Category Archives: Breast Cancer

Mammogram Screening Comes under Question

Denise Grady frames the recent debate on mammogram screening in today’s New York Times. The article tag teams and improves upon Gina Kolata’s recent story on the topic.

These articles highlight what we health professionals have known for some time about mammograms – they are not perfect.

About 10% of cancers will be missed by mammography alone. About 65% of so-called “positive mammograms” end up being benign on biopsy. We really don’t know what we are supposed to be doing with DCIS – is it precancerous, and should we be treating it? And finally, some cancers are faster-growing and more likely to kill you than others, and mammography is not so good at figuring out which is which.

Countering this imperfection is the one very important little piece of information that barely gets mentioned in these articles about mammogram screening – the mortality rate from breast cancer is lowered by mammography, by about 20% or so, depending upon which study you quote.

If you’ve never really heard all this before, it’s not surprising. The debate now being played out on the pages of the Times has until now been held pretty exclusively among health care experts, with the results of that debate becoming the recommendations we all know and love – mammograms every 1 to 2 yrs from ages 40 to 50, then annually thereafter, till an as yet not defined upper age, when one weighs the need for mammograms against the overall health and projected longevity of the individual.

If it sounds complicated, well, that’s because it is. And until now, the approach doctors and patients took to complex issues like this was simply – we docs know more than you do. Allow us to weigh and measure the risks and benefits for you, consider costs while we’re are at it, and then we’ll tell you what we think is best and you’ll do it.

The price we are now paying for this simplistic approach to screening is a loss of faith on the part of the public, who have taken our endorsement of mammograms to be a guarantee of infallibility and a promise to lower breast cancer mortality across the board. We’ve struck out on both counts.

So now, like a parent whose child one day sees us as the imperfect humans we are, we docs are having a bit of a mid-life crisis. Do we stick to our guns and keep the same old recommendations, imperfect as they are? Or do we arm our patients with the facts and let them begin to make their own decisions about mammography?

One thing I think we do need to be careful about is allowing the pendulum to swing too far in the other direction – making the decision to advise women to forgo mammography due to a risk of over-diagnosis and over-treatment. This approach, framed in terms of prevention of anxiety and morbidity, but with an underpinning of financial cost savings, uses the same simplistic thinking we’ve used in the past to aim patients in the opposite direction, away from screening.

While there is much talk about how screening may not benefit more indolent cancers, the fact remains that we don’t have reliable non-invasive testing to identify which cancers are slower growing and which are not. Nor do we know how to stratify women into high and low risk groups for these cancers, other than genetic testing and imperfect modeling, which only identify a subset of at-risk women. To substitue another imperfect screening methodology for current guidelines just trades one set of problems for another.

I am more than happy to entertain the mammography debate with my patients, some of whom may want to forgo annual screening when they learn what I know. If I know my patients, I predict that most will continue to accept a chance of a false positives in return for a potentially reduced mortality from breast cancer.

But stay tuned – this discussion is likely to go one for some time.
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Orac takes on the topic. Nice discussion of the issues.

What is the Role for Breast Sonogram?

The WSJ has an article this week discussing MRI and breast sonogram as adjuncts to mammogram, and the debate going on in the medical community as to how these modalities should be used. The article does a nice job framing the debate that is occurring among physicians regarding when to use these modalities.

Medical practitioners are divided about the proper role of ultrasound in breast-cancer screening. Wendie Berg, a radiologist at a clinic in Lutherville, Md., who was the lead author of the study published in JAMA, says she recommends ultrasound screening to some women who don’t have evidence of very high risk that would justify an MRI. “It is a judgment call. The denser the breast, the more difficult the mammogram is to read, the more likely I am to recommend an ultrasound,” she says.

But Constance Lehman, a University of Washington professor of radiology who led a study published last year in the New England Journal on MRI screening, says she never advises ultrasound for patients. “We find it ineffective as a screening tool,” she says. “It’s not even in the same ballpark” as an MRI.

