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Bone Density and Breast Cancer

The Link between Bone Density and Breast Cancer Risk

Understanding and Monitoring Risk Factors

Bone density, or bone mineral density ( BMD ), is the amount of bone mineral in bone tissue.  Bone mineral density (BMD) is a lifetime marker of estrogen exposure in a woman's body and has been associated with increased breast cancer risk. Estrogen is a crucial factor in maintaining bone density and gradually decreases over age. While there are many factors that influence bone density and bone health, the presence of estrogen contributes to the capacity of bone to continuously remodel and maintain the dynamic balance between bone resorption and bone formation.  A woman’s exposure to estrogen over the life cycle may contribute to her risk of breast cancer.

Bone density measurement is used in clinical medicine as an indirect indicator of osteoporosis and fracture risk.  There is a clear association between poor bone density and a higher probability of fracture.  There is a clear association between poor bone density and low estrogen levels.  Conversely, there is a clear association between increased and healthy bone density and higher estrogen levels.

Screening for risk of breast cancer should ALSO include assessment of estrogen levels and bone density along with well-recognized risk factors which include first degree relatives, obesity, increased visceral fat, smoking, alcoholism, early menarche, late menopause, sedentary lifestyle, hormone replacement therapy, and prolonged estrogen exposure, increased density of breast tissue. 

I would also add exposure to environmental endocrine disruptors and imbalances in the intestinal microbiome influencing estrogen metabolism.  Breast density and bone density are related to endogenous and exogenous estrogen exposure in a woman’s body.  There is a correlation between estrogen exposure, high breast density, high bone density, and increased risk of breast cancer.

 

Bone is living metabolically active tissue. “Bone remodeling is the process by which bone is renewed to maintain bone strength and mineral homeostasis. Remodeling involves continuous removal of discrete packets of old bone, replacement of these packets with newly synthesized proteinaceous matrix, and subsequent mineralization of the matrix to form new bone begins before birth and continues until death.  Bone remodeling increases in perimenopausal and early postmenopausal women and then slows with further aging, but continues at a faster rate than in premenopausal women. Bone remodeling is thought to increase mildly in aging men.”  Normal Bone Anatomy and Physiology 10.2215/CJN.04151206

Engaging in a health model for all patients includes assessing and managing bone health to promote healthy bone over the life cycle. A health model for cancer patients, due to the typically older age demographics will inherently include a large population of patients already at risk for loss of bone mass, osteopenia and osteoporosis. Screening for bone mineral density and managing bone health should be part of whole-person, whole health care. Taking a thorough history that includes family history, bone health and bone mineral density can bring attention to patients at higher risk for low bone density and fracture as well as patients with a higher risk of estrogen driven breast cancers.

Bone density measurement is used in clinical medicine as an indirect indicator of osteoporosis and fracture risk.  There is a clear association between poor bone density and higher probability of fracture.  There is a clear association between poor bone density and low estrogen levels.  Conversely there is a clear association between increased and healthy bone density and higher estrogen levels.

The Most Common Risk Factors for Low Bone Density and Primary Considerations for a Bone Density Test include:

  • Females age 65 or older
  • Males aged 70 or older
  • People over age 50 with
    • previous bone fracture from minor trauma
    • rheumatoid arthritis
    • low body weight
    • a parent with a hip fracture
  • Individuals with vertebral abnormalities
  • Individuals receiving, or planning to receive, long-term glucocorticoid therapy
  • Individuals with primary hyperparathyroidism
  • Individuals being monitored to assess the response or efficacy of an approved osteoporosis drug therapy
  • Individuals receiving androgen deprivation therapy 
  • Individuals with a history of eating disorders

Additional factors that are related to the risk of low bone density and the need for assessment include smoking, alcohol intake, long-term use of corticosteroid drugs, sedentary or convalescent lifestyle, protein status, mineral status, digestion, and absorption function, chronic inflammation and vitamin D status.  

For cancer patients and survivors also consider periods of poor nutrition, calorie, protein status, convalescence, lack of exercise, effect of hormonal therapies, oophorectomy, orchiectomy, chemotherapy, immunotherapy, treatment induced thyroiditis, gastritis, enteritis and colitis,  chronic pain impacting appetite, digestive and absorptive dysfunction, surgical loss of gastrointestinal organs and function as contributors to risk of loss of bone density and as well as multiple and varied adverse effects of cancer physiology and cancer treatments upon nutritional status and active lifestyle.

