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Recognizing Signs of Metastatic Breast Cancer

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 

From Moles to Melanoma: The ABCDE Rule for Identifying Melanoma Skin Cancers

Melanoma of the skin the 5th most common cancer in the United States.

Melanoma is a potentially lethal form of skin cancer that begins in the melanocytes, the cells that make the pigment melanin.  Melanoma represents one of the deadliest forms of skin cancer and is characterized by early metastasis and rapid development

 It may begin as a mole (skin melanoma) but can also begin in other pigmented tissues such as in the eye or in the intestines.

It can appear anywhere on the skin, but is often found on the arms, back, face, and legs, which are most often exposed to the sun. 

Melanoma can be very treatable if caught early, and over 95% of skin cancers can be successfully treated if found early.  However, the survival rate for advanced stage melanomas is only 32%. Therefore, early diagnosis is crucial.

There is an ABDCE RULE that describes warning features that could signify a skin melanoma:

  • A is for asymmetry, if the shape of one half of the mole does not match the other.

  • B is for border. A mole with blurred, irregular edges could be concerning.

  •  C is for color, meaning a mole that has multiple colors and shades.

  • D is for diameter. Some melanomas can be very small, but most are over 6 millimeters, about ¼ inch, wide.

  • E is for evolving, meaning that the mole has changed over the past weeks or months.

Anyone who notices these features of a mole should be assessed by a dermatologist.  In addition, people who notice a new growth, a spot or bump that is increasing in size over time, a skin discoloration that is causing discomfort or a sore that does not resolve should also seek medical attention.

The exact cause of all melanomas is not clear. Most melanomas are caused by exposure to ultraviolet light. from sunlight or tanning lamps and beds.

Limiting exposure to ultraviolet light can help reduce the risk of melanoma.

Hidden melanomas

Melanomas also can develop in areas of the body that have little or no exposure to the sun. These areas may include the spaces between the toes and on the palms, soles, scalp or genitals. These are sometimes referred to as hidden melanomas because they occur in places most people wouldn't think to check. When melanoma occurs in people with brown or Black skin, it's more likely to occur in a hidden area.

Hidden melanomas include:

  •   Melanoma inside the body. Mucosal melanoma develops in the mucous membrane. This tissue lines the nose, mouth, esophagus, anus, urinary tract and vagina. Mucosal melanomas are especially difficult to detect because they can easily be mistaken for other far more common conditions.
  •   Melanoma in the eye. Eye melanoma also is called ocular melanoma. It most often occurs in the layer of tissue beneath the white of the eye. This layer is called the uvea. An eye melanoma may cause vision changes and may be diagnosed during an eye exam.
  •   Melanoma under a nail. Acral-lentiginous melanoma is a rare form of melanoma that can occur under a fingernail or toenail. It also can be found on the palms of the hands or the soles of the feet. Acral-lentiginous melanoma tends to be very dark, flat and have very unusual borders. It's more common in people of Asian descent and people with brown or Black skin.

https://www.mayoclinic.org/diseases-conditions/melanoma/symptoms-causes/syc-20374884

A sun safe lifestyle includes avoiding midday sun, seeking shade, regular use of and frequent re-application of non-toxic and reef safe SPF 30 or higher sunscreen, wide brimmed sun hats and UV blocking sunglasses, clothing and swimwear for a comprehensive approach. 

Oxidative stress and redox homeostasis are implicated in all phases of the development and progression of melanoma as well as in the emergence of drug resistance.

Improving intracellular antioxidant capacity may be achieved through dietary nutritional optimization.

Nutritional interventions may include a diet that provides

Antioxidant, sulforaphane, flavonoid and polyphenol rich fruits and vegetables and green tea catechins

as well as foods and supplements rich in Vitamin A, E, C, Niacinamide, N-Acetylcysteine, Selenium, Zinc, and Taurine have been shown to be mildly protective. 

Curcumin and resveratrol have also been shown to increase intracellular antioxidant status.

Omega 3 Fatty Acids EPA and DHA promote inflammation control and have been shown to impact melanoma development and progression

We encourage our patients to EAT THE RAINBOW and include a wide variety of plant pigments from colorful fruits and vegetables. Patients can also include concentrated greens and reds powders as an additional and convenient source of protective phytochemicals

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10252072/

OutSmart Cancer® recommends non-toxic chemical free reef safe sunscreens.

Mineral based sunscreens are generally safe and rarely irritate the skin

We recommend checking the Environmental Working Group sunscreen ratings to identify the safest sunscreen products: https://www.ewg.org/sunscreen/

 

Misleading Article Linking Progesterone to Brain Meningiomas

In a recently published paper titled “Use of progestogens and the risk of intracranial meningioma: national case-control study” by Noémie Roland, Anke Neumann et al* the authors assessed the impact of multiple forms of progesterone on the development of brain meningiomas.   The statements in this paper could lead a journalist or patient or anyone not performing a close reading of this study to the false conclusion that all forms of progesterone are linked to brain lesions.  This is not true.

A meningioma is type of lesion is usually noncancerous tumor that arises from the membranes surrounding the brain and spinal cord.  Sixty percent of intracranial meningiomas examined expressed progesterone receptors.  

