Women with breast cancer, and even some of those who want to prevent breast cancer, will know of the Holy Trinity: Tamoxifen, Aromatase Inhibitors and Herceptin – the ‘chemotherapy’ drugs that can fight breast cancer; the drugs that can help a woman beat breast cancer.
So here is a little guide to those important cancer drugs. It is part of a new ‘CANCERactive Patients’ Drug Encyclopedia’ we will be loading onto our web site shortly. And it will be a special feature in our December 2009 icon Magazine. Don’t miss it!
Oestrogen and progesterone can each drive some breast cancers. Tests will be conducted to find out whether you are reacting to either of these hormones and, if so, hormone therapy will then be prescribed.
Oestrogen is known to drive many breast cancers – by causing changes inside healthy cells, by causing stem cells to stay in this rapidly dividing state, and by even causing damaging mutations. Oestrogen is the female sex hormone, but it is not a single entity; more it exists in a family of forms, some dangerous, others far less so. You can also absorb chemicals from some pesticides and in-home products that can act like oestrogen in your body.
You can find out far more about Oestrogen and cancer, and ways of naturally combating it in our article ‘Pillar II – Toxins and Oestrogen’, one of our ‘4 Pillars of cancer’. (Click here to read it.)
Tamoxifen is used to block the action of oestrogen on both healthy cells and cancer cells.
Aromatase inhibitors (AI’s) aim to block the production of oestrogen in your body in the first place. These include Anastrozole (Arimidex); Exemestane (Aromasin) and Letrozole (Femara). Oestrogen is principally made in the ovaries pre-menopause, but up to 60 per cent of it can be made in other tissues. Thus AI’s are most often used in women who have reached menopause.
Finally, much work is being done on women who are neither oestrogen positive (ER+) or Progesterone positive (P+). One breakthrough was finding a group of women (about 20 per cent in total) who were HER-2 positive. About half of these respond positively to a monoclonal antibody called Herceptin.
Newer work is focussing on PARP inhibitors for women who are not any of the above, and on drugs to kill cancers caused by stem cell developments, and more.
But for this article we will cover Tamoxifen, AI’s and Herceptin.
Remember drugs can't do it all One thing to remember is that drugs can’t do it all. Japanese women have been shown to have a much lower incidence of recurrence of breast cancer than Western women. Diet and lifestyle were the reasons given by the researchers (Int Radiation Oncol 2005; 62). Other research we havecovered has signalled the importance of good levels of omega 3 and vitamin B-12. In a 2008 Study from the University of Toronto, women with good blood levels of vitamin D survive far longer than those with deficiencies. And women who take daily exercise double their survival rates.
Tamoxifen ( Nolvadex D, Soltamox, Tamofen)
Tamoxifen has been the most commonly prescribed drug in the UK to treat breast cancer since its approval in the 1970s. It is given to both pre- and post-menopausal women. It is given after surgery to prevent breast cancer returning; it is given in advanced cases to reduce spread; and it is given as a preventative supplement to prevent breast cancer in high risk cases. It is still the pre-eminent drug for pre-menopausal oestrogen positive women with breast cancer. It is also given to men with breast cancer.
Tamoxifen has played a huge role in breast cancer treatment and in a 30 per cent reduction in mortality from breast cancer since 1990 despite an increase in incidence. It is normally prescribed for a period of a maximum of 5 years.
Tamoxifen is often described as ‘the anti-oestrogen’ as the simple explanation for its action has always been that it blocks the oestrogen receptor site on the walls of cells, preventing oestradiol (a dangerous member of the oestrogen family) causing its havoc inside your cells. It is thus prescribed for women who are oestrogen positive (ER+). It will not work if your cancer is not oestrogen positive.
In blocking oestrogen receptor sites, tamoxifen helps slow the growth and reproduction of breast cancer cells. In 1998, tamoxifen became the first drug to be approved by the American FDA to prevent breast cancer after research showed it halved the chances of the disease developing in women at high risk.
Research shows it can:
Lower breast cancer risk in high-risk women by almost 50 per cent
Shrink larger ER+ tumours prior to surgery
Slow, or even stop, tumour growth and spread in advanced breast cancers
Reduce the risk of a cancer returning in the same breast by 30-40 per cent in pre-menopausal women; and by 40–50 per cent in post-menopausal women who are ER+
Reduce the risk of a cancer appearing in the other breast by 50 per cent
At the same time as blocking oestrogen’s action in breast cells, it appears to stimulate its action in liver and bone cells. Thus there are claims that it can stop bone loss in older women, and even lower your cholesterol!
