3 Differences between Prostate and Breast Cancer Screening

Days ago, the USPSTF issued a new draft for its recommendations on routine PSA measurements in asymptomatic men. The panel’s report is published in the Annals of Internal Medicine. The main findings are two: first, the absence of evidence that routine PSA testing prolongs men’s lives, and second, that PSA evaluation may, on balance, cause more harm than good.

Not surprisingly, there’s been considerable coverage of this by the media, and some controversy. For decades, many men have had their PSA checked, knowingly or not, by their physicians. The PSA test  measures the level of Prostate Specific Antigen, a protein produced and sometimes secreted by prostate cells, normal, inflamed or malignant, into the bloodstream.

As an oncologist, I don’t find the panel’s recommendations surprising. There’s never been strong data to support the hypothesis that routine PSA testing reduces mortality for men in any age group. Prostate cancer is often indolent, a slow-growing kind of tumor for which a “watch and wait” approach may be best, especially when it occurs in elderly men who are most likely, even in the absence of treatment, to die of another cause. The complication rate of prostate surgery is fairly high, although this “cost” of screening likely varies, depending on the skill of the surgeon. Still, and understandably, there are men who swear by this measurement, whose lives have been, in some cases, saved by early detection of a high-grade tumor upon screening.

For today, I’d like to consider some key differences between breast and prostate cancers, and the potential value of screening:

1. Breast cancer tends to affect younger patients than prostate cancer.

Based on SEER data, the median age of a breast cancer diagnosis in the U.S. is 61 years. The median age of death from breast cancer is 68 years. For prostate cancer, the SEER data show a median age of 67 years at diagnosis, and for death from prostate cancer, 80 years.

So the potential number of life-years saved by early detection and intervention is, on average, greater for breast cancer than for prostate cancer.

2. Screening for breast cancer has improved over the past 25 years.

Because the blood test for PSA hasn’t changed much in decades, it’s reasonable to consider studies and long-term survival curves based on data going back to the 1980s.

Mammography, by contrast, is much safer and better than it was 25 years ago, for various reasons: increased regulation of mammography facilities (more care with the procedure, better training and credentialing of technicians) according to the FDA’s Mammography Quality Standard Acts Program ; development of ultrasound methods to supplement mammograms in case of suspicious lesions (lessens the false positive rate overall); the advent of digital technology (lessens the false positive rate in younger women and others with dense breasts); more breast radiology specialists (expertise).

The data reviewed by the USPSTF in issuing their 2009 recommendations for BC screening were decades old, and, as I’ve considered previously, irrelevant to modern medical practices. A recent article in the NEJM points to the problem of the panel’s reliance on the Age trial for women in their 40s. That trial involved the obsolete method of single-view mammography.

3. Mammography involves a woman’s consent (in the absence of dementia – a separate ethical issue).

A woman knows if she’s getting a mammogram. She may not ask sufficient questions of her doctor, or her doctor may not answer them well, but in the end she does or doesn’t enter into a radiology room, volitionally. She decides to get screened, or not. She can choose to have a mammogram every year, or every other year, or not at all.

There’s no ethical problem, as reported for some men, of patients learning they have an abnormal PSA, after blood was drawn indiscriminately, without their knowing the test was being performed.

This perspective might, and should, later extend to consider additional differences between these two kinds of malignancies (each of which is really a group of cancer subtypes), a fuller discussion of the impact of treatment on survival for each type, and the relative risks of screening due to differential complication rates of biopsies and other procedures.

To be clear, there’s no perfect screening test for either cancer type. Far from it. But the merits and risks of each procedure should be weighed separately, and with care.

All for today.

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1 in 70 Women Develops Breast Cancer Before Reaching 50 Years

A post in yesterday’s Well column, about coverage of breast cancer by the media, focused on the first-person narrative of NBC’s Andrea Mitchell. Journalist Tara Parker-Pope writes:

Her announcement has generated much discussion in the blogosphere, including an analysis by Gary Schwitzer, publisher of HealthNewsReview.org, who writes that Ms. Mitchell made some missteps in discussing her cancer.

The Times column goes on to consider what was said, and how it might have been said better, and I agree with much of it. But mainly it’s a meta discussion, journalists talking about how other journalists consider breast cancer facts, figures and narratives.

Buried deep is this number, that according to the NCI, one in 69, or for the sake of simplicity – approximately 1 in 70 – women in the U.S. will receive a diagnosis of BC in her forties. That is an astonishingly enormous proportion of women under 50 years affected by a devastating disease.

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Considering Steve Jobs, Medical Diagnoses and Privacy

Yesterday morning I wrote a short post on CelebrityDiagnosis.com. By evening, news broke that Apple founder and CEO Steve Jobs resigned from his position, presumably for reasons of his health.

What’s public, by Jobs’ decision, is that he had a relatively good, typically slow-growing kind of malignancy in the pancreas, a neuroendocrine islet cell tumor. He informed Apple employees by email about his diagnosis in 2004, when he was 49 years old. Since then he’s had a liver transplant. Possible complications of that surgery, or the tumor itself, have led to considerable speculation. But little is known about the details of why he took medical leave in January and is stepping down now.

