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BLOG: June 2010 - December 2013

I - Breast cancer risk factors

3. Breast cancer risk factors - overview

 2 good choices to prevent breast cancer

I - BREAST CANCER
 RISK FACTORS
  

II - SCREENING X-RAY MAMMOGRAPHY

III - ALTERNATIVE TESTS

The biggest risk factor
 Risk factors overview
Times change

END OF A MYTH
The whistle
Contra-argument
Last decade
Current picture

 OTHER  X-RAY TESTS
Digital standard
Tomosynthesis
Breast CT

Predisposing factors
Diet     Other

BENEFIT
Earlier diagnosis
Fewer breast cancer deaths

Gamma-ray tests
BSGI/MBI 
PEM

INITIATING  FACTORS
Radiation
Chemicals
Viruses

RISK  &  HARM

OTHER  TESTS
Breast MRI
Ultrasound
Thermography
AMAS test

INACCURACY RISKS False negative
False positive
Overdiagnosis
PROMOTING  FACTORS
Hormonal: HRT, xenoestrogens, frame size
BMI, bra, screening

RADIATION

Radiation primer
Screen exposure
Radiation risk
PHYSICAL EXAM
Clinical
Self-exam

Higher all-cause mortality?

• Minimizing breast cancer risk

In the most simplified context, we can say that all it takes for breast cancer - or any other - to start growing and keep growing unopposed is two things:

(1) fatally compromised cell-cycle integrity and

(2) immune system insufficiency.

The former invariably involves malfunction of the cellular DNA which, in turn, requires multiple alterations to it, with the combined effect producing malignant cell. These DNA alterations can be either passed through hereditary line (most or, very seldom, all of them) or, much more often, result of a damage to the DNA by carcinogens.

And such damage can only occur if all protective lines - set by the body's detox system and body's oxidative protection - fail. This can protective inefficiency may and may not be due to the great magnitude of exposure to the carcinogen.

Finally, the damage only counts if repair mechanism, for whatever reason, fails.

So, the typical cancer path is:

multiple exposure to carcinogen
multiple protective systems failure
accumulated DNA damage/repair failure
malignant cell cycle alteration
immune system failure
cancer

Considering how incredibly complex all this is - from the protective systems to the cell cycle and immune system  - it is no wonder that the list of known or suspected breast cancer risk factors is a mile long. In order to make it easier to grasp, these factors can be grouped according to their primary role in the disease.

Those that exist before the cancer forms are predisposing breast cancer risk factors.

Those that actually push the cell into cancerous transformation by damaging or inhibiting some of its vital functions, are initiating factors, or carcinogens.

And those that in some way stimulate or make easier growth and proliferation of the existing cancerous cells are breast cancer promoting factors.

The distinction is often vague, since predisposing factors before cancerous transformation often become promoting factors after it. Most of the factors involved with breast cancer formation can have such a dual role.

Following is a lists of major breast cancer risk factors grouped according to this general scheme, with each factor given an expanded window in a table below.

 BREAST CANCER RISK FACTORS

(A)  PREDISPOSING

1 - Compromised detox system (including body's oxidative protectioon) due to toxic overload and nutritional deficiencies, chronic stress and/or negative emotions
2 - Compromised oxidative protection
3 - Genetic polymorphism compromising neutralization of carcinogens,  DNA repair and cell cycle control
4 - Compromised immune system increasing likelihood of an
active viral infection
5 - Other
 • Nutritional deficiencies/imbalances
 • Regular alcohol consumption
 • Smoking

