Integrative approaches for the prevention and management of Breast, Colorectal and Prostate Cancer

• Mariah Stump, MD, MPH, FACP, DipABLM, ABOIM
• Assistant Professor of Medicine, Alpert Medical School, Brown University
• Women’s Primary Care, Women’s Medicine Collaborative
• Medical Acupuncturist, Lifespan Physician Group
• Diplomate, American Board of Lifestyle and Integrative Medicine
• January 11, 2024

Disclosures

• I have no disclosures or financial relationships.

My Background

• Board certified in Lifestyle Medicine (DipABLM) and Integrative Medicine (ABOIM)
• Completed 1,000 hours (2 year) Integrative Medicine Fellowship including special focus in Integrative Cancer Prevention/Management
• Certified Medical Acupuncturist (>300 hours), member of AAMA

Objectives

• Discuss how the development of breast, colon and prostate cancers may be specifically influenced by lifestyle factors
• Be able to discuss evidence related to lifestyle changes that can impact risk modification for development of common cancers
• Once cancer may be present, be able to identify how an integrative approach optimizes patient outcomes as well as improves patient satisfaction and quality of life
• Identify evidence based integrative modalities and how to incorporate in management or survivorship plan

What is lifestyle medicine?

• The American College of Lifestyle Medicine (ACLM) is the medical professional society for physicians and other medical professionals dedicated to clinical and worksite practice of lifestyle medicine as the foundation of a transformed and sustainable health care system.
• Lifestyle medicine is a medical specialty that uses therapeutic lifestyle interventions as a primary modality to treat chronic conditions including, but not limited to, cardiovascular diseases, type 2 diabetes, and obesity.

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The Core Principles of Lifestyle Medicine

Integrative Medicine: Defining the Terms

• If a non-mainstream approach is used together with conventional medicine, it’s considered “complementary”
• If a non-mainstream approach is used in place of conventional medicine, it’s considered “alternative”
• NICAM is now NCCIH
• Integrative Medicine (IM) is healing-oriented medicine that takes account of the whole person, including all aspects of lifestyle. It emphasizes the therapeutic relationship between practitioner and patient, is informed by evidence, and makes use of all appropriate therapies

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Top Medical Centers have Integrative Cancer Programs

• The Leonard P. Zakim Center for Integrative Therapies and Healthy Living at Dana-Farber is dedicated to the belief that cancer patients can enhance their quality of life through integrative therapies such as acupuncture and massage, and healthy living programs such as exercise and nutrition counseling
• Extensive research, grants and faculty support and involvement
• Driven by patient interest and large endowments for research and patient care�

Patient Information

Providers need to ask questions about use

• Patients don’t think it’s important for their doctors to know, or their physicians never asked about CAM usage (Ann Intern Med 2001)
• As there are many drug-drug, drug-herb and antioxidant-drug interactions, it is extremely important for physicians to ask about CAM usage and for patients to share their use of CAM (Ann Intern Med 2002)
• It is our duty as medical professionals to encourage this conversation (in a collaborative and open way)

For all cancer and cancer related mortality

• European Prospective Investigation into Cancer and Nutrition found that 4 lifestyle measures were critical in reducing risk of cancer as well as chronic diseases (heart disease and diabetes):
• Not smoking
• BMI <30
• 3.5 hours of exercise per week
• Diet rich in fruit, vegetables and whole grains with little meat consumption
• Having all four of these reduced the risk of cancer by 36%

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Breast Cancer

• 1. Modifiable risk reduction
• 2. Treatment specific strategies
• 3. Management and risk of recurrence

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Common thread: Lifestyle Modifies Risk

• 1/3 of all incident breast cancers within a study population of 5,000 Italian women between 1991 and 1994 could be attributed to alcohol, low-vegetable diet, overweight, and lack of exercise (Journal of National Cancer Institute, Mezzetti, 1998)

Modifiable Risk & Lifestyle�

• Alcohol use (stay within guidelines or less)
• Adult weight gain/BMI <30, specifically visceral abdominal fat and metabolic syndrome
• Exercise (at least 150 min, ideally 3.5 hours per week)
• Diet (Mediterranean or whole food plant based)
• Stress/social isolation
• Environmental toxins
• 2009 JNCI advises that clinicians recommend these interventions to all women, without regard to a particular woman’s risk of breast cancer (Colditz, 2014)

