Intermittent Fasting and Cancer Metabolism:   A Four Part Series

PART 3: Intermittent Fasting and Insulin Like Growth Factor (IGF-1)

 

Intermittent fasting (IF) reduces insulin-like growth factor 1 (IGF-1) levels through several specific mechanisms:

1. Protein Restriction: The reduction in IGF-1 is primarily attributed to the restriction of protein intake, particularly essential amino acids, during fasting periods8.

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1. Calorie Restriction: The decrease in overall calorie intake during fasting supports the reduction in IGF-1 levels8.
2. Insulin Reduction: Fasting leads to a significant decrease in circulating insulin levels, which in turn promotes the reduction of IGF-182.
3. Metabolic Switch: IF induces a metabolic switch that mimics water fasting, leading to a decrease in IGF-1 levels. For example, a 4-day fasting-mimicking diet (FMD) can reduce IGF-1 levels by approximately 45%3.
4. IGFBP-1 Increase: Fasting causes a substantial increase in IGF binding protein 1 (IGFBP-1), which can bind to IGF-1 and reduce its bioavailability. Studies have shown that prolonged fasting can lead to a 5-fold increase in IGFBP-13.
5. Signaling Pathway Modulation: IF down-regulates nutrient signaling pathways such as TOR-S6K and PKA, which are involved in IGF-1 regulation3.
6. Hepatic Gene Expression: Fasting specifically decreases IGF-1 mRNA in the liver, indicating a direct effect on IGF-1 gene expression4.

It's important to note that the effects of IF on IGF-1 levels can vary depending on the specific fasting protocol. For instance, while prolonged fasting and fasting-mimicking diets have shown significant reductions in IGF-1, some studies on time-restricted eating (TRE) have not observed changes in IGF-1 levels over shorter periods6.

These mechanisms collectively contribute to the reduction of IGF-1 levels during intermittent fasting, which may have implications for various health outcomes, including cancer prevention and treatment123.

Intermittent fasting (IF) has shown promising effects on tumor growth across various cancer types, though the impact can vary depending on the specific cancer and fasting protocol.

 Overview of how IF affects tumor growth in different cancers:

Breast Cancer

IF has demonstrated significant potential in reducing tumor growth and progression in breast cancer. It lowers insulin-like growth factor 1 (IGF-1) levels, which are associated with cancer cell proliferation. This reduction in IGF-1 enhances the efficacy of breast cancer treatments by making cancer cells more susceptible to apoptosis1.

Hepatocellular Carcinoma

In hepatocellular carcinoma, IF has been shown to prime the tumor microenvironment, enhancing the delivery and effectiveness of nanomedicine. Fasting improved vascular normalization and increased the permeability of tumor blood vessels, allowing for more efficient delivery of therapeutic agents1.

Leukemia

IF has shown promising results in B cell and T cell acute lymphoblastic leukemia. Through the regulation of the leptin receptor via the protein PR/SET domain 1 (PRDM1), fasting can suppress and potentially reverse the course of these types of leukemia4.

Colon and Prostate Cancer

IF has been associated with a reduction in IGF-1 levels, which is particularly relevant for colon and prostate cancers. Increased IGF-1 levels are attributed to these cancers due to suppressed apoptosis, boosted cell proliferation, and genetic instability4.

Intermittent Fasting and Cancer Metabolism:   A Four-Part Series

 Intermittent fasting (IF) has emerged as a promising dietary intervention in cancer prevention and treatment. Recent studies have shed light on the potential mechanisms by which IF may influence cancer progression and therapy outcomes.

The OutSmart Cancer® System recommends intermittent fasting for 13 hours of calorie restriction per 24 hour cycle with the appropriate assessment, monitoring and guidance of a health care provider.

PART 1 Intermittent Fasting: Mechanisms of Action

IF has been shown to modulate several key pathways involved in cancer biology:

1. Metabolic Regulation: IF can reduce circulating levels of insulin-like growth factor 1 (IGF-1), which is associated with cancer cell proliferation1. This reduction may enhance the efficacy of cancer treatments by making cancer cells more susceptible to apoptosis.
2. Autophagy Enhancement: IF induces autophagy, a cellular “housekeeping” mechanism that can selectively target and destroy cancer cells4. This process may improve the effectiveness of anticancer therapies.
3. Immune System Modulation: Fasting periods can increase the activity of natural killer (NK) cells and cytotoxic T lymphocytes, enhancing the immune response against tumors1.
4. Oxidative Stress Reduction: IF has been observed to decrease levels of proinflammatory cytokines and increase anti-inflammatory markers, creating a less favorable environment for cancer progression1.

General Tumor Growth Inhibition

Across various cancer types, IF has been observed to:

1. Alter energy metabolism of tumor cells, inhibiting their growth2.
2. Enhance antitumor immune responses2.
3. Increase cancer sensitivity to chemotherapy and radiotherapy2.
4. Reduce glucose levels in the blood, making it harder for glucose-dependent cancers to grow6.

Mechanisms of Action

The impact of IF on tumor growth is mediated through several mechanisms:

• Metabolic Switch: IF induces a state of ketosis, which can be detrimental to cancer cells that rely heavily on glucose for rapid proliferation1.
• Immune System Enhancement: Fasting increases the activity of natural killer (NK) cells and cytotoxic T lymphocytes, improving the immune response against tumors1.
• Oxidative Stress: IF can increase reactive oxygen species (ROS) in cancer cells while decreasing their antioxidant defenses, leading to increased oxidative stress and enhanced chemotherapeutic action4.
• Signaling Pathway Modulation: IF affects the IGF-1/mTOR signaling pathway, which is known to influence cancer etiology4.