(C)  PROMOTING

1
- Compromised immune function due to chronic stress, negative emotions and/or chronic internal infections
2
- Compromised detox system due to toxic overload and nutritional deficiencies, chronic stress and/or negative emotions
3
- Mitogenic/antiapoptopic hormones
• Ovarian hormones high/unbalanced
• Hormonal medical treatments
• Exposure to environmental estrogens
• Elevated insulin
• Elevated IGF
4
- Genetic polymorphism compromising cell cycle control
and immune system efficiency
5 - Other
 • Nutritional deficiencies/imbalances
 • Regular alcohol consumption
 • Smoking
 • Low melatonin due to lack of sleep
 • Wearing bra extensively
 • Obesity/weight gain (postmenopausal)
 • Lean body (premenopausal)
 • Insufficient/inadequate checkups

-


(A)  FACTORS PREDISPOSING FOR BREAST CANCER
 

A1 - Compromised detox system

toxic overload

toxins from food, air, water, dental implants, medications, internal microorganisms. Overburdened and/or compromised by genetic/nutritional deficiencies detox system can't efficiently metabolize and dispose of toxins; toxic metabolites inflict injury by causing oxidative damage or cross-linking with body molecules, including DNA

nutritional deficiencies

detox function is dependant on the wide spectrum of nutrients

chronic stress
psychological trauma

negatively affects entire metabolism, detox and other functions

negative emotions

negative self-image, pessimism,  suppression of emotions,
poor organizing

chronic dehydration 

sufficient water intake is a must for efficient detox function

A2 - Compromised oxidative protection

oxidative exposure

tobacco smoke, chlorine, pesticides, food additives, drugs, air pollutants, heavy metals, ultraviolet light...

nutritional deficiencies

oxidative protection depends on many antioxidant nutrients

A3 - Inherent genetic aberrations

BRCA1/2 gene mutation

  tumor-suppressor genes, short for BReast CAncer; mutation increases the risk up to tenfold; estimated 5-10% of all breast cancer cases carry mutated BRCA1 or 2

ATM gene mutation

  also part of tumor-suppressing mechanism, Ataxia-telangiectasia mutated gene is estimated to be  altered (heterozygous carriers) in up to 1% of women; up to 10% of all breast cancer cases are carriers, possibly more

CHEK2 gene mutation

  cell cycle checkpoint regulator gene, acting on signals of DNA damage to prevent cellular division; functionally associated with BRCA1 and TP53; its 1100delC heterozygous polymorphism has estimated <1% incidence and threefold increase in breast cancer risk

TP53 gene mutation

tumor (suppressor) protein p53 gene is mutated in more than half of all cancers, but only in about 20% of breast cancer cases; however, research indicates that TP53 mutations are nearly three times more frequent in BRCA1/2 germline mutation carriers; TP53 is regulated by CHEK2 (which is, in turn, activated by ATM), which activates TP53 to arrest cell cycle for an attempt at DNA repair, and then breaks it down to prevent apoptosis (programmed cell death) if repair succeeds; illustrates genetic interactions and interdependency 

FOK1 gene mutation

vitamin D receptor gene, whose proper function is needed for efficient cellular use of vitamin D, which inhibits cell proliferation, and downregulates both estrogen and progesterone receptors; significantly lower risk increase than for above polymorphisms (indicated ~25% for Ff and ~60% for ff FOK1 polymorphism), but much higher incidence (about 40-50% and 10%, respectively)

PALB2 gene mutation

partner and localizer of BRCA2 protein enables accumulation of BRCA2 protein in the cell nucleus; it is altered in less than 1% of women, doubling the risk of breast cancer

 PTEN gene mutation

  another gene encoding tumor-suppressing protein (phosphatase and tension homolog enzyme), PTEN mutations are very rare, usually associated with Cowden syndrome; carriers have up to 6 times higher breast cancer lifetime risk

