Breast Cancer Rate in the U.S. is No Longer Declining

A worrisome report on breast cancer trends in the U.S. appeared on-line today, ahead of print in an AACR journal, Cancer Epidemiology, Biomarkers & Prevention.

The analysis, based on the NCI’s SEER data from 2000 – 2007, shows that the incidence of breast cancer in the U.S. is no longer declining. (A drop after 2002 in BC incidence is generally attributed to an abrupt reduction in HRT around that time.)

Since 2003 the overall BC rate has been steady overall, with a few exceptions:

The incidence of BC in non-Hispanic white women ages 60-69 rose by 4.8% in this period. “It remains to be seen if this trend will continue,” according to the study authors.

Among white women ages 40-49 rates of estrogen receptor (ER) positive (ER+) breast cancer significantly increased by an average of 2.7% per year during this period. In contrast, the rate of ER- breast tumors decreased, overall, although the trends were statistically significant only for women ages 40-49 and 60-69.

Apart from women younger than 40, overall BC rates and ER+ case rates were highest among non-Hispanic white women, followed by non-Hispanic black and Hispanic women. Among black women ages 40-49, the incidence of ER+ BC increased (5.2% per year) during 2003-2007, and there were non-significant, recent increases in ER+ BC among older black women.

Of note, in contrast to the pattern for ER+ breast cancer, non-Hispanic black women have the highest rates of ER- breast cancer in every age group. (These ER- cases would include triple negative BC.)

Sorry for the jargon, readers – I hadn’t planned to post now. But I think this information warrants attention.

This matters for a number of reasons. First, it’s bad news in terms of women’s health, plain and simple. Second, these numbers relate to the mammography math, which has been on my mind lately. The point is that if more women between the ages of 40 and 49 are developing ER+ (read: most treatable) tumors, this would influence the net benefit of cancer screening in that age group.

And please don’t misread me here: This is not an academic argument I want to win. Rather, I wish the incidence of breast cancer were declining. And I wish, even more, that so many middle-aged women I know personally weren’t affected by this devastating illness.

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A Video About a Robot and a Patient

Since Watson won on Jeopardy, there’s been lots of talk of robots assuming doctors’ roles. Ten years into our future, machines with programmed empathy and nuanced diagnostic skills will solve diagnostic dilemmas, deduce optimal treatment and make us well.

Yesterday I found a new Xtranormal video, this one crafted by Dr. Charles of his excellent Examining Room blog, on Dr. Watson and the 7 Qualities of an Ideal Physician.

from the Examining Room of Dr. Charles

Dr. Charles cites a 2006 Mayo Clinic Proceedings review on what patients say are essential characteristics of a good physician: The ideal doctor is confident, empathetic, humane, personal, forthright, respectful, and thorough. In this clever, short movie crafted by Dr. Charles, the robot-doctor tries to demonstrate his capability in each of these dimensions in his interaction with a cartoon patient.

I hope the folks over at IBM, who are collaborating with real medical centers now about designing artificial doctors’ intelligence, might take a close look at this video.


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Opening Up a Dialogue on the R-Word

Today a short article in the NY Times, New Kidney Transplant Policy Would Favor Younger Patients, draws my attention to a very basic problem in medical ethics: rationing.

According to the Washington Post coverage, the proposal comes from the United Network for Organ Sharing, a Richmond-based private non-profit group the federal government contracts for allocation of donated organs. From the Times piece:

Under the proposal, patients and kidneys would each be graded, and the healthiest and youngest 20 percent of patients and kidneys would be segregated into a separate pool so that the best kidneys would be given to patients with the longest life expectancies.

This all follows last week’s front-page business story on the monetary value of life.

I have to admit, I’m glad to see these stories in the media. Any reasoned discussion of policy and reform requires frank talk on health care resources which, even in the best of economic times, are limited.

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Radiologists’ Experience Matters in Mammography Outcomes

There’s a new study out on mammography with important implications for breast cancer screening. The main result is that when radiologists review more mammograms per year, the rate of false positives declines.

The stated purpose of the research,* published in the journal Radiology, was to see how radiologists’ interpretive volume – essentially the number of mammograms read per year – affects their performance in breast cancer screening.  The investigators collected data from six registries participating in the NCI’s Breast Cancer Surveillance Consortium, involving 120 radiologists who interpreted 783,965 screening mammograms from 2002 to 2006. So it was a big study, at least in terms of the number of images and outcomes assessed.