Is there a safe level of alcohol consumption?

In January of 2025, the US surgeon general issued a report warning that alcohol is associated with multiple cancers.

 More than half of Americans are unaware of the link between alcohol consumption and cancer.  This includes many health care providers.  There is still an outdated belief that a moderate amount of red wine is beneficial to cardiovascular health and has additional health benefits.  The link between the benefit of alcohol to cardiovascular disease is also becoming controversial in light of more recent evidence.

 I would challenge this view and state that an abundance of phytophenols and stilbenes, including resveratrol found in red wine are the source of any benefit, not the alcohol, which is a known hepatotoxin, neurotoxin, cardiotoxin, endocrine disruptor, and carcinogen. 

 An abundance of plant pigment-derived compounds are the good actors in red wine, providing a rich source of antioxidants and phytochemicals with positive epigenetic health effects that can be readily consumed in many other healthier sources in fruits and vegetables and botanical medicines without the accompanying risk factors of alcohol consumption. 

While alcohol, like tobacco, has been a socially acceptable and even medically acceptable social intoxicant, “alcohol use is a leading risk factor for global disease burden and causes substantial health loss. We found that the risk of all-cause mortality, and of cancers specifically, rises with increasing levels of consumption, and the level of consumption that minimizes health loss is zero. The widely held view of the health benefits of alcohol needs revising.”.

 In other words, there is no safe level of alcohol consumption.  All levels of alcohol consumption come with significant risk factors.

Which cancers are linked to alcohol consumption

“Alcohol increases risk of cancer of oral cavity and pharynx, oesophagus, colorectum, liver, larynx and female breast. There is accumulating evidence that alcohol drinking is associated with some other cancers such as pancreas and prostate cancer and melanoma.”

 

How does alcohol cause damage?

o   Metabolic by products bind to DNA, damaging cells and fueling tumors

o   Dysregulation of hormonal metabolism of estrogen

o   Acts as a solvent for other environmental toxins increasing toxic exposure

o   Increases inflammation

While some believe that the social aspects of alcohol consumption contribute to health and longevity, as noted in the super healthy long lived Blue Zone cultures where alcohol is part of a way of life, there is a growing interest in non-alcoholic designer beverages  that serve the same social and celebratory function.   In fact, one can toast with a glass of sparkling water with a splash of flavor added for conviviality and connection.

As many cancer treatments can damage heart function, I also recommend limiting alcohol intake to patients who have been treated with doxorubicin which damages the myocardium and to those patients with have arrythmia for which alcohol increases dysregulation.

I do advise all patients to avoid alcohol use as it is a known carcinogen.  And if this is not something they wish to adopt as a way of lifelong term, I recommend that they refrain from alcohol use if they have known body burden of cancer, during cancer treatment and strictly for the first 2 years after completing cancer treatment.  This is the period when recurrence is most common.   I also recommend, if abstinence is not an option, that they limit alcohol intake to one glass a few times a year at a wedding or holiday celebration.  

 OutSmart Cancer patients are highly motivated to do everything that they can to contribute to a good outcome.  In this patient population, particularly those patients who are looking for a health outcome and a health model, implementing the OutSmart Cancer® System starting with the OutSmart Cancer® Diet guidelines can be a reasonable first step and foundation to Getting Well, Staying Well and Living Well Beyond Cancer and to Creating a Body Where Cancer Cannot Thrive.

 

Selected References

(1)   Griswold, Max G et al. Alcohol use and burden for 195 countries and territories, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016 The Lancet, Volume 392, Issue 10152, 1015 – 1035

(2)   Alcohol and Cancer Risk 2025, Report of US Surgeon General Alcohol and Cancer Risk 2025. Report of US Surgeon General  https://www.hhs.gov/surgeongeneral/priorities/alcohol-cancer/index.htmlchrextension://efaidnbmnnnibpcajpcglclefindmkaj/https://www.hhs.gov/sites/default/files/oash-alcohol-cancer-risk.pdf

(3)   https://peterattiamd.com/alchohol-intake-and-cardiovascular-disease-risk/

(4)   Biddinger KJ, Emdin CA, Haas ME, et al. Association of Habitual Alcohol Intake With Risk of Cardiovascular Disease. JAMA Netw Open. 2022;5(3):e223849. doi:10.1001/jamanetworkopen.2022.3849

(5)   Bagnardi, V., Rota, M., Botteri, E. et al. Alcohol consumption and site-specific cancer risk: a comprehensive dose–response meta-analysis. Br J Cancer 112, 580–593 (2015). https://doi.org/10.1038/bjc.2014.579

(6)   Di Credico, G., Polesel, J., Dal Maso, L. et al. Alcohol drinking and head and neck cancer risk: the joint effect of intensity and duration. Br J Cancer 123, 1456–1463 (2020). https://doi.org/10.1038/s41416-020-01031-z

(7)   https://www.bluezones.com/2018/09/new-study-says-theres-no-safe-level-of-alcohol/

(8)   CDC Alcohol Use and Your Health https://www.cdc.gov/alcohol/index.html

(9)   https://www.nytimes.com/wirecutter/reviews/best-non-alcoholic-drinks/

(10)Dulf PL, Mocan M, Coadă CA, Dulf DV, Moldovan R, Baldea I, Farcas AD, Blendea D, Filip AG. Doxorubicin-induced acute cardiotoxicity is associated with increased oxidative stress, autophagy, and inflammation in a murine model. Naunyn Schmiedebergs Arch Pharmacol. 2023 Jun;396(6):1105-1115. doi: 10.1007/s00210-023-02382-z. Epub 2023 Jan 16. PMID: 36645429; PMCID: PMC10185623.

