Patient case: 67-year-old female with Breast cancer. Genetic variant: FGFR1 Amplification, PTEN (Q171). Other conditions: Depression, Hypertension, Heart Disease.

Clinical trial: Natural Supplements and a Special Diet in Eliminating Cancer-impacting Hormones From Sources Outside the Body in Patients With Early-Stage or Remission Prostate Cancer, Breast Cancer, or Uterine Cancer

Summary: RATIONALE: Natural supplements and a special diet may help rid the body of estrogen and testosterone and may slow the growth of tumor cells.
  PURPOSE: The purpose of this randomized Phase I trial is to first IDENTIFY, through laboratory analysis and validating cellular biochemical pathways, and HELP CONTROL, using natural supplements and a special diet work, extemporaneous and environmental (man-made) hormones, hormone impacting compounds and hormone-mimicking compounds that are made outside the body, found in manufactured products or in-taken to the body of cancer patients through life-style, environmental or consumption products. Patients with early-stage or remission stage prostate cancer, breast cancer, or uterine cancer have a much greater sensitivity to these extemporaneous hormonal or hormonal influencing compounds.

Detailed description: OBJECTIVES:
  To utilize multiple naturally-occurring micro-trace element compounds to sequester exogenous estrogens, estrogen-mimicking and estrogen-influencing compounds, from multiple sources, including environmental and metabolic sources, and eliminate them from the body prior to influencing prostate, breast, and uterine cancer pathways in cancer patients and cancer patients in remission.
  To utilize specific naturally-occurring flavonoids to suppress proliferation-stimulating activities induced by normal metabolism and environmental estrogen, estrogen-mimicking, estrogen-influencing and testosterone-type compounds.
  To utilize DPPH radical-scavenging activity to reduce secondary bonding of TMPRSS2-ERG fusing and negative-bonded environmental estrogen.
  To utilize endocrine system related immune response compounds as a means to help control and/or chemically influence/impact extemporaneous environmental and accumulated life-style estrogen, estrogen-mimicking, estrogen-influencing and testosterone-type compounds for preventing or controlling recurrence of breast, uterine or prostate cancers; hormonally influenced cancers.
  To utilize a full diet of specifically grown inclusion produce to maintain normal metabolic function.
  BACKGROUND DATA:
  Laboratory analytical instrumentation has improved the ability to measure, track and analyze extemporaneous environmental and accumulated life-style estrogen, estrogen-mimicking, estrogen-influencing and testosterone-type compounds.
  The initial data accumulation of spheres of chemical influence from human hormonal, hormonal-mimicking or hormonal-influencing compounds has radically changed since the beginning of this Phase 1 clinical trial.
  For example, endocrine disruptor compounds (EDCs) also commonly called hormonally active agents (1) have been shown to have strong estrogenic-type effects on the body of both female and male cancer patients. Whereas xenoestrogenic compounds, example PCBs, BPA, DDT and phthalates, have been found to have direct body influence, other hormonally-influencing compounds, like nicotine and atrazine, are not as easily predictable in how they affect existing and remission cancers.
  The pharmacological actions of nicotine, for example, have been shown to impact hormonal and growth factors and Marinucci et al (2) showed concretely that nicotine differently regulated cell growth. With the work of Camargo, et al (3) the effect of nicotine on androgen over-production was settled as factual. The tobacco industry has seemingly allowed the connection of smoking and cancer to be investigated when the causal agent for the cancers are limited to carcinogens found in "smoke." However, newer analyses show clearly that nicotine itself, found in the cigarette smoke and today in e-cigarettes, as having an influence on estrogen synthesis in the body as well as blocking monoxygenase control of HMG-CoA Reductase and thereby control of oncogenic expression. The pathway is clear that nicotine-induced sympathetic activation could account for also the increased thyroid hormone secretion and as a result the nicotine-influenced estrogen metabolic pathway, resulting in lower estrogen levels but higher androgen levels also affects TSH levels. Combined these two factors, influenced by nicotine, show real biochemical pathway to both influencing benign breast cancer and remission breast cancer to have a more androgen-influenced aggressive behavior. The androgen influenced recurrence breast and prostate are less controllable by any current level of pharmaceutical control method.
