The usual answer doctors like to give to the question “what are the causes of breast cancer” is “we do not know what causes breast cancer”. Here I am correcting this notion as we do know an awful lot about what causes breast cancer. There are many known factors that cause breast cancer and these often work in synergy. In addition it is also known that apart from the physical factors mentioned below breast cancer can also be caused by chronic stress.
As I will explain further below, we do know now that unopposed estrogen and xenoestrogens (these are estrogen-like substances in the environment like pesticides etc.) are the major cause for breast cancer, often in combination with several other breast cancer risk factors. For instance, it is known that the length of ovarian estrogen activity between the first period (menarche) and the last period (menopause) of a woman is directly related to breast cancer risk. The incidence curve of breast cancer is highest just prior to menopause and flattens out after. Another observation, which supports this, is the fact that removal of both ovaries (oophorectomy) at a younger age reduces the risk for breast cancer later in life. Ref. 8 explains that the reason for the peak about 5 years before menopause is the dropping off of progesterone production (missing ovulations, corpus luteus insufficiency). The longer a woman is under the influence of estrogen dominance (unopposed by progesterone), the higher the risk for cancer initiation, promotion and progression of breast cancer cells. Dr. Lee says that the “smoking gun” is estradiol (one of the three estrogen molecules in humans). Here is a list and some brief remarks about the risk factors for breast cancer.
The birth control pill (=oral contraceptives or BCP), which was originally feared to possibly produce breast cancer, does not pose an increased risk during the reproductive years as the ovarian function gets suppressed by it making the BCP breast cancer risk neutral or even 20% less frequent. Other authors point out that when taken more than 5 years there is a risk of 1.6 to 1.8-fold of causing breast cancer (likely because of estrogen dominance).
However, in the menopause postmenopausal estrogen replacement (HRT) carries with it an estrogen side effect consisting of a 1.5 to 2-fold accumulative risk for breast cancer over a 10 to 20 year time span. In the past it was thought that a reduced rate of osteoporosis and reduction in heart attacks would increase life expectancy overall with hormone replacement therapy following menopause. However, this has been proven wrong in large trials that came out in 2004 and now the issue of hormone replacement therapy (HRT) is in flux. Currently the thinking is that one has to individualize therapy, use good nutrition and exercise to prevent osteoporosis and in the case of control of hot flashes use the lowest possible estrogen hormone replacement for less than a total of 5 years. However, discuss this with your family doctor and/or gynecologist. Dr. Lee et al (Ref. 8) explains the effect of the birth control pill (BCP) and HRT side-effects this way. Both of these synthetic hormone-like mixtures of estrogenic and progesterone-like substances from the drug companies block estrogen receptors in the woman’s body. This leads to a lack of ovulation in the case of the BCP with associated suppression of progesterone production. The end result is an estrogen dominance as there is still enough estrogen that is produced, but it is unopposed by progesterone that would have modified the effect of estrogen (see table on “Important Properties of Bioidentical Estrogen and Progesterone in Women and Men”) under this link. HRT on the other hand is using high doses of a number of estrogens (Premarin) and when this is combined with progestins (as synthetic progesterone like drugs are called) there is not the balancing effect of natural progesterone. Again the “smoking gun” is pointing at estrogens as the cause of breast cancer as these estrogens were unopposed (HRT had induced a state of estrogen dominance).
There is a peculiar linear relationship between total fat intake per day and the death rate from breast cancer. Epidemiological studies show that the daily fat intake in the Netherlands is about 160 grams/day. In El Salvador it is only 40 grams/day. The adjusted death rate from breast cancer in the Netherlands is 25-fold higher than in El Salvador. Although we do not have all the answers why breast cancer deaths (and by the way many other cancer rates as well) are lower with less fat intake, it is self explanatory that a diet with less than 40 grams of fat per day is highly recommendable to prevent breast cancer and also heart attacks. Dr. Lee et al. (Ref. 8) explains that there are free radicals contained in bad fats (the trans-fats and in polyunsaturated fatty acids such as in corn oil that turn rancid easily). Butter and olive oil are more stable and will not cause these problems except that they need to be limited in the total daily dose as indicated. When too many calories are consumed the body will store the excess calories as fat in the body. This fat does not sit there in isolation. It is metabolized, leads to hardening of arteries, and causes insulin to get elevated (the syndrome of hyperinsulinism or metabolic syndrome). As insulin has growth hormone-like attributes, any breast cancer cell will get stimulated in growth and metastasize earlier than in a lean woman with normal fasting insulin levels. Secondly, obese women convert androgenic hormones in fatty tissue, particularly in the ductal cells of breast glands that border to the surrounding fat tissue, into estradiol, which as you guessed right is the “smoking gun” for breast cancer. Again, there is an estrogen dominant state with a lack of progesterone production, which would have balanced the cell division effects of estrogen.
