Final Word on Avastin, and Why We Need Better Physicians

Today’s breaking breast cancer news is on Avastin. The FDA has just announced, formally, that it will rescind approval for the drug’s use in people with metastatic breast cancer. Commissioner Dr. Margaret Hamburg writes this her statement:

I know I speak on behalf of the many physicians that have been involved with this issue here at the Food and Drug Administration and elsewhere in saying that we encourage patients, and those who support them, to ask hard questions and demand explanations concerning the drugs that are recommended to treat serious illnesses.

On this much I agree with Dr. Hamburg – that patients and others, including doctors who prescribe treatments to patients with likely incurable illnesses, and all medical conditions, for that matter, should ask hard questions.

Others have already, immediately expressed that the FDA did the right thing. Because they think the FDA’s decision was rational, and it was. Likely there’ll be an editorial in the paper I usually read, celebrating the victory of reason over anecdote. The WSJ, whose words tend to align more with business interests, will likely be critical. Opponents of health care reform will, inappropriately and mistakenly, use this as an example of rationing, which it isn’t.

The fact is that many, and possibly most, medical treatments are given in the absence of studies to justify their use. So you might ask, instead, why give chemotherapy to most stage IV cancer patients. Or why give it in the adjuvant setting? Apart from some tumors, like some kinds of lymphoma and leukemia, and common breast and testicular cancers, and a few others, when carefully measured the benefit is often slim.

What I think is that Avastin is a scapegoat of sorts, a costly drug not particularly worse than many others, nor better, and that helps a small minority of women with a lethal disease for reasons their doctors can’t predict or explain.

We experiment, on insurance and Medicare dollars, with so many costly treatments. Bone marrow transplants, at a cost of hundreds of thousands of dollars per patient, for example, are given to some with little formal proof of benefit for the approved indications. But there’s a lobby for these treatments. Support comes from hospitals profiting from transplant procedures and, more subtly, from academic physicians who’ve built careers in that field and write papers about their benefits, complications and management. I might cite other complex, costly and unproved examples in oncology, surgery and other fields of medicine, but that’s not the real point for today.

What I wonder is, ironically, because the data on Avastin were collected so carefully, that its lack of effectiveness over a population of women was better-documented than has been the lack of evidence for other drugs and regimens. Besides, there’s no group of hospitals and doctors whose profit and livelihood, respectively, depends on giving Avastin to just a few people with metastatic breast cancer. There was just Genentech, an easy big-Pharma target, and a few women, pleading for continued access to a drug that’s helped to keep them alive.

(I wonder, also, had those patients who testified been men, would their words have been taken more seriously?)

Meanwhile, doctors can keep giving Avastin to patients with other forms of cancer, for which its efficacy is not so different as you might think. Like any drug, this drug’s response varies from patient to patient for every tumor type that it might be given. And the physicians can still give Avastin, as the commissioner points out in her decision, to women who can pay for it, by circumstances of their particular insurance, or good fortune of wealth. But some of these women’s families will be hurt hard by this FDA decision. Most are in the 99%.

And so maybe what we really need are better doctors, not only in oncology, who would carefully monitor patients when they give any and every medical treatment and stop it if it’s not working, and continue only if it helps, and would communicate and obtain informed consent through meaningful discourse.

If we had that, we’d save a lot of money, and get better care.

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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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Considering Evidence for a New Drug for Immune Thrombocytopenia Purpura

I’ve been wondering, lately, why so many of the medical blogs cover the same topics, like last week’s lung cancer detection trial, which are often the exact same studies as are reported by conventional news outlets. I’ve been trying, here, to sometimes consider new published articles that seem important to me but, for whatever reasons, don’t get so much attention.

Here’s one:

Yesterday’s NEJM includes an article Romiplostim or Standard of Care in Patients with Immune Thrombocytopenia.* It’s about a drug, manufactured and sold by Amgen as NPlate, that received FDA approval for treatment of chronic immune thrombocytopenia purpura (ITP) in August, 2008. Some consider ITP a rare disease, and I suppose it is; my perception is skewed by the fact that as a practicing hematologist I saw patients with ITP almost constantly in the clinic and hospital. In patients with this autoimmune condition, the body produces pathologic antibodies that bind and lead the tiny, clot-forming blood cells to destruction. Sometimes patients with chronic ITP need treatment, such as steroids, surgical removal of the spleen (splenectomy) or other drugs that raise the platelet count and reduce their risk of bleeding.

The new-ish drug, romiplostim, is effective in raising the platelet count in most patients who are said to have chronic ITP. It’s similar to another platelet-stimulating agent, eltrombopag, that’s manufactured and sold by GlaxoSmithKline under the brand name Promacta. Eltrombopag received FDA approval for the same condition in November, 2008.

