Cancer Support – Breast Naturopathic Protocol

Cancer Support – Breast Naturopathic Protocol

This Cancer Support – Breast Naturopathic Protocol is provided as information for patients of HealthMasters Naturopath Kevin Tresize ND as part of a treatment plan to assist patients with understanding of their treatment plan and should not be substituted for medical advise, diagnosis or treatment. It is important to note that this is a summary only and is intended to assist discussion between practitioner and patient as part of consultations. This Cancer Support – Breast Naturopathic Protocol may be changed to suit the individual requirements of the patient and should not be substituted for medical advice, diagnosis or treatment.

HealthMasters Naturopath Kevin Tresize ND

 

Overview: Cancer Support – Breast

Integrative oncology that complements orthodox medical treatment allows for improved health outcomes for patients living with cancer. Although Complementary Therapies such as natural medicines provide effective patient-centred care, optimising treatment efficacy and reducing treatment side effects, they are not a first-line therapy or a substitute for conventional pharmacological treatment. Rather, Complementary Therapies provide beneficial outcomes when part of a multi-disciplinary approach that is oncologist-led. Sustainable and effective patient care occurs when health professionals communicate and work collaboratively rather than as isolated independent Practitioners.

 

Pathophysiology: Cancer Support – Breast

  • Breast cancer occurs when abnormal cells grow in an uncontrolled way within breast tissue, forming either a benign (non-cancerous or precancerous) or malignant tumour.[1],[2]
  • Invasive ductal carcinoma (IDC)[*]  and ductal carcinoma in situ (DCIS)[†]  are the most common histology, accounting for 70% of breast cancer, while invasive lobular carcinoma[‡] accounts for most of the remaining cases.[3]
  • Both genetic and hormonal factors play a role in breast cancer pathogenesis, with prolonged oestrogen exposure associated with early menarche, late menopause and use of hormone replacement therapy (HRT) correlating with an increased risk.[4] The affected tissue is known to have increased levels of oestrogen synthesising enzymes, such as sulphatase, β-glucuronidase and aromatase, resulting in intracellular oestrogen excess.[5]
  • For cells to initiate carcinogenesis successfully, they require the following key characteristics, collectively referred to as the hallmarks of cancer (Figure 1):

Genetic instability: Cancer cells display an incfreased rate of mutation and reduced deoxyribonucleic acid (DNA) repair, which allows for further mutations and enables the pathogenesis of additional hallmarks[6];

Sustained proliferation: Cancer cells can sustain proliferation beyond what occurs in normal cells. This is typically due to growth factors, which are able to bind to cell surface-bound receptors that activate an intracellular tyrosine kinase-mediated signalling cascade, ultimately leading to changes in gene expression and promoting cellular proliferation and growth[7];

Growth suppressor evasion: Normal cells contain antigrowth signals that divert cells from proliferation towards quiescence (inactivity) or differentiation. Mutations in tumour suppressor genes can deactivate growth suppressors or render cells impervious to their actions,[8] resulting in the affected cell accumulating genomic defects[9];

Replicative immortality: Mutations in tumour suppressor genes allow cancer cells to replicate unchecked,[10] enabling them to acquire an ability for unlimited proliferation.[11] Cancer cells also display an upregulation of telomerase, an enzyme that allows continued cell division, therefore preventing premature arrest of cellular replication. The telomerase enzyme is almost absent in normal cells but is expressed in significant levels within many human cancers.[12]

Sustained angiogenesis: All cancers require a functional vascular network to ensure continued growth, requiring sustenance via nutrients and oxygen, as well as an ability to clear metabolic waste products and carbon dioxide. Angiogenesis is dependent on the production of angiogenic growth factors, including vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF).[13]

Apoptosis evasion: Programed cell death (apoptosis) protects healthy tissue by halting proliferation of cells in response to sufficient levels of genomic damage.[14] Apoptosis evasion can involve oncogenes and mutations in tumour suppressor genes, as well as changes in mitochondrial death signalling[15];

Invasion and metastasis: This complex process involves local tissue invasion, followed by infiltration of nearby blood and lymphatic vessels from cancer cells. Malignant cells are eventually transported through haematogenous and lymphatic spread to distant sites within the body, where they form micrometastases that will eventually grow into macroscopic metastatic lesions[16];

Dysregulated energy metabolism: Under aerobic conditions, oxidative phosphorylation functions as the main metabolic pathway for energy production, while under anaerobic conditions, glycolysis is favoured to produce adenosine triphosphate (ATP). Cancer cells can reprogram their glucose metabolism to limit energy production to glycolysis, even in the presence of oxygen (termed ‘aerobic glycolysis’). Up-regulation of glucose transporters, such as glucose transporter 1 (GLUT1), is the main mechanism through which aerobic glycolysis is achieved[17];

Immune evasion: Cancer cells actively evade immune surveillance, therefore allowing them to avoid detection and elimination from the immune system. Additionally, cancer cells may evade immune destruction by inducing immune dysfunction, often via inflammatory mediators[18]; and

Inflammation: Tumour-associated inflammatory responses promote tumour formation and cancer progression. Cytokines are able to alter blood vessels to permit migration of leucocytes (mainly neutrophils), in order to permeate from the blood vessels into the tissue (a process known as extravasation). Pro-angiogenic factors are also released by inflammatory immune cells into the surrounding tumour microenvironment (TME), causing release of reactive oxygen species (ROS).[19] These actions perpetuate other hallmarks of cancer, including upregulating growth factors and altering the extracellular matrix, thereby encouraging angiogenesis, invasion and metastasis.[20]

  • Oncogenes (genes that have the potential to cause cancer) are derived from proto-oncogenes (genes that regulate healthy cellular growth and division) that have undergone genetic mutation. These mutations are mostly acquired (rather than inherited) and can be caused by carcinogens such as radiation, smoke and other environmental toxins, as well as from specific pathogenic infections.[21]
  • While oncogenes lead to sustained proliferation, tumour suppressor genes lose their ability to slow down/regulate replication. Mutated tumour suppressors originate from genes that regulate cell cycle arrest, apoptosis, senescence, DNA repair and differentiation.[22] The tumour suppressor gene, p53, known as the ‘guardian of the genome’, is the most commonly mutated gene in human cancer, being present in more than half of cases.[23]
  • When a tumour forms, innate, adaptive and complement immune systems collaborate to mediate an anti-tumour immune response that coordinates eradication.[24] Key cells involved include cytotoxic natural killer (NK) cells,[25],[26] type one dendritic cells (DC1),[27],[28] CD4+ T cells and CD8+ T cells.[29] However, tumour immunogenicity[§] and immunosuppression can increase the chances of cancer cells becoming resistant to immune control, contributing to tumour growth.
Figure 1 The hallmarks of cancer Cancer at HealthMasters Support – Breast Protocol

Figure 1: The hallmarks of cancer.

 

Consultation Overview: Cancer Support – Breast

Identify Risk Factors

In Clinic Investigations- Refer to Key Drivers and the Clinical Investigation and Pathology sections below for further guidelines:

  • Attain a detailed case history of the patient’s current health status and cancer progression. Include:

The type of cancer and stage of the disease (1 to 4)

Timeline of cancer progression from diagnosis through to present day

Assess patient’s family history for evidence of cancer (genetic predisposition)

Metastases (if present, determine location)

Past/present/future treatment options (surgery, chemotherapy, radiation, hormone treatment and/or pain management)

Signs and symptoms that the patient is currently experiencing (nausea, vomiting, fatigue etc.)

Request relevant test results and medical scans

  • Using the Distress Thermometer, routinely screen/monitor distress levels (mental, physical, social and spiritual) in all cancer patients.
  • Have patient complete the Health Appraisal Questionnaire (HAQ).
  • Review potential for prolonged endogenous oestrogen exposure including early menarche, late menopause and HRT use, as well as late first pregnancy, which have been associated with increased breast cancer risk.
  • Assess patient’s history of environmental carcinogen exposure including alcohol, tobacco, radiation, and occupational pollutants (dye and rubber manufacturing, asbestos mining, construction work, shipbuilding, vinyl chloride manufacturing, and petroleum industry).
  • Assess patient’s infectious history, particularly chronic or recurrent infections, as well as infections with known associations to cancer development.
  • Measure the patient’s height and weight and calculate their basal metabolic index (BMI) to assess their weight range and determine if obesity is a contributing factor to cancer development/progression. Additionally, use BMI to monitor metabolic derangements associated with chemotherapy and radiotherapy, including weight loss/anorexia or cachexia (loss of muscle mass), caused by systemic inflammation and nutritional insufficiency.
  • Screen for comorbid chronic inflammatory diseases that can further increase inflammatory load.
  • Use the Circadian Hygiene Review to assess circadian rhythm disruptions, which may promote cancer development and contribute to poor therapeutic outcomes.
  • Assess patient’s current and/or past stress level, as this can be a trigger or sustaining factor of inflammatory diseases and immune dysregulation. Consider using the Depression Anxiety Stress Scales (DASS) and/or the Mood and Stress Questionnaire to evaluate the impact of stress.
  • Review the macro and micronutrient composition and quality of the diet, including assessment of a high caloric diet, which is considered carcinogenic.
  • If patient presents with symptoms of microbiome disruption, consider using a MetaBiome™ Test Kit to examine commensal microbiota populations, as well as pathogenic bacteria levels.
  • Consider evaluating omega-3 status via the OmegaQuant®Omega-3 Index Test, which may be low in inflammatory states.

Pathology Investigations- Refer to Key Drivers and the Clinical Investigation and Pathology sections below for guidelines:

  • Monitor relevant tumour marker(s), which may be indicative of the patent’s response to treatment.
  • Monitor patient’s white cell count (WCC), which can indicate low immunity/immune suppression.
  • Consider oestrogen metabolites spot urine test to detect the urinary products of oestrogen metabolism, indicating oestrogenic activity in the body.
  • Consider testing sex hormone-binding globulin (SHBG) levels, which are significantly associated with breast cancer risk.

 

Identify Signs of Cancer: Cancer Support – Breast

Please note, cancer is serious illness that requires a diagnosis from a medical professional such as a General Practitioner or Oncologist. If a patient presents with any signs or symptoms outlined below, refer the patient to a medical professional for assessment.

Generalised signs and symptoms of breast cancer include[30]:

  • Fatigue
  • Weight loss/anorexia
  • Jaundice

Physical signs and symptoms include[31]:

  • Palpable lump or mass, which can be self-detected or physician-detected.
  • Breast cancer that is too small to be felt can be identified using screening/diagnostic mammography detection. A screening mammogram every two years is recommended for women aged 50 to 74 years.
  • Skin and/or nipple retraction and skin oedema, erythema, ulcer, and/or satellite nodule.
  • Nodal enlargement in axilla and supraclavicular areas.
  • Nipple discharge, which may be serous or bloody.

