Questions for ASCO – on Tamoxifen, ATLAS and aTTom

On Sunday in Chicago, oncologists and others at the plenary session of the annual ASCO meeting will be talking about an abstract that matters a lot to women with breast cancer. It’s a study on Tamoxifen that bears on how long women with estrogen-receptor positive (ER+) tumors should take adjuvant hormonal therapy after initial treatment for early-stage BC.

tamoxifen binding an ER receptor (Wikimedia Commons)

tamoxifen binding an ER receptor (Wiki-Commons)

Why this matters so much is that ER+ tumors account for most BC cases. So if you’re a pre-menopausal woman who’s had a tumor removed by surgery, there’s a good chance your doctor will recommend adjuvant (“extra”) treatment with Tamoxifen for 5 or (probably) 10 years. The reasoning behind this recommendation is that the recently-published ATLAS study demonstrated a clear lengthening of life among women with ER+ tumors who took the longer course.

The usual dose of Tamoxifen (Nolvadex) is 20 milligrams per day. The bargain-rate cost is around $9 for a month’s supply GoodRx.com  – so we’re talking just over $110/year x 5 or 10 years. That’s small change as oncology drugs go, although the numbers add up over so many patients affected…

Tamoxifen carries a small but real risk for what most doctors consider side effects, like blood clots and occasional, typically low-grade uterine cancers. The problem with Tamoxifen – which is not so much a risk as a definite consequence of taking this medication – is that it has anti-estrogen effects that many young (and older) women consider undesirable. Already our breasts have been cut. Feeling “feminine” is not trivial. Many don’t want it!

(Mental exercise: imagine hundreds of thousands of men ages 35-55 agreeably accepting a prescription for partial chemical castration to reduce the chances of a tumor recurring, after they’ve already had significant treatment to reduce those odds)

Your author has been in rooms filled with doctors where the overwhelming consensus expressed was that hormonal treatments in women with BC are terrific. Indeed, they extend life and, in some cases – such as those with low Oncotype scores – afford women the option of skipping chemo. But how are they so sure we’d rather take an anti-estrogen for 5-10 years rather than 3-6 months of chemo? Answer: I don’t think anyone knows.

One limitation of the ATLAS study (and as best I can tell the same for aTTom) is that the trial doesn’t distinguish between women who got adjuvant chemo and those who didn’t get chemo. So it’s unclear whether Tamoxifen helps prevent recurrence, or extend life, in women who’ve also received chemotherapy for the disease.

Here are 2 questions for aTTom:

1. How do we know that women with small, node-negative (low risk) tumors who receive chemotherapy, as is standard in many communities, get additional benefit from Tamoxifen after chemo?

2. Should pre-menopausal women with small, ER+ tumors be given a choice between taking chemo or Tamoxifen?

In other words, is there evidence to support the combination – chemo followed by hormonal Rx – as the standard, adjuvant care for women with early-stage, ER+ tumors? or that women prefer hormonal pills over a short course, like 4 cycles, of chemo?

I’m eager to hear about the updated aTTom (adjuvant Tamoxifen Treatment offers more?) findings, to be published and presented on Sunday. I hope my colleagues – doctors, patients, advocates and journalists will ask good questions!

All for now,

ES

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Should People With Health Problems Talk About their Conditions?

Before I became a journalist, I rarely talked about my medical problems. When I was working at the hospital I tried not to mention, or show, the pain I was experiencing in my back to colleagues or even friends. Eventually I had to tell a higher-up about it, because I didn’t take narcotics and the pain became limiting. Rounding was difficult. I needed a chair.

And so I was struck by an essay in today’s Times by a woman who has dystonia, a neurological condition. She writes:

Long after “coming out” to my friends about my diagnosis, I realize now that what’s most important is telling people about the disease. Telling waiters why I’ve brought a special pillow with me to a restaurant; legislative aides who want to know what their bosses can do; and strangers who ask, almost rhetorically, if I am in pain.

The point of the article, as I understand it, is that big-name diseases like cancer get loads of media attention and sympathy from strangers. Relatively few people “get” the suffering of those with rare or less mortifying conditions. This is especially true when there’s no celebrity who speaks, writes, sings or otherwise whines or rails on it. People who don’t feel well want empathy, or at least a bit of consideration.

OK, now I’m going to say what’s hard, and I might regret, but I’m not sure that everyone needs to hear about all of our ailments: Sure, if you’re a writer, you can sort through your medical issues and feel better by expressing yourself, as I sometimes do here, and in principle and occasional reality help others facing similar disorders. And if you’re an employee somewhere and you need to take time off or accommodation for a disability, you may need to talk with your boss about what’s going on.

But do you need explain to the person on the checkout line or, say, a mother organizing a bake sale, why your back hurts? Why you frequent the women’s room? Or why you need a seat on the bus?

I am truly ambivalent about this.

My only way out is to tell you of an error I think I made, in withholding information. After my spine surgery, when I couldn’t sit up without assistance, or raise my arm to brush my teeth, and then eventually was practicing walking with a cane, wearing a brace in warm weather under modest clothing, I deliberately didn’t visit or walk by my place of work. I didn’t want my colleagues to see me looking frail. I wanted to return to work looking strong and standing straight up, as if nothing were wrong inside.

Already I’d had the cancer treatment – surgery and chemo – and they knew about that, although we didn’t speak of it much. Mainly it was women coworkers who visited me when I was hospitalized. That is understandable. Most of my colleagues didn’t know about my back. Not really. A lot of people have back pain, after all. What’s the difference, scoliosis, fusion, a revision, a clot, whatever…Or about my other conditions. It was TMI.

Over time I was becoming a burden to the group and – astonishingly in retrospect, I felt badly about that. I worked harder than most, to compensate for my disability (which I had trouble acknowledging, internally), and that further damaged my health. I sometimes wonder, now, if I had told my colleagues earlier, and let my non-cancerous conditions “show,” would I still be practicing medicine today?

Maybe.

Not everyone wants to hear about it. Or know. Besides, plenty of people have stuff they don’t mention –

“Everything is copy,” is a phrase Nora Ephron learned from her mother. That’s according to her son, Jacob Bernstein, who  detailed some of her final days in the New York Times Magazine. But Ephron kept quite a bit to herself. She was a sharp and successful lady.

Thoughts?

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Dr. Edward Shortliffe, on the History and Future of Biomedical Informatics

Last week I had the opportunity to hear and meet Dr. Edward Shortliffe at the New York Academy of Medicine. He’s a maven in the field of biomedical informatics (that would be the “other” BMI), and a pioneer at that. He mentioned that he began working on an electronic health record (EHR) when he was an undergraduate at Harvard in 1968.

Shortliffe emphasized the multidisciplinary nature of the field – that clinicians and computer science-oriented types need be involved for health information technology (HIT) to be effective. “Human health is at the core of it,” he said. The goal of biomedical informatics isn’t for computers to replace humans, he said, but for doctors to learn how to use it – as a tool – so that we (human doctors) can practice better medicine.

He reviewed the 50-year history of the field. The super-simple summary goes something like this: in the 1960s hospitals developed early information systems; in the 1970s, early decision support and electronic health records (EHRs) emerged at hospitals and large institutions; in the 1980s clinical research trials led to databases involving patients across medical centers; in the 1990s, progress in science (especially genetics) led to modern biomedical informatics. Now, the vast work includes clinical, imaging, biology (molecular, genomic, proteomic data) and public health.

Clinical informatics is the newest field supported by the American Board of Medical Specialties.  The first boards will be offered in October of this year, he mentioned.

If you’re interested in the future of health IT, as I am, you might want to take a glance at a perspective published recently by Dr. Shortcliffe and two coauthors, Putting Health IT on the Path to Success, in JAMA. The authors consider the slow pace of implementing HIT, and suggest that the solution rests with patient-centric Health Record Banks (HRBs):

“…Health record banks are community organizations that put patients in charge of a comprehensive copy of all their personal, private health information, including both medical records and additional data that optionally may be added by the patient. The patient explicitly controls who may access which parts of the information in his or her individual account.

I’d like to see these emerge.