 The authors investigated multiple forms of progesterone including synthetic progestogens. The forms of progesterone included in the study were progesterone, hydroxyprogesterone, dydrogesterone, medrogestone,medroxyprogesterone acetate, promegestone,dienogest, and intrauterine levonorgestrel.

 

In naturopathic and integrative medicine bioidentical compounded progesterone is typically used and is labelled “progesterone” and may be used in oral, topical or vaginal forms.

 The study was conducted in France over 10 years from January 2009-December 2018.  The study investigated 108, 366 women who had surgery for meningiomas and these were matched to controls.

The authors concluded that no excess risk of meningioma was associated with the use of progesterone, dydrogesterone, or spironolactone, or the hormonal intrauterine systems used worldwide, regardless of the dose of levonorgestrel they contained.”

Meningiomas may also be associated with age over 65, neurofibromatosis type 2 and exposure to ionizing radiation. Meningiomas are also associated with and may enlarge during pregnancy when progesterone levels are normally elevated in support of the pregnancy.  Furthermore, the authors observed decreasing dosing and withdrawal of  progestogens generally led to a reduction in meningioma volume.

“Prolonged use of medrogestone, medroxyprogesterone acetate, and promegestone was found to be associated with an increased risk of meningioma. Future studies should further clarify the association between the duration of use and risk for the progestogens studied and extend the discussion of meningioma risk to dienogest and hydroxyprogesterone.”

Should you receive questions from concerned patients who are using bio-identical progesterone or levonorgestrel found in many intra-uterine devices on the basis of this study, please do review with them the safety, risks and benefits. 

This is yet another example that in the realm of prescribed hormone replacement therapies that it is vital to be clear about the difference between different forms of  hormones and synthetic hormone mimetic drugs.   Too often these are all labeled progesterone or estrogen in the news and are misunderstood by the general public, our patients.  It is our responsibility to make sure patients are well educated and fully informed and have access to reliable information about their health and medical choices.

 Using any type of hormone therapy is a decision made between a patient and their healthcare provider after carefully weighing the risks and benefits. Bioidentical hormones have been controversial, and many are not FDA-approved, but that doesn't mean a healthcare provider will rule them out as a treatment option.

*Roland N, Neumann A, Hoisnard L, Duranteau L, Froelich S, Zureik M, Weill A. Use of progestogens and the risk of intracranial meningioma: national case-control study. BMJ. 2024 Mar 27;384:e078078. doi: 10.1136/bmj-2023-078078. Erratum in: BMJ. 2024 Mar 28;384:q776. PMID: 38537944; PMCID: PMC10966896.

Can Breast Cancer Patients Avoid Lymph Node Removal?

Historically women diagnosed with breast cancer have received surgery, chemotherapy, targeted therapy, radiotherapy and if estrogen receptor positive, hormonal therapy as standard of care, all of which come with short term and long-term adverse effects.  This approach is now considered to be over-treatment for some patients.  All women should receive thorough assessment to determine if they will or will not benefit from radiotherapy, chemotherapy, hormonal therapy and targeted therapies.  Individualized care plans must become the norm for all women with breast cancer.

In the era of personalized medicine, there are now assessments such as Oncotype DX**, that can determine if chemotherapy or hormonal therapy would provide the most benefit, or no benefit. As a result, many women who previously would have received chemotherapy, no longer suffer exposure to toxic systemic therapy as part of their treatment plan without compromise to survival.

Another study*** has demonstrated that radiotherapy may be unnecessary for some breast cancer patients who are diagnosed at an early stage. After breast conserving surgery a subset of patients who have received neoadjuvant systemic therapy may be able to forgo adjuvant radiotherapy with no impact on long term survival.  This avoids the early and late adverse effects of radiotherapy and contributes to preserving quality of life.

Additionally a recent study* determined that it is feasible and safe to omit axillary lymph node resection surgery in early breast cancer patients who have an excellent response to primary systemic neo-adjuvant therapy. Annemiek Van Hemert, MD, of the Netherlands Cancer Institute in Amsterdam reported that “Breast cancer patients with lymph node positive breast cancer may avoid extensive axillary surgery if they have clear nodes after systemic neoadjuvant chemotherapy.

 

She further states, “If we are able to predict the response based on the removal of only one lymph node, it means we can safely avoid extensive removal of the lymph nodes if no living tumor cells are left,” Van Hemert said in a statement. “This will avoid serious complications, such as painful swelling in the arm, known as lymphedema.”   This allows effective treatment as well as less harm to patients.

This study was conducted over a period of 8 years from 2014-2021 and is ongoing and there will be more long-term outcomes data in the future.

Patients in this study were both hormone receptor negative and positive.  Patients were both her2neu negative and positive. There were triple negative patients in the study as well.  Patients who had 3 or more axillary nodes were selected to participate in this study.  Node staging was ascertained by PET-CT prior to systemic treatment.  The largest node was marked with radioactive iodine. After systemic treatment this node was excised and evaluated for response to treatment.

Patients who achieved a complete lymph node response to neoadjuvant chemotherapy or targeted treatment (47%) received only radiation therapy and no lymph node dissection.  Patients with residual lymph node disease (53%) received surgical lymph node dissection followed by radiotherapy.