Selected References 

Clarke B. Normal bone anatomy and physiology. Clin J Am Soc Nephrol. 2008 Nov;3 Suppl 3(Suppl 3):S131-9. doi: 10.2215/CJN.04151206. PMID: 18988698; PMCID: PMC3152283.

Fraenkel M, Novack V, Mizrakli Y, Koretz M, Siris E, Norton L, Shafat T, Geffen DB. Bone mineral density in women newly diagnosed with breast cancer: a prospective cohort study. NPJ Breast Cancer. 2022 Feb 17;8(1):21. doi: 10.1038/s41523-022-00388-z. PMID: 35177701; PMCID: PMC8854387.

Zain NM, Seriramulu VP, Chelliah KK. Bone Mineral Density and Breast Cancer Risk Factors among Premenopausal and Postmenopausal Women A Systematic Review. Asian Pac J Cancer Prev. 2016;17(7):3229-34. PMID: 27509955.

Biomarker Lactic Acid Dehydrogenase Predicts Cancer Progression and Overall Survival

Aberrant metabolism and inefficient fuel production are characteristic of tumor cells, which are dominated by aerobic glycolysis, increased lactate production, and a higher uptake of glucose (the Warburg effect). Elevated LDH is a marker of these aberrant metabolic processes in cancer cells. High serum LDH levels are associated with poor prognosis in patients with cancer and predict progression and overall survival.

Aerobic glycolysis was described for the first time about a century ago by Otto H. Warburg who showed that cancer cells metabolize glucose differently than normal cells (Warburg effect) and that tumors derive energy mainly from the conversion of glucose to lactic acid and minimally via cellular respiration involving oxygen. Tumors produce massive amounts of the aerobic glycolysis waste product, lactic acid. This is evidence of deregulated metabolism, hence the understanding of cancer as “disorder of cellular metabolism”.  Lactic Acid itself may promote the growth and spread of cancer cells, especially at high concentrations by changing the tumor microenvironment.

Lactate dehydrogenase (LDH) is an enzyme that catalyzes the reduction of pyruvate to lactate at the end of the glycolytic pathway.

The normal range for LDH is 100-333 u/L, with levels greater than 245 u/L considered to be in the upper quartile of normal.  Elevated LDH, above 245 u/L, is suggestive of early carcinogenesis, tumor cell proliferation, tumor progression, and poor prognosis.

LDH is often highly elevated in aggressive forms of cancer and hematological malignancies including melanoma, lymphoma, acute leukemia, seminoma germ cell, pancreatic, gastric, lung, renal cell, nasopharyngeal, esophageal, cervical, and prostate cancers.

The OutSmart Cancer System® recognizes cancer as a metabolic syndrome and leverages the abnormal metabolism of tumor cells to exert influence over the tumor microenvironment and the behavior of tumor cells. Attending to the Cancer Terrain is a fundamental approach for influencing cancer cell metabolism.  

EGCG, a catechin found in Green Tea (H. Camellia sinensis) has been identified as an agent which inhibits LDH activity in normal and low oxygen environments by influencing the conversion of pyruvate to lactate at the end of the glycolytic pathway.  This may deprive cancer cells of their preferred fuel, glucose, and metabolites, including lactate that produces a favorable environment for malignant proliferation, growth, and progression. Recommended Therapeutic Dose 1-3 grams daily.

Monitoring trends in LDH is a method of both identifying abnormal cellular metabolism found in many solid and hematologic malignancies and is also of value in identifying early signs of recurrence as well as disease progression.

For patients achieving remission, during the first two years after completion of cancer treatment, LDH and other biomarkers of the Cancer Terrain are monitored every 3 months.  Thereafter, every six months for 3-10 more years to track and identify early signs of recurrence.  

For patients living with cancer as a chronic illness, LDH and biomarkers of the Cancer Terrain are monitored every 3 months to track evidence of recurrence and treatment resistance.

