The Preventive Medicine Center Of Gainesville

Identifying causal relationships between environmental factors and breast cancer is difficult to almost impossible. Animal models are used to generate hypotheses about the carcinogenicity of different chemicals or environmental exposures. Rats and mice are commonly used, but they metabolize substances at different rates and have different thresholds for certain toxins from humans. There is also a problem with experimental design in that animals do not live as long as humans and are therefore exposed to higher doses of toxins for shorter periods, whereas humans are exposed to lower doses over longer periods of time. The process of bio-accumulation of a harmful substance may take decades before damage is apparent. I attended an ACAM (American College for the Advancement of Medicine) conference in November 2003 where this very subject was brought up as it related to Gulf War Syndrome. Soldiers were exposed to low or non-detectable levels of poisonous chemicals during the war on a repeated basis. These servicemen returned home and later a significant number began experiencing neurological disorders and other problems that were found to be related to this type of chronic, low level exposure.

Cluster analyses are also used to develop hypotheses. For instance, Long Island and other parts of New York City have high breast cancer rates compared to other areas of the country. Unfortunately, this type of analysis does not show what the causative agent(s) is or whether there are lifestyle factors such as socioeconomic status or occupation that come into play.

Another area is that of genomics where genetic factors may affect the development of breast or other cancers if a patient is placed in the wrong type of environment or exposure. Genetic risk factors include several known mutations in the BRCA1 and BRCA2 genes, which predispose a woman to breast cancer. Only 5% of breast cancers are directly related to this type of genetic risk, however.

There are multiple other risk factors such as early age at menarche, later age at menopause, not having children, later age at first full-term pregnancy, and not breast feeding, alcohol consumption, long term use of hormonal replacement therapy, and ionizing radiation [14,15, 16, 17].

Pesticides and other organochlorines:

The group of chemicals known as organochlorines cause tumors in rats. This group includes substances such as DDT, PCB’s, and dioxins. Almost everyone is exposed to these chemicals, primarily through the consumption of fish, dairy products, and meats. These substances mimic estrogen and may influence a woman’s risk of breast cancer. There have been studies where blood levels of these chemicals were measured against risk of breast cancer. The results have been inconclusive.

Electromagnetic fields:

It has been hypothesized that increased exposure to electromagnetic fields and light at night is associated with an increased risk of breast cancer. This type of exposure reduces melatonin production. Melatonin is a hormone that has a protective effect against cancers. Most people are familiar with taking Melatonin for sleep disturbance. We know that electromagnetic fields (such as from high voltage transformers) in some studies are associated with an increased risk of developing certain types of cancers, but further study is needed.

Diet:

There have been many studies on the effect of different diets and the use of vitamins in cancer prevention. We do know there is a lower cancer risk among people who consume fruits and vegetables [18]. There is also evidence that high consumption of meat may increase the risk of breast cancer [19]. This may be related to a number of factors such as hormones in meat, or heterocyclic amines that are produced when meat is cooked at high temperatures, such as in BBQing. Diets high in fat have been shown to increase breast cancer in rats, but the results in humans have been inconsistent [20, 21].

There is also evidence that phytoestrogens (estrogen compounds found in plants and vegetables) may substantially reduce the risk of breast cancer [22, 23]. These would include products such as soy (e.g. miso and tofu), chickpeas, blueberries. We also know cruciferous vegetables such as cabbage, broccoli, cauliflower, Brussel sprouts, kale, kohlrabi are protective against many types of cancers.

Physical exercise:

Some studies have shown that both recreational and occupational physical activity can reduce the risk of breast cancer anywhere from 12% to 60%. Some studies have shown there is no reduction in risk. So there is confusion in this area. It is only common sense, however, that a person who exercises will be more healthy than a couch potato, and may have a better immune system to fight cancer development or illness.