I’ve been actively debating the songram issue with an internal medicine colleague. She’s anti-sono, I tend to favor the screening method, but with caveats. She and I decided the issue is pervasive enough to discuss publicly, and are setting up a debate forum this fall with a panel of respected breast specialists and radiologists to see if we can come to some resolution on the matter.

Will let y’all know how that turns out.

Living a Life After Cancer

I have some amazing patients.

Take Carrie Wells. Carrie’s a breast cancer survivor who has done so much more than survive – she’s moved beyond her diagnosis and used what she has learned to master the art of living a life.

If you do not let cancer dissolve your spirit, it will be the doorway to learning… I faced my long, losing battle to control change, to put reason to the cancer, and decided to heal.

Carrie credits her energy for life to her experiences at the Life Beyond Cancer Retreat in Arizona in 2004. It was there that she healed, de-stressed and discovered that she had the inner resources and energy to create and live a life after cancer.

Such retreats make so much sense. So many women with cancer get their diagnosis and then move through treatment while working either in or out of the home, leading busy lives and often caring for children and even parents while fighting the battle of their lives.

You know these women – heck, you may be one yourself. Fitting in radiation treatments before work or during lunch hours, heading back to work two weeks after surgery, popping chemo pills between meetings. Most barely take the time to heal physically, let alone emotionally and spiritually. Certainly few take the time to rejuvenate and regroup.

Carrie is determined to help other women heal the way she has. She has created a web portal called Survivor’s Retreat, where cancer survivors can search for retreats, workshops and other destinations that offer healing experiences, relaxation, exercise or just plain pampering – whatever you think you need to heal. You can search on Carrie’s site by location, cost and type of retreat to find just the right escape you need.

Do send a link to the site to a friend or loved one dealing with a cancer diagnosis. And if you know someone who sponsors a retreat, let Carrie know so she can include it on the site.

Carrie’s just been named as one of 25 Yoplait champions, an award that honors “ordinary women and men from across the country doing extraordinary things in their local communities to help in the fight against breast cancer”.

See? Amazing.

HPV and Breast Cancer? Interesting, but too soon to say

Read a fascinating post in Aetiology regarding the potential role of HPV in the etiology of breast cancer.

Although we are nowhere near proving a direct causation, studies have found HPV DNA in anywhere from 20-85% of tumors studied. (Types 16, 18 and 33 most commonly) However, some studies have found HPV DNA in normal breast tissue as well. So is HPV a cancer-causing agent in the breast or just a bystander? It’s too soon to say. Lots more work is needed on this one, folks.

The data are at odds with known risk factors for breast cancer, such as never having been pregnant. And if there is a link, one should see that breast cancer risk is increased with number of sexual partners, which as far as I know, is not the case.

So be careful before making the leap between hypothesis and recommending HPV vaccination for breast cancer protection. It’s way, way to soon…

An Inflammatory Video on Inflammatory Breast Cancer

An email with an absolutely frightening You Tube Video attachment is screaming its way across cyberspace to your inbox with the subject line “For all women – watch this video. It is no joke!” The video is a news story called “Inflammatory Breast Cancer – the Silent Killer”.

The news story first aired in 2004, as a response to a Seattle woman’s personal campaign to make sure every woman in America knows about this cancer that afflicted her daughter. Since then, according to the station that originally aired the story, the video has made its way to over 10 million women via the internet. The response has been an upswing in information about IBC both on the web and in conventional media, the creation of a foundation that is raising money for IBC research and treatment, and the opening of the first Center for IBS treatment and Research.

And that’s a good thing.

What’s not a good thing

What’s not such a good thing is the tone of the news story. It has all the makings of a viral scare campaign, not the least of which is the “Silent Killer that strikes without warning” phrase. If you didn’t know about IBC before, you sure as heck know about it now, and probably, like me, were up till 3 am scouring the web to learn more because you were convinced that you had it. And that’s what’s wrong with this latest “tell someone” campaign. It’s knowledge predicated on fear.

