The paper trail linking excess weight to increased cancer risk is long.
As obesity rates climb worldwide, research into the complications
associated with diagnosing and treating cancer in this portion of the
population is becoming more prevalent.
Some of the findings are self-evident: Due to body-image issues and
other psychosocial concerns, for example, obese women are less likely to get
Pap smears and other invasive tests that may detect gynecologic cancers.
Other data present a more confounding picture. Many obese patients seek
treatment for cardiovascular disease, diabetes or other conditions that arise
from being overweight. In some cases, their relationship with the health care
system gives clinicians an opportunity to diagnose and treat
cancer in a timely manner. Other times, the health concerns that necessitated
the initial visit require so much attention, cancer may go undetected.
Obesity rates the percentage of people with a BMI of 30 or
greater have doubled worldwide since 1980, with an estimated 9.8% of men
and 13.8% of women meeting that criteria, according to research published last
year in The Lancet.
Nearly one-third of Americans are obese now, and if trends continue,
half of the US population could be classified as such by 2030, findings
published in The Lancet show.
A. Meyerhardt, MD, MPH, associate professor in the department of medicine at
Harvard Medical School and a gastrointestinal oncologist at Dana-Farber Cancer
Institute, said more research must be done to help clinicians understand how to
manage the increasing number of obese cancer patients.
Photo courtesy of Dana-Farber Cancer
HemOnc Today spoke with several physicians and researchers
about the extent to which these populations are screened for cancers,
challenges related to surgical options and chemotherapy dosing, the increased
risk for drug interactions among those who are taking medications to control
other diseases, and obstacles to effective post-treatment care.
Perhaps the most basic challenge is determining what is overweight
or obese, said Heather Bittner Fagan, MD, FAAFP, MPH, associate
professor at Thomas Jefferson University and director of health services
research in the department of family and community medicine at Christiana Care
Health System. Given how heavy people in the United States are, it is
difficult to know where to draw the line. This may also impact the direction of
the research and the outcomes we see. Many of the data are still
Fagan and colleagues recently published a review paper in the
Journal of Obesity that examined the association between weight
and cancer screening, while also examining screening rates across
race/ethnicity and gender.
Among the findings:
- Obesity is associated with higher rates of prostate cancer screening
among all races.
- Obesity is associated with lower rates of cervical cancer screening,
particularly among white women.
- No correlation appeared between weight and mammography use in
- Obese women were less likely to be screened for colorectal cancer,
while the relationship between weight and colorectal screening in men was
It is striking how variable the relationship between obesity and
screening can be, Fagan said. There are big differences based on
the type of screening and the type of cancer.
More clinical barriers to screening overweight women for certain cancers
Many severely obese women need special accommodations such as
larger examination tables, but even with these in place, it may be difficult to
examine all the reproductive organs satisfactorily, Bryan C. Bordeaux,
DO, MPH, of the division of general internal medicine at Johns Hopkins
University School of Medicine, and colleagues wrote in a review paper in the
Cleveland Clinic Journal of Medicine. Clinical breast
examinations may be less reliable because increased tissue volume may make some
tumors difficult to palpate.
The results of Fagans paper indicated that fewer body image-based
effects were seen in men than in women, but that screening men also can be
Most data indicate that obese men are less likely than nonobese men to
undergo a digital rectal exam to screen for prostate cancer. However, because
prostate cancer can be detected by a much less invasive blood test, obese men
are being screened.
In prostate cancer, obesity can actually facilitate
screening, Fagan said. Obese men are already in the [health care]
system for other things and are therefore likely to get tested.
The data is far less consistent for colorectal cancer screening, the
only test recommended for both men and women.
Two studies Fagan and colleagues examined indicated obese men had lower
colorectal cancer screening rates. One study indicated a higher rate among
obese men, and three studies found no association. Four of six studies that
examined the same factors in women demonstrated a negative association between
obesity and colorectal cancer screening.
