks. Surprisingly, that discussion has rarely deterred a patient from starting on hormonal birth control. It may be that pill patients are younger and feel more invincible than the older women being targeted by the makers of Evista. But I think most of them are actually weighing their risks of pregnancy against the risks of blood clots, comparing this to their perceived downsides of barrier methods and/or the IUD, and coming out on the side of using the pill.

Prevention is the holy grail for Big Pharma

Let’s face it – an indication for prevention of a disease grows the potential market of a drug by millions. But if you’re going to market a drug to healthy individuals, it better be free of risk or have some other benefit that patients can see right away.

Otherwise, it just ain’t gonna’ sell.

Which probably explains why Kolata tells the story of the cancer prevention challenge as though it were a failed pharmaceutical marketing campaign. Missing from her article, unfortunately, is the question that asks whether pharmaceuticals are really the right strategy to prevent cancer. Or that asks if we really mean to ask 100% of men over 50 to take a drug to prevent prostate cancer, when, in the same breath, we are telling them we should stop screening for it? Or whether 100% of women over 60 take a drug that increases their risk for thromboembolism and uterine cancer so that 20% of them won’t get breast cancers that some are suggesting may regress or be so indolent that they will die of something else before it kills them?

Of course, we could just sell them another drug to lower their clotting risks..