Archive for the 'Cancer' category

Another worry for breast cancer patients?

Jan 05 2011 Published by under Cancer, Medicine

Breast cancer is the most common (non-skin) cancer in women, and despite advances in treatment, it is still deeply feared, and with good reason.  But breast cancer is really several different diseases.  Breast cancers can arise from several different cell types, they can occur during the pre- or post-menopausal period, and they can have various cell surface receptors, all of which can change their behavior (and their lethality) significantly.

One of the things common to all cancers is that cells that were formerly normal begin to proliferate inappropriately, and fail to die when they should.  The h0rmone estrogen tells normal breast cells to proliferate, which maintains normal, functional breast tissue.   Estrogen can also tell breast cancer cells to proliferate, which is not a good thing.  One of the great advances in the treatment of breast cancer is the drug tamoxifen, which can block the action of estrogen on breast cells.

When an estrogen molecule enters a breast cell, it binds to a receptor molecule and knocks off a molecular "lock", allowing two estrogen receptors to bind together.  This "dimer" enters the cell's nucleus and interacts with DNA, increasing the activity of certain genes which lead to increased cell growth.  Tamoxifen works similarly, but when the tamoxifen-activated dimers interact with DNA, they inhibit cell proliferation.  This is a good thing, and tamoxifen has been shown to save lives in breast cancers that have estrogen receptors.

But when you take a tamoxifen tablet, it's not the tamoxifen itself that enters the breast cells.  The drug is absorbed by the stomach and eventually transported to the liver where it is converted to a chemical called "endoxifen".  It is the endoxifen that is the active molecule that helps prevent breast cancer recurrence and reduces mortality.  In order for tamoxifen to become endoxifen, it is processed in the liver by an enzyme called cytochrome P450.  The P450 system serves as a factory for changing chemicals into other chemicals, often in order to help eliminate them from the body; it is essentially a "detoxifying system".  Cytochrome P450 comes in many different flavors, each one working to transform different chemicals, especially drugs.  Drugs can be transformed in a way that makes it easier to eliminate them, or can be transformed in a way that activates them, as with tamoxifen/endoxifen. The P450 that transforms tamoxifen to endoxifen is called CYP2D6.

P450 is a tricky system.  While one drug may be metabolized by P450, another may inhibit or ramp up the enzyme.  This means that if, for instance, I give a patient tamoxifen, and also give them a drug that inhibits CYP2D6, the tamoxifen may not be turned into endoxifen efficiently.  And this is what apparently  happens with the antidepressant paroxetine (Paxil).

Paroxetine is a very potent inhibitor of CYP2D6.  It's also a very popular drug.  Depression is very common, especially in breast cancer patients.  Paroxetine is also used to treat hot flashes, a symptoms of both menopause and of tamoxifen treatment.  Given the relatively high chance of a woman being treated with both of these drugs, it would be good to know how significant this drug interaction might be.

A 2010 study published in the British Medical Journal did just that.  It used Canadian health records to look at usage of both drugs and at mortality in post-menopausal women with breast cancer.  What they found was that concomitant use of tamoxifen and paroxetine, but not other similar antidepressants, increased the risk of death.

This is a really, really big deal, but there are some limitations to the study.  First, they did not actually measure endoxifen levels, so that particular link in the causal chain is assumed.  They also did not evaluate patients to see which type of CYP2D6 they had; some people naturally have a more or less functional version, and we don't know how these patients may have been distributed in the groups.

But the hypothesis is plausible, and the fact that other SSRI antidepressants did not show a significant association with increased mortality should give us pause.  There are many, many inexpensive and reasonably effective choices for the treatment of depression, and after reading this study, as a clinician I would hesitate before prescribing paroxetine to a woman being treated for breast cancer with tamoxifen.

References

Kelly, C., Juurlink, D., Gomes, T., Duong-Hua, M., Pritchard, K., Austin, P., & Paszat, L. (2010). Selective serotonin reuptake inhibitors and breast cancer mortality in women receiving tamoxifen: a population based cohort study BMJ, 340 (feb08 1) DOI: 10.1136/bmj.c693

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To live deep and suck out all the marrow of life

Aug 13 2010 Published by under [Medicine&Pharma], Cancer, Medicine, Science-y stuff

There are few procedures in medicine more complex, dangerous, and remarkable than stem cell transplantation. This procedure has enabled us to successfully treat cancers that were previously uniformly fatal. For certain types of acute myeloid leukemia, for example, stem cell transplant increases 5-year survival from less than 15% to about 44%.

But the full story of stem cell transplant is much more complicated.  The data are complicated and the research is full of fits and starts, new questions and dead-ends.