Note: Refer to the Clinical Investigations and Pathology section for instructional guidance around breast self-examination techniques and identifying unusual changes to breast tissue. If a change in breast tissue is detected, advise the patient to schedule a mammogram appointment (refer to Additional Resources section for state/territory links to BreastScreen clinics) or see a doctor without delay.

 

Key Drivers: Cancer Support – Breast

Immunogenicity: Tumours of very low or no immunogenicity are less likely to respond to therapeutic strategies that enhance the immune response.[32] Tumour immunogenicity is determined by two factors: the antigenicity of tumour cells and the processing and presentation of tumour antigens, both of which can be influenced by the TME.[33] Mutations within cancer cells may lower or completely stop expression of specific antigens recognised by the immune system. For instance, the major histocompatibility complex (MHC) class I receptor expression may be retracted or degraded, allowing cancer cells to evade cytotoxic CD8+ T cells[34],[35] and contributing to the exponential growth of the tumour and the development of the TME.[36]

Immune suppression: A combination of inflammatory proteins and antigens produced directly from the tumour, as well as the recruitment of additional cells that build the TME, contribute to the generation of cancer cells that can resist immune recognition and invoke immunosuppression.[37] Mechanisms include:

High expression of interleukin-6 (IL-6) by tumour cells is involved in proliferation, migration and angiogenesis. The continued secretion of IL-6 interrupts MHC II antigen presentation and suppresses CD4+ T cell mediated immunity (involved in coordinating tumour eradication)[38];

Tumour secretion of IL-6 increases dendritic cell (DC) and macrophage release of arginase, which reduces CD4+ T cell-mediated immunity[39] and blunts cytotoxic CD8+ T cell function (which release cytotoxic granules, tumour necrosis factor alpha [TNF-α] and interferon gamma [IFN-γ] required for tumour elimination).[40] Therefore, tumour synthesis of IL-6 slows anti-tumour immunity,[41] allowing for exponential tumour growth;

Production of prostaglandin (PG) E2 affects communication between DC1 and NK cells,[42],[43] which monitor the internal environment for abnormalities,[44] thereby blocking the expression of NK cell receptors and allowing tumours to remain hidden[45];

Secretion of lactate by the tumour inhibits DC1 functions,[46] which include the activation of antigen-specific CD4+ T cells via MHC II ligands, the secretion of IL-12, which shifts CD8+ T cells into cytotoxic mode and elevates NK cell synthesis of interferon (IFN)-γ,[47] as well as the recruitment of macrophages for cleanup and repair[48];

The expression of a transmembrane protein that inhibits phagocytic function of macrophages[49];

The synthesis of transforming growth factor beta (TGF-β) which lowers NK cell tumour recognition and communication with DC1 cells[50];

Recruitment of immune cells to build the TME, which subsequently protect the tumour from NK and CD8+ T cells, and secrete substances to enhance tumour growth[51],[52]; and

Tumour cells induce CD8+ T cell exhaustion[53] via overexpression of inhibitory ligands, such as programmed death ligand-1 (PD-L1), that bind with inhibitory receptors (PD-1 receptors) on CD8+ T cells.[54],[55] This phenomenon leads to apoptosis and subsequent reduction in T cell numbers,[56] as well as reduced production of IFN-γ, decreased TNF-α and subsequent poor cytotoxicity (killing ability).[57]

  • Hormonal factors: Increased oestrogen signaling, which occurs due to up-regulation of multiple oestrogen receptors (most commonly oestrogen receptor alpha [ER-α] and beta [ER-β]) is implicated in breast cancer pathogenesis. Oestrogen binding to ER-α stimulates cell proliferation, excitation and inflammation (tumour promoting).[58],[59],[60],[61],[62] In contrast, activation of ER-β enhances oestrogen metabolism and anti-inflammatory effects.[63],[64],[65],[66] Additionally, sex hormone binding globulin (SHBG), a glycoprotein that binds to sex hormones and regulates their availability, is significantly associated with reduced breast cancer risk. SHBG prevents the proliferative oestrogenic effect on breast cancer cells, with oestrogen-positive breast cancer cells binding to SHBG twice as frequently as oestrogen-negative cells. SHBG also binds ‘free’ oestrogen, further reducing oestrogen levels that promote breast cancer cell growth.[67] Hormone-associated risk factors for breast cancer include postmenopausal HRT (increases the risk of breast cancer development by 1.5 times), menarche <12 years of age (increases risk by 1.1 to 1.9 times), menopause >55 years (increases risk by 1.1 to 1.9 times), and late first pregnancy (increases risk by two to four times).[68]
  • Poor oestrogen metabolism: The path through which oestrogen is metabolised influences its activity within the body, affecting an individual’s risk for hormonally driven cancer. Oestradiol and oestrone are metabolised by three competitive pathways (2-, 4- and 16-hydroxylation), subsequently resulting in their conjugation with glucuronic acid and sulphate (by hepatic phase II enzymes, UDP-glucuronosyltransferases and sulfotransferases), and excretion via urine and faeces. Two-hydroxylated (2-OH) oestrogen possesses low binding affinity for the oestrogen receptor, resulting in reduced hormonal potency, cell growth and proliferation. In addition, 2-OH has been associated with normal cell differentiation and apoptosis. Comparatively, 4-hydroxylated (4-OH) oestrogen possesses carcinogenic potential due to its ability to cause DNA damage, generating mutations with subsequent oxidative damage and initiation of breast cancer. The 16-hydroxylation (16-OH) pathway is also associated with increased proliferation of mammary cells and therefore a potential tumour initiator. Refer to Figure 2 for a summary of the pathways of oestrogen metabolism.
  • Exposure to environmental carcinogens: Approximately 90% of cancers are associated with mutations caused by environmental exposures, as well as some somatic (acquired) mutations.[69] Alcohol, tobacco, radiation, occupational pollutants (dye and rubber manufacturing, asbestos mining, construction work, shipbuilding, vinyl chloride manufacturing, and petroleum industry) and high-calorie diets are recognised carcinogens.[70],[71] Synthetic chemicals that mimic or disrupt hormones, particularly oestrogen signalling, are also proposed to elevate breast cancer risk. Endocrine-disrupting chemicals include bisphenol A, parabens, phthalates, perfluoroalkyl substances, benzene, ethylene oxide, and polycyclic aromatic hydrocarbons.[72]
  • Infectious exposure: Some viruses contain oncogenes, which, when inside human cells, can drive sustained proliferation. Viral oncogenes do this by activating proto-oncogenes within the human cell, increasing their expression while also inhibiting tumour suppressor genes. For instance, Human papillomavirus (HPV) contains the oncogene, E6, which produces a protein that binds to and inactivates p53; therefore preventing apoptosis and promoting cellular proliferation.[73] Viruses identified as having oncogenic influences in breast cancer include HPV, mouse mammary tumour virus (MMTV), bovine leukaemia virus (BLV) and Epstein-Barr virus (EBV), with gene sequences and proteins detected in human breast cancer tissue.[74]
  • Cell danger response (CDR) dysfunction: The mitochondria are involved in cellular healing processes, known as the cell danger response (CDR). Progression through the CDR enables recovery from a stressor and avoidance of chronic disease, however in cancer cells, pathological mitochondria cause dysfunction within the CDR cycle, resulting in impaired/incomplete cellular healing processes.[75] The three sequential phases/checkpoints that form the CDR include:

CDR1: Innate immunity stimulates proinflammatory ROS to prevent/neutralise pathogenic infection. Cell communication to neighbouring cells is disrupted to prevent infectious spread.[76]

CDR2: Increased proliferation involving stem cells and genetic material to rebuild tissue lost during CDR1.[77]

CDR3: Cellular energy and resources are used to differentiate the new cells into their specialised roles, and cellular communication is restored.[78]

If the CDR is blocked at any checkpoint, the innate immunity, proliferation or differentiation phases are left ‘switched on’, causing them to become pathogenic and a trigger of cellular abnormalities and tumour growth.[79] For example, cancer patients, despite potentially having any number of triggers, share a common profile of a prolonged CDR2 state.[80]

  • Obesity: Overweight or obesity significantly increases the risk of 14 types of cancer, including breast cancer. Adipose tissue is involved in regulation of inflammation and metabolism, with excessive adipose tissue exerting carcinogenic effects via the up-regulation of growth factors and hormones (e.g. oestrogen), while also causing metabolic-induced inflammation (meta-inflammation). Additionally, neighbouring adipocytes in breast tissue aromatise androgens to create a local source of oestrogen, with studies associating greater BMI with increased oestrogen production in breast tissue.[81] Adipose expansion also differentiates adipose-derived tumour supporting cells, which can migrate, infiltrate and progress tumour activity.[82] Breast cancer risk also increases with physical inactivity, which is a driver of obesity.[83]
  • Inflammatory diseases: Certain non-cancerous chronic diseases may also predispose to cancer independent of their shared risk factors. For instance, diabetes affects up to one-third of patients with breast cancer, and evidence shows that women with diabetes have a 40% higher risk of mortality after breast cancer than women without diabetes.[84] Additionally, evidence suggests a positive association between hypertension and breast cancer incidence, particularly in postmenopausal women.[85] Linking these chronic diseases is their potential to fuel chronic inflammation, either locally in tissues or systemically, therefore promoting the malignant transformation of susceptible cells and tumorigenesis.[86] Inflammation promotes the increased expression of oestrogen synthesising enzymes, which then drives excessive proliferation.[87],[88]
  • Circadian disruption: Loss of circadian homeostasis is thought to promote cancer development, as well as contribute to poor therapeutic outcomes and early mortality.[89] Specifically, night-shift work may increase the risk of developing cancer, notably breast cancer.[90],[91] Chronic disruption of the circadian rhythm tips the balance between tumour-suppressive and tumour-progressive gene expression to favour tumour growth.[92] The underlying mechanisms to date are not yet clear,[93] however several hypotheses have been put forward including night time light exposure (eliminating the nocturnal anti-carcinogenic effects of melatonin),[94] dysregulation of the biological clock genes that control cell proliferation,[95] and a weakening of the immune system due to sleep disturbances.[96]
  • Chronic stress: Changes in neuroendocrine function, caused by chronic stress, are associated with increased inflammation and immune dysregulation, which may increase cancer progression and negatively impact quality of life (QOL) and survival.[97] Additionally, activation of the sympathetic nervous system by stress releases neurotransmitters that act on β-adrenergic receptors on tumour cells and tumour-associated immune cells to promote metastasis.[98] Reducing stress improves survival and health outcomes in cancer patients.[99]
  • Microbiome disruptions: The gut microbiome influences a patient’s risk of developing cancer, as well as altering patient response to cancer treatment.[100] Key organisms and functions of the gut microbiome are associated with reduced cancer risk including the production of short chain fatty acids (particularly butyrate), which induces cell differentiation and apoptosis. Additionally, certain organisms have been demonstrated to metabolise phytochemicals (polyphenols, flavonoids and glucosinolates) to compounds that reduce DNA damage and inflammation, while also inhibiting tumour growth. Conversely, pathogenic microbes have been found in the TME, interacting with cancer cells and encouraging growth. Pathogenic organisms also produce a host of metabolites that stimulate inflammation and DNA damage.[101] Since breast is composed of fatty tissue with extensive vasculature and lymphatic drainage, the breast microbiome can be a favourable environment for the growth of bacteria. Local dysbiosis has been observed in breast cancer tissue compared to non-cancerous tissue. For instance, studies have demonstrated a higher abundance of Enterobacteriaceae, Bacillus and Staphylococcus spp. in breast cancer patients, while Escherichia coli and Staphylococcus epidermidis have been shown to induce double-stranded DNA break in breast cancer cells, which can trigger pathological changes in breast cells.[102]
  • Dietary factors: Poor dietary habits have long been associated with cancer risk. For instance, diets rich in saturated fats are associated with an increased breast cancer, as well as cancer of the lung, colon, rectum, endometrium, and prostate, while excessive alcohol intake has been linked to an increased risk of breast, liver, colon, rectum, oral and oesophageal cancers.[103]
  • Genetic factors: Inherited cancer syndromes account for 5% to 10% of all cancers and generally result from inherited mutations in genes that regulate cell growth, cell death and apoptosis. Specifically, the BRCA1, BRCA2, AT (ataxia telangiectasia) and TP53 gene mutations are associated with increased breast cancer risk. Although carriers of these gene mutations have a greatly elevated risk of cancer, none has 100% penetrance[**] and additional factors, both genetic and environmental, likely contribute to cancer onset.[104]

