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Understanding Breast Cancer

Natural Strategies in Collaborative Cancer Care

Compiled by John G. Connor, M.Ac., L.Ac.

edited by Barbara Connor, M.Ac., L.Ac.

April 6, 2011

Table of Contents

1. Introduction
2. Natural Strategies in Collaborative Cancer Care
3. Examples of Natural Compounds that Protect against Breast Cancer
4. Examples of Pathology and Blood Test to Perform in Breast Cancer
5. Examples of Chemotherapeutic Agents Used in Breast Cancer
6. Tumor Markers in Breast Cancer
7. Examples of Natural Compounds that Target Growth Factors and Genes in Breast Cancer
8. Breast Cancer and Bone Metastasis
9. Examples of Natural Compounds that Protect against Bone Cancer
10. Comprehensive Cancer Care Consultations
11. References

 

Introduction

 

Breast cancer is the most common type of malignancy diagnosed in women with more than 180,000 estimated new cases in USA in 2008. Almost one third (32%) of all cancers diagnosed in women are breast cancer. (Miele et al 2009)

 

Individual studies estimate that as many as 69% of US cancer patients employ some type of complementary and alternative medicine, 76% of patients in a study of Midwestern cancer patients and 95% of radiation oncology patients in another study.  (Wargovich et al 2010)

 

Barbara and I feel that the emerging concept and practice of targeted therapies which have a high specificity toward tumor cells provides a broader therapeutic window with less toxicity than the current chemotherapeutic agents. They are also often useful in combination with cytotoxic chemotherapy or radiation to produce additive or synergistic anticancer activity because their toxicity profiles often do not overlap with traditional cytotoxic chemotherapy. Targeted therapies represent a new and promising approach to cancer therapy, one that is already leading to beneficial clinical effects. There are multiple types of targeted therapies available, including monoclonal antibodies, receptor tyrosine kinase inhibitors, and growth factor receptor inhibitors.

 

The wonderful thing about botanicals and nutritives is that they target many of the same growth factors, receptors and pathways as conventional drugs and chemos but in a gentler and less toxic way thereby allowing for decreased dosages in the more toxic chemos and drugs. One of the characteristics of plants is that they are pleiotrophic, i.e., they exert multiple effects. Therefore botanicals and herbs by their very nature not only enhance the effectiveness of chemos and drugs but they can reduce or eliminate many of their unwanted side effects.

 

There is an ever growing interest in treatment with natural compounds as an adjuvant cancer therapy along with conventional cancer therapy. (Virk-Baker et al 2010) For example the combination of a natural VEGF inhibitor along with lower doses of a pharmacological agent may prove helpful in reducing the unwanted side effects of chemotherapy. (Wargovich et al 2010)

Natural Strategies in Collaborative Cancer Care

 

The following is a list of natural strategies we employ and the issues we address in our approach to integrative cancer care:

 

·         Alkalinity and Acidosis in Cancer

·         Angiogenesis Blood Markers

·         Appendix of Cancer Pathways

·         Blood Tests for Cancer-Related Cachexia

·         Blood Tests that Detect Various Polymorphisms that Relate to the Metabolism or Detoxification of Chemotherapy

·         Blood Tests to Assess Hypercoagulation

·         Bone Building Protocol for Bone Related Cancer

·         Cancer and Sugar

·         Chemotherapy and Predictive Bio-markers

·         Copper Reduction Protocol

·         Counteracting Cancer Related Cachexia with Natural Compounds

·         Cytotoxic Herbs & Their Functions

·         Factors that Increase the Risk of Blood Clots and Thrombosis.

·         Glossary of Chemotherapeutic Drugs

·         Growth Factors and Genes Involved in Cancer

·         How Elevated Glucose and Insulin Promote Cancer

·         Immunotherapy - Activating the Immune System with Natural Compounds

·         Inflammatory Blood Markers

·         Inhibiting Angiogenesis with Natural Compounds

·         Managing the Side Effects of Chemotherapy with Natural Compounds

·         Markers for Assessing Bone Health

·         Natural Aromatase Inhibitors

·         Natural Compounds that Act as Biological Response Modifiers

·         Natural Compounds That Alleviate the Side Effects of Chemobrain

·         Natural Compounds that are Radiation Protective or Synergistic with Radiation Therapy

·         Natural Compounds that Downregulate HPV

·         Natural Compounds that Downregulate IGF and are Insulinotrophic, and Anti-cancer.