First – and before reaching any conclusions – the variance among seasoned radiologists’ everyday experience reading mammograms is striking. From the paper:

…We studied 120 radiologists with a median age of 54 years (range, 37–74 years); most worked full time (75%), had 20 or more years of experience (53%), and had no fellowship training in breast imaging (92%). Time spent in breast imaging varied, with 26% of radiologists working less than 20% and 33% working 80%–100% of their time in breast imaging. Most (61%) interpreted 1000–2999 mammograms annually, with 9% interpreting 5000 or more mammograms.

So they’re looking at a diverse bunch of radiologists reading mammograms, as young as 37 and as old as 74, most with no extra training in the subspecialty. The fraction of work effort spent on breast imaging –presumably mammography, sonos and MRIs – ranged from a quarter of the group (26%) who spend less than a fifth of their time on it and a third (33%) who spend almost all of their time on breast imaging studies.

The investigators summarize their findings in the abstract:

The mean false-positive rate was 9.1% (95% CI: 8.1%, 10.1%), with rates significantly higher for radiologists who had the lowest total (P = .008) and screening (P = .015) volumes. Radiologists with low diagnostic volume (P = .004 and P = .008) and a greater screening focus (P = .003 and P = .002) had significantly lower false-positive and cancer detection rates, respectively. Median invasive tumor size and proportion of cancers detected at early stages did not vary by volume.

This means is that radiologists who review more mammograms are better at reading them correctly. The main difference is that they are less likely to call a false positive. Their work is otherwise comparable, mainly in terms of cancers identified.**

Why this matters is because the costs of false positives – emotional (which I have argued shouldn’t matter so much), physical (surgery, complications of surgery, scars) and financial (costs of biopsies and surgery) are said to be the main problem with breast cancer screening by mammography. If we can reduce the false positive rate, BC screening becomes more efficient and safer.

Time provides the only major press coverage I found on this study, and suggests the findings may be counter-intuitive. I guess the notion is that radiologists might tire of reading so many films, or that a higher volume of work is inherently detrimental.

But I wasn’t at all surprised, nor do I find the results counter-intuitive: the more time a medical specialist spends doing the same sort of work – say examining blood cells under the microscope, as I used to do, routinely – the more likely that doctor will know the difference between a benign variant and a likely sign of malignancy.

Finally, the authors point to the potential problem of inaccessibility of specialized radiologists – an argument against greater requirements, in terms of the number of mammograms a radiologist needs to read per year to be deemed qualified by the FDA and MQSA. The point is that in some rural areas, women wouldn’t have access to mammography if there’s more stringency on radiologists’ volume. But I don’t see this accessibility problem as a valid issue. If the images were all digital, the doctor’s location shouldn’t matter at all.


*The work, put forth by the Group Health Research Institute and involving a broad range or investigators including biostatisticians, public health specialists, radiologists from institutions across the U.S., received significant funding from the ACS,  the Longaberger Company’s Horizon of Hope Campaign, the Breast Cancer Stamp Fund, the Agency for Healthcare Research and Quality (AHRQ) and the NCI.

**I recommend a read of the full paper and in particular the discussion section, if you can access it through a library or elsewhere. It’s fairly long, and includes some nuanced findings I could not fully cover here.

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A Vitamin Chart From the National Women’s Health Information Center

Lately I’ve been worrying about Kevin’s refusal to eat broccoli, and wondering what exactly is so good about those green bunches of roughage. In browsing the Web for more detailed information on the matter, I found a helpful vitamin chart.

This table comes from the HHS-sponsored National Women’s Health Information Center – a good spot to know of if you’re a woman looking on-line for reliable sources. It’s a bit simple for my taste. In the intro, we’re told there are 13 essential vitamins our bodies need. After some basics on Vitamin A – good for the eyes and skin, as you probably knew already – the chart picks up with a quick review of the essential B vitamins 1,2,3,5,6, 9 and 12 (my favorite), followed by a rundown on Vitamins C, D, E, H (that would be biotin) and K:

