As I was compiling information for my upcoming January 2015 Top Holistic Health Reads, I came across some compelling reviews and studies on the subject of cancer. Cancer is probably one of the hottest, polarized, and most controversial topics among conventional and integrative physicians. This especially holds true regarding efficacy in screening, treatments, and various integrative approaches. For this reason, I was hesitant to highlight the topic; however, the more I dug into the research, the more hope I felt. Rather than creating more of a divergence between different types of practitioners and philosophies, these new sources of information each could have a unique potential to unite them .
Specifically, several articles discussed:
- Reports on the efficacy of screening for prevention
- New theories regarding the reasons for re-occurrence of tumors and the metabolic physiology of cancer
What do these topics have in common…they each present evidence that perhaps the issue isn’t so much in the therapy or training of the practitioner, but in individualizing treatment strategies for the patient.
The issues are quite complex, not to mention insanely political. However, the whole purpose of my blog is about education and allowing you, my readers, to review my findings, provide sources of references, and encouraging you to make your own educated decisions.
So, let’s dive in. First, I have to remind you of my disclaimer. This is definitely not standard of care or meant to diagnose, treat, or prescribe. It is meant to make you feel informed and curious about what’s best for you and your body.
Does Screening Save Lives In Asymptomatic People?
Choosing Wisely
The topic of unnecessary screening has been one of the major subjects in medicine recently. According to the American Board of Internal Medicine (ABIM), “In 2009, Putting the Charter into Practice grants were awarded to several organizations that developed initiatives to advance the professional values and behaviors articulated in the Physician Charter among practicing physicians.”
Among the recipients was the National Physicians Alliance (NPA). The NPA assembled working groups and used field testing which included over 200 practicing physicians to validate their list of the “Top Five” tests and procedures which are commonly used but may be unnecessary and/or cause harm.
The ABIM further stated that, “This project also provided a successful model for the ABIM Foundation’s Choosing Wisely® campaign in which medical specialty societies, along with Consumer Reports, identified tests or procedures commonly used in their field, whose necessity should be questioned and discussed.” (1)
Although not everyone agreed with the NPA’s suggestions, the need to limit unnecessary screening and individualize suggestions had made a major impact in mainstream medicine. In fact one the two the most controversial updated recommendations was issued the same year by United States Preventive Services Task Force (USPSTF). At that time, the USPSTF released an update of their 2002 mammography recommendations advising against routine mammographic screening for women aged 40–49 years, as the data failed to show that benefit outweighed harm. (2)
Support for this conclusion was found in a 2013 Cochrane Analysis of seven eligible trials that included 600,000 women aged 39 to 74 years. The results from studies that had the most reliable information did not show a reduction in breast cancer mortality after 13 years of follow-up. The authors stated the following (bold emphasis mine):
If we assume that screening reduces breast cancer mortality by 15% and that overdiagnosis and overtreatment is at 30%, it means that for every 2000 women invited for screening throughout 10 years, one will avoid dying of breast cancer and 10 healthy women, who would not have been diagnosed if there had not been screening, will be treated unnecessarily. Furthermore, more than 200 women will experience important psychological distress including anxiety and uncertainty for years because of false positive findings. To help ensure that the women are fully informed before they decide whether or not to attend screening, we have written an evidence-based leaflet for lay people that is available in several languages on www.cochrane.dk. Because of substantial advances in treatment and greater breast cancer awareness since the trials were carried out, it is likely that the absolute effect of screening today is smaller than in the trials. Recent observational studies show more overdiagnosis than in the trials and very little or no reduction in the incidence of advanced cancers with screening. (3
Self and Clinical Exam for Breast Tumors ARE Effective At Detection, Swiss Study Says
Interestingly, a new Swiss study of 948 women treated in Switzerland between 1990 and 2009 did report evidence that both women’s self-exams and physical exams did detect breast tumors about the same size. As reported in Medscape:
Women’s self-exams and physical exams by a doctor both detect breast cancer tumors at about the same size, but older women are more likely to have a tumor discovered via doctor’s examination, according to a new Swiss study.