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Image Share Project (Finally) Enables People to Share and Access Radiology Results

Today Laura Landro reports in the WSJ on the Image Share Project. According to her Informed Patient column, people who want to access and share radiology images pertaining to their health, such as MRIs or CT scans, can do so using this program. The platform enables easier transmission of electronic versions of large, detailed images. Pilot medical centers involved include New York’s Mount Sinai Hospital, UCSF and the Mayo Clinic.

a doctor looks at a medical image on a computer (NIH, NIBIB)

a doctor looks at a medical image on a computer (NIH, NIBIB)

The Radiological Society of North America is on board with the program. This makes sense, among other reasons because funding comes from the NIH’s National Institute of Biomedical Imaging and Bioengineering (NIBIB). According to the WSJ: “This is all about giving patients control of their health information and engaging them in their own care,” said David Mendelson, director of radiology-information systems at Mount Sinai and a principal investigator on the project.

I’m fine with this – how could I not be? Great, super, and of course patients should have access to electronic files of their x-ray images! Except why has it taken so long? Hard to fathom that in 2013 we’re exploring “pilot” sites where patients can enroll in a program that allows them to transmit their electronic health images to doctors in other cities.

Sooo 2003, you’d think.

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Can Anyone Be a Patient Advocate?

The first time I met an official patient advocate, it was the spring of 1991. I was a first-year fellow, learning by treating patients with blood disorders and all kinds of cancers.

A young gay man with low platelets came to see me in consultation. It was his first visit to the clinic. As I walked by the desk on the way to greet him, the receptionist mentioned that the patient was accompanied by an advocate. “He’s from an organization,” she whispered. “Just thought you’d want to know.”

“OK,” I agreed, not sure what to expect.

My patient was a frail, tired-appearing and polite young man in his 20s. He lived in the West Village and was no longer employed, suffering from AIDS. The man who accompanied him was also thin, perhaps 30 years old – like me, then – and what you might call assertive. The advocate explained that he’d stay with the patient during the evaluation and discussion of recommendations. He added that he’d seen a file on me at ACT UP, and that I was “all right.”

We walked into one of the small consultation rooms. I took detailed notes on the patient’s medical history – too long for his age, approximately 23 years. His body was frail and bruised. A bouquet of tiny red spots lined his palate. Similar marks, a bit darker, coated his legs over and above both ankles. We called those – a manifestation of low platelets – petechiae. I reviewed the patient’s prior blood tests, and drew a sample that I might examine his cells under the microscope.  Later on, the patient, advocate and I spoke about his likely diagnosis and treatment options.

This encounter – my first with an advocate – happened approximately 22 years ago. I don’t know the long-term outcome of the patient’s story, but it’s likely he died of AIDS within a year or two of that encounter. He’d already had several serious infections, and his T cells were quite low as I recall. The advocate may have died, too, but I was not privy to his medical history. All I learned about the advocate – over the course of a few visits, and never by my asking him questions – was that he was involved with ACT-UP, that he was extremely familiar with AIDS manifestations, and that he cared that my patient have access to treatment by a considerate doctor.

So who’s a patient advocate, today?

I’ve been wondering about this, in part because I’d like to serve as a patient advocate on a committee and help decide on priorities, meeting agendas and funding for, say, breast cancer research. Some agencies consider that someone like me – a physician who’s had significant illness – can’t serve as a patient advocate at a table with limited chairs, because I have a medical degree. The problem is, I’m on “the other side,” or something along those lines.

"The Sick Woman," aka "The Doctor and His Patient," by Jan Steen, 17th Century, Rijksmuseum Amsterdam (WikiCommons)

“The Doctor and His Patient,” by Jan Steen

It happens that some physicians, including your author at Medical Lessons, are among the fiercest proponents of patients’ rights I know. I support patients’ unrestricted access to information about medicine and new research, to reasonable treatments matching their preferences and values, and to respect from health care providers. At the same time, I’ve seen doctors who, it seems, promote or outright advertise themselves as “patient advocates” on blogs, websites, in books and elsewhere. Suspicious, yes, but not necessarily untrue –

So here’s the question for the crowd: Can a good doctor, or a nurse, or a physical therapist, or any other person employed by the health care system, serve as a patient advocate?

I’m sure I served an advocate for my patients, years ago, while I was practicing, just as I might now, for people with various illnesses. Tell me I’m wrong.

Comments please! How, exactly, might we define a patient advocate? And, while we’re at it – who’s a patient navigator, and what’s the difference?

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What Do We Need Doctors For?

One of the first questions I asked on this blog was, Are Doctors Necessary? In  2010, I wondered if the Internet and other open resources could replace physicians’ advice. Say you’re feeling OK and not obviously sick, you might prefer to just read and draw upon the wisdom of the crowds, Google and books. If you have a pesky symptom, you might just look it up, or pretend it’s not there, and see if it goes away, without seeking a doctor’s input.

Marcus Welby, M.D. (1969–1976), IMDb image

Marcus Welby, M.D. (1969–1976), IMDb

But if you’re sick – if you’re a patient, and not a consumer, in this blog’s lingo – well, then, of course you need a doctor if you want to get well. Physicians are necessary, still, especially if you’ve got a serious illness, like colon cancer, malaria, catatonic depression, rheumatoid arthritis or Type I diabetes, to name a few doctor’s attention-worthy conditions. Even for someone like me, who’s gone through med school, residency, fellowship and spent years giving medical care to other people, having a thoughtful physician – someone whose experience and intelligence I trust – is indispensible.

My doctors help me sort through the literature, if I choose to read it (I don’t always) and figure out what makes sense for me to live without pain and as fully as possible. I value their work immeasurably. But, as much as I have been helped by nurses, physical therapists, pharmacists and peer patients, the doctor’s opinion matters most. Admittedly, I’m lucky in this. Over the years, I’ve accrued a team of excellent physicians whom I trust. That’s not a common scenario now, which is part of why this question matters so much.

The updated part of the question, now, is whether nurse practitioners (NPs), straight RNs, physician assistants (PAs), pharmacists, social workers and others including, yes, peer patients, should take up much – or even most, of doctors’ tasks. As outlined in a recent editorial, these non-physician health care workers can be paid less and may do a better job at certain chores that, historically, have been carried out by MDs. They can order scans and contact patients about the results, fill out forms for home physical therapy, measure your blood pressure and give injections, like flu shots.

At one level, assigning minor and not-so-minor tasks to other kinds of health care providers sounds great. It’s a partial, 2-for-1 solution, because it relieves the physician shortage and, simultaneously, lowers health care costs. It makes perfect sense, to a point, for efficiency.  There are, legitimately, some tasks that nurses are better-trained to do, such as giving medications. Pharmacists are more likely to pick up on dangerous drug combinations than busy pediatricians, because that’s the focus of their work and training. Peer patients are valuable too. Etc.

But if doctors are just thinking about your “case” or doing complex  procedures, and not being the ones to call you back, or putting in intravenous catheters, or even just sitting and taking a thorough history – they’ll know you less well. And if they spend less time with you, a patient with a serious illness, they – according to the laws of human nature, and my observations on rounds on hospital wards over many years – will not care so much about the outcome of your case. When and if a doctor spends time with a patient, that builds trust, concern, and – possibly, better outcomes.

Reality dictates that we have to protect doctors’ time so they can read, sleep, and spend at least a few minutes each day with the people they care about outside of the workplace, and take care of themselves. If we don’t unload some of the tasks to other health care workers, we’d have to assign fewer patients to each physician. That would exacerbate the shortage…

No simple answer –

ES

 

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Contemplating Breast Cancer, Beyond October 2012

It’s foggy today, October 3, ten years since the last mammogram I had and will ever need. I’ve been remiss in updating the blog. The reasons include family concerns and other projects. Meanwhile, I’ve been thinking about the big picture – what’s most important for progress against breast cancer in the decade ahead.

So here’s what I see, now – in terms of three priority areas: improving treatment, prevention, and education to inform treatment decisions.

Pumpkins, organized by subtype (WikiCommons image)

As an oncologist, I perceive huge strides in understanding BC since the time of my diagnosis. But these advances are largely invisible to patients because they’re in the realm of pathology and classification of different subtypes. What was essentially a 3-type malignancy with a handful of treatment options has expanded under the molecular microscope to a spectrum of 4, 10 or – what’s probably most accurate – hundreds or thousands of patient-particular conditions, depending on the level of precision by which you define a disease. I’m optimistic, because it looks as though, in my lifetime, BC treatment will be tailored to each patient. There’ll be less surgery and better drugs.