Genetic risk for breast cancer and genetic tests
Some families have a higher than normal risk for breast cancer. In such families the risk is 1.5 to 3 times higher than for the average population. This is due to an inherited mutation in a BRCA1 or BRCA2 breast cancer susceptibility gene, which can now be determined with special blood tests. As the lifetime incidence of breast cancer in mutation carriers is above 50 percent, these women have to be screened much more vigorously as the rest of the female population. These women come from families where close female relatives had early onset breast cancers (late twenties to mid thirties). In the meantime more genetic research has come to light. Ref. 10 shows that there was a breakthrough in treatment success when triple negative breast cancer (estrogen receptor negative, progesterone receptor negative, HERS negative) was treated with gemcitabine and carboplatin, which are so-called PARP inhibitors (pharmacological inhibitors of the enzyme poly ADP ribose polymerase), normally used for ovarian cancer. The cancer genome ATLAS network has further characterized at least 4 genetically distinct types of breast cancer when they analyzed the biopsy material from 802 patients with breast cancer (Ref.11).
1. The triple negative breast cancer (also called basal-like breast cancer) had a great similarity to ovarian cancer and this likely is the reason why it responds to PARP inhibitors, which had previously been used successfully for ovarian cancer.
2. Luminal breast cancer cells have their origin from the luminal cells that line milk ducts. The study divided them into luminal A breast cancer and luminal B breast cancer. Luminal A breast cancer responds well to anti estrogen measures as it has estrogen receptors. This is the largest group of breast cancer patients.
3. Luminal B breast cancer responds poorly to hormone treatments. Luminal B breast cancer needs to be treated with a combination of hormone therapy and chemotherapy and may still have a poorer prognosis than luminal A breast cancer.
4. The forth breast cancer is HER2-enriched breast cancer, where additional copies of the gene HER2 stimulates breast cancer growth. Herceptin is a drug (trastuzumab) that blocks HER2 and changed this type of cancer from one of the worst cancers to treat to one with the best outcome. However, it is expensive and has a potentially serious side-effect (heart damage).
Future research will focus on improving the third group, luminal B breast cancer, which now has the poorest prognosis and try to optimize the drugs (hopefully less side-effects) used for treating the other types.
New Hereditary Breast Cancer Gene
A Polish/Canadian study showed a new hereditary breast cancer gene, a mutation in the RECQL gene.
One mutation of this gene causes a 5-fold increase of breast cancer in Polish women, but another mutation of the same gene in French Canadian women makes it 50-times more likely that these women come down with breast cancer. The authors of this study mention that they concentrated on women with a European ancestry and a history of familial breast cancer. They found 11 genes that were associated with hereditary breast cancer. The one that stood out was the RECQL gene. The normal function of this RECQL gene is to ensure DNA repair.
When this gene is mutated, it cannot do its normal job and cells can develop cancer. This research was a collaborative study between McGill University in Montreal, Canada and the Pomeranian Medical University in Poland.
Analyzing the genes of 195 Polish and French-Canadian breast cancer patients with a history of breast cancer in their families completed the RECQL study; 20,000 genes were examined in this group. The results of this were compared to 25,000 other patients without a history of breast cancer to get a baseline. Based on this it was apparent that women with mutated RECQL genes were highly susceptible to developing breast cancer.
So far the main genes associated with hereditary breast cancer were BRCA1 and BRCA2.
