Most people have never heard of aromatase inhibitors even though they’ve been used for years to prevent breast-cancer tumour regrowth among women who’ve already been diagnosed and treated for the disease. The exceptions are bodybuilders who take steroids to develop muscle mass, as they also frequently take this class of drugs, which interferes with oestrogen function in the body, to counteract steroid side-effects like breast development and loss of libido. In effect, they are using one hormone-affecting drug to avoid the unwanted effects of another hormone-affecting drug.
This is the most popular ‘off-label’ use of these drugs, which are only officially approved for prevention of recurring breast cancer.
But now doctors are being urged to prescribe aromatase inhibitors for another off-label use to hundreds of thousands of healthy women.
The headlines splashed across newspapers recently hailed this pennies-a-day drug as an innovation that could slash women’s risk of breast cancer and save tens of thousands of lives.
Britain’s public-health watchdog, the National Institute for Health and Care Excellence (NICE), has released its draft guidelines recommending that healthy women should start taking the aromatase inhibitor anastrozole after menopause to cut their risk of breast cancer.
In the US too, doctors are being encouraged to prescribe the drug off-label—for purposes that America’s drugs watchdog, the Food and Drug Administration (FDA), has not yet approved—to ‘treat’ women with no personal history of cancer, but with factors that put them at higher risk of the disease.
Ordinarily, the off-label use of drugs is not marketed, and is rarely publicly encouraged because the possible effects of drug toxicity for such purposes haven’t been studied and so are unknown.
Clearly so-called ‘chemoprevention’ is the exception, with anastrozole the latest drug to join the arsenal of cancer-prevention therapy. Tamoxifen and raloxifene are two others used as ‘adjuvant’ (additional) therapies for years to prevent tumour regrowth in women who have undergone surgery, radiation and other chemotherapy, but are also prescribed to healthy women as well.
Each of these drugs targets a woman’s oestrogen production, as doctors believe elevated oestrogen levels are linked to certain types of cancer. Tamoxifen works selectively to prevent oestrogen from attaching to breast cells—it’s a ‘selective endocrine receptor modulator’, or SERM—whereas anastrozole systemically stops oestrogen production by blocking production of the enzyme aromatase (hence its classification as an aromatase inhibitor).
In 2013, NICE advised doctors to give either tamoxifen or raloxifene to healthy premenopausal women at high risk of breast cancer, but only if—given these drugs’ risks of dangerous blood clots and endometrial cancer—they have no history or increased risk of blood clots or endometrial cancer. The latest recommendation is that anastrozole be prescribed for five years to postmenopausal women at high risk of breast cancer unless they suffer from severe osteoporosis.
This new advisory means that more than 620,000 UK women will be eligible to take the drug on a daily basis, while millions more in the US will also become candidates, according to cancer advocacy groups.
Stepping forward or back?
Cancer campaigners have hailed anastrozole as the drug to bring women “one step closer to creating a future without breast cancer”. Baroness Delyth Morgan, chief executive of Breast Cancer Now, enthused that the recommendation for the drug’s routine use is “fantastic news”.
Yet, despite the thumbs-up from regulatory agencies, doctors have so far been unwilling to risk prescribing it off-label, prompting the Baroness to add, “We now need to ensure that these risk-reducing options actually make their way to patients that could benefit.”
Little wonder that cancer activists are so enthusiastic, considering how the media so optimistically reported on the results of an 18-country trial, comparing nearly 2,000 women taking the drug with about the same number taking a placebo, which concluded that women at high risk of developing breast cancer taking anastrozole for five years cut their risk
of developing the disease by around 50 per cent.1
But Vivianne Tjan-Heijnan, head oncologist at the Maastricht University Medical Centre in The Netherlands, says the popular interpretation of the study grossly inflates the significance of the drug’s benefits. The study actually reports a reduction of the hazard ratio for breast cancer, she notes, which measures the probability of an event happening. In other words, for the women at high risk of breast cancer, taking anastrozole reduced their risk of being diagnosed with cancer from 4 per cent to 2 per cent (the reported halved reduction).2
“The actual size of the effect is a very small reduction of breast cancer,” Tjan-Heijnan told WDDTY.
Conflicts of interest
Indeed, a closer look at the study results reveals that the study did not improve women’s overall survival rate from breast cancer.2 Women at high risk of breast cancer taking long-term anastrozole fared no better than those not taking the drug (18 deaths in the anastrozole group vs 17 taking a placebo).1 In other words, the drug didn’t save lives.
Not surprisingly, drug companies AztraZeneca and Sanofi-Aventis, which manufacture and supply the blockbuster drug anastrozole, funded the study, along with Cancer Research UK, which has financial and structural ties to AstraZeneca, and the National Health and Medical Research Council of Australia.