The take-home message is that specialists need to understand obese
populations have a patchier history of being screened, Fagan said.
Obesity has unique impacts on imaging, said Munir Ghesani, MD,
attending radiologist at St. Lukes-Roosevelt Hospital Center and Beth
Israel Medical Center and a HemOnc Today Editorial Board member.
There are essentially two things to look at, Ghesani said.
How does obesity impact image quality, and (for studies involving
ionizing radiation) how does it impact radiation exposure?
The quality of the image depends on the type of scan.
Fat in areas like the abdomen can provide better image contrast
and actually be helpful in reviewing a CT scan, he said. However,
if you are doing a nuclear scan, you can get more severe attenuation artifacts
in obese patients, and the image quality suffers. Consequently, the quality of
PET and nuclear scan images is usually poorer in obese patients.
In order to achieve similar image quality, radiation doses may be higher
in overweight or obese patients. Increased radiation exposure may, in turn, be
linked to increased risk for other cancers.
That said, the advantage of most current-generation machines is
that they are able to adapt to different-sized patients, Ghesani said.
Socioeconomic factors also can be barriers to imaging.
Obesity is more common in poorer people who are more likely to be
uninsured and may be less likely to follow through with expensive procedures,
according to Bordeaux and colleagues.
Then there are clinical obstacles to imaging in overweight patients.
Unfortunately, many of our imaging machines are not designed to
handle people who are morbidly obese, Bordeaux told HemOnc Today.
Sometimes the tables on which patients rest during the procedure cannot
safely support the patients weight, they might be too narrow to prevent
them from falling, or the machine openings are too narrow (in the case of a CT
or MRI machine) to allow a patient to pass through to the sensors.
In some cases, patients must be transported to veterinary hospitals so
larger imaging machines can be used, Bordeaux said.
The challenges related to screening and performing imaging on obese
patients often lead to later diagnosis, said Dale R. Shepard, MD, PhD,
an associate staff member in solid tumor oncology at the Taussig Cancer
Obese individuals are less likely to detect tumors by self-exam
because the patients are so large, Shepard said. When the tumor is
found so late, it is not surprising that the patients do not do as well.
Bordeaux echoed that point.
Obese individuals, particularly those with a BMI greater than 35,
are more likely to have deeper and wider pelvic structures, making it harder to
palpate their cervix, ovaries or prostate, he said. Also, examining
joints, the heart and lungs, breasts, thyroid and testes are more challenging
because of the increased adipose tissue overlying these areas.
Conversely, there are instances when a cancer diagnosis is unexpected.
People often get a diagnosis because they are obese,
Bordeaux said. They are in the health care system because of obesity,
which means they may be more likely to get scanned for something else. They
felt fine, or at least cancer wasnt on the horizon, but they got a CT
scan for another reason and a cancer was discovered. How many times do we have
people in the system and they find things sort of accidentally?
Little is known about the relationship between obesity and cancer
diagnosis because little research has been done about it.
The focus of research is largely on risk prevention,
Bordeaux said. It would be difficult to conduct this kind of study, to
follow obese individuals and nonobese individuals and see what kind of
diagnosis and outcomes might occur. This is a huge undertaking, and data like
this usually come out of studies like [the National Health and Nutrition
Examination Survey] big studies looking at dozens of associations.
The most comprehensive research on obesity and cancer treatment has
focused on drug dosing.
A landmark paper by Smith and Desch, published in Southern Medical
Journal in 1991, provided a defining statement on how obese patients
should be dosed.
We propose that patients being treated with curative intent
receive full-dose intensity, using body surface area calculated on actual body
weight or on ideal body weight with dose escalations if tolerated, they
The discussion in the clinical community eventually evolved to whether
the doses should be capped and, if so, what the limit should be.
Under-dosing of chemotherapy for breast cancer among obese women
has been reported and may be associated with poorer outcomes, Bordeaux
and colleagues wrote. Nevertheless, data on the appropriate dosing of
chemotherapeutic agents in obese patients are limited, and the effects that
this potential under dosing might have on mortality rates are unclear.