…In 236 women, tumors were detected during clinical exam, while 712 women had discovered their own tumors. Women who found their own tumors had an average age of 60, compared to an average age of nearly 66 for women whose tumors were found through clinical breast exam. Both methods found the same number of tumors in the same locations and of similar size, averaging 22 mm (about 9/10ths of an inch), the authors write. (4)
Prostate Screening Controversy
The second major controversy was with the USPSTF’s 2012 update from 2008 which advised against prostate cancer screening for all ages. (5) In fact, a 2013 Cochrane Review of 5 studies, which included 341,342 participants, reported that:
Among men aged 55 to 69 years in the ERSPC study, the study authors reported that 1055 men would need to be screened to prevent one additional death from prostate cancer during a median follow-up duration of 11 years. Harms included overdiagnosis and harms associated with overtreatment, including false-positive results for the PSA test, infection, bleeding, and pain associated with subsequent biopsy. (6)
More Evidence Screening Broadly May Not Be “Choosing Wisely” In All Circumstances
More recently, on January 14, Science Daily reported on a paper published online in the International Journal of Epidemiology. (7-8) The study evaluated 39 screening tests for 19 diseases where mortality is a common outcome. The results were based on findings from 48 randomized controlled trials and 9 meta-analyses addressing disease-specific or all-cause mortality. According to the authors of the publication:
Among the results of the meta-analyses, reductions where the 95% confidence intervals (CIs) excluded the null occurred for four disease-specific mortality estimates (ultrasound for abdominal aortic aneurysm in men; mammography for breast cancer; fecal occult blood test and flexible sigmoidoscopy for colorectal cancer) and for none of the all-cause mortality estimates. Among individual RCTs, reductions in disease-specific and all-cause mortality where the 95% CIs excluded the null occurred in 30% and 11% of the estimates, respectively.
Conclusions: Among currently available screening tests for diseases where death is a common outcome, reductions in disease-specific mortality are uncommon and reductions in all-cause mortality are very rare or non-existent. (9)
Confused About Screening?
You should be, because generalizations may not be the answer. I believe that what the studies are indicating is that it is becoming more evident that just screening for a disease without altering lifestyle may not be the most effective means of prevention. It may be that a more comprehensive approach is needed and selective testing should be based on an individual’s unique lifestyle factors, history, genetic risks, and one’s biochemistry. For example, for a woman with a history of breast cancer who is over 50, and who has a family history of cancer, and a genetic predisposition, screening might be more warranted than for an asymptomatic, low risk, 39-year-old female. Furthermore, could perhaps some integrative considerations be applied in reducing the risk of radiation or other screening methods as well?
(You can read more on expectation biases in interventions and screening here.)
Cancer Cell Stem Theory and Plants
Previously, I discussed that we can modulate our risk for cancer through various epigenetic mechanisms. An interesting theory I came across was the role of cancer stem cells in tumor relapse. (10) Specifically of interest were several studies that reported that these stem cells could be an explanation for chemo-radiotherapy tumor relapse. As noted in the studies on mammography, radiation might be a contributing factor to increased harm from screening.
A 2012 in vitro study in Stem Cell reported that ionizing radiation induced differentiated breast cancer cells into breast cancer stem cells. (11) Interestingly, two recent studies demonstrated that natural modalities may mitigate these “tumor relapse” cells.