In fact, no study advocating chemoprevention with any drug to prevent breast cancer, including tamoxifen and anastrozole, has found any benefit in terms of long-term survival or actual prevention of cancer.
With no evidence that the drugs prolong life, women have to consider the considerable risks of the treatment, said David Cameron, clinical director and chair of oncology at the University of Edinburgh, Western General Hospital, when the study was published in The Lancet. “The financial costs of breast cancer chemoprevention might have decreased, but the toxicity cost to women has not,” he wrote.3
Numerous side-effects are associated with oestrogen deficiency as a result of oestrogen-blocking drugs. To begin with, anastrozole should not be taken by premenopausal women because it stops ovulation and induces infertility, while both tamoxifen and raloxifene can increase the risk of endometrial and uterine cancer, so women may actually be trading one cancer risk for another.4
The drugs are also linked to the formation of blood clots, which can cause potentially fatal deep vein thrombosis and pulmonary embolism, increasing the risk of heart attack and stroke.5
While the risk of blood clots with anastrozole is considered rare or infrequent, 6 severe joint pain and stiffness are reported by at least a third to two-thirds of women taking anastrozole in several studies,7 and significantly more women complain of carpal tunnel syndrome with the drug.8 Furthermore, more than 100–200 more women experienced vasomotor and muscle or joint symptoms with anastrozole than with a placebo—quite often to moderate or severe levels.1,3
Arimidex is also documented to weaken bones and cause osteoporosis, leading to an increased risk of fractures, with the risk being even higher than the risk with tamoxifen—10 per cent vs 7 per cent, according to AstraZeneca’s own data.
AstraZeneca also admits to clinical studies showing increased levels of cholesterol and skin and allergic reactions, while changes in blood and liver function tests have also been reported, as have dry eyes, cataracts and headache. Common side-effects include hot flashes and joint pain, weakness, mood changes and depression, back pain, sore throat, vomiting, fractures, swelling and insomnia.
One 2014 study of tamoxifen and aromatase inhibitors found that the “list of side-effects experienced and attributed to adjuvant endocrine therapy was extensive, and more than a third [of women] described the profound impact these had on their daily lives”. In addition to the extreme menopausal symptoms, some women reported feeling suicidal, while other women’s side-effects led to bone scans and further investigations to rule out endometrial cancer.9
Little wonder that so many women fail to comply with chemopreventive therapy: for example, near the end of their five-year plans, 46 per cent of them had already stopped taking tamoxifen.10 And these were women in the so-called Sister Study, who were themselves cancer-free but had a sister diagnosed with breast cancer and so were considered at high risk. If the side-effects were not worth it to these women, why would healthy women without such risks tolerate them?
The issue boils down to the usual problem of using a highly toxic substance that is difficult to tolerate as a treatment, admitted oncologist David Margileth of Saint Joseph Hospital in Orange, California, on the website BreastCancerAnswers.
And according to the American Cancer Society, identifying exactly who these ‘high-risk’ women are who are to be subjected to this extreme toxicity is a statistical challenge too.11
In fact, as far back as 2002, Cameron noted in The Lancet that doctors were aware that, for chemoprevention to claim benefit, it had to translate into a reduction of actual breast cancer mortality, demonstrate a “better safety profile” and find a way to “target the drugs to those women who will benefit most”. Fifteen years on, chemoprevention is no further ahead at meeting these criteria.
In the introduction to the 2014 international anastrozole study mentioned on page 52,1 the authors observed that, while “improvements in lifestyle are an important part of breast cancer prevention”—changes that are also acknowledged in the breast-cancer scientific literature—the primary emphasis has nevertheless remained on prevention using drugs.
Plastic surgeon Christine Horner realized this disconnect back in the 1990s. Horner, who was doing reconstructive surgery on women after mastectomy, fought against the American insurance companies who were refusing to pay for breast reconstruction because they considered it “unnecessary”. Her efforts resulted in a federal law requiring private insurers to cover all steps of breast reconstruction after conventional cancer treatment.
But Horner also saw that her mastectomy patients were becoming younger and younger—she was even carrying out reconstructions on women who were only in their 20s. She began scouring the published medical research and “what I found inspired me, gave me hope, and then outraged me”, she recounts in her book, Waking the Warrior Goddess (Basic Health Publications, 2007).
Horner discovered that many ‘natural’ foods, herbs, spices, supplements and lifestyle choices were proven by research to significantly lower the risk of breast cancer, while increasing the effectiveness of the standard medical treatments and protecting against harmful side-effects. Indeed, she writes, “good solid research published in peer-reviewed journals shows that they can also help women already diagnosed with breast cancer by slowing down tumour growth, preventing metastasis, and even shrinking the size of their tumours.”12
Breast cancer risk
The risk of developing breast cancer increases with age. At age 20, the risk is around one in 1,681 whereas, by age 40, it’s about one in 68. But most (around 77 per cent) of all breast cancer cases arise in women aged over 50 years and, by age 80, the lifetime risk of breast cancer reaches about one in eight.