Chimera. Apulian red-figure dish, ca. 350-340 BC. The Louve, Paris, France. Image from Wikimedia Commons

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Cancer 201--treatment basics

Aug 05 2010 Published by under Cancer, Science-y stuff

Once a cancer has been diagnosed, we must use our knowledge of biology, medicine, and clinical trials to plan treatment. Treatment can be curative or palliative (that is, with a goal of reducing symptoms or extending life, rather than effecting a cure).

Understanding cancer treatment requires a little bit of basic biology, and as with all of my more "science-y" posts, please forgive any oversimplification (but please also note that this complexity stands in stark contrast to the simplistic altmed cancer "cures"), or for overtopping the head of the hapless non-scientist.

As you recall from Cancer 101, cancer is a proliferation of abnormal cells. This fact alone, that the cells are actively dividing, gives us a target for therapy.

Cells go through particular phases in their lifetimes, but these phases aren't as simple as "birth, growth, death". The life of a cell is roughly divided into the cell cycle, during which the cell is preparing for and conducting cell division, and the G0 (G sub zero, or G-naught) phase, where the cell simply goes about all of it's non-reproductive business, such as structural support and protein production. Normal tissue has a fairly balanced growth fraction, that is the number of cells dividing is roughly equal to the number of cells being lost (to normal programmed cell death and other normal attrition). Cancerous tumors have a higher growth fraction than normal tissue, that is the number of cells in cycle is higher than the number of cells being lost (to programmed cell death, etc.).

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Time well spent

Aug 04 2010 Published by under Cancer, Medical Musings

This was first published April 26th, 2010.  While I'm Up North, I'll be reprising some of my favorite pieces. Thanks for your patience.  --PalMD.

A few years ago I was walking through a local mall with my daughter and saw a kid about her age wearing a backpack and holding hands with a young woman. He was a gorgeous little boy, with black hair and huge black eyes. His eyes reminded me of my daughter's. There was a name tag on the backpack. The last name was unusual but one that I recognized as that of a guy I grew up with---and this little boy looked just like him.

So I politely asked the woman if she was D's wife. She laughed and introduced herself as a family friend. My friend D and his wife were in California getting her cancer treatment.

I'd heard that D's wife had been diagnosed with cancer shortly after giving birth, but I hadn't really seen D in years. He was one of the nice kids in the neighborhood, brilliant but not overly nerdy, kind, and not into torturing other kids. I figured he must have married a wonderful woman. And I was right.

I'm not sure how we all became friends, but somehow we did. My wife and his hit it off immediately. She was never "our friend with cancer" but just our friend. Still, there were reminders that she wasn't entirely well. A couple of years ago, she started to experience a cough and some pain in her side. Despite this, we went to a side-splittingly funny movie where she alternately laughed and cried. We found out a little later that she had broken a rib.

My friend has been in the hospital for a while. It's a long story, and not a good one, so we'll leave that be, but it's given me an opportunity to spend a lot of time with her. And while I'd rather hang out at their pool with the kids eating Chinese food, this time together has been remarkable.

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Cancer 101

Aug 03 2010 Published by under Cancer, Science-y stuff

Cancer is the second leading cause of death in the U.S., and at any moment directly affects almost 4% of the population, or about 10.8 million Americans. A diagnosis of cancer can be one of the most frightening moments in someone's life, and yet most people understand little about the disease. I hear the same questions about cancer over and over again, so it's well past time to give a bit of an explanation of this set of diseases.
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Cannabis and cancer cachexia

Nov 24 2009 Published by under Cancer, Medicine

One of the most frightening symptoms of advanced cancer is "cachexia", or severe, unintentional weight-loss and wasting. It's a terrible prognostic sign, and the only truly effective treatment is removal of the cancer. Treatment of this syndrome has the potential to improve quality of life in patients with advanced cancers. Various types of medications, including antidepressants, hormones, and cannabis derivatives have been tried with little effect. Treating the symptoms of incurable cancers is difficult and although we're pretty good at it, we sometimes fail. Cannabis seems a plausible intervention, given the anecdotal and clinical data associating it with increased appetite, although appetite in normal, healthy individuals may be mediated by different pathways than the cachexia in cancer patients. Still, it's worthy of investigation.