You need to know that the medical facts in the video are correct. But the context is not. Statements like “Hope for millions of women” give the sense that this is a very common cancer, when it is just not.

IBC is rare. So rare that docs typically never see a case in their entire career, or like me, see one or two cases in twenty years. But instead of having that knowledge reassure you, the news story uses it to scare you. Because if your doctor never sees a case, they are sure to misdiagnose it, so you’d better be sure that you know how to diagnose it yourself.

Would that it were so simple. The problem with IBS is that it’s early symptoms are so common – breast itch, rash, redness, pain. I’m sure all of us have had these symptoms at some point in our lives. And when it presents, IBC looks a heck of a lot like mastitis, a condition that many, many of us (including me) have had at some point.

Thus, another very important fact this that the video doesn’t tell you is this – If you have the symptoms they describe, the odds are overwhelming that it is not IBC.

Some Context

If you read this blog, you know that I applaud anything that empowers women, and I do believe knowledge is power. But knowledge packaged with hype and fear is the wrong kind of knowledge.

So, let me try and do what the video did not. Let me try to give you some context.

The incidence of breast cancer in the US is 100 per 100,000 women per year. Compare that to the incidence of IBC, which is 2 per 100,000 women per year. That’s about 3000 cases of IBC occurring annually in the whole country.

Now, note that 4.3 million Americans are injured and 40,000 more die in auto accidents every year.

I’ll bet you’re really scared now, aren’t you?

That’s okay. There’s always the subway.
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If you want to learn about IBC in a way that will not frighten you, skip the video and visit MayoClinic.com or the National Cancer Institute Website.

Thanks to Linda for tipping me off about this video.

BRCA Mutations and Familial Breast Cancer Risks

A study published this week in JAMA examines the risk for breast cancer in the families of women with breast cancer.

The researchers studied 2000 women with breast cancer diagnosed before age 55. Of these, about 5% of the women with unilateral breast cancer were found to have either the BRCA 1 or BRCA 2 gene mutation, while 15% of women with bilateral breast cancers were gene mutation carriers.

Overall, 75% of women with breast cancer were the only person in their immediate family to have had the disease. Among BRCA mutation carriers, 58% were the only member of the immediate family with breast cancer.

The risk for breast cancer in family members varied widely, from 30-90%, and was highest in families of women with cancers at an early age and with bilateral breast cancers.

Significant weaknesses of this study, in my opinion, were that family history of second and third degree relatives was not assessed, cancers up to age 55 (and not the usual age 50 cut off) were considered, and data on family history of ovarian cancer was not included. Family members were not assessed for the prevalence of the gene mutation, and their histories were taken second hand from the breast cancer subjects. This, the penetrance of the BRCA gene in these families was only presumed, not measured.

What To Do with this Info

The take home messages for me from this study were these –

1. BRCA testing is still uncommon, even in women who have had breast cancer. The younger your age at diagnosis, the higher the odds you will have a BRCA mutation. I believe testing is worthwhile in women who have had pre-menopausal breast cancer. But even in this group, most will test negative.

2. If your Mom or sister had breast cancer under age 55, odds are still that it was not a BRCA-related cancer. The more family members and the younger the age, the higher the risk. The best way to find out is for that person to get tested. If that person is positive, the next best step would be to get yourself tested.

But before doing this, talk to your doctor, and think hard about what you would do differently if your test was positive.

3. Even if you are a BRCA carrier, we really can’t reliably quantify your risk of breast cancer other than to say it is somewhere between 30 and 90% by age 70. That’s not very helpful, is it? The variability in risk is probably due to other genetic factors that interact with BRCA.

Family history itself may be your best indicator of your own risks. If your relative had breast cancer at a young age or had bilateral breast cancer, your risk is higher than if their cancer was at an older age and unilateral.