In a 2006 study published in Hospital Pharmacy, DuBeshter
and colleagues found most oncologists use a dose limit less than that for a
body surface area of 2.2 m2.
This user set limiting dose was rarely exceeded, with 97% of
dosages below the limits set in this computer order entry system, they
In a 2005 study published in Archives in Internal Medicine,
Griggs and colleagues studied chemotherapy doses in women with breast cancer.
Overweight and obese women with breast cancer often receive
intentionally reduced doses of adjuvant chemotherapy, they wrote.
Administration of initial and overall full weight-based doses of adjuvant
chemotherapy in overweight and obese women is likely to improve outcomes in
this group of patients.
Adam M. Brufsky, MD, PhD, professor of medicine and associate
chief of hematology-oncology at the Womens Cancer Center at
Magee-Womens Hospital of UPMC and the University of Pittsburgh Cancer
Institute, acknowledged the under-dosing of patients but noted the opposite
also is a concern.
Like many clinicians, I have been cautious because the fear is
that we are going to overdose patients, said Brufsky, who also is a
HemOnc Today Editorial Board member. There are just too many
complications that can arise, such as the links between carboplatins and
thrombocytopenia and neutropenia.
Brufsky emphasized the importance of understanding body fat content.
The difference between 20% body fat content and 40% body fat
content is huge, he said.
Shepard noted some drugs go into the bloodstream, while others are
absorbed into fatty tissue.
We need to account for this, but the complications do not stop
there, Shepard said. A man who is 6 feet and 300 lb may be nearly
twice the size of a man who is 6 feet and 180 lb, but that does not mean he
will have twice the blood volume. It is a complex equation.
Obese patients particularly those who are older tend to be
on more medications to treat conditions such as cardiovascular disease, kidney
disease or diabetes, Shepard said. On a basic level, these drugs interfere with
cancer treatment. They also can reduce liver function.
It is sort of an indirect complication from the obesity, and it
can make things particularly tricky if you are trying to treat a cancer with
drugs that are metabolized by the liver, Shepard said.
There also is another complication with cancer drugs, said Carrie
Tompkins Stricker, PhD, RN, director of clinical programs and oncology
nurse practitioner at the Livestrong Survivorship Center of Excellence at the
Abramson Cancer Center of the University of Pennsylvania.
A particular concern is weight gain associated with treatments for
hormonally mediated cancers, including breast and testicular cancers,
said Stricker, who also is a clinical assistant professor of nursing at Penn,
where she leads a pilot study of an Internet-based weight loss program for
survivors of these two cancers. Chemotherapy has been linked to weight
gain. The classic thought, supported by a wealth of research in these cancers,
is that you are going to gain weight as you move into and beyond
Women who gained weight under these circumstances had an increased risk
for breast cancer death. Such weight gain could also affect adherence to
life-saving hormonal therapy in these women, although no studies have
specifically examined this, Stricker said.
Despite the fact that most studies including randomized
clinical trials have failed to link tamoxifen to weight gain, many
breast cancer survivors attribute their weight gain to it since this is the
only medication they are taking as they continue to gain weight
post-chemotherapy, Stricker said. This perception could reduce
adherence to prolonged tamoxifen treatment, and poor adherence has been linked
to increased breast cancer death. Patients also report weight gain on aromatase
Weight gain and an increased risk for metabolic syndrome are
increasingly being recognized as effects of testicular cancer treatment,
contributing to the increased risk of cardiovascular death in this population,
The complications associated with surgery in obese patients cause a
similar level of concern as drug interactions, according to Jeffrey A.