So long before reading the thoughtful editorial* by Dr. James George, this hematologist was impressed by the availability of two agents that work by stimulating platelet production in the bone marrow. Dr. George considers the possibility that these new drugs alter the usual but debatable algorithms that most hematologists use in caring for patients for ITP. He acknowledges having consulted to the study’s sponsor, Amgen, on this drug and serving as an investigator in clinical trials, and considers:

…In this randomized study, 85 investigational sites in 14 countries enrolled 234 patients…The conclusions are clear. The outcomes were better in patients receiving romiplostim than in patients receiving standard care (short of splenectomy): romiplostim was associated with a greater incidence of a sustained platelet response, less bleeding and fewer transfusions, a decreased requirement for other treatments (including splenectomy), and greater improvement in quality of life. The side effects of romiplostim therapy were minimal, but …confidence about the safety of the drug requires that more patients be observed for a longer time. Because patients treated with romiplostim had better outcomes, does the work of Kuter and colleagues establish romiplostim as the new standard of care?

As I read the original study results, this issue – of possibly changing the standard of care in this disease – became evident. His question is on-point.

The problem is this: In the study, the authors treat a total of 234 patients who are said to have chronic ITP. But, if you look closely at the eligibility for enrollment, besides having a low platelet count (defined for the study as less than 50,000 platelets per microliter of blood, which in itself is a questionable criterion), examination of a bone marrow-biopsy specimen was required to confirm the diagnosis of immune thrombocytopenia in patients older than 60 years. According to Table 1 in the paper, the median age for study participants was 57 years. This means that more than half of the participants were under 60 years and, as far as we know, they did not have a diagnostic pathology test for ITP. They might instead have a myelodysplastic syndrome or other bone marrow disorder that was missed.

Why this matters, besides to patients who have low platelets and their hematologists, is that it’s really a problem in the practice of evidence-based medicine. If data are derived and published from fundamentally flawed studies, in which the patient groups who respond or don’t to a particular intervention are not well-defined by careful diagnostic parameters, the conclusions we draw from those studies may be incorrect.

I am definitely in favor of evidence based medicine, but we need to be careful in how we evaluate the results of published studies, even in the best of journals, and how we incorporate those findings into recommendations for care.


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News, and Thoughts, on Comparative Effectiveness Research

Last week the U.S. Government Accountability Office (GAO) appointed several new members to the board of the Patient-Centered Outcomes Research Institute (PCORI). This group will oversee the application of comparative effectiveness research in health care reform. The panel’s composition was the subject of two posts today by Merrill Goozner, a long-standing observer of health care economics and journalist.

The group may play a key role in forming health care policy in the years ahead. According to the Patient Protection and Affordable Care Act, signed into law in March of this year, the PCORI is slated as a private, non-profit agency. The Institute’s purpose is:

to assist patients, clinicians, purchasers, and policy-makers in making informed health decisions by advancing the quality and relevance of evidence concerning the manner in which diseases, disorders, and other health conditions can effectively and appropriately be prevented, diagnosed, treated, monitored, and managed through research and evidence synthesis that considers variations in patient subpopulations, and the dissemination of research findings with respect to the relative health outcomes, clinical effectiveness, and appropriateness of the medical treatments, services, …”

This is no small task, to say the least.

What is comparative effectiveness research and why does it matter? The idea, basically, is to inform medical decisions with relevant data derived from well-designed clinical trials. This sort of research will provide the foundation for evidence-based medicine (EBM).

Some casual readers of this blog may not appreciate the extent to which I support these endeavors. I do, 100 percent. I say this for several reasons:

First, as a patient: We need to obtain as much information as possible on the best way to treat common and rare medical conditions that arise in humans. Knowing which treatments work, and don’t, ultimately will promote care that’s effective and diminish use of procedures, devices and medications that are ineffective and/or harmful.

Second, as a citizen: We don’t have a surplus of health-care resources to throw around, so to speak, in vain efforts to treat things that can’t be fixed.

As an oncologist, I was not one to give treatments that I didn’t believe would help a patient to feel better and, ideally, get well. Rather, I think the value of chemotherapy and other treatments needs be demonstrated in clinical trials prior to their routine administration, or that their worth be measured otherwise – such as by careful testing of how a drug might work in a subset of patients or even in a particular patient who has a condition like breast cancer and, upon careful monitoring, it is apparent that nothing helps except Avastin in her case.