Alcohol use

• By far, the most consistent dietary component associated

with breast cancer risk is alcohol (Jung, 2016 )

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• 7-year prospective British study of 1 million women found a

dose-response relationship between alcohol and breast cancer

(Allen, 2009)

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• Binge drinking is associated with greater risk of breast cancer,

especially among premenopausal women, compared to non-

binge drinking (Sánchez-Bayona, 2020)

• Postmenopausal women are most susceptible to effects of alcohol with every 10g (1 drink) of alcohol associated with an 11% increased risk of breast cancer (Sun, 2020)

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Body Weight

• Weight gain after the age of 20 ("adult weight gain”) is associated with an increased risk only of postmenopausal breast cancer (Huang, 1997; Trentham-Dietz, 2000)
• In contrast, higher BMI and adult weight gain appear to be protective against premenopausal breast cancer

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• Adult weight gain and obesity is associated with an increased

risk of breast cancer mortality in all ages and more important

than weight may be metabolic health (Picon-Ruiz, 2017)

• Weight status influences breast cancer differently in BRCA1 vs BRCA2 mutation carriers

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�Exercise

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• Although exercise at any age is beneficial, activity undertaken during adolescence (14 and 20 years), appears to have more impact on breast cancer risk than exercise undertaken later (Kruk, 2007)
• The risk of being diagnosed with the most common breast cancer subtype, hormone-receptor-positive breast cancer, is most sensitive to the benefits of regular moderate exercise (Bernstein, 2005; Hoffman, 1989)
• Intense physical activity appears necessary to reduce the risk of the most dangerous breast cancer subtype, triple-negative breast cancer (Ma, 2016)

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Benefits of Exercise

• Postmenopausal women in the lowest quartile of physical activity daily (less than 31 MET h/day) had a 40% higher incidence of post-menopausal breast cancer than those in the highest quartile (>38 MET h/day)
• Obese postmenopausal women who are sedentary have a doubled risk of breast cancer compared to normal weight, physically active postmenopausal women (Bellocco, 2016)
• A case-control study of 542 women found that being sedentary increases the risk of breast cancer in pre-menopausal women by 108% and by 81% in postmenopausal women. (Godinho-Mota, 2019).

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Diet for prevention of breast cancer

• Dietary phytochemicals, found exclusively in plant foods, have

anti-inflammatory and antioxidant activity—the are colorful:

eat the rainbow!

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• Mediterranean diet and whole food, plant-based diet have most

evidence in reduced breast cancer risk

• PREDIMED randomized control trial found that a Mediterranean diet supplemented with extra virgin olive oil was associated with a 68% reduction in breast cancer risk, while the same diet supplemented with nuts was associated with a 41% reduced risk (Toledo, 2015)
• Conversely, a Western dietary pattern is associated with a 46% increase risk of breast cancer (Castelló, 2014)
• Mediterranean dietary pattern was most protective against triple negative breast cancer, with a 68% reduced risk

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Specific foods: nutrients and dietary components

• Omega 3-fatty acids: EPA and DHA
• Dosing: 1,000 mg combined in <3g, take before eating to reduce taste
• Can decrease adhesiveness of platelets/increase bleeding; stop 1 week before surgery
• Present in fatty fish (salmon, sardines, mackerel), walnuts, flaxseed
• VITamins And Lifestyle (VITAL) study: fish oil reduced risk of ductal (but not lobular) breast cancers (White 2004)

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• Mechanism: anti-inflammatory properties of omega-3 and the role of inflammation in carcinogenesis (Thun, 2004)

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• High levels of inflammatory COX-2 enzymatic activity found in breast and colon tumors: the omega-3 (DHA) down regulates COX-2 activity (Tapiero, 2002)

Green tea

• Camellia sinensis
• Polyphenol, natural aromatase inhibitor
• Consumption of at least 3 cups per day may reduce the risk of breast cancer recurrence (Gianfredi 2018)
• Green tea components, especially epigallocatechin-3-gallate, possess anti-breast cancer effects (Li 2014)

Uncovering the Soy Controversy

• Breast cancer incidence is lower in populations whose traditional diets include generous amounts of soy consumed in childhood and adolescence (Warri, 2008)

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• Protective effects of soy on the breast are related to high

concentrations of a class of compounds called isoflavones

(Limer, 2004; Guha, 2009; Fink, 2007).

