The Ecology of Breast Cancer: Opportunities for Prevention by Ted Schettler MD, MPH
This article by Dr. Schettler was just published in the June/July 2016 San Francisco Medical Journal. The entire issue, which includes some interesting contributions on integrative cancer care is available here
The Ecology of Breast Cancer: Opportunities for Prevention
by Ted Schettler MD, MPH
Breast cancer is the most common cancer in women in the US. While a number of risk factors contribute to its incidence, one or two do not stand out nearly as strongly as the impact of tobacco smoking on lung cancer risk. Rather, dynamic interactions among multi-level variables, beginning early in life, create conditions out of which breast cancer emerges. This means that breast cancer is a systems problem requiring systems-level responses for prevention.
Migration studies show that breast cancer risk remains relatively low in adult women who move from low- to high-risk countries but increases when they live their entire lives in a high-risk country. This illustrates the importance of early life events, but what makes a country high-risk for breast cancer?
A systems, or ecologic, framework recognizes that people are progressively nested in families, communities, ecosystems, and societies. Qualities of each of those levels interact and differ from person to person and place to place, impacting personal biology and population-wide disease risk. Although difficult to study, this framework best depicts the contextual origins of many common diseases and aligns well with integrated approaches to care.
A life-course approach to prevention is essential since the timing of environmental exposures can impact hormone levels, gene expression, the age of puberty, breast tissue dynamics and architecture—influencing cancer risk decades later. Colditz et al. recommend beginning breast cancer prevention at age two. But data from laboratory animal and epidemiologic studies show that opportunities for breast cancer prevention actually begin in the womb.
Opportunities for breast cancer prevention:
Generally-accepted breast cancer risk factors include age, family history, genetic susceptibility, personal history of breast cancer, dense breast tissue, benign breast disease, early age of menarche, late age of first pregnancy or nulliparity, late age of menopause, chest radiation, recent oral contraceptive use, combination hormone replacement therapy, cigarette smoking, alcohol consumption, and overweight (post-menopausal breast cancer). Some of these are modifiable and can inform clinical practice. But additional risk factors are clearly involved and offer additional opportunities to prevent this disease.
Diet and Nutrition:
Adult diets with abundant fruits and vegetables, particularly those brightly colored with carotenoids, whole grains, fiber, more plant-based proteins, healthy fats (e.g. olive oil, more omega 3s) are associated with decreased breast cancer risk and improved outcomes after diagnosis and treatment.
An even more compelling story that has emerged over the past few years highlights the importance of diets in childhood and adolescence. High intake of animal protein in childhood can result in earlier menarche and in adolescence is associated with increased risk of both pre- and post-menopausal breast cancer.  Emphasis on plant-based proteins and fats, nuts, fruits, and vegetables in childhood and adolescence is associated with even lower risk than in adults.
Childhood diets with higher amounts of whole or lightly processed soy are also more protective than high-soy diets in adults. This does not apply to highly processed soy or soy supplements, which have different biologic impacts. High milk intake in childhood is associated with increased risk of benign breast disease and faster peak height growth, both of which increase breast cancer risk.   Breast feeding not only benefits infant health but also modestly reduces maternal breast cancer risk.
Physical activity, exercise, and weight control:
Many studies show that regular exercise not only reduces breast cancer risk but also other cancers, diabetes, and heart disease. Three-four hours per week of moderately strenuous exercise (e.g. brisk walking) reduces breast cancer risk by about 20-25 percent. Exercise levels during adolescence are most strongly associated with premenopausal breast cancer risk.
Overweight and obesity are strongly associated with increased post-menopausal breast cancer risk. Exercise can be an important part of a weight control program and add to the benefits of maintaining a healthy weight.
Calcitriol, the biologically active form of vitamin D, influences gene expression in most tissues, including the breast. It regulates signaling pathways involved in cell proliferation, apoptosis, differentiation, and inflammation and down-regulates aromatase. Many in vitro and laboratory animal studies support a role for vitamin D in inhibiting or delaying cancer development and progression. Most, but not all, observational studies show lower levels of vitamin D associated with increased breast cancer risk.
Unfortunately, vitamin D insufficiency is quite common in the general population and additional supplementation could have significant public health benefits. The Institute of Medicine acknowledges a safe upper limit of 1000-1500 IU vitamin D daily in infants, 2500-3000 IU in children, and 4000 IU in adolescents and adults. The American Academy of Pediatrics recommends that all breast fed infants and formula-fed infants without adequate amounts of vitamin D in their formulas should receive vitamin D supplements. The American Congress of Obstetricians and Gynecologists (ACOG) recommends testing pregnant women at risk of low vitamin D and supplementing when necessary.