In a published letter to the Apple Board and Community, he wrote yesterday: “I have always said if there ever came a day when I could no longer meet my duties and expectations as Apple’s C.E.O., I would be the first to let you know. Unfortunately, that day has come.”

The letter was “short and classy,” in David Pogue’s words, and I agree. I respect Jobs’ decision to keep the details of his medical condition private. That’s the thing – and where this is post is heading.

When public figures are open about their illnesses, it can be helpful, instructive and even necessary. For example, if a political figure, say Fidel Castro or Hugo Chavez or Dick Cheney, with considerable power develops a cancer or has a stroke or a heart attack or some other serious medical problem, the citizens have the right to know that the condition of the person they rely on has changed.

Sometimes it’s instructive to learn about famous people’s medical stories, as is illustrated in Barron Lerner’s book, When Illness Goes Public: Celebrity Patients and How We Look at Medicine. Openness about breast cancer by women like Happy Rockefeller, Rose Kushner and more recently Elizabeth Edwards (to name a few among many) have helped women move forward, from being ashamed of having BC to understanding about what it’s like to live with the disease. They helped other women to understand this disease, through their generosity of personal stories and experience.

The problem is that in our culture there’s so much openness about medical conditions, individuals may feel compelled to tell what’s happening if they have cancer or a recurrence or some other unfortunate medical event. But not everyone wants to do so, nor should they feel obliged.

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FDA Approves Adcetris for Refractory Hodgkin’s Disease and a Rare T-Cell Lymphoma

Late Friday afternoon, the FDA announced its approval, upon accelerated review, of a new drug, Adcetris (brentuximab) for patients with Hodgkin’s lymphoma that has relapsed after bone marrow transplant and for some patients with T-cell anaplastic large cell lymphoma (ALCL).Hodgkin's Disease pathology image shows classic "Reed-Sternberg" cell in center, W-C image

This interests me for a lot of reasons, among them that I used to work in the field of lymphoma immunology and spent some time in my life studying molecules like CD30, the protein to which the new antibody binds.

First, a mini-primer on the disease and numbers of patients involved:

Lymphomas are almost always tumors of lymphocytes, usually of T or B-cell type. In adults, around 80% of cases derive from malignant B lymphocytes; T-cell lymphomas form a varied minority. Approximately 66,000 people receive a diagnosis of non-Hodgkin’s lymphoma (NHL) every year in the U.S.; if a third of the 13,000 or so T-cell tumors are ALCL, there would be just over 4,000 cases of T-ALCL per year, of which only a fraction would require aggressive treatment (see below).

There are nearly 9,000 cases of Hodgkin’s lymphoma (a related condition, usually of B cells) each year in the U.S. Only a small fraction of the Hodgkin’s cases undergo bone marrow transplant and, of those, a smaller percent would relapse and need further treatment.

T-cell ALCL is a rare lymphoma subtype in which malignant T-lymphocytes express proteins including CD30, a complex signaling molecule of the TNF receptor protein family. Clinicians generally classify the disease based on whether it predominantly affects the skin, in which case it tends to be indolent, or if it affects internal organs like the bone marrow, liver and brain, in which case it tends to be aggressive and be unresponsive to standard chemo regimens like CHOP. The T-cell form of ALCL is unlikely to respond to Rituxan, a monoclonal antibody that binds to CD20 on B-cells.

Pathologists classify ALCL based on whether or not the malignant cells have a chromosomal translocation or subtler mutation involving the ALK (anaplastic lymphoma tyrosine kinase) gene. Presumably ALK (anaplastic lymphoma kinase inhibitors) are and will be tested in ALCL tumors with ALK mutations. Meanwhile, patients with ALK+ or ALK- variants seek better treatment options.

The new drug is a specially-designed monoclonal antibody that’s conjugated to a toxin. It binds a receptor, CD30, that’s found at the surface of activated T cells, normal and malignant, and on the most definitive Hodgkin’s lymphoma cells, aka Reed Sternberg cells.

As is the case for many cancer drugs, how Adcetris works is not perfectly clear. Prescribing information from the drug’s manufacturer, Seattle Genetics, says the antibody would be given every 3 weeks by intravenous infusion “until a maximum of 16 cycles, disease progression or unacceptable toxicity.”

The drug was developed by Seattle Genetics (Seagen.com) in collaboration with Millennium Pharmaceuticals, a pharma giant subsumed by Japan’s Takeda company. There’s a lot of money at stake.

Today Ed Silverman at Pharmalot reports on the price of the new drug:

…Seattle Genetics disclosed that the annual cost for Adcetris, which the FDA approved late last week to combat Hodgkin’s disease and another rare lymphoma, will cost $13,500 per dose. In clinical trials, patients received an average of eight infusions, which works out to $108,000 a year, which Xconomy reports was in line with several Wall Street estimates.