 

Learn more about monitoring the Cancer Terrain and the Tumor Microenvironment.
Receive training in Dr. Nalini’s OUTSMART CANCER SYSTEM ®.
www.aiiore.com

By using biomarkers of the Cancer Terrain and cellular metabolism, it is possible to identify trends that allow for early intervention. LDH is one of the most valuable and reliable biomarkers reflecting the active presence of the aberrant physiology of tumor cells and is prognostic and predictive of progression and overall survival in cancer patients.

 

Selected References:

Innovative MRI without Toxic Gadolinium Contrast Media

PreNuvo: Innovative MRI Technology

High-resolution radiology is used in oncology for both diagnoses as well as screening and monitoring. Because cancer cell physiology is metabolically different from healthy cells, contrast media are preferentially taken up by cancer cells allowing for more precise imaging.

Magnetic Resonance Imaging (MRI)  was invented in the 1980s.  It is a magnetic technology and does not expose patients to ionizing radiation, but to magnetic fields.  Hence it is considered safer than exposure to the damaging, oncogenic ionizing radiation found in X-Rays and PET and CT scans

Say No to Gadolinium
The most commonly used contrast medium used with MRI imaging to enhance resolution is Gadolinium. Gadolinium is a  magnetic metal that is engineered into a nanoparticle solution and injected into the vein.

Gadolinium can damage both nephrons and neurons and is not completely excreted leading to toxic load over time.  Because cancer patients may have multiple scans per year over many years, exposure to Gadolinium can become damaging and increasingly toxic. Gadolinium also acts as a calcium channel blocker and even at low concentrations can interfere with the contraction of smooth, skeletal, and cardiac muscle, nerve impulses, and blood coagulation.  Furthermore, there is a syndrome called Gadolinium deposition disease that is a gadolinium storage condition for which the long-term effects are not well understood.  A common adverse effect of Gadolinium exposure and retention is renal fibrosis.

Patients should discuss the risks of ALL contrast media with the radiology team to evaluate risks and benefits and be fully informed before proceeding with any scan.  Because all contrast media has toxicity, the opportunity to have a high-resolution scan without the use of Gadolinium contrast media is a very important innovation.

Patients with compromised cardiovascular, renal and neurologic function should use cautions before authorizing the performance of any scan without a full understanding of toxicity, risks, and benefits of contrast media

What if A High-Resolution MRI was possible without toxic contrast media?

PreNuvo has developed a High-Resolution MRI Scan that does not require the use of Gadolinium contrast media.

As with all technologies, MRI technology is advancing. Prenuvo is a company on the forefront of MRI Innovation bringing new safe and effective techniques not requiring contrast medium for high-resolution whole-body imaging, making accurate diagnosis possible.

Prenuvo uses innovative new hardware, software, and sequencing to create more detailed comprehensive images along with the use of Artificial Intelligence to enhance accurate analysis in less time.  Prenuvo claims a 0.7% false-positive rate due to the higher resolution, often decreasing the need for additional follow-up imaging, biopsies, or surgeries.  All without the use of Gadolinium or any other contrast media.

A more comfortable patient-centric experience:
A whole-body scan at Prenuvo typically takes 60 minutes compared to 5 hours for a conventional MRI.  The scanner itself is wider and more open and less claustrophobic with fresh air vents.  The machine is much quieter as opposed to the loud clanking of the conventional MRI.  The design also allows the patient’s head to remain outside of the scanner for most of the scan.  Innovative design and technology also solve many of the issues that lead to stress and anxiety for the patient that is common with MRI scans.  Additionally, a headset and a music menu are provided to support relaxation.

For a faster, safer, less toxic, and highly accurate MRI without contrast, I recommend that you explore the use of prenuvo.com for your patients.

(NB: I have no financial relationship whatsoever with  Prenuvo.)

Selected References:

Modulating Extreme Adverse Effects of Immunotherapy Treatments

Today, more and more patients are avoiding toxic chemotherapy in favor of targeted cancer therapies.  Among the many new therapies available are a class of immunotherapy drugs that take the brakes off of the immune system and mobilize T cells against tumor cells.