Viruses:

For a long time it has been hypothesized that viruses may play a role in cancer development. We do known that EBV (Epstein-Barr virus) which is in the herpes virus family and causes infectious mononucleosis, is associated with the development of several cancers, including Hodgkin’s disease, Burkitt’s lymphoma, and nasopharyngeal carcinoma. One recent study found that EBV was more frequently associated with aggressive breast tumors. MMTV (mouse mammary tumor virus) causes breast tumors in mice. Studies have shown sequences of MMTV virus and also EBV in human breast cancer cells, but not in normal breast tissue [24, 25, 26, 27]. It is still unknown if these viruses cause breast cancer in humans, or if they simply are able to infect tumor cells that already exist.

Radiation:

It is known that radiation causes oxidative tissue damage and DNA damage and can lead to cancer.
As mentioned in our previous newsletter, there are no long term studies showing what the effects of annual mammograms are on healthy breast tissue. We do know that there is a correlation between thyroid cancer patients who have been treated with radioactive iodine post operatively and an increased risk of developing breast cancer 5 -20 years later. Limiting radiation exposure from all sources (mammograms, routine chest x-rays, dental x-rays, etc) is highly recommended.

Breast feeding:

What count’s is the accumulated time of breast-feeding during the whole of a woman’s lifetime. Cancer’s arise in the milk ducts. Short breast feeding has not shown any protective effect, but in some studies a lifetime total of 25 or more months of breast-feeding reduced the breast cancer risk by 33% compared with women with natural children who did not breast-feed.

Antiperspirants:

Antiperspirants are strong chemicals, usually containing aluminum, which prevent sweating. Sweating is one of the ways the body eliminates toxins, and by blocking this system, toxins can accumulate in the body. The Center has a far infra-red sauna detoxification program where patients are able to reduce fat-soluble toxins and heavy metals from the body through their sweat.

The National Cancer Institute and American Cancer Society positions are that there is no causal relationship between antiperspirant use and the development of breast cancer. Ester-bearing parabens from underarm deodorants have been found in breast tumors removed from women.

Bras:

There are articles on the Internet on underwire or tight bras causing cancer. Supposedly this is from blocking lymphatics or energy flows. Again, there are no objective studies showing this to be a risk factor at this time.

Oral Contraceptives, Xenoestrogens and other Synthetic Hormones:

Although oral contraceptives and prescription hormones are not environmental per se, xenoestrogens from the environment from things such as plastics and certain chemical exposures are felt to influence breast cancer risk. Therefore, a brief discussion of hormones is included in this article.

The Lancet, a prestigious British Medical journal, published an article on 150,000 women who were on The Pill and found they had a 25% greater risk of developing breast cancer. A study in 1994 found that women who started on the Pill before the age of 20 had a 3.5 times higher risk.

The Women’s Health Initiative study was a large scale study designed to determine the effects hormones had on breast cancer rates. Premarin (a synthetic estrogen derived from horse urine) was given by itself to one group of women, and Premarin + Provera (a synthetic progestin) was given to another group of women. The Premarin + Provera study was stopped prematurely in 2002 after it was determined there were, on average, 8 additional cases of breast cancer for every 10,000 women over one year. This calculated to be a 24% increase in risk. There was also a similar increase in strokes in this group – 8 additional strokes for every 10,000 women. One might expect the same or similar results from the Premarin group by itself, but there was no increase in breast cancer and this study was stopped in February 2004. An article stating hormonal replacement was unsafe was published in JAMA (Journal of the American Medical Association) and many women were taken off hormones.