The hitch, now, is not so much with science as with funding– funding to analyze each patient’s tumor at the genetic and protein levels, funding to pay for treatments selected by patients (which might include less treatment and/or palliative care in advanced cases), and funding to educate doctors about BC subtypes and medical progress, so they might offer “modern” advice to each patient in ordinary clinics, apart from clinical trials and academic centers. Newer is not always better in medical care. Same goes for more treatment (especially when it comes to higher doses). Still, the lag between advances in BC science and application of distinct, targeted and better treatments is frustrating at best.

Some of my colleagues call for patience – emphasizing that studies need be confirmed, drugs tested in mice, etc. Their point is that we can’t jump from pathology research and new BC classifications to new therapy. But one lesson I take from progress against AIDS is that maybe we shouldn’t be so patient. At least not for young people with poor-prognosis BC subtypes or stage. We could do studies and studies of particular BC treatments, and studies of studies (those would be meta-analyses) and debate 8 or 10 years from now whether a particular drug or combination of drugs worked in clinical trials that selected for patients with an antiquated subtype of the disease. Or we could move toward “n=1” trials, with smart, well-trained physicians assessing each patient by a combination of old-fashioned physical exams and the most modern of molecular studies of the tumors, considering the options, and moving forward with individual, mini-experimental treatment plans.

I vote for the latter. If the drug works in a patient with advanced BC and the patient feels better, why not?

For people with early-stage BC, prescribing or taking new and essentially untested drugs makes less sense at first glance. That’s because standard treatments are “successful” – leading to long-term remissions and possible cures in over 80 percent of those affected. But these relatively good results may have, paradoxically, hampered development of better drugs that could obviate the need for breast-deforming surgeries and radiation in many women. The possible application of BC drug cocktails, in lieu of surgery for early-stage patients, is a huge question for the future, and one for which trials would be necessary. Just getting those projects going – applying BC science to treatment of early-stage cases – would be a step in the right direction.

As for BC prevention, of course that would be infinitely better than detecting or treating the disease. Unfortunately, I think we’re farther away from preventing the disease than we are from having effective and less brutal treatments for most patients. The problem with lifestyle modification – like staying active and not obese – is that it’s far from full-proof: You can be seemingly fit as a fiddle and get a lethal case of BC. Still, there are plenty of other health-related reasons for women to exercise and eat sensibly. As for avoiding carcinogens or, first, just knowing what chemicals contribute to BC formation and growth, the science isn’t there yet.  It’ll be a long haul before anyone can prove that a particular chemical causes this disease. That said, I advocate research in the slow-growing field of environmental oncology and wish there’d be more enthusiasm for regulating our exposure to likely-toxic chemicals.

The third priority is for improving education in math and science, starting at the elementary school level. Doctors need to understand statistics, but many don’t. They need to know about genomics and basic science in medicine. Patients need this kind of knowledge if they want to have a clue, if they want to engage meaningfully in decisions about which antibody to take, or pill, or whether they want to participate in a clinical trial of pills instead of surgery for a Stage II tumor with high levels of Her2, for example. That’d be a tough decision for an oncologist. I only wish that we could reach the point where we could have those kinds of truly informed conversations about clinical treatment of breast cancer, which happen every day.

We’ve got a lot of information in hand, but we need to learn how to apply that to more patients, faster and more openly.

All for a while. I’m open to ideas on this. Happy October!

ES

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Why Hurricanes Remind Me of Patient Care

Last week, Tropical Storm Isaac started tracking toward the Gulf of Mexico. As usual, the prediction models offered varying forecasts. Nonetheless, by this weekend a consensus emerged that the tempestuous weather system would, most likely, affect the City of New Orleans.

National Hurricane Center image

The Mayor, Mitch Landrieu, didn’t panic. I watched him on TV on Sunday evening in an interview with CNN’s Wolf Blitzer and Erin Burnett. Isaac wasn’t a hurricane yet, although a Category I or II storm was predicted by then. He didn’t order an evacuation. Rather, he emphasized the unpredictable nature of storms. There’d be business as usual the next day, on Monday morning August 27. Mind the weather reports, and do what you need to do, he suggested to the citizens. He did mention there’d be buses for people who registered.

“Don’t worry,” was the gist of his message to the citizens of New Orleans. The levees should hold. He exuded confidence. Too much, perhaps.

Some people are drawn to leaders – or doctors – who blow off signs of a serious problem. “It’s nothing,” they might say to a woman who fell after skiing and hit her head, or to a man with a history of lymphoma who develops swollen glands and fever. It’s trendy, now, and sensible, to be cost-conscious in medical care. This is a terrific approach except when it misses a treatable and life-threatening condition or one that’s much less expensive to fix earlier than later.

“Every storm is different,” meteorologist Chad Myers informs us.

Like tumors. Sometimes you see one that should have a favorable course, like a node-negative, estrogen-receptor breast tumor in a 65 year old woman, but it spreads to a woman’s bones within a year. Or a lymphoma in a 40 year old man that looks to be aggressive under the light microscope but regresses before the patient has gone for a third opinion. But these are both exceptions. Cancer can be hard to predict; each case is a little different. Still, there are patterns and trends, and insights learned from experience with similar cases and common ways of spreading. Sometimes it’s hard to know when to treat aggressively. Other times, the pathology is clear. Sometimes you’re wrong. Sometimes you’re lucky….

In New Orleans, the Mayor’s inclination was to let nature take its course. He’s confident in the new levees, tested now by Isaac’s slow pace and prolonged rains. I do hope they hold.

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Three Reasons to Celebrate the Supreme Court’s Decision on Obamacare

I’m thrilled about today’s SCOTUS decision. The Supreme Court upheld the gist of the Affordable Care Act (ACA). Am I surprised? Yes, like pretty much everyone – I didn’t anticipate Chief Justice Roberts’ clever argument about the individual mandate.

What I see in this is first, a win for patients, who now are more likely to get health care if and when they need it – preventive and otherwise. L’Chaim!

Second, it’s a win for the Obama administration and the Democrats. And although I went to journalism school at Columbia University and was told that “real journalists don’t share their opinions,” I do: I’m a registered, reliable, primary-voting Democrat. The ACA is, so far, President Obama’s signature achievement. This SCOTUS decision supports the President’s goal of simultaneously reining in health care costs and expanding coverage to all. It raises the likelihood of President Obama’s re-election. Cheers!

Finally, and at a deeper level, the decision reflects the power of one man’s thoughtfulness to change the outcome of a seemingly bleak situation. (This can happen in oncology and other kinds of medicine, when most of the doctors or specialists on a case throw up their hands or say “it’s impossible because of blah, blah, blah,” and they might refer to some old published studies on old drugs, or something like that.) What Chief Justice Roberts did was think out-of-the box, carefully and within a legal framework. Like a good, smart doctor, morally grounded and, perhaps, influenced by compassion (hard to tell), the Chief Justice figured out a legally acceptable way for his court to do the right thing. By his wisdom, he will have saved more than a few lives. Bravo!

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Reading Between the Lines, and Learning from an Epidemiologist

Early on in Between the Lines, a breezy new book on medical statistics by Dr. Marya Zilberberg, the author encourages her readers to “write, underline, highlight, dog-ear and leave sticky notes.” I did just that. Well, with one exception; I didn’t use a highlighter. That’s partially due to my fear of chemicals, but mainly because we had none in my home.

I enjoyed reading this book, perhaps more than I’d anticipated. Maybe that’s because I find the subject of analyzing quantitative data, in itself, dull. But this proves an easy read: it’s short and not boring. The author avoids minutia. Although I’m wary of simplified approaches – because as she points out, the devil is often in the details of any study – this tact serves the reader who might otherwise drop off this topic. Her style is informal. The examples she chooses to illustrate points on medical studies are relevant to what you might find in a current journal or newspaper this morning.

Over the past year or two, I have gotten to know Dr. Zilberberg, just a bit, as a blogging colleague and on-line associate. This book gave me the chance to understand her perspective. Now, I can better “see” where she’s coming from.

There’s a lot anyone with an early high school math background, or a much higher level of education, might take away from this work. For doctors who’ve attended four-year med schools and, of course, know their stats well (I’m joking, TBC*), this book provides an eminently readable review of basic concepts – sensitivity, specificity, types of evidence, types of trials, Type II errors, etc. For those, perhaps pharmacy student, journalists and others, looking for an accessible source of information on terms like “accuracy” or HTE (heterogeneous treatment effect), Between the Lines will fill you in.

