Cancer Survival: Time to Get Moving? Data Accumulate Suggesting a Link Between Physical Activity and Cancer Survival

1. Cancer Survival: Time to Get Moving? Data
Accumulate Suggesting a Link Between Physical
Activity and Cancer Survival
Wendy Demark-Wahnefried, School of Nursing and Department of Surgery, Duke University Medical Center, Durham, NC
Last year, an article by Holmes et al1
rocked the research
community involved in cancer survivorship. The article reported a
significant protective association between increased physical activ-
ity that occurred after the diagnosis of breast cancer and recur-
rence, cancer-related mortality, and overall mortality among a
cohort of 2,987 stage I to III breast cancer survivors nested within
the Nurse’s Health Study. This year, Meyerhardt et al2,3
add to this
growing body of research with findings from two separate studies
that appear in this issue of the Journal of Clinical Oncology. Both of
these prospective studies focused on colorectal cancer and each
found a protective association with postdiagnosis physical activity.
One of these studies closely paralleled the previous work of
Holmes et al1
as it explored the association between physical activ-
ity undertaken after diagnosis and its relationship to mortality
(overall and cancer specific) using the same cohort, the same
survey instrument to assess physical activity, the same exclusionary
criteria, and a similar analysis plan.2
Given the lower incidence of
colorectal cancer, as compared with breast cancer, far fewer cases of
colorectal cancer (573 v 2,987) were identified within the Nurse’s
Health Study cohort. Even with fewer cases, the study by Meyer-
hardt et al2
found significant protective associations with increas-
ing levels of physical activity. Both studies found reductions in
overall risk of mortality with 9ϩ metabolic equivalent task (MET)
-hours per week of physical activity; however, although significant
benefits were observed for breast cancer–specific mortality at the
9ϩ MET-hours per week cut point, for colorectal cancer–specific
mortality, the cut point was 18ϩ MET-hours per week. In trans-
lating this information into useful clinical guidelines, 9 MET-
hours per week is roughly equivalent to four to five weekly 30-
minute sessions of brisk walking, whereas 18 MET-hours per week
assumes exercise sessions that are double in duration or frequency,
or more strenuous in nature (see Table 2 in Meyerhardt et al3
). In
this report, Meyerhardt et al2
present additional analyses and evi-
dence that distinguishes that these protective associations are in-
dependent of premorbid levels of physical activity. Indeed, the
research team is to be applauded for their careful work, which
clearly suggests that it is physical activity that occurs postdiagnosis
that is associated with an improved prognosis, rather than exercise
habits established before disease. Such data have obvious import
for clinical practice, as do the confirmatory findings of the second
study by Meyerhardt et al3
appearing in this journal.
This study was performed on a cohort of 832 patients partic-
ipating in the Cancer and Leukemia Group B adjuvant therapy trial
sponsored by the National Cancer Institute comparing weekly
fluorouracil (FU) and leucovorin versus weekly irinotecan, FU,
and leucovorin (CALGB 89803) in stage III colon cancer.3
One of
this study’s primary strengths was its reliance on the clinical trial
framework. As such, the effects of confounding may have been
minimized, given that the sample was composed solely of individ-
uals who underwent a complete surgical resection and were found
to have regional lymph node metastases (no evidence of distant
metastases), and who had received one of two specified chemother-
apeutic regimens. In addition, physical activity assessments were
specifically timed in relation to treatment course (6 months post-
therapy) and standardized methods were used for follow-up of
cancer-related end points. Indeed, this study provides a successful
example of how clinical research can augment classic epidemio-
logic studies to answer research questions. One approach relies on
well-defined, circumscribed samples and assessing outcomes spe-
cifically in relation to disease or treatment course, and the other
approach relies on broad-based samples to obtain results that are
more readily generalizable.
Findings of this clinical study indicated significantly lower
rates of recurrence and increased disease-free survival with 18ϩ
MET-hours per week of physical activity, with data showing rela-
tive reductions in risk of recurrence that approached 50% in both
crude and adjusted analyses—associations that were durable even
after the exclusion of participants who may have had underlying
occult disease (such as those who had died or were found to have
recurrences within 6 months of physical activity assessment). As-
sociations with overall survival were not as strong and 95% CIs
were much broader; nevertheless, the association was still significant
in adjusted analyses. From the article, it is not known whether these
other causes of death were from diseases where proven associations
with physical activity exist, such as cardiovascular disease, or from
other causes of mortality not traditionally linked to exercise.
