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

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/

 

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.

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

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]

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 survival.  Results 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.