The work reads as a skinny, statistical guidebook with commentary. It includes a few handy tables – on false positives and false negatives (Chapter 3), types of medical studies (Chapter 14), and relative risk (Chapter 19). There’s considered discussion of bias, sources of bias, hypothesis testing and observational studies. In the third chapter the author uses lung cancer screening scenarios to effectively explain terms like accuracy, sensitivity and specificity in diagnostic testing, and the concept of positive predictive value.

Though short, this is a thoughtful, non-trivial work with insights. In a segment on hierarchies of evidence, for example, the author admits “affection for observational data.” This runs counter to some epidemiologists’ views. But Zilberberg defends it, based on the value of observational data in describing some disease frequencies, exposures, and long-term studies of populations. In the same chapter, she emphasizes knowing – and stating – the limits of knowledge (p. 37): “…I do think we (and the press) do a disservice to patients, and to ourselves, and to the science if we are not upfront about just how uncertain much of what we think we know is…”

Mammography is, not surprisingly, one of few areas about which I’d take issue with some of the author’s statements. For purposes of this post and mini-review, I’ll leave it at that, because I think this is a helpful book overall and in many particulars.

Dr. Zilberberg cites a range of other sources on statistics, medical studies and epistemology. One of my favorite quotes appears early on, from the author directly. She considers the current, “layered” system of disseminating medical information through translators, who would be mainly physicians, to patients, and journalists, to the public. She writes: “I believe that every educated person must at the very least understand how these interpreters of medical knowledge examine, or should examine, it to arrive at the conclusions.”

This book sets the stage for richer, future discussions of clinical trials, cancer screening, evidence-based medicine, informed consent and more. It’s a contribution that can help move these dialogues forward. I look ahead to a continued, lasting and valuable conversation.

 —

*TBC = to be clear

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How Much Do You Want Your Doctors To Say About Risks of Treatment?

When I was diagnosed with breast cancer, I was working as a board-certified oncologist. The initial decisions most patients face – which doctor to see, what kind of doctor to see, and at which medical center to see them – were basically non-decisions. I knew, within an instant of my diagnosis, who I’d ask to be my oncologist, surgeon and plastic surgeon. Those choices were straightforward, because I knew what those physicians were like in terms of how they cared for patients, their knowledge and other aspects of their practices and personalities.

The harder decisions were what treatment to take, or not, for my early-stage breast cancer. I was perhaps the most informed cancer patient who could walk into an oncologist’s office. I was familiar with the different regimens. I knew that adjuvant chemotherapy would, roughly and over the long haul, reduce my odds of recurrence by a third. I was aware that, if I opted for a lumpectomy, radiation treatment would reduce the local recurrence rate but was unlikely to affect my long-term survival. I understood that dose-intense regimens were more likely to make me sick and more likely to cause problems down the road.

And yes, in the back of my head I knew that chemotherapy can cause another cancer. Did I think about that possibility? The best answer is, probably, not so much. I was coping with the present.

But that knowledge did influence the decision I made to take a relatively “light” dose of chemotherapy. I was lucky, also, in that I understood my pathology. My tumor, at 1.5 cm, with a negative sentinel node and generous expression of hormone receptors, was a good-prognosis tumor. I was 42 years old, and wanted to live for a few more decades if I survived my spine surgery (another story). I chose the minimal amount of chemo that had been shown in clinical trials to reduce the odds of recurrence.

Last week, I wrote a piece for the Atlantic on how doctors and patients talk about the risks of chemotherapy, or not, and whether patients listen or necessarily want to listen. The reason I put it out there is because I’ve seen doctors shy away from this part of the conversation about cancer treatment. I’m a firm believer in informed consent, and in patients’ access to as much information as they choose to have. If you get chemotherapy, you have the right to know about these risks, and to ask your doctor about them.

I’ve been there with patients who’ve said: “please, don’t tell me this. I can’t deal with it.” Some might even consider it cruel to tell patients with a serious, urgent and treatment-needing condition details of all the possible side effects. Many ask, “what would you do, doctor, if it were someone in your family?” And if they like and respect you, they go with your recommendation.

This kind of paternalism, when a doctor assesses the risks and benefits, and spares the patient’s “knowing” seems anachronistic. But it may, still, be what many people are looking for when and if they get a serious illness. Not everyone wants a “tell me everything” kind of physician. What do you think?

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The NBCC Holds Annual Summit and Pushes for Deadline 2020

Last week the National Breast Cancer Coalition (NBCC) held its annual summit. The meeting drew over 600 women to its opening rally in a Crystal City ballroom on Saturday, along with students who participated in sessions for Emerging Leaders, and a few men who joined in lectures and panels, and lobbied on Tuesday on Capitol Hill.

The NBCC aims to get HR 3067, the Accelerating the End of Breast Cancer Act, passed by the House of Representatives and, ultimately, into law. The bill ties in with Deadline 2020 and with the conference theme: “It’s Time.”

The opening rally, organized in the style of a political convention, was lively. When I entered, participants – or “activists,” as they might be called – were rocking to Three Dog Night’s Joy to the World. Attendees congregated by state and region. Most wore festive garments and signs over black tee shirts carrying the Deadline logo: women from Maine wore floppy red lobster hats; a contingent from Pennsylvania held brightly-decorated kite-posters; a group from Oregon played kazoos (to We’re Not Gonna Take It) and supported multicolored umbrellas over their heads; members of the CBCC lifted Rosie the Riveter boards proclaiming: “We Can Do It!” Each region offered a progress report. In videos, these demonstrated a mix of activism (“waving breast cancer goodbye” on a Rhode Island beach) and seriousness (scientist in a lab, explaining why the research matters).

Fun aside – the meeting’s mood was overwhelmingly serious. Each day’s session opened with a moment of silence to recall women who have died from breast cancer. There were plenary lectures, and smaller educational meetings on topics like “A Critical Review of New Therapies for Metastatic Breast Cancer,” “Estrogen Exposure throughout the Life Cycle,” “Nuts and Bolts of Congress,” “and “The Environment and Breast Cancer.” Many of the women there have metastatic cancer, or had cancer. I had lunch one day with a woman whose early-stage cancer came back after 15 years. Many of the college-age people attending have moms with advanced disease or who died from that. There were young people who’d had breast cancer – some under 30 years old. The few men I spoke with were affected by their wives and mothers’ illnesses. You couldn’t walk a few feet without hearing a sad tale, or seeing the outcome of loss, in motivating people to take action.

In her remarks, Fran Visco, the NBCC Founder and leader, reminded the group that breast cancer remains a leading cause of cancer deaths. Each day, on average, 110 women die in the U.S. from breast cancer. That’s the equivalent of a woman dying every 14 minutes from the disease, she explained. “This should not be considered success, or even meaningful progress.”

“We need to take a less comfortable approach,” she said. “The system rewards safe ideas. We need to take risks.” She spoke of the Artemis project, an NBCC-supported research program to develop a preventive breast cancer vaccine. “There’s a moral imperative to do these trials,” she said. “We’ll get scientists to form new collaborations, to change their focus not on the next grant, or publication, but on the real goal, which is saving patients’ lives.”

In the 20 years since NBCC was founded there’s been progress, she said. “But we’re nowhere near close enough.” She referred to Dr. Jonas Salk, whose polio vaccine came through after just seven years in the lab, and – as did others at the same meeting – to JFK’s 1961 promise to put a man on the moon. That seemingly impossible mission got done in less than nine years. The idea of the Accelerating the End of Breast Cancer Act is to leverage our nation’s prior investment in biotechnology, and to use that work – including much research already done – to end to breast cancer and stop metastases. Visco hopes to deliver a petition to the President on inauguration day in January, 2013.

Through the meeting, I gained a better sense of the organization and Deadline’s purpose. In the words of Senator Kirsten Gillebrand, who met with a delegation from New York on Tuesday: “It creates an urgency about the issue.”

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10 Newly-Defined Molecular Types of Breast Cancer in Nature, and a Dream

Breast cancer is not one disease. We’ve understood this for decades. Still, and with few exceptions, knowledge of BC genetics – information on tumor-driving DNA mutations within the malignant cells – has been lacking. Most patients today get essentially primitive treatments like surgical hacking, or carving, traditional chemotherapy and radiation. Some doctors consider hormone therapy as targeted, and thereby modern and less toxic. I don’t.

