In an earlier article on this website, we pointed out the importance of estrogen and the perils of postmenopausal hormonal profile:
“the dominant opinion among the researchers in cancer is that even slightly higher levels of estrogen in postmenopausal women cause an increased risk of breast cancer…
Thus, it would seem that if we restore estrogen levels in postmenopausal women to the levels necessary to prevent osteopenia and osteoporosis, the risk of breast cancer would also increase. ”
It is therefore very interesting to learn the arguments of those who oppose the dominant opinion and argue against the causal link between estrogen levels and breast cancer.
Avrum Bluming, MD, and Carol Tavris, PhD in social psychology, recently appeared on different podcasts where they talked about their book “Estrogen Matters”.
One of the screenshots below shows “the credentials” of the authors. Before reading the credentials (i.e. academic and professional achievements), note the following “survival rule”:
Survival Rule: In the modern world, credentials do not guarantee intelligence or competence.
Does estrogen cause breast cancer? The opinion of Avrum Bluming and Carol Tavris.
Instead of being mesmerized by credentials, to assess a presumed expert, you need to analyze thoroughly what he or she says and writes. Look for the presence of common sense, pattern recognition, capacity to think logically. Analyze how the person spends his or her career, how the person deals with the dominant dogmas and “The Party Line”.
Avrum Bluming and Carol Tavris were guests on a recent podcast of Peter Attia, a celebrity medical doctor and health personality. The impression they gave was mixed. “Social psychologist” Carol Tavris constantly brought up the theme of “oppression of women” as the reason behind unnecessary surgeries and all other evils in the world. Medical researcher and practitioner Avrum Bluming was more relevant to the discussion. However, Bluming talks readily about the experiences of his wife with hormone replacement and is apparently influenced by this personal bias. Many of Avrum Bluming’s other arguments have flaws. Bluming criticizes a large study published in 2002, the Women Health Initiative (WHI), that found an association between hormone replacement therapy and breast cancer (2). But, strangely, Bluming never brings up the problem of overdiagnosis of breast cancer. Overdiagnosis became rampant in the late 1980s. There is evidence that overdiagnosis continues at present. Overdiagnosis and its confounding impact may be the strongest critic of the 2002 WHI study (2) results.
On the graphs from a recent paper by Welch and colleagues (see below), you can see how, at one point, the incidence, that is the diagnosis, increased for both breast and prostate cancers, while mortality did not increase in breast cancer or increased a lot less than the diagnosis in prostate cancer.
In summary, Avrum Bluming and his “social psychologist” side-kick Carol Tavris list several interesting factoids, at times, quite convincing, against estrogen being a causative factor in breast cancer. Their interpretation of these factoids is, however, often flawed. For instance, in our review of the published literature, we did notice a correlation between breast cancer and a phenotype where both estrogen and IGF-1 were elevated at the same time.
Additional research in this area is needed. Simply dismissing estrogen involvement in postmenopausal breast cancer and being enthusiastic about hormone replacement are not the conclusions that we draw at our current understanding of the problem. The “Optimal Phenotype” that minimizes the risk of breast and other cancers in postmenopausal women is yet to be determined. The “Optimal Phenotype” here is the right combination of different hormonal and metabolic markers.
Now, the long citation from Avrum Bluming and Carol Tavris, 2009 (1). Notwithstanding our critic of the authors, their 2009 article is still informative and useful.
DOES ESTROGEN CAUSE CANCER?
