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Obesity, cancer, and chemotherapy

In medicine, particularly oncology, it’s often the little things that matter. Sometimes, however, the “little things” aren’t actually little; they just seem that way. I was reminded of this by a story that was circulating late last week in the national media, often under titles like “Obese cancer patients often shorted on chemo doses”, ”Are obese people with cancer getting chemotherapy doses too small for them?”, and “Obese Cancer Patients Not Getting Full Doses of Chemotherapy Drugs”. It’s also interesting to me because it stands in marked contrast to something I’ve written about a lot on this blog: The overtreatment of cancer. In this case, this story is about the undertreatment of cancer in patients who are obese, and it’s a problem that has definite adverse effects on an obese person’s odds of surviving cancer.

I’ve been aware of this issue for some time and had been thinking of blogging about it for at least three years. The reason is that the oncologist who is best known for sounding the alarm on this issue is Jennifer Griggs at the University of Michigan and, being local and all, I’ve seen her speak on the topic several times at local breast cancer conferences. Now that I work with a statewide breast cancer care quality improvement initiative, I’m becoming more aware of her work. Indeed, I was rather puzzled why this issue bubbled up enough to be reported widely on the national news last week when the Nature Clinical Oncology paper by Gary H. Lyman and Alex Sparreboom that drew attention to the issue was published in August, and the original American Society of Clinical Oncology (ASCO) guidelines were published last year. Whatever the reason this issue has been getting more attention, it’s a good thing.

Although the issue is simple in concept, namely that obese patients are not always getting full weight-based doses of adjuvant chemotherapy after cancer therapy, it’s not so simple to change attitudes. In chemotherapy dosing, most doses are calculated based on body weight or body surface area (BSA), which depends upon the weight. However, which “weight” to use in the BSA calculation has been a matter of controversy. When the actual body weight (ABW) is used, the BSA calculated can be huge, making it understandable why some oncologists might balk at the doses that they calculate, which can look staggering and provoke a reaction of “Holy crap, I can’t give anyone that much chemotherapy!” (Of course, the word used is usually not “crap.”) As a result, many oncologists “cap” chemotherapy doses, regardless of how large the patient is and how much chemotherapy the patient’s weight mandates, or use various forms of “adjusted” body weights in the BSA calculation, such as the ideal body weight.

The issue is summed up nicely in an AP story by Marilynn Marchione:

Obese people are less likely to survive cancer, and one reason may be a surprising inequality: The overweight are undertreated.

Doctors often short them on chemotherapy by not basing the dose on size, as they should. They use ideal weight or cap the dose out of fear about how much treatment an obese patient can bear. Yet research shows that bigger people handle chemo better than smaller people do.

Even a little less chemo can mean worse odds of survival, and studies suggest that as many as 40 percent of obese cancer patients have been getting less than 85 percent of the right dose for their size.

Now, the largest organization of doctors who treat cancer, the American Society of Clinical Oncology, aims to change that. The group has adopted guidelines urging full, weight-based doses for the obese.

Being reluctant to give full doses in such patients is not entirely unreasonable on the surface. For instance, in breast cancer, one of the most commonly used drugs is Adriamycin (generic name: doxorubicin), and one of its most serious potential complications is cardiac toxicity that in extreme cases can lead to congestive heart failure. Also, given the association of diseases like type II diabetes with obesity, many oncologists will see multiple comorbidities in their obese patients and decide that the better part of valor is to dial back the doses a bit in order to avoid doing more harm than good. Recent evidence, however, is suggesting that these concerns are overblown. Worse, recent evidence is also suggesting that there is a very real potential for doing harm by not giving full, weight-based chemotherapy doses, hence the recent ASCO guidelines and the article by Dr. Lyman in Nature Clinical Oncology.