After 44 months, the group with complete lymph node response after neoadjuvant treatment had a Recurrence Rate of 3.2%, Disease Free Survival rate of 85% and and Overall Survival Rate of 93%.   The group with residual disease after neoadjuvant therapy had had similar outcomes of 3.5%. 90% and 82% respectively.

The study concluded that “Surgical removal of axillary nodes can be safely omitted in about 80% of patients treated with primary systemic therapy.”

This is an ongoing study that will continue long-term follow-up.

Dr Fiorita Poulakaki, Head of the Breast surgery Department at Athens Medical Centre Hospital, Greece, and Vice President Europa Donna, the European Breast Cancer Coalition, commented

 “When we treat patients for breast cancer, it is important to ensure that treatment itself causes as little harm to the patients as possible. The results from this study suggest a way to help us avoid side effects that affect the quality of life and can sometimes cause considerable long-term distress to patients. Every day we cure patients, making sure they live long lives, but at the same time we should care also about survivorship issues.”

 As advocates, guides and counselors for our patients, we can educate our patients to initiate a discussion with her oncology team to practice highly individualized decision making so that the most appropriate care plan is put in place for each patient which considers quality of life, life span as well as health span. 

This is fundamental to the OutSmart Cancer® System which includes individualized assessments, consideration of the tumor microenvironment and a whole biosystem approach.  Furthermore, the OutSmart Cancer® provides for a HEALTH PLAN, not just a disease plan for each patient at every stage of their cancer journey.

 

Selected References

*Charles Bankhead, Senior Editor, Study Shows Feasibility, Safety of Omitting Axillary Surgery in Early Breast Cancer. Pathologic CR to guide treatment decisions led to similar 

outcomes in node-positive disease    MedPage Today March 22, 2024

 

van Hemert AKE, van Olmen JP, Boersma LJ, et al. De-ESCAlating RadioTherapy in breast cancer patients with pathologic complete response to neoadjuvant systemic therapy: DESCARTES study. Breast Cancer Research and Treatment. 2023 May;199(1):81-89. DOI: 10.1007/s10549-023-06899-y. PMID: 36892723.

 

**The Oncotype DX Breast Recurrence Score® test https://precisiononcology.exactsciences.com

Study: Managing Cancer Treatment Side Effects with Chinese Herbs

In January 2023, Memorial Sloan Kettering Cancer Center published a study* demonstrating the safe and effective use of Chinese Herbal Medicines for the management of short-term adverse effects of cancer treatments. The study was a joint effort between the Cancer Center, Pharmacy, Herbal Oncology Program and Integrative Medicine Departments and demonstrates the safe and effective concurrent use of selected Chinese Herbal Formulas to manage and resolve selected adverse effects and promote and restore normal healthy function.

The following Chinese Herbal Formulas were studied in the management of three common adverse effects of cancer treatments:

         Chronic Insomnia: Jia Wei Suan Zao Ren

         Constipation: Ma Zi Ren Wan

         Chronic Diarrhea: Shen Ling Bai Zhu San


These common formulas are readily available from multiple high-quality suppliers and can be found in capsule, tablet and freeze-dried granule forms. **  These formulas can also be compounded by a Chinese Herbal Pharmacy and made into teas.  Chinese Herbal Formulas are typically dosed 2-4x per day taken with warm water or tea and with meals. 

There were 851 outpatients in the study.  84% of participants were undergoing active treatment for multiple cancers.  The Herbal Oncology Program dispensed 1,266 prescriptions over the course of the study to address pain, fatigue, poor appetite, gastrointestinal and mood disorders as well as disrupted sleep related to treatment.   Participants surveyed expressed the need to seek treatment for unmet needs for management of adverse effects and support for health and quality of life. 

The study demonstrated a high level of participant satisfaction and relief while incorporating Chinese Herbs into their care plan with the support of their oncology team.  The formulas selected were of high-quality vetted ingredients, supported by research, and provided excellent symptom management as well as restoration of healthy function, and did not interfere with their oncology treatments.

 

The study team reports that patients requested and received support for acid reflux, bloating and indigestion, dizziness, fatigue inflammation, insomnia, mood, nausea and vomiting, pain, and other unspecified adverse effects.  Additional herbal prescriptions were dispensed for acute cold and flu, cough, as well as for symptoms of fatigue, allergy, dizziness, and hot flashes, but were not part of the study formulations.

 Comments:   

The use of Modern Chinese Herbal medicine is well supported by research and wide clinical use.  

Many Chinese Herbal formulas, such as those used in this study, fall into a “nutritive” category in which tissue repair and normalization and enhancement of structure and function can be achieved without deleterious drug-herb, radiotherapy-herb, immune-therapy or targeted therapy-herb interactions.  

I regularly recommend Chinese Herbal Medicines as well as Acupuncture for management of adverse effects of treatments and for nurturing, promoting, and restoring normal healthy function. This allows patients not only to be able to successfully complete their course of treatments, but also to enjoy and maintain healthy function and quality of life.  This also gives the patient a sense of agency and control and the feeling that they are taking something life giving and non-toxic as well as efficacious.