The hypothesis that hormones are linked to breast cancer was originally derived from 2 well-documented facts: the incidence of breast cancer is 100 times greater in women than in men, and the earlier a woman’s menarche and the later her menopause, the greater her risk of breast cancer.123 These observations suggested, reasonably, that perhaps having more years of circulating estrogen was the culprit. As we noted in the example of cigarette smoking and lung cancer, the first step in the scientific process is to document a reliable association, and the second step is to demonstrate the biologic mechanism that might account for it. In the case of the hypothesis that estrogen causes breast cancer, not only has the association turned out to be weak or nonexistent, but also the second step has been contradicted by various lines of evidence: Y Birth control pills, which used to contain far more estrogen than HRT does, should therefore increase the risk of breast cancer. Although controversy continues on this question,124 most published studies find that oral contraceptives do not increase the risk.125–141 Y Women taking estrogen alone (ERT) should have a higher risk of breast cancer. They do not. The WHI itself found that they have no increased risk, even after an average follow-up of 6.8 years; if anything, these women have a slight decrease in breast-cancer risk.90 Y The incidence of breast cancer increases as women grow older. If taking estrogen is part of the reason, the breast cancer rate among postmenopausal women who do not take HRT should decrease with age, along with their naturally declining estrogen levels. It does not.142–144 Y According to the National Cancer Institute’s Division of Cancer Etiology, estrogens are not direct carcinogens for mammary cells.145 Estrogen can, however, induce cell proliferation. So the WHI modified their original hypothesis into this version: mutation-inducing agents are all around us, and the higher the rate of cell proliferation, the more possible it is that a proliferating cell will be exposed to a mutagen and become malignant. The problem with this argument is that the endometrium, the lining of the uterus, is more sensitive to the proliferative effect of estrogen than is the breast. As we mentioned, women who take estrogen alone have a 5– to 6-fold increased risk of uterine cancer, but no increased risk of breast cancer. If prolonged stimulation of estrogen solely from an early menarche and a late menopause predisposed women to cancer, we would see its effects on rates of endometrial cancer. We do not.146 Mammary gland cells are divided into those that have an estrogen receptor (ER) molecule on their surface, ER positive, and those that do not have this estrogen receptor, ER negative. Some researchers hypothesize that HRT might cause an increase in breast cancer by stimulating the estrogen-receptor-positive cells. The problem with this seemingly logical notion is that ER positive cells are, most often, not the ones proliferating in breast cancer. The really dangerous cells are the 5% that constitute the cancer stem cell, and they are not ER positive. ER expressing cells of the mammary epithelium are distinct from the stem cell population, and any effect of estrogen on the stem cells is mediated indirectly.147,148 But what about drugs like tamoxifen, an “estrogen antagonist,” which are given to breast-cancer patients to reduce the chance of recurrence? One of the arguments that estrogen causes or promotes breast cancer is that tamoxifen helps to reduce or retard the growth of ER positive breast cancer by competitively blocking the binding of estrogen to the estrogen receptor on breast cancer cells.149 However, several lines of research dispute this belief. For one thing, when tamoxifen is given to premenopausal women, their natural estrogen levels increase up to 5-fold.150 This rise in estrogen should block any competitive binding of tamoxifen, yet tamoxifen’s effect against breast cancer works as well in these premenopausal as in postmenopausal women.151–153 Second, approximately 40% of ER positive patients fail to respond to tamoxifen.154 Third, laboratory studies have shown that tamoxifen inhibits the stimulatory effects of growth factors involved in breast cancer155–158 even in the absence of estrogen.159 In addition, after treatment with tamoxifen, some breast cancer cells actually acquire the ability to proliferate160—and low doses of estrogen have been shown capable of killing them.161–164 Finally, tamoxifen has also been shown to have a therapeutic effect on ER negative breast cancer cells, both in laboratory studies and in human patients.165 In other words, tamoxifen works in a variety of ways that are exclusive of its action on estrogen receptors. Because the precise mechanisms responsible for its therapeutic effect remain unknown,166,167 it seems inadequate and simplistic to claim that the success of tamoxifen supports the view that estrogen causes breast cancer or stimulates cellular proliferation in breast cancer. The overall picture to date, therefore, persuades us that HRT is not a major risk factor for breast cancer.
Selected References:
1. Avrum Z. Bluming, MD, and Carol Tavris, PhD, Cancer J 2009;15: 93–104.
2. Rossouw JE, Anderson GL, Prentice RL, et al., JAMA. 2002;288:321–333.