While that may sound terrifying, these stats need to be kept in perspective. The reality is that most women—88 per cent—will never face breast cancer in their lifetime.
Even those who, like actress Angelina Jolie, are carrying the BRCA1 or BRCA2 gene, these genetic mutations affect only 5–10 per cent of all cases of breast cancer. Put another way, only 2 per cent of all people with breast cancer have an abnormal BRCA gene, and between 40 and 85 per cent of that 2 per cent are at risk of developing breast cancer in their lifetime—but not all of them do.13
Clearly, many other factors are at play in breast cancer besides genes. Pregnancy, early childbearing and breastfeeding are all highly protective in women with BRCA genes. Those who’ve had their first child before age 20 have a 50 per cent lower lifetime risk of the disease, which is cut even further by breastfeeding.14
Other lifestyle factors that can influence breast health include avoiding clinical examinations like mammograms that, ironically, increase the risk of cancer, while others are as simple as getting regular doses of sunshine to boost vitamin D, sipping green tea, and eating more greens and flaxseed.15
The bottom line: you don’t have to take a pill to prevent breast cancer. You can protect yourself simply by cleaning up your lifestyle and including a number of natural cancer killers in your daily diet.
Take in the sunshine vitamin
As an explosion of research on vitamin D shows, this vitamin—actually a hormone produced by the body on exposure to sunlight—is vital for countless health-related functions, such that low levels of D are linked to dozens of diseases, including Alzheimer’s, Parkinson’s and other autoimmune diseases, premature ageing, and 18 tumours, including breast cancer.
In fact, huge swathes of the American population (30–80 per cent) are deficient in vitamin D as a result of shunning the sun.
If you can’t get it from sunshine, take supplements. Healthy people usually need around 2,000 IU/day of vitamin D3 (considerably more than the standard recommendation of 400 IU/day), although amounts can vary widely based on current D levels, skin colour and sun exposure, so testing for it is essential.
By now, doctors should be aware of the connection and so should order the blood test on the patient’s request if they haven’t already done so.
A study published last year was the first to reveal that, of 1,666 postmenopausal breast-cancer survivors, those with the highest levels of vitamin D had the best chances—at around 30 per cent in this study—of avoiding disease progression and death.1
Soy is one of those controversial foods that comes with both benefits and warnings attached. Many doctors advise women against eating soy products like soybeans, natto and tempeh, which they believe will increase dangerous hormone levels, yet plastic surgeon Christine Horner calls it a “superstar in your arsenal against breast cancer”, largely because Asian women historically have lower rates of breast cancer than Western women.
A 2003 study by Japan’s National Cancer Center Research Institute in Tokyo found that women who ate at least three bowls of miso soup (made with fermented soybean paste) every day cut their risk of breast cancer by around half compared with those who consumed less than one bowl of miso soup per day.1
An analysis of the food habits of more than 9,000 American and Chinese breast-cancer survivors found that the mean daily soy isoflavone intake among US women was just 3 mg compared with 46 mg consumed by women in Shanghai.
Those who ate the most soy foods—with at least 10 mg/day of soy isoflavones—had a significantly lower risk of breast cancer recurrence compared with those with the lowest intakes (3.68 mg/day or lower) when followed for more than seven years. The researchers suggested that, while women could safely include natural soy foods as part of a healthy diet, amounting to 2 oz of tofu a day, even if they’d had breast cancer, this does not include soy protein powder.2
Maitake mushrooms (Grifola frondosa) have immunomodulatory and antitumour activities that may improve quality of life in cancer patients by “inhibiting or regressing the cancer cell growth”.3 In one Japanese study, patients with cancer were given a combination of whole maitake and its bioactive MD fraction in tablet form. Cancer regression or significant improvement was seen in 69 per cent) of breast cancer patients.4
Green tea has hundreds of studies to support its potent anti-inflammatory and antioxidant actions, and its ability to curtail the growth of at least 11 different kinds of cancer.