Vitamins, Some of their Actions, and Good Food Sources
Vitamin Actions Sources
  • Needed for vision
  • Helps your body fight infections
  • Helps keep your skin healthy
Kale, broccoli, spinach, carrots, squash, sweet potatoes, liver, eggs, whole milk, cream, and cheese.
  • Helps your body use carbohydrates for energy
  • Good for your nervous system
Yeasts, ham and other types of pork, liver, peanuts, whole-grain and fortified cereals and breads, and milk.
  • Helps your body use proteins, carbohydrates, and fats
  • Helps keep your skin healthy
Liver, eggs, cheese, milk, leafy green vegetables, peas, navy beans, lima beans, and whole-grain breads.
  • Helps your body use proteins, carbohydrates, and fats
  • Good for your nervous system and skin
Liver, yeast, bran, peanuts, lean red meats, fish, and poultry.
  • Helps your body use carbohydrates and fats
  • Helps your body make red blood cells
Beef, chicken, lobster, milk, eggs, peanuts, peas, beans, lentils, broccoli, yeast, and whole grains.
  • Helps your body use proteins and fats
  • Good for your nervous system
  • Helps your blood carry oxygen
Liver, whole grains, egg yolk, peanuts, bananas, carrots, and yeast.
B9 (folic acid or folate)
  • Helps your body make and maintain new cells
  • Prevents some birth defects
Green leafy vegetables, liver, yeast, beans, peas, oranges, and fortified cereals and grain products.
  • Helps your body make red blood cells
  • Good for your nervous system
Milk, eggs, liver, poultry, clams, sardines, flounder, herring, eggs, blue cheese, cereals, nutritional yeast, and foods fortified with vitamin B12, including cereals, soy-based beverages, and veggie burgers.
  • Needed for healthy bones, blood vessels, and skin
Broccoli, green and red peppers, spinach, brussels sprouts, oranges, grapefruits, tomatoes, potatoes, papayas, strawberries, and cabbage.
  • Needed for healthy bones
Fish liver oil, milk and cereals fortified with vitamin D. Your body may make enough vitamin D if you are exposed to sunlight for about 5 to 30 minutes at least twice a week.
  • Helps prevent cell damage
  • Helps blood flow
  • Helps repair body tissues
Wheat germ oil, fortified cereals, egg yolk, beef liver, fish, milk, vegetable oils, nuts, fruits, peas, beans, broccoli, and spinach.
H (biotin)
  • Helps your body use carbohydrates and fats
  • Needed for growth of many cells
Liver, egg yolk, soy flour, cereals, yeast, peas, beans, nuts, tomatoes, nuts, green leafy vegetables, and milk.
  • Helps in blood clotting
  • Helps form bones
Alfalfa, spinach, cabbage, cheese, spinach, broccoli, brussels sprouts, kale, cabbage, tomatoes, plant oils. Your body usually makes all the vitamin K you need.

(from, table accessed 2/19/2011)

Overall I’d say the chart is useful, a good place to start if you want to know, say, what’s a good, non-citrus source of Vitamin C. It could be improved by provision of more details, like the precise amount of Vitamin B2 per cupful of Swiss chard, and how preparing foods in distinct ways – like roasting, sautéing, boiling, or serving them raw – affects the nutritional value.


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May I Call You ‘Doctor’?

Last week I considered the relationship between the Prince Albert and his speech therapist in The King’s Speech. One aspect I wanted to explore further is why the future king initially insisted on calling the practitioner “doctor.”

In real life, now, patient-doctor relationships can be topsy-turvy. This change comes partly a function of a greater emphasis on patient autonomy, empowerment and, basically, the newfangled idea that the people work “together, with” their physicians to make informed decisions about their health. It’s also a function of modern culture; we’re less formal than we were a century ago.

Patients enter the office with their own set of information and ideas about what they need. The recent Too-Informed Patient video highlighted this issue, effectively.

Doctors are human, we are painfully aware in 2011. They make mistakes and they sometimes need to have dinner with their families. They may even let us down.

When I was a young physician, my patients almost universally called me

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New Numbers Should Factor Into the Mammography Equation

On Friday the New York Times reported that surgeons are performing far too many open breast biopsies to evaluate abnormal mammogram results. A new American Journal of Surgery article analyzed data for 172,342 outpatient breast biopsies in the state of Florida. The main finding is that between 2003 and 2008, surgeons performed open biopsies in an operating room – as opposed to less invasive, safer biopsies with needles – in 30 percent of women with abnormal breast images.

I was truly surprised by this should-be outdated statistic, which further tips the mammography math equation in favor or screening. These numbers matter, and should be based in modern medical practice.