But how high is too high? What’s your personal risk tolerance? Does it vary with age? At what point would you take a medication (Tamoxifen or Evista) to reduce that risk? At what point would you have your ovaries removed? Not easy questions. Here’s the story of one woman who had to deal with these issues.

Myriad, the company that makes the test, has begun aggressively marketing the BRCA screening test, a step that I believe is premature. What we know about BRCA was largely learned from testing Ashkenazi Jews, a group known to be at increased risk. But we still don’t know the true prevalence or penetrance of this gene in the general population, and what it really means to be a carrier. Before we start mass screening and mass mastectomies and oophorectomies, we better know what the risks truly are for having this gene.

Studies such as this one are helpful in better defining that risk, but we have a long way to go before mainstreaming this genetic screening test.
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Screening Mammograms After Age 70

There are no universal recommendations for routine mammograms in women over age 70. That’s because we don’t have robust mortality data from mammogram use in this population. And so, older women are advised to make their own individual decisions about mammogram along with their doctor, based on other medical issues, life expectancy and health beliefs.

But do women have the information they really need to be deciding this question?

That’s what researchers at the University of Sydney asked when they did a study to determine what would happen if they gave women over age 70 Decision Aids (simple, visual aids) to inform their decision about having screening mammograms.

Here is an example of a decision aid. It visually represents the risk in 1,000 women over age 70 of being diagnosed with breast cancer over the next 10 years (brown boxes) if you do (right group) or don’t (left group) have a mammogram, as well as the chance you’ll have an unnecessary biopsy as a result of a false positive mammogram (dark purple boxes on the right).

The researchers found that while the women using Decision Aids made more informed decisions about having mammograms, the information did not impact the rate of mammogram use in the study population. There was an impact in that undecided women tended to get off the fence and make a choice, and women felt less anxiety and insecurity about the choice they made.

So, for most women, what Decision Aids do is make them feel better about their choices. Which says to me that most patients (and I suspect, doctors) make pre-determined decisions about mammography based on factors unrelated to the statistics of outcome, but use those statistics to support their beliefs, whichever way they decide.

Sort of like politics.

But unlike politics, those designing the decision aids are not trying to move votes, they’re trying to help you find the choce that’s right for you. If you’re undecided, or ucomfortable with your choice, a decision aid may be just the right thing for you.

Now if someone would just come up with a decision aid for the 2008 elections…
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The researchers are conducting a similar but web-based trial for younger women (over age 40). If you want to participate, or see what a decision aid is, click on the link below.

http://www.mammogram.med.usyd.edu.au/

It’s really interesting, I encourage you to do it. See if it changes your choice about mammogram or not. Or just makes you feel better about your choice.

Declining Breast Cancer Rates – The Plot Thickens…

Breast Cancer Rates (From NEJM 2007. 356 (16): 1670)
The decline in breast cancer rates that begain in mid-2002 appears to have been sustained through 2004, according to a recent paper in the New England Journal of Medicine. This unprecedented drop in new breast cancer cases occured just after the publication of the results of the Women’s Health Initiative, when millions of American women stopped taking hormone replacement.

The coincidence in timing between the drop in HRT use and the decline in breast cancer rates is postulated as additional evidence for the link between post-menopausal hormone use and breast cancer.

But a paper being published in the June 15 issue of Cancer suggests another possible explanation for the drop in breast cancer rates – a decline in mammogram screening. According to researchers at the National Cancer Institute, mammogram screening rates declined by 4% between 2000 and 2005.

Mammogram Screening Rates (Breen et al. Cancer. Online 14 May 2007)

If this is the case, then the decline in breast cancer incidence is not good news, but rather a harbinger of not-so-good things to come – namely, an increase in later stage cancers.

I suspect that the drop in breast cancer rates will ultimately be found to be due to a mixture of both effects – a decline in HRT use and a decline in mammography. But it’s going to be sometime before all of this is sorted out.