However, it is not without controversy. In icon magazine’s Cancer Watch (which publishes the latest research from all over the world) over the last 6 years we have covered, for example:
That four fifths of US women who have the side effects fully explained to them, subsequently do not want to take it as a preventative agent (Cancer 2005)
That researchers in the UK concluded it should not be used as a preventative agent – the risks outweighing the benefits
That tamoxifen’s effects stay with you for 5 years after the end of usage (J Nat Can Inst 2007; 99, 272-282)
That tamoxifen can increase the chances of endometrial cancer three fold (Int Journal Gyn Cancer 2007)
That tamoxifen usage for 5 or more years can cause a more dangerous ER-ve cancer in the other breast (Cancer Research online August 2009)
As if that was not enough, recent research studies have shown that the common view of how it works are not entirely correct. Cancer Research UK (December 2008) stated, ‘ Previously it was known that tamoxifen worked by blocking oestrogen from causing unchecked cell growth in breast tissue............. by switching certain genes on........ but the mechanism by which this occurred was unknown’. Hardly reassuring to users, and difficult to understand how it was originally approved if we didn’t know how it worked. Herbalists have been called quacks for less. tamoxifen can itself cause genetic mutation
Other research studies covered in Cancer Watch have suggested that tamoxifen can itself cause genetic mutation.
A big concern has been ‘tamoxifen resistance’ which can develop in some women users and no one seems to know ‘why’. The CRUK statement above prefaced a study by CRUK Cambridge Research Institute workers into the problem. They discovered (Nature, Dec 2008) ‘for the first time the mechanism by which tamoxifen operates’. It switches off a breast cancer gene ErbB2 via a protein Pax2, which keeps it off. Tamoxifen resistence occurs when the gene is ‘on’.
On the knotty problem of tamoxifen resistance German Researchers seem to have shed some light too. Researchers from three German Universities have shown that Electromagnetic Fields (thought by many to be capable of causing breast cancer) ‘can result in a lower sensitivity to tamoxifen’. The researchers were convinced that EMF’s reduce the efficacy of tamoxifen.
Also identified has been the need for an enzyme (CYP2D6) to convert the drug tamoxifen to its active form. In about 10 per cent of cases this conversion doesn’t happen. It can be worsened by certain drugs such as Prozac and other anti-depressants (SSRI’s and SNRI’s) and drugs like Benedryl. You must check out all other medications – they might stop your tamoxifen working.
Side effects can include: hot flushes, irregular menstrual cycles, unusual vaginal discharge or bleeding, irritation of skin around vagina. Rarely there can be blood clots, cancer of the womb lining (endometriosis) and an increased risk of stroke or thrombo-embolism.
Developments: US research showed that the use of natural vitamin E (especially tocotrienols) meant 25 per cent less tamoxifen needed to be prescribed. Similar research has shown that indole 3 carbinol supplementation means less drug is needed for the same positive effect. Indole 3 carbinol (I3C) is being studied by pharmaceutical companies as an alternative, with less side-effects and an ability to denature not just the aggressive oestrogens, but their by-products. Readers should read our article about Indole 3 Carbinol. You can get I3C from greens and broccoli, or from natural supplements. (You should read our article on indole 3 carbinol) Phytoestrogens from vegetables, fruits and particularly pulses (like chick peas, beans etc) and red clover have been shown to block oestrogen receptor sites in the same way as tamoxifen. (You should read our article on Natural Alternatives)
Usage: Tamoxifen is taken orally in tablet form or in a sugar-free syrup. Most doctors recommended it is taken at the same time each day.
Aromatase Inhibitors (AI’s)
Approximately two in three breast cancers rely on oestrogen to grow. Oestrogen is the female sex hormone commonly understood to be produced in the ovaries. At menopause the oestrogen production in the ovaries declines just enough to stop egg production - the total oestrogen level in the body falls by about one third.
However, women do produce oestrogen elsewhere in the body; a source of the precursors being fat. In post-menopausal women oestrogens are mostly produced in the adrenal glands' fatty tissues, or in muscle and within the fatty layers under the skin. These are termed endogenous oestrogens.
The production mechanism is carried out by an enzyme called aromatase and the conversion process is known as aromatisation. AI’s thus work by blocking oestrogen synthesis and they reduce oestrogen in post-menopausal women to very low levels.
Of course, you can have external chemicals in your body, for example from certain pesticides, BPA, phthalates, toluene, perfumes, parabens etc which are known to act like oestrogens – they are termed xenoestrogens and are exogenous oestrogens.
An oestrogen positive female with breast cancer may typically have five years of tamoxifen followed by three years of an Aromatase Inhibitor. The makers of AI’s have questioned this and, unsurprisingly, there have been studies to show that AI’s can be used much earlier in the treatment pattern. NICE now recommends AI’s for early stage breast cancer too.
Cutting oestrogen production to very low levels is obviously an extreme measure. There are many ways of cutting both natural endogenous, and chemical exogenous oestrogens.
Being overweight is a counter-active factor Being overweight is a counter-active factor as fat can provide the building blocks for oestrogen, and is also an excellent solvent and so will store both endogenous and exogenous oestrogens that you would be better to excrete. Having good blood levels of plant oestrogens (phytoestrogens) has been shown to be protective, as has Indole3carbinol (from broccoli and greens. But one of the biggest factors in excreting excess oestrogen has now been shown in clinical trials to be the involvement of certain beneficial bacteria in the gut, and their ability to use whole foods like lignans to bind to (chelate with) oestrogenic products and help excrete them.