My personal opinion is different from that in JAMA. First of all, it is unfortunate that both traditional medical journals and also the lay press categorize synthetic hormones as being the same thing as your body’s natural hormones. Nothing could be farther from the truth. Premarin and Provera have very different chemical structures from human hormones. The human body had never seen these chemicals until they were introduced by the pharmaceutical industry. Hormones such as estriol or estradiol, or progesterone, are naturally occurring and have metabolic pathways in place in the human body. Natural hormones have been around for hundreds of thousands of years and do not require FDA approval. In other words, foreign chemicals may or may not be handled by the human body and can be harmful, whereas the body’s natural hormones are easily handled. Most cancers take a long time to develop – not the few years the study ran. I feel what happened was in the Premarin + Provera group the 8 additional women who developed cancers per 10,000 already had the cancer cells present. These cells were stimulated by the drugs to grow and multiply rapidly and form a tumor within several years. What this study did show was synthetic hormones are not safe as was previously assumed and can accelerate the rate of growth of hormonally sensitive cancers. This is not to say caution is not necessary when prescribing natural hormones as there are also risks. However, there is evidence that a woman’s naturally occurring estriol has a cancer protective effect. We do know it acts as an antioxidant and has membrane stabilization properties. Estriol scavenges peroxyl radicals that cause tissue damage.

Antibiotics

Researchers earlier this year reported in JAMA that women who took antibiotics for more than 500 days or who had more than 25 prescriptions in the course of a 17-year period more than doubled their risk of breast cancer compared to women who had not taken any antibiotics. It was hypothesized that the antibiotics affected bacteria in the intestine and altered the way cancer-fighting foods were handled. Other theories centered around antibiotics altering the immune system itself. An earlier study from Finland in 1999, involving almost 10,000 women, found similar results.

The reason I include this in this section is that antibiotics are not from prescriptions given from physicians, but are also placed in animal feed for cattle and chickens, and then are indirectly passed on to humans consuming beef and poultry. The study did not prove a causal relationship between taking antibiotics and causing breast cancer, but there is a definite association that warrants further investigation.

REFERENCES

14. Kelsey, JL, Gammon MD, John EM. Reproductive factors and breast cancer. Epidemiol Rev 1993;15:36-47.

15. Rosenberg L, Metzger LS, Palmer JR. Acohol consumption and risk of breast cancer: a review of the epidemiologic evidence. Epidemiol Rev 1993; 15:133-44.

16. Sillero-Arenas M, Delgado-Rodriquez M, Rodigues-Canteras R, et al. Menopausal hormone replacement therapy and breast cancer: a meta-analysis. Obstet Gynecol 1992;79:286-94.

17. John EM, Kelsey JL. Radiation and other environmental exposures and breast cancer. Epidemiol Rev 1993;15:157-62

18. Gandini S, Merzenich H, et al. Meta-analysis of studies on breast cancer risk and diet: the role of fruit and vegetable consumption and the intake of micronutrients. Eur J Cancer 2000;36(5):636-46.

19. Bingham SA. High-meat diets and cancer risk. Proc Nut Soc 1999;58(2):243-8.

20. Clavel-Chapelon F, Niravong M, Joseph RR. Diet and breast cancer: review of the epidemiologic literature. Cancer Detect Prev 1997;21(5):426-40.

21. Hunter DJ, Willett WC. Diet, body size, and breast cancer. Epidemiol Rev 1993;15:110-32.

22. Gottlieb N. Soybean in a haystack? Pinpointing an anti-cancer effect. J Natl Cancer Inst 1999;91(19):1610-2.

23. Ingram D, Sanders K, Kolybaba M, Lopez D. Case-control study of phytoestrogens and breast cancer. Lancet 1997;350(9083):990-4.

24. Labrecque LG, Barnes DM, Fentiman IS, Griffin BE. Epstein-Barr virus in epithelial cell tumors: a breast cancer study. Cancer Res 1995;55:39-45.

25. Luqmani YA, Shousha S. Presence of Epstein-Barr virus in breast carcinoma. Int J Oncol 1995;6:899-903.

26. Bonnet M, Guinebretiere JM, Kremmer E, et al. Detection of Epstein-Barr virus in invasive breast cancers. J Natl Cancer Inst 1999;91(16):1376-81.

27. Wang Y, Holland JF, Bleiweiss IJ, et al. Detection of mammary tumor virus envgene-like sequences in human breast cancer. Cancer Res 1995;55(22):5173-9.