A4 - Compromised immune system

chronic stress

stimulates production of adrenal hormones, inhibiting immune function, shrinking the thymus gland and weakening antiviral response

chronic internal infections,
intestinal bacterial/fungal overgrowth,
insufficient rest (sleep) time,
high sugar intake,
high blood lipids,
nutritional deficiencies,
smoking, alcohol, overweight,

negative emotions

poor lifestyle choices negatively affect the immune function

A4 - Other predisposing factors

nutritional deficiencies/imbalances

compromising detox, antioxidative, and/or cellular function

regular alcohol consumption

regular, even quite moderate consumption inked with higher blood estrogen levels; other possible mechanisms include increased solubility of carcinogens, interfering with folate metabolism, elevated oxidative stress and mutagenic effects of its primary metabolite, acetaldehyde

tobacco smoke

contains over 4000 chemicals, most of them toxic, and over 50 known carcinogens

(B) FACTORS INITIATING BREAST CANCER (CARCINOGENS)

B1 - Radiation exposure

early-life
medical exposures

radiation exposures before age 20, beginning with fetal exposures and subsequent X-ray and nuclear medicine diagnostic (γ-rays) exposures

mammography

cumulative doses in extended periods of time can be significant

galactography

imaging of breast's milk ducts by mammography unit; similar exposure as low-level mammography

other adult chest or whole body exposures

other radiology diagnostic procedures, occupational exposures, nuclear fallout, smoking (from Polonium 210), air travel, radon, background radiation

non-ionizing radiation
(power field)

although the evidence is inconclusive, there are clear indications that exposure to non-ionizing radiation can be significant breast cancer risk factor

B2 - Viral infections

sexual intercourse,
physical contact, food (grains), 
pets (?)

human papilloma virus (HPV), mouse mammary tumor virus (MMTV), Epstein-Barr virus (EBV) and bovine leukemia virus (BLV) have been identified at higher to much higher incidence in breast cancer patients; each has the ability to alter cellular DNA, transforming normal cells into malignant

B3 - Chemical carcinogens

industrial chemicals (including food additives, pesticides and herbicides) in construction and household products, food, water and environment

many chemicals have been identified as carcinogenic, mainly in experiments with laboratory animals; little research is done on the role of unknown number of such chemical carcinogens in the initiation and growth of breast cancer, but it is reasonable to assume it to be significant


(C) FACTORS PROMOTING BREAST CANCER
 

C1 - Mitogenic/antiapoptopic hormones

ovarian hormones level/balance

nominal blood estrogen level is an indicator, although somewhat loose, of the free (bioavailable, active) estrogen, which stimulates cell proliferation; higher estrogen level is likely to result in early menarche and late menopause (also, as a part of the elevated overall hormonal activity, in accelerated growth)
hormonal balance is regulated by a complex co-action of the pituitary gland and hypothalamus, but also affected by other factors, such as exposures to xenoestrogens (environmental estrogens) or chronic stress

exposure to environmental estrogens (xenoestrogens)

Phthalates (plasticizers) - chemicals leaking into foods form plastic containers and wraps, tend to accumulate in the body and may disrupt endocrine function
Pesticides - present in many foods and drinking water, may negatively affect body's regulatory functions, including hormonal
Detergents, trichloro-ethylene,
PCBs...
many environmental chemicals can act as estrogen mimics; level of exposure and individual vulnerability vary, but can be significant
Cadmium - toxic contaminant present in food, water and environment (also, in tobacco) that steadily accumulates in the body, acting like estrogen; it can also raise testosterone levels, as additional breast cancer risk factor
Natural food components - some natural food components, for instance, soybean isoflavones genistein and daidzein, can have estrogenic effect; however, Asian populations with high soybean intake have low breast cancer incidence, which suggests that (1) the effect may be more complex, and/or dependant on the overall diet and lifestyle (2) soy isofavones generally act as anti-estrogens, taking estrogen receptors while having much lower estrogenic potency (less than 2%)
Herbal extracts - natural herbal components can also have estrogenic potency; among commonly used herbs with such compounds are angelica, reishi mushroom, licorice, fo-ti and astragalus (they are all considered healthful, hence the above applies here as well)

elevated insulin

From high-glycemic diet,
insulin resistance, diabetes;
insulin stimulates cell division and increases the level of free (active) estrogen