Figure 2 Oestrogen detoxification pathways at HealthMasters Support – Breast Protocol

Figure 2: Oestrogen detoxification pathways.

Key: ER-α: Oestrogen receptor alpha; ER-β: Oestrogen receptor beta; GST: Glutathione S-transferase; DNA: Deoxyribonucleic acid; NQO1: NAD(P)H quinone dehydrogenase 1 ; COMT: Catechol-O-methyltransferase; SULT: Sulfotransferase; CYP1A1/A2: Cytochrome P450 family 1 subfamily A member 1; CYP1A2: Cytochrome P450 family 1 subfamily A member 2; CYP1B1: Cytochrome P450 family 1 subfamily B member 1; CYP2C11/3A4: Cytochrome P450, subfamily 2, polypeptide 11; CYP3A4: Cytochrome P450 family 3 subfamily A member 4; 2-hydroxylation of oestrogen; 4OH of oestrogen; 4-hydroxylation of oestrogen; 16αOH oestrogen; 16α-hydroxylation of oestrogen; 17β-HSD1: 17β-Hydroxysteroid dehydrogenase type 1; UDG; Uridine diphosphate glucuronic acid.

 

Treatment Priorities: Cancer Support – Breast Naturopathic Protocol

  • Enhance immune surveillance and the function of innate and adaptive immune cells, including DC1, NK cell cytotoxicity and CD4+ and CD8+ T cells, to facilitate anti-tumour immunity.
  • Modulate oestrogen signalling by down-regulating oestrogen binding to ER-α and up-regulating ER-β receptor activity, therefore enhancing oestrogen metabolism and anti-inflammatory effects that inhibit oestrogen proliferation in breast cancer cells.
  • Encourage endogenous detoxification to promote the elimination of toxicants from the body, reducing oxidative damage and toxic accumulation that up-regulates oestrogen signalling, while also improving resilience against environmental toxin exposures.
  • Attenuate chronic inflammation and meta-inflammation by stimulating endogenous synthesis of anti-inflammatory mediators, often supressed by tumour-associated inflammation, to encourage inflammation resolution, modify the immunity in tumour cells and promote anti-tumour activity.
  • Relieve painful neuropathies associated with antineoplastic agents by encouraging microglial migration and phagocytosis to injured nerves, stimulating an anti-inflammatory microglial phenotype, reducing excitatory glutamate neurotransmission, and enhancing inhibitory gamma-aminobutyric acid (GABA) activity, thereby improving QOL.
  • Support patients during conventional treatment by offsetting side effects associated with chemotherapy and radiotherapy, including nausea, vomiting, delayed gastric emptying, mucositis, dysbiosis, fatigue, and chemotherapy ‘brain fog’, as well as symptoms associated with hormone therapy such as hot flushes, night sweats and headaches.
  • Enhance nutritional status, often compromised during anti-cancer therapy, to maintain optimal body weight and prevent significant weight loss and cachexia or, conversely, mitigate obesity, which can drive cancer progression.
  • Increase antioxidant capacity to protect mitochondrial membranes from free radical damage, improving their structure and function to facilitate cellular bioenergetics and foster CDR healing.
Caution: It is recommended that supplemental antioxidants are avoided during radiotherapy and chemotherapy, as co-administration may impede treatment efficacy. However, antioxidants may still be provided through a whole-food diet.
  • Modulate neuroendocrine function and sympathetic nervous system activity, reducing excessive production of glucocorticoids and excitatory neurotransmitters that perpetuate inflammation and immune dysregulation, which may increase cancer progression and negatively affect QOL.
  • Minimise drivers of immune dysfunction including inflammation, exposure to environmental and infectious carcinogens, overweight/obesity, circadian disruptions, chronic stress, microbiome disruptions, and inadequate nutrition, to improve immune function and reduce/arrest tumour growth.
  • Ensure nutrient precursors for mitochondrial ATP generation, immune function, musculoskeletal strength and metabolic health are replete.
  • Draw on psycho-oncologic interventions to improve QOL and survival rate, including establishing social support, encouraging adjustment and adaptive skills, managing stressors of disease and treatment (pain, fatigue, physical weakness and distress), and mitigating the effects of stress on tumour progression.

 

Red Flags: Cancer Support – Breast Naturopathic Protocol

  • Metastatic disease: Metastatic disease is the major cause of death in cancer patients and the principal cause of morbidity. Brain metastases occur in 10% to 30% of adults and 6% to 10% of children with cancer, and most commonly metastasise from breast, lung, melanoma and colon tumours. Lung metastases are common in breast cancer, colon cancer and tumours of the head and neck. Bone metastases are a major clinical complication in patients with myeloma, breast or prostate cancers (bone is the third most common organ involved by metastasis, after lung and liver). If distant spread is suspected, a computerised tomography (CT) scan and/or bone scan are required; immediately refer the patient for assessment by an overseeing medical Practitioner/General Practitioner. For the majority, the aim of treatment is palliative, preserving or restoring function, skeletal stabilisation and local tumour control,[105] and supporting QOL.
  • Thromboembolism: Thrombosis and disseminated intravascular coagulation[††] are common complications in patients with cancer. The prothrombotic state is caused by cancer cells activating the coagulation system via factors such as tissue factor, cancer procoagulant and inflammatory cytokines. The interaction between tumour cells, monocytes/macrophages, platelets and endothelial cells can promote thrombus formation as part of a host response to the cancer (i.e. inflammation, angiogenesis) or via a reduction in the levels of inhibitors of coagulation or impairment of fibrinolysis. Additionally, the prothrombotic tendency can be enhanced by therapy such as surgery, chemotherapy, hormone therapy (particularly tamoxifen and aromatase inhibitors) and radiotherapy, and by in-dwelling access devices (i.e. central venous catheters).[106] Signs of thromboembolism include acute onset of shortness of breath (dyspnoea), chest pain, cough (may occur with haemoptysis), syncope, tachypnoea (respiratory rate >18 breaths/min), tachycardia, fever, and cyanosis. Complaints related to signs of deep vein thrombosis include lower-extremity swelling, and warmth and tenderness upon palpation. Thromboembolism is a serious condition that can result in pulmonary artery obstruction, cardiac shock and death. If the patient presents with signs of thromboembolism, call Triple Zero (000) in case of emergency or immediately refer them for assessment by an overseeing medical Practitioner/General Practitioner.
  • Neurological paraneoplastic syndromes: These form a group of conditions associated with cancer that are thought to be due to an immunological response to the tumour, resulting in damage to the nervous system or muscle. The cancers most commonly implicated are those of the breast, lung, pancreas, prostate, ovary and lymphoma. Syndromes include:

Peripheral neuropathy, which results from axonal degeneration or demyelination.[107]

Encephalomyelitis, caused by perivascular inflammation and neuronal degeneration.[108]

Cerebellar degeneration presents with rapid onset of cerebellar ataxia, resulting in loss of coordination of motor movement.[109]

Retinopathy presents with blurred vision, episodic visual loss and impaired colour vision, and may lead to blindness.[110]

Lambert–Eaton myasthenic syndrome (LEMS) presents with proximal muscle weakness that improves on exercise and is caused by the development of antibodies to pre-synaptic calcium channels.[111]

    If the patient presents with signs of neuromuscular dysfunction, refer them for assessment by an overseeing medical Practitioner/General Practitioner or call Triple Zero (000) in case of emergency.