Third, as a doctor: I would never want to cause avoidable harm to a patient. If a drug, device or procedure is ineffective or damaging, we shouldn’t often prescribe that, if ever. The best way to help patients get well, and harm them less, is by knowing what works and what doesn’t in most cases and by knowing the limitations of aggregated, statistically-valid data applied to individual patients.

Cost analyses are needed, too, but that’s a somewhat separate issue.

I wish the panel good luck in their important work ahead.

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More News, and Considerations, on OncotypeDx

This week I’ve been reading about new developments in breast cancer (BC) pathology.

At one level, progress is remarkable. In the 20 years since I began my oncology fellowship, BC science has advanced to the point that doctors can distinguish among cancer subtypes and, in principle, stratify cases according to patterns of genes expressed within tumors. This sort of information – cancer cell profiling – might inform prognosis and influence treatment decisions that BC patients and their doctors, usually oncologists, make every day.

What disappoints is the slow pace by which this knowledge infiltrates the clinic. In practice, women and their physicians rarely have much more information on BC pathology than what was available two decades ago – the tumor size in its largest dimension (crudely measured in centimeters), whether it’s spread to the lymph nodes (and if so, how many nodes), the type of cancer (based on the cells’ appearance under a light microscope: infiltrating ductal, lobular carcinoma and other BC forms) and whether the cells express a few key molecules including estrogen receptors (ER).

In the past five years, more laboratories are offering data on Her2 in BC samples. This complex molecule, an epidermal growth factor receptor, normally transmits signals from a cell’s surface to the interior. Her2 expression dictates the BC subtype in some newer classifications of the disease and usually determines the cells’ responsiveness to Herceptin, a monoclonal antibody treatment. Still, there’s been some controversy, in part due to variation among lab facilities in the reproducibility of Her2 testing results.

The problem is this: if pathologists don’t provide accurate, valid results on Her2 expression in BC cells – which can be measured by various methods – it’s hard for women and their physicians to make sound decisions based on the molecule’s expression. And Her2 is just one of dozens of molecules that can be measured in BC. The reason it’s tested, for the most part, is to foster decisions on Herceptin treatment and also, perhaps to a lesser extent, to provide prognostic information.

What puzzles me is why so few use better, modern pathology and other decision tools. Technologies like Mammaprint, Adjuvant! and OncotypeDx have been available for years but aren’t used routinely in most clinical settings. So I thought I’d do some more research and, in future posts, will consider each of these and other, relevant technologies.

For today I’ll focus on OncotypeDx.  This test, manufactured by the Redwood City, California-based Genomics Health, assesses BC recurrence risk in cases that are ER+, node negative (see below). As cancer gene testing panels go, OncotypeDx is a baby, based on expression of just 21 genes by a two-decade old method called quantitative RT-PCR. The test intrigues me; I’ve posted on it once before.

No doubt, my interest in OncotypeDx is intensified by my personal history of BC. My case was exactly the sort of ER+, node-negative tumor for which OncotypeDx is intended; often I’ve wondered what would have been my tumor’s recurrence score (RS) and if knowing that would have affected my decision to undergo treatment with adjuvant chemotherapy.

Some background terms –

ER+ means that the cells express hormone receptors, for estrogen, at the surface;

Node negative means that the breast cancer has not spread to the lymph nodes, or glands, of the armpit. (Axilla is the medical term for armpit. Axillary lymph nodes are normal immune organs that drain fluid including potentially foreign particles from the breast, chests and nearby arm. The nodes can swell if there’s an infection to which the body reacts, if malignant cells infiltrate the gland and sometimes due to autoimmune diseases like lupus.)

So an ER+, node negative breast tumor is one in which the cancer cells are sufficiently differentiated, or mature, to produce and bear hormone receptors at their surfaces and in which the tumor cells haven’t yet migrated to the armpit (or at least haven’t done so at a level that can be detected by a pathologist).

Real-Time, Reverse Transcriptase (RT) – Polymerase Chain Reaction (PCR) is a standard method for amplifying tiny amounts of nucleic acids such that they can be measured and sequenced. Standard PCR usually amplifies DNA whereas in RT-PCR, RNA transcripts are converted to DNA before amplification in a machine. This method can assess the amount of RNA, or message for a particular gene, that’s expressed in a pathology sample.

Adjuvant therapy refers to additional, or extra, treatment that’s given after initial cancer surgery to reduce the chances of the tumor’s recurrence.

Back to OncotypeDx -

This pathology tool predicts the likelihood that ER+, node-negative BC tumors will come back within 10 years of a woman’s primary treatment (mastectomy, or lumpectomy with radiation) usually followed by tamoxifen. The assay measures each of 21 genes in a panel and, using those results, calculates a “recurrence score” (RS) between 1 and 100. The higher the RS, the more likely the cancer will re-emerge after treatment.