 (11)Steven K Clinton, Edward L Giovannucci, Stephen D Hursting,
The World Cancer Research Fund/American Institute for Cancer Research Third Expert Report on Diet, Nutrition, Physical Activity, and Cancer: Impact and Future Directions, The Journal of Nutrition, Volume 150, Issue 4,2020, https://doi.org/10.1093/jn/nxz268

Approximately 20% of all patients who die of lung cancer in the US are non-smokers.  Cases of lung cancer in non-smokers are on the rise.  While a history of smoking is the primary cause of lung cancer, 10-20% of all lung cancer diagnoses occur in non-smokers or in people who have smoked less than 100 cigarettes in their lifetimes.

• Take a Thorough Toxic Exposures History
• Identify Environmental Risk Factors for Lung Cancer in Non-Smokers
• Nutriceutical and Botanical Interventions
•               Support Healthy Lung Structure and Function
•               Enhance Cancer Immunity
• Employ Appropriate Lung Cancer Screening
• Recognize Signs and Symptoms of Lung Cancer
• Apply The OutSmart Cancer System

Include a comprehensive history of known toxic exposures

at home, work, medical treatments and travel over the lifetime of your patient as part of a thorough intake and assessment.

Identify Environmental Risk Factors for Lung Cancer in Non-Smokers include exposures to

 Radon Gas: an invisible odorless gas that may concentrate inside homes in areas where there is a naturally high level of uranium in the soil. The Environmental Protection Agency publishes a guide to testing and reducing radon gas at home. Radon gas gives off radioactive particles that can damage genetic material in  the lung epithelia increasing risk of lung cancer.  1 in 15 homes in the US may have unsafe levels of radon gas.

 Secondhand Smoke is environmental tobacco smoke from cigarettes, pipes and cigars containing nicotine and carcinogens.  There is no safe level of exposure for secondhand smoke. 20-30% of lung cancers in non-smokers are linked to exposure to secondhand smoke.

 Carcinogens in the workplace include asbestos, heavy metals, nickel, cadmium, beryllium, arsenic, uranium, diesel exhaust and coal fumes.  There is a higher rate of lung cancer among gas station attendants, bus and truck drivers and hairdressers. Firefighters are exposed to a wide range of toxic chemicals and fumes from burning materials.

 Air pollution: Twenty nine percent of lung cancer deaths can be attributed to air pollution which is more prevalent in urban environments, automobile plants, oil refineries,  dry cleaning plants and around construction sites and wood-burning stoves.  Some artists may work with paints and materials that contain heavy metals and use volatile solvents and glues in their work.

 Gene Mutation and Family History of a first degree relative or multiple family members a family member diagnosed at a young age increase risk.  Eight percent of lung cancers are linked to genetic mutations.

 Nutriceutical and Botanical Interventions

• Support healthy Lung Structure and Function
• Enhance Cancer Immunity 

Vitamin A deficiency is linked to histopathological changes to the pulmonary epithelial lining.  Vitamin A deficiency during pregnancy leads to compromised lung development in the fetus.   Chronic Vitamin A deficiency is a common problem in many parts of the world.

Vitamin A plays a main role in regulating antioxidant defences, cell growth and differentiation. Consequently, numerous studies have focused on the association between vitamin A and various types of cancer (1, 2)

 Recommended dose of Vitamin A as retinol : 1500-3000mcg per day. This is a conservative dose.  Higher doses can be administered when tracking serum levels to achieve optimum but not excessive levels.

 Serum Zinc levels and Zinc: Copper ratios are inversely related to lung cancer risk as well as resistance to respiratory infections. (3).  Zinc supplementation has been shown to induce apoptosis and enhance anti-tumor efficacy of chemotherapy agents in the treatment of lung cancer (4)

Recommended Dose of Zinc chelate: 30mg three times per day

The Chinese herb Astragalus is widely used as a lung tonic and for promoting lung immunity and cancer immunity in traditional and modern Chinese Medicine and has been shown to enhance survival and reduce mortality from lung cancer.  (5) Astragalus may contraindicated with concurrent use of immunotherapy treatments with  PD-1 and PDL-1 inhibitors due to its immune stimulating effects and may exacerbate adverse effects of immunotherapy treatment. Caution is advised.

Recommended dose of Astragalus root (available in capsules and granules) 1000-2000mg 3x per day.

 Lung cancer is the leading cause of cancer related deaths in the US.  Lung cancer accounts for more deaths than breast cancer, colorectal cancer and prostate cancer combined.  These four cancers are the most prevalent cancers in the US. However, we have active screening and more effective treatments and more long term survival with breast, prostate and colorectal cancers than with lung cancer.  We do not have any regular screening programs for lung cancer and less success with treatment and survival.  Lung cancer is usually a lethal cancer.  Early detection is crucial.