Vitamin D and Stem Cells
A 2014 study with breast cancer stem cells demonstrated the impact of treatment with vitamin D on the growth of these stem cells in vitro. (12, 13)
Epigenetics & Stem Cells
A article in Food and Chemical Toxicology summarized the role of epigenetic influences on cancer risk prevention in the past few decades. It discussed how nutritional habits, lifestyle, and reducing toxic exposure can be of benefit. However, what may be missing is the role that phytocompounds could address in modulating and targeting the resistant cancer cells: (14-15)
In the last decades cancer has been considered as an epigenetic dysfunction, given the profound role of diet and lifestyle in cancer prevention and the determination of cancer risk. A plethora of recent publications have addressed the specific role of several environmental factors, such as nutritional habits, behavior, stress and toxins in the regulation of the physiological and cancer epigenome. In particular, plant-derived bioactive nutrients have been seen to positively affect normal cell growth, proliferation and differentiation and also to revert cancer related epigenetic dysfunctions, reducing tumorigenesis, preventing metastasis and/or increasing chemo and radiotherapy efficacy. Moreover, virtually all cancer types are characterized by the presence of cancer stem cell (CSC) subpopulations, residing in specific hypoxic and acidic microenvironments, or niches, and these cells are currently considered responsible for tumor resistance to therapy and tumor relapse. Modern anti-cancer strategies should be designed to selectively target CSCs and modulate the hypoxic and acidic tumor microenvironment, and, to this end, natural bioactive components seem to play a role. This review aims to discuss the effects elicited by plant-derived bioactive nutrients in the regulation of CSC self-renewal, cancer metabolism and tumor microenvironment. (15)
In fact, a study in Nutrition suggested that although chemotherapy may reduce tumor size; it may increase tumor resistance (16-18). The authors conclude that diet and bioactive compounds could provide a role in addressing these resistant cancer stem cells (bold emphasis mine):
Colon cancer strikes more than 1 million people annually and is responsible for more than 500,000 cancer deaths worldwide. Recent evidence suggests that the majority of malignancies, including colon cancer are driven by cancer stem cells (CSCs) that are resistant to current chemotherapeutic approaches leading to cancer relapse. Wnt signaling plays a critical role in colon stem cell renewal and carcinogenesis. Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), a Wnt target gene, and aldehyde dehydrogenase 1 B1 (ALDH1B1) are good markers for normal and malignant human colon stem cells. Diet contributes to 20% to 42% of all human cancers and 50% to 90% of colon cancer. Recent evidence shows that the Western diet has a causative link to colon cancer; however, mechanisms of action are not fully elucidated. Western diet-induced obesity elevates systemic insulin-like growth factor-1 and insulin levels, which could lead to elevated proliferation and suppressed apoptosis of CSCs through PI3K/AKT/Wnt pathway. Although conventional chemotherapy targets the PI3K/AKT pathways and can significantly reduce tumor size, it fails to eliminate CSCs and has serious side effects. Dietary bioactive compounds such as grape seed extract, curcumin, lycopene, and resveratrol have promising chemopreventive effects, without serious side effects on various types of cancers due to their direct and indirect actions on CSC self-renewal pathways such as the Wnt pathway. Understanding the role of CSCs in diet-induced colon cancer will aid in development of evidence-based dietary chemopreventive strategies and/or therapeutic agents targeting CSCs.(18)
Metabolic Unification- Connecting All of the Above
Another fascinating topic is the emerging role of cancer as a “metabolic disease.” This theory states that the genomic instability of tumor cells are downstream effects in cellular energy resulting from a dysfunctional metabolism based in the mitochondria. What this translates to is that the true target in preventing and modulating risk is in manipulating an individual’s unique metabolism to decrease the fuel source for the tumor cells. This theory could integrate the role of conventional treatment (killing tumor cells), epigentics (lifestyle factors and diet, targeted treatment), screening, and using natural compounds prior to or after treatments for addressing stem cells.
A 2013 article in Carcinogenesis states (bold emphasis mine):
Emerging evidence indicates that cancer is primarily a metabolic disease involving disturbances in energy production through respiration and fermentation. The genomic instability observed in tumor cells and all other recognized hallmarks of cancer are considered downstream epiphenomena of the initial disturbance of cellular energy metabolism. The disturbances in tumor cell energy metabolism can be linked to abnormalities in the structure and function of the mitochondria. When viewed as a mitochondrial metabolic disease, the evolutionary theory of Lamarck can better explain cancer progression than can the evolutionary theory of Darwin. Cancer growth and progression can be managed following a whole-body transition from fermentable metabolites, primarily glucose and glutamine, to respiratory metabolites, primarily ketone bodies. As each individual is a unique metabolic entity, personalization of metabolic therapy as a broad-based cancer treatment strategy will require fine-tuning to match the therapy to an individual’s unique physiology.