• A 2020 meta-analysis of 18 studies found that the highest intake of soy was associated with a 12% reduced risk of breast cancer, independent of subtype, compared to the lowest intake (Fink, 2007)
• The beneficial impact of soy is most evident among premenopausal women, with high consumption associated with a 21% reduced risk (Okekunle, 2020).

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��Shanghai Women’s Health Study (Zheng 2005)�

• 73,223 Chinese women followed for more than 7 years
• Largest and most detailed study of soy and breast cancer risk in a population with high soy consumption
• Women who ate the most soy had a 59% lower risk of premenopausal breast cancer compared with those who ate the lowest amounts of soy
• Risk was 43% lower when soy was eaten during adolescence
• Seven years later follow-up analysis from the same cohort (Estrogen [ER] +/-Progesterone [PR] +/-) Key highlights of the study:
• A 22% lower risk of breast cancer when comparing the highest to lowest intakes of soy during adulthood.
• A 28% lower risk of hormone positive (ER+, PR+) breast cancer in postmenopausal women.
• A 54% lower risk of hormone negative (ER-, PR-) breast cancer in premenopausal women.
• A 47% lower risk of premenopausal breast cancer when comparing high to low intakes of soy during adolescence and adulthood.

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Flax and Fiber

• Flax seed—excellent source of omega-3 and lignans (phytoestrogen) decreases inflammation and inhibits aromatase activity
• Reduces risk of breast cancer and decreases breast cancer cell growth
• RCT 99 postmenopausal women: 2 tbsp of ground flaxseeds daily for 7 weeks altered estrogen metabolites which underlie the protective effect of the flaxseed lignans Chang, 2018
• Recommended dosing: 2 tbsp/day flax seed added to food—oil can become rancid—keep airtight and refrigerate or use promptly!
• Dietary fiber has been associated with decreased risk of breast cancer
• A systematic review found that each 10-gram increase in daily fiber intake was associated with a 4% decrease in breast cancer risk (Chen, 2016)
• Protective effect of fiber is evident only with a high level of intake, specifically at least 25g/day (but this is what is recommended to all women!) and with greater effect from soluble fiber (seeds, legumes, cereals) (Aune, 2012).

Cruciferous vegetables

• Rich in sulforaphane, flavones, and indole-3-carbinol (I3C) which decrease cancer cell proliferation
• They are also potent anti-cancer compounds; I3C increases the hepatic metabolism of the active 16-hydroxyl estrogen to the relatively inactive 2-hydroxyl form (Meng, 2000)
• A meta-analysis of thirteen studies (11 case-control and 2 cohort studies) found that high cruciferous vegetables intake was significantly associated with reduced breast cancer risk (RR = 0.85, 95% CI = 0.77-0.94) (Liu, 2013)
• Sulforaphane is found in particularly high concentrations in broccoli sprouts and has been shown to inhibit breast cancer cells in vitro (Li, 2010), and its chemoprotective metabolites have been found in human breast tissue after a single consumption (Cornblatt, 2007).

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Patient Case

• Sofia is a 35-year-old woman who was found to carry a BRC2 mutation. She has consulted a genetic counselor who told her that her risk of breast cancer is 70% and of ovarian cancer 20% by age 70
• She has seen a breast surgeon regarding prophylactic mastectomy and a gynecologic oncologist about prophylactic oophorectomy. In addition, she has discussed undergoing five years of prophylactic tamoxifen therapy with a medical oncologist.
• While considering whether to proceed with any of these options, she comes to see you for lifestyle advice. She has read that lifestyle modification can decrease breast cancer risk, even in those with BRCA mutations.
• She is on no current medications and is taking a supplement recommended by a friend because it will "boost immunity," but the label is not adequate to determine the exact ingredients. She has been slightly overweight since sixth grade, but began eating healthier after learning of her genetic status, and has been vegan for about 2 months now but her weight has not changed as she had hoped. She is wondering if she should try harder to lose the 15 extra pounds she's carried since before high school (BMI 28). She is also asking you for medical advice on foods, supplements, and herbs which can increase her chances of avoiding breast cancer.