Symptom management of adverse effects in conventional oncology usually adds more pharmaceuticals to the care plan and rarely results in repair or sustained restoration of healthy function and can come with additional drug toxicities.

This study serves as a prototype for future studies and demonstrates both the safety and efficacy of Chinese Herbal Medicines for managing and resolving common adverse effects of cancer treatments.  This study is also a model of collaborative teams composed of clinicians with diverse skilsl and training working together with mutual respect in service to best outcomes for patients.  

This is inherently the model of the OutSmart Cancer® System which is devoted to multi-disciplinary, multi-faceted, cooperative, and inclusive teams that offer both the best disease care along with a health model for cancer patients and cancer survivors. 

If health is the desired outcome, there must be a plan for HEALTH designed and implemented by health experts on the team. This fills in the missing health side of the cancer equation in conventional oncology care which remains disease focused and is therefore limited and not comprehensive.  

I have been privileged and honored to be able to demonstrate the value of this model over 35 years of clinical practice in concert with leading oncology teams that realize the value of including a multi-faceted integrative approach that contributes a health model for their patients.

 

 *Hou YN, Chimonas S, Gubili J, Deng G, Mao JJ. Integrating herbal medicine into oncology care delivery: development, implementation, and evaluation of a novel program. Support Care Cancer. 2023 Jan 21;31(2):128. doi: 10.1007/s00520-023-07577-x. PMID: 36680628; PMCID: PMC9860233.

**I recommend and have no affiliations with these high quality Chinese Herbal Suppliers: Sun Ten, Blue Poppy, Evergreen, May Way Herbs, TCMZone, to name a few.

Additional Selected References

Yang M, Feng Y, Zhang YL, Smith CM, Hou YN, Wang H, Deng G, Mao JJ. Herbal formula MaZiRenWan (Hemp Seed Pill) for constipation: a systematic review with meta-analysis. Phytomedicine. 2021;82:153459.doi: 10.1016/j.phymed.2021.153459. [PubMed] [CrossRef] [Google Scholar]

 Wang H, Hou YN, Yang M, Feng Y, Zhang YL, Smith CM, Hou W, Mao JJ, Deng G. Herbal formula Shenling Baizhu San for chronic diarrhea in adults: a systematic review and meta-analysis. Integr Cancer Ther. 2022;21:15347354221081214. doi: 10.1177/15347354221081214. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Xiang Y, Guo Z, Zhu P, Chen J, Huang Y. Traditional Chinese medicine as a cancer treatment: modern perspectives of ancient but advanced science. Cancer Med. 2019;8(5):1958–1975. doi: 10.1002/cam4.2108. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Soy Intake Linked to Improved Survival in Breast Cancer

Confused about soy isoflavones, soy foods and risk of breast cancer? A recent study concluded that natural phytoestrogens including isoflavone compounds derived from soy and other plants reduce breast cancer recurrence and improve survivalResults from a study conducted at Johns Hopkins Kimmel Cancer Center, “Phytonutrients and outcomes following breast cancer: a systematic review and meta-analysis of observational studies.” were published in January 2024.

Researchers concluded that soy isoflavones were associated with a 26% reduced risk of breast cancer recurrence among post-menopausal women breast cancer survivors. The most significant results were realized at 60 milligrams per day.

 

Soy contains isoflavone compounds including genistein and daidzein. Isoflavones are phytoestrogens, that have a similar structure to human 17-β estradiol hormone. Phytoestrogens bind to and mildly activate estrogen receptors and act as selective estrogen receptor modulators. Phytoestrogens block the binding of native estrogen and thus block the effects of human estradiol.  Phytoestrogens exert a very mild effect on estrogen activation compared to human estradiol.  Therefore, there is less estrogen activation and signaling in the presence of isoflavone phytoestrogens.

Another review, Soy Isoflavones and Breast Cancer Risk: A Meta-analysis, conducted by Ioannis Boutas, et al in 2022 concluded, “The consumption of soy isoflavones can reduce the risk of breast cancer in pre-menopausal and post-menopausal women.

A review conducted in 2023, .” Benefits of Soybean in the Era of Precision Medicine: A Review of Clinical Evidence, Jung Hyun Kang, et al, examined the current clinical evidence focusing on the benefits and risks of soybean ingredients and concludes “In breast, prostate, colorectal, ovarian, and lung cancer, epidemiological studies showed an inverse association between soybean food intake and cancer risks. Soybean intake was inversely correlated with risks of type 2 diabetes mellitus (T2DM), and soy isoflavones ameliorated osteoporosis and hot flashes. Notably, soybean was one of the dietary protein sources that may reduce the risk of breast cancer and T2DM.”

Additionally, as early as 2010 Dr. Mary Hardy MD of UCLA Simms Mann Center for Integrative Oncology, Dr. Donald Abrams MD of UC San Francisco Center for Integrative Medicine and Dr. Mark Messina, Ph.D., professor of nutrition a Loma Linda University, CA, co-authored a paper, Can clinicians now assure their breast cancer patients that soyfoods are safe? (Women's Health (2010)6(3), 335–338, addressing the confusion that exists among physicians and patients regarding the health consequences of soy foods and soy isoflavones.  In this paper they identify soy isoflavones as selective estrogen receptor modulators.  They conclude that it is safe for women to include whole, minimally processed soy foods including tofu, soy milk, whole soybeans (like edamame), miso, soy yogurt, and tempeh, in their diets, but that soy foods and soy isoflavones should not be considered as treatment for breast cancer.

