Kronos Longevity
Research Institute
2942 N. 24th Street
Suite 101
Phoenix, AZ 85016
Toll-Free: (866) 878-1221
Fax: (602) 778-7490
KEEPS@KronosInstitute.org
Research Institute
2942 N. 24th Street
Suite 101
Phoenix, AZ 85016
Toll-Free: (866) 878-1221
Fax: (602) 778-7490
KEEPS@KronosInstitute.org
Breast Cancer
The greatest fear women have about taking hormones is that they may develop breast cancer. This has been driven by multiple surveys of women, particularly after the initial results of the Women's Health Initiative study (WHI) were published. While it is clear that breast cancer is a prevalent disease and warrants close attention and should not be trivialized, this review attempts to put breast cancer risks into perspective.
While surveys of women have suggested that most women feel the leading cause of death in women is breast cancer, in fact, the leading cause of death is cardiovascular disease. Indeed, among cancer deaths in women, it is lung cancer and not breast cancer, which is the leading cause of death in women.
So what is the actual risk of breast cancer in women taking hormones? As common as breast cancer is today, there is a 2.8% chance of getting breast cancer between the ages of 50 to 60 (2.8 women out of 100). This is the normal risk in the United States without hormones. If we take the worst case scenario from WHI, women who took standard doses of E + P over 5 years, (the data suggested that there will be a 24% increase in the rate of breast cancer over the 5 years), then over this period of time 3.47 women out of 100 (rather than 2.8) will get breast cancer. This is less than one more woman (less than 1%). Compare this with other every day risks (remember the hormone risk is not even 1½ times the baseline risk): The risk of being overweight or obese is three-fold; some studies have suggested antibiotic use increases the risk two-fold; being a flight attendant increases the risk almost two-fold; and for some women, using an electric blanket increases the risk almost five-fold.
Recent news stories have suggested that there has been a substantial reduction in breast cancer since women stopped using hormones (after the results of WHI were made public). However, close analysis of this observation clearly does not show a cause and effect relationship. There are several other possible explanations for these findings which cannot be detailed here. However, it is clear that over this period of time, mammography use and breast exams also decreased. Thus, at least some of this decline, unfortunately, is merely due to less detection of breast cancer. More important data on this issue will become available in the future.
There is no question that the breast is an organ which responds to and is sensitive to estrogen. However, how breast cells respond to estrogen is complex and not completely understood. For example, it is not merely the estrogen which circulates in blood which may affect breast cells; but the estrogen produced locally in breast tissue, which is under a different type of control and has been difficult to study. Similarly, progesterone also affects breast cells and in the second half of the normal menstrual cycle, when progesterone levels are high, there is increased breast cell division, which is followed closely by natural cell death, because unlike the lining of the uterus which is shed at this time (menstruation), breast cells cannot be shed.
The current view as to how breast cancer develops is that at least two different mutations or "hits" in the genes controlling breast cell growth and/or death occur. This causes a cancer to develop which takes up to 10 years to be clinically recognizable by exam or mammography. It is not completely known what causes these "hits", but clearly a familial gene abnormality, e.g., a mutation in BRCA 1 or 2 would constitute one possible hit. It's not believed that either estrogen or progesterone are carcinogenic or can cause a "hit" to occur. However, if an existent small cancer is responsive to estrogen and progesterone (receptor positive status) then higher concentrations of the hormones (either in the breast tissue or in the circulation) can make the cancer grow faster (and be detected earlier than it would be otherwise). This is the so-called "promotional" theory.
What is the relationship between hormones and cancer? More than 30 years of research has looked into this issue and the fact that the field is still somewhat unclear is because the associated risk is relatively small; unlike the association between smoking and lung cancer. In the WHI, standard doses of estrogen (E) and a synthetic progesterone (P) were used in combination, and this treatment was associated with a small increase in the rate of breast cancer over 5 years of use. But this only occurred in women who had received hormones in the past, i.e., more than 5 years of exposure to standard doses. With standard estrogen doses, used alone, in women who had had a hysterectomy, there was an increase over about 7 years, and some suggestion for a decrease in breast cancer rates. Note that in these women who had had a hysterectomy, up to half the women had used hormones in the past, suggesting a total duration of therapy of more than 7 years. A recent report from the Nurses Health Study suggested that standard dose estrogen therapy in women with a hysterectomy did not increase breast cancer rates for up to 20 years.
If one puts all the important information together, the data would suggest that there is an approximate 20 to 30% increase in the breast cancer rate; not 20 to 30 times, but less than 1½ times the expected rate of breast cancer with about 5 years of use of E and P. It is clear in my view that the risk is somewhat higher with the combination of estrogen and synthetic progesterone than with estrogen alone, and this is with standard doses of hormones. We expect this risk to be less with lower doses of estrogen, and perhaps with the use of natural progesterone rather than synthetic progesterone, although this is unproven. Some French studies using natural progesterone have suggested this. Using lower estrogen doses and using natural progesterone is the protocol we have adopted for KEEPS.
Also, among women who, unfortunately, get breast cancer while on hormones, the majority of studies have suggested no increase in mortality, and others have suggested a better prognosis, presumably due to earlier diagnosis and treatment.