Until there’s a way to prevent BC, we need better ways to treat it. Which is why, upon reading the new paper in Nature on genetic patterns in breast cancer, I stayed up late, genuinely excited. As in thrilled, optimistic..The research defined 10 molecular BC subgroups. The distinct mutations and gene expression patterns confirm and suggest new targets for future, better therapy.

The work is an exquisite application of science in medicine. Nature lists 31 individuals and one multinational research group, METABRIC (Molecular Taxonomy of Breast Cancer International Consortium), as authors. The two correspondents, Drs. Carlos Caldas and Samuel Aparicio, are based at the University of Cambridge, in England, and the University of British Columbia in Vancouver, Canada. Given the vastness of the supporting data, such a roster seems appropriate, needed. The paper, strangely and for all its worth, didn’t get much press –

Just to keep this in perspective – we’re talking about human breast cancer. No mice.

The researchers examined nearly 2000 BC specimens for genetic aberrations, in 2 parts. First, they looked at inherited and acquired mutations in DNA extracted from tumors and, when available, from nearby, normal cells, in 997 cancer specimens – the “discovery set.” They checked to see how the genetic changes (SNPs, CNAs and/or CNVs) correlated with gene expression “landscapes” by probing for nearly 29,000 RNAs. They found that both inherited and acquired mutations can influence BC gene expression. Some effects of “driver” mutations take place on distant chromosomal elements, in what’s called a trans effect; others happen nearby (cis).

Next, they honed in on 45 regions of DNA associated with outlying gene expression. This led the investigators to discover putative cancer-causing mutations (accessible in supplementary Tables 22-24, available here). The list includes genes that someone like me, who’s been out of the research field for 10 years, might recall – PTEN, MYC, CDK3 and -4, and others. They discovered that 3 genes, PPP2R2A, MTAP and MAP2K4 are deleted in some BC cases and may be causative. In particular, they suggest that loss of PPP2R2A may contribute to luminal B breast cancer pathology. They find deletion of MAP2K4 in ER positive tumors, indicative of a possible tumor suppressor function for this gene in BC.

Curtis, et al. in "Nature": April 2012

The investigators looked for genetic “hotspots.” They show these in Manhattan plots, among other cool graphs and hard figures, on abnormal gene copy numbers (CNAs) linked to big changes in gene expression. Of interest to tumor immunologists (and everyone else, surely!), they located two regions in the T-cell receptor genes that might relate to immune responses in BC. They delineated a part of chromosome 5, where deletions in basal-like tumors marked for changes in cell cycle, DNA repair and cell death-related genes. And more –

Cluster Analysis (abstracted), Wikipedia

Heading toward the clinic, almost there…

They performed integrative cluster analyses and defined 10 distinct molecular BC subtypes. The new categories of the disease, memorably labeled “IntClust 1-10,” cross older pathology classifications (open-access: Supplementary Figure 31) and, it turns out, offer prognostic information based on long-term Kaplan-Meier analyses (Figure 5A in the paper: Supplementary Fig 34 and 35). Of note, here, and a bit scary for readers like me, is identification of an ER-positive group, “IntClust 2” with 11q13/14 mutations. This BC genotype appears to carry a much lesser prognosis than most ER-positive cases.

Finally, in what’s tantamount to a 2nd report, the researchers probed a “validation set” of 995 additional BC specimens. In a partially-shortened method, they checked to see if the same 10 molecular subtypes would emerge upon a clustering analysis of paired DNA mutations with expression profiles. What’s more, the prognostic (survival) information held up in the confirmatory evaluation. Based on the mutations and gene expression patterns in each subgroup, there are implications for therapy. Wow!

I won’t review the features of each type here for several reasons. These are preliminary findings, in the sense that it’s a new report, albeit a model of what’s a non-incremental published set of observations and analysis; it’s early for patients – but not for investigators – to act on these findings. (Hopefully, this will not be the case in 2015, or sooner, preferably, for testing some pertinent drugs in at least a subset of the subgroups identified.) Also, some of the methods these authors used came out in the past decade, after I stopped doing research. It would be hard for most doctors to fully appreciate the nuances, strengths and weaknesses of the study.

Most readers can’t know how skeptical I was in the 1990s, when grant reviewers at the NCI seemed to believe that genetic info would be the cure-all for most and possibly all cancers. I don’t think that’s true, nor due most people involved with the Human Genome Project, anymore. The Cancer Genome Atlas and Project should help in this regard, but they’re young projects, larger in scope than this work, and don’t necessarily integrate DNA changes with gene expression as do the investigators in this report. What’s clear, now, is that some cancers do respond, dramatically, to drugs that target specific mutations. Recently-incurable malignancies, like advanced melanoma and GI stromal tumors, can be treated now with pills, often with terrific responses.

Last night I wondered if, in a few years, some breast cancers might be treated without surgery. If we could do a biopsy, check for the molecular subtype, and give patients the right BC tablets. Maybe we’d just give just a tad of chemo, later, to “mop up” any few remaining or residual or resistant cells. The primary chemotherapy might be a cocktail of drugs, by mouth. It might be like treating hepatitis C, or tuberculosis or AIDS. (Not that any of those are so easy.) But there’d be no lost breasts, no reconstruction, no lymphedema. Can you imagine?

Even if just 1 or 2 of these investigators’ subgroups pans out and leads to effective, Gleevec-like drugs for breast cancer, that would be a dream. This can’t happen soon enough.

With innovative trial strategies like I-SPY, it’s possible that for patients with particular molecular subgroups could be directed to trials of small drugs targeting some of the pathways implicated already. The pace of clinical trials has been impossibly slow in this disease. We (and by this I mean pharmaceutical companies, and oncologists who run clinical trials, and maybe some of the BC agencies with funds to spend) should be thinking fast, way ahead of this post –

And given that this is a blog, and not an ordinary medical publication or newspaper, I might say this: thank you, authors, for your work.

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A JAMA Press Briefing on CER, Helicopters and Time for Questions

This week the Journal of the American Medical Association, JAMA, held a media briefing on its current, Comparative Effectiveness Research (CER) theme issue. The event took place in the National Press Club. A doctor, upon entering that building, might do a double-take waiting for the elevator, curious that the journalists occupy the 13th floor – what’s absent in some hospitals.

CER is a big deal in medicine now. Dry as it is, it’s an investigative method that any doctor or health care maven, politician contemplating reform or, maybe, a patient would want to know. The gist of CER is that it exploits large data sets – like SEER data or Medicare billing records – to examine outcomes in huge numbers of people who’ve had one or another intervention. An advantage of CER is that results are more likely generalizable, i.e. applicable in the “real world.” A long-standing criticism of randomized trials – held by most doctors, and the FDA, as the gold standard for establishing efficacy of a drug or procedure – is that patients in research studies tend to get better, or at least more meticulous, clinical care.

The JAMA program began with an intro by Dr. Phil Fontanarosa, a senior editor and author of an editorial on CER, followed by 4 presentations. The subjects were, on paper, shockingly dull: on carboplatin and paclitaxel w/ and w/out bevacizumab (Avastin) in older patients with lung cancer; on survival in adults who receive helicopter vs. ground-based EMS service after major trauma; a comparison of side effects and mortality after prostate cancer treatment by 1 of 3 forms of radiation (conformal, IMRT, or proton therapy); and – to cap it off – a presentation on PCORI‘s priorities and research agenda.

I learned from each speaker. They brought life to the topics! Seriously, and the scene made me realize the value of meeting and hearing from the researchers, directly, in person. But, NTW, on ML today we’ll skip over the oncologist’s detailed report to the second story:

Dr. Adil Haider, a trauma surgeon at Johns Hopkins, spoke on helicopter-mediated saves of trauma patients. Totally cool stuff; I’d rate his talk “exotic” – this was as far removed from the kind of work I did on molecular receptors in cancer cells as I’ve ever heard at a medical or journalism meeting of any sort –

Haider indulged the audience, and grabbed my attention, with a bit of history:  HEMS, which stands for helicopter-EMS, goes back to the Korean War, like in M*A*S*H. The real-life surgeon-speaker at the JAMA news briefing played a music-replete video showing a person hit by a car and rescued by helicopter. While he and other trauma surgeons see value in HEMS, it’s costly and not necessarily better than GEMS (Ground-EMS). Helicopters tend to draw top nurses, and they deliver patients to Level I or II trauma centers, he said, all of which may favor survival and other, better outcomes after serious injury. Accidents happen; previous studies have questioned the helicopters’ benefit.