He wonders about the cost, and whether it’s justified. My view is that the drug’s use in T-cell ALCL seems reasonable because those patients have so few options. As for using it as a “salvage” drug in Hodgkin’s patients who’ve already undergone bone marrow transplant, a costly and toxic procedure, I’m less confident.

“Early clinical data suggest that patients who received Adcetris for Hodgkin lymphoma and systemic anaplastic lymphoma experienced a significant response to the therapy,” said Richard Pazdur, M.D., in the late-Friday press release. Dr. Padzur heads the FDA’s Office of Oncology Drug Products.

According to the press release, Adcetris was tried in a single-arm (non-randomized) trial of 58 patients with systemic ALCL. The tumors shrank partially or completely in 86 percent of patients. Their responses lasted 12.6 months on average. So far there’s been no demonstrated benefit in survival.

The data to support the drug’s use in Hodgkin’s patients after transplant come from a single-arm study of 102 patients who relapsed after autologous bone marrow transplantation. According to the FDA,  73 percent had a complete or partial response that lasted 6.7 months, on average, upon receiving the experimental drug. Again, there’s no demonstrated survival benefit, just a response rate reported by the agency.

There are over a dozen trials listed with ClinicalTrials.gov for Brentuximab Vedotoxin (SGN-35).

Meanwhile, we await FDA Commissioner Dr. Hamburg’s decision for Avastin in women with metastatic breast cancer.

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Big Melanoma News: FDA approves Vemurafenib (Zelboraf)

Vemurafenib (PLX4032) structure, NCBI image

This morning the FDA announced approval of Zelboraf (vemurafenib) for treatment of some patients advanced melanoma. This is the second drug the agency has approved for this disease in recent months, after nearly two decades of a lack of new or effective therapies for melanoma.

Zelboraf is a pill. This small-molecule drug is thought to work by inhibiting an enzyme in malignant melanoma cells that have a specific BRAF mutation. A few months ago I wrote on this promising new drug, which goes by other names including PLX-0432.

The FDA also approved a companion test, cobas 4800 BRAF V600 Mutation Test, to check for the relevant mutation in patients’ tumors. Both the drug and the test are manufactured by Roche.

The other recently-approved melanoma drug, Yervoy (ipilimumab) is an antibody that’s given by intravenous infusion. This immune modulator, manufactured by Bristol-Meyers Squibb, works by a completely different mechanism: it blocks an immune system inhibitor, CTLA-4, and so “revs up” the body’s healthy immune cells in their capacity to destroy malignant melanoma cells.

Both new drugs are costly. A clinical trial, to test how the two drugs might work together in patients with the relevant BRAF mutation, should open for enrollment in September.

H/T to Sally Church @maverickny‘s early post on Pharma Strategy Blog.

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News on an Unusual Cancer Treatment by Heat in Surgery (Hipec)

There’s so much weird and exciting cancer news this week, it’s hard to keep up!

Double-kudos to Andrew Pollack on his front-page and careful coverage in the New York Times of the hyperthermic intraperitoneal chemotherapy (Hipec) technique that’s being used at some name-brand health care facilities to treat colon cancer.

First, he spares no detail in the Times describing the seemingly primitive, crude method:

….For hours on a recent morning at the University of California, San Diego, Dr. Andrew Lowy painstakingly performed the therapy on a patient.

After slicing the man’s belly wide open, he thrust his gloved hands deep inside, and examined various organs, looking for tumors. He then lifted the small intestine out of the body to sift it through his fingers…

….After about two hours of poking and cutting, Dr. Lowy began the so-called shake and bake. The machine pumped heated chemotherapy directly into the abdominal cavity for 90 minutes while nurses gently jiggled the man’s bloated belly to disperse the drug to every nook and cranny.

As a patient, I have to wonder, who’d sign up for this? And yet it seems they can’t complete a good randomized trial, for patients fear they’ll get the regular treatments only, without the Hipec. As an oncologist, I have to think, how can they possibly do a randomized clinical trial for this sort of method; the results would vary, enormously, from surgeon to surgeon, and from patient to patient – depending on the tumor load and responsiveness to heat, besides all the other tumor variables, even if the Hipec did help a patient or a few.

Pollack supplements the lead story with a shorter piece on hipectreatment.com, a website that obviously promotes the treatment but doesn’t reveal industry ties. According to his article, a competing site, HipecDoctor.com, lists doctors who do it (Hipec), but only includes those who use the site’s sponsoring company’s equipment.

At times like this, Nixon’s “war on cancer” takes on new meaning.

The business of oncology gets messy, on-line and in real patients’ guts. If you ask me, the Hipec approach might be labeled “alternative.” It’s certainly unconventional.

FDA, how do you classify this stuff?

HIPEC Surgery Featured on Grey’s Anatomy (KXLY news clip)

Hard not to contrast the Hipec news with the neatly-designed, high-tech and scientifically-detailed approach published yesterday in the NEJM for treatment of patients with chronic lymphocytic leukemia. That limited but fascinating report, of intense interest to cancer immunologists and gene therapists, serves mainly as proof of principle.