Meyerhardt, MD, MPH, associate professor in the department of medicine at
Harvard Medical School and a gastrointestinal oncologist at Dana-Farber Cancer
Meyerhardt and colleagues conducted a study of nearly 1,700 rectal
cancer patients participating in an adjuvant therapy clinical trial. Patients
who were obese had a significantly higher likelihood of having a permanent
colostomy in analyses adjusted for tumor stage and location of rectal cancer.
Obese men also had a higher likelihood of a local recurrence compared with
Meyerhardt concluded it is more difficult to perform rectal surgery on
an obese patient. That may limit the effectiveness of the surgery or lead to
adverse outcomes, including a higher risk for colostomy and local recurrence.
In Shepards opinion, the problem is more fundamental.
Obese patients are just not fit enough to have surgery, he
said. They have poor lung function, which makes it difficult to go under
Bordeaux and colleagues cited other similar complications, noting obese
patients are more prone to blood loss requiring transfusions and are more
likely to have pulmonary complications.
They also run a higher risk of pneumonia, Brufsky said.
Surgeons are getting better at performing on obese patients, but
there is still the healing issue, Brufsky said. These patients can
go through the surgery OK, but there is difficulty tolerating postoperative
Much of Strickers research has focused on breast cancer treatment
We are looking at the next step: As they come out of treatment,
what future risks do they face? she said. Obesity and weight gain
may increase the risk of recurrence and has also been linked to greater risk
for certain late effects such as lymphedema, not to mention increasing risk of
cardiovascular disease and other comorbidities. Obese patients thus face unique
Although breast cancer treatment has been linked to weight gain, most
clinicians are faced with the opposite problem.
We fall victim to seeing patients who are sick, not eating well
and losing weight, so we sometimes encourage them to eat high-fat foods simply
because we want them eating something, Shepard said. The problem is
that, at a certain point when their condition has stabilized, you have to stem
Many obese patients had poor diet and exercise habits long before they
were diagnosed with cancer, Shepard said.
Clinicians often must battle a lifetime of unhealthy behaviors when they
advocate for post-treatment wellness, a challenge made much more formidable
given that the majority of research suggests poorer outcomes
particularly recurrence and death among patients with higher BMI.
Yoon and colleagues found that excess BMI among never smokers was linked
to poorer disease-specific survival, DFS and OS in 778 patients who underwent
potentially curative esophagectomy.
In the Cancer Prevention Study II, Calle and colleagues found that men
in the heaviest cohort had a 52% higher rate of cancer death than normal-weight
men after adjusting for several variables. After adjusting for the same
variables, the heaviest women were 62% more likely to die of cancer than
normal-weight women. About 14% of cancer deaths in men and 20% of cancer deaths
in women are linked to overweight or obesity, indicating that about 90,000
preventable cancer deaths occur per year, according to the results.
Fagan emphasized that clinicians should take these types of data as a
If current trends in obesity continue, it becomes increasingly
important to understand if, how and when this condition confers a disparity in
health outcomes, she said.
Some of the data are conflicting, but the trend is clear, he
said. With the growing rate of obesity in the US and other countries, the
percentage of our cancer patients who will be obese will continue to grow.
There needs to be much more research to understand how to manage these
Further, strategies to break the increasing trend toward increased
adiposity in our population are critical, Meyerhardt added. This
will have a twofold effect it may decrease the incidence of certain
cancers that obesity is associated with and help with the management of
patients who do develop cancer. by Rob Volansky
Disclosure: Drs. Bordeaux, Brufsky, Fagan, Ghesani, Meyerhardt,
Shepard and Stricker report no relevant financial disclosures.
For more information:
- Bordeaux BC. Cleve Clin J Med. 2006;73:945-950.
- Calle EE. N Engl J Med. 2003; 348:1625-1638.
- DuBeshter B. Hospital Pharmacy. 2006;41:136-142.
- Fagan HB. J Obes. 2011;218250.
- Griggs JJ. Arch Intern Med. 2005;165:1267-1273.
- Meyerhardt JA. J Clin Oncol. 2004;22:648-657.
- Smith TJ. South Med J. 1991;84:883-885.