The problem is, there’s been no solid randomized trial of HEMS vs. GEMS, nor could there be. (Who’d want to get the slow pick-up with a lesser crew to a local trauma center?) So these investigators did a retrospective cohort study to see what happens when trauma victims 15 years and older are delivered by HEMS or GEMS. They used data from the National Trauma Data Bank (NTDB), which includes nearly 62,000 patients transported by helicopter and over 161,000 patients transported by ground between 2007 and 2009. They selected patients with ISS (Injury severity scores) above 15. They used a “clustering” method to control for differences among trauma centers, and otherwise adjusted for degrees of injury and other confounding variables.

“It’s interesting,” Haider said. “If you look at the unadjusted mortality, the HEMS patients do worse.” But when you control for ISS, you get a 16% increase in odds of survival if you’re taken by helicopter to a Level I trauma center. He referred to Table 3 in the paper.  This, indeed, shows a big difference between the “raw” and adjusted data.

In a supplemental video provided by JAMA (starting at 60 seconds in):

When you first look, across the board, you’ll see that actually more patients transported by helicopter, in terms of just the raw percentages, actually die.” – Dr. Samuel Galvagno (DO, PhD), the study’s first author.

The video immediately cuts to the senior author, Haider, who continues:

But when you do an analysis controlling for how severely these patients were injured, the chance of survival improves by about 30 percent, for those patients who are brought by helicopter…

Big picture:

What’s clear is that how investigators adjust or manipulate or clarify or frame or present data – you choose the verb – yields differing results. This capability doesn’t just pertain to data on trauma and helicopters. In many Big Data situations, researchers can cut information to impress whatever point they choose.

The report offers a case study of how researchers can use elaborate statistical methods to support a clinical decision in a way that few doctors who read the results are in a position to grasp, to know if the conclusions are valid, or not.

A concluding note –

I appreciated the time allotted for Q&A after the first 3 research presentations. There’s been recent, legitimate questioning of the value of medical conferences. This week’s session, sponsored by JAMA, reinforced to me the value of meeting study authors in person, and having the opportunity to question them about their findings. This is crucial, I know this from my prior experience in cancer research, when I didn’t ask enough hard questions of some colleagues, in public. For the future, at places like TEDMED – where I’ve heard there was no attempt to allow for Q&A – the audience’s concerns can reveal problems in theories, published data and, constructively, help researchers fill in those gaps, ultimately to bring better-quality information, from any sort of study, to light.

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Illness is Not Discrete. On Feeling Sick, and Not Knowing What’s Next

This post is probably a bad idea. But I’ve been pondering it for two days now, since the room around me starting spinning. And I wish I were Jack Kerouac now, so that it wouldn’t matter so much if my thoughts are clear but that I tapped them out. Rat tat tat. Or Frank Sinatra with a cold. You’d want to know either of those guys, in detail. Up-close, loud, even breathing on you. You’d hire ‘em. Because even when they’re down, they’re good. Handsome. Cool, slick, unforgettable. Illness doesn’t capture them, or define them.

Two days ago I was feeling great. I went to the National Press Club for the first time, and was excited about some presentations I heard there, about which I took careful notes and intend, eventually, to share with some commentary. It was a sunny day, and I bought some groceries, planning a bunch of posts and to finish a freelance piece. In the evening I had dinner with my husband, and it seemed like my life was on track.

The rash was the first thing. Just some red, itchy bumps on the back of my neck. And then fatigue. Not just a little tired, but like I couldn’t write a sentence. And since then I’ve been in the center of a kaleidoscope, everything moving clockwise around my head. It’s not bright purple or hot pink and blue and stained glass-green kinds of colors circling, but the drab objects in the bedroom: the lamp, the shadow cast by the top of the door, the rows of light through the blinds, the brown and beige sheets, the back cover of last month’s Atlantic and my reading glasses on the nightstand, the gray bowl I’ve placed at hand, just in case I barf again. Walking is tricky. I’m dehydrated and weak, and my vision’s blurred.

This is not a pretty scene, if you could see it. And that’s the thing. The point.

Because in my experience, which is not trivial, people on both sides of illness – professionals and people you just know – are drawn to healthy people. A broken arm, a low-stage breast cancer that’s treated and done with, a bout of pneumonia – these are things that a career can afford, an editor can handle, friends can be supportive. But when you have one thing, and then another, and then another, it gets scary, it weighs you down. Just when you start feeling OK, and confident, something happens and you’re back, as a patient.

Today, in the apartment on this spring day, with fever and fatigue, I’ve got no choice. I am not a consumer now. Not even close. That is my role, maybe, when I go to the dentist and decline having x-rays or my teeth whitened. No choice, except if I go to a hospital, to have a bunch of blood drawn and my husband would fill in the forms before the doctors who don’t know me in this city inform me I’ve got a viral infection, and labrynthitis as I’ve had a dozen times before, all of a sudden, disabling. Nothing to do but rest and hydrate. And wish I’d gotten some other work done, but I couldn’t.

I’ve got to go with it, my health or illness, be that as it is. No careful critiques of comparative effectiveness research today. No reading about the Choosing Wisely guidelines. No post on Dengue, as I’d planned for yesterday.  Like many people with illnesses – and many with far more serious conditions – I’m disappointed. Maybe because I was sick as a child and missed half of tenth grade, I have trouble accepting these kinds of disruptions. Illness represents a loss of control, besides all the physical aspects.

I might try to watch TV, but more likely I’ll just fall sleep again. That happened yesterday. And for those of you health IT or gadget guys reading, who talk about smart phones and how useful they are for patients seeking info, or maybe even checking vitals, I’ll say this: I’m just glad I’ve got such a device, simply that I can call for help, that I can be in touch,  call my doctor and family. That makes being sick less scary.

This is a drag of a post, but it’s real. No point in blogging if I don’t say it like it is, what I am. If nothing else, this proves I’m alive. So there!

Better tomorrow –

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Review: Dr. Eric Topol’s Creative Destruction of Medicine

Before reading Dr. Eric Topol’s Creative Destruction of Medicine, I wasn’t sure what to expect. Topol, a cardiologist with a background in genetics, was a prominent figure in the take-down of Vioxx. He was at the Cleveland Clinic back then, around 2004, and has since moved to direct the Translational Science Institute at Scripps. He was a few years ahead of me in academic medicine and, by almost any parameter, far more successful.

He’s a TED speaker, I knew. From the TED bio: “Eric Topol uses the study of genomics to propel game-changing medical research.” His work sounds exciting! I first read of the new book in a recent, tech-minded interview in Wired. Seemed like it might be all theory, no touch-y, little reality. With this lead-in, I wasn’t quite prepared to like this book, although I was interested.

Topol’s book is fantastic. I couldn’t put it down because it’s chock-full of good, critical ideas about clinical medicine. The title, “Creative Destruction,” is a reference to Joseph Schumpeter’s theory of radical transformation through innovation. In Chapter 1, he outlines the “Digital Landscape” and explains, simply, how a convergence of advances in technology over the past 40 years – like personal computers, cell phones, the Internet, connectivity and instant access to data – have set the stage for a dramatic shift in medical culture and practice. Doctors, for some reason, have been slow to adapt digital technology to health care, but this is changing, fast.

One theme that emerges through the book is the capacity for technology – by “knowing” and processing so much real-time information about each person’s condition – to inform more effective, individualized treatments. This comes up in his critique of evidence-based medicine and later, when he considers progress in molecular oncology and again, in a section on the pitfalls of old-fashioned, large clinical trials involving many (hundreds or thousands of) patients unlikely to benefit.

Topol’s comfortable writing about the intersection of science and medicine as few physicians are. He describes several clinical episodes, like when the first patient with a stroke received TPA, a clot-dissolving agent. The point is, he’s been there, at some of the world’s best hospitals, where innovative treatments have been applied. But he’s also seen first-hand disappointment, too. This grounds the work. There’s a long chapter on “Biology” which offers, among other insights, a realistic critique of genetic information that many doctors don’t understand. He identifies value in hypothesis-free research, and considers high-throughput screening.