These genes are involved in the suppression of cancer cells through the production of proteins that help to repair damaged DNA. It will take some time to delineate the importance of the RECQL gene in addition to the known BRCA1 and BRCA2 genes with regard to the development of hereditary breast cancer. About 10% of all breast cancers are due to hereditary breast cancer (Ref. 13).
Pregnancy has always be known to have a breast cancer diminishing effect. During pregnancy the progesterone level gets raised as the placenta stimulates the corpus luteum to produce more progesterone. This protects the pregnancy, but has a long-lasting effect of protecting the woman from breast cancer. The earlier a woman gets pregnant and the more pregnancies she has, the more breast cancer protection she gets. On the other hand the removal of the ovaries (bilateral ovariectomy), which leads to a sudden lack of estrogens, progesterone and testosterone, causes a reduction in breast cancer also. However, the latter condition causes heart disease and osteoporosis and physicians have long treated this with HRT. Unfortunately, many physicians treated with estrogens only as this will take care of the hot flashes, but due to estrogen dominance will also cause breast cancer. The proper biological hormone replacement is to determine hormone levels and replace what is missing (with bioidentical estrogen, progesterone and testosterone creams from a compounding pharmacist).
Radiation causes free radicals in the breast tissue that can lead to mutations of the DNA with a simple lung X-ray and within the course of 10 years this can cause a palpable breast cancer. Fortunately the body’s immune system gets rid of most of these mutations. Girls who here exposed to the ionizing radiation during the bombing of Hiroshima during World War II had a two-fold risk of developing breast cancer. Unfortunately, there is a risk of breast cancer as a result of yearly mammograms, which are done with the best of intentions of early detection of breast cancer. On page 11 to 14 of Ref. 8 Dr. Lee explains that mammography will detect breast cancer about 1 year earlier than a woman can through breast self examination. However, as breast cancer has a relatively good prognosis with early detection he cites literature from Sweden that showed that most studies were flawed with selection bias and that the two studies that were well designed showed no effect of mammography screening on breast cancer mortality. In view of newer technologies without the use of radiation, I would suggest that the occasional MRI mammography study likely will show survival benefits when combined with self breast examination, early surgical intervention and other life style changes.
There is a host of food related factors that translate into risks of breast cancer. Trans-fatty acids, also known as hydrogenated oils or partially hydrogenated oils on food labels are a source of free radicals that lead to breast cancer. Dr. Peter Ellison of Harvard University has noted that higher calorie intake and lower exercise levels are risk factors for the development of breast cancer (mentioned on page 43 of Ref. 8). But intake of milk produced in the US also is a risk factor for breast cancer due to the common practice of giving cows the milk stimulant recombinant bovine growth hormone. Humans who consume this type of contaminated milk produce the growth factor IGF-1 in their livers, which is a known cause of breast cancer. If you want to drink milk, insist on certified hormone free milk or organically certified milk. Goat milk does not have this problem.
Vitamin D3 deficiency can seriously affect the prognosis for breast cancer as this link shows.
Only about 4% of breast cancer is caused by alcohol intake, but only if a woman drinks more than 1 alcoholic drink per day. With more drinks there is competition in the liver between elimination of alcohol and estrogen metabolites. As a result alcoholic women will develop estrogen dominance (also because progesterone production decreases). Unopposed estrogen (estradiol) causes breast cancer. Ref. 9 reports that the Nurses’ Health Study found that women consuming between 3-9 drinks per week were 30% more at risk of developing breast cancer than women who were non-drinkers.
Effect of exercise
Dr. Lee (Ref. 8, p. 45) mentions that the Harvard Nurses’ Health Study compared a large cohort of nurses who exercised moderately (seven or more hours per week) with those who exercised less than 1 hour per week. The end result was a 20% less risk for developing breast cancer in the group who exercised moderately. It was more important how frequent the exercise was rather than how strenuous it was. Ref. 9 cites a National Cancer Institute study where risk reduction for breast cancer was studied in young women. It showed that exercise from 1 to 3 hours per week lowered the risk of breast cancer by 30%. However, exercising 4 hours per week or more reduced the risk for breast cancer by 50%!