When the Annals of Internal Medicine published the since-adjusted recommendations for breast cancer screening by mammography in November 2009, the stated considerations were not about dollars and cents – which were incalculable – but about the number of women needed to be screened to save one life, and the incidence of false positives which cause harm – worrying, needless biopsies, complications of procedures, overtreatment, etc.

In the context of the health care reform discussion, and considering our country’s out-of-the-sky-and-rising medical bills, some (hopefully) well-intentioned economists heard about those trumped-up mammography papers and concluded that we shouldn’t screen women under 50 for breast cancer because it’s harmful and, what’s more, we can’t keep paying for this sort of care because it’s not evidence-based.

Those conclusions were flawed, though, because the data in those papers were old, as I’ve written previously, and didn’t include studies of digital mammography – which is better for detecting cancer in younger women who tend to have denser breast tissue. In December 2009, I noted that it was unreasonable to consider the costs of open needle biopsies in O.R.’s in any calculation of the harms of mammography, as had the Annals authors, because those kinds of procedures are outdated, or so I thought they were.

It turns out I’ve been living, still, in an academic medical enclave. According to the Timescoverage by Denise Grady:

The reason for the overuse of open biopsies is not known. Researchers say the problem may occur because not all doctors keep up with medical advances and guidelines. But they also say that some surgeons keep doing open biopsies because needle biopsies are usually performed by radiologists. The surgeon would have to refer the patient to a radiologist, and lose the biopsy fee…

The Times article suggests this pattern of over-doing open-biopsies, as documented in Florida, likely reflects national tendencies, including variation among different types of practices – academic, hospital-based, etc.

According to the article published in the American Journal of Surgery, the costs of a core needle biopsy using imaging guidance is around $5,000, or – if a vacuum biopsy device is used, around $6,000; the costs of an open procedure in the O.R. run in the range of $11,000 or more. The Times article indicates that doctors’ fees for a needle procedure range from $750 to $1500, and for an open, surgical biopsy from $1,500 to $2,500. For a ballpark estimate of the cost difference, say a core needle procedure is $5,500 + $1,000 for the doctor’s fees – that’s ~$6,500; a surgical procedure is $11,000 + $2,000 for the surgeon’s fees – that’s $13,000, an easy double.

So let’s say, for the sake of future calculations on mammography, that 10 percent of breast biopsies really do need to take place in the O.R. (which is a generous over-estimate, I think it should be 5 percent or fewer). But if 10 percent need be in the O.R.: then 20 percent of breast biopsies in the U.S. each year – said in the surgery paper to be 1.6 million per year in the U.S. – are being performed through an unnecessary, costlier technique.

An extra $6,500 x 20 percent of 1.6 million procedures = $2.08 billion additional costs, per year.

Let’s call it an even $2.1 billion, or $2 billion, we should shave off the collective amount we spend on mammography and appropriate follow-up. The last digit doesn’t matter; these are huge numbers. No wonder the Times put this story on the front page.

These results should be factored into any proper calculation of costs in breast cancer screening. Now add (or better, subtract) the implications of the findings of two weeks ago – that full lymph node dissection is usually not necessary in women, even if the sentinel node is found to be positive at the time of definitive surgery for what turns out to be a cancer.

What needs be reassessed by public health specialists and economists who weigh in on these issues – and please help me out here, Task Force members and Dartmouth friends, if you would, because your input affects public thinking and, ultimately, policy – are the legitimate costs of screening (every other year, as opposed to annually), doing needle biopsy procedures (instead of open biopsies) and reducing the costs and long-term complications of surgery by eliminating routine lymph node dissection from the equation.

And then we should assess those numbers relative to the costs of treating a woman with metastatic breast cancer, which still has not yet been determined.

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Stunning Comments on the Risk of Breast Implants, and Cancer

The FDA recently identified a link between breast implants and a rare form of lymphoma. From today’s report in the New York Times:

When talking to patients about a rare type of cancer linked to breast implants, plastic surgeons should call it “a condition” and avoid using the words cancer, tumor, disease or malignancy, the president of the American Society of Plastic Surgeons advised members during an online seminar on Feb. 3.

This is how doctors spoke to patients 50 and 100 years ago, and in some cultures still do, by not mentioning scary words – especially to women, and not calling a cancer what it is.

Cosmetic verbage?