To find out more on Hipec, I intend to watch the segment of Grey’s Anatomy (see one of many related news clip here, scroll down) which may have popularized – and increased demand – for this procedure among desperate patients.

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Breast Cancer Avastin Update

This afternoon Ed Silverman of Pharmalot reports that Roche has proposed a compromise to the FDA over Avastin’s use in women with metastatic breast cancer. The drug would be approved for use only in combination with paclitaxel (Taxol), for which the data are strongest, and with special warnings.

He writes:

The deal includes revised labeling in which Avastin would be recommended only for patients displaying “aggressive disease” and who have the fewest treatment options. Roche also suggests a Risk Evaluation and Mitigation Strategy, or REMS, as well as a Medication Guide.

This sounds like a reasonable solution. As I have considered elsewhere, the FDA commissioner’s decision is pending.

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On Deaths in the New York City Triathlon, and Pushing Ourselves to Limits

Yesterday some 3900 people swam, biked and ran in New York City’s 11th annual triathlon in what might be a celebratory event of human strength and perseverance.

According to this morning’s paper, a 40-year-old woman suffered a heart attack during the 1500 meter swim in the Hudson. She was hospitalized and said to be in stable condition. A man, aged 64, became unconscious mid-way through the swim and was pronounced dead. The man’s death was the second in the history of NYC’s triathlon; three years ago someone else didn’t make it through the water segment.

In March, 2009, the LA Times ran a piece on Death by Triathlon. Most who died in triathlons were men between the ages of 35 and 55 years. Most of the deaths occurred during the swimming portion of the race.

Triathlon (Wikimedia Commons image)

At the pool where I swim, I see people training for the triathlon, and I admire them.

Still, you have to wonder, do people not know their own limits? Or do they choose to ignore them?

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Implications of the Oncology Drug Shortage

Today’s New York Times features an op-ed by Dr. Ezekiel Emanuel, on the oncology drug shortage. It’s a serious problem that’s had too-little attention in the press:

Of the 34 generic cancer drugs on the market, as of this month, 14 were in short supply. They include drugs that are the mainstay of treatment regimens used to cure leukemia, lymphoma and testicular cancer.

Emanuel considers that these cancer drug shortages have led to what amounts to an accidental rationing of cancer meds. Some desperate and/or influential patients (or doctors or hospitals) get their planned chemo and the rest, well, don’t.

Unfortunately, what’s behind this harmful mess is neither a dearth of ingredients nor unsolvable problems at most of the manufacturing plants. Rather, the missing chemotherapies are mainly old and inexpensive, beyond their patent protection, i.e. they’re not so profitable, and not high-priority.

Emanuel proposes that the prices of old oncology meds – drugs that can cost as little as $3 per dose – be raised so that the companies will make it their business to provide them. This seems like a reasonable idea, although I find it a bit too compromising. Why should we raise the costs of any medications above what’s necessary for their manufacture and distribution?

The underlying problem is that we rely on a profit motive to deliver needed health care in the U.S. This kind of financial incentive, even if you find it morally acceptable, doesn’t seem to be working.

That’s why I favor scrapping the system – in which insurance companies siphon off some 30 percent or so of expenses, and pharmaceutical companies take another big cut – and giving patients the care they need, profits aside.

The health care reform bill of 2010 didn’t go far enough. Not even close.

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Thoughts on the Death of Amy Winehouse

I feel compelled to write at least a short note on Amy Winehouse, a young woman who was found dead in her London apartment a few days ago. I don’t like to speak ill of the dead, but the truth is I was never a big fan of her music. I wasn’t fond of her highly-stylized hair or her weirdly-curved eyebrows.

Once, when I was 17, a friend told me he always tries to see the good in people, no matter how much they behaved disagreeably. Ever since he said that, it’s stuck. Today his words come through, in contemplating Amy Winehouse’s personality and short life.

I like her for her willfulness, even though it was so destructive.

Amy Winehouse, in 'Rehab' Video

Not a good medical lesson, for sure – or the message most people are telling their kids upon this “teaching moment,” but not everything I care for is just how it should be.

Yes, she should have gotten more help for her addictions. She needed it, that’s obvious. Family and friends, take note!… You can intervene and make a difference in a troubled person’s life.

But sometimes this happens in medicine, when you’re caring for a patient who smokes or drinks or smokes and drinks or does something else unhealthy, or in a family, or among friends – it’s not always so helpful to simply criticize and judge or lecture and point the person to the door.

So here’s another take: to identify something good in the person, and focus on that, and remember that.

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Mammography Update!

This week I’ve come across a few articles and varied blog posts on screening mammography. The impetus for rehashing the topic is a new set of guidelines issued by the American College of Obstetricians and Gynecologists. That group of women’s health providers now advises that most women get annual mammograms starting at age 40.