Pollution of the environment
Unfortunately not everybody can live in the country where the air is cleaner and we are not exposed to as many industrial chemicals. Many of these industrial pollutants of the city act like artificial estrogens (xenoestrogens). However, exposure to other xenoestrogens from nail polish, nail polish removers, pesticides in the house or garden, herbicides or plastic that leaches into soft drinks of plastic bottles, will all also lead to estrogen dominance and thus poses a breast cancer risk. Whenever possible, drink fluids from glass bottles. Organochlorines (pesticides, insecticides) such as DDT accumulate in breast tissue and function as xenoestrogens causing breast cancer. The good news is that natural progesterone cream has been shown by Dr. Lee to counter some of the cancer causing xenoestrogen effects (Ref.8).
Cigarette smoking leads to an accumulation of toxic heavy metals and carcinogenic substances in breast tissue. Overall the effect is that women who smoke developed breast cancer about 8 years earlier than controls that were not smoking (Ref.9).
Lumpy and painful breasts
When a woman has painful or lumpy breasts, it is more difficult for the woman or the physician to examine the breasts in order to detect early breast cancer. It can also be more difficult to get reliable mammography readings; with the introduction of MRI breast scans these patients have now another tool available that is reliable. However, it is important to note Dr. Lee’s finding (Ref. 8, page 39 and 40) that these types of patients have estrogen dominance due to a lack of progesterone leading to persistent cysts and the gradual development of lumpy breasts. After transdermal application of natural progesterone cream the lumpy breasts will normalize within 3 to 6 months. A woman with estrogen dominance is significantly at risk to develop breast cancer at a later date, but following hormone balancing with progesterone this risk disappears.
Other Factors Leading to Breast Cancer
Some other hormones can be contributing factors in the causation of breast cancer as follows.
DHEA (dehydroepiandrosterone) is a steroid hormone that is made by the adrenal glands. It is a precursor of estrogen and testosterone. We need DHEA production to have normal sex hormones and to have a normally functioning immune system. Men produce more of it than women and the peak production of it is at age 20 to 25. After the age of 25 we produce 2% less every year and this likely is the reason for immune weaknesses and autoimmune diseases as we age. Dr. Lee (Ref.8) says that DHEA levels are a biomarker of aging as much as grey hair or the need for bifocals is.
Another hormone is insulin, which is often elevated in the metabolic syndrome or insulin resistance, as it used to be called. Fasting insulin levels when elevated will confirm this syndrome. With the obesity wave in the US this syndrome has been well studied. When people eat too much sugar and starch the pancreas gets over stimulated to produce insulin. On the one hand the excess insulin functions as a growth factor and early breast cancer cells will respond to this by multiplying faster. On the other hand under the influence of high insulin the pituitary gland produces relatively more LH (luteinizing hormone) in relation n to FSH (follicle stimulating hormone). This in turn changes how ovaries function in that with the relative low FSH a dominant follicle never develops for ovulation, but instead many follicles develop in the ovaries that finally lead to polycystic ovary syndrome. With persistent follicles there is a lack of progesterone production as there is no corpus luteum (no ovulation). The more anovulatory cycles there are, the more estrogen dominant the woman becomes (can be measured in blood or saliva tests) and this is a risk for developing breast cancer. Metformin can be prescribed by your doctor to reduce hyperinsulinism. Exercise and a sensible low fat, low refined (but high unprocessed) carbohydrate diet will turn this condition around and help you to shed pounds with ease.
Other risk factors for breast cancer can be hypothyroidism with high thyroid stimulating hormone (TSH) levels, which is known to be carcinogenic.
Dr. Lee mentions that fluoride in tooth paste or fluoridated water replaces iodine in the body, which can lead to thyroid dysfunction and autoimmune thyroiditis (Hashimoto thyroiditis). This will often lead to hypothyroidisms (with high TSH) in the long run.