I should mention two provocative details, among many. One appears in Chapter 3, on “empowered” medical consumers. At the Cleveland Clinic Foundation, where he’d worked and served on the Board of Governors, Topol observed busy, otherwise-occupied trustees who contributed significant time and money to the hospital. One reason they did so, he says, was so they might have access to the best doctors “in case anyone in my family or I get sick” (p. 50). He cites flaws in popular hospital ranking systems, like U.S. News & World Report, and offers tips for how to find a good doctor for a particular condition, like checking publications in Google Scholar and looking for senior authors of highly-cited papers. He writes:

“The heterogeneity of the quality of care is not adequately appreciated, and all too often consumers accept the convenient, easy alternative…If this involves a physician or surgeon who does procedures or operations, it is essential to ask for the exact number of procedures performed per year and cumulatively over his or her career…” (pp. 52-53).

The point here is that physicians are not machines. Some are more capable than others, and the quality of care received depends on the doctor’s training, experience and other human qualities.

Another gem, in Chapter 11, pertains to the “science of individuality.” We’re at a threshold, Topol says, of eliminating ignorance in medicine. For doctors and informed patients who happen upon this review: idiopathic, essential and cryptogenic diseases will be gone. Instead, we’ll have conditions defined molecularly or, even if not understood, rooted in the concept of N=1. He writes:

…a new body of data that can be derived from any individual, both at baseline and after an intervention……This opportunity leverages the immense molecular biological, physiologic, and anatomic data that can be determined for any individual, and reinforces that the ultimate goal of an intervention is to have a markedly favorable impact on each n-of-1, rather than the current model, which emphasizes population medicine with the relatively small chance that any individual may derive benefit.

What he’s saying is that the more quickly and inexpensively we can gather and process details about a patient’s medical condition, the more cleverly we can apply treatments designed to help, even in the absence of large trials.

I love this idea.

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The Outlier’s Message, and Evolutionary Science in Breast Cancer

This past week I read several attitude-altering articles about breast cancer.

Kathy Rich, as featured in ‘O’ Magazine

The first lesson, if I might call it that – in the way an oncologist can learn from variations in her patients’ pathology and clinical outcomes – comes from the case of Katherine Russell Rich, who died last week at the age of 56. As reported by Katherine O’Brien in the I Hate Breast Cancer Blog, Rich lived with metastatic BC (MBC) for 18 years. That’s phenomenal, was my first reaction to this news. The prognosis for MBC is said to be around 3 years, and Rich lived for 18 years beyond her tumor’s recurrence with stage IV disease.

As sad and unsatisfactory as this outcome may seem, and it is, Rich’s story offers hope for life beyond the 3 or 4 or 5 years some women with MBC pray, “ask” or otherwise bargain for, fingers-crossed…

As she detailed in an O article, Rich’s initial diagnosis came when she was 32 years old, in 1988. The Times, in an obituary, tells of her lumpectomy, chemo and radiation. In 1993 her cancer came back in bones including her spine. She had a bone marrow transplant, but the disease progressed. Ultimately, she coursed through various and some archaic hormone treatments.

Along the way, she lost or quit a job in publishing, or both, and traveled to India, and authored two books. In a 2010 first-person story about her case, she told of updating her status – of being alive – at Breastcancer.org each year. She wrote:

…I tell the women how deeply I believe there’s no such thing as false hope: all hope is valid, even for people like us, even when hope would no longer appear to be sensible.

Life itself isn’t sensible, I say. No one can say with ultimate authority what will happen — with cancer, with a job that appears shaky, with all reversed fortunes — so you may as well seize all glimmers that appear.

My take, as an oncologist and former clinician, is that patients sometimes surprise you. Hard to know which woman will respond to a non-targeted treatment, or even a drug like an estrogen modulator, without trying. And I wonder – and this is speculative, but maybe, likely, the two together – doctor and patient – worked together to see what worked in Rich’s case over nearly 2 decades, and what didn’t work.

A Bell Curve

If a drug helps, keep it going; if it hurts, stop. There are so many algorithms in medicine, and molecular tools, but maybe the bottom line is how the, one, your patient is doing.

Which leads me to another post, by Dr. David Gorski, a breast cancer surgeon and researcher who blogs as Orac – what once was imagined as a fabulously capable information processor, at Respectful Insolence. He describes how tough it can be to define, and thereby target or destroy, any individual patient’s breast tumor because the cancer cells are constantly changing. Within each woman’s tumor, an evolution-like process is ongoing, leading to selection of treatment-resistant cells. This is not news in oncology; the concept has been understood for years as it applies to “liquid” tumors like leukemia, as he points out.

In breast cancer, understanding the complexity of each case is more recent. Gorski considers a genetic analysis of 104 triple negative breast cancer (TNBC) cases presented at the recent AACR meeting and published last week in Nature:

“…The 59 scientists involved in this study expected to see similar gene profiles when they mapped on computer the genomes of 100 tumours.

But to their amazement they found no two genomes were similar, never mind the same. “Seeing these tumours at a molecular level has taught us we’re dealing with a continuum of different types of breast cancer here, not just one,” explains Steven Jones, co-author of this study.

…TNBC is not a single disease. In fact, even an individual TNBC tumor is not a single disease. Tumor cells evolve as they proliferate, so that the cells in them are genetically heterogeneous. The cells growing in one area of a tumor can and often do harbor markedly different genetic mutations from the cells growing in another part of the tumor…

The team found that each tumor displayed multiple “clonal genotypes,” suggesting that the cancer would have to be treated as multiple diseases, rather than a single entity.

So besides that there are distinct subtypes of breast cancer, those labeled as TNBC are diverse and contain variation within; each patient harbors sub-clones of malignant cells that, in principle, respond differently to treatment.

Orac, the fictional supercomputer (Wiki-Commons image)

Putting these links together –

The message from Katherine O’Brien, who lives with MBC and blogs about it, is that one outlier – like Katherine Russell Rich – can provide hope to other patients and, maybe, clues for scientists about why she lived for so long with metastatic BC. The message from Orac, a physician-scientist blogger, is how hard it is to pinpoint an individual breast tumor’s molecular aspects, because the disease is so mutable and diverse.

The problem, and this reflects evolution in my thinking over a long while, is that published data – the gold standard, what supports EBM – are largely limited to findings based on trials of groups. We understand now, better than we did 10 or 20 years ago, that each patient’s tumor is unique and can evolve over time, naturally or in response to therapy. Clinical trials, though rigorously planned and elaborately structured, are incredibly expensive and flip-floppy, disappointing overall.

What I’m thinking –

Algorithms – except in the broadest sense – may not offer the optimal approach to cancer treatment. Maybe the median doesn’t matter so much as we’d thought.

Here’s a ~retro idea: In 2012, maybe the ideal and most cost-effective oncology practice would blend low-tech observations – like findings on physical examination and how the patient’s feeling – with occasional, high-tech analyses – like markers for genetic drift within a tumor. If doctors are well-trained and non-robotic, in either the literal or figurative sense, and if they lack COIs regarding treatment decisions, they’d provide better, more effective and personalized treatments than what’s typically offered based on evidence reached through elaborate, costly clinical trials of many patients with similar but non-identical cancers.

All for now,

ES

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Why I Support Health Care Reform

One advantage of blogging is that I can share my ideas, directly, with people who find them interesting, provocative or otherwise read-worthy. So for those who are curious, here is my general view on health care reform (HCR) by any name, in 3 points:

First, we need it. The U.S. health care system doesn’t work. It doesn’t serve doctors. Good physicians are few and far between in some geographical regions, in primary care and in needed specialties (like oncology and geriatrics). It doesn’t serve people who might be patients, except if they happen to work for a generous employer that offers a good plan (few do), they are rich enough so they might spend thousands each year out-of-pocket and out-of-network, or they are most fortunate of all, having no serious medical problems to contend with or pay for.

Second, although I wholeheartedly support the Affordable Care Act, because it’s a step in the right direction, I don’t think the legislation goes far enough. We need a simpler, single-payer solution, as in a national health care program, Medicare-style, for all. Why? Because the quasi-plan for state-based exchanges, each with competing offerings and not necessarily interpretable terms of coverage, is too complicated. There’s no reason to think a free market operating at the state level would match the public’s or many individuals’ medical needs. As long as each provider is trying to make a buck, or a billion, it won’t put patients’ access to good care first. Besides, there’ll be administrative costs embedded in each exchange that we could live better without. As for private insurers, well, I couldn’t care less about the well-being of those companies or their executives’ incomes.