    • Spinal cord compression: Complicates approximately 5% of cancers and is most common in myeloma, prostate, breast and lung cancers that involve bone. Cord compression often results from posterior extension of a vertebral body mass but intrathecal spinal cord metastases can cause similar signs and symptoms. The thoracic region is most commonly affected. Spinal cord compression initially presents with back pain, particularly when coughing and lying flat. Subsequently, sensory changes develop in dermatomes below the level of compression and motor weakness distal to the block occurs. Advanced progression is associated with sphincter disturbance, causing urinary retention and bowel incontinence.[112] Spinal cord compression is a medical emergency and should be treated with analgesia and high-dose glucocorticoid therapy, with neurosurgical intervention required in some cases. If suspected, immediately refer the patient for assessment by an overseeing medical Practitioner/General Practitioner or call Triple Zero (000) in case of emergency.
    • Hypercalcaemia: Hypercalcaemia is the most common metabolic disorder in patients with cancer and has a prevalence of up to 20% in cancer patients. The incidence is highest in myeloma and breast cancer (approximately 40%), intermediate in non-small cell lung cancer, and uncommon in colon, prostate and small cell lung carcinomas. Elevations of parathyroid hormone-related peptide (PTHrP) account for 80% of malignancy-associated hypercalcaemia, whereby PTHrP binds to the parathyroid hormone receptor and elevates serum calcium by stimulating osteoclastic bone resorption and increasing renal tubular reabsorption of calcium. Direct invasion of bone by metastases accounts for around 20% of cases. Symptoms of hypercalcaemia are often non-specific and may mimic those of the underlying malignancy such as drowsiness, delirium, nausea and vomiting, constipation, polyuria, polydipsia and dehydration. The diagnosis is made by measuring serum total calcium and adjusting for albumin.[113] Refer the patient to their overseeing medical Practitioner/General Practitioner for assessment.    
    • Comorbid depression and anxiety: Cancer diagnosis can have a wide-ranging impact on patient mental health, increasing the prevalence of depression and anxiety even among those with no previous psychiatric history. In addition to adversely affecting QOL, mood disorders in cancer patients may adversely affect cancer treatment and survival. Patients with pre-existing psychiatric illness are particularly vulnerable and at greater risk of mortality following a cancer diagnosis.[114] Using the Distress Thermometer, routinely screen/monitor distress levels (mental, physical, social and spiritual) in all cancer patients. Use the DASS and MSQ to evaluate the patient’s mental wellbeing and refer to the Treatment Recommendations section for supportive options based on specific patient needs.
    • Anticancer drug treatment side effects: Cytotoxics, including chemotherapy and radiotherapy, have a narrow therapeutic index and can have significant systemic adverse effects, seen in Figure 3 and Table 1. Myelosuppression (bone marrow suppression resulting in reduced production of blood cells) is common to almost all cytotoxics, which often limits the treatment dose in addition to causing life-threatening complications. Chemotherapy also induces a high rate of neutropenia, requiring chemotherapy doses to be given at shorter intervals where the rate-limiting factor is the time taken for the neutrophil count to recover. Supportive therapy such as antiemetics to treat nausea and vomiting is often required to enable patients to tolerate therapy and achieve benefit.[115]

     at HealthMasters Support – Breast Protocol

    Figure 3: Adverse effects of chemotherapy and radiotherapy, including acute (marked in pink) and late effects (marked in blue).[116] 

    Table 1: Common side effects from chemo- and radiotherapy.[117]

    Side effect Prevalence Mechanism/contributing factors
    Fatigue 50–90% Inflammation, anaemia, pain, stress
    Anxiety and depression 80% Stress of cancer diagnosis and therapy, uncontrolled pain, metabolic abnormalities e.g. anaemia, endocrine abnormalities, medications
    Sleep issues 50-90% Medication side effect, stress, altered diurnal rhythm, physical inactivity, pain, environmental
    Pain and neuropathy >40% Can originate from primary and metastatic sites or from treatment
    Anorexia and cachexia 50-80% Systemic inflammation, nutritional insufficiency
    Nausea and vomiting ~60% Medication side effects
    Mucositis 40-60% Inflammation, neutropaenia, barrier degeneration

     

    Treatment Recommendations: Cancer Support – Breast

    Core Recommendations

     

    AHCC™ and Ginger

    Dosage: Take 2 capsules twice daily.

    Active hexose correlated compound (AHCC™) and ginger to promote immune stimulation and surveillance, including enhanced innate and adaptive immune cell function, while also reducing anticancer drug treatment side effects.

    Mechanism of Action/Clinical Research:

    • AHCC™ promotes immune stimulation, as demonstrated in numerous human and animal studies (refer to Table 2).[118],[119],[120],[121],[122],[123],[124],[125],[126],[127],[128]

    AHCC™ at 3 g/d for four weeks was shown to increase circulating populations of DCs including DC1, essential to cancer cell elimination.[129]

    • AHCC™ has been shown to increase CD8+ T cell numbers at a dose of 3 g/d for three weeks,[130] as well as enhancing CD4+ T cells and INF-γ secretion;[131] all of which are essential for cancer elimination.
    • Increased survival time has also been observed in cancer studies using AHCC™ in both humans and animals.[132],[133],[134],[135],[136],[137],[138],[139]

    Forty-four patients with advanced liver cancer, known for poor survival rates, self-administered either placebo or 6 g/d of AHCC™. After six weeks of treatment, the placebo group had a 50% mortality rate compared with no fatalities in the AHCC™ group.[140]

      • Ginger has been shown to be protective against cisplatin[‡‡]-induced hepatotoxicity, where supplementation lowered the liver enzymes, alanine transaminase (ALT) and aspartate aminotransferase (AST). Additionally, ginger reduces lipid abnormalities, which are often associated with chemotherapy.[141]
      • The constituent 6-shogoal, from ginger, provides protection against treatment-induced intestinal damage by inhibiting intestinal villi apoptosis, lowering bacterial translocation and attenuating oxidative stress and inflammation,[142] as well as enhancing expression of protein, E-cadherin, involved in preserving intestinal barrier structure.[143]
      • In combination with chemotherapy treatment, ginger extract, at doses ranging from 500 mg/d to 1.2 g/d can reduce nausea.[144],[145]

      Table 2: Immune enhancing effects of AHCC™ and ginger – Animal and in vitro studies.

      Pathology Study Type Treatment Dose Duration Summary
      Salmonella typhi and Escherichia coli In vitro Ginger (dry extract) NA NA The antibacterial activity of an ethanolic extract of ginger against E. coli and S. typhi was positive. Additionally, an aqueous extract of ginger was effective in inhibiting S. typhi. These results were observed with a dilution between 75 mg and 250 mg/L, anything below this had a reduced effect.[146]
      M. avium, Mycobacterium tuberculosis In vitro 6-, 8- and 10-Gingerol NA NA The isolation of 6-, 8-, and 10-gingerol from fresh ginger rhizome show positive results for the inhibition of M. avium and M. tuberculosis in vitro. 10-gingerol was identified as the most active inhibitor of the tested bacteria.[147]
      K. pneumoniae Animal AHCC™ 1 g/kg body weight One week AHCC™ protected mice from death when infected with K. pneumoniae. Greater effects were found in mice that were profoundly immunosuppressed.[148]
      K. pneumoniae (surgical wound infection) Animal AHCC™ NA Eight days prior to and during infection Survival, mean time to death and infection clearance were increased significantly in the AHCC™ treated group.[149]
      K. pneumoniae (intramuscular infection) Animal AHCC™ NA One week prior to and throughout infection Mice receiving AHCC™ had significantly reduced numbers of bacteria at day five, and cleared bacteria entirely at day six. No bacterial clearance observed in control mice. Levels of IL-12, TNF-α, and IL-6 peaked earlier in this group compared with controls and a significant increase in macrophages and lymphocytes numbers was demonstrated with AHCC™ treatment.[150]
      Chlamydia trachomatis Animal AHCC™ 300 mg/kg One week prior and throughout infection AHCC™ fed mice had increased bacterial clearance, reduced bacterial shedding, and increased body and spleen weight compared with control infected group. There was a beneficial elevation in cytokines, including TNF-α and IL-6 by peritoneal cells and IL-2 and IFN-γ in splenic T cells demonstrated in AHCC™ fed mice. Moreover, production of TNF-α, IL-6, and IFN-γ in AHCC™ fed stressed mice was higher than that of AHCC™ fed non-stressed mice suggesting AHCC™ restores cytokine production under experienced stress.[151]
      Influenza A (H1N1, PR8) Animal AHCC™ 0.05, 0.1, 0.5, and 1 g/kg One week prior to and throughout infection Supplemented mice demonstrated a dose-dependent increase in survival, enhanced viral clearance and reduction in the loss of body weight with AHCC™ dosed at 0.1, 0.5 and 1 g/kg.[152]
      H5N1 avian influenza Animal AHCC™ 1 g/kg body weight One week prior to and throughout infection Data suggests that AHCC™ supplementation boosts NK activity, improves survival, and reduces the severity of influenza infection in mice Supplementation with AHCC™increased survival, decreased the severity of infection, and shortened infection recovery time. NK cell cytotoxicity in lungs had doubled by day four. Spleen NK cells were 50% greater than controls. AHCC™ also reduced the infiltration of lymphocytes and macrophages in the lungs compared with controls.[153]
      West Nile Virus (WNV) Encephalitis Animal AHCC™ NA One week prior to and throughout infection AHCC™ reduced viremia and mortality following lethal WNV infection in young mice. WNV-specific IgM and IgG production and T cell expansion were enhanced. AHCC™ administration in aged mice enhanced the protective T cell response as well as WNV-specific IgG but not IgM antibodies production. AHCC™ administration in aged mice attenuated viremia levels but led to no difference in mortality rate.[154]

       


      Specialised Pro-Resolving Mediators[§§]

      Dosage: 1 capsule twice daily.

      Specialised Pro-resolving Mediators (SPMs) to promote the resolution of chronic inflammation without suppressing immunity.

      Mechanism of Action/Clinical Research:

      • SPM supplementation promotes anti-tumour immunity via dual anti-inflammatory and pro-resolving activity. In particular, lipoxins and resolvins have an ‘adaptogenic’ effect to reverse cancer biology, compared to resolving non-cancer inflammation.[155] Evidence has shown that inducing these pro-resolving lipid mediators can beneficially modify immunity in target tumour cells, the TME and pre-cancerous lesions.[156]
      • The anti-cancer actions of SPMs also include increasing NK cell cytotoxicity and survival, decreasing angiogenesis, reducing tumour cell proliferation and migration, inhibiting tumour cell invasion, and reducing endothelial-mesothelial transition.[157]
      • SPMs encourage resolution by regulating macrophage polarisation. SPMs trigger the switch from proinflammatory M1 macrophages to anti-inflammatory M2 macrophages, reducing inflammation and tissue damage, and promoting resolution. Additionally, M2 macrophages have been shown to inhibit polymorphonuclear neutrophils (PMNs) and promote efferocytosis and tissue repair.[158]

       

      High Strength, Enhanced Absorption PEA for Nerve Pain

      Dosage: Take 1 capsule twice daily.

      Highly bioavailable palmitoylethanolamide (PEA), providing endocannabinoid-like actions to support pain relief in cancer patients, including chemotherapy-induced peripheral neuropathy.