  Raval (4) showed chemically that nicotine, not other compounds in "smoke," reduces circulating estrogen. Therefore in the metabolic pathway, preventing the final metabolite, estrogen, increases the precursor compounds, increasing circulating androgen. While Holloway, et al, (5) showed that in utero exposure to nicotine had a demonstrable influence of endocrine effect on placental development and corresponding (decrease) of fetomaternal circulation.
  Newer research, Bavarva, et al, (6) indicates that environmental impact and/or lifestyle addictions, nicotine in this example, alter actual gene expression and, in and of itself, can cause the genetic basis for induced cancer development.
  EDCs, (endocrine disruptor/disrupting compounds), are found in multiple industry arenas. Due to advances in detection techniques, endocrine disruption, known as far back as the early 1990s, was generally thought to be "specie-specific." However, newer research has found that not to be the case.
  On a worldwide scientific research basis, the triazine family of nitrogen containing six-membered heterocyclic benzene aromatic ring compound herbicides are regarded as an endocrine disrupting compound. Hayes (7) found significant sex gland aberrations and gender-bending in amphibians exposed to varied levels of atrazine in field/natural conditions that were then validated in laboratory conditions.
  In 2007 the EPA found cause to suspect triazine/atrazine as having endocrine/hormonal impact on developing children (8) but as atrazine is the number one selling herbicide in the USA, pressure from the agricultural and chemical manufacturing industry keeps the product in the marketplace.
  Research by Mizota (9) clearly showing "atrazine exerts inflammatory activity through activation of putative G(q/11)-coupled neurosteroid receptor and phospholipase C" then allows for the atrazine-induced biochemical estrogen impacting pathway with altered receptors of male versus female developmental hormonal response. More specifically; progesterone receptor-modulation of atrazine-induced mast cell degranulation changes the pathway of estrogen/ estriol, 17β-estradiol and progesterone creating an accumulation of precursor compound, 17β-estradiol, and therefore the androgen precursor, without the final product of the synthesis: estriol.
  17β-estradiol has an extreme level of hormonal activity and as a result, when over-produced or found in amounts not of specific ration to other estrogenic hormones, specifically estriol (the down-stream product of 17β-estradiol synthesis) the result is a higher affinity in receptors for 17β-estradiol instead of the lower DNA influencing compound estriol. This bondage impairs G1, S, or G2 phases of DNA repair in the cell cycle and directly accelerates the proliferation of DNA damaged cells, cancerous, in breast, uterine and ovarian organs. (10) Due to the persistence of the triazine family of herbicides in soils and ground/drinking water and its apparent impact on hormonal reactions, the EU banned atrazine/triazine from use in any EU country. Further, atrazine residue on products imported into the EU is also severely restricted.
  Atrazine is found in virtually every USA woman's body, notably in breast and ovarian tissue. It is found in more US state drinking water tests than any other pollutant. It is second in usage to glyphosate on USA crop acres but, as it was in use decades before glyphosate, it is higher in groundwater sampling as of 2011.
  As a result of these newer levels of cellular research, extemporaneous influences on cancer, notably hormonal cancers, are being found as having a crucial role in the continuing rate of breast, prostate, uterine and ovarian cancers.