According to the Genomics Health website, the test measures RNA in BC tumor specimens for the following transcripts:

Groups of genes measured in OncotypeDx assay, according to the manufacturer
cell proliferation tumor invasiveness growth factor receptors hormone responsiveness other genes of interest reference** genes



Cyclin B1


Stromelysin 3

Cathepsin L2




PR (progesterone receptor)






Beta actin





*In my opinion, survivin and bcl-2 might be better classified distinctly; the products of these genes inhibit apoptosis (programmed cell death).

**These “housekeeping” genes are not of known significance in BC pathology. Rather, they serve as controls in the assay for the quality of the RNA sample, and for comparison to other measured genes.

The OncotypeDx results are reported by risk group, as follows:

Low risk (RS <18, the 10-year recurrence rate was 7% in NSABP study – see below)

Intermediate (RS 18 – 30, the 10-year recurrence rate was 14%, in same);

Higher risk (RS >31, the 10-year recurrence rate was 30%, in same).

The tool has been tested in multiple clinical trials for its capacity to predict BC recurrence after surgery and tamoxifen in women with ER+, node-negative tumors. The study most-cited, and from which the above statistics are drawn, was published in the New England Journal of Medicine in 2004, based on a retrospective analysis of 668 cases by Genomics Health in collaboration with investigators of the National Surgical Adjuvant Breast and Bowel Project (NSABP, a large, NIH-sponsored, multicenter cancer research effort).

OncotypeDx has been on the market since 2004. The cost of one assay runs near $3800, and most U.S. insurance plans including Medicare will cover it. Tumor samples, set in fixative, are sent to a single lab – a Genomic facility – that’s regulated according to the Clinical Laboratory Improvement Amendments of 1988 (CLIA). The whole process takes 10-14 days. Still, the FDA has not approved the test for use as a decision-making tool.

Meanwhile, an NCI-sponsored trial called TAILORx will recruit and evaluate 10,000 women with ER+, node negative disease. Those investigators will determine, prospectively, if decisions based on OncotypeDx results can safely spare women with low RS the side effects and toxicity of chemotherapy without compromising their survival.

Why Oncotype and other new BC pathology tools matter –

In the U.S., the number of women who learn they have an ER+, node-negative BC approximates 100,000 per year. The question of adjuvant therapy – whether a woman should take tamoxifen or another hormonal agent and/or chemotherapy after surgery to reduce the risk of recurrent disease – is crucial.

If patients and their doctors could access more detailed molecular information about each case, they’d have a better sense of whether adjuvant treatment is likely to help in their particular situation. This approach would, potentially, spare many individuals with early-stage BC the costs, toxicity and hassle of unneeded chemotherapy. At the same time, it would help patients with small but riskier tumors by informing them that they have a high RS and thereby would more likely benefit from added therapy. Fewer women would receive chemotherapy, driving down costs, and the risks of additional treatment would be assumed only by those with a high likelihood of recurrence.

Some numbers here might help:

Overall, for women with ER+, node-negative tumors the chances of cancer recurring five years after primary treatment (mastectomy, or lumpectomy and radiation) followed by tamoxifen are around 15%. Over time that risk rises – BC can strike back after 10, 15 years or even later; the recurrence rate is said to approach 30% over time. In general, a basic chemotherapy regimen – something like CMF – cyclophosphamide (Cytoxan), methotrexate and 5-fluorouracil (5FU) reduces the probability of recurrence by about a third.

So if 100 women with node-negative tumors have to decide whether to take chemotherapy after surgery +/- radiation, or not, without a tool like OncotypeDx or another modern pathology test, they’re making those decisions based on very crude approximations of their odds. Because they don’t know whose tumors will recur, most if not all of their oncologists will recommend chemotherapy. And most women do choose to undergo the extra treatment because they’re afraid that, otherwise, there’s a greater chance the cancer will come back.

This is exactly the situation I faced in November, 2002, when I had an ER+, node negative, 1.5 cm tumor. Then, I reasoned that BC tends to be more aggressive in younger women. With hopefully more decades ahead in my life – more time, in effect, for the disease to recur – an 85% disease-free rate at 5 years wasn’t good enough. So I went for the chemo and upped my chances to the 90% range. Not a big difference in the stats, but I wanted to position myself on the upper branch of that Kaplan-Meier curve. Now, had I known my recurrence score based on the pattern of gene expression in the tumor cells, that information would have been useful. But it wasn’t an option then and, unfortunately, it’s still rarely available to most women who are undergoing treatment for BC in 2010.