Because tumor cells have the capacity to disable T cells, this therapy addresses the huge problem of immune resistance in many cancers.  Drugs in the class of PD1 and PDL1 inhibitors were some of the first to be developed.  These drugs bind to PD1 or PDL1 receptors on the tumor surface and unleash the fury of the immune system upon the tumors by removing the inhibitory function of these ligands.

Nature has designed the immune system with both a gas pedal and a brake.  The PD1 and PDL1 inhibitors are the brakes.  Take off the brakes and the immune system is activated.

The best of outcomes with these treatments may result in complete tumor eradication, a truly miraculous outcome for some patients.  I have a patient who came to me with Stage 4 Endometrial Cancer with Lung Metastases some years ago.  After reduction of some of her tumor burden with surgery and rather brutal chemotherapy, her very forward-thinking Gynecologic Oncologist included a course of Keytruda (Pembrolizumab), which was a new immunotherapy treatment at the time. 

The historical prognosis for this patient would have been certain eventual mortality for her metastasized aggressive cancer.  However, she achieved a complete response and has been in remission and designated NED or No Evidence of Disease for many years now.   This is a patient who most likely would not be alive today without the advent of PD1 -PDL-1 inhibitor therapy.

The problem with this class of drugs is that their use is very unskillful and very unpredictable. Some patients will respond with a modicum of mild to moderate systemic autoimmune inflammation while other patients will be disabled by furious, extreme, and damaging autoimmune syndromes.  Some patients may die from extreme autoimmune activity.  I had one patient who developed myocarditis and died within a few days of receiving his first dose.  This was a prostate cancer patient whose sudden death was completely unexpected and not predicted.   

These patients require a health model and safe, effective modulation of extreme auto-immune inflammation not provided by their oncology teams. 

Some patients will have immune activation similar to a nice warm burning ember.  They get the therapeutic benefit without extreme adverse effects.  While other patients will respond with a forest fire of inflammation that must be suppressed aggressively with steroid medications for long periods of time.  The adverse effects of long-term steroid therapy then become part of the clinical picture and challenge for these patients.  In these circumstances, it IS reasonable to ask if the cure is worse than the disease itself? 

My patient developed such severe colitis (a common adverse effect) that she visited the emergency room multiple times for fluid and electrolyte replacement due to extreme persistent watery diarrhea.  Additionally, the nutritional status of this patient was also compromised and she became depleted in both calories and nutrients and developed sarcopenia.

Many cancer patients receiving PD1 and PDL 1 inhibitors are left with lifelong autoimmune disease.   Most common are autoimmune arthritis, colitis, thyroiditis, dermatitis, pneumonitis, and associated loss of normal tissue and organ function.  Some patients suffer ongoing chronic inflammatory pain syndromes.

Less prevalent, but also part of the long list of adverse effects are myocarditis, pericarditis, nephritis, hepatitis, pancreatitis, neuritis, vasculitis. Essentially, any tissue or organ can be impacted with associated loss of function and sequelae.

It is my practice to screen and monitor patients receiving cancer immunotherapies for the development of autoimmune syndromes and intervene early.  If I have a patient with a history of inflammatory or autoimmune disorders I can predict that such patients are more likely to develop adverse effects. 

Additionally, high levels of inflammation not only lead to pain syndromes but are also contributors to ongoing chronic fatigue as well as agitation,  cognitive changes, sleep disruption, anxiety, and depression, and the stress of living not only as a cancer survivor but with a chronic and distressing autoimmune syndrome difficult to control and manage.  It is my firm goal that Quality of Life must be a goal in all treatment plans for cancer patients and survivors.

 If a patient has NO inflammatory adverse effects it is assumed that the patient is not going to benefit from the PD1/PDL1 inhibitor because there is no sign or symptom indicating immune activation.   I always tell patients we should celebrate if they develop a rash or diarrhea because we know the drug is working!   

In fact, it is my observation over many years of following patients who have received these therapies that when the course of immunotherapy treatment is completed those patients who continue to have low levels of inflammation continue to have the therapeutic benefit of tumor control.  This is only an empirical observation on my part.  For example, the endometrial cancer patient described above continues to have mild colitis and has remained in remission.  Before the availability of these therapies, we would expect this patient to have a recurrence and to die of her advanced stage 4 metastatic disease within a few years of her diagnosis.   Patients such as this with lung metastases historically had very poor prognoses and very high mortality rates.  Patients with powerful and manageable responses to PD1 and PDL1 inhibitors may live a long time.  While some patients do recur, some have not.  We have not had decades of time to follow these patients as these treatments are relatively new.  If nothing else, these treatments do extend the life of many patients.