      Mechanism of Action/Clinical Research:

      • PEA as a standalone therapy or in conjunction with pharmaceutical analgesics[159],[160],[161],[162] is shown to enhance patient QOL and relieve the intensity of several painful neuropathies, with no serious side effects reported.[163],[164],[165],[166],[167]

      The safety and efficacy of PEA was demonstrated in a study involving 20 multiple myeloma patients experiencing neuropathy whilst undergoing chemotherapy (thalidomide and bortezomib). After eight weeks of PEA (300 mg twice daily), pain scores reduced by 24% compared to controls, indicating significant protection of nerve function.[168]

        • PEA is an endocannabinoid-like lipid mediator influencing a variety of receptors and immune cells to provide anti-neuroinflammatory, analgesic and neuroprotective actions. PEA is endogenously produced in the body, with levels declining during chronic disease, tissue damage, inflammation, pain syndromes and ageing.[169]
        • PEA has an association with the endocannabinoid system (ECS) and key bioactive endocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol (2-AG).[170]The ECS regulates an array of physiological functions in the body,[171] with imbalances contributing to the development of several psychological and neurodegenerative disorders.[172],[173],[174]PEA supports the ECS via directly modulating endocannabinoid signalling (via receptor expression of PPAR-α or orphan G protein-coupled receptor [GPR55] or G protein-coupled receptors [GPCR]) and indirectly activating transient receptor potential vanilloid receptor type 1 (TRPV1) and cannabinoid receptors (CB1, CB2).[175],[176],[177]

         

        Soy, Methylating Nutrients & BCM-95™ Turmeric to Clear Oestrogen

        Dosage: Take 1 tablet twice daily with food.

        Herbs and nutrients to modulate oestrogen production and signalling, and to promote optimal 2-OH oestrogen metabolism, reducing oestrogenic stimulation.

        Mechanism of Action/Clinical Research:

        • Soy isoflavones[***] competitively antagonise the ER-α receptor, blocking the binding of more potent oestrogens to reduce overall oestrogenic activity.[178] Soy has been shown to preferentially bind to ER-β,[179] down-regulating oestrogen signalling and supporting healthy phase I and II oestrogen metabolism.[180]

        Consumption of 129 mg/d of isoflavones[†††] has been shown to reduce the amount of 4-OH oestradiol in women through inhibition of CYP1B1, responsible for 4-hydroxylation.[181]

          • Diets high in soy are associated with a lower incidence of oestrogen-dominant conditions, including breast, prostate and endometrial cancers.[182]

          A meta-analysis of 16 studies encompassing 11,169 breast cancer cases and 648,913 participants found a significantly reduced risk of breast cancer with high soy and isoflavone consumption,[183] indicating that soy consumption is protective against breast cancer.

            • Curcumin has been shown to activate nuclear factor erythroid 2-related factor 2 (Nrf2), which increases the expression of several detoxification enzymes required for oestrogen metabolism including glutathione S-transferase (GST) and NAD(P)H quinone dehydrogenase 1 (NQO1).[184]
            • Milk thistle up-regulates Nrf2 expression,[185] increasing levels of GST and NQO1, required during increased phase II metabolism.[186] Additionally, silybinin inhibits β-glucuronidase activity, helping prevent deconjugation and recycling of oestrogens.[187],[188]
            • Carnosol, from rosemary, directly antagonises ER-α, therefore modulating oestrogen signalling.[189] Additionally, rosemary has been shown to increase glucuronidation, promoting phase II metabolism of oestradiol and oestrone.[190]
            • Vitamin B6 and vitamin B12 are required for phase II methylation, upregulating phase II detoxification and therefore assisting clearance of excess oestrogens in oestrogen-dependent conditions.[191]

             

            Additional Considerations: Cancer Support – Breast

            Modulate oestrogen signalling and enhance 2-OH oestrogen metabolism:

            Indole-3-Carbinol

            Dosage: For oestrogen dominant conditions/to increase 2:16 hydroxyoestrone ratios: 300 mg/day. For oestrogen-dependent cancer prevention: 300 mg/day. For support with anti-oestrogen therapy: 300 mg/day.

            Indole-3 Carbinol (I3C) to support healthy oestrogen metabolism and to correct the 2:16 OH ratio, which is commonly associated with oestrogen-dependent cancers.

            Mechanism of Action/Clinical Research:

            • I3C has been found to increase levels of three key enzymes involved in oestrogen detoxification, quinone reductase (which reverses the formation of quinones), glutathione transferase and uridine diphosphate glucuronyltransferase (UGT), which mediate phase II glutathionation and glucuronidation, respectively.[192]
            • I3C stimulates multiple transcription factors that are involved in the regulation of cellular apoptosis and proliferation, including oestrogen receptors and aryl hydrocarbon receptors (AhR), which up-regulate the expression of genes involved in metabolising xenobiotic compounds and oestrogen including cytochrome p450 (CYP) enzymes, CYP1A1 and CYP1A2.[193]
            • I3C influences oestrogen signalling via suppression of ER-α induced gene expression,31 reducing the expression of ER-α proteins (possibly via an AhR-mediated mechanism)[194],[195] and by reducing oestrogen binding to ER-α.[196]

            Seventeen women from a high-risk breast cancer cohort were administered 400 mg/d of I3C for four weeks, followed by an increased dose of 800 mg/d for an additional four weeks. Results demonstrated a 66% increase in the urinary 2:16 OH ratio observed at a dose of 400 mg/d, indicating enhanced oestrogen metabolism, with no further increase found at 800 mg/d.[197]

               

              Calcium D-Glucarate

              Dosage: For oestrogen/xeno-oestrogen detoxification: 1500 mg to 3000 mg daily. For cancer support: 1500 mg to 3000 mg daily.

              Calcium D-glucarate to promote oestrogen detoxification by enhancing glucuronidation and preventing deconjugation of oestrogen metabolites, attenuating conditions associated with excess oestrogenic activity.

              Mechanism of Action/Clinical Research:

              • Calcium D-glucarate is endogenously metabolised to its active form, D-glucaro-1,4-lactone (1,4-GL), where it participates in glucuronidation (phase II detoxification) by attaching to intermediate metabolites and making these water-soluble for excretion. Calcium D-glucarate has the potential to mitigate deconjugation of glucuronidated compounds, such as oestrogen, and promotes safe excretion of the otherwise reactive substances.[198]
              • Calcium D-glucurate acts as a systemic inhibitor of β-glucuronidase, an enzyme that reverses the process of glucuronidation and deconjugates substances (including sex hormones and toxins), allowing these to re-circulate throughout the body.[199],[200] Inhibition of β-glucuronidase with calcium D-glucarate has been associated with a 20% to 50% reduction in serum oestrogen levels.[201]

               

              Magnesium and Broccoli for Women’s Health

              Dosage: Add 2 level scoops (9.0 g) to 200 mL of water twice daily. Stir well and take immediately.

              Herbs and nutrients that support hormonal balance by promoting the detoxification of oestrogen metabolites while also attenuating inflammation, increasing the expression of oestrogen synthesising enzymes that drive excessive proliferation.

              Mechanism of Action/Clinical Research:

              • Bioactive compounds from broccoli sprouts, such as sulforaphane, modulate oestrogen metabolism by stimulating the antioxidant response element (ARE).[202] ARE activation induces the expression of phase II enzymes including uridine 5'-diphosphate (UDP)-glucuronyltransferases (UGTs), sulphotransferases (SULTs), glutathione S-transferases (GSTs) and N-acetyltransferases (NATs), which are responsible for phase II glucuronidation, sulphation, glutathionation and acetylation, respectively.[203]
              • Vitamin B6, vitamin B12 and folic acid improve oestrogen and xeno-oestrogen detoxification by supporting methylation; the most common pathway of oestrogen conjugation in extrahepatic tissue. The enzyme, catechol-O methyltransferase (COMT), and the availability of methyl groups, require these nutrients to promote the activity of the methylation cycle.[204]
              • Magnesium deficiency is associated with several biomarkers of inflammation, including increased prostaglandin E2, thromboxane A2, substance P, histamine, C-reactive protein, tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-1.[205] Boswellia’s key constituent, 3-0-acetyl-11-keto beta-boswellic acid (AKBA), reduces inflammation via inhibiting 5-lipoxygenase and leukotriene production,[206] as well as inhibiting the activation of nuclear factor kappa-B (NFkB), a protein transcription factor that controls cytokine production.[207]
              • Chamomile compounds have demonstrated anti-inflammatory effects, with the flavonoid apigenin shown to reduce IL-6 and TNF-α.[208]

               

              Improve innate and adaptive immune function:

              Vitamin D3

              Dosage: Take 1 capsule daily with food.

              Vitamin D to modulate the innate and adaptive immunity, supporting an anti-tumour immune response.

              Mechanism of Action/Clinical Research:

              • Evidence suggests that vitamin D may suppress cancer cells and cancer stem cells, while also regulating a range of stromal cells within the TME including cancer-associated fibroblasts, tumour-derived endothelial cells, cancer stem cells, and infiltrating immune cells.[209]
              • Vitamin D exerts anti-inflammatory effects through suppression of inflammatory mediator production including cytokines, chemokines and prostaglandins. Additionally, vitamin D has been shown to inhibit mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) signalling in cancer cells, macrophages and epithelial cells, therefore reducing inflammatory processes that contribute to cancer progression.[210]
              • The anticancer actions of 1,25(OH)2D3 include the induction of cell cycle arrest, cell differentiation, cell apoptosis, autophagic cell death, as well as inhibition of metastasis tumour angiogenesis.[211]

              A meta-analysis of five randomised controlled trials with an intervention period of 3 to 10 years found that supplementation with 400 IU/d to 2,000 IU/d of vitamin D was associated with a 13% reduction in total cancer death.[212]

                • It is well known that vitamin D plays an important role in regulating immune function, with deficiency impacting the activity of Tregs,[213],[214] as well as the production of antibodies and regulation of dendritic cell function.[215]
                • Vitamin D enhances the adaptive immune response by increasing the differentiation of monocytes to macrophages and stimulating white blood cell proliferation.[216]
                • With receptors expressed on a wide variety of cell types, vitamin D is involved in the modulation of activated T and B lymphocytes.[217]
                • Vitamin D has been shown to regulate T helper cell function.[218]

                 

                Regulate aberrant proliferation of cancer cells:

                Cell Signalling, Detoxification and Antioxidant Support for DNA Replication

                Dosage: Take one tablet twice daily with food.

                Herbs and nutrients to regulate cell cycle control mechanisms, reducing cellular hyperproliferation, altered cellular metabolism, production of angiogenic factors, and subsequent tumourigenesis to slow/arrest cancer progression and development.