Screening for detection of lung cancer includes high radiation exposure from CT scans which carries its own inherent risks.  Screening is typically done only in high-risk individuals.   There is now the option of a new MRI technology that can identify lung cancer without the use of radioactive gadolinium.   As this technology becomes more widely available and more cost effective, it may come into wider use and lead to earlier diagnosis and better outcomes.   Currently this MRI technology is provided by Prenuvo (prenuvo.com) in several cities in the US. The five-year survival rate for lung cancer caught at stage 1 is 65% vs. 5% for those diagnosed at Stage 4 I recommend making use of  Prenuvo MRI technology for lower risk radiation free screening for early detection.

 Signs and Symptoms of Lung Cancer

• A cough that doesn’t go away or gets worse over time
• Coughing up blood
• Chest pain or discomfort
• Trouble breathing
• Wheezing
• Hoarseness
• Loss of appetite
• Weight loss for no reason
• Fatigue
• Trouble swallowing
• Swelling in the face and/or the neck
• Recurrent lung infections, including pneumonia

 The OutSmart Cancer® System is a health model for creating a body where cancer cannot thrive.  The OutSmart Cancer® System includes the promotion of robust health and enhanced cancer immunity through the OutSmart Cancer® Diet, OutSmart Cancer® Nutriceutical and Phytochemical Supplements and OutSmart Cancer® Lifestyle and Self Care Guidelines.

Every cancer patient deserves a plan for their health

and not just a plan for their disease.

 Selected references:

1. Herzog R., Cunningham-Rundles S. Immunologic impact of nutrient depletion in chronic obstructive pulmonary disease. Curr. Drug Targets. 2011;12:489–500. doi: 10.2174/138945011794751500

 2. Yu N., Su X., Wang Z., Dai B., Kang J. Association of dietary vitamin A and β-carotene intake with the risk of lung cancer: A meta-analysis of 19 publications. Nutrients. 2015;7:9309–9324. doi: 10.3390/nu7115463

3. Wang, Y., Sun, Z., Li, A. et al. Association between serum zinc levels and lung cancer: a meta-analysis of observational studies. World J Surg Onc 17, 78 (2019). https://doi.org/10.1186/s12957-019-1617-5

4. Kocdor H, Ates H, Aydin S, Cehreli R, Soyarat F, Kemanli P, Harmanci D, Cengiz H, Kocdor MA. Zinc supplementation induces apoptosis and enhances antitumor efficacy of docetaxel in non-small-cell lung cancer. Drug Des Devel Ther. 2015 Jul 27;9:3899-909. doi: 10.2147/DDDT.S87662. PMID: 26251569; PMCID: PMC4524380.

5. Dugoua JJ, Wu P, Seely D, Eyawo O, Mills E. Astragalus-containing Chinese herbal combinations for advanced non-small-cell lung cancer: a meta-analysis of 65 clinical trials enrolling 4751 patients. Lung Cancer (Auckl). 2010 Jul 8;1:85-100. doi: 10.2147/lctt.s7780. PMID: 28210109; PMCID: PMC5312465.

Many women with a history of estrogen receptor positive breast cancer suffer from genito-urinary symptoms of menopause as a sequela of hormone blockade treatment and from treatment induced menopause. These symptoms include vulvo-vaginal atrophy, vaginal dryness, pain and bleeding, painful intercourse and urinary incontinence.   

 Despite vulvovaginal atrophy (VVA) being a common side effect, affecting 19–91% of patients treated for onco-gynecological conditions surveys indicate that only about half of oncologists discuss this complication before treatment, and 65–85% report lacking sufficient knowledge about VVA treatment options.

Discussing this complication in advance is beneficial not only for patient awareness but also for prevention. . Consideration of use of local preparations applied before the onset of symptoms may reduce their intensity later.  Furthermore, timely interventions not only relieve symptoms but also enhance the quality of life in cancer survivors.***

There is concern about the risks of using vaginal estrogen therapies with this patient population as prior trials have demonstrated risk of recurrence with the use of systemic estrogen therapies.  The question remains as to whether local vaginal use of estrogen is safe for this patient population.

 A study* was performed comparing 2 large cohorts of women with breast cancer who used vaginal estrogen therapy with women who did not use hormone replacement therapy (HRT). This trial assessed over 49,000 breast cancer patients and demonstrates the safety of vaginal estrogen therapy for this patient population. This cohort study analyzed 2 large cohorts of women aged 40 to 79 years with newly diagnosed breast cancer.

In vaginal estrogen therapy users compared with HRT nonusers, there was no evidence of a higher risk of breast cancer–specific mortality in the pooled fully adjusted model (HR, 0.77; 95% CI, 0.63-0.94).

 Results of this study showed no evidence of increased early breast cancer–specific mortality in patients who used vaginal estrogen therapy compared with patients who did not use HRT.

 This finding may provide some reassurance to prescribing clinicians and support the guidelines suggesting that vaginal estrogen therapy can be considered in patients with breast cancer and genitourinary symptoms.

 A Danish study involving 8461 patients with breast cancer that observed no association between vaginal estrogen therapy and cancer recurrence (adjusted HR, 1.08; 95%CI, 0.89-1.32).