	BREAST CANCER AND THE ENVIRONMENT ROBERT A. ERICKSON, M.D. 2004© INTRODUCTION Identifying causal relationships between environmental factors and breast cancer is difficult to almost impossible. Animal models are used to generate hypotheses about the carcinogenicity of different chemicals or environmental exposures. Rats and mice are commonly used, but they metabolize substances at different rates and have different thresholds for certain toxins from humans. There is also a problem with experimental design in that animals do not live as long as humans and are therefore exposed to higher doses of toxins for shorter periods, whereas humans are exposed to lower doses over longer periods of time. The process of bio-accumulation of a harmful substance may take decades before damage is apparent. I attended an ACAM (American College for the Advancement of Medicine) conference in November 2003 where this very subject was brought up as it related to Gulf War Syndrome. Soldiers were exposed to low or non-detectable levels of poisonous chemicals during the war on a repeated basis. These servicemen returned home and later a significant number began experiencing neurological disorders and other problems that were found to be related to this type of chronic, low level exposure. Cluster analyses are also used to develop hypotheses. For instance, Long Island and other parts of New York City have high breast cancer rates compared to other areas of the country. Unfortunately, this type of analysis does not show what the causative agent(s) is or whether there are lifestyle factors such as socioeconomic status or occupation that come into play. Another area is that of genomics where genetic factors may affect the development of breast or other cancers if a patient is placed in the wrong type of environment or exposure. Genetic risk factors include several known mutations in the BRCA1 and BRCA2 genes, which predispose a woman to breast cancer. Only 5% of breast cancers are directly related to this type of genetic risk, however. There are multiple other risk factors such as early age at menarche, later age at menopause, not having children, later age at first full-term pregnancy, and not breast feeding, alcohol consumption, long term use of hormonal replacement therapy, and ionizing radiation [14,15, 16, 17]. Pesticides and other organochlorines: The group of chemicals known as organochlorines cause tumors in rats. This group includes substances such as DDT, PCB’s, and dioxins. Almost everyone is exposed to these chemicals, primarily through the consumption of fish, dairy products, and meats. These substances mimic estrogen and may influence a woman’s risk of breast cancer. There have been studies where blood levels of these chemicals were measured against risk of breast cancer. The results have been inconclusive. Electromagnetic fields: It has been hypothesized that increased exposure to electromagnetic fields and light at night is associated with an increased risk of breast cancer. This type of exposure reduces melatonin production. Melatonin is a hormone that has a protective effect against cancers. Most people are familiar with taking Melatonin for sleep disturbance. We know that electromagnetic fields (such as from high voltage transformers) in some studies are associated with an increased risk of developing certain types of cancers, but further study is needed. Diet: There have been many studies on the effect of different diets and the use of vitamins in cancer prevention. We do know there is a lower cancer risk among people who consume fruits and vegetables [18]. There is also evidence that high consumption of meat may increase the risk of breast cancer [19]. This may be related to a number of factors such as hormones in meat, or heterocyclic amines that are produced when meat is cooked at high temperatures, such as in BBQing. Diets high in fat have been shown to increase breast cancer in rats, but the results in humans have been inconsistent [20, 21]. There is also evidence that phytoestrogens (estrogen compounds found in plants and vegetables) may substantially reduce the risk of breast cancer [22, 23]. These would include products such as soy (e.g. miso and tofu), chickpeas, blueberries. We also know cruciferous vegetables such as cabbage, broccoli, cauliflower, Brussel sprouts, kale, kohlrabi are protective against many types of cancers. Physical exercise: Some studies have shown that both recreational and occupational physical activity can reduce the risk of breast cancer anywhere from 12% to 60%. Some studies have shown there is no reduction in risk. So there is confusion