·         Natural Compounds that Enhance the Effectiveness of Paclitaxel

·         Natural Compounds that Enhance the Effectiveness of Platinums

·         Natural Compounds that Inhibit Multi Drug Resistance

·         Natural Compounds that Lower Homocysteine

·         Natural Compounds that Protect against Bone Cancer

·         Natural Compounds that Protect against the Side Effects of Doxorubicin

·         Natural Compounds that Reduce the Side Effects of Carboplatin

·         Natural Compounds that Reduce the Side Effects of Paclitaxel

·         Natural Compounds that Reduce the Side Effects of Platinol (Cisplatin)

·         Natural Compounds that Reduce the Side Effects of Platinum Drugs

·         Natural Compounds that Synergize with Doxorubicin (Anthracyclines)

·         Natural Compounds that Target Growth Factors and Genes Involved in Cancer

·         Natural Compounds which Hasten Recovery from Surgery

·         Neuropathy and Cancer Pain Management

·         Nutritional Support for Glutathione and Optimal Liver Detoxification

·         Radiation and Cancer

·         Reducing Inflammation with Natural Compounds

·         Suppressing Hypercoagulation with Natural Compounds

·         Surgery and Cancer

·         Teas and Soups which Alleviate the Side Effects of Chemo and What to Eat During Chemo

·         Tissue Pathology Reports

·         Understanding the Mechanism behind Bone Metastasis

 

Examples of Natural Compounds that Protect against Breast Cancer

 

1.       Andrographolide - posseses potent anti-tumor actions against breast cancer. (Zhi 2007) (Zhen 2007)

 

2.       Black cohosh – A population-based case control study involving 949 breast cancer cases found that use of black cohosh had a significant breast cancer protective effect. (Rebbeck et al 2007)

 

3.       Carotenoids – A nested case-control study of 295 cases found that carotenoids may protect against the development of breast cancer. (Sato et al 2002)

 

4.      Coenzyme Q(10), Riboflavin and Niacin (CoRN) - Tamoxifen on coadministration with CoRN has a favorable impact on various blood chemistry profiles. However, large scale randomized studies over a longer time span are required to ascertain the safety and efficacy of co-administrating antioxidants with conventional chemotherapy. (Yuvaraj et al 2008)

 

5.       Curcumin - In addition, curcumin exerts strong anti-invasive effects in vitro that are not estrogen dependent in the ER-negative MDA-MB-231 breast cancer cells.  These anti-invasive effects appear to be mediated through the downregulation of MMP-2 (matrix metalloproteinase) and the upregulation of TIMP-1 (tissue inhibitor of metalloproteinase), 2 common effector molecules that have been implicated in regulating tumor cell invasion. This study also demonstrates that curcumin inhibits the transcript levels of 2 major angiogenesis factors VEGF (vascular endothelial growth factor) and b-FGF (basic fibroblast growth factor) mainly in ER-negative MDA-MB-231. (Shao et al 2002)

 

6.       Curcumin - The inhibition of cell growth and induction of apoptosis by curcumin in MCF-7 breast cancer cells might be mediated, at least partially, by its ability to down-regulate the insulin-like growth factor-1 (IGF-1) axis. (Yangqui et al 2007)

 

7.       Curcumin inhibits cell proliferation of MDMA-MB-231 and BT-483 breast cancer cells mediated by down-regulation of NFκB, cyclin D and MMP-1 transcription.  (Liu et al 2009)

 

8.       DIM synergizes with chemotherapeutic agents by inhibiting multi-drug resistance through downregulation of P-glycoprotein (P-gp), and is a potent chemopreventive agent for hormonal-dependent cancers such as breast, prostate and cervical cancer. (Aggarwal and Ichikawa, 2005)

 

9.       Fish oil – In a study involving 980 cases of incident invasive breast cancers it was found that current use of fish oil was associated with reduced risk of breast cancer. Ten-year average use was suggestive of reduced risk. These results held for ductal but not lobular cancers. (Brasky et al 2010)

 

10.   Ginseng – In a study involving 1,455 breast cancer patients it was found that ginseng use after cancer diagnosis, particularly current use, was positively associated with QOL (Quality of Life) scores, with the strongest effect in the psychological and social well-being domains. Additionally, QOL improved as cumulative ginseng use increased. (Cui et al 2006)

 

11.   Honokiol - Here we show that Honokiol, a natural dietary product isolated from an extract of seed cones from Magnolia grandiflora, can decrease PI3K/mTOR pathway-mediated immunoresistance of glioma, breast and prostate cancer cell lines, without affecting critical proinflammatory T cell functions. (Crane et al 2009)

 

12.   Honokiol inhibits in vitro and in vivo growth of breast cancer through induction of apoptosis and cell cycle arrest.  (Wolf et al, 2007)

 

13.   I-3-C (indole-3-carbinol) – which converts into DIM, induced marked reduction of EGFR in human breast cancer cell lines prior to cell death. (Moiseeva, Heukers & Manson 2006)

 

14.   Mistletoe - 3 controlled human studies using viscum album (mistletoe) extracts reported statistically significant benefit in women with breast of gynecological cancer. (Kienle et al 2009)

 

15.   Omega-3 fatty acids - Diets high in omega3 fatty acids exert suppressive effects on cancer growth and are associated with impaired angiogenesis.  Both EPA and DHA have shown to inhibit metastasis of several cancer cell lines including breast, prostate and colon cancer.  For example, one study found that total n-6 poly-unsaturated fatty acids may be contributing to the high risk of breast cancer in the United States and that specific long chain n-3 poly-unsaturated fatty acids derived from fish oils may have a protective effect. (Bagga et al 2002)