 

There is now a clear body of evidence not only demonstrating the safety of phytoestrogens contained in soy and other botanicals, but also their benefits which include the potential reduced risk and reduced recurrence of breast cancer, support for control of menopausal symptoms such as hot flashes and osteoporosis as well as reduced risk of Type 2 Diabetes.

Guiding Patients Through All Stages of The Cancer Journey: The Final Chapter

 

Over many decades I have created and honed my OutSmart Cancer® System so that patients have a Health Plan not just a disease plan as well as the tools and knowledge to Create A Body Where Cancer Cannot Thrive.

 

 

My OutSmart Cancer® System includes addressing the unique needs and challenges of five major stages of the Cancer Journey. 

  • Just Diagnosed/Shock, Overwhelm, Acceptance/Preparation
  • In Treatment/Staying Healthy/Managing Side Effects/Quality of Life
  • After Treatment/Recovery/Restoration/Rejuvenation
  • Life Beyond Cancer/Remission/Cure/No Evidence of Disease
  • Living with Cancer As a Chronic Illness/Living Well, Managing Side    Effects/Quality of Life

There is indeed a Sixth Stage. Some patients will die while under our care. 

We must support them, or refer appropriately so that they can accept that they are facing End of Life and that the cancer is stronger and smarter than the treatments we have available and that it is time to prepare on all levels and in all ways for the dying process and the final exhale.

It is always difficult to begin the conversation, but it is essential that at least ONE of the patient’s care providers be comfortable with a very frank and real and compassionate conversation with the patient, their family and circle of care of what MAY lie ahead.

It is our role to be available for this process and dialogue or to refer appropriately to clinicians who will address their questions and concerns and make sure they have the resources for a peaceful, healing, comfortable and compassionate dying process and final exhale.  If you are not comfortable or trained to do so, please explicitly tell the patient you will refer them to a clinician who can do so.  Make sure you have trusted resources in your community for them.

It is shocking to me HOW MANY oncologists do not have this conversation until the patient is perhaps not even capable of planning for themselves and their loved ones.

It is my personal and professional belief that every person deserves to know what is happening to them and what to expect and that they may indeed be facing their mortality.  But before that final breath, there is a potential to create a healing and integrative journey and a plan for a peaceful and conscious dying process.  

I am thinking now of one particular patient whom I treated for many years for extremely aggressive and recurrent fallopian tube cancer

She engaged fully in an integrative approach including OutSmart Cancer diet, lifestyle, supplements, acupuncture, high dose IV Vitamin C and mistletoe therapies. Her very forward thinking and collaborative oncologist offered her many many options, but her cells became resistant quickly after only a month or two of treatment with each try. Eventually she developed malignant ascites, a dire prognostic sign. 

Finally her care providers’ and the patient’s collective decision was to have her enter into compassionate hospice care. The patient accepted this decision with grace as I had started talking with her about her treatment resistance, the aggressive nature of her cancer and what it means prognostically when malignant ascites develops and progresses.  She was well aware that she could die of this cancer with this presentation and history.  I knew that she had not properly prepared fully for her children and that she would have to entangle her business and plan for that transition as well.   And it was time for her to accept and begin to reflect and ponder the end of life and death and dying.   We talked frankly and explicitly about the need to prepare practically, emotionally and spiritually.   

Although she accepted her death, she stated that she was fearful.  She was in a lot of pain which gave her the most anxiety.   This is true of many patients, it is the pain, suffering and anxiety and not having any familiarity with the dying process that makes them most uncomfortable.

Because I made sure she had lead time, she prepared legally, financially and practically for herself and her children.  I encouraged her to work with a therapist to help her to talk with her children.   But she really did not have the tools or the inner development to meet the dying process, contemplate it and find a way to dissipate her fear and have a peaceful transition.

My last conversations with her were about this very process, what to expect, how to plan a peaceful process, how to create the environment and support she wanted to have and to reassure her that hospice physicians and nurses are exceptionally thoughtful and compassionate and attuned human beings who would keep her comfortable, manage her pain and let her know what was unfolding at every step of the way.

Although her oncologist ordered hospice care for her, these most important conversations were not included.   

In person-centered models of medicine, it is the RELATIONSHIP between the patient and the doctor….two tender human beings that matters most at the end.   

I encourage all of you to step into these conversations with your patients.  The only way to become comfortable with them is to practice practice practice.   Start by contemplating your own death and you will find your way.

And so I have realized that there is indeed a Sixth Stage of the Cancer Journey in my OutSmart Cancer® System for some patients and that is the acceptance and conscious, compassionate and potentially healing and transformational journey to the End of Life.