The derivation of these guidelines is actually interesting in that it shows how tricky and complex it is to derive science- and evidence-based guidelines for oncology. Because there has never been a randomized clinical trial comparing full, weight-based dosing of chemotherapy versus dose-capped regimens, what we are left with are observational and retrospective studies, which have a variety of shortcomings that can be hard to overcome, particularly confounding by other factors. However it is certainly plausible, from both a basic science and clinical perspective, that the common practice of underdosing the obese could potentially lead to poorer outcomes. Moreover, there is now good evidence that not only is obesity itself is a risk factor for various cancers (e.g., breast) but that it is a negative prognostic factor for patients who do develop cancer, meaning that such patients are more likely to die of their disease. Indeed, a recent meta-analysis concluded that obesity very likely contributes significantly to the risk of death due to breast, prostate, and colorectal cancer.

In terms of the association of obesity to various cancers, there is now robust evidence linking obesity to an increased risk of cancer. Indeed, in 2002 the International Agency for Research on Cancer (IARC), using obesity prevalence data from Europe and relative risks from a meta-analysis of published studies, concluded that obesity was a cause of 11% of colon cancer cases, 9% of postmenopausal breast cancer cases, 39% of endometrial cancer cases, 25% of kidney cancer cases, and 37% of esophageal cancer cases. Meanwhile, data from the American Cancer Society suggested that obesity was related to mortality from liver cancer, pancreatic cancer, non-Hodgkin’s lymphoma, and myeloma. This effect on mortality reflects both the excess incidence and excess mortality among those with cancer. Overall, it has been estimated that obesity causes approximately 20% of all cancer cases. Over 32 years ago, Sir Richard Doll estimated that “overnutrition” (i.e., being overweight or obese) caused a combined 35% of all cancer cases. For the cancer to which I’ve devoted my professional life, breast cancer, as pointed out by Lyman and Sparreboom it’s been known for over 40 years that in animal models a reduction in chemotherapy dose by as little as 20% can reduce complete remission and cure rates by up to 50%. It has also been known for at least 20 years that breast cancer recurrence and survival are negatively impacted by obesity. The dose-response curve for chemotherapy can be steep in many tumors.

Why it is the case that obesity is both a risk factor for the development of cancer, particularly more aggressive forms of the cancers for which it is a risk factor, as well as a risk factor for mortality from cancer is not fully understood yet. Various molecular mechanisms have been proposed, including insulin resistance common in the very obese and in people with type II diabetes, altered levels of insulin-like growth factors, oxidative stresses, adipokines (growth factors secreted by adipose—fat—tissue), and obesity-related inflammatory markers. Whatever the biological mechanisms behind the increased risk related to obesity for developing cancer and for any cancers that develop to be more aggressive subtypes, it is certainly plausible from a basic and clinical scientific standpoint that undertreating such cancers could potentially lead to higher rates of recurrence.

In obese patients, this appears to happen a lot. Back in 2005, Dr. Griggs published a paper in JAMA Internal Medicine looking at how often such dose reductions occurred. She found that dose reductions on the first dose (usually called “cycle”) of chemotherapy, which would eliminate dose reductions due to toxicity, were instituted in 9% of the healthy weight, 11% of the overweight, 20% of the obese, and 37% of the severely obese women. She also found that first cycle dose reductions were independently associated with being overweight (P = .03), obese (P< .001), severely obese (P<.001), older than 60 years (P<.001), and having a serious comorbid condition (P = .03). Interestingly, she also found that severe obesity was actually associated with a lower likelihood of being admitted for febrile neutropenia (fever with a low white blood cell count, indicating potential infection in an immunosuppressed patient), was actually less common (odds ratio, 0.61; 95% confidence interval, 0.38-0.97) in the severely obese even in patients who received full dose, and there was a trend towards less admissions for febrile neutropenia associated with increasing body mass index that only became statistically significant at a BMI ≥ 35.