Why every year? I have no idea. To the best of my knowledge, there are no data to support that annual mammograms are cost-effective or life-saving for women in any age bracket at normal risk for BC.

Pertinent also, is a recent paper* in the Annals of Internal Medicine supporting a personalized approach to BC screening and mammography for women over the age of 40, and an editorial* to go with it.

“Talk to your doctor,” is the point for patients. (Women’s breasts are not all the same.)

“Talk with your patient,” is the point for doctors: Consider your patient’s breast density, family health history and personal preferences. Great idea!

We need an Annals paper to tell us this?

My personal view, synthesizing all the medical literature of which I’m aware, and taking account all of my prior experiences as a practicing oncologist, and not forgetting I’m a woman, now 50, who had an early-stage breast cancer discovered by a radiologist – and this is not medical advice – is as follows:

For women of normal risk, such as without a strong family history or a prior cancer:

1. Start with a baseline, digital mammogram at age 40. The image should be digital first, because this kind of technology is better for visualizing dense breast tissue which is more common in pre-menopausal, younger women and second, because digital images can more easily be shared with another doctor, for a second or more expert opinion if necessary.

2. Get mammograms every other year, unless there’s a significant abnormality that requires follow-up sooner. Until what age? Hard to say. (A complex topic… hold that thought for another post.)

3. Supplement mammography every other year with monthly self-examination of the breast. This inexpensive method of feeling one’s own breasts, regularly and methodically, has not been shown to save lives in randomized clinical trials. But I am convinced that if it’s done right – when a gynecologist, PCP, internist or other caregiver takes the time to teach her patients how to do the breast self-exam properly  – as I used to instruct my patients in the clinic, women can help themselves to catch breast tumors early.

4. Mammograms should be done, exclusively, by appropriately-trained radiologists who spend the bulk of their time reading mammograms, performing sonograms of the breast and taking occasional biopsies, as appropriate. (Sorry, general radiologists, but that’s how it is. Would you want your mother’s breast image examined by a radiologist who also reads hip films and MRIs of the brain?) The rate of false positives is lower when mammograms are performed by specialized “breast” radiologists.

5. Take advantage of the fact that mammography centers have been regulated for nearly two decades by the FDA. Be sure that the place where you get your mammogram is MQSA-accredited.

All for now –

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*subscription required for full text

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The Trouble With Placebos

The latest NEJM features a big story about a small trial, with only 39 patients in the end, on the potential for placebos to relieve patients’ experience of symptoms. This follows other recent reports on the subjective effectiveness of pseudo-pharmacology.

My point for today is that placebos are problematic in health care with few exceptions. First, in clinical trials, patients sometimes agree to take what might be a placebo so that researchers can measure effects of a drug, by comparison. A second instance is, possibly, when doctors treat children. Even then, I’m not sure it’s wise to “train” kids to take a pill and expect to feel better.

The relationship of an adult patient with a physician involves, or should involve, trust and mutual respect. A person cannot possibly give informed consent for a treatment he or she doesn’t know about. So if the doctor’s giving a placebo to the patient, and making the decision for the patient because it might help, that diminishes the patient’s autonomy, or self-determination. In simpler terms, it’s condescending.

You might consider the hypothesis that there’s nothing wrong with something if it makes you, or someone else, feel better. But that’s kind of like saying the ends justify the means.

A placebo is, by definition, manipulative. I wouldn’t want any doctor to treat me that way.

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Patients’ Words, Unfiltered, Medical Journalism and Evidence

Yesterday’s post was not really about Avastin, but about medical journalism and how patients’ voices are handled by the media.

L. Husten, writing on a Forbes blog, cried that the press fawned, inappropriately, over patients’ words at the FDA hearing last week, and that led him to wonder why and if journalists should pay attention to what people with illness have to say, even if their words go against the prevailing medical wisdom.

There’s a fair amount of controversy on this. For sake of better discussion in the future, I think it best to break it up into 3 distinct but inter-related issues:

1. About health care journalism and patients’ voices:

A general problem I perceive (and part of why I started blogging) is how traditional medical journalists use patients’ stories to make a point. What some of my journalism professors tried to teach  me, and most editors I’ve dealt with clearly want, is for the reporter to find a person with an illness, as a lead,  and then tell about the relevant news, and provide some expert commentary – with at least one person speaking on each “side” of the issue, of course – and then end the story with some bit about the patient and the future.

I argue that this form of medical journalism reduces the patient to an object, used by the story-teller in order to capture the reader’s attention. So, with exceptions and always with the person’s consent, I prefer to offer my own story, from my perspective, so as not to use the patient as a vehicle or literary device.

So it appears that Husten is OK with using patients’ voices to tell a story (and sell papers/clicks?), but not with presenting their views unfiltered if they don’t mesh with the party line or a particular point an editor wants to make. This lies at the center of the journalism issue.

(As an aside, a few recent published studies have found value in analyses of patient-reported symptoms, unfiltered even by their doctors.)