  Negating these near-human and human-like EDCs and/or their influence on the body has, to date, been overlooked as a therapy and under-emphasized as the course of action for cancer treatments. This study both advances the roles EDCs play in hormonally controlled cancers and the effect natural plant compounds, coupled with ultra-trace mineral/elemental molecules, have in reducing or eliminating them from negative impact in the human body.
  OUTLINE: Patients are randomized to 1 of 2 arms.
  Arm I: Patients receive oral natural supplements comprising indole-3-carbinol, perillyl alcohol, glucuronic acid, and flavonoids daily for 12 months. Patients also consume whole foods comprising indole-3-carbinol and a diet that eliminates exogenous growth hormones.
  Arm II: Patients do not receive natural supplements or consume whole foods or a special diet.
  Levels of compounds of interest are measured by inductively-coupled plasma mass spectrometry, high performance liquid chromatography, gas chromatography, and matrix-assisted laser desorption/ionization time of flight mass spectrometry.
  After completion of study therapy, patients are followed periodically for 6 months and monitored for a second 6 months period.
  1. Krimsky S (December 2001). "An epistemological inquiry into the endocrine disruptor thesis". Ann. N. Y. Acad. Sci. 948 (1): 130-42. doi:10.1111/j.1749-6632.2001.tb03994.x. PMID 11795392.
  2. Marinucci L, Bodo M, Balloni S, Locci P, Baroni T. "Sub-Toxic Nicotine Concentrations Affect Extracellular Matrix and Growth Factor Signaling Gene Expressions in Human Osteoblasts." J Cell Physiol. 2014 Apr 29. doi: 10.1002/jcp.24661. PMID: 24777817
  3. Camargo IC, Leite GA, Pinto T, Ribeiro-Paes JT. "Histopathologycal findings in the ovaries and uterus of albino female rats promoted by co-administration of synthetic steroids and nicotine." Exp Toxicol Pathol. 2014 Jul;66(4):195-202. doi: 10.1016/j.etp.2014.01.005. Epub 2014 Feb 18. PMID: 24556002
  4. Raval AP. "Nicotine addiction causes unique detrimental effects on women's brains." J Addict Dis. 2011 Apr;30(2):149-58. doi: 10.1080/10550887.2011.554782. Review. PMID: 21491296
  5. Holloway AC, Salomon A, Soares MJ, Garnier V, Raha S, Sergent F, Nicholson CJ, Feige JJ, Benharouga M, Alfaidy N. "Characterization of the adverse effects of nicotine on placental development: in vivo and in vitro studies." Am J Physiol Endocrinol Metab. 2014 Feb 15;306(4):E443-56. doi: 10.1152/ajpendo.00478.2013. Epub 2013 Dec 24. PMID: 24368670
  6. Bavarva JH, Tae H, Settlage RE, Garner HR. "Characterizing the Genetic Basis for Nicotine Induced Cancer Development: A Transcriptome Sequencing Study." PLoS One. 2013 Jun 18;8(6):e67252. Print 2013. PMID: 23825647
  7. Hayes, Tyrone B.; Anderson, Lloyd L.; Beasley, Val R.; de Solla, Shane R.; Iguchi, Taisen; et al. (2011). "Demasculinization and feminization of male gonads by atrazine: Consistent effects across vertebrate classes". The Journal of Steroid Biochemistry and Molecular Biology 127 (1-2): 64-73. doi:10.1016/j.jsbmb.2011.03.015. PMID 21419222
  8. Atrazine: Chemical Summary. Toxicity and Exposure Assessment for Children's Health (Report). U.S. Environmental Protection Agency. 4/24/2007
  9. Mizota, K.; Ueda, H. (2006). "Endocrine Disrupting Chemical Atrazine Causes Degranulation through Gq/11 Protein-Coupled Neurosteroid Receptor in Mast Cells". Toxicological Sciences 90 (2): 362-8. doi:10.1093/toxsci/kfj087. PMID 16381660
  10. Thomas, Christoforos; Strom A.; Lindberg K.; Gustafsson J. (22 June 2010). "Estrogen receptor beta decreases survival of p53-defective cancer cells after DNA damage by impairing G2/M checkpoint signaling". Breast Cancer Research and Treatment 127 (2): 417-427. doi:10.1007/s10549-010-1011-z. PMID 20623183

Eligibility: DISEASE CHARACTERISTICS:
  -  Diagnosis of prostate, breast, or uterine cancer
  -  Early-stage disease
  -  Currently waiting to initiate conventional therapy or radiotherapy OR receiving concurrent conventional chemotherapy or radiation therapy
  -  Hormone receptor status not specified
  PATIENT CHARACTERISTICS:
  -  Menopausal status not specified
  PRIOR CONCURRENT THERAPY:
  -  See Disease Characteristics
  -  Prior or concurrent chemotherapy or hormonal therapy for cancer allowed

Relevance to patient case: not relevant