Most cancers aren’t lethal* is one message for 2011: the “big  C” turns out to be a spectrum of hundreds of diseases, each with distinct subtypes, and patients shouldn’t panic when they hear the word. Some are benign in behavior although technically malignant; others behave live chronic illnesses; some, unfortunately, grow fast and can kill.

Oncologists can have a hard time persuading patients that a slow-growing tumor doesn’t need much treatment. It would help if other doctors don’t shy away from the term – keeping it taboo and, ultimately, promoting fear.


*NCI – cancer incidence and mortality summary data, accessed 2/18/11

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A New Source of Potential Error in Scientific Research

In today’s Times, Nicholas Wade reports on a potentially serious, besides costly, problem for biomedical researchers: Human DNA Contamination Seen in Genome Databases. He writes:

Nearly 20 percent of the nonhuman genomes held in computer databases are contaminated with human DNA, presumably from the researchers who prepared the samples, say scientists who chanced upon the finding while looking for a human virus…

The full report was published yesterday in PLoS One. The investigators, based at the University of Connecticut, screened for a common human sequence in 2,749 non-primate public databases – NCBI, Ensembl, JGI, and UCSC – and found 492 were contaminated with human DNA. Affected sequences included include bacterial, fish, plant and other genomes.

The implications are broad because if the findings in this report are true, scientists throughout the world have drawn inferences and conclusions and published papers based on incorrect DNA sequence information. As the PLoS authors write in their introduction:

The danger in the propagation of errors in scientific discourse has been demonstrated in cases of both scientific fraud as well as incorrectly described or referenced experiments in reviews [1], [2].

abstract double helix (Wikimedia Commons)

Sound familiar? Think of Lies, Damn Lies and Medical Science, as I considered in a December post on the Decline Effect and other problems that cast doubt on research findings we take for granted.

What happened is likely that, over the years and at many separate institutions, researchers handling cells from which DNA would be extracted, or perhaps just handling the DNA and doing sequencing and other experiments with that, contaminated the specimens with their own genetic material. This is a real headache for researchers, or should be.

Yesterday an on-line colleague and patient advocate, Trisha Torrey, (via a Twitter conversation) to the “HeLa bomb” as recounted in Rebecca Skloot’s The Immortal Life of Henrietta Lacks. In that, Skloot describes 1960s researchers who realized that the cells they’d been using for cancer research experiments were contaminated in vitro. HeLa cells tended to grow so rapidly, they’d sometimes overwhelm other cultures growing in nearby petri dishes or flasks. Once scientists realized that the cells they were using weren’t what they thought they were, and that HeLa cells weren’t all the same due to acquired mutations, their results became questionable.

My take is that researchers need to take care, and not make assumptions, such as “the cells I have received for analysis from a colleague’s lab are the cells they are said to be on the label.” Vials get mislabeled, sometimes. Cultures get contaminated by bacteria and fast-growing cell lines. And now it’s evident that at least some published genomes are incorrect.

But also – and more generally, we should constantly be questioning and checking and reviewing our methods and reagents, and whatever forms evidence, especially when results are surprising (think Madoff) and/or have implications for patient care and therapy, because errors do really happen in all realms of medical and scientific research.

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A Glimpse into the Cochrane Library

I’m taking notes on the Cochrane Library. The site – a collection of databases and reviews – drew my attention yesterday when an embargo was breached for an article to be published there having to do with zinc’s putative power to squelch the common cold.

From the website, published John Wiley & Sons, Ltd.: the Library is put forth by the Cochrane Collaboration, an international group established in 1993. This on-line set includes the Cochrane Database of Systematic Reviews, which so far has published over 4000 papers. The stated aim is to help people make well-informed decisions about human health.

Professor Archibald Leman Cochrane, a health care researcher and pioneering epidemiologist, was born in Scotland in 1909. He attended Cambridge and studied medicine in London. His work was interrupted, extensively. According to the Cochrane site, he served in the International Brigade in the Spanish Civil War and was a captain in the Royal Army Medical Corps during WWII. At one point he was taken as a POW, in Crete. Later on, after a stint studying tuberculosis in Philadelphia, among other endeavors, he became a full Professor at the Welsh National School of Medicine in Cardiff, Wales.

In some countries and Canadian provinces, the Cochrane Library is freely and fully available to anyone with Internet access, based on funding for the collaboration. Here in the U.S., you might view the complete database through a public or university library subscription.

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