In conclusion, there is an association between hormones and breast cancer, and this risk is primarily with the use of standard doses of E and P. The relationship is most likely the "promotion" or growth of existing small breast cancers. Since there is no means to determine which woman has small undetectable cancers, we do not know how to screen those women "at risk". However, the overall risk is small, particularly when compared to other every day exposures. This risk is likely to be even less in women using lower doses of estrogen and intermittent natural progesterone for up to 5 years as we have prescribed in KEEPS.
While surveys of women have suggested that most women feel the leading cause of death in women is breast cancer, in fact, the leading cause of death is cardiovascular disease. Indeed, among cancer deaths in women, it is lung cancer and not breast cancer, which is the leading cause of death in women.
So what is the actual risk of breast cancer in women taking hormones? As common as breast cancer is today, there is a 2.8% chance of getting breast cancer between the ages of 50 to 60 (2.8 women out of 100). This is the normal risk in the United States without hormones. If we take the worst case scenario from WHI, women who took standard doses of E + P over 5 years, (the data suggested that there will be a 24% increase in the rate of breast cancer over the 5 years), then over this period of time 3.47 women out of 100 (rather than 2.8) will get breast cancer. This is less than one more woman (less than 1%). Compare this with other every day risks (remember the hormone risk is not even 1½ times the baseline risk): The risk of being overweight or obese is three-fold; some studies have suggested antibiotic use increases the risk two-fold; being a flight attendant increases the risk almost two-fold; and for some women, using an electric blanket increases the risk almost five-fold.
Recent news stories have suggested that there has been a substantial reduction in breast cancer since women stopped using hormones (after the results of WHI were made public). However, close analysis of this observation clearly does not show a cause and effect relationship. There are several other possible explanations for these findings which cannot be detailed here. However, it is clear that over this period of time, mammography use and breast exams also decreased. Thus, at least some of this decline, unfortunately, is merely due to less detection of breast cancer. More important data on this issue will become available in the future.
There is no question that the breast is an organ which responds to and is sensitive to estrogen. However, how breast cells respond to estrogen is complex and not completely understood. For example, it is not merely the estrogen which circulates in blood which may affect breast cells; but the estrogen produced locally in breast tissue, which is under a different type of control and has been difficult to study. Similarly, progesterone also affects breast cells and in the second half of the normal menstrual cycle, when progesterone levels are high, there is increased breast cell division, which is followed closely by natural cell death, because unlike the lining of the uterus which is shed at this time (menstruation), breast cells cannot be shed.
The current view as to how breast cancer develops is that at least two different mutations or "hits" in the genes controlling breast cell growth and/or death occur. This causes a cancer to develop which takes up to 10 years to be clinically recognizable by exam or mammography. It is not completely known what causes these "hits", but clearly a familial gene abnormality, e.g., a mutation in BRCA 1 or 2 would constitute one possible hit. It's not believed that either estrogen or progesterone are carcinogenic or can cause a "hit" to occur. However, if an existent small cancer is responsive to estrogen and progesterone (receptor positive status) then higher concentrations of the hormones (either in the breast tissue or in the circulation) can make the cancer grow faster (and be detected earlier than it would be otherwise). This is the so-called "promotional" theory.
What is the relationship between hormones and cancer? More than 30 years of research has looked into this issue and the fact that the field is still somewhat unclear is because the associated risk is relatively small; unlike the association between smoking and lung cancer. In the WHI, standard doses of estrogen (E) and a synthetic progesterone (P) were used in combination, and this treatment was associated with a small increase in the rate of breast cancer over 5 years of use. But this only occurred in women who had received hormones in the past, i.e., more than 5 years of exposure to standard doses. With standard estrogen doses, used alone, in women who had had a hysterectomy, there was an increase over about 7 years, and some suggestion for a decrease in breast cancer rates. Note that in these women who had had a hysterectomy, up to half the women had used hormones in the past, suggesting a total duration of therapy of more than 7 years. A recent report from the Nurses Health Study suggested that standard dose estrogen therapy in women with a hysterectomy did not increase breast cancer rates for up to 20 years.
If one puts all the important information together, the data would suggest that there is an approximate 20 to 30% increase in the breast cancer rate; not 20 to 30 times, but less than 1½ times the expected rate of breast cancer with about 5 years of use of E and P. It is clear in my view that the risk is somewhat higher with the combination of estrogen and synthetic progesterone than with estrogen alone, and this is with standard doses of hormones. We expect this risk to be less with lower doses of estrogen, and perhaps with the use of natural progesterone rather than synthetic progesterone, although this is unproven. Some French studies using natural progesterone have suggested this. Using lower estrogen doses and using natural progesterone is the protocol we have adopted for KEEPS.
Also, among women who, unfortunately, get breast cancer while on hormones, the majority of studies have suggested no increase in mortality, and others have suggested a better prognosis, presumably due to earlier diagnosis and treatment.
In conclusion, there is an association between hormones and breast cancer, and this risk is primarily with the use of standard doses of E and P. The relationship is most likely the "promotion" or growth of existing small breast cancers. Since there is no means to determine which woman has small undetectable cancers, we do not know how to screen those women "at risk". However, the overall risk is small, particularly when compared to other every day exposures. This risk is likely to be even less in women using lower doses of estrogen and intermittent natural progesterone for up to 5 years as we have prescribed in KEEPS.
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