 Another 4.5-year cohort study involving 13,479 breast cancer survivors found that local estrogen therapy did not increase the risk of cancer recurrence. Therefore, low-dose local estrogen therapy can be an option when other local treatments are ineffective

  Additionally, a case-control study showed no association between vaginal estrogen therapy and breast cancer recurrence among tamoxifen users but did not adjust for cancer stage

 Two small cohort studies found no increase in cancer recurrence in patients with breast cancer.

 An alternative to vaginal estrogen therapy is Intravaginal Dehydroepiandrosterone (DHEA )therapy.  According to the North American Menopause Society, intravaginal dehydroepiandrosterone (DHEA) may be prescribed to women with hormone-dependent cancers when non-hormonal treatments are ineffective. DHEA demonstrates positive effects on symptoms and vaginal pH.  DHEA is converted to estrogens intracellularly, avoiding systemic estrogen elevation.  It has not been reported to significantly alter active sex hormone levels after 12 weeks of use and does not affect endometrial cells.  However, since estrogen is a metabolite of DHEA, caution is advised when prescribing it to women with a history of hormone-sensitive cancer.***

 Use of phyto-estrogen vaginal preparations derived from plant sources has not demonstrated significant efficacy in this patient population.

 For a comprehensive discussion of assessment and management see” Vulvovaginal Atrophy Following Treatment for Oncogynecologic Pathologies: Etiology, Epidemiology, Diagnosis, and Treatment Options.” ***

 

 Selected References
*JAMAOncol.2024;10(1):103-108. doi:10.1001/jamaoncol.2023.4508
Published online November 2, 2023.

 ** Le Ray I, Dell’Aniello S, Bonnetain F, Azoulay L, Suissa S. Local estrogen therapy and risk of breast cancer recurrence among hormone-treated patients: a nested case-control study. Breast Cancer Res Treat. 2012;135(2):603-609.

***Narutytė R, Žukienė G, Bartkevičienė D. Vulvovaginal Atrophy Following Treatment for Oncogynecologic Pathologies: Etiology, Epidemiology, Diagnosis, and Treatment Options. Medicina (Kaunas). 2024 Sep 27;60(10):1584.

 The 2022 Hormone Therapy Position Statement of The North American Menopause Society” Advisory Panel. The 2022 hormone therapy position statement of The North American Menopause Society. Menopause. 2022;29(7):767- 794.

Cancer is on the rise in young adults

“Between1990 and 2019 the incidence of 29 cancers, including breast, lung and colorectal cancers has increased worldwide in people under the age of 50, particularly in women.  Mortality from these cancers has declined but the total number of deaths has risen Nature 627, 258-260 (2024) doi: https://doi.org/10.1038/d41586-024-00720-6

Historically we have considered cancer a disease of primarily persons over 50 years old.  While this is still the largest percentage of patients, there is an alarming rise in multiple cancer diagnoses in younger patients.

Comparing Gen X generation to their Baby Boomer parents:

Generation X is being diagnosed with more cancer than earlier generations in the United States  Gen X women had projected increases in thyroid, kidney, rectal, uterine, colon, pancreatic and ovarian cancers, as well as non-Hodgkin’s lymphoma and leukemia. Gen X men have forecasted rises in thyroid, kidney, rectal, colon and prostate cancers.

https://www.sciencenews.org/article/gen-x-more-cancers-baby-boomer-parents

The OutSmart Cancer® System is designed to teach all patients HOW TO CREATE A BODY WHERE CANCER CANNOT THRIVE.  Learn about it here: OutSmartCancer.com

 For colorectal cancer it is now recommended that the age for first screening should be lowered to age 45, five years earlier.

https://www.yalemedicine.org/news/colorectal-cancer-in-young-people

 Patient teaching should also change, making sure that any patient who has any change in their bowel habits that persists, if there is any rectal bleeding that persists, a colonscopy should be ordered to rule out colorectal cancer without delay.

Patients should learn about the importance of a high fiber, plant strong, colorful diet and the inclusion of fermented foods to fuel a healthy intestinal microbiota and importance of avoiding processed foods in favor of whole foods.

Breast Cancer rates have also steadily increased in women under 50 over the past 20 years with steep increases in more recent years. This is due to a surge of women diagnosed with estrogen receptor positive tumors.  https://medicine.wustl.edu/news/breast-cancer-rates-increasing-among-younger-women/

Because breast screening typically does not start until age 45, younger women should be instructed to perform self-breast exams monthly so that they can be familiar with their breast tissue and be able to identify changes early and seek an evaluation from a care provider without delay.

Lung cancer is on the rise in young non-smokers.  While overall rates of lung cancer have declined as smoking has declined, there is now a surge of lung cancer diagnoses among non-smokers and in patients under 40.  10% of lung cancer patients are below age 55.  Approximately 12% of all lung cancer patients are non-smokers. https://utswmed.org/medblog/lung-cancer-young-nonsmokers/

While etiology is not clear, it is reasonable to correlate the changes in lifestyle, food supply, eating habits and environmental toxic exposures over this period. 

Modern life is a risk factor for cancer with increasingly sedentary habits, less diverse and more processed foods and increased exposures to a wide variety of environmental chemicals from in-utero, to breast milk to processed baby foods as the first foods for many children, the disruption of microbiome  and the intestinal barrier by overuse of antibiotics and steroids and NSAIDs, the depletion of our soil and subsequent loss of nutrient dense food supply, the low intake of fiber in the modern diet along with high levels of stress and disrupted sleep cycles all impact our normal physiology and immunity and increase risk of cellular, mitochondrial and DNA damage and disruption setting the stage for many chronic illnesses including cancer.