More importantly, it’s been known since the 1990s that decreased chemotherapy dose delivered is associated with significant increases in recurrence and decreases in survival. For instance, in 1996, in a retrospective analysis of a randomized trial of women with lymph-node-positive early stage breast cancer, Rosner et al. found that obese women receiving adjuvant chemotherapy experienced no greater toxicity or poorer outcomes than similarly treated healthy weight patients, and overweight women receiving full dose chemotherapy experienced better failure-free survival than those receiving reduced doses. More recent studies, such as this meta-analysis by Hourdequin et al., show that obese patients receiving chemotherapy based on the use of their actual body weight experienced the same or fewer chemotherapy-related complications as compared to the non-obese when they received the full ABW-based dose of chemotherapy, and survival outcomes did not differ between the obese and non-obese who received their full dosage of chemotherapy. Couple that with studies linking decreased dose to poorer outcomes, and the likelihood that obese patients not receiving their full doses are at significantly increased risk of dying of their cancers. As ASCO put it in their guidelines:

Recommendation 1.1: The Panel recommends that actual body weight be used when selecting cytotoxic chemotherapy doses regardless of obesity status. There is no evidence that short- or long-term toxicity is increased among obese patients receiving full weight–based chemotherapy doses. Most data indicate that myelosuppression is the same or less pronounced among the obese than the non-obese administered full weight–based doses.

However:

Recommendation 1.2: The Panel recommends full weight–based chemotherapy dosing for morbidly obese patients with cancer, subject to appropriate consideration of other comorbid conditions. Data are extremely limited regarding optimal dose selection among the morbidly obese and other special subgroups. More studies are needed to evaluate optimal agents and agent combinations for obese and morbidly obese patients with cancer; however, based on available information, it seems likely that the same principles regarding dose selection for obese patients apply to the morbidly obese.

And finally:

The Panel recommends that full weight–based chemotherapy doses (IV and oral) be used in the treatment of the obese patient with cancer, particularly when the goal of treatment is cure. Selecting reduced doses in this setting may result in poorer disease-free and overall survival rates. There are compelling data in patients with breast cancer that reduced dose-intensity chemotherapy is associated with increased disease recurrence and mortality. Although data in other malignancies are more limited, based on improved survival observed with chemotherapy compared with controls, a dose-response relationship exists for many responsive malignancies. Therefore, although data are not available to address this question for all cancer types, in the absence of data demonstrating sustained efficacy for reduced dose chemotherapy, the Panel believes that the prudent approach is to provide full weight–based chemotherapy dosing to obese patients with cancer, especially those receiving treatment with curative intent. Most of the data in support of full weight–based dosing come from the treatment of early-stage disease. Data supporting the use of full weight– based doses in the advanced disease setting are limited.

At this point, it is worth reiterating that medicine is rarely black and white (one notable exception is the case of something like homeopathy, which violates multiple laws of physics and chemistry and is, without a doubt, total quackery). It exists in shades of gray, which is where these recommendations come from. The panel examined evidence from multiple sources, including preclinical evidence from cell culture and animal models that dose reduction of chemotherapy can compromise “cure” rates, coupled it with evidence from humans that obese patients are more prone to cancer and more likely to die of cancer if they get it, noted that obese patients frequently don’t receive the full recommended dose of chemotherapy and that decreased dose of chemotherapy is associated with increased risk of cancer recurrence and death. From these data, they made the connection that quite likely at least part of the increased mortality due to cancer in the obese is because many of them don’t receive their full dose of chemotherapy based on a BSA calculated from their ABW. They also noted that obese patients are no more likely—and, in fact, may be less likely—to suffer chemotherapy-related complications than the non-obese when they receive full chemotherapy doses. Putting it all together, the panel was quite reasonable to recommend that chemotherapy dosing based on BSA be calculated using ABW, not the various other “capped” dosing methods or methods using adjusted body weights.

At the same time, weaknesses and uncertainties were acknowledged. For instance, as has been pointed out before, there has never been a randomized controlled clinical study comparing full, ABW-based dosing to capped doses and/or doses based on various adjusted weights. Given the confluence of evidence above, such a trial would likely fail the ethical test of clinical equipoise and therefore never be approved by an institutional review board. As I’ve said many times before, the reason we call it “science-based” medicine rather than science is because ethical and practical considerations limit how rigorous we can be. Moreover, we don’t know enough about the pharmacokinetics of chemotherapy drugs in the morbidly obese to determine whether a different strategy for calculating their doses would result in decreased recurrences and decreased toxicity.