In the Shanghai Breast Cancer Study, which ran from 1996 to 2005, green tea consumption was associated with a significant reduction of breast cancer risk in postmenopausal women; the more they drank, the greater the reduction.5 A similar of risk and green tea consumption was seen in Chinese, Japanese and Filipino women living in Los Angeles county.6
Turmeric added to the diet enhances the effectiveness of green tea by more than eight times. More than 5,000 studies have shown that turmeric is a potent natural medicine—it has 300 times more antioxidant power than vitamin E, and is a powerful anti-inflammatory and primes the immune system. Many studies have also indicated that turmeric can adapt, blocking cancer-feeding blood-vessel growth under certain pathological conditions. Its role in fighting cancer may be related to the fact that it helps the liver detoxify, so removing carcinogens like benzopyrene from cigarette smoke and charcoal-grilled meats. One recent study confirmed that its major curcuminoid compounds, which give turmeric its orange-yellow colour, are active agents in its fight against breast cancer.7
Seaweed is rich in iodine, which plays a vital role in breast health as an antioxidant and by inhibiting cancer cell growth,8 which may be why seaweed has been repeatedly demonstrated to protect against breast cancer. In one animal study from Malaysia, the tropical edible red seaweed (Eucheuma cottonii) suppressed breast tumour growth in rats (by 27 per cent) more effectively than did tamoxifen—with little toxicity to the liver and kidneys.9
What to do instead
Christine Horner’s book Waking the Warrior Goddess cites dozens of easy evidence-based things that women can do to prevent breast cancer—from avoiding cancer-causing toxins like pesticides and radiation to eating foods rich in antioxidants and phytochemicals. Here are some of her top recommendations.
What medicine and pharmaceutical companies often call ‘prevention’ is really only early diagnosis of disease, which has some benefits. But this diagnostic test to catch cancer uses ionizing radiation that itself can cause cancer.
In her book, Horner cites a European study, published in 2012, which found that women carrying the BRCA1 or BRCA2 gene mutation exposed to any diagnostic radiation before age 30 raised their risk of breast cancer by 90 per cent.1 However, digital breast tomosynthesis, a new type of mammography, can have absorbed doses that are around 45 per cent lower to only slightly higher than those with traditional mammography.2
Nevertheless, mammograms have now repeatedly been demonstrated to make no difference to lifetime survival while carrying a risk of doing harm in themselves.3
False positives happen so frequently that, according to one study, for every woman saved from the disease by screening, three other women are overdiagnosed, emotionally traumatized, and needlessly treated with radiation and drugs for cancer they don’t have or would not be affected by.4
Dr Horner instead recommends a kind of breast-screening ultrasound called ‘sonoelectrography’, which measures changes in breast-tissue. This is important because breast-tissue composition is an important risk factor for breast cancer. She also mentions ‘thermography’, a promising breast-screening innovation, which can safely detect very early changes in tissue temperature related to inflammation. While, so far, neither technique has the support of public-health advocates, at least one study of the effectiveness of sonoelectrography for differentiating benign from malignant breast lesions was published last year.5
Eat your greens
A plant-based diet high in organic vegetables, especially cruciferous ones (broccoli, bok choy, brussels sprouts, cabbage, cauliflower, collard greens, horseradish), and whole grains is the simplest and best defence against breast cancer, says Horner.
Although preliminary findings of one large-scale study found that women who ate the most cruciferous vegetables reduced their overall risk of dying of breast cancer by 62 per cent compared with those who ate the least amount, and were also 35 per cent less likely to see their breast cancer return,6 a final analysis of more than 11,000 women could find no such association.7
Nevertheless, there is ample evidence that these vegetables lower the risk of cancers of the prostate, colon, stomach, lung, brain and possibly cervix. .
Bioflavonoids, the phytochemicals that give blueberries their blue colour and strawberries their tangy flavour, are also potently anticancer. One 2003 US study found that just half a milligram of flavonoids (as found in leafy green vegetables and herbs) can dramatically lower the risk of breast cancer. Just 0.5 mg/day of flavones—about what one-eighth of a sweet green pepper contains—decreased the risk of breast cancer by 15 per cent. For every additional 0.5 mg of flavones eaten every day, breast cancer risk fell by an additional 15 per cent.8
Look to lignans
Flaxseed (linseed) is high in beneficial anti-inflammatory omega-3 fats and fibre, and also contains 100 times more lignans than any other edible food. Lignans are also found in other seeds, vegetables, beans, legumes and dried fruit like apricots and prunes, and give plants their structure.
Lignans also have extraordinary anticancer properties. When oestrogen levels are too high, they block oestrogen receptors (like tamoxifen does) and oestrogen production by inhibiting the aromatase enzyme.9 Lignans also provide “significant protection against the development of degenerative diseases like cancer.10
Trials have shown that flaxseed oil, rich in alpha-linolenic acid (ALA), can reduce breast tumour size by 33 per cent and slow cell growth, while increasing natural cell death (apoptosis), at least in animals.11 In another animal study, mice fed diets containing flaxseed showed significant inhibition (by up to 38 per cent) of tumour growth.12 And in humans, postmenopausal women eating 25 g/day of flaxseed, or 50 mg/day of lignans, have the lowest risk of breast cancer.13