Books I recommend for Patients and Families:

A Beginner’s Guide to The End, Practical Advice for Living Life and Facing Death, BJ Miller 

The Art of Dying Well, A Practical Guide to a Good End of Life, Katy Butler

Maintaining and Increasing Muscle Mass in Cancer Patients

Sarcopenia (loss of muscle mass) is an integral and deleterious component of cancer physiology. The metabolism of the tumor microenvironment is catabolic even at the earliest stages of cancer, long before the patient or care provider can see that muscle mass is declining. It is therefore my practice to include a plan for preserving and maintaining muscle mass in all patients.   For those patients who have already lost significant muscle mass it is very challenging.  When a patient has already suffered abnormal weight loss it is still possible to at least stop the decline and at best produce weight gain as muscle.

Tumor burden drives catabolism along with physiologic and behavioral contributors that include adverse effects of cancer treatments, nausea, loss of appetite, pain, changes in digestive function along with the emotional and traumatic stressors of the cancer experience that impact self care and eating behaviors.

Additionally, as the age demographic for cancer patients is typically patients over 50 years of age, the physiology of aging itself is already contributing to the loss of muscle mass that becomes more catabolic each year.   The increased catabolic state that accompanies tumor burden compounds the fact of loss of muscle mass.

 

The guideline for optimized protein intake for older patients is about 1 gram of protein per pound of body weight.  I therefore recommend that patients include 30 grams of protein three times daily from food at a minimum.   And an additional 20-30 grams on top of that.  The supplement can come in the form of free form amino acids or a serving of protein powder in water which are very easy for patients to implement.  

Leucine is a primary branch chain amino acid that is the anabolic signal to skeletal muscle. 

Leucine is abundant primarily in animal proteins.  I recommend vegans consider a branch chain amino acid supplement that supplies 2.5-3 grams of leucine per serving.  A person who eats 30 grams of animal protein will be getting a sufficient dose of leucine and does not need to supplement their meals.

Here is my general recommendation for supplements in addition to 30 grams of protein from food 3 times daily for retaining and building muscle mass:

Branch Chain Amino Acids 1 serving in water twice daily on empty stomach (containing 2.5-3.0g leucine per serving)

Some BCAA products also contain L-glutamine which also contributes to and is the most abundant amino acid in skeletal muscle tissue.

The use of L-Glutamine in cancer patients is controversial as some cancer cells change their metabolism to glutaminolysis using glutamine as the preferred fuel to product ATP (rather than glucose).  However, oral glutamine supplementation is unlikely to amplify glutaminolysis as there is plenty of glutamine available in the large muscle depot at all times.

L-Carnitine 1.5-2.0 grams per day

If patients are having a difficult time eating sufficient protein with meals I will also include a serving of an Complete Essential Amino Acids Formulation along with the BCAA supplementation noted above.

Omega 3 Fatty Acids have also shown anabolic potential.  They are already included in my OutSmart Cancer® Plans due to their multi-faceted contributions to healthy cell and mitochondrial membranes,  inflammation control, reduction of thrombus risk and tumor cell adhesion so important in the tumor microenvironment.  I recommend 2-6 grams daily of EPA-DHA in triglyceride form.

I also recommend that patients use Bone Broth which contains 10grams of protein per cup and often contains electrolytes as well depending upon how it is prepared.  Bone broth contains glutamine which is very healing to the intestinal epithelium and is considered a therapeutic food for cancer patients experiencing intestinal inflammation secondary to their cancer treatments.  Glutamine is one of the primary fuels for the colonocytes and has been in wide use for repair and to restore normal barrier function even in the hospital setting.  The primary protein in bone broth is collagen derived and is not very high in leucine. Collagen is not the best form of protein for muscle mass, but it is still a complete protein and an easy source for patients who may drink 2-4 cups a day as part of their daily fluid intake.  2-4 cups of bone broth daily would provide an additional 20-40 grams of protein.

I also prescribe protein shakes  with 20-30 grams of protein per shake.  This is very effective as many cancer patients become uninterested in food and food preparation, lose their appetite, become nauseous or suffer poor self care due the exhaustion and overwhelm of cancer and cancer treatments.   A protein shake can be designed to be a meal replacement or a supplement to calories and macronutrients.   Whey protein has been shown to be an excellent form for building muscle mass.

Muscle mass is also a function of muscle use and weight bearing.  Therefore an exercise program should also be in place, not only for healthy muscle mass but also because regular exercise has been shown to increase survival and reduce not only cancer related, but all cause mortality and of course is good for stress management and emotional well being.  The statistics on including a minimum of 30 minutes of exercise daily are compelling.   I ask my patients to engage in four 15 minute walks daily to accumulate one hour of walking.  Almost all patients can accomplish this.

Additionally, patients must include strength training with resistance.

Strength Training can be done with weights, whole body weight or resistance bands at least twice per week.  There are many excellent videos to be found only for every age group and level of fitness. No matter how inexperienced or out of shape, anyone can begin.   This makes a huge difference in strength vs frailty in cancer patients and elderly patients and should be part of standard of care within a health model.

I also want to highly recommend the work of Dr. Gabrielle Lyon DO who has devoted herself to the what she calls “Muscle-Centric Medicine”.  Her book, Forever Strong: A New Science Based Strategy for Aging Well” written for the general audience. She clearly explains the science and provides concrete and clear guidelines for eating and exercise to preserve and build muscle at every stage of life.  She also has additional resources for clinicians.