Another important hormone is melatonin, which helps us to fall asleep naturally when it is getting dark. It is produced by the pineal gland at the base of the brain. It is a powerful antioxidant and supports the immune system. When experiments were done with human breast cancer cells in tissue culture, added melatonin was able to suppress breast cancer cell growth by 75%. Clinical studies in women with breast cancer showed that they had much less nighttime melatonin levels in urine than a control group of women with no breast cancer ((Ref.8, p. 87 and 88). As melatonin is similar to DHEA in that we produce it at much lower levels when we age, it is wise to take supplemental melatonin of 1 mg at bedtime. It is freely available in drug stores in the US (in Europe it is more difficult to get).
Prolactin is another hormone that can be a contributory factor to breast cancer development. It is known that estradiol will stimulate prolactin production of the pituitary gland, but not estriol. This can lead to milk production (discharge of milk from the nipples), an annoying symptom to the woman affected by it. Natural progesterone cream gets absorbed systemically and will reduce Prolactin levels and the symptoms stop. According to Dr. Lee progesterone is inhibiting the actions of estrogen and prolactin by down-regulating the receptors for these hormones (Ref. 8, p.90).
Summary about causes and prevention of breast cancer
Breast cancer is caused by genetic damage to the DNA of breast cells by unopposed estradiol due to poor diet habits, life style choices and environmental factors. Only the minority of all breast cancers are due to inherited factors (BRCA1 gene etc.). Eat organic meat to avoid growth factors from the food industry, lots of vegetables and fresh fruit for protective nutrients and enzymes. Avoid sugar, alcohol (except for the occasional glass of wine), cut down or best cut out flour and pasta and engage in regular exercise to complete your simple breast cancer prevention program. Read Ref. 8 for more suggestions, if you want to be more aggressive about prevention. I have written a book where all of these factors are summarized as well (Ref.12). Bio-identical hormone supplementation based on saliva hormone testing as described under Ref. 8 is also very effective on top of these other recommendations (melatonin, DHEA, bio-identical progesterone cream).
The following references were used apart from my own clinical experience:
1. Cancer: Principles &Practice of Oncology, 4th edition, by V.T. De Vita,Jr.,et. al J.B. LippincottCo.,Philadelphia, 1993.Vol.2: Chapter 48.
2. The Merck Manual, 7th edition, by M. H. Beers et al., Whitehouse Station, N.J., 1999. Chapter 177.
3. Cancer: Principles&Practice of Oncology. 5th edition, volume 1. Edited by Vincent T. DeVita, Jr. et al. Lippincott-Raven Publ., Philadelphia,PA, 1997. Chapter 36: 1541-1616.
4. BS Herbert et al. Breast Cancer Res 2001;3(3):146-149.
5. BS Herbert et al. J Natl Cancer Inst 2001 Jan 3;93(1):39-45.
6. Conn’s Current Therapy 2004, 56th ed., Copyright © 2004 Elsevier
7. Ferri: Ferri’s Clinical Advisor: Instant Diagnosis and Treatment, 2004 ed., Copyright © 2004 Mosby, Inc
8. Dr. John R. Lee, David Zava and Virginia Hopkins: “What your doctor may not tell you about breast cancer – How hormone balance can help save your life”, Wellness Central, Hachette Book Group USA, 2005. Page 29 – 38 (Chapter 2): Risk factors for breast cancer. Page 360 to 374 explains about xenohormones and how they cause estrogen dominance.
9. Ross Pelton: “How to prevent breast cancer” in : “The Science of Anti-Aging Medicine”, editors:Dr. Ronald Klatz, Dr. Robert Goldman, 2003, p. 205-209.
10. http://www.ncbi.nlm.nih.gov/pubmed/20647696 (“Breakthrough breast cancer treatment–PARP inhibitor, BRCA, and triple negative breast cancer”. Article in Japanese by Hashimoto K and Tamura K.
, published July 2010 . (Pubmed link shows English translation of summary).
11. The Cancer Genome Atlas Network (Charles M. Perou et al.) “Comprehensive molecular portraits of human breast tumours”. Published online, Nature, 23 September 2012. See link: http://www.nature.com/nature/journal/vaop/ncurrent/full/nature11412.html#/significantly-mutated-genes-in-breast-cancer
12. Dr. Ray Schilling: “A Survivor’s Guide to Successful Aging”, Amzon.com 2014.
13. Nature Genetics 47, 373–380 (2015); published online March 09, 2015.