Rates of Confusion about HRT and Breast Cancer

In the meantime, I would not recommend using this new data as carte-blanche to restart HRT, nor am I changing my Rules for Prescribing HRT.

And ladies, please get your mammograms.

When Cancer Strikes Close to Home

I saw a very concerned patient last week. Her 59 year old sister had recently been diagnosed with early stage breast cancer on a routine mammogram. All of my patient’s friends were telling her she had better see her doctor right away and get additional testing because she was now at increased risk.

My patient, who is 50 years old, had a normal breast exam and a recent negative mammogram. Her sister had had a negative BRCA test. There was no other family history of breast or ovarian cancer, or any other cancers identified with known gene mutations.

My patient was shocked when I told her that her sister’s breast cancer did not increase her risk of breast cancer high enough to warrant anything other than routine screening. Her sister’s breast cancer, being post-menopausal, the only one in the family and occuring in the absence of a BRCA mutation, was almost certainly a sporadic cancer. I explained that only 10% of breast cancers are genetically-linked.

We went through my patient’s Gail Model predictions together, and I showed her that her sister’s cancer raised her 5 year breast cancer risk infinitesimally, and her lifetime risk from 9 to 15%. But the Gail and other risk assessment models do not take BRCA results into account, and her sister’s negative BRCA result pretty much nullified that increased risk based on family history. Of course there is always a tiny chance that the test was a false negative, but in the absence of any other family history and her sister’s age at diagnosis, I felt that these odds were low. Finally, even if she did have a 15% risk, that risk is not high enough to warrant routine breast MRI at this time.

We looked at her last mammogram report. I explained that I usually order routine sonograms when the radiologist reports that the breasts are of increased density that limits the sensitivity of the mammogram. But my patient’s breasts were described in the report as being “heterogeneously dense”, a very common descriptor in routine mammograms in her age group. I did not see an indication to order routine sonogram.

I gave her my mantra – Everyone who gets a cancer is part of a family, but not all cancers are familial.

She understood but remained worried. Couldn’t we do something?

So we agreed that we would add a sonogram for now. I explained that because it was not clearly indicated, her insurance would most likely decline to pay for it and she was comfortable with that. My plan was definitely not evidence-based and unquestionably a medico-legal punt, but my patient left feeling her fears had been addressed.

I made her repeat the mantra back to me. “Everyone who gets cancer is part of a family, but not every cancer is familial.” I hoped if she repeated it enough it would sink in.

But when cancer strikes so close to home, it’s hard not to worry that your home is the one with a bull’s eye on its roof.

Abortion and Breast Cancer – Once Again, There is No Link

Once again, a well-done study, this time a prospective cohort study from the Nurse’s Health Study, has failed to reveal a link between abortion and breast cancer. The findings were published in the Archives of Internal Medicine this week.

This study joins the ranks of a myriad of other well-done studies showing the same thing. To top it off, a large workshop convened at the National Cancer Institute in 2003 found no causal link between abortion and breast cancer.

And yet, if you were to google “abortion and breast cancer” or “breast cancer and abortion”, almost every result in the first 10 pages of the search results are links to non-medical sites stating that there is a causal link between abortion and breast cancer. The only exception is the NCI’s fact sheet on the topic, and occasional news articles about the “controversy”, which give equal voice to the facts and those who would distort the data for political reasons.

This is where the web’s power breaks down as far as I’m concerned. Those who know how to can manipulate the web so that a search for real medical data becomes akin to finding a needle in a haystack.

Here are just two links to information on this topic from reputable medical organizations:

National Cancer Institute Fact Sheet on Breast Cancer Risks

American Cancer Society Information on Breast Cancer Risks

and a good article by CNN:

Harvard Study Latest to Discount Abortion -Breast Cancer Link

I challenge those of you who value scientific opinion and review over politics to blog about this topic and to provide your readers a link to one of the above information sites on your blog. Let’s give these sites the hits they deserve and get them their well-deserved place on a google search.