Carcinogens and endocrine disruptors:
Historically, studies of environmental chemicals and breast cancer risk focused primarily on exposures in adults. The earliest reported increased risk of breast cancer mortality in hairdressers, workers in a PVC production facility, and women exposed to a rust-inhibiting chemical in a manufacturing facility. A recent review finds that nurses, firefighters and women working with chemicals in plastics, rubber, solvents, pesticides and textiles are at increased risk. The Institute of Medicine found strongly suggestive evidence that exposures to organic solvents including benzene, ethylene oxide, 1,3 butadiene, and polycyclic aromatic hydrocarbons increase risk. Over 200 chemicals can cause mammary gland cancer in laboratory animals, but most have not been investigated in epidemiologic studies.
Recently, the importance of exposure to chemicals, including endocrine disruptors, during early development has gained wider attention. For example, exposure to diethylstilbestrol (DES) or higher levels of the pesticide DDT in utero or childhood is associated with increased breast cancer risk decades later.   Studies in laboratory animals show that in utero exposures to DES and bisphenol A, among others, alter breast tissue architecture and gene expression, increasing susceptibility to breast cancer in adulthood. It will always be difficult to tease out the relationship between developmental exposures and breast cancer risk decades later. Based on what we know now, however, avoiding exposures to endocrine disrupting chemicals to the extent possible makes sense. The ACOG finds reducing those exposures to be a critical area of intervention for health care providers.
Shift work, light at night, and exposure to ionizing radiation are also associated with increased breast cancer risk. Studies of non-ionizing radiation from cell phones and other wireless technologies suggest a possible increased cancer risk, although the field is fraught with controversy. Case reports of breast cancer in young women who carried cell phones in their bras are alarming and indicate that this should be avoided.
Opportunities for breast cancer prevention begin in the womb and continue throughout life. Although we have inadvertently designed higher risk into the community fabric, individuals, health care providers, public health officials, community planners, businesses, governments, teachers, farmers, and others can play key re-design roles. Strategic interventions that shift complex system dynamics can help prevent this all-too-common disease not only in individuals but in entire populations.
 Schettler T. The Ecology of Breast Cancer: The Promise of Prevention and the Hope for Healing. October, 2013. Available at: http://tinyurl.com/j3y42yv Includes more detail and citations for conclusions in this brief summary.  Colditz G, Bohlke K, Berkey C. Breast cancer risk reduction starts early: prevention must also. Breast Cancer Res Treat. 2014; 145(3):567-579.  Berkey CS, Gardner JD, Frazier AL, Colditz GA. Relation of childhood diet and body size to menarche and adolescent growth in girls. Am J Epidemiol. 2000;152:446-452.  Liu Y, Colditz G, Cotterchio M, et al. Adolescent dietary fiber, vegetable fat, vegetable protein, and nut intakes and breast cancer risk. Breast Cancer Res Treat. 2014;145:461-470.  Messina M, Hilakivi-Clarke L. Early intake appears to be the key to the proposed protective effects of soy intake against breast cancer. Nutr Cancer. 2009; 61(6):792-798.  Hopkins D, Steer C, Northstone K, Emmett P. Effects on childhood body habitus of feeding large volumes of cow or formula milk compared with breastfeeding in the latter part of infancy. Am J Clin Nutr. 2015; 102(5):1096-1103.  De Beer. Dairy products and physical stature. Econ Hum Biol. 2012; 299-309.  Berkey C, Colditz G, Rockett H, et al. Dairy consumption and female height growth: prospective cohort study. Cancer Epidemiol Biomarkers Prev. 2009;18:1881-1887.  Victora C, Bahl R, Barros A, Franca G, et al. Breastfeeding in the 21st century: epidemiology, mechanisms, and lifelong effect. Lancet 2016; 387(10017):475-490.  The Institute of Medicine (20 ng/mL) and the Endocrine Society (30 ng/mL) differ with respect to what they believe is the cut point for insufficient levels of 25(OH)D3, the circulating form of the hormone measured in blood. Regardless, levels fall below either level in many people in the general population.  Breast Cancer Fund. Working Women and Breast Cancer. Available at: http://www.breastcancerfund.org/media/publications/reports/working-women-and-breast-cancer.html?referrer=https://www.google.com/  Hilakivi-Clarke L. Maternal exposure to diethylstilbestrol during pregnancy and increased breast cancer risk in daughters. Breast Cancer Res. 2014; 16(2):208.  Cohn B, Wolff M, Cirillo P, Sholtz R. DDT and breast cancer in young women: new data on the significance of age at exposure. Environ Health Perspect. 2007; 115(10):1406-1414.  Cohn B, La Merrill M, Krigman N, Yey G, et al. DDT exposure in utero and breast cancer. J Clin Endocrinol Metab. 2015; 100(8):2865-2872.  http://www.acog.org/Resources-And-Publications/Committee-Opinions/Committee-on-Health-Care-for-Underserved-Women/Exposure-to-Toxic-Environmental-Agents  See http://www.cancer.gov/news-events/press-releases/2011/IARCcellphoneMay2011  West J, Kapoor N, Liao SY, Chen J, et al. Multifocal breast cancer in young women with prolonged contact between their breasts and their cellular phones. Case Reports in Medicine. 2013; Article ID 354682. Available at http://www.hindawi.com/journals/crim/2013/354682/ .