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Lifestyle Recommendations

• Routine exercise (at least 150 min per week)
• Dietary examination: whole food? Vegan does not always = healthy
• Weight management/goal for BMI <25
• Ask about alcohol use and other toxins
• Supplements should be examined always for their ingredients and should be from reliable sources
• Best prevention is through DIET alone and not supplements for risk modification/reduction of breast cancer

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Environmental toxins

• A review of epidemiological studies included 134 environmental chemicals in association with breast cancer risk (Rodgers, 2018)
• Additional evidence that exposures to environmental chemicals is associated with breast cancer comes from therapeutic, incidental, or occupational exposures (Hiatt, 2011).

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Environmental Risk Reduction

• Eat hormone-free meat and dairy
• Avoid charred foods, especially meats
• Reduce consumption of animal fat
• Use stainless steel or glass containers
• Do not microwave in plastic containers
• Eliminate phthalate-containing household items (PVC plastic), toys, personal care products
• Eliminate products containing "fragrance"
• Use non-toxic cleaning products
• Avoid chemical based dry cleaning
• Use a water filter which removes chemicals
• Only eat fish low in mercury
• Remove shoes before coming into the home
• Minimize use of pesticides around the home and on pets and subscribe to integrated pest management techniques
• Test homes for radon and use carbon monoxide monitors

  (Gray, 2009; Sathyanarayana, 2012; NCI, 2015)

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Part 2: Management of Existing Breast Cancer

• Pre-surgery: distress and response expectancies can be highly predictive of post-surgical outcomes
• In a prospective study of 101 women undergoing breast cancer surgery, women with higher negative pre-surgical expectancies and higher levels of emotional distress were at greater risk for experiencing side effects such as severe post-surgery pain (p<0.03), fatigue (p<0.03), and nausea (p<0.05) (Montgomery, 2010)

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PCP visit

• Ask about mind-body practices/support: mindfulness, positive psychology, counseling
• Discontinue most herbal supplements at least a week prior to surgery, unless a specific reason to continue them is clear and agreed upon by all treating physicians, including the surgeon and anesthesiologist—many increase bleeding risk

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Supplements that increase bleeding risk

• Garlic—may inhibit platelet function, discontinue 7 days prior
• Ginkgo- may inhibit platelet function, discontinue taking ginkgo at least 36 hours prior to surgery
• Ginseng- because platelet inhibition caused by ginseng may be irreversible, it is probably prudent to recommend that patients discontinue ginseng use at least 7 days prior to surgery
• St John’s Wort—long half life, CYP metabolizer, discontinue use at least 5 days prior to surgery

(Ang-Lee, 2001; Wang, 2015)

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Treatment with Hormonal Agents

• The most common side effects of tamoxifen are menopausal symptoms including diaphoresis and hot flashes
• Side effects of the AIs can include myalgias, arthralgias, and hot flashes in approximately 30% of patients
• A decrease in bone mineral density of about 2% per year is expected.
• Vaginal dryness is common, and dyspareunia can affect relationships and quality of life. Most oncologists feel comfortable prescribing vaginal estrogen, as the amount absorbed systemically is not thought to significantly affect prognosis (ACOG, 2016; Melisko, 2016)

Integrative Modalities during treatment

• Treatment complications that lend themselves well to integrative modalities:
• Pain
• Neuropathy
• Digestive dysfunction: nausea, vomiting, anorexia, diarrhea or constipation
• Endocrine dysfunctions: hair loss, hot flashes, cold extremities, decreased libido
• Mental and cognitive dysfunctions: anxiety, depression, insomnia, poor memory, and concentration, and slower thinking processes/ “brain fog”

Acupuncture for Breast Cancer management

• Most positive data on chemotherapy-induced nausea and vomiting (O'Regan, 2010), and aromatase inhibitor-associated joint pain and stiffness (Crew, 2010).
• Found to be as effective, and less toxic, than venlafaxine/Effexor (standard drug therapy for relieving vasomotor symptoms in breast cancer patients) (Walker, 2010)
• Boosted libido and improved mental clarity, with no adverse effects (Walker, 2010)
• Relieves chemotherapy-induced peripheral neuropathy in many patients. Studies confirm that both subjective and objective improvements are obtained, as measured by symptom scores and nerve conduction studies (Schroeder, 2012; Ben-Horin, 2017).