Women deserve nothing less.

The STAR Trial

Three days ago, in a media blitz reminiscent of the Women’s Health Initiative, the National Cancer Institute released preliminary findings of the STAR trial in the most prestigious, rigourously peer-reviewed scientific (not) journal in existance – The American Media. For those of you who haven’t heard, the STAR Trial is a head-to-head comparison of Tamoxifen and Raloxifene (Evista) in preventing breast cancers in high risk post-menopausal women. Everyone has been waiting to see if Evista would prove to be as effective as Tamoxifen in preventing breast cancers without the same risks of uterine cancer and blood clotting.

I had intially intended this post to be a summary of the STAR Trial findings, and why I am thrilled to hear them. But when I went to find the journal article where the results were published, I discovered that there is no paper. There is not even a meeting abstract. Just a press release that tells us the “results are being submitted for publication”.

This appears to be yet another in a new and, in my opinion, disturbing trend among medical scientists – the announcement of study data by press release rather than by publication in a peer review journal.

Look, you want to hold a press conference on your cloned sheep? Be my guest. If your data sucks, you’ll get caught at publication, and no one gets hurt (except the sheep). But when you study involves humans, and expecially when it also deals with the incredibly sensitive and inflammatory topic of breast cancer, your data should be released in the forum best-designed to allow physicians and patients to responsibly and reliably assess the study findings – the peer reviewed medical journal. To do otherwise is unfair to the American public and their physicians.

Don’t tell me your data is too important to wait for the peer review process. Most journals have a fast track for important timely studies. But the study results are always embargoed from the press until publication.

Don’t get me wrong. If the STAR trial results stand up to peer review, I’ll be the first to cheer. But you tell me – How am I supposed to counsel my patients about this data when it is being presented without the oversight of peer review, and with no discussion of study methods, statistical analysis or data interpretation?

Trust me, my patients want to talk to me about this study. I’ve had five phone calls abut it so far, and more, I know, in the coming weeks.

What am I to say? “Sorry, Mrs. Daughter of a Mother with Breast Cancer who lies awake at night worried that she’s next in the cancer line. Call me back in June. That ‘s when the abstract is being presented at the American Society for Clinical Oncology in Atlanta. Better yet, let’s wait for the paper. An abstract really is not something on which to base medical care.”

When will the paper be published? Gee, I don’t know because it hasn’t even been submitted yet!

I pity the poor person who has to review that paper. Judge the data to be wrong, and you set off shockwaves among the public, who already think they know the trial results. Criticize the statistical methods, and you’ll just confuse everyone. Rubber stamp it, and you lose your credibility. I’m telling you, the researchers had better be right on this study. Because the American female public, still staggering from the roller coaster ride of the Women’s Health Initiative, can’t take another one.

The Roller Coaster at Coney Island
And one more thing. I find it fascinating that the STAR data were released just 3 days prior to Evista manufacturer Eli Lily’s quarterly results, and 1 week prior to the stockholder’s annual meeting.

Oh, I’m sorry. I’ll stop…

Mammograms – The Brits vs the Yanks

It appears that my recent post about the Lancet study has stirred things up a bit over at Dr Crippin’s blog. The trans-Atlantic discussion in the comments section is quite an interesting read, and I encourage you to head one over there for it. From what I read, we Americans have slightly different recommendations for mammogram screening than do our counterparts in the UK.

Mammograms in America

We recommend routine mammograms every 1-2 years in women age 40 and over. (Read the NCI justifications for this recommendation here) Although this screening is not universally free, it is covered by all insurances (some annually, some every 2 years). For women without insurance, there is a free national screening program, and many local screening programs exist as well. Women can self–refer, but must identify a physician to receive the mammogram report.