2.  About Avastin:

My impression is that some beast cancer advocates, including a National Breast Cancer Coalition representative who spoke at the FDA hearing, have chosen to “take the hit” on this particular issue because they need and want to appear rational. The straightforward-seeming argument is that the data show Avastin doesn’t work and is often harmful, so it shouldn’t be FDA-approved for women with metastatic BC. From the perspective of a BC advocacy group, it may not be worth pushing for a drug that helps only around 5% of patients.

The problem is there’s no biomarker for Avastin responsiveness, because this drug doesn’t target a particular genetic marker. Rather it works by cutting the blood supply, which could vary even within a particular patient’s mets in different organs. The only way to test if Avastin works in a patient is to give the drug, with informed consent, and see how it goes. Unlike, say, a bone marrow transplant, which runs in the range of hundreds of thousands of dollars and, once done, is irreversible, you can give one dose of Avastin and stop it, or two and stop it, if it doesn’t work or it is not well-tolerated.

Based on my experience as an oncologist and patient who’s received some risky interventions, I don’t think Avastin is more toxic than many or even most cancer drugs. Rather, its side effects have been heavily pushed by the media and public health/epidemiology academics in the past two years, who perhaps wish to make a larger point about this costly drug and evidence based medicine (EBM).

3. About evidence-based medicine: I’m in favor of EBM, especially in principle. The problem is that published medical data is too-often flawed and also, that some patients are, really, outliers.

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No Room For Emotion or Exceptions to the Rule (on Avastin)

My cousin testified before the FDA oncology advisory board on Tuesday about her experience taking Avastin. This is a tragedy, to deny the only drug that is keeping a 51 year old woman alive.

image from p.3 of today’s NYTimes business section

You have to wonder, are the advisory panel members so rational in all their behavior and choices? Are they always so razor-like in their oncology decisions?

Unlikely.

These experts have an agenda, here: It’s to be perceived as scientists, even when their knowledge is imperfect and exceptions to the rule stand right in front of their eyes. But clinical medicine calls for flexibility, and tailoring of treatment to each case, and caring about each person, including those who fall at the tail, or in this case better end, of any Kaplan-Meier survival curve.

What would Larry Kramer do about this, I’ve been thinking: He’d scream, really loud, so loud he might break his eardrums. He’d wonder why others, affected and near, aren’t doing the same. And he’d understand why this picture is on page 3 of the business section, and not on the front cover; it’s because people don’t want to look or see or know or think about it too much, because it hurts.

That is the normal heart, and this is a normal response to what’s happening to women with metastatic breast cancer.

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Gregg Allman Stars in Hepatitis C Awareness Campaign, with Merck

This weekend I learned that Gregg Allman, of the Allman Brothers, has hepatitis C. Not just that; he underwent a liver transplant last year for treatment of liver cancer. This information came my way via CNN, in a clip narrated by Dr. Sanjay Gupta. The cable TV crew filmed the old rocker in Macon, Georgia, at the band’s Big House.

Gregg Allman, performing in 2010 (Wikimedia Commons)

“He’s taping a public service announcement for the drug company Merck, about hepatitis C,” Gupta says 40 seconds or so into the clip (italics added, ES).

Hepatitis C stays silent in many carriers, meaning that most people with the virus are unaware of their infected state. The liver-infecting virus spreads most often by contaminated needles, sexual relations or transfusion of infected blood. Over time, the virus tends to cause liver damage and blood problems including anemia and, rarely, a condition called mixed cryoglobulinemia. In patients with long-standing hepatitis C, there’s a significantly elevated risk of developing liver cancer.

For two decades there have been a few, fairly effective anti-viral drugs available for hepatitis C. Treatment generally reduces patients’ anemia and liver disease, which leads them to feel better, and also reduces the risk of the long-term effects of infection, including liver cancer. Last month the FDA approved two new drugs for hep C: Victrelis (boceprevir), manufactured by Merck, and Incivek (telaprevir), by Vertex Pharmaceuticals.

While I have no formed opinion as to which of these new drugs is most effective or less toxic or more affordable in the long term for patients with hepatitis C, I do find it strange that Gregg Allman will be singing for Merck.

Eat a Peach (album cover)

The ethics of this are complicated: On the one hand, it might be a good thing for a music icon to raise public awareness about hepatitis C, so that more people at risk might get tested and then treated early before they develop severe liver disease and cancer, and would feel better. Gregg Allman is in a position to spread that message effectively: “If I have hep C, you might have hep C. Let me tell you about it…” (somewhat in the style of Magic Johnson, on HIV).

On the other hand, the notion of a post-transplant musician serving as the public’s primary source for information on hepatitis C seems preposterous, especially if he’s tied in with a pharmaceutical company with a stake in the matter. The situation is reminiscent of Sally Fields starring in commercials for Boniva, an osteoporosis drug.

You might ask yourself – and it’s not a trivial exercise – who can best, and objectively, inform the public about viral liver infections and the potential benefits of treatment: doctors? (we harbor biases; many have industry ties); patient peers? (Allman is a heightened example, but he’s hardly objective about this, either); newspapers? (or radio…

Will Allman’s be wasted words? (Hard to resist.) Really I’m not sure.

