After the ASCO Integrated Media and Technology Committee meeting I was delayed at Reagan National Airport with poor Wi-Fi access. I resorted to reading a physical (yes, paper!) journal (Oncology. Oct 2011, Volume 25, Number 11). I was struck by two seemingly unrelated manuscripts (and commentary).

Goals and Costs of Cancer Therapy
The first article was by fellow ASCO member and blogger L. Michael Glodé, MD: “Oncology Perspectives: Is Cancer the Answer?” Some of his main points were that humans are not immortal, cancer care is expensive, early palliative care appears to have a survival benefit (at least in some cancers), and we should consider all treatment options including non-pharmacological interventions.

Obesity, Diet, Exercise, and Breast Cancer
The other article was “Obesity and Breast Cancer” by Jennifer Ligibel, MD. Commentary articles followed that manuscript. I was aware of data suggesting that obesity and related medications or biomarkers such as metformin, insulin level, metabolic syndrome, diabetes, etc., were related to breast cancer risk or recurrence. However, I admit I was unaware of the depth and number of studies evaluating this. I was also unaware of some holes in our information, i.e. “…no studies examining the impact of purposeful weight loss on breast cancer prognosis.” Please read the full manuscript and accompanying commentaries. I was struck by the consistency of hazard ratio (HR) risk reduction from various interventions including diet and exercise (often intensive and individualized, not just an offhanded statement to eat more veggies; see article's Table 1) as well as the risks with high insulin, metabolic syndrome or other biomarkers (see article's Table 3).

Sparano and Strickler in “Breast Cancer Patients Who Are Obese at Diagnosis: Alea Iacta Est? or "Is the Die Cast?" pointed out the concept of the “healthy obese” patient exists that may not have the same risk of recurrence (a hypothesis) as other “morbid obese” (where morbid is unhealthy, not BMI) and that we may need to risk stratify obese patients based on biomarkers.

The juxtaposition of the Glodé and “Obesity and Breast Cancer” articles resonated with me. Given the data (and not just a vague warm and fuzzy sentiment for a healthier lifestyle), why isn’t there an algorithm in the NCCN (or other) guidelines for dietary interventions as adjuvant therapy? To be fair, NCCN does mention diet and exercise (p. 26/148 - BINV-16 and p. 99/148 – MS-35 in version 2.2011): “Evidence suggests that active lifestyle, achieving and maintaining an ideal body weight (20-25 BMI) may lead to optimal breast cancer outcomes.” So, maybe this should be mentioned more prominently in the upfront algorithm, rather than after other adjuvant therapies?

Clinical trials (as mentioned in the Ligibel article) are evaluating various interventions. One currently accruing study is the MA.32 trial "Phase III Trial of Metformin versus Placebo in Early-Stage Breast Cancer" by the National Cancer Institute of Canada (NCIC) Clinical Trials Group and the U.S. NCI.

QUESTIONS

• I suspect that some of these interventions may have a higher magnitude of benefit than chemotherapy. Can the effects of diet and exercise as adjuvant therapy be incorporated into Adjuvant! Online to help better personalize treatment planning?
• Would an adequately informed patient choose chemo over a POTENTIALLY (based on individual patient/tumor characteristics) larger risk reduction with diet/exercise?
• In an Accountable Care Organization (ACO) world with limited resources isn’t this highly important for a potential way to contain costs?
• Should we be hiring more registered dieticians, physical therapists, personal trainers, and paying for gym memberships rather than chemo?
• Can we save money, improve health, and spare toxicities (in selected patients)?

I am still trying to decide how to implement these interventions, but I will certainly refer more quickly to diet and exercise programs in the future.

What do you think?


ADDENDUM:
Other Links:

NCI Cancer Bulletin (11/15/11) - "The Emerging Evidence about the Role of Obesity in Cancer" - http://ht.ly/7vlLL

Nature Medicine (10/30/11 online) - "Adipocytes promote ovarian cancer metastasis and provide energy for rapid tumor growth" - http://www.nature.com/nm/journal/v17/n11/full/nm.2492.html

amednews (11/16/11) - AMA helping physicians broach the subject of obesity - http://www.ama-assn.org/amednews/2011/11/14/prsf1116.htm

Metformin and thiazolidinediones are associated with improved breast cancer-specific survival of diabetic women with HER2+ breast cancerHe et al. Ann Oncol (2011) - http://annonc.oxfordjournals.org/content/early/2011/11/09/annonc.mdr534.short?rss=1 
Conclusions: Thiazolidinediones and metformin users are associated with better clinical outcomes than nonusers in diabetics with stage ≥2 HER2+ breast cancer. The choice of antidiabetic pharmacotherapy may influence prognosis of this group.

12/2011
Obesity linked to worse survival in #BreastCancer adjuvant therapy - Dr. Sao Jiralerspong @bcmhouston http://ow.ly/aDzaa & @ASCO YIA 2007 http://ow.ly/aDzov

Fasting Might Boost Chemo's Cancer-Busting Properties: Scientific American -- http://bit.ly/zPzm9W

From NPR 4/26/12 -- 
http://www.npr.org/blogs/health/2012/04/25/151387672/evidence-mounts-that-diet-exercise-help-survivors-cut-cancer-risk?ft=1&f=1128&sc=tw


Effects of a Caloric Restriction Weight Loss Diet and Exercise on
Inflammatory Biomarkers in Overweight/Obese Postmenopausal Women: A
Randomized Controlled Trial
Ikuyo Imayama, Cornelia M. Ulrich, Catherine M. Alfano, Chiachi Wang, Liren
Xiao, Mark H. Wener, Kristin L. Campbell, Catherine Duggan, Karen E.
Foster-Schubert, Angela Kong, Caitlin E. Mason, Ching-Yun Wang, George L.
Blackburn, Carolyn E. Bain, Henry J. Thompson, and Anne McTiernan
Cancer Res 2012;72 2314-2326
http://cancerres.aacrjournals.org/cgi/content/abstract/72/9/2314?etoc
Findings suggest that weight loss with or without exercise may reduce risk
of breast cancer, possibly due to a reduction in systemic inflammation that
may support tumor development or progression.