Selected References

Exercise and Cancer Survivorship (book) 2010 ISBN : 978-1-4419-1172-8 https://link.springer.com/book/10.1007/978-1-4419-1173-5

Matei B, Winters-Stone KM, Raber J. Examining the Mechanisms behind Exercise's Multifaceted Impacts on Body Composition, Cognition, and the Gut Microbiome in Cancer Survivors: Exploring the Links to Oxidative Stress and Inflammation. Antioxidants (Basel). 2023 Jul 14;12(7):1423. doi: 10.3390/antiox12071423. PMID: 37507961; PMCID: PMC10376047.

Anjanappa M, Corden M, Green A, Roberts D, Hoskin P, McWilliam A, Choudhury A. Sarcopenia in cancer: Risking more than muscle loss. Tech Innov Patient Support Radiat Oncol. 2020 Nov 9;16:50-57. doi: 10.1016/j.tipsro.2020.10.001. PMID: 33385074; PMCID: PMC7769854.

Williams GR, Dunne RF, Giri S, Shachar SS, Caan BJ. Sarcopenia in the Older Adult With Cancer. J Clin Oncol. 2021 Jul 1;39(19):2068-2078. doi: 10.1200/JCO.21.00102. Epub 2021 May 27. PMID: 34043430; PMCID: PMC8260902.

Larsson L, Degens H, Li M, Salviati L, Lee YI, Thompson W, Kirkland JL, Sandri M. Sarcopenia: Aging-Related Loss of Muscle Mass and Function. Physiol Rev. 2019 Jan 1;99(1):427-511. doi: 10.1152/physrev.00061.2017. PMID: 30427277; PMCID: PMC6442923.

D'Hulst G, Masschelein E, De Bock K. Resistance exercise enhances long-term mTORC1 sensitivity to leucine. Mol Metab. 2022 Dec;66:101615. doi: 10.1016/j.molmet.2022.101615. Epub 2022 Oct 14. PMID: 36252815; PMCID: PMC9626937.

Melone MAB, Valentino A, Margarucci S, Galderisi U, Giordano A, Peluso G. The carnitine system and cancer metabolic plasticity. Cell Death Dis. 2018 Feb 14;9(2):228. doi: 10.1038/s41419-018-0313-7. PMID: 29445084; PMCID: PMC5833840.

Takagi A, Hawke P, Tokuda S, Toda T, Higashizono K, Nagai E, Watanabe M, Nakatani E, Kanemoto H, Oba N. Serum carnitine as a biomarker of sarcopenia and nutritional status in preoperative gastrointestinal cancer patients. J Cachexia Sarcopenia Muscle. 2022 Feb;13(1):287-295. doi: 10.1002/jcsm.12906. Epub 2021 Dec 22. Erratum in: J Cachexia Sarcopenia Muscle. 2023 Apr;14(2):1142. PMID: 34939358; PMCID: PMC8818668.

Reidy PT, Rasmussen BB. Role of Ingested Amino Acids and Protein in the Promotion of Resistance Exercise-Induced Muscle Protein Anabolism. J Nutr. 2016 Feb;146(2):155-83. doi: 10.3945/jn.114.203208. Epub 2016 Jan 13. PMID: 26764320; PMCID: PMC4725426.

Moro T, Brightwell CR, Velarde B, Fry CS, Nakayama K, Sanbongi C, Volpi E, Rasmussen BB. Whey Protein Hydrolysate Increases Amino Acid Uptake, mTORC1 Signaling, and Protein Synthesis in Skeletal Muscle of Healthy Young Men in a Randomized Crossover Trial. J Nutr. 2019 Jul 1;149(7):1149-1158. doi: 10.1093/jn/nxz053. PMID: 31095313; PMCID: PMC7443767.

anxiety-and-depression

Integrative Resources for Cancer-related Anxiety and Depression

The OutSmart Cancer® System is a WHOLE PERSON approach to supporting the health of cancer patients, survivors and their loved ones.  This includes addressing the psycho-social and spiritual needs of our patients.

Anxiety and depression are common human responses both for patients and loved ones  during every phase of the cancer journey, from diagnosis, active treatment, recovery, living with cancer as a chronic illness or as a cancer survivor long term.  Psychological and spiritual concerns often go untreated.

Most patients require some encouragement to talk about their emotional, psychological and spiritual challenges. It is vital to include thoughtful support and resources to all patients, family members and significant others

ASCO

Cancer is a collective experience and everyone close to the patient is touched by the diagnosis and the suffering.   Everyone is transformed by the depth and intensity of the experience.

“I very much like to frame the cancer journey as an opportunity, as a meaningful and sacred gateway in

 one’s life.  It is a time for reflection and inquiry and for clarifying one’s priorities and core values.  

Many patients and families find the depth and intimate nature of the experience to be ultimately transformational and healing, especially when shared.”

I ask  patients to ponder the questions:

  • What gives me strength?
  • What gives me courage?
  • What are my fears?
  • What are my hopes and dreams?