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Barriers to Acupuncture Usage

• COST/INSURANCE COVERAGE
• Now in RI several major insurances cover MD acupuncture sessions (with a specialist Co-pay) for common musculoskeletal conditions and likely cancer related treatments
• Provider lack of comfort with and knowledge of acupuncture creates hesitation with referrals to acupuncturists

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Community Acupuncture

Exercise during treatment

• During and after cancer treatment, exercise benefits mood, strength, balance, energy levels, overall health and well-being, survival, prevention of recurrence and quality of life
• Patients can face treatments with less fatigue, muscle weakness, better balance and fewer falls (Pizot, 2016)
• Improved effects on pain, lymphedema and improved self image (McTiernan, 2019)
• Simple, moderate paced walking interventions reduce pain and maintain cardiorespiratory fitness when undergoing radiation and chemotherapy (Ma, 2016 )
• Greatest benefits with >=150 minutes per week

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Mind-Body Therapies

• Mind-body medicine therapies generally include: clinical

hypnosis, guided imagery, mindfulness and meditation,

breath work, yoga, music therapy, biofeedback

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• An integrative approach may help decrease the spectrum

of side effects and has the potential to provide women

undergoing treatment a greater sense of control,

resilience, and self-efficacy

(Lengacher, 2012; Matousek, 2011; Witek-Janusek, 2008)

• Mind-body medicine therapies are gentle, versatile, and allow patients to harness their strengths and reduce the need for as much medication for pain or anxiety (Haller, 2020)
• Cochrane Review of yoga in breast cancer patients affirms its positive effects and low risk profile (Cramer, 2017)
• A 2021 meta-analysis of randomized clinical trials that included 26 trials representing 2069 women with breast cancer concluded that yoga improves quality of life, emotional and functional well-being and sleep quality (Hsueh, 2021)

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Mindfulness

• 229 women with stage 0 to 1 breast cancer, women randomly assigned to a 12-week MBSR program had statistically improved scores for fatigue (p=.03) , vigor (p=.02), and emotional and functional wellbeing (p=.04) at 12 weeks (Hoffman, 2012)
• Randomized controlled trial involving over 300 subjects with breast cancer found MBSR techniques resulted in durable improvement in anxiety and fatigue (Reich, 2017)
• Randomized control trial of 92 women with early stage breast cancer receiving adjuvant paclitaxel chemotherapy found that a 12-week progressive muscle relaxation intervention and/or mindfulness meditation reduced fatigue and improved coping styles (Gok Metin, 2019)

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3. Prevention of recurrence

• Weight management (particularly reducing visceral adiposity
• Fasting morning blood glucose should be maintained in the low 80s
• Clinical Pearl: prolonging the overnight fast to at least 13 hours significantly decreased the hazard ratio of breast cancer recurrence over an average of 7 years following a breast cancer diagnosis. Fasting= taking no calories (although water and black coffee are allowed) (Marinac, 2016)
• Mechanism of action is thought to be related to modulation of the insulin-glucose axis and perhaps to increased length or quality of sleep

Reducing recurrence risk

• Women's Healthy Eating and Living Study (WHELS) assessed the effects of a dietary intervention (low fat, high fiber, high fruit/vegetable group) combined with high physical activity (>9 MET-hrs/week) on breast cancer mortality after diagnosis: physical activity intervention group had a significantly lower mortality (50%) (Pierce, 2007).
• A nested case-control analysis of a WHELS sub-cohort showed that in postmenopausal breast cancer, decreasing carbohydrate intake by 27 grams daily was associated with a halving of breast cancer recurrence risk (Emond, 2014)
• Data from the WINS trial showed that, in ER(-) patients, the risk of recurrence at 5 years was decreased by 56% by following a low fat diet.
• The American Cancer Society guidelines recommend that all cancer survivors exercise at least 150 minutes a week, and include strength training 2 days per week for general health, and for chronic disease prevention and management (Rock et al., 2012)