Mark Crislip likes to quote a certain not-so-popular former defense secretary, “As you know, you go to war with the army you have, not the army you might want or wish to have at a later time.” It was one of the rare bits of actual near-wisdom that ever came out of the mouth of Donald Rumsfeld. Patients need to be treated now and clinicians can only use the tools they have at the time. Right now weight-based dosing is the tool that we have. Maybe someday there will be “personalized” (or “precision”) dosing based on expression levels of various proteins that metabolize the drug, weight, and who-knows-what other personal factors. That doesn’t help patients today; so we go with what we have, especially since the evidence that we have strongly supports not reducing chemotherapy dose in the obese just because they are obese. As Gary Lyman put it, while more research is clearly needed in this important area, it is essential that the science that we do have is applied appropriately and effectively in the optimal treatment of patients with cancer.

Finally, it’s a mistake to refer to this problem as “discrimination” against the obese, as Melissa Ford at BlogHer did:

We’ve seen a lot of discrimination towards obese individuals in various areas of health care not to mention a wide-range of businesses from airlines to restaurants. Yet in this case, we’re talking about a person’s survival. For 40% of obese cancer patients, before they’ve taken their first dosage of chemotherapy, the odds are stacked against them — not by science or fate, but by the doctor treating them.

While there is certainly discrimination against obese people because they are obese, dose reduction of chemotherapy in the obese is not an example of it. Rather, this practice derives from a concern that did not seem unreasonable in the past but that we now know to be almost certainly misplaced; that dosing obese patients the same way we dose non-obese patients will harm them. As Dr. Lyman says:

Don’t call it supersizing; it’s right-sizing cancer care, said Dr. Gary Lyman, a Duke University oncologist who led the panel that wrote the advice.

“There’s little doubt that some degree of undertreatment is contributing to the higher mortality and recurrence rates in obese patients,” he said.

Finally, there’s another lesson to be had here. Based on these data, there is a growing consensus to link the receiving of adequate chemotherapy doses to quality metrics in oncology care. Most people, including physicians, think that it’s all about saving money when they see evidence-based guidelines. Sometimes it is, particularly with initiatives like Choosing Wisely, which is designed to discourage the use of unnecessary tests and procedures. In this case, though, it isn’t. Treating with the full dose of chemotherapy is likely to cost more in the short term. Whether the amount by which it will decrease recurrences will be such that there will be a net savings because of fewer relapsed cancer patients is currently unknown. It might not be. In this case, higher quality care is likely to cost more. Such is likely to be the cost of “right-sizing cancer care.”

Posted in: Cancer

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35 thoughts on “Obesity, cancer, and chemotherapy

  1. Dosing drugs by weight is a poor practice – a small obese patient should not get the same dose as a large slim patient. Their weight might be the same in pounds, but one will have a higher drug concentration in blood than the other.

    I dont know what “discrimination” the porkers are complaining about.. there is one airline in the world that prices tickets by overall weight (passenger+luggage) and I wouldnt even call that discrimination. Not aware of any clinics that charge patients by body weight.

    1. windriven says:

      Citation? Or is this just your usual braying?

    2. Andrey Pavlov says:

      @FBA:

      You do understand the concepts of apparent volume of distribution right? Who am I kididng, of course you don’t. You probably also aren’t aware that most drugs do actually behave the same* based on weight regardless where that weight comes from. And that certain drugs don’t, and so we actually dose them differently. Sometimes based on ideal weight (i.e. what that person should weigh without the fat) and less oftenly with a correction for fat content using a different coefficient of distribution.

      But hey, thinking about that stuff is what folks like MDs and especially PharmD’s do, and it certainly wouldn’t work well for someone trying to score points against “the system” and how bad we are at what we do. Shame that it shares so little with reality that it may as well be entirely wrong.

      But you must have actually gotten your PharmD in order to know that “Dosing drugs by weight is poor practice” right?

      * Obviously not exactly the same but well within the therapeutic ranges we are looking for and are thus clinically indistinguishable.

      1. You probably also aren’t aware that most drugs do actually behave the same* based on weight regardless where that weight comes from.