The results of this clinical study corroborate the epidemio-
logic findings of Holmes et al1
and Meyerhardt et al2
reviewed in
the preceding paragraphs and suggest reduced relative risks that
approximate 50% to 60% for both recurrence and overall mortality
among those who reported higher levels of physical activity, as
compared with those who were sedentary.3
Again, it should be
JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L
VOLUME 24 ⅐ NUMBER 22 ⅐ AUGUST 1 2006
3517Journal of Clinical Oncology, Vol 24, No 22 (August 1), 2006: pp 3517-3518
DOI: 10.1200/JCO.2006.06.6548; published online ahead of print at www.jco.org on July 5, 2006
Downloaded from jco.ascopubs.org on May 9, 2015. For personal use only. No other uses without permission.
Copyright © 2006 American Society of Clinical Oncology. All rights reserved.

2. noted that although all three studies employed a designated refer-
ent of less than 3 MET-hours per week to define those with seden-
tary lifestyles, significant benefits for breast cancer survivors were
observed at 9ϩ MET-hours per week, whereas for colorectal and
colon cancer patients, physical activity of at least 18 MET-hours
per week was needed before significant benefits were observed. It is
unknown whether this difference relates to issues inherent in study
sample, power, or design, or whether different physical activity
thresholds exist for different cancers. Indeed, this is an area that
requires additional research. It is of particular interest that in the
study of breast cancer by Holmes et al,1
the greatest benefits of
physical activity were observed among women with stage III breast
cancer (for 9ϩ MET-hours per week of physical activity, relative
risk ϭ 0.36; 95% CI, 0.19 to 0.71). Thus, in taking all three of
studies together,1-3
we see a protective association with increased
physical activity after diagnosis and firm, cancer-specific out-
comes—findings that suggest favorable effects across the spectrum
of cancer, from early-stage cancer to later stage disease.
As clinicians, researchers, and policy makers, we have long
awaited such confirmatory findings. To date, our exercise inter-
ventions, as well as the current guidelines for cancer survivors,4
and
what we ultimately tell our patients, is that exercise may be bene-
ficial, with guidance based largely on proven associations that exist
between physical activity and specific comorbid conditions (such
as heart disease or osteoporosis) to which cancer survivors are
especially prone, or associations between physical activity and
other factors, such as quality of life, functional decline, and fatigue.
Given the high-risk nature of cancer survivors and the fact that they
are high users of health care who have a profound impact on the
health economy at large, the benefits of exercise or a healthy diet on
outcomes other than those that are cancer specific are still impor-
tant and cannot be discounted.5,6
Nor can we discount the several
biologic mechanisms that are influenced by physical activity and
that may play a potent role in hindering neoplasia.7,8
However,
what we, as clinicians or interventionists, truly want to be able to
say—and what cancer patients truly want to hear—is the following:
“Through exercise you may be able to prevent progression or
recurrence of your cancer.” Unfortunately, the science is still not
quite there—yet.
While exceptionally valuable, it must be remembered that the
findings of Meyerhardt et al,2,3
as well as those of Holmes et al,1
are
observational in nature. Therefore, cause and effect cannot be
assumed. Furthermore, many questions still remain regarding the
effects of physical activity among cancer survivors. Is increased
physical activity safe, especially among groups of survivors in
which cardiotoxicity is frequently reported? What effort is required
for benefit? What types of exercise are most beneficial? Does exer-
cise exert its effects independently of or through weight control?
What are the characteristics of cancer patients most responsive to
exercise, based on cancer type, stage, receptor status, and so forth?