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Breast Cancer Survivorship: Group Visits

• As there are a limited number of oncologists available to serve a growing population of breast cancer survivors, it is often necessary to incorporate other health care providers
• ASCO suggests that primary care providers can potentially follow patients with early breast cancer (< 5 cm tumors and < 4 LN) after 1 year from diagnosis (Runowicz, 2016)
• Shared medical visits are an excellent model for breast cancer survivorship care

Colorectal Cancer

• Up to 70% of colorectal cancers can be prevented by diet and lifestyle changes including:
• High fiber diet: fruits, vegetables (especially cruciferous!) and omega-3 fatty acids
• Diet low in red and processed meats
• Moderate exercise 150 min/week or vigorous 75 min/week
• Maintenance of healthy body weight: BMI<25
• Limiting alcohol use to no more than 7/week in women, 14/week men (w/no more than 2 drinks at a time)
• Avoid tobacco
• Good glycemic control

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American Cancer Society, Colon Cancer Fact Sheet, 2022

FOOD IS MEDICINE

• “Food is not just calories. It’s actually information, and it changes your brain chemistry, your hormones, your immune system, your gut flora and your gene expression with every bite.”—Dr Mark Hyman, The Cleveland Clinic

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Dietary CRC Recommendations

• Increased incidence of CRC among Japanese migrants from low-risk (rural) to high-risk (urban) areas and in countries that adopt a Western lifestyle strongly suggest dietary factors are important determinants of colorectal carcinogenesis (Haenszel, J Nat Canc Inst 1968)
• Fiber intake shows linear dose-response negative correlation with CRC risk—every 10 g of fiber intake results in 10% risk reduction in colon cancer (Aune D, BMJ 2011)
• Dietary fiber stimulates butyrogenic activity of the gut microbiota, providing high amounts butyrate that shows extensive anti-neoplastic effects (Ocvirk, S. Curr Gastroenterol Rep 2019)
• A high-fat diet promotes CRC risk through stimulated bile acid metabolism, facilitating bile acid conversion by the gut microbiota to tumor-promoting deoxycholic acid

Red & Processed Meat Risk

• Greater consumption of red meat is linked to an increased risk for colorectal cancer with processed meats contributing to highest risk (36% increased risk for CRC for every 100g/day of red meat and 25% increased risk for every 50 g/day of processed meat) (Norat, J Nat Canc Inst 2005)
• Heterocyclic amines and polycyclic aromatic hydrocarbons (form during frying and barbecuing of meats) are carcinogenic
• Processed lunchmeats and anything with sausage or casing or smoked/cured (bacon) w/sodium nitrates 🡪 oncogenic to colon
• Choose lean cuts, trim away excess fat, and avoid charring your meat on a grill
• Limit processed, cured, and salted meats as much as possible

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Prostate Cancer

• Same lifestyle recommendations as with colon cancer including high fiber diet and limiting red meat and processed meat consumption (American Cancer Society)
• Additional findings specific for Prostate Cancer:
• Soy protein isoflavones (genistein) inhibits prostate cancer growth
• 16 yr long prospective study, men who consumed several glasses of soy milk daily lowered risk of prostate cancer by 70% (Applegate C, Nutrients 2018)
• Lycopene: cancer fighting anti-oxidant which gives tomatoes, strawberries and watermelon their color—beneficial effect for risk reduction and management—4x/week tomato products reduce prostate cancer risk by 20% (Chen, Medicine Baltimore 2015)

Conclusions

• Lifestyle Measures are critical in reducing risk of cancer as well as chronic illnesses (heart disease and diabetes)
• Discussion with patients regarding their nutrition, physical activity level, sources of support and connection in their lives are essential to management of their cancer management and survivorship
• Integrative therapies such as acupuncture and mind-body practices (yoga, Tai Chi, mindfulness) are evidence based for reducing the side effects of cancer treatments and should be included for optimal care

Thank you!

• Please contact me with questions or if interested in working with me in the Lifestyle Medicine Center
• Mariah_Stump@brown.edu