Profit is not what medical care is about, or should be about. What we need is a simple, national health plan, Europe-style, available to everyone, with minimal paperwork and, yes, limits to care.

Third point – on rationing.

Some of my readers may wonder how I, who support some costly components of good medical care, like providing breast cancer screening for middle-aged women and sometimes giving expensive drugs to people with illness, favor health care reform. New cancer meds cost around $100,000 year, more or less, as do innovative treatments for cystic fibrosis, inflammatory bowel disease, rheumatoid arthritis and other conditions. I don’t think the sane solution is abandoning expensive but life-saving and quality-of-life-improving treatments.

The hardest part of this debate and what’s so rarely discussed is the appropriate limits of medical treatment, not based on costs – which we can certainly afford if we pull back on administrative expenses of health care and insurers’ huge profits – but on factors like prognosis and age. So, for example, maybe a 45 year old man should get a liver transplant ahead of an 80 year old man. Screening for breast cancer, if it is valuable as I think it is, should perhaps be limited to younger women, maybe those less than 70 or 75, based on the potential for life-years saved. Maybe we shouldn’t assign ICU beds to individuals who are over 85, or 95, or 100 years old.

The real issue in HCR, if you ask me, is who would decide on these kinds of questions. That conversation’s barely begun, and I would like to participate in that…

Meanwhile, the Supreme Court is busy doing its thing, sorting out whether the Affordable Care Act is constitutional or not. I’m glad they’re on the case, so that they might find that it stands and we can move on and forward.

#Obamacare is right –

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Harsh Words, and Women’s Health at Risk

I’ll open with a confession –

Women’s health has never really been at the heart of ML. Your author has, historically, relegated subjects like normal menstruation, healthy pregnancy and reproduction and natural menopause to her gynecologist friends. Sure, I learned about the facts of life. I even studied them in med school and answered questions, some correctly, along the way. By now, I’ve lived through these real life-phases directly. But these topics never drew me. That’s changed now.

Women’s care – and lives, in effect – are jeopardized on three fronts:

First, on birth control. Last week the Senate narrowly tabled a move to limit insurers’ responsibility to cover contraception. The vote on the so-called “conscience” amendment was 51-48. What this tells us is that essentially half of that powerful group either agrees with limiting women’s access to birth control or sees it as dispensable in the context of political aims.

The very fact that the proposal reached the Senate floor is disturbing. Without access to birth control, women –  including teenagers, people with significant medical problems that can be exacerbated by pregnancy, those who can’t afford to feed another child, and some who are already troubled or otherwise might not be ready or prepared to have children – are much more likely to become pregnant. It shouldn’t take a doctor to articulate this obvious point, and I can’t understand why so many are silent on it, but since so few physicians and the AMA in particular hasn’t issued any statement on this, I’ll stick my neck out and say it clearly: Lack of contraception puts women and their conceivable future-kids at risk for health problems that could be avoided.

The language surrounding the amendment is problematic, besides. Who are the anti-birth control legislation-writers to imply that “conscience” is involved in withholding contraception, and not the other way around? It’s like the “pro-lifers” who’ve implied that the rest of us aren’t.

Second, on access to safe abortions. I respect that some people think it’s wrong to terminate a pregnancy. But I also know that plenty of women, especially young women, get pregnant who don’t want to be pregnant. Regardless of who’s “responsible” – and any reader of this blog knows I’m no sucker for finger-pointing and behavior blame games – the bottom line is that if abortions become out-of-reach, women will suffer hemorrhage, life-threatening infections, permanent infertility  and premature deaths.

Hard to know how many women had ill effects or died from botched abortions before January, 1973, when the Supreme Court issued its decision on Roe vs. Wade. Like most women of my generation, I know of those unfortunate outcomes only indirectly. Still, I can’t rid my brain of the scary, unclean place Natalie Wood visits with a wad of cash in the 1963 movie Love with the Proper Stranger, or the tragic outcome when actor Gael García Bernal takes his pregnant love to an abortionist in the film Crime of Padre Amaro, set a decade or so ago in Mexico. But the real scoop comes from older physicians and nurses, here and now. When I was in med school in the 1980s, they told me stories of women and girls showing up in the emergency room bleeding, pale… dead.

As outlined by editorialists and writers elsewhere, mergers of Catholic hospitals with other medical centers threaten to reduce or eliminate access to abortions in some rural areas. In states like Texas, the physical and emotional rigmarole to which pregnant women are subjected prior to an abortion – including mandatory listening to a description of the fetal organs and a discussion loaded make what might be a tough decision unbearable, especially if the woman lacks confidence.

Which leads me to the third point of vulnerability – that women should be able to obtain care without intimidation or emotional abuse.

When Rush Limbaugh spoke last week, he wasn’t just talking about one Georgetown Law student. He was speaking to and about millions of young women who are sexually active. He called them sluts and insinuated they are like prostitutes. Adding insult to verbal injury, he said he’d like to watch videos of the sex. You could say who cares, he’s just some right-winged showman blowing off steam and misogyny. But this is a man who speaks to conservative leaders and feeds ideas to many households in America. Scary that the Republican front-runners, men who would be President of the United States next year, didn’t call Rushbo out. Rather, they let it go. As they might your daughter’s health, or access to birth control, or to a safe abortion.

In this new climate of shame, it’s easy to imagine a girl in some communities might feel really, really bad about herself simply for being sexually active. Whether she’s 17 years in high school, or 21 years in college, or 25 and maybe a department store clerk – and possibly lonely or confused – she may be embarrassed to ask for birth control. The Scarlet C, Robert Walker aptly called it yesterday.

The paradox is that this kind of rough talk, posturing and in some states, puritanical law-making, make it more likely that a sexually active young woman will become pregnant. And if she does become so, now, she may delay seeing a doctor because she fears his or her moral judgment about her behavior. And that leads to less healthy outcomes, and more deaths – fetal and maternal.

This is a serious health issue. I wish more doctors would speak out about it.

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Counterfeit Drugs, A New Concern for Patients

This week the FDA issued an alert about fake Avastin. The real drug is a Genentech-manufactured monoclonal antibody prescribed to some cancer patients. Counterfeit vials were sold and distributed to more than a dozen offices and medical treatment facilities in the U.S. This event, which seems to have affected a small number of patients and practices, should sound a big alarm.

Even the most empowered patient – one who’s read up on his drug regimen, and engaged with his physician about what and how much he wants to receive, and visited several doctors for second opinions and went on-line to discuss treatment options with other patients and possibly some experts – can’t know, for sure, exactly what’s in the bag attached to his IV pole.

Counterfeit Avastin (images from FDA)

Scary because patients are so vulnerable –

The problem is this. If you’re sick and really need care, at some point you have to trust that what you’re getting, whether it’s a dose of an antibiotic, or a hit of radiation to a bone met, or a drug thinner, is what it’s supposed to be. If vials are mislabeled, or machines wrongly calibrated, the error might be impossible to detect until side effects appear. If you’re getting a hoax of a cancer drug in combination with other chemo, and it might or might not work in your case, and its side effects – typically affecting just a small percent of recipients – are in a black box, it could be really hard to know you’re not getting the right stuff.

What this means for providers is that your patients are counting on you to dot the i’s. Be careful. Know your sources. Triple-check everything.

The bigger picture – and this falls into a pattern of a profit motive interfering with good care – is that pharmacists and doctors and nurses need time to do their work carefully. They need to get rest, so that they’re not working robotically, and so that they don’t assume that someone else has already checked what they haven’t. And whoever is buying medications or supplies for a medical center, let’s hope they’re not cutting shady deals.

This issue may be broader than is known, now. The ongoing chemo shortage might make a practice “hungry” for drugs. And with so many uninsured, some patients may seek treatments from less-than-reputable infusion givers. The black market, presumably, includes drugs besides Avastin.

If I were receiving an infusion today, like chemo or anesthesia or an infusion of an antibody for Crohn’s disease, I’d worry a little bit extra. I mean, who will check every single vial and label and box? Think of the average hospital patient, and how much stuff they receive in an ordinary day – including IV fluids that might be contaminated with bacteria.

It’s scary because of the loss of control. This circumstance might be inherent to being a patient – in being a true patient and not a “consumer.”

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