Mammograms in Britian

In the UK, breast cancer screening appears to be free to all for women through the NHS Screening Programme, but is not routinely offered until after age 50, and then every 3 years:

The NHS Breast Screening Programme provides free breast screening every three years for all women in the UK aged 50 and over. Around one-and-a-half million women are screened in the UK each year. Women aged between 50 and 70 are now routinely invited.

Because the programme is a rolling one which invites women from GP practices in turn, not every woman will receive an invitation as soon as she is 50. But she will receive her first invitation before her 53rd birthday. Once women reach the upper age limit for routine invitations for breast screening, they are encouraged to make their own appointment.

Higher risk women can be identified by their physicians and referred to more intensive screening programs in the UK. The women in these programs either have BRCA mutations or a 20% or higher chance of being a BRCA carrier. The intensive screening programs offer individualized risk assessment and screening, including mammography, sonograms and MRI.

It appears from the NICE guidelines (see below) that only women who raise concerns about their family history to their GP get referrals to high risk centers:

1.3.1.2 Healthcare professionals should respond to women who present with concerns but should not, in most instances, actively seek to identify women with a family history of breast cancer.

Some thoughts

Both the UK and American program recommendations are evidence-based, but appear to be relying on either different evidence, or making different conclusions based on the same evidence. Perhaps concerns about liability and very strong breast cancer awareness and concerns among American women are driving our guidelines a bit more than those in the UK.

The increase in mammogram use in the US and the UK has been associated with a decline in mortality from breast cancer in both countries. Advances in treatment, however, may be as much responsible for the decline in mortality, since in the US, the rate of new advance breast cancers has not changed, despite a marked increase in diagnosis of early stage and in-situ cancers.

One could argue that the increase in mammograms has done nothing more than diagnose early indolent cancers that would never have killed anyone. It’s a salient argument, but until we have some way of distinguishing who is going to get the aggressive vs indolent tumors, it doesn’t change screening. However, advances in proteomics and DNA testing are rapidly being made, and currently are driving treatment decisions so that women with more agressive tumors get more agressive treatments.

Someday, we’ll have a better screening than mammogram. It may be MRI, it may be a serum test. It may even be a genetic test to identify the women at risk, so that those at no risk can avoid mammograms altogether. Wouldn’t that be great?

Category: Second Opinions

Mammograms in Women Under 50 – The Lancet Study Reviewed

That graph up there shows the main outcomes of the AGE Trial, a large study of mammography screening in England that asked the question “Does offering mammograms to women in their 40’s save lives?” The dotted red line represents the mortality from breast cancer in women offered mammograms annually between ages 40 and 48 through the National Health Service (or NHS). The solid line represents the control group of women who were not offered mammogram screening by the NHS until after age 50.

The investigators are interpreting that graph to mean that mammograms in women under age 50 are not worth doing.

Let’s talk, shall we?

The study, which was published Dec 9 in the Lancet, randomized 160,921 women on a 1:2 basis to either annual mamograms from age 40-48 or to a control group of “usual care”, which in the NHS is an invitation to a first mammogram between ages 50-52. Deaths were identified through the NHS central registry for a mean follow up of 10.7 years.

There was a 17% reduction in breast cancer mortality in the early screen group. (That’s the graph up there)

As it turns out, only 69% of the women invited to screen actually came for the initial screening, and overall, only 81% of them ever got a mammogram during the study. The women who never showed up for the mammograms had a higher rate of breast cancer deaths than those who got the screening. When adjusting for these two factors, the investigators found that women who actually showed up for the early mammograms had a 24% reduction in mortality from breast cancer compared with the control group.

Sounds pretty clear, doesn’t it?

Well, unfortunately, it’s not. You see, neither the numbers I quoted nor the difference up there in the graph between the red and black lines is statistically significant.

