Arimidex – An effective adjuvant therapy in post-menopausal women with hormone receptor positive early breast cancer

Arimidex is a hormonal treatment that is primarily used as an adjuvant therapy in the fight against hormone receptive breast cancer. Adjuvant therapies are used in addition to the primary treatment (i.e. the surgical removal of the tumor would be the primary treatment). The purpose of adjuvant therapies is to try and decrease the risk of breast cancer from returning by destroying any cancer cells that evade surgery.  These therapies include chemotherapy drugs, radiation, targeted therapy, hormone therapy or a combination of the above.

Arimidex (the brand name for anastrozole) is especially helpful for post menopausal women who have been diagnosed with early hormone receptor positive breast cancer. The tumour cells in hormone receptor positive breast cancer contain molecules that recognize and bind with specific hormones. The tumor cells rely on the hormones to grow. Hormone receptor positive cancers are a very common form of breast cancer - around 75% of breast cancers are estrogen-receptor-positive ("ER-positive" or "ER+") and about 65% of ER-positive breast cancers are also progesterone-receptor-positive ("PR-positive" or "PR+").

As breast tissue is stimulated by estrogens, decreasing the production of estrogens is a way of suppressing the recurrence of the breast tumor tissue. Clearly therefore, if you can reduce estrogen levels in those patients suffering from estrogen receptor positive early breast cancer, you have a useful weapon in the fight against the cancer. By reducing the amount of estrogens available, the tumor cells cannot grow in the same way, if at all. The process that Arimidex uses to achieve this outcome is ‘aromatase inhibition’.

It is that fact that Arimidex is an aromatase inhibitor which means that it can be targeted at women who have reached the menopause. Prior to the menopause, a woman’s main source of estrogen production is via her ovaries. However, the menopause means that her ovaries stop estrogen production and her adrenal glands (the star shaped glands that sit on top of her kidneys) become her main estrogen producer via a process known as aromatization.  Aromatization involves using the aromatase enzyme to convert androgens into estrogens. By binding to aromatase, Arimidex inhibits (stops) aromatase carrying out this hormone conversion and thereby significantly reduces the levels of certain estrogens.
 
Also because Arimidex is an aromatase inhibitor, it is not usually used in the treatment of ER+ early breast cancers in pre-menopausal women. This is because the ovaries are the main source of estrogens in pre-menopausal women and stopping the conversion of androgens into estrogens via inhibiting the action of aromatase in the adrenal glands will have little effect on their estrogen levels.

Indeed, treating a pre-menopausal woman may even prove to be counter-productive. If aromatase inhibition does result in decreased circulating levels of estrogens in a pre-menopausal woman, the hypothalamus/pituitary axis maybe activated. If this is triggered, gonadotropin secretion will increase, which will then lead to the ovaries increasing androgen production. Androgens are the precursors to estrogens so an increase in androgen production will inevitably lead to an increase in estrogen levels.

The effectiveness and safety of Arimidex was proven out by an ATAC (Arimidex, Tamoxifen Alone or in Combination) clinical trial - one of the largest clinical studies into the treatments used in post-menopausal women with early breast cancer. As part of the study, over 6,000 post-menopausal women with localized breast cancer (i.e. breast cancer that had not spread or metastasized) received either Arimidex alone or Tamoxifen alone as an adjuvant treatment for a period of 5 years. The study followed how the women fared throughout the 5 year treatment period and, in most cases, for a period of time well beyond that.

The ATAC trial demonstrated that Arimidex was a significantly better treatment than Tamoxifen for lowering the risk of breast cancer reoccurrence in post-menopausal women with hormone receptor positive early breast cancer, increasing disease free survival or, if relapse did occur, increasing the time to relapse. Arimidex was also found to perform significantly better than Tamoxifen in reducing the risk of cancer occurring in the other breast and from spreading to other organs (metastasizing).

Although the primary use for Arimidex is as an adjuvant therapy in post-menopausal women with hormone receptor positive early breast cancer, post-menopausal women with advanced breast cancer may also be able to benefit from Arimidex treatment. This is because Arimidex slows the growth of advanced cancer within the breast and of cancer that has spread to other parts of the body.

Even some men may be able to benefit from Arimidex. Aromatization also occurs in men as they too have estrogens circulating in their bodies although not to the same extent as women. And, just as with women, it is very important for male hormone levels (including estrogens) to be balanced otherwise disease may develop. In particular, excessive estrogens in men can result in benign prostatic hyperplasia (BPH), gynecomastia (the development of male breasts), and symptoms of hypogoadism (lack of function in the testes). By taking Arimidex, a man can increase his free testosterone levels and reduce his estrogen levels, because Arimidex prevents fewer adrenal hormones and less testosterone being converted into estrogens through the aromatization process.

Dosage

Your doctor’s instructions with regard to dosage must be followed. The usual adult dose is one tablet daily taken with a drink of water. You should try to take your tablets at the same time each day. Each tablet contains 1mg of anastrozole.

Men who wish to reduce their estrogen levels and increase their free testosterone levels should take an average of 0.25mg to 0.50mg Arimidex per week.

Side effects

As was demonstrated by the ATAC clinical trial, Arimidex provides powerful, proven protection against the risk of breast cancer reoccurring whilst being much better tolerated than Tamoxifen. The most common side effects included hot flushes, thinning of the hair, joint symptoms, weakness, mood changes, pain, sore throat, nausea and vomiting, loss of appetite, depression, high blood pressure, osteoporosis, swelling of arms/legs, vaginal dryness, vaginal bleeding (usually within the first few weeks) and headache. These are only possible side effects and you may not suffer any side effects at all. If you are at all concerned talk to your doctor, but continue to take Arimidex unless advised by your doctor to do otherwise.

Caution

You must ensure that your doctor is fully informed about any other medicines that you are taking, both ‘over the counter’ and on prescription. Do not take Arimidex if you are:

• Premenopausal
• Pregnant or breast feeding your baby
• Experiencing a kidney or liver disease or disorder (consult your doctor further about this)
• Taking tamoxifen