How can we modulate the auto-immune adverse effects of these potentially curative immunotherapy treatments?   I have taken the approach that we employ in Functional and Naturopathic Medicine in the management of auto-immune syndromes to turn down the volume on the immune inflammation just enough to reduce extreme side effects, damage, and loss of function without losing the therapeutic benefit of these immunotherapy treatments.   

While we can rely on studies that have demonstrated that Omega 3 Fatty Acids, Vitamin D3, and Curcumin and a healthy microbiome can modulate auto-immune inflammation, there is a paucity of research on managing autoimmune syndromes related to immunotherapy adverse effects with the exception of steroids. (See selected references below.)

I share with you here my empirical clinical experience.  I have employed this approach with several hundred patients since immunotherapies have come into wider use in oncology.  Clinicians experienced in managing autoimmune syndromes will recognize the basic principles of care.

  • Anti-Inflammatory, Low Antigen Diet
  • Support for the healthy intestinal microbiome 
  • Specific Nutriceutical-Phytochemical Interventions
    • Omega 3 Fatty Acids (EPA DHA)  recommended dose 4-6 grams daily SPMs Specialized ProResolving Mediators can also be considered 1-2grams daily
    • Fat soluble Curcumin recommended dose 2-6 grams daily
    • Vitamin D3 5,000-25,000iu daily  (125mcg-625mcg). 
      • Consider a loading dose of 50,000iu (1.25mg)

I always start at the lower end of the dose range and spread the dosing out into 3-4 doses over the day.  The goal is to MODULATE but not SUPPRESS the therapeutic impact.  It is also important to be mindful of the anticoagulant/platelet aggregation inhibitory effect of such an approach and to determine which patients may NOT be a candidate for high dosing due to thrombocytopenia or anticoagulant pharmaceutical therapies.

This approach has few negative drug-nutrient interactions. I have continued these inflammation-modulating therapies continuously for many years with most patients.  Dosing is highly individualized to each patient towards the goal of supporting and promoting healthy function and quality of life.

For front-line clinicians interested in supporting the health of cancer patients and cancer survivors and learning and implementing my OutSmart Cancer® System developed over 35 years in practice, I encourage you to join our training program, Foundations of Integrative Oncology, self-paced online training with clinical supervision and mentoring.  Go to aiiore.com.  

There is a huge population of patients whose lives have been touched by cancer searching for a health model and skilled and knowledgeable clinicians.

Selected References:

Vitamin D and autoimmune diseases.
Illescas-Montes R, Melguizo-Rodríguez L, et al Life Sci. 2019 Sep 15;233:116744. doi: 10.1016/j.lfs.2019.116744. Epub 2019 Aug 8. PMID: 31401314 

Vitamin D intake is associated with decreased risk of immune checkpoint inhibitor-induced colitis.
Grover S, Dougan M, et al Cancer. 2020 Aug 15;126(16):3758-3767. doi: 10.1002/cncr.32966. Epub 2020 Jun 22. PMID: 32567084

Therapeutic Potential of omega-3 Polyunsaturated Fatty Acids in Human Autoimmune Diseases.
Li X, Bi X, Wang S, Zhang Z, Li F, Zhao AZ.
Front Immunol. 2019 Sep 27;10:2241. doi: 10.3389/fimmu.2019.02241. eCollection 2019.  PMID: 31611873 

Resolvins: Emerging Players in Autoimmune and Inflammatory Diseases.
Abdolmaleki F, Kovanen PT, et al 
Clin Rev Allergy Immunol. 2020 Feb;58(1):82-91. doi: 10.1007/s12016-019-08754-9. PMID: 31267470 

Curcumin in Autoimmune and Rheumatic Diseases.
Yang M, Akbar U, Mohan C.
Nutrients. 2019 May 2;11(5):1004. doi: 10.3390/nu11051004.
PMID: 31052496 