Patients and families are encouraged to take the opportunity to enter into a new phase of life with new learned self-care and lifestyle tools and resources in alignment with the health focused and proactive principles of my OutSmart Cancer® System.

patients-and-families

The Society for Integrative Oncology(SIO) and ASCO (The American Society of Clinical Oncology) have co-published a resource outlining an integrative approach and research supported resources and recommendations for patients during active treatment as well as post-treatment.

“ I think of post-treatment as the rest of your life, not a finite period of time.”

Recommended Interventions from SIO and ASCO include:

  • Mindfulness based interventions/meditation
  • Yoga
  • Tai Chi/Chi Gung
  • Hypnosis
  • Acupuncture
  • Music/Music Therapy
  • Reflexology (Massage)
  • Aromatherapy: Lavender Essential Oil

SIO and ASCO convened a multi-faceted and diverse expert panel. Their literature search included systematic reviews, meta-analyses, and randomized controlled trials published from 1990 through 2023. This team developed evidence-based guideline recommendations. The literature search identified 110 relevant studies (30 systematic reviews and 80 randomized controlled trials) to inform their guidelines.

I also encourage patients to seek appropriate psychological and spiritual counseling, spend time in nature, engage in creative activities  through art, dance, movement, writing, journaling and poetry as well as the recommendations outlined above.

It is possible to transform challenges and suffering into the pearls of new insights, loving-kindness, compassion and wisdom that can richly inform our inner and outer lives at every phase of the cancer journey.

Additional information is available at www.asco.org/survivorship-guidelines

Reference:

Integrative Oncology Care of Symptoms of Anxiety and Depression in Adults With Cancer: Society for Integrative Oncology–ASCO Guideline

Linda E. Carlson, Nofisat Ismaila, Elizabeth L. Addington, et al

Rhodiola

Rhodiola, Mitochondria and Cancer Chemoprevention

Rhodiola (rosea and crenulata spp.) is a botanical adaptogen with broad application in cancer chemoprevention and mitochondrial support for cancer patients undergoing and recovering from cancer therapies.

Rhodiola is considered an adaptogen. It supports multiple functions that enhance resilience, responsiveness and recovery in the face of stress.

mitochondriaRhodiola came to widespread prominence when it was used by Olympic athletes, high altitude mountain climbers and long distance runners to enhance endurance and sustained energy over 50 years ago.

Rhodiola rosea and its primary active phytochemicals, salidroside and rosavins, have been widely studied for effects on cellular metabolism, energy production, inflammation control, oxidative stress, autophagy and cell death.

Salidroside is known to bind to the cell membrane and enter the cytosol via a membrane transporter where it influences AMPK and improves endothelial function and nitric oxide production, enhances glucose uptake and fatty acid oxidation and inhibit and gluconeogenesis and glycogen synthesis.

AMPK activity is required for cells to respond to stress and changes in energy balance.  It is primarily through this pathway that Rhodiola appears to enhance normal mitochondrial function and energy metabolism.  

Salidroside is water soluble and highly bioavailable via oral administration and its metabolites are excreted in the urine.

Rhodiola has also been shown to inhibit tumor promoting mTOR pathway and reduce angiogenesis and metastasis by down-regulating expression of HIF1a/HIF2a signaling. Reducint mTOR expression is a goal in chemoprevention and in optimizing the tumor microenvironment.

Rhodiola has demonstrated positive synergistic effects when combined with the chemotherapy agent cyclophosphamide.  

Rhodiola metabolites are excreted through the urine and one human study showed that patients with superficial bladder carcinoma who consumed Rhodiola orally reduced the average frequency of recurrence by 50%. 

Murine studies have shown that Rhodiola has Immuno-stimulating properties and increases, CD3 and CD4 T cells, Interferon-g and IL-2 cytokines.

Rhodiola demonstrates anti-inflammatory activity by inhibition of COX2, PLA2, NfkB, TNFa, IL-1B and IL-6 which are all upregulated in the tumor microenvironment. Additionally Rhodiola has inhibits expression of the NLRP3 inflammasome which is activated in the lung epithelia both during viral infections as well as malignancy.  (As a side note, this property of Rhodiola may also enhance vaccine adjuvant effect and maturation of dendritic cells and promote immune response to vaccine innoculation)

rhoRhodiola rosea and Rhodiola crenulata  are available as liquid botanical extract and in capsule form. Rhodiola extracts typically contain 3% salidrosides and 1% rosavins.  A therapeutic dose of Rhodiola is 3000mg/day.

A maintenance dose for cell protection and healthy aging ranges from 200-1000mg per day. Always use professional grade supplements and suppliers.

Rhodiola has a wide range of applications in chronic syndromes, healthy aging, and chemo-prevention and recovery by positively influencing multiple pathways in the cancer terrain and tumor microenvironment.

Selected References

Rhodiola and salidroside in the treatment

of metabolic disorders                                               
Xiang-Li Bai, et al, DOI : 10.2174/1389557519666190903115424

Rhodiola rosea L.: an herb with anti-stress, anti-aging, and immunostimulating properties for cancer chemoprevention

Yonghong Li , et al DOI: 10.1007/s40495-017-0106-1

mTOR, AMPK, and Sirt1: Key Players in Metabolic Stress Management                            
Silvia Cetrullo
, et al DOI: 10.1615/critreveukaryotgeneexpr.2015012975