But I might go to Allman’s concert for the American Liver Foundation, at the Beacon Theater, scheduled for July 27.

All for now.

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Quotes on Oncology, Via Forbes, and a Spiraling Helix

Forbes kept a close eye on the annual ASCO meeting in Chicago. On THE MEDICINE SHOW, Forbes’ Matthew Herper provides a précis of a speech by outgoing ASCO President Dr. George Sledge.

Here are my two favorite parts:

“So what happens when, a few years from now, a patient walks into a doctor’s office and hands a physician a memory stick loaded with gigabytes of personal genomic data?” Sledge asks. His answer: the flood of data will help doctors and patients, but things will get “very, very complicated.”

and

…Doctors will need real-time access to clinical data from all practice settings. This in turn will require interoperable databases using common terminology. Health information technology should offer on-the-spot decision support to oncologists and patients facing the increasingly complex tapestry revealed by modern genomics. It should provide individualized, ready access to a clinical trials systems. It should support appropriate coverage and reimbursement for services. And it should aggregate data so that we can learn from every patient’s experience.

DNA orbit animated smallWhat he’s saying, in a nutshell, is that oncologists will need to know science and have access to effective HIT to interpret and act upon the ever-growing pile of info on cancer genetics as it applies to people in general and individual patients. I recommend the full read.

An added perk in the MEDICINE SHOW piece is a terrific, gyrating DNA model courtesy of Wikipedia (@Forbes!).

For an additional twist (PM, 6/7), turns out Wikipedia offers a mutable Medicine Show of its own.

What goes around…?

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Considering Aromasin for Healthy Women, and the New Breast Cancer Prevention Study

I’m minding the annual meeting of the American Society of Clinical Oncology from a distance this year.

So far, the big breast cancer story syncs with a NEJM paper published yesterday on-line, on the use of exemestane (brand name: Aromasin, manufactured by Pfizer) to prevent invasive breast cancer. These patent-protected pills block the body’s normal production of estrogen.

The main finding was that for women deemed “at risk” for developing BC – as defined by the investigators – the incidence of cancer was significantly reduced when they took Aromasin as compared to a placebo. At a median observation point of 35 months, there was no observed effect on the women’s survival.

What’s right about the study: it’s prospective, randomized and large, including over 4560 women. The results are clear in terms of percents and relative risks: There was a 65% relative reduction in the annual incidence of invasive breast cancer (0.19% vs. 0.55%) and a hazard ratio of 0.35 (with confidence interval 0.18 to 0.70; P=0.002). So they’ve got strong stats.

Estrogen, typically depleted but not absent in post-menopausal women, can promote growth of breast cancer cells. From the paper’s first section: “Aromatase inhibitors profoundly suppress estrogen levels in postmenopausal women and inhibit the development of breast cancer in laboratory models.” So the findings are plausible, which helps, too.

The first problem (or non-problem, really) is there were only 43 cases of invasive BC in total; there wasn’t much cancer, or its reduction, in either arm of the study in terms of absolute numbers. This makes the divergent percents reported seem far less impressive. Second, and more importantly – the long-term consequences of taking this relatively new estrogen-inhibiting drug, in terms of women having thinner bones, possibly more cardiovascular disease, diminished libido and other side effects, are unknown.

Already there are two drugs marketed to prevent breast cancer in some women: tamoxifen and raloxifene. These drugs, also anti-estrogens, have significant side effects including blood clots, and few women choose to take them as prophylaxis for breast cancer. The new study suggests Aromasin is better because it’s got fewer side effects; Pfizer’s idea is that it’s a safer option for women who want to reduce their risk of developing BC.

But what caught my attention is who qualified for this trial: Most healthy women over the age of 60 – that’s a whopping, growing population of potential Aromasin-takers, besides the relatively small number of women with known pathology such as precancerous or stage 0 breast cancer (conditions like LCIS and DCIS, for which a preventive drug seems justifiable) or high risk-conferring BRCA-1 or -2 mutations.

Reading over the trial’s eligibility, I had to wonder, how could anyone think it reasonable to treat all women over the age of 60 with an estrogen inhibitor? And who populated the IRBs that approved this protocol? (Imagine if oncologists were to propose testing the effects of chemical castration in thousands of men over the age of 60; few would support such a trial, although in all likelihood androgen ablation would reduce the incidence of prostate cancer in men.)

The NEJM article lists support for the work from the Canadian Cancer Society Research Institute, the Canadian Institutes for Health Research, Pfizer, and the Avon Foundation. Among my many questions, I’d like to know what exactly what fraction of the study’s support came from Pfizer. The Journal (and every) should break this down for a published non-advertisement: If Pfizer provided 5% or 50% or 95% of funding for the trial, readers should be informed, as should women who might choose to take this drug and their doctors who might prescribe it.