                Mechanism of Action/Clinical Research:

                • Curcumin induces apoptosis, as well as inhibiting proliferation and invasion of tumours by suppressing multiple cell signalling pathways and intracellular transcriptions factors (NF-κB, activator protein 1 [AP-1], cyclooxygenase-2 [COX-2], nitric oxide synthase, matrix metalloproteinase-9 [MMP-9], and signal transducer and activator of transcription 3 [STAT3]). Several studies have reported curcumin’s antitumor activity on breast cancer, lung cancer, head and neck squamous cell carcinoma, prostate cancer, and brain tumours, demonstrating its capability to target multiple cancer cell lines.[219]
                • Resveratrol activates sirtuins, specifically the class 1 phenotype (SIRT1), which regulate biochemical pathways involved in energy production, DNA transcription, cellular apoptosis and cellular stress resistance. Sirtuins increase the production of endogenous antioxidants, such as glutathione, as well as encouraging metabolic flexibility via stimulation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1-α), involved in energy metabolism.[220]
                • Quercetin has been shown to inhibit cancer progression via antioxidant, anti-proliferative and pro-apoptotic actions, as well as influencing cell signaling and growth factor suppression.[221] Evidence also suggests that quercetin may increase the bioavailability of resveratrol when used concurrently.[222],
                • Green tea polyphenols enhance antioxidant activity by scavenging ROS and nitrogen species, chelating redox-active transition metal ions and inhibiting pro-oxidant enzymes by inducing antioxidant enzymes. These antioxidant effects have the potential to protect tissues against mitochondrial damage induced by oxidative stress.[223]
                • Epigallocatechin gallate (EGCG), found in green tea, has been found to directly inhibit the phosphatidylinositol-3-kinase (PI3K) cell signaling pathway (a key regulator of normal cellular processes). Decreasing PI3K activity indirectly increases expression of PGC1-α, which is required to improve mitochondrial numbers and efficiency.[224]
                • Panax ginseng stimulates heat shock proteins[‡‡‡] that upregulate several cellular response mechanisms including antioxidant enzymes and energy metabolism pathways.[225] Ginsenosides present within Panax ginseng also demonstrate anti-angiogenic and pro-apoptotic effects in cancer cells.[226]

                 

                If patient presents with symptoms of mitochondrial dysfunction, including fatigue:

                Enhanced Bioavailability Ubiquinol for Energy and Cardiovascular Health

                Dosage: Take 1 capsule daily with food.

                Active ubiquinol (CoQ10) to enhance mitochondrial function and cellular bioenergetics, and regulate cellular healing adversely affected by tumour-associated inflammation and oxidative stress.

                Mechanism of Action/Clinical Research:

                • CoQ10, in both its reduced (ubiquinol) and oxidised forms (ubiquinone), is involved in oxidative phosphorylation, facilitating ATP production within the mitochondria.[227],[228]
                • CoQ10 also functions as a membrane antioxidant, therefore protecting the mitochondrial membrane from oxidation and lipid peroxidation.[229],[230]

                 

                If pain or inflammation are present:

                BCM-95™ Turmeric & Devil's Claw to Treat Chronic Inflammation

                Dosage: Acute dose: 3 capsules twice daily, reducing to the maintenance dose of 1 capsule morning and two capsules evening, once symptoms have improved.

                Anti-inflammatory and analgesic herbs to attenuate the tumour-associated inflammatory response, therefore reducing oxidative stress, tissue damage, angiogenesis and subsequent tumour growth.

                Mechanism of Action/Clinical Research:

                • Curcumin has broad anti-inflammatory effects, decreasing many inflammatory mediators including phospholipase, lipoxygenase (LOX), COX-2, leukotrienes (LTs), thromboxane, PGs, nitric oxide (NO), collagenase, elastase, hyaluronidase, monocyte chemoattractant protein-1, interferon-inducible protein, TNF-α, and IL-12.[231],[232]
                • Boswellic acid, acetyl-11-keto-beta-boswellic acid (AKBA), demonstrates anti-inflammatory actions via allosteric regulation of 5-LOX, resulting in LT inhibition.[233] Additionally, boswellia exerts anti-inflammatory activity further up the inflammatory cascade, inhibiting the activation of proinflammatory signalling pathway, NFĸB.[234]
                • Devil’s claw provides significant analgesic effects by reducing pain sensations in the brain via increasing GABA levels and opioid activity, while also reducing glutamate signalling.[235]

                 

                Support microbiome diversity[§§§]:

                 

                If neutrophil count is within normal limits (between 2,500 Mm to 6,000 Mm):

                Strain Specific Probiotics for Gut Microbiota Restoration and Support

                Dosage: Take 1 capsule twice daily.

                Probiotic strains to protect commensal groups and encourage gut microbiota restoration in dysbiotic contexts, displace potential pathogens, enhance gastrointestinal mucosal integrity, and beneficially impact gastrointestinal function.

                Mechanism of Action/Clinical Research:

                • Saccharomyces cerevisiae (boulardii)(SB), Lactobacillus rhamnosus (LGG®) and Bifidobacterium animalis ssp lactis (BB-12®) have demonstrated efficacy in assisting in the restoration of commensal microbiota, creating an environment representative of a healthy gut microbiome.[236],[237]
                • SB, LGG®and BB-12®exert direct antimicrobial actions upon pathogens via secreting antimicrobial peptides such as bacteriocins,[238],[239] disrupting the activity of pathogenic species by reducing gut pH (via short chain fatty acid [SCFA] production)[240] and enhancing host immune surveillance and response via dendritic cell modulation and secretory IgA stimulation; allowing more effective detection and elimination of pathogenic threats.[241]
                • LGG® supplementation reduces β-glucoronidase enzymatic activity, which is a marker associated with functional and/or pathogenic imbalance in gut microbiota.[242]

                 

                If neutrophil count is low (between 500 Mm to 2,500 Mm):

                Double Strength, Researched, Authentic LGG®

                Dosage: Take 1 capsule daily.

                Lactobacillus rhamnosus (LGG®) to enhance the gut microbiota by replenishing levels of beneficial bacteria, often compromised during chemo– and radiotherapy, as well as inhibiting the growth of pathogenic bacteria that adversely affect treatment outcomes.

                Mechanism of Action/Clinical Research:

                • LGG® supports restoration of microbial diversity, promotes the formation of SCFAs and normalises the mucosal barrier through modulation of protein mediators (occludin, zonula occludens, E-cadherin, and β-catenin) that influence barrier functionality.[243]
                • LGG®’s mucosa-binding pili prevents the binding of potential pathogens to the gut mucosa.[244]
                • LGG® (10 to 20 billion colony forming units) prescribed to patients receiving 5-fluorouracil based chemotherapy for colorectal cancer was shown to reduce abdominal discomfort and severe diarrhoea frequency compared to those who did not receive the probiotic. Reduced bowel toxicity, fewer chemotherapy dose reductions and less hospital care was also associated with LGG® supplementation.[245]

                 

                Support stress adaptation and the patient’s ability to adapt to a diagnosis of cancer, its physical symptoms and treatment:

                 

                If patient presents with low mood/depression:

                BCM-95™ Turmeric & Saffron for Depression

                Dosage: Take 1 capsule twice daily with food

                An anti-inflammatory herbal blend that reduces hypothalamic-pituitary-adrenal (HPA) activity, preventing stress-induced elevation of cortisol, glutamate excitotoxicity and subsequent inflammation and immune dysregulation.

                Mechanism of Action:

                • Both saffron and turmeric  have been found to inhibit the activity of transcription factors, such as nuclear factor kappa beta (NFκB) and mitogen activated protein kinase (MAPK).[246],[247]  Saffron and turmeric also inhibit pro-inflammatory cytokines including TNF-α, IL-1β and IL-6, all of which can affect neurotransmitter metabolism.

                A randomised, double-blind, placebo controlled study involving 123 participants that were prescribed 500 mg/d of BCM-95®Turmeric combined with 30 mg/d of saffron revealed significant reductions in depression and anxiety symptoms after 12 weeks.[248]

                  • Safranal and crocin, present in saffron, have been shown to reduce HPA axis activity and decrease stress-induced plasma corticosterone levels.[249]
                  • Safranal has also been shown to have anxiolytic and sedative effects via innervation of the GABAergic pathway.[250]  In vitro, crocin was found to have a weak, but significant affinity to the NMDA receptor and to reduce ethanol-induced depression via this affinity with the NMDA-receptor.[251]
                  • Turmeric activates glutamate decarboxylase (GAD), which converts glutamate to GABA.[252]

                  A randomised, double-blind, placebo controlled study involving 123 participants that were prescribed 500 mg/d of BCM-95™Turmeric combined with 30 mg/d of saffron revealed significant reductions in anxiety and depressive symptoms after 12 weeks.[253]

                     

                    If patient presents with anxiety:

                    Herbal Support for Hyper HPA and Stress

                    Dosage: Take 1-2 tablet three times daily

                    Anxiolytic herbs that enhance GABA activity, working against glutamate-mediated excitability in the brain to alleviate anxiety, nervous tension and agitation.

                    Mechanism of Action/Clinical Research:

                    • Zizyphus has been shown to modify the GABAα receptor subunits expressional levels,[254] which opposes glutamate-mediated excitability in the brain, contributing to its anxiolytic effects.[255]
                    • Passionflower has been found to modulate the GABA system, demonstrating an affinity for both GABAα and GABAβ receptors, increasing its inhibitory effects.[256]

                    A clinical trial involving 154 participants with prolonged nervous tension were treated with 1,020 mg/d of passionflower for 12 weeks. Passionflower significantly improved stress-associated symptoms including restlessness, sleep disturbances, exhaustion, anxiety, poor concentration, nausea, tremors, and palpitations.[257]

                      • Kudzu has demonstrated β-adrenoceptor blocking activity[258],[259] similar to pharmacological beta-blockers, which are used to reduce the physical effects of anxiety and stress such as palpitations, high blood pressure, tremor and sweating.
                      • Magnolia exhibits muscle relaxing effects via GABAergic mechanisms,[260] as well as neuroprotective properties.[261],[262]

                       

                      Mitigate malnutrition to improve recovery:

                      High Absorption Multi Mineral with Apple Cider Vinegar

                      Dosage: Add 1 1/2 metric teaspoons (6.1 g) to 200 mL of water once daily with food.

                      Bioavailable minerals to offset malnutrition and metabolic derangements associated with carcinogenesis and cancer treatments, providing basic nutrients for immune system function, musculoskeletal strength and metabolic health.