        The same, really? No matter “where the weight comes from”? What a simple world would that be..
        Being a PharmaD surely you heard of things like Lipophilic Efficiency , pKa and absorption of ionized drugs in lipid membranes?

        1. Young CC Prof says:

          Yes, we know that for SOME drugs, straight weight-based dosing can result in overdoses for the obese. The point of this article is that, according to recent studies, chemo doesn’t work that way, and full weight-based dosing is the safest course of action.

          1. “Chemo doesnt work that way”, how do you think it works??
            It kills cells. Thats the whole purpose of chemo – Cell murder. There is nothing safe about this. You up the dose, you up the rate of cell destruction, in the lungs, the heart, the kidneys, etc..

            Do you think a 300lbs porker has a heart that can take 2x the chemo damage of a 150lbs long distance runner?

            Weight-based dosing is lazy and poor medical practice. But it does maximize chemo drug sales! Dr Farid Fata’s favourite dosing method.

          2. David Gorski says:

            Dr Farid Fata’s favourite dosing method.

            Um, no. Dr. Fata’s favorite dosing method was to administer chemotherapy to patients who were either in remission or didn’t have cancer in the first place.

            http://www.sciencebasedmedicine.org/when-conventional-doctors-betray-science-based-medicine-for-money/

          3. David Gorski says:

            Weight-based dosing is lazy and poor medical practice. But it does maximize chemo drug sales!

            Of course, you seem not to understand that we’re not talking about weight-based dosing. We’re talking about dosing based on calculated body surface area (BSA), which is not the same thing. True, weight is in the formula, but so is height. In any case, the ASCO recommendation is to use the actual body weight when calculating BSA for purposes of dosing.

        2. windriven says:

          A PharmaD? Does a PharmaD work in a PharmaC?

          1. David Gorski says:

            Dr Farid Fata’s favourite dosing method.

            Um, no. Dr. Fata’s favorite dosing method was to administer chemotherapy to patients who were either in remission or didn’t have cancer in the first place.

            http://www.sciencebasedmedicine.org/when-conventional-doctors-betray-science-based-medicine-for-money/

      2. Nick Theodorakis says:

        re: “But you must have actually gotten your PharmD in order to know that “Dosing drugs by weight is poor practice” right?”

        Why bother? There’s nothing easier to understand than pharmacokinetics/pharmacodynamics, right? ;-)

    3. WilliamLawrenceUtridge says:

      How would you know? You don’t even understand how the influenza vaccine can protect those who can’t be vaccinated, how on earth could you possibly be credible for something as complicated as chemotherapy? Perhaps you should defer to real experts instead of pretending to be one. Perhaps they know what pharmacokinetics are, perhaps they understand how much muscle versus fat versus a bloated, fat-streaked liver might absorb or metabolize drugs better than whatever pretend qualifications you have.

    4. elburto says:

      FBA spewing bigoted, incorrect, $CAM-trope riddled, wide-of-the-mrak* bollocks again? Must be a day ending in ‘y’.

      Your persistent guanotosis should be a priority for SBM in general, as curing you would be doing the world a favour.

      I almost pity you- being so full of partially-digested meadow muffins must be terrible, and is obviously the reason for the ceaseless flow of effluent that pours out of you and onto the keyboard.

      Tell me – what amazing set of qualifications do you possess that makes your expertise on cancer superior to that of Dr Gorski? Where did you study – the Dunning-Kruger campus of Mountain View University?

      1. Windy says:

        “wide-of-the-mrak* bollocks again?”

        Nicely done! Where is our boy Stan? His appearance with FBA would be a perfecta of perfidy, the rhetorical equivalent of a flashdark.

    5. Zaphod says:

      @FastBuckArtist, food for thought… like using the “N-word” to refer to people with dark skin, use of the word “porker” to refer to obese or overweight people says far more about the person using the term than it does about the person to whom the insult is directed.

      If I heard a pharmacist use that term to refer to an obese person, I would tell his employer that he can keep that pharmacist as an employee, or he can keep me as a customer, but he can’t keep both, and everyone I know will know of his choice.

      If you are, in fact, a pharmacist, you are a disgrace to your profession. If you are not a pharmacist, you are just a disgrace in general.