in this area. It is only common sense, however, that a person who exercises will be more healthy than a couch potato, and may have a better immune system to fight cancer development or illness. Viruses: For a long time it has been hypothesized that viruses may play a role in cancer development. We do known that EBV (Epstein-Barr virus) which is in the herpes virus family and causes infectious mononucleosis, is associated with the development of several cancers, including Hodgkin’s disease, Burkitt’s lymphoma, and nasopharyngeal carcinoma. One recent study found that EBV was more frequently associated with aggressive breast tumors. MMTV (mouse mammary tumor virus) causes breast tumors in mice. Studies have shown sequences of MMTV virus and also EBV in human breast cancer cells, but not in normal breast tissue [24, 25, 26, 27]. It is still unknown if these viruses cause breast cancer in humans, or if they simply are able to infect tumor cells that already exist. Radiation: It is known that radiation causes oxidative tissue damage and DNA damage and can lead to cancer. As mentioned in our previous newsletter, there are no long term studies showing what the effects of annual mammograms are on healthy breast tissue. We do know that there is a correlation between thyroid cancer patients who have been treated with radioactive iodine post operatively and an increased risk of developing breast cancer 5 -20 years later. Limiting radiation exposure from all sources (mammograms, routine chest x-rays, dental x-rays, etc) is highly recommended. Breast feeding: What count’s is the accumulated time of breast-feeding during the whole of a woman’s lifetime. Cancer’s arise in the milk ducts. Short breast feeding has not shown any protective effect, but in some studies a lifetime total of 25 or more months of breast-feeding reduced the breast cancer risk by 33% compared with women with natural children who did not breast-feed. Antiperspirants: Antiperspirants are strong chemicals, usually containing aluminum, which prevent sweating. Sweating is one of the ways the body eliminates toxins, and by blocking this system, toxins can accumulate in the body. The Center has a far infra-red sauna detoxification program where patients are able to reduce fat-soluble toxins and heavy metals from the body through their sweat. The National Cancer Institute and American Cancer Society positions are that there is no causal relationship between antiperspirant use and the development of breast cancer. Ester-bearing parabens from underarm deodorants have been found in breast tumors removed from women. Bras: There are articles on the Internet on underwire or tight bras causing cancer. Supposedly this is from blocking lymphatics or energy flows. Again, there are no objective studies showing this to be a risk factor at this time. Oral Contraceptives, Xenoestrogens and other Synthetic Hormones: Although oral contraceptives and prescription hormones are not environmental per se, xenoestrogens from the environment from things such as plastics and certain chemical exposures are felt to influence breast cancer risk. Therefore, a brief discussion of hormones is included in this article. The Lancet, a prestigious British Medical journal, published an article on 150,000 women who were on The Pill and found they had a 25% greater risk of developing breast cancer. A study in 1994 found that women who started on the Pill before the age of 20 had a 3.5 times higher risk. The Women’s Health Initiative study was a large scale study designed to determine the effects hormones had on breast cancer rates. Premarin (a synthetic estrogen derived from horse urine) was given by itself to one group of women, and Premarin + Provera (a synthetic progestin) was given to another group of women. The Premarin + Provera study was stopped prematurely in 2002 after it was determined there were, on average, 8 additional cases of breast cancer for every 10,000 women over one year. This calculated to be a 24% increase in risk. There was also a similar increase in strokes in this group – 8 additional strokes for every 10,000 women. One might expect the same or similar results from the Premarin group by itself, but there was no increase in breast cancer and this study was stopped in February 2004. An article stating hormonal replacement was unsafe was published in JAMA (Journal of the American Medical Association) and many women were taken off hormones. My personal opinion is different from that in JAMA. First of all, it is unfortunate that both traditional medical journals and also the lay press categorize synthetic hormones as being