References
(1) ABIM. 2009 Grantees. http://www.abimfoundation.org/Initiatives/Putting-the-Charter-Into-Practice-Grants/2009-Grantees.aspx
(2) Force USPST. Screening for breast cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2009;151(10):716-726.http://annals.org/article.aspx?articleid=745237
(3) Gotzsche PC, Jorgensen KJ. Screening for breast cancer with mammography. Cochrane. Database Syst Rev. 2013;6: CD001877. http://onlinelibrary.wiley.com/enhanced/doi/10.1002/14651858.CD001877.pub5#js-feedback
(4) Doyle, K. Self-Exam and Clinical Exam Find Similar Breast Tumors. Reuters Health Information. Medscape. December 29, 2014. http://www.medscape.com/viewarticle/837246?src=wnl_edit_medn_wir&uac=146852BY&spon=34
(5) Force USPST. Final Recommendation Statement. Prostate Cancer Screening. March 2012. Available at: http://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/prostate-cancer-screening
(6) Ilic D, Neuberger MM, Djulbegovic M, Dahm P. Screening for prostate cancer. Cochrane Database of Systematic Reviews. 2013. DOI: 10.1002/14651858.CD004720.pub3.
(7) Oxford University Press (OUP). Does screening asymptomatic adults for major disease save lives? It seems not. Science Daily. January 14, 2015. www.sciencedaily.com/releases/2015/01/150114205631.htm.
(8) Ji, S. Cancer $creening Doesn’t Save Lives, Meta-Study Reveals. Green Med Info. January 15, 2015.
(9) Nazmus Saquib, Juliann Saquib, and John Ioannidis. Does screening for disease save lives in asymptomatic adults? Systematic review of meta-analyses and randomized trials. International Journal of Epidemiology, 2015 DOI: 10.1093/ije/dyu140
(10) Review Paper: Cancer Stem Cells and Cancer Nonstem Cells: From Adult Stem Cells or from Reprogramming of Differentiated Somatic Cell. Veterinary Pathology March 2009; 46(2): 176-193. doi: 10.1354/vp.46-2-176
(11) Lagadec, C., Vlashi, E., Della Donna, L., Dekmezian, C. and Pajonk, F. Radiation-Induced Reprogramming of Breast Cancer Cells. Stem Cells. 2012; 30: 833–844. doi: 10.1002/stem.1058
(12) Vitamin D compounds reduce mammosphere formation and decrease expression of putative stem cell markers in breast cancer. J Steroid Biochem Mol Biol. 2014 Oct 31. pii: S0960-0760(14)00251-9. doi: 10.1016/j.jsbmb.2014.10.016. [Epub ahead of print]
(13) Ji, S. Sunlight Holds a Key To Killing Breast Cancer. Green Med Info. January 1, 2015. http://www.greenmedinfo.com/blog/sunlight-holds-key-killing-breast-cancer-2?page=2
(14) The use of plant-derived bioactive compounds to target cancer stem cells and modulate tumor microenvironment. Food and Chemical Toxicology. January 2015.75: 58-70. doi:10.1016/j.fct.2014.11.004
(15) Research: Plants Cure Cancer, Not Chemicals, Green Med Info. December 21, 2014. http://www.greenmedinfo.com/blog/research-plants-cure-cancer-not-chemicals?page=2
(16) Colon cancer cells escape 5FU chemotherapy-induced cell death by entering stemness and quiescence associated with the c-Yes/YAP axis. Clin Cancer Res. 2014 Feb 15;20(4):837-46. doi: 10.1158/1078-0432.CCR-13-1854. Epub 2013 Dec 9. PubMed PMID: 24323901.
(17) Colon carcinogenesis: influence of Western diet-induced obesity and targeting stem cells using dietary bioactive compounds. Nutrition. 2014 Nov-Dec;30(11-12):1242-56. doi: 10.1016/j.nut.2014.02.016. Epub 2014 Mar 12.
(18) Ji, S. Food Not Chemicals Holds “Cure” for Colon Cancer. Green Med Info. January 7, 2014. http://www.greenmedinfo.com/blog/food-not-chemo-holds-cure-colon-cancer?page=2
(19) Cancer as a metabolic disease: implications for novel therapeutics. Carcinogenesis. 2014; 35(3):515–527.doi:10.1093/carcin/bgt480
images courtesy istockphotos.com and Anna (5 years old)
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