A challenge with younger patients is that they may tend to be less self-aware, have a self-perception of low risk and engage with health care providers less frequently, thus are often diagnosed at later stages of cancer development.

Education and awareness targeting high-school, college age as well as younger adults in their 20s, 30s and 40s is key to promote healthy life style choices, avoid toxic exposures, improve quality of nutrients and promote healthy sleep habits as well as understand how to access preventive health care and screenings is crucial.

The OutSmart Cancer® System is designed to teach all patients HOW TO CREATE A BODY WHERE CANCER CANNOT THRIVE.  Learn about it here: OutSmartCancer.com

 

Early Assessment and Early Intervention are required

Ovarian cancers are most often diagnosed when they are already advanced and difficult to treat.

In 2021, there were an estimated 238,484 women living with ovarian cancer in the United States.

According to the National Cancer Institute over 50% of all women diagnosed with ovarian cancer die of this disease within 5 years.  These are tragic statistics.

Approximately 1.1 percent of women will be diagnosed with ovarian cancer at some point during their lifetime, based on 2018–2021 data, excluding 2020 due to COVID.

Symptoms of ovarian cancer can be hard to identify as they are vague and often resemble other common conditions. Pap smears are not diagnostic  and routine pelvic exams do not typically detect ovarian cancer at early stages.

But new study* shows promising signs ovarian cancer can be detected in its early stages. The study targeted women with four specific symptoms – bloating, abdominal pain, needing to pee frequently, and feeling full quickly – and put them on a fast track to see a specialist.

As a result, even the most aggressive forms of ovarian cancer could be detected in their early stages.

Frequently primary care providers will not take crucial step to RULE OUT ovarian cancer and often assume the woman is having only digestive, genito-urinary or menstrual symptoms.  It is crucial to look for ovarian cancer even when symptoms are mild and appear similar to common conditions.  After all, ovarian cancer is life threatening, hard to treat in advanced stages and takes the lives of many women.

So, what did the study find? And what could it mean for detecting – and treating – ovarian cancer more quickly?

Why is ovarian cancer hard to detect early?

Current gynecology guidelines state that women get tested for ovarian cancer only if they have symptoms for more than one month.  But many of the symptoms of ovarian cancer such as tiredness, constipation and changes in menstruation – are vague and overlap with other common illnesses.   Women must be taken seriously as reliable reporters of significant changes in their bodies and clinicians should not diminish their reporting. Rather than take a wait and see approach, a proactive, initiation of a diagnostic process should ensue without delay.

If diagnosed at Stage 1 and confined to the primary site with no spread, the five-year survival rate is 92%.  This makes early detection critical. 

Survival rates are linked to the stage at diagnosis.  Most women are diagnosed at Stage 3 or 4 with metastatic advanced disease.  If the cancer has spread to nearby lymph nodes, the survival rate is reduced to 72%. If the cancer has already metastasized and spread to distant sites at the time of diagnosis, the rate is only 31%.

Monitoring four key symptoms

Between June 2015 and July 2022, the researchers recruited 2,596 women aged between 16 and 90 from 24 hospitals across the UK.

They were asked to monitor for these four symptoms:

• persistent abdominal distension (women often refer to this as bloating)
• feeling full shortly after starting to eat and/or loss of appetite
• pelvic or abdominal pain (which can feel like indigestion)
• needing to urinate urgently or more often.

Women who reported at least one of four symptoms persistently or frequently were put on a “fast track pathway”. That means they were immediately referred to and seen by a gynecologist within two weeks.

A cancer antigen 125 (CA125) blood test was performed. (Positive in some but not all ovarian cancers).  And the patient also received a transvaginal pelvic ultrasound to visualize the ovaries and the pelvis.

 

Findings

Some 12% of women on the fast-track pathway were diagnosed with some kind of ovarian cancer.

A total of 6.8% of fast-tracked patients were diagnosed with high-grade serous ovarian cancer. It is the most aggressive form of cancer and responsible for 90% of ovarian cancer deaths.

Out of those women with the most aggressive form, one in four were diagnosed when the cancer was still in its early stages. That is important because it allowed treatment of the most lethal cancer before it had spread significantly through the body.

There were some promising signs in treating those with this aggressive form. The majority (95%) had surgery, and three quarters (77%) had chemotherapy. Complete cytoreduction – meaning all the cancer appears to have been removed – was achieved in six women out of ten (61%).

Because women may receive a thorough gynecologic exam only once every 1-2 years, this contributes to late diagnosis.  Furthermore, it is often the primary care provider who first hears complaints of fatigue, bloating, urinary frequency, dull abdominal pain, changes in bowel function, pain with intercourse.   It is the primary care provider who should take action and order a CA125 and a pelvic ultrasound.

What does this mean for detection?

The study’s findings suggest this method of early testing and referral for the symptoms leads to earlier detection of ovarian cancer

This study  points to the importance of public awareness  and primary care provider awareness about symptoms and timely assessment.

Clinicians should be able to recognize all the ways ovarian cancer can present, including vague symptoms like general fatigue.

Empowering women to recognize a set of four symptoms can help trigger testing, detection and treatment of ovarian cancer earlier.  Women can also ASK FOR serum testing and pelvic ultrasound and a thorough and thoughtful gynecologic workup.