- Wang YC. Lancet. 2011;378:815-825.
- Yoon HH. J Clin Oncol. 2011; 34:4561-4567.
Jennifer J. Griggs
We have done a lot of research in this area and found that heavy women
with breast cancer frequently receive lower doses of chemotherapy than
There are systematic differences in the treatment of these populations.
In 1996, Rosner and colleagues demonstrated that obese patients whose doses
were reduced by a mere 5% had a higher rate of recurrence or death. Moreover,
they found that toxicity was not increased in fully dosed obese patients, but
that more than 50% of obese patients were given reduced doses.
For obese patients, there is much less wiggle room for dosing. Research
we published in 2005 demonstrated that practices varied greatly in the use of
dose reductions in overweight and obese patients.
Obese women were more likely (37%) to receive reduced chemotherapy doses
compared with healthy-weight women (9%). Furthermore, among those patients who
were obese and did receive full weight-based dosing, rates of hospitalization
for febrile neutropenia were actually lower than in lean and overweight women
who were fully dosed. Conversely, 63% of severely obese patients received full
weight-based dosing, indicating that many physicians are aware of what I
consider ideal dosing strategies.
Although we do not have data that dose escalation in obese patients will
achieve the same level of neutropenia as in lean women, the key point is that
we should avoid dose reduction (capping or limiting doses). Administration of
full chemotherapy doses may improve cancer outcomes at the population level,
given the increasing rates of obesity and the fact that obesity is associated
with a higher risk of many cancers.
The American Society of Clinical Oncology is currently developing
practice guidelines to address the uncertainties in chemotherapy dose
selection. The hope would be that standardizing chemotherapy dose selection
will improve care among this growing population.
Jennifer J. Griggs, MD, MPH, is associate professor in the
department of internal medicine, hematology and oncology division, associate
professor in the department of health management and policy, and director of
the breast cancer survivorship program at the University of Michigan School of
Public Health. References: Griggs JJ. J Clin Oncol.
2007;3:277-284. Rosner GL. J Clin Oncol. 1996;14:3000-3008.
Disclosure: Dr. Griggs reports no relevant financial disclosures.
Lisa K. Lohr
The majority of the data do not support capping, but individual
decisions need to be based on several factors, including curative vs.
palliative intent; the healthiness of the patient; the disposition
of the chemotherapy agent in the body; and the specific dose-limiting side
effects of the particular chemotherapy agent and whether the patient would be
particularly sensitive to that agent.
Regarding intent of therapy, the risk/benefit analysis for a patient
receiving potentially curative chemotherapy would lean toward giving the full
calculated dose to ensure the patients best chance at cure, and in this
case, the potentially higher risk of toxicities would be better tolerated.
However, if the patient is receiving palliative chemotherapy for metastatic
cancer, without any realistic chance for cure, you would not want to cause much
Although the weight of the patient is a factor, a bigger predictor of
whether a patient can tolerate chemotherapy is based on the underlying health
or performance status of the patient.
As for the disposition of the agent in the body, pharmacokinetic
prediction of the risk would depend on whether the chemotherapy agent would
have a larger or smaller volume of distribution depending on obesity, and
whether the clearance of the chemotherapy would be faster or slower depending
on organ function changes in obesity.
With regard to dose-limiting adverse events, myelosuppression may serve
as an example. If the dose-limiting side effect is myelosuppression and the
patient already has poor marrow reserve, perhaps the dose ought to be capped.
In summary, most obese patients would not be best served by
across-the-board policies regarding capping of chemotherapy doses. In general,
doses should not be peremptorily capped, but individual dosing decisions should
be made based on additional considerations as outlined above.
Lisa K. Lohr, PharmD, BCOP, BCPS, is an oncology pharmacy
specialist and oncology medication therapy management provider at the
University of Minnesota Masonic Cancer Center. Disclosure: Dr. Lohr
reports no relevant financial disclosures.