elevated IGF

insulin-like growth factor, mitogenic, antiapoptotic hormone, enhancing estrogen activity, and vice versa; high levels linked to increased risk of several common cancers, including breast cancer

hormonal medical treatments

lHRT - large trials consistently come up with significantly increased risk
Birth control pills - the earlier in life starts the use, and the longer it lasts, the more of the risk factor they become
SERM drugs - Selective Estrogen Receptor Modulator, including those like Tamoxifen, that are used for breast cancer treatment and prevention, evidently are the additional risk factor for some woman

C2 - Compromised immune function

chronic internal infections

toot/jaw/root canal infections - appears to have significantly higher incidence in breast cancer patients

intestinal bacterial/fungal overgrowth

often accompanied with leaky gut and nutritional deficiencies, burdens and weakens the immune system

chronic stress

stimulates production of adrenal hormones, inhibiting immune function, shrinking the thymus gland and weakening protective responses against cancer

insufficient rest (sleep) time, high sugar intake,
high blood lipids, nutritional deficiencies,
smoking, alcohol, overweight,
negative emotions

many poor lifestyle choices alone negatively affect immune function, and their combined negative effect is disproportionally larger

C3 - Compromised detox system

due to toxic overload, toxic intestines (bacterial/fungal overgrowth), leaky gut, nutritional deficiencies, chronic stress and/or
negative emotions, chronic dehydration 

C4 - Genetic aberrations

compromising cell cycle control and immune system efficiency

C5 - Other promoting factors

nutritional deficiencies/imbalances

high-glycemic diet - causing elevated blood level of both, insulin (with or without insulin insensitivity) and IGF, which promotes cell proliferation similarly to estrogen
high-sugar diet - in addition to being a high-glycemic food, sugar inhibits the immune system; higher rate of glycolysis (burning glucose for energy within cell) increases concentration of its by-product, lactic acid, making cell more acidic, hence compromising its optimum functioning
low fiber - evidence supports inverse relationship between dietary fiber intake and breast cancer risk
specific mineral/vitamin deficiencies compromising detox, immune, and/or cellular function

regular alcohol consumption

regular, even quite moderate consumption inked with higher blood estrogen levels; other possible mechanisms include increased solubility of carcinogens, interfering with folate metabolism, elevated oxidative stress and mutagenic effects of its primary metabolite, acetaldehyde

smoking

contains over 4000 chemicals, most of them toxic, and over 50 known carcinogens

low melatonin

melatonin is an estrogen antagonist hormone; it also acts as antioxidant, antimitotic and immune-enhancing agent; body produces melatonin mainly during nighttime sleep, in darkness; thus lack of nighttime sleep, or lighted room, inhibit melatonin production, and so does exposure to power (electrical) field

breast compression

the risk seems to become the more significant the longer bra is worn over several hours a day, on daily basis

overweight/obesity

according to research data, overweight and obesity are risk factors for postmenopausal women;

weight gain (postmenopausal)

can enhance estrogen production and lead to estrogen dominance state

lean body (premenopausal)

if resulting from diet restriction,
metabolic disturbance or deficiency

insufficient/inadequate checkups

latter stages at the time of diagnosis significantly lower chances for recovery
risk of false negatives,
compression risk, radiation risk

The above list of breast cancer risk factors, as overwhelming as it is, is neither complete nor clear with respect to mechanisms leading to carcinogenic transformations. It is barely scratching the surface of the complexity behind the onset and progress of this disease. Many factors are involved, and

their significance and interplay can vary greatly
from one individual to another.

In addition, there are certainly some pieces of the puzzle that we are still unaware of. But what is known so far is both, best reference and best starting point for understanding the disease, and for taking steps to efficiently minimize the risk of becoming a part of the breast cancer statistic.

Obviously, there is much more that can be said about each of these factors. That journey starts with the following page.

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