Why not? Very possibly because the study wasn’t big enough to detect the difference in breast cancer mortality with enough certainty to call it real . You see, the NHS ran out of money and personnel partway throught the study, so the sample size was smaller than initially planned. Secondly, mortality in the control group was much lower than initially estimated, making it even harder to find a statistically significant difference with the smaller sample size. Here’s what the investigators said about this:

The power of the trial to show a reduction was diminished both by the smaller than planned sample size and by the lower than anticipated mortality from breast cancer in the control group (2·35 per 1000 vs 3·3 per 1000), resulting in a revised power of 60% to detect a 20% mortality reduction, and the CI does not exclude a reduction of 34% or an increase of 4%.

Most studies are powered at 80%, meaning that, going into the study, there is an 80% possibility that the study has enough subjects to be able to detect a difference with 95% certainty between the groups. (or something like that – statisticians, feel free to correct me.). If the study is too small, then the odds are stacked from the get-go against finding anything to hang your hat on in terms of results. And that’s what happened here.

Finally, the mammograms performed in this study were below standard. Although the first screens were standard two view mammos, subsequent screens in the under 50 group were single view only. This was done in an attempt to diminish radiation dose, but likely resulted in lower detection rates in the screened group, since single view mammograms are less sensitive and specific than two view mammos. (Current standards in both UK and US are two view mammograms.)

The end result is that the Lancet study failed to show a benefit to mammograms before age 50. What a shame – to do all that work, and have your final study size to small to detect a difference between your two groups with any confidence.

Perhaps to ease our disappointment with their study, the investigators did make a very nice graph of the clinical trials of mammograms in women under 40 to date:

For the lay crowd, what this graph means is that the risk of dying from breast cancer in women getting mammograms before 50 is smaller relative to those who wait till after 50. (The black boxes up there) But the 95% confidence intervals (the thin lines) of almost all of these studies crosses one, meaning that the protective effect of mamograms is still not statistically significant overall. However, I would say there is a clear trend to protection against dying in the early mammogram group, wouldn’t you? (All the black boxes except one fall below 1)

What about other outcomes?

Dying or living are not the only two possible outcomes that might be affected by earlier diagnosis of breast cancer. We all know that cancers picked up earlier are more likely to be amenable to breast-conserving surgery and less likely to require chemotherapy. I don’t know about you, but if I am going to get breast cancer, I would rather have it diagnosed at a stage where I can keep my breast and avoid chemo. Also, chemo can be associated with secondary cancers years later, something a 10 year study would not pick up.

Bottom line – this study adds little to our understanding of the role of today’s mammograms in women under age 50 as practiced in the United States. For my patients, I will continue to recommend mammograms every 1-2 years beginning at age 40, and annually at age 50 and above. I advise women with dense breasts to have digital mamograms and ultrasound in addition to mammography, especially if there is a family history of breast cancer.

Hopefully, the data from this latest Lancet study will not be used by the NHS to continue to deny this same screening to women in the UK. ________________________________________________

United States Preventive Services Taskforce recommendations for mammograms

NCI statement on mammograms in women under age 50

Info on Digital Mammography from the NCI

University Of Pennsylvania’s Med Page Today critique of the Lancet Study (excellent read)

Thanks to Rachel for pointing the Lancet article out to me.

Category: Second Opinions

Ear Wax & Breast Cancer

Today’s NY Times tell us that Japanese researchers reporting in Nature Genetics have identified a single gene responsible for determining whether a person has wet or dry ear wax (cerumen).

I remember reading a few years back that there may be an association between cerumen type and breast cancer risk. I decided to read the article itself in Nature Genetics to see if the Japanese researchers had also remembered this connection. They did, only to dismiss it as “controversial”, based on a reference from 1971. However, more recent articles I found, including these studies from 1975, 1981 and 1990, appear to support the connection.

The researchers hypothesize in their article that because folks with dry ear wax also produce less sweat, the genetic variation found may be due to an adaptive mutation that allowed survival in cold climates.

Interestingly, the countries with the highest incidence of breast cancer are Sweden and Denmark, both Northern countries with colder climates. Hmm… Maybe this gene will turn out to be more important than its discoverers realize.