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A New E. Coli Outbreak, Hemolytic-Uremic Syndrome, and Eating In or Out

There’s a newly-identified E. coli strain that’s causing a serious illness called hemolytic uremic syndrome (HUS). The recent cases, mainly in northern Europe, have been attributed to eating raw vegetables like cucumbers, lettuce and tomato. So far, authorities aren’t sure of the exact source.

Like any stomach bug, these bacteria can cause diarrhea, fever and other symptoms related to the gut. When people develop HUS, the kidneys fail and they may need dialysis. (Uremic Syndrome refers to uremia, when toxins normally cleared by the kidneys circulate in the bloodstream and cause problems in other body parts.)

blood smear reveals fragmented red blood cells (schistocytes), image from Wikimedia Commons

The “H” in HUS is for hemolytic, which describes how red blood cells are destroyed in the bloodstream. This occurs sometimes from effects of a bacterial toxin, such as might happen upon ingestion of a toxic strain of E. coli bacteria. This condition results in jaundice – a visible yellowing of the eyes and skin, and anemia – a paucity of red blood cells.

According to NatureNews, the culprit’s genome has been sequenced. It encodes broad-spectrum beta-lactamases. This means these toxic E. coli will, in general, resist antibiotics that exert their antiseptic powers by means of beta-lactam rings.

What’s my take-home message, as a home-maker and mom?

If I were traveling in areas affected now, I wouldn’t panic or change my plans. But I would avoid eating salad and any raw fruits or vegetables that can’t be peeled. I’d be mindful of foods like guacamole and salsa with fresh cilantro or other imperfectly-washed ingredients. Better to order cooked food, especially in restaurants where you don’t know who’s rinsing the greens.

The same rules apply at home, except that I’ll eat salad and fresh vegetables that I’ve prepared diligently.

Hand-washing after touching any part of a toilet, bathroom sink or faucet is always wise. The point is to avoid accidentally putting germs in your mouth that come from animal or human feces.

Yuck.

My next post will be on another topic, entirely.

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News on Niaspan, Cholesterol Drugs and Biomarkers

The Times alerted me, this evening:

Lowering bad cholesterol levels reduces heart attack risks, and researchers have long hoped that raising good cholesterol would help, too. Surprising results from a large government study announced on Thursday suggest that this hope may be misplaced….

Common wisdom has been that such patients should take a statin drug like Lipitor or Zocor to lower bad cholesterol and, in many cases, the vitamin niacin to raise their good cholesterol. But in the trial, niacin provided no benefit over simple statin therapy.

It wasn’t clear to me which was the study, but Bloomberg News explains:

Niaspan failed to prevent heart attacks and may have boosted stroke risk in a U.S.-funded study that calls into question the benefit of raising good cholesterol to combat the leading cause of death.

The National Institutes of Health said today it stopped a 3,414-person study early after the addition of Niaspan to simvastatin, a standard therapy for high cholesterol, was linked to strokes in 1.6 percent of patients, compared with 0.7 percent in the control group. The combination failed to reduce heart attacks, heart-related hospitalizations and the need for procedures to reduce chest pain and restore strong blood flow.

So Niacin, what’s supposed to lower triglycerides and raise HDL – the “good” cholesterol – turns out to be a bust, at least when it’s given in the form of Abbot’s Niaspan.

As to how well cholesterol levels reflect a person’s real risk for heart and other vascular disease, I’ve been skeptical for years.

blueberries with oatmeal (at breakfast this morning, with a bit of grapefruit juice nearby, photo taken by sheer coincidence)

Still, I have faith in oatmeal, with skim milk and fruit, for breakfast.

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Zombies are For Children, and Hits

A few more thoughts on the CDC’s zombie ploy

Today’s Disruptive Women in Healthcare features a post applauding the agency’s out-of-the-box “thinking” to get the public’s attention turned to emergency preparedness. (As if that should be necessary, just after the worst radiation disaster in decades, as tornadoes rip through hospitals here in the U.S.)

The approach seems like it might be confusing to people who are uneducated and perhaps can’t distinguish between the probability of a zombie invasion, UFOs and, say, re-emergence of the plague or the complete loss of electricity in North America. It seems careless, even unprofessional. I prefer the CDC be serious, 365/7/24.

The approach is patronizing, besides. I’m a woman who assumes responsibility for her health. Telling stories to gain people’s attention is how we treat children and early adolescents. It’s not for me.

As a blogger and journalist who looks at medical media, I can see that the topic garnered lots of hits. So for the WSJ health blog, the NPR Shots and podcast and (admittedly) for yours truly here at Medical Lessons, the topic has value. (Except that no one would turn to ML for emergency preparedness, and I wouldn’t want them to do so – see disclaimer.)

Maybe the CDC likes getting hits, too. Perhaps the subject of imaginary medical stories is good for the job security of people who run websites at any salary-paying organization. But I don’t think coverage of a health story by a responsible news outlet should be determined by how many people will click on it.

So this isn’t just about the zombies, really.

Just saying –

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