the same thing as your body’s natural hormones. Nothing could be farther from the truth. Premarin and Provera have very different chemical structures from human hormones. The human body had never seen these chemicals until they were introduced by the pharmaceutical industry. Hormones such as estriol or estradiol, or progesterone, are naturally occurring and have metabolic pathways in place in the human body. Natural hormones have been around for hundreds of thousands of years and do not require FDA approval. In other words, foreign chemicals may or may not be handled by the human body and can be harmful, whereas the body’s natural hormones are easily handled. Most cancers take a long time to develop – not the few years the study ran. I feel what happened was in the Premarin + Provera group the 8 additional women who developed cancers per 10,000 already had the cancer cells present. These cells were stimulated by the drugs to grow and multiply rapidly and form a tumor within several years. What this study did show was synthetic hormones are not safe as was previously assumed and can accelerate the rate of growth of hormonally sensitive cancers. This is not to say caution is not necessary when prescribing natural hormones as there are also risks. However, there is evidence that a woman’s naturally occurring estriol has a cancer protective effect. We do know it acts as an antioxidant and has membrane stabilization properties. Estriol scavenges peroxyl radicals that cause tissue damage. Antibiotics Researchers earlier this year reported in JAMA that women who took antibiotics for more than 500 days or who had more than 25 prescriptions in the course of a 17-year period more than doubled their risk of breast cancer compared to women who had not taken any antibiotics. It was hypothesized that the antibiotics affected bacteria in the intestine and altered the way cancer-fighting foods were handled. Other theories centered around antibiotics altering the immune system itself. An earlier study from Finland in 1999, involving almost 10,000 women, found similar results. The reason I include this in this section is that antibiotics are not from prescriptions given from physicians, but are also placed in animal feed for cattle and chickens, and then are indirectly passed on to humans consuming beef and poultry. The study did not prove a causal relationship between taking antibiotics and causing breast cancer, but there is a definite association that warrants further investigation. REFERENCES 14. Kelsey, JL, Gammon MD, John EM. Reproductive factors and breast cancer. Epidemiol Rev 1993;15:36-47. 15. Rosenberg L, Metzger LS, Palmer JR. Acohol consumption and risk of breast cancer: a review of the epidemiologic evidence. Epidemiol Rev 1993; 15:133-44. 16. Sillero-Arenas M, Delgado-Rodriquez M, Rodigues-Canteras R, et al. Menopausal hormone replacement therapy and breast cancer: a meta-analysis. Obstet Gynecol 1992;79:286-94. 17. John EM, Kelsey JL. Radiation and other environmental exposures and breast cancer. Epidemiol Rev 1993;15:157-62 18. Gandini S, Merzenich H, et al. Meta-analysis of studies on breast cancer risk and diet: the role of fruit and vegetable consumption and the intake of micronutrients. Eur J Cancer 2000;36(5):636-46. 19. Bingham SA. High-meat diets and cancer risk. Proc Nut Soc 1999;58(2):243-8. 20. Clavel-Chapelon F, Niravong M, Joseph RR. Diet and breast cancer: review of the epidemiologic literature. Cancer Detect Prev 1997;21(5):426-40. 21. Hunter DJ, Willett WC. Diet, body size, and breast cancer. Epidemiol Rev 1993;15:110-32. 22. Gottlieb N. Soybean in a haystack? Pinpointing an anti-cancer effect. J Natl Cancer Inst 1999;91(19):1610-2. 23. Ingram D, Sanders K, Kolybaba M, Lopez D. Case-control study of phytoestrogens and breast cancer. Lancet 1997;350(9083):990-4. 24. Labrecque LG, Barnes DM, Fentiman IS, Griffin BE. Epstein-Barr virus in epithelial cell tumors: a breast cancer study. Cancer Res 1995;55:39-45. 25. Luqmani YA, Shousha S. Presence of Epstein-Barr virus in breast carcinoma. Int J Oncol 1995;6:899-903. 26. Bonnet M, Guinebretiere JM, Kremmer E, et al. Detection of Epstein-Barr virus in invasive breast cancers. J Natl Cancer Inst 1999;91(16):1376-81. 27. Wang Y, Holland JF, Bleiweiss IJ, et al. Detection of mammary tumor virus envgene-like sequences in human breast cancer. Cancer Res 1995;55(22):5173-9. Back to Topics of Interest Table of Contents Welcome \| About Dr. Erickson \| Practice Philosophy \| Services Available Hours & Location \| Insurance & Fees \| F.A.Q. Whats New \| Topics of interest \| Contact us \| Home Contact Webmaster