The slow pace of progress, science in hand, is kind-of shocking.

So what’s new with OncotypeDx?

Two months ago, I reviewed a small study published in the ACS Cancer journal on the experiences of most of 100 women with newly-diagnosed breast cancer whose oncologists used the OncotypeDx assay to evaluate their cases. In that, two-thirds of the women reported they “understood a large amount or all” of what the doctors told them about the results and nearly all said they would undergo the test if they had to decide again.

In its April 1 issue the Journal of Clinical Oncology (JCO) published two relevant reports and an editorial. These papers support that OncotypeDx offers useful information to women with early-stage breast cancer and that it can assist patients and doctors in care decisions, in some cases providing support for them to choose a chemotherapy-free treatment regimen.

One study, a “Prospective Multicenter Study of the Impact of the 21-Gene Recurrence Score Assay on Medical Oncologist and Patient Adjuvant Breast Cancer Treatment Selection” by Dr. Shelly Lo and colleagues, followed the analysis and prescribing patterns of 17 medical oncologists at 3 diverse academic medical centers and one community hospital. Genomic Health, provided free OncotypeDx kits and testing at their central lab for all 93 patients with ER+, node-negative BC who enrolled in the trial.

The mean age of the women was 55 years (range 35 – 77). The oncologists were asked to state their treatment preferences (hormonal treatment with or without chemo) before and after receiving the OncotypeDx results for their patients. What happened was this:

Before seeing the OncotypeDx results, the oncologists recommended chemo and hormonal therapy (CHT) to 42 of the 89 women for whom the study was completed. In 20 of those 42 cases (22% of the total, and nearly half of those women who were to receive chemo) the doctors changed their recommendation from CHT to HT (hormones only) upon reviewing the OncotypeDx report. In 8 cases, the oncologists switched their recommendation to include chemotherapy. In total, the OncotypeDx results influenced the oncologists’ preferences in 31% of the cases – nearly a third.

As for the patients – 74 of the 89 (83%) said the OncotypeDx results influenced their treatment decision. The assay report persuaded 9 patients in the group to opt for a less aggressive (chemo-free) approach. The majority (78 women, 95% of those responding) said they were glad they used the OncotypeDx assay. According to the paper, many patients felt reassured by the assay findings and benefited from a diminished perceived risk of recurrence (less worry, in effect).

The upshot is that the OncotypeDx assay – which costs around $3800 per evaluation – led to significantly fewer women with early-stage breast tumors getting chemotherapy in this trial of 89 patients. The doctors were more confident in their decisions to not give chemotherapy in cases with low RS and, overwhelmingly, the women felt glad about the decision-making process.

In the second JCO study in the April 1 issue, the number of patients evaluated was much greater – over a thousand. But this was a more complicated analysis in which the investigators applied OncotypeDx to old tumor samples and then, upon reviewing those cases in some well-documented randomized trials, examined how the cases fared in relation to the RS. What they found was that OncotypeDx score predicted the likelihood of loco-regional recurrence (LRR) in women who had node-negative, ER+ disease.

Bottom line –

The OncotypeDx tool has been on the market for 6 years. It has, in multiple and well-done studies, identified patterns of BC gene expression that accurately predict the likelihood of recurrence in women with early-stage, ER+, node-negative tumors. This should, in principle, reduce administration of chemotherapy – along with its attendant risks, costs and side effects – to women whose tumors are unlikely to relapse. Recent trials show that doctors find the results useful and that patients find it helpful in their decisions.

I can’t know for sure why the tool’s not used more often. But I have some concerns:

1. It takes time for doctors – even knowledgeable oncologists – to learn about this device, to know how it differs from other BC pathology tests like Mammaprint and decision tools (like Adjuvant!) and then it takes even more time for those physicians to discuss the results with their patients.

From the perspective of a physician sitting behind her desk or at a table with a newly-diagnosed BC patient, saying “this is what I think, you need treatment X” may be a lot easier than “well, let’s go over these OncotypeDx results…”

2. If the OncotypeDx report does indeed identify large subgroups of early-stage breast cancer patients who don’t need chemotherapy, the use of this test would reduce the number of patients who get chemotherapy. Oncologists, infusion centers and others generate income by prescribing chemotherapy. So there’s a potential conflict of interest.

3. Perhaps some physicians fear lawsuits for not giving chemotherapy to women who, without the OncotypeDx results, would receive it.

4. Some doctors might not recommend OncotypeDx because they don’t really understand the test, its merits and limitations.

5. Maybe OncotypeDx isn’t the best of the new BC adjuvant therapy decision tools. For this reason, among others, I will consider some of the other methods available in future posts.

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