                      Mechanism of Action/Clinical Research:

                      • Delivers chelated iron, zinc and magnesium bound to a bisglycinate molecule for enhanced bioavailability. Bisglycinate mineral compounds increase mineral absorption across the gut mucosa, thereby lowering levels of free minerals in the intestinal lumen, which can contribute to digestive symptoms.[263]
                      • Magnesium supports protein synthesis, muscle contraction, nerve transmission and immune system health.[264],[265],[266]
                      • Phosphorus and calcium are both essential for forming new bone and the maintenance of existing bone.[267] When bound to phosphorus, calcium has been shown to support greater bone mineral content and bone density compared with non-phosphorous bound calcium.[268]
                      • Zinc and selenium are involved in the survival, proliferation and differentiation of immune cells, mediating innate and adaptive immunity. Acute zinc deficiency has been found to down-regulate immunity, while chronic deficiency induces proinflammatory cytokine release, commonly influencing inflammatory diseases.[269]
                      • Apple cider vinegar has been attributed with promoting health by improving digestion and metabolism.[270]

                       

                      COMBINE WITH

                      Undenatured Whey Protein Isolate

                      Dosage: Add 1 serve (20.2 g) (3 metric tablespoons) into your choice of beverage, or add 1 serve (20.2 g) (3 metric tablespoons) into your choice of food.

                      High bioavailability whey protein to support growth, development, remodelling and regeneration of the human body, essential to anabolic muscle growth and preservation of muscle mass/prevention of muscle wasting (cachexia).

                      Mechanism of Action/Clinical Research:

                      • Whey protein provides a complete amino acid profile of essential and non-essential amino acids. Whey protein also provides a rich source of branched chain amino acids (BCAAs), with highest levels of isoleucine, leucine and valine. These BCAAs are key to the growth and repair of tissues,[271] and have the ability to stimulate enzymes required to repair muscle.[272]Amino acids possess a range of metabolic and regulatory functions required for optimal physiological function, including gene expression, synthesis and secretion of hormones, nutrient absorption and metabolism, oxidative defence, intracellular protein degradation, immune function, acid/base balance, and neurotransmission.[273]

                      Whilst there are some concerns regarding the use of glutamine and whey protein, and their potential to ‘feed’ cancer and increase systemic glutathione respectively, supplementation has been found beneficial to cancer patients. For instance, glutamine has been found to mitigate gastrointestinal side effects of cancer therapy, improve wound healing after surgery and support immune function,[274]while whey protein may help to prevent muscle wasting in cancer patients.[275]

                       

                      If patient has been exposed to environmental carcinogens or has a history of infectious exposure:

                      Refer to the Metagenics Clinical Detoxification Program under Supportive Programs 

                       

                      Supportive Programs:

                      The Metagenics Clinical Detoxification Program is designed to reduce toxic burden, increase toxin resilience and improve the efficiency of waste elimination. In particular, the Liver Chemical Clearance or Gut Pathogen Elimination Detoxification streams may be used to address environmental or infectious exposures that contribute to carcinogenesis.

                      The Wellness and Healthy Ageing Program combines diet, lifestyle and supplemental interventions to support optimal health, wellbeing and quality of life, while also reducing factors that contribute to cellular ageing and chronic disease development. The Wellness diet reduces dietary sources of inflammation to promote a healthy and nourishing diet, mitigating micronutrient deficiencies that are associated with immune dysregulation.

                       

                      Diet and Lifestyle Recommendations

                      Diet:

                      • Current dietary guidelines provided for cancer patients by Cancer Council Australia recommend eating a healthy, balanced diet and consuming small meals more frequently, with a possible increase in calories and protein over time.[276]
                      • In consideration of the current guidelines from Cancer Council Australia, a wholefood diet high in plant-based foods and with moderate levels of protein is the first line recommendation for cancer patients. The Metagenics Wellness Diet reflects these wholefood principles, offering clear guidelines on a healthy eating plan while also optimising macronutrient balance.
                      • Additional dietary strategies that have been found to benefit cellular metabolism in cancer include:
                      Ketogenic diets (KD): Defined as a diet high in fat (in some cases, up to 90% fat) and low in carbohydrates, with low to moderate levels of protein. KDs are designed to drive cells to utilise fats as their primary energy source, shifting metabolism away from aerobic glycolysis. As a result, there is a rise in serum ketone bodies, which cancer cells find difficult to metabolise, further restricting their fuel source. Additionally, KDs in oncology have demonstrated beneficial effects on body composition including the maintenance of skeletal muscle mass in both overweight and frail individuals.[277]
                      Vegan/plant-based diets: Research has suggested that plant-based diets have the ability to alter cellular metabolic processes, down-regulating carbohydrate metabolism[278] and lowering glucose levels.[279] Additionally, consuming a vegan diet has been shown to significantly lower the incidence of total cancer,[280] with large population studies suggesting it could reduce the incidence by up to 19% compared to an omnivorous diet.[281]

                      Fasting diets: Short-term fasting (STF) has the ability to lower glucose, insulin-like growth factor 1 (IGF-1) and insulin, whilst activating autophagy. In cancer cells, this down-regulation causes a reduction in fuel supply, leading to an increase in intracellular ROS that stimulates cell death.[282],[283]Additionally, STF prior to chemotherapy and/or radiotherapy may reduce DNA damage and protect healthy cells from the impact of oxidative stress, reducing the toxicity of cancer therapy and increasing treatment efficacy with reduced side effects for cancer patients.[284]

                        • Specific foods such as oranges, grapes, mushrooms, celery, onion, coriander and fennel exhibit aromatase inhibitory activity, reducing the excessive production of oestrogen.[285],[286]
                        • Foods from the cruciferous family activate phase I and phase II metabolism of hormones,[287] while fibre-rich foods improve bowel clearance,[288],[289] contributing to effective hormone detoxification.
                        • Selective oestrogen receptor modulators (SERMs) including rosemary,[290] soy and turmeric[291],[292],[293] can up-regulate ER-β receptor activity, as well as antagonise oestrogen binding to ER-α.
                        • Isoflavone-containing foods including soy and flaxseed competitively antagonise oestrogen binding, as evidenced by epidemiological and intervention trials to reduce the risk of breast cancer.[294], [295]
                        • Please ensure that the patient’s dietary plan is conveyed to the overseeing oncologist, so that the patient is receiving integrated care.

                        Lifestyle:

                        • An accumulation of data has shown that exercise targets and improves several outcomes relative to cancer management including reducing cancer incidence,[296] inhibiting tumour growth,[297] alleviating cancer-related adverse events,[298] improving anti-cancer treatment efficacy,[299] lowering the risk of recurrence,[300] and improving QOL in patients.[301]
                        • More than 100 clinical exercise intervention studies have shown that exercise-induced alterations in the systemic environment influence key regulatory mechanisms in the TME, including angiogenesis, immune regulation and metabolism.[302]
                        • During exercise, the rise in heart rate and blood pressure drives blood circulation, thereby increasing tumour perfusion, angiogenesis and intratumoural vascularisation, and subsequently improving the health of the TME and reducing tumour hypoxia.[303],[304] Increased oxygen and blood flow to the TME has been shown to enhance treatment efficiency and recovery via supporting the delivery of chemo- and radiotherapy; treatments that work to reduce tumour cell volume via the generation of ROS.[305]
                        • Exercise has been proven safe, feasible and effective, even in fragile and advanced-stage cancer patients.[306] Refer to Table 3 for exercise recommendations.
                        • Exercise benefits the health of cells overall. As such, commonly reported side effects of cancer are significantly reduced, with patients often reporting improved tolerance and better recovery from treatment.[307],[308]
                        • Improved circadian rhythm has been shown to enhance cancer treatment efficacy, as evidenced by randomised clinical trials involving patients undergoing treatment for advanced-stage cancers, including metastatic ovarian, lung, colorectal, and breast cancers. Improved circadian rhythmicity has been associated with better therapeutic outcomes.[309]
                        • Psycho-oncological care forms a central part of cancer treatment. The positive impacts of psycho-oncology and stress management can improve QOL and positive health outcomes.[310] Psychosocial approaches to support the mental and emotional needs of cancer patients include cognitive behavioural therapy (CBT) techniques, psychotherapy, crisis intervention, couple and family therapy, group therapy, self-help groups and relaxation-based interventions such as meditation, progressive relaxation, guided imagery and hypnosis. Refer to Figure 4 for additional psycho-oncological targets.
                        • Hyperbaric oxygen (HBO) therapy may be used as an adjuvant treatment to enhance the efficacy of chemo- and radiotherapy. HBO assists in reducing tumour hypoxia by increasing the concentration of oxygen in the plasma. Additionally, radiation treatment is found to be most effective in well-oxygenated tumour tissue. The combination of HBO and radiation appears to reduce tumour growth, improve local tumour control and subsequently increase survival time.[311]

                         

                        Table 3: Exercise recommendation for cancer patients.[312]

                        Exercise Recommendations for Cancer Patients
                        30 minutes of exercise daily, 5 days per week (totalling 150 min of exercise per week).[313]
                        Specific side effect Exercise
                        Anxiety and/or depression 30 to 60 minutes of moderate-intensity exercise 3 times per week for 12 weeks
                        Fatigue 30 minutes of moderate-intensity aerobic exercise 3 times per week
                        Quality of life Combined 30 minutes of moderate-intensity exercise plus 2 sets of 12 to15 repetitions of resistance exercise 2 to 3 times per week for at least 12 weeks
                        Lymphoedema A supervised resistance exercise program completed 2 to 3 times per week
                        Physical function 30 to 60 minutes of moderate-intensity aerobic exercise and 2 sets of 8 to 12 repetitions of resistance exercises, 3 times per week for 8 to 12 weeks

                         

                         Figure 4: Targets of psycho- oncology.[314]

                        Figure 4 Targets of psycho- oncology at HealthMasters Support – Breast Protocol

                         

                        Clinical Investigation and Pathology: Cancer Support – Breast

                        Clinical Screening Rationale
                        Breast Self-examination

                        Breast self-examinations remain an important tool in detecting breast changes and possibly breast cancer. The following video may be used to instruct patients on how to conduct a thorough self-examination and identify unusual changes:

                        Breast self-examinations do not replace mammograms. If a change in breast tissue is detected, advise the patient to schedule a mammogram appointment or see a doctor without delay.