Indeed, the only way that we will be able truly to assess whether
increased physical activity can reduce recurrence or deaths due to
cancer is to pursue studies that lead up to and include randomized
controlled clinical trials that ultimately are able to answer whether
or not physical activity is beneficial for cancer control. Data from
these three observational studies suggest a reduced risk of recur-
rence of 50% to 60%.1-3
Such an effect parallels that of trastuzumab
forHER-2–positivebreastcancerpatients,9,10
anagentheraldedbythe
oncologiccarecommunityandbytheDirectoroftheNationalCancer
Institute, Andrew C. von Eschenbach, MD, as “a major advance and
turning point in eliminating suffering and death from cancer.”11
To be sure, behavioral interventions are complex and have a
host of barriers in that they are difficult to deliver and require
careful attention to issues of adherence; perhaps the largest barrier
of all is the lack of industry funding. There is no doubt that the
pharmaceutical industry would back an agent with potential to
reduce cancer recurrence by at least 50%, but who will back a trial
that evaluates the potential benefit of sneakers and sweatpants?
Would Nike “Just do it?” Perhaps, and indeed, it would be a
magnificent gesture of goodwill. But likely, this is a research ques-
tion that will require a large multisite trial and fall on the shoulders
of the government to support. Every 1.5 minutes, another person
in the United States is diagnosed with either breast or colon cancer;
indeed, it is these individuals, as well as the more than 4 million
survivors of these cancers,12
who would benefit from the answer.
It’s time to get moving!
© 2006 by American Society of Clinical Oncology
REFERENCES
1. Holmes MD, Chen WY, Feskanich D, et al: Physical activity and survival
after breast cancer diagnosis. JAMA 293:2479-2486, 2005
2. Meyerhardt JA, Giovannucci EL, Holmes MD, et al: Physical activity and sur-
vival after colorectal cancer diagnosis. J Clin Oncol 24:3527-3534, 2006
3. Meyerhardt JA, Heseltine D, Niedzwiecki D, et al: The impact of physical
activity on cancer recurrence and survival in patients with stage III colon cancer:
Findings from CALGB 89803. J Clin Oncol 24:3535-3541, 2006
4. Brown JK, Byers T, Doyle C, et al: Nutrition and physical activity during and
after cancer treatment: An American Cancer Society guide for informed choices.
CA Cancer J Clin 53:268-291, 2003
5. Yabroff KR, Lawrence WF, Clauser S, et al: Burden of illness in cancer
survivors: Findings from a population-based national sample. J Natl Cancer Inst
96:1322-1330, 2004
6. Demark-Wahnefried W, Aziz N, Rowland J, et al: Riding the crest of the
teachable moment: Promoting long-term health after the diagnosis of cancer.
J Clin Oncol 23:5814-5830, 2005
7. McTiernan A: Physical activity after cancer: Physiologic outcomes. Cancer
Invest 22:68-81, 2004
8. Schmitz KH, Holtzman J, Courneya KS, et al: Controlled physical activity
trials in cancer survivors: Systematic review and meta-analysis. Cancer Epidemiol
Biomarkers Prev 14:1588-1595, 2005
9. Piccart-Gebhart MJ, Procter M, Leyland-Jones B, et al: Trastuzumab after
adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 353:1659-
1672, 2005
10. Romond EH, Perez EA, Bryant J, et al: Trastuzumab plus adjuvant
chemotherapy for operable HER2-positive breast cancer. N Engl J Med 353:
1673-1684, 2005
11. National Cancer Institute: Herceptin combined with chemotherapy im-
proves disease-free survival for patients with early-stage breast cancer. http://
www.cancer.gov/newscenter/pressreleases/HerceptinCombination2005
12. American Cancer Society: Cancer Facts and Figures–2006 http://www
.cancer.org/downloads/STT/CAFF2006PWSecured.pdf
■ ■ ■
Acknowledgment
Supported by National Institutes of Health Grants No. CA81191,
CA85740, CA106919, and AR52186, and the American Institute for
Cancer Research.
Author’s Disclosures of Potential Conflicts of Interest
The author indicated no potential conflicts of interest.
Wendy Demark-Wahnefried
3518 JOURNAL OF CLINICAL ONCOLOGY
Downloaded from jco.ascopubs.org on May 9, 2015. For personal use only. No other uses without permission.
Copyright © 2006 American Society of Clinical Oncology. All rights reserved.