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31 responses so far

HPV vaccinination---this is real, people

Oct 14 2009 Published by under Cancer, Vaccination inanity

First let me remind you that I've written extensively about HPV infection, cervical cancer, and Gardasil, the vaccine to prevent these. The links are at the bottom of the post for your reference.
OK, here's the deal. A bloggy friend of mine is dealing with some serious health concerns due to HPV infection. I've written lots of pieces about the more intimate side of medicine, but no one can tell it like a patient. How someone deals with disease is a personal matter, and she has decided to "come out" and share her story in order to help others. (Digression: a great book called Everything Changes about dealing with cancer as a young adult is out, and it is also a bit harsh on our current health care system. It's a Studs Terkel type oral history, and a good read.)
I'm sorry to keep getting derailed here, but for some reason, a lot of my friends have cancer, and it's right in my face these days. I have one friend who's had ovarian cancer since her baby was born four years ago, another who just had a bilateral mastectomy, another with metastatic melanoma---you get the idea. If there had been some way to prevent these cancers, either by aggressive screening to identify early disease or by primary prevention through, say, vaccination, I'd be a much happier person.
Which brings me back to my friend. The internet is a funny place. Stephanie and I certainly don't agree about everything, but we do read each other's stuff fairly regularly and have had the chance to meet in person, albeit far too briefly. I'm hoping she and her hirsute hubby will make it to ScienceOnline this winter. Anyway, like many Americans, Stephanie hasn't always been able to get regular screening exams, and whether it's because of insurance, finances, laziness, or aliens, the point is that screening (that is, Pap smears) requires an action on the part of the patient to understand risk and to present themselves to a doctor for an invasive and expensive exam at least once a year.
Like many American women, Stephanie harbors the human papillomavirus, and apparently her guest is one of the cancer-causing strains. This virus lives in her cervix and messes with the genes of cervical cells, causing them to reproduce uncontrollably. In her case, the malignant cells haven't yet figured out how to invade very deeply, but they are spread out rather diffusely, making cure certain, but not easy. Stephanie has a good picture up at her place, but let me give you a little more detail. I find that people who don't actually dig into other people regularly don't always have a good feel for more hidden anatomy. You can check out the linked picture, but more helpful (at least for women) would be to ask for a mirror at your next gynecology appointment.

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27 responses so far

Cancer 202---Radiation therapy

Jun 28 2009 Published by under Cancer, Medicine, Science-y stuff

(NB: as is usual with my more "science-y" posts, oversimplification is the rule. --PalMD)
It's been a very long while since I've updated my series on cancer. I keep meaning to, but you know how things go. Lately, though, I've been curious about radiation oncology, the use of ionizing radiation to treat cancers. What set me off was a recent Times article about some pretty crappy practices. Radiation oncology requires a very thorough education in physics and medicine and the field attracts some of the best minds, but no field is immune to unethical behavior (which in this case I feel is more important than the incompetence itself).
Anyway, radiation---it scares the crap out of people. We call magnetic resonance imaging "MRI" instead of the original "NMR" (nuclear magnetic resonance) mostly because the idea of being in a machine with the word "nuclear" on it freaks people out. Of course, radiation is a normal part of living. We are exposed to high energy electro-magnetic radiation daily, both from the Earth and from space. If fact, ionizing radiation from the sun is the primary cause of skin cancer.
Very shortly after ionizing radiation was discovered in the late 19th century, it was applied to the treatment of cancerous tumors, albeit in a very crude way. As knowledge of physics and medicine grew, so did the sophistication of treatments. Early on, of course, it wasn't understood exactly how radiation damaged living tissue. If you aim x-rays at healthy skin for long enough the skin starts to turn red in a way similar to a sun burn. If you want to get that radiation to a tumor somewhere under the skin, then simply aiming an x-ray at the skin above it is going to kill skin long before it kills tumor. Thankfully, people are rather clever. In the early 20th century, doctors tried inserting radium directly into tumors, and tried fractionating treatments of external beam radiation so that each individual dose was not too toxic to the overlying structures. These techniques allowed killing more tumor cells than normal cells.
But let's back up a little here and examine some of the basics.

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Cancer, cults, and kids

I've been reluctant to write about the Daniel Hauser case. I don't even want to imagine what his parents are going through. If you're not a parent, I can't explain it to you, so you'll have to trust me---having a kid with a life-threatening illness can drive you to do the unimaginable.
And what Daniel's parents have chosen to do is nearly unimaginable, but until you've been there, judgment must be tempered by compassion. But that compassion is only for the parents and the patient, not for those who are supporting their horrible decisions.
The basics
Daniel is 13 year old boy with Hodgkin's disease, a form of cancer that is curable with radiation and chemotherapy. Without it, it's deadly, and the death isn't pretty. I've diagnosed patients with Hodgkin's and had the pleasure of watching them go on to live normal lives. None has ever regretting being treated.
Daniel's parents apparently belong to a cult called Nemenhah, some sort of New Age-Christian gamisch of beliefs with a Native American patina. Like most cults, it wants your money, your absolute obedience, and ideologic purity. In return you get to abandon your money and your access to modern medical care.
Daniel's parents, after one cycle of chemotherapy, decided to follow the Nemenhah dictates and eschew modern, curative medical care. They may or may not realize that the suffering they are inflicting on their child is much worse than anything he could experience with treatment. When the courts ordered him back to treatment, the mother took Daniel and ran. She is currently wanted by the police.
The basic ethical principles here recognize that children, while autonomous beings with rights, have a limited decision-making capacity, and must rely on adults, preferably their parents, for guidance. If the parents cannot provide a safe environment, the State becomes involved, as it did in this case.

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14 responses so far