                        Distress Thermometer A useful screening tool that has been utilised by oncology nurses and other healthcare professionals in hospital settings. The Distress Thermometer specifically provides the opportunity for patients to voice their concerns, identify areas where immediate support is needed and to indicate if further referral to psychosocial services is required.[315]
                        Health Appraisal Questionnaire (HAQ) The HAQ provides a comprehensive assessment of physical health, allowing Practitioners to gain insight into patient symptoms and evaluate overall health and wellbeing.
                        Body Mass Index (BMI) An index to assess weight range and determine if obesity is a contributing factor to cancer development/progression or if the patient is experiencing significant weight loss due to chemotherapy and radiotherapy treatments.
                        Circadian Hygiene Review The Circadian Hygiene Review identifies factors that disrupt circadian homeostasis, which is associated with a broad range of acute and chronic conditions.
                        Depression Anxiety Stress Scales (DASS) A self-report questionnaire designed to measure the three related negative emotional states of depression, anxiety and tension/stress.
                        Mood and Stress Questionnaire (MSQ) A questionnaire designed to help Practitioners establish levels of stress, anxiety and mood concerns, prioritised in relation to each other. Appropriate treatment strategies are outlined based on common response patterns under stress, and neurotransmitter patterns associated with stress-related symptoms.
                        Omega-3 Index Test A validated test that measures red blood cell (RBC) levels of omega-3 fatty acids, EPA and DHA. An Omega-3 Index in the desirable range of 8% to12% is an indicator of better overall health.

                         

                        Pathology Testing Ideal Reference Range Rationale
                        Cancer Antigen 15-3 (CA 15-3) Normal value: <31 U/mL Tumour marker produced in breast cancer, as well as lung, ovarian, endometrial, bladder, and gastrointestinal cancers. CA 15-3 may also be elevated in benign breast conditions.
                        Cancer Antigen 27.29 (CA-27.29) Normal value: <40 U/mL Levels >100 U/mL may signify cancer Note: Approximately 30% of patients experience elevated CA-27.29 for 30 to 90 days post-treatment. Tumour marker produced in breast cancer, as well as colon, gastric, liver, lung, pancreatic, ovarian, and prostate cancers.
                        Cancer Antigen 125 (CA-125) Normal value: <35 U/mL Tumour marker produced in ovarian epithelial cancer (75%), gastrointestinal cancer (10%), lung cancer (5%) and breast cancer (5%).
                        Carcinoembryonic Antigen (CEA) Normal value: <2.5 µg/L Tumour marker produced in colorectal cancer, particularly with liver metastasis, gastric cancer, breast cancer, lung cancer, and mucinous cancer of the ovary.
                        White Cell Count (WCC)

                        Normal value: 4.0 to 11.0 x199/L

                        Differential counts:

                        Cell count x 109 /L
                        1-3 years 4-7 years 8-12 years Adult
                        Neutrophils 1.5-7.0 1.6-9.0 1.4-7.5 2.0-7.5
                        Lymphocytes 2.2-5.5 2.0-5.0 1.4-3.8 1.5-4.0
                        Monocytes 0.1-1.5 0.06-1.0 0.06-0.8 0.2-0.8
                        Eosinophils 0.1-0.5 0.1-1.4 0.04-0.75 0.04-0.4
                        Basophils <0.1 <0.2 <0.2 <0.1
                        Abnormalities including neutrophilia, neutropenia, lymphocytosis, lymphocytopenia, monocytosis, eosinophilia, basophilia, and pancytopenia may indicate malignancy.
                        MetaBiome™ Test Kit Refer to MetaBiome™ Insight Report A simple, non-invasive sampling kit performed at home and conveniently posted in the supplied reply-paid envelope for assessment. A comprehensive overview of easy-to-interpret results are emailed to the Practitioner, providing a complete picture of gut microorganisms and their function.

                         

                        Pharmaceutical Treatments:

                        Contact HealthMasters to ensure product recommendations are suitable for use in conjunction with pharmaceutical medications.

                        • Surgical Treatment: Surgery has a pivotal role in the management of cancer. Three main situations in which it is necessary include:

                        Biopsy: In the vast majority of cases, a histological or cytological diagnosis of cancer is necessary. Tissue biopsy also provides important information such as tumour type and differentiation, to assist subsequent management.[316]

                        Excision: Surgery is the mainstay of treatment for most patients and can range from a lumpectomy, where only the tumour is removed, to mastectomy, where the whole breast is removed.[317]

                        Palliation: Surgical procedures are often the quickest and most effective way of palliating symptoms. Examples include the treatment of faecal incontinence with a defunctioning colostomy, fixation of pathological fractures and decompression of spinal cord compression.[318]

                          • Chemotherapy: Chemotherapy is a broad term for a number of drugs that act to inhibit the cell cycle (i.e. cell division), causing oxidative stress, DNA damage and subsequent cellular apoptosis.[319] They have the greatest activity in proliferating cells, providing the rationale for their use in the treatment of cancer. Chemotherapeutic agents do not act specifically on cancer cells, therefore the side effects of treatment are a result of their antiproliferative actions in normal tissues such as the bone marrow, skin and gut.[320]
                          • Radiation Therapy: Adjuvant radiotherapy is given to breast cancer patients, reducing the risk of local recurrence to 4 to 6%. Radiation therapy (radiotherapy) involves treating cancer with ionising radiation. Ionising radiation can be delivered by radiation emitted from the decay of radioactive isotopes or by high-energy radiation beams, usually X-rays.[321] Three methods are usually employed:

                          Teletherapy: Application from a distance by a linear accelerator (most commonly used).[322]

                          Brachytherapy: Direct application of a radioactive source on to or into a tumour. This allows the delivery of a very high, localised dose of radiation and is integral to the management of localised cancers of the head and neck, and cancer of the cervix and endometrium.[323]

                          Intravenous injection of a radioisotope: This includes iodine for cancer of the thyroid and strontium for the treatment of bone metastases from prostate cancer.[324]

                            • Hormone Therapy: Hormone therapy is most commonly used in the treatment of breast cancer and prostate cancer. Breast tumours that are positive for expression of the oestrogen receptor respond well to anti-oestrogen therapy, and assessment of ER status is now standard in the diagnosis of breast cancer. Several drugs are now available to reduce oestrogen levels or block the effects of oestrogen on the receptor. When targeted appropriately, adjuvant hormone therapy reduces the risk of relapse and death.[325] Hormonal agents include:

                            Selective oestrogen receptor modulators (e.g., tamoxifen and toremifene): Bind to oestrogen receptors and inhibit oestrogen-induced stimulation of cell replication.[326]

                            Aromatase inhibitors (e.g. letrozole, anastrozole and exemestane): Inhibit the conversion of androgens into oestrogen by targeting the aromatase enzyme.[327]

                              • Immunotherapy: Immune-stimulants including IL-2, interferons and antibodies may increase treatment response rates and improve survival when combined with chemotherapy. However, treatment is often accompanied by systemic toxicity.[328]
                              • Biological Therapies: New generation treatments to block the signalling pathways responsible for the growth of specific tumours. Biological therapy has created the potential to target cancer cells more selectively, with reduced toxicity to normal tissues.[329] Examples include:

                              Monoclonal antibodies (e.g., trastuzumab and lapatinib): Target the human epidermal growth factor receptor 2 (HER2), an oncogene that is over-expressed in around one-third of breast cancers.[330]

                              Mammalian target of rapamycin (mTOR) inhibitor (e.g., everolimus): Inhibits mTOR to prevent the downstream signalling required for cell cycle progression, cell growth, and proliferation in patients with metastatic breast cancer.[331]

                                 

                                Additional Resources: Cancer Support – Breast

                                • How to Perform a Breast Self-examination: An instructional video that teaches patients to look and feel for changes to breast tissue.
                                • BreastScreen Clinics: There are more than 500 screening locations around Australia, including permanent screening clinics, assessment clinics and mobile units. A screening appointment can be arranged by calling ph: 13 20 50 or, alternatively, select the corresponding website of your state/territory BreastScreen service:
                                • Cancer Council Australia: Cancer Council Australia provides information and support to people affected by cancer, from the point of diagnosis through to treatment and survivorship, with the intent of lessening the detrimental impact of cancer on QOL.
                                • Breast Cancer Network Australia: Breast Cancer Network Australia is the peak national organisation for Australians affected by breast cancer.
                                • Cancer Voices Australia: Cancer Voices Australia is a national consumer advocacy organisation representing Australians affected by cancer and advocating for them at a national level.
                                • CanTeen: CanTeen is a national support organisation for young people living with cancer, aged 12 to 24 years.
                                • National Breast Cancer Foundation: The National Breast Cancer Foundation funds all forms of research into the prevention and treatment of breast cancer.
                                • Patient Education Resource: Patient education plays a pivotal role in treatment efficacy. A core component of providing education is the ability to communicate effectively and build trust and rapport with patients of all ages and learning characteristics. The Patient Education Resource outlines considerations and approaches that promote learning experiences and streamline the education process.

                                 

                                Footnotes: Cancer Support – Breast

                                [*] IDC occurs when cancer begins in the cells that line the milk duct, subsequently growing through the duct walls and into surrounding breast tissue.

                                [†] DCIS is characterised by cancer in cells that line the milk ducts of the breast, without spreading to surrounding breast tissue.

                                [‡] Invasive lobular carcinoma begins in milk-producing glands (lobules), subsequently spreading to surrounding breast tissue.

                                [§] Immunogenicity refers to the ability to provoke an immune response.

                                [**] The proportion of people with a particular genetic change (such as a mutation in a specific gene) who exhibit signs and symptoms of a genetic disorder.

                                [††] The development of small blood clots throughout the bloodstream, causing blockages in small blood vessels. The increased clotting depletes platelets and clotting factors required to control bleeding, resulting in excessive bleeding.

                                [‡‡] Cisplatin is a chemotherapy medication used to treat numerous cancers.

                                [§§] Ensuring patients maintain an omega-3 index above 8% is essential to SPM production. Omega-3 status can be evaluated/monitored using the Omega-3 Index Test (refer to Pathology Testing section). In the instance of deficiency, consider co-prescribing High Purity, Low Reflux, Concentrated Fish Oil Liquid or Capsules.

                                [***] The oestrogenic activity of soy has caused apprehension among Practitioners regarding consumption and therapeutic use in hormone-dependent cancers such as breast cancer. The current body of existing human evidence supports the safety of soy in relation to breast cancer and other reproductive conditions. For further information and literature on the safety of soy, please contact the Clinical Support team.

                                [†††] A daily dose of Soy, Methylating Nutrients & BCM-95™ Turmeric to Clear Oestrogen contains 115 mg of soy isoflavones.

                                [‡‡‡] Heat shock proteins are a class of proteins induced when cells are exposed to stressful conditions such as cellular insult, environmental changes, temperature alterations, infections and tumours. Heat shock proteins increase mitochondrial biogenesis and the expression of antioxidant enzymes.

                                [§§§] Probiotics should not be used during haematopoietic stem cell transplants or in instances of neutropenia (<500 Mm).

                                 

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