Many women as well as many primary care providers remain unaware of early signs and symptoms of ovarian cancer. This study shows recognizing and reporting symptoms early and taking action to measure serum CA-125 and perform a pelvic ultrasound may help early detection and treatment and improve survival rates.

The OutSmart Cancer® System promotes regular screenings, early assessment and early intervention, empowering both patients and their primary care and specialty care providers to engage in a pro-health model.  With ovarian cancer, this saves lives.

 

Selected References

*Kwong FLA, et al. Int J Gynecol Cancer 2024;0:1–7. doi:10.1136/ijgc-2024-005371 Symptom-triggered testing detects early stage and low volume resectable advanced stage ovarian cancer

Ovarian Cancer: The Recognition and Initial Management of Ovarian Cancer. Cardiff (UK): National Collaborating Centre for Cancer (UK); 2011 Apr. PMID: 22479719.

Brain KE, Smits S, Simon AE, Forbes LJ, Roberts C, Robbé IJ, Steward J, White C, Neal RD, Hanson J; ICBP Module 2 Working Group. Ovarian cancer symptom awareness and anticipated delayed presentation in a population sample. BMC Cancer. 2014 Mar 10;14:171. doi: 10.1186/1471-2407-14-171. PMID: 24612526; PMCID: PMC3975332.

Bloomfield HE, Olson A, Greer N, Cantor A, MacDonald R, Rutks I, Wilt TJ. Screening pelvic examinations in asymptomatic, average-risk adult women: an evidence report for a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2014 Jul 1;161(1):46-53. doi: 10.7326/M13-2881. PMID: 24979449.

 

 

 

Transforming the management of cancer with personalized testing

Signatera™(by natera.com  laboratories)  is a highly sensitive and personalized molecular residual disease assay (MRD) using circulating tumor DNA (ctDNA), custom designed for each patient to help identify relapse earlier than standard of care tools.

Medicare and many private insurance carriers now cover the cost of cftDNA monitoring.

Why circulating tumor DNA (ctDNA) for MRD assessment?

• Cancer cells release circulating tumor DNA (ctDNA) into the bloodstream
• ctDNA is a powerful tool that can be measured to assess the absence or presence of molecular residual disease (MRD)
• Dynamic real-time biomarker: the normal half-life is less than an hour

Signatera™ is covered by Medicare for monitoring disease progression, disease recurrence, or relapse for patients with:

• Stage II-IV and oligometastatic colorectal cancer (CRC) in the adjuvant and recurrence monitoring settings
• Muscle invasive bladder cancer (MIBC) in the adjuvant and recurrence monitoring settings
• Stage II-IV breast cancer in the neoadjuvant setting, regardless of subtype
• Stage IIb and higher breast cancer in the adjuvant and recurrence monitoring settings
• Stage II-IV ovarian, fallopian tube, or primary peritoneal cancer in the adjuvant and recurrence monitoring settings
• For monitoring of response the immune-checkpoint inhibitor (ICI) therapy for patients with any solid tumor

Clinical applications of ctDNA testing for MRD assessment:

Signatera™ has significant predictive value for long-term patient outcomes

The only significant risk factor in stage II-III colorectal cancer5‑8

In multivariate statistical analysis, MRD status as measured by Signatera™ was the only significant predictor of long-term cancer patient outcomes, after adjusting for all known clinicopathological risk factors including disease stage and lymph node status.1

Will my patient benefit from adjuvant chemotherapy?

When to use Signatera™ MRD test?

Adjuvant setting

• Use after to surgery to evaluate the need for adjuvant chemotherapy
• To personalize and help inform when to escalate or right-size treatment

Surveillance setting

• Detect MRD with greater sensitivity than current standard of care tools
• Use Signatera™ alongside CEA to detect relapse earlier and reduce false positive CEA results

 Determining which colorectal cancer patients benefit from adjuvant chemotherapy isn’t always clear using current standard of care tools. The GALAXY study set out to better understand if a personalized ctDNA assay can aid risk stratification, better than TNM staging for recurrence.

Check out recent findings published in Nature Medicine

Study Overview: CIRCULATE-Japan (prospective large-scale registry)

• 1,039 patients with Stage II-IV colorectal cancer (CRC), enrolled into the observational GALAXY arm of CIRCULATE-Japan, with median clinical follow up of 16.7 months; a subset of patients received adjuvant treatment (ACT) at physicians’ discretion
• Results were analyzed to determine 18-month disease-free survival (DFS), by molecular residual disease (MRD) status and by treatment status.1

Signatera™ Residual Disease Test (MRD) positivity may be prognostic of survival outcomes post-surgery:

• MRD positivity in patients 4 weeks after surgery were associated with a significantly higher risk of recurrence and inferior disease-free survival (DFS) at 18 months of follow-up (HR 10.0, p value <0.0001), regardless of stage.

Medicare Coverage

Signatera™ is covered by Medicare for monitoring disease progression, disease recurrence, or relapse for patients with:

• Stage II-IV and oligometastatic colorectal cancer (CRC) in the adjuvant and recurrence monitoring settings
• Muscle invasive bladder cancer (MIBC) in the adjuvant and recurrence monitoring settings
• Stage II-IV breast cancer in the neoadjuvant setting, regardless of subtype.
• Stage IIb and higher breast cancer in the adjuvant and recurrence monitoring settings
• Stage II-IV ovarian, fallopian tube, or primary peritoneal cancer in the adjuvant and recurrence monitoring settings
• For monitoring of response to immune-checkpoint inhibitor (ICI) therapy for patients with any solid tumor

NB: OutSmart Cancer® has no financial relationship with natera.com laboratories

Other laboratories are emerging that also monitor cftDNA.