Curcumin and autoimmune disease.
Bright JJ.
Adv Exp Med Biol. 2007;595:425-51. doi: 10.1007/978-0-387-46401-5_19. PMID: 17569223  

Curcumin as an Adjuvant to Cancer Immunotherapy.
Paul S, Sa G.
Front Oncol. 2021 Aug 16;11:675923. doi: 10.3389/fonc.2021.675923. eCollection 2021.
PMID: 34485117 

Gut Bacteria Influence Effectiveness of a Type of Immunotherapy. https://www.cancer.gov/news-events/cancer-currents-blog/2018/gut-bacteria-checkpoint-inhibitors. Feb 2018  NCI Staff

Let The Oncologist Be The Disease Expert. Become The Health Expert That Cancer Patients Are Looking For.

You may not treat cancer in your practice, but you do have patients who are at risk due to personal and family history, patients who may be undergoing or recovering from treatments, patients who are survivors worried about recurrence and patients living with cancer as a chronic illness.  And you may also have patients who are family members concerned about their loved ones. 

 

There is no HEALTH MODEL in conventional oncology care, yet health and wellbeing, peace of mind and sense of agency are in the center of the hearts and minds of cancer patients, cancer survivors and their families. 

 

There will be 19 million cancer survivors in the US alone by 2024.  Who is supporting their health?  Who is trained to help them recover and keep them well??  …not the oncologist.

 

How can you help these patients?

A  breast cancer survivor who successfully completed her treatments 8 years ago comes into your office as a new patient complaining of persistent peripheral neuropathy and ongoing cognitive changes since her treatment.  How can you resolve these long-term adverse effects?

 

An ovarian cancer patient currently undergoing aggressive treatment every 21 days comes into your office complaining of severe diarrhea, neuropathy and sleep disruption.  What can you do to help her get through her treatments with less adverse effects, maintain her weight and nutritional status?

 

A colorectal cancer survivor who completed his treatment 3 months ago is continuing to have 10-15 bowel movements daily and is profoundly fatigued.  What will you do to restore normal bowel function?


A prostate cancer patient on endocrine blockade therapy is suffering from
hot flashes. Should you also be concerned about loss of bone mass and sleep cycle disruption?

 

An endometrial cancer survivor is suffering from dermatitis and colitis, adverse effects of her dramatically successful immunotherapy treatment and now has chronic autoimmune inflammation. How will you manage this?

 

A head and neck cancer patient who has trouble swallowing is losing weight and muscle mass.


How can you provide a plan for repair from oral mucositis, restoration of the oral mircrobiome and repletion of calories and nutrients?

 

These patients are searching for clinicians that can guide and support them through every phase of their cancer journey.  Just as in helping your patients navigate other chronic illnesses, patients look to you for a plan, for monitoring and guidance so that they can maintain and regain their health during and after their treatments.

 

When a patient has a collaborative team providing integrative care everyone wins, the patients, families and care providers.  Patients who have a clear plan and support have the opportunity for better outcomes, better prognosis, greater peace of mind, a sense of control and agency and an improved quality of life. 

 

Let the oncologist be the cancer expert. You can be the health expert on their team.

 

Standard of care in oncology must  change such that care includes not only a team of disease experts (usually medical oncologist, surgeon, radiologist) but ALSO a team of health experts.

 

Towards this end  I founded the American Institute of Integrative Oncology Research and Education and  have created an online self-paced training program for front line clinicians who want to expand their skills and their practice and  fill the huge need in our communities and serve these patients.  If you did not specialize in oncology, you probably had one course on this topic but you need to fill the gap in your training to feel confident in doing so.

 

The Foundations of Integrative Oncology Training is not for clinicians who want to practice oncology.  It is front-line clinicians who want to feel confident, knowledgeable and well trained in supporting the health side of the cancer equation. This self- paced online training is for clinicians who want to increase their impact, expand and grow their practice and represents 35 years of clinical practice and experience.

 

The first step is learning how to take a comprehensive and complete history of patients whose lives have been touched by cancer.  

 

You can receive a complimentary copy of the

OUTSMART CANCER CARE PLANNER History and Intake Form

and learn more about the Foundations of Integrative Oncology training here

 

OutSmart Cancer Care Planner