Category Archives: Breast Cancer

04.09.12

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.

6 Comments
02.06.12

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.

11 Comments
08.05.11

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.

1 Comment
07.25.11

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.

7 Comments
07.22.11

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.

7 Comments
03.22.11

The Doctor’s Wife Has Breast Cancer

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.

6 Comments
01.18.11

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.

5 Comments
11.07.10

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.

4 Comments
09.20.10

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.

5 Comments
09.08.10

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

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