 

Breast cancer (BRCA) is a highly heterogeneous systemic disease.
Breast cancers can relapse and metastasize to multiple organs.
Metastatic Breast Cancer (mBRCA) is cancer that has spread (metastasized) to other organs.

An estimated 168,000 women in the United States are living with metastatic breast cancer.

 

Nearly 30% of women initially diagnosed with early-stage breast cancer will ultimately develop metastatic breast cancer.

Approximately 85% of patients diagnosed with metastatic breast cancer have had an early-stage breast cancer diagnosis. However, most patients with early-stage breast cancer do. not go on to develop metastatic disease. 

Some women may live for 10 years or longer with metastatic breast cancer

Approximately 15% of patients with metastatic breast cancer are found to have metastatic spread at the time of the initial breast cancer diagnosis. This is called de novo metastatic breast cancer.

Over half of advanced breast cancers metastasize to the bone. 

Recent studies have revealed that breast cancer subtypes differ not only in primary tumor characteristics but also in their metastatic behavior.

• Luminal type breast cancers commonly metastasize to the bone.
• Her2neu breast cancers commonly metastasize to the liver
•  Her2neu has been associated with increased metastasis and invasiveness.
• Triple-negative breast cancers are predisposed to lung and brain metastases.
• Triple-positive breast cancer (TPBC) , positive for receptors for Estrogen, Progesterone and can metastasize to bone,  lungs, brain and liver.

          

Metastatic breast cancer symptoms can vary based on the location of metastatic lesion

• General: Profound fatigue or malaise, loss of well being, unexplained weight loss,             difficulty with urination or bowel movements
• Lungs – Dry cough, hoarse voice, shortness of breath and difficulty breathing
• Liver – Jaundice, nausea, pain or swelling in the belly, change in bowel habits, loss of appetite and itchy skin or rash
• Brain – Blurred vision, dizziness, headaches, loss of balance, frequent nausea or vomiting, confusion and memory problems, change in speech or handwriting, seizures, mood and behavior changes
• Bones – Swelling, bone fractures and back, neck, bone or joint pain

Teach patients to listen to their body and to report symptoms that persist for more than 5 days. Patients are usually the first to notice when something is not right.

Many oncologists do not monitor the tumor microenvironment, or the “cancer terrain”.  In integrative oncology we assess the whole biosystem that may host cancer development and progression.

Screening for metastatic  progression includes:

Radiology scans: Bone Scan, CT, PET, PET-CT, MRI

Blood tests, including 

• BRCA Tumor markers: CEA, CA 15-3. CA 27.29
• Cell free tumor DNA (liquid biopsy)
• Biomarkers of cancer metabolism reflective of the tumor microenvironment including,but not limited to 
  • Inflammation: CRP, IL-1, IL-6, IL-8, ceruloplasmin, ferritin, sedimentation rate (ESR)
  • Hypercoagulation: fibrinogen, d-dimer
  • Growth, Progression and Metastastis: VEGF, TGFb, FGF, IGF-1, Her2neu, copper, ceruloplasmin

Breast cancer survivors who have been in remission or those who are living with breast cancer as a chronic illness must be followed closely and screened for disease progression by their care teams over the long term.  This team may include be primary care, gynecologist, surgeon, radiologist, medical oncologist and integrative care providers. 

Patients must be educated about the importance of ongoing screening and monitoring and keeping their appointments

Because of the typical age demographic for BRCA patients, there are commonly co-morbid conditions.  

The OutSmart Cancer® is a whole person, whole health system. We advise patients to receive ongoing health monitoring along with disease monitoring including assessment for 

• Healthy weight
• Healthy Body Composition: Bone Mass, Muscle Mass, Fat Mass
• Healthy Cognitive Function
• Cardiovascular Health
• Immune Health and Inflammation Control
• Joint and Musculoskeletal Health and Mobility
• Neurological Health and Function
• Emotional and Psychological Health
• Digestive, Intestinal and Microbiome Health
• Healthy Sleep Cycle
• Healthy Stress and Life Management
• Support System: Community, Family 
• Activities of Daily Living
• Healthy Dietary Patterns: Follow OutSmart Cancer® Dietary Guidelines
• Healthy Endocrine Function
• Healthy Glycemic Control
• Vitamin, Mineral, Macro and Micro-nutrient status
• Monitor and Manage Nutriceutical, Botanical and Phytochemical supplementation
• Monitor Lifestyle factors that influence risk and promote health

In order for health and healthy function to be our outcome, there must be a plan for creating and sustaining health over the long term.

There is an explosion of BRCA research and promising advancements and deeper understanding that is continually developing.

Metastatic BRCA must be monitored and can be managed and treated. Best outcomes result from combining the best of modern oncology and integrative health focused screening and  care.

Selected References 

• Quick facts on metastatic breast cancer
• Metastatic Breast Cancer
• Breast cancer as a systemic disease: a view of metastasis
• Bone metastasis risk factors in breast cancer