 

16.   Resveratrol – IGF-II is a potent mitogen and inhibitor of apoptosis in breast cancer. Resveratrol regulates insulin-like growth factor-II (IGF-II) in breast cancer cells.  (Vyas, Asmerom and DeLeon, 2005)

 

 Examples of Pathology and Blood Tests to Perform in Breast Cancer

 

Specific Breast Cancer markers:

• CEA
• CA 27-29
• CA 15-3
• CTCs (Circulating Tumor Cells)
• serum p53 antibodies

 

Blood tests relative to ER/PR+ breast cancer

• Estradiol
• Estrone Sulfate
• Prolactin
• SHBG (Sex hormone binding globulin)

 

Blood test relative to HER II neu+ breast cancer

• Serum HER II neu

 

General Tissue Pathology and Blood Tests:

• Bcl-2 – suppresses apoptosis, high expression mean less-favorable prognosis – poor response to chemo.
• BRCA-1 & 2 – are tumor suppressor genes.  You want them to be “wild type” i.e., not mutated, because when they are mutated they become repressed.  BRCA 1 and 2 “negative” means “no mutation detected”.
• CD-24 – Breast cancer, more aggressive predicts tamoxifen resistance
• CK-19 – low levels associated with poor outcome in triple negative breast cancer
• ER/PR (CD 24 over-expression predicts tamoxifen resistance)
• Her 2 neu (FISH method) (Co Her II and ER expression predicts tamoxifen resistance)
• Her I (EGFR) – overexpressed in TNBC
• KI-67 (<10% favorable)
• Mutant proteins: p53, Bcl-2, PTEN, p21, p27, p63, nm23.

 

Examples of Chemotherapeutic Agents Used in Breast Cancer

 

·         Abraxane – Breast Cancer: the relative efficacy of Abraxane was significantly higher compared with taxol in HER2-negative tumors (three of three) and in HER2-positive tumors with high levels of SPARC*. (Anticancer Drugs. 2008 Oct;19(9):899-909)

 

o        SPARC (Secreted Protein Acidic Rich in Cysteine) is an extracellular matrix protein found in the tumor cell surface and which is rapidly internalized into the tumor cell.

 

o        Patients with SPARC-positive tumors, that is, those with the worst prognosis, will respond favorably to Abraxane therapy, whereas other taxanes will not. (Transl Oncol. 2009 May;2(2):59-64)

 

·         Aromasin – an aromatase inhibitor.

o        Loss of E-cadherin expression is associated with better response to aromatase inhibitors versus tamoxifen. (Borley et al 2008)

 

·         Herceptin – is a monoclonal antibody.

o        PTEN is essential to long-term success with Herceptin, i.e., inactivation of PTEN causes resistance to Herceptin. 

o        Single nucleotide polymorphisms associated with herceptin include:  P95HER2, EGF, IGFIR & PI3-K.

o        Used for metastatic HER2 positive breast cancer.

 

·         Paclitaxel with DIM synergistically inhibits the growth of HER2/neu breast cancer cells.

 

·         Tamoxifen – an anti-extrogen/SERM.

o        Single nucleotide polymorphisms associated with tamoxifen include: CYP2D6, BRCA1, Pak1, A1B1 & HER-2, CK-19, AP-1, CYP17.

o        Upregulation of Met expression in breast cancer cells promotes resistance to the Erb B2-targeted TAM antibody (Shattuck 2008). 

o        Combined HerII & ER expression predicts TAM resistance.

o        Loss of E-cadherin expression is associated with better response to aromatase inhibitors vs. TAM. (Borley 2008)

o        Tamoxifen use is associated with increased risk of venous thrombo-embolism, pulmonary embolism and stroke, endometrial cancer and uterine sarcoma.

 

·         Tykerb (Lapatinib) -. Is a small tyrosine kinase inhibitor.

o        Tykerb crosses the blood brain barrier. It is used with herceptin & Xeloda.

o        It targets Her2 & Her1.

 

·         Xeloda – is a nucleic acid blocker, an anti metabolite.

o        Lower levels of MTHFR correspond to less toxicity of Xeloda at standard dosing. (Etienne-Grimaldi 2007).

o        MTHFR, thymidylatesynthase (TS), and dihydropyrimidinedehydrogenase (DPD), relate to resistance and increased toxicity of 5FU and Xeloda. Clin Cancer Res 2006;12 (18 ) September15, 2006 DPD (Dihydropyrimidine dehydrogenase) is the 1^st and rate-limiting enzyme in the pathway involved in the degradation of pyrimidine bases uracil and thymine. DPD is responsible for catabolism of 5-fluorouracil

o        MTHFR C677T and A1298C mutations are associated with increased toxicity and side effects of methotrexate 5-FU/ Xeloda, as well as Almita. Ann Rheum Dis. 2004;63(10): 1227-31. Br J Cancer. 2004;90(2):526-34

o        If thymidylate synthase is low it shows us that Xeloda is useful.

o        Xeloda use is associated with ischemia, pericarditis and CHF.