Natural Progesterone hormone is also an oestrogen ‘balancer, as is the hormone Melatonin, produced about 90 minutes after falling asleep in a darkened room. Details on all of these ways of reducing oestrogen are covered on the CANCERactive web site.
Readers should also look at our article ‘Aromatase Inhibitors – are there natural alternatives to the drugs?’ click here.
Side effects can typically include: hot flushes and sweats, tiredness, vaginal dryness, nausea, and vomiting, diarrhoea, hair thinning, headaches, vaginal bleeding (very rare and usually in first few weeks of treatment), joint pains/stiffness and increased or decreased appetite. Long-term risk: osteoporosis is the big worry – although bisphosphonates can be given to prevent bone loss.
Anastrozole (Arimidex) is licensed for use on post-menopausal women with operable ER+ (oestrogen driven) breast cancer who can't take tamoxifen, for example due to problems with hot flushes or thrombo-embolism. In clinical trials it has proved more effective than Tamoxifen post-menopausally due to its general action on the various sources of endogenous oestrogens. Cancer Research UK is conducting a 10-year-study using anastrozole on 10,000 post-menopausal women with a family history of breast cancer to see whether it will prevent it.
Usage: It is taken orally.
Exemestane (Aromasin) is an aromatase inhibitor used in the treatment of a breast cancer stimulated by the body’s oestrogen levels. Stopping the body’s own oestrogen reaching the tumour can cause the cancer cells to stop growing and in some cases shrivel up and die completely (self destruct - apoptosis). Exemestane effectively blocks the production of oestrogen from these sites.
Interim findings of the TEAM (Tamoxifen Exemestane Adjuvant Multicenter) trial reported on 11th December at the 2008 San Antonio Breast Cancer Symposium (SABCS) suggest women with early invasive breast cancer can expect fewer breast cancer recurrences and a longer time to the occurrence of distant metastases if they are treated with the exemestane rather than the standard adjuvant therapy tamoxifen after initial therapy (surgery plus chemotherapy and/or radiotherapy).
TEAM includes almost 10,000 postmenopausal women with invasive hormone-receptor-positive early breast cancer from nine countries.
Letrozole (Femara) was approved by the FDA in 1997 to help treat advanced breast cancer in post-menopausal women whose breast cancer tumours have not responded well to Tamoxifen. Recent publication of a trial has shown that using Letrozole, after five years of Tamoxifen, is more effective than continuing Tamoxifen for women who have primary operable breast cancer.
Herceptin is the only monoclonal antibody treatment currently available for breast cancer. The drug was first approved in the USA in 1998 for women whose advanced, metastatic breast cancer was HER2 positive. In 2006 it was approved for use in early stage patients too. At the moment it is licensed in the UK to treat advanced breast cancer in women who over-express the HER2 gene.
HER2 is a growth factor found on the surface of cells and plays a key role in regulating cell growth. Some 20 per cent of breast cancer cells have an excess amount of the HER2 protein on their surface, which makes the cancer more aggressive.
Thus Herceptin is not for every women, just the one in five who have this HER2 positive test result. Herceptin is not for every women
The over-expression of HER2 causes cells to grow, divide, and multiply more rapidly. Herceptin seeks out HER2 and attaches itself to the protein receptor on the surface of cells. By binding to the cells, Herceptin has been shown to slow the growth and spread of tumours that have this overabundance of HER2 protein receptors.
Herceptin received ‘Big Press’ – but some sensibility needs to be applied. Recent studies covered in Cancer Watch, for example, show:
It has been shown in studies to shrink tumours and extend women's survival by an average of about 13 months
To repeat, it is applicable to about 20 per cent of breast cancer patients – and does have a marked effect in approximately half of those.
When treated with Herceptin prior to surgery 50 per cent of HER2 positive women show no signs of disease immediately after (M.D.Anderson, Texas)
But resistance does occur to the drug. MD Anderson recommend all women are regularly tested during its usage and those that stop being HER2 positive come off it. A new drug is being developed to ‘protect’ Herceptin and extend its effects.
Researchers in Gerona have shown that phenolic compounds directly extracted from olive oil are effective against both HER2-positive and HER2-negative breast cancers cells. Polyphenols (especially those known as secoiridoids and lignans) found in extra virgin olive oil not only inhibited the activity of cancer-promoting HER-2 proteins but also promoted their degradation.
Side effects can include: weakening of the heart muscle, reduction of white blood cells (neutropenia), diarrhoea, anaemia, abdominal pain, infection or allergies. Some people who received Herceptin with Adriamycin (doxorubicin) experienced heart problems, because of the cardiac toxicity of both drugs. This combination is no longer recommended.
Usage: Herceptin is usually given intravenously in the outpatients department.