      1. lagaya1 says:

        Thank you Zaphod ( as in Beeblebrox?). I was trying to craft a similar reply, but your said it beautifully.

        1. Egstra says:

          I agree… and much more civilly than I could have.

  2. windriven says:

    If chemotherapy agents are lipid soluble it might suggest an increased dose for the first cycle for the obese rather than a truncated one. I was not able to find anything in Pubmed that directly addressed the issue but lipid solubility of anesthetic agents has been a concern in anesthesiology for some years. Most inhalation anesthetics are now fairly lipophobic allowing rapid induction and emergence.

  3. While waiting in line to buy beans at the coffee place I saw a very obese woman in a bright pink turban with a built-in headband and flower, (she didn’t seem to have any hair at all) sitting with her iPad and not one, but three pink pastry bags on the table which she munched on alternatively–the line was looonnngggg. I felt awful for thinking that if she was a chemo patient, this kind of indulgence couldn’t be helping.

    On the other hand, if I am ever diagnosed with anything terminal, not only will I spurn treatment (considering my age), but I will eat chocolate and drink good scotch until I explode.

    This really has little to do with the post, but it’s interesting how these posts jog my memory of recently peripherally related events.

    1. If possible enjoy your chocolate and scotch now (in moderation of course). Sadly, none of the people I know who were diagnosed with terminal cancer were able to enjoy food or alcohol very much, due to the symptoms of the cancer. ;(

      I’m sure that can’t be generalized to all cancers, but still…

  4. Harriet Hall says:

    There are a lot of different chemotherapy drugs. Are they all enough alike to apply the same rules across the board?

  5. Carl says:

    I guess the answer is “no”, but don’t they have a blood test to do after a chemo infusion to see what blood concentration the patient ends up with?

    1. Self Skeptic says:

      @Carl,
      Good question. (This is way out of my field, so it’s a perfect case to see how long it takes for a scientist to figure out what the basic issues and arguments are, and whether there’s any obvious Achilles’ heel in the most currently popular method.) Anybody have the refs at hand for blood concentration study reviews and key influential papers? I do realize there are a lot of different drugs to consider; but the guidelines under discussion suggest that blanket generalities can be made, with a few exceptions.

      So far, I’m finding arguments for BSA, weight-based, and fixed dosing; the fixed dosing arguments say that there is so much individual variation in drug elimination, etc. that it’s not worth adjusting the dosage. I’ve always thought it a little strange that most drug doses (outside of cancer chemo and presumably a few other cases) aren’t adjusted for body size in some way. Can someone explain why, preferably in a civil tone? I’m guessing it has to do with the much lower toxicity of most drugs, and that there’s a wide range of concentrations that are effective, so it’s not worth the inconvenience of taking body size into account except for children.

      1. I’ve always thought it a little strange that most drug doses (outside of cancer chemo and presumably a few other cases) aren’t adjusted for body size in some way.

        Toxicity of the drug is the issue here.. with toxic drugs you want to give as little as possible so the dose is adjusted. (unless you are getting prescribed by Dr Farid Fata or a likeminded MD shill)

        The pharma companies dont like this one bit as reduced dose means less sales. They LOVE weight-based dosing, its no secret that americans are getting heavier and weight-based doses are a big revenue booster.

        To avoid overdosing the obese patients, I recommend reading about LBW dosage scaling

      2. weing says:

        The fixed doses assume a certain body size and others have a maximum dose. A lot of meds are titrated to the effect of the drug. How low the LDL falls in response to a given dose, for example. I don’t know if they still do it like this, but I recall the hemonc people titrating chemo to the nadir in the white count. You also need to keep track of interactions with other meds that share the same enzymatic pathways for elimination or may induce the enzymes for elimination. A lot of the meds need to be adjusted for liver and/or kidney function also.

  6. Why it is the case that obesity is both a risk factor for the development of cancer, particularly more aggressive forms of the cancers for which it is a risk factor, as well as a risk factor for mortality from cancer is not fully understood yet. Various molecular mechanisms have been proposed, including insulin resistance common in the very obese and in people with type II diabetes, altered levels of insulin-like growth factors, oxidative stresses, adipokines (growth factors secreted by adipose—fat—tissue), and obesity-related inflammatory markers.

    Here’s my super-naive question: could it be that obesity = more cells = more chances for unfavorable mutations?

    1. @Heather:

      Not a bad thought. And certainly not exactly wrong, either. However the key is not the absolute number of cells but the number of cell divisions. The more a cell divides the more likely its daughters are to accumulate the right (for cancer, wrong for us) mutations. Having more absolute number of cells means that they divided more, so that does increase the odds. However, once you became an adult you stay relatively stable in your adipose cell number. It is the cell size that increases as you eat too much food around the holidays. Which is why having kids stay thin until after puberty is actually rather important – they will never lose that final cell number, just shrink down fat cells as they lose weight. Making that “chiseled” look much more difficult if not impossible to attain but, more importantly, making weight gain later in life much easier.

      So yes, in a small sense more cells = more chance for cancer, but really by far the largest driver is cell turnover. Plus, the cancers we find in obese people are typically not fat-cell derived ones (like lipomas and liposarcomas; at least not much more than the average person, to my knowledge) so having more fat cells doesn’t explain why obese people have more of those cancers, directly at least. Fat cells do release hormones including estrogen like and other growth hormone like hormones, so this could be playing a role.

      1. David Gorski says:

        Also, fat tends to be pro-inflammatory, and chronic inflammation predisposes certain organs to cancer.

    2. WilliamLawrenceUtridge says:

      I believe once you hit adulthood, your fat cells don’t divide further, they merely inflate (put another way, morbid obesity is due to hypertrophy rather than hyperplasia). You have to get really, really fat as a kid to develop a greater than average number of fat cells, and even then I think they pretty much stop dividing once you hit adulthood, and you aren’t really at much risk at that point.

    3. There are a few issues that makes obesity a cancer risk:

      - Obesity impaires the effectiveness of certain chemotherapy drugs,
      - Cancer can seek refuge within fat cells, this has been observed in leukemia for example
      - fat-embedded cancer cells demonstrate increased resistance to chemotherapy.
      - obesity causes insulin resistance and chronic inflammation, both leading to more tumors

      just to name a few

      quantity of cells is not the problem here, its the quality.

    4. corky says:

      obese people do not generally have more cells of the type that give rise to cancer. For example there is not an increase in the number of epithelial cells in the breast or colon, so that is not a good explanation.
      I would have to disagree with the wording that obesity “causes” cancer. Being obese is associated with an increased risk of cancer, that does not mean it is the CAUSE. As we don’t really understand the observation of increased cancer in obese people we should be agnostic about causation. Maybe obesity decreases the age at which cancers are detected, which could lead to an apparent increase in number. This could be explained by obesity increasing the growth rate of tumor cells, or decreasing the time of transition from benign to malignant lesions.

  7. Katherine says:

    Anyone suffering from cancer.. Run and run fast from this blog. Just my humble opinion from one whom has battled cancer with and successfully without chemo. I shall never do chemo again. Don’t let them give you false promises or use scare tactics.

  8. WilliamLawrenceUtridge says:

    Anyone suffering from cancer.. Run and run fast from this blog. Just my humble opinion from one whom has battled cancer with and successfully without chemo. I shall never do chemo again. Don’t let them give you false promises or use scare tactics.

    Dear Katherine,

    What kind of cancer?

    How long ago were you treated?

    How were you treated?

    What sorts of tests have you had to indicate you are now cancer free?

    How do you know your recovery was due to whatever non-chemo intervention you used? How do you know the chemo wasn’t what made you better, and your attribution of recovery to the nonchemo isn’t simply wrong?

    How do you know any initially solid tumor you had hasn’t metastasized and is now burrowing its way through your bones and organs?

    Sincerely,

    Anyone who knows anything about cancer

  9. Lisa from NY says:

    An old neighbor died at age 55 from cancer. She didn’t have to. She chose an alternative health-care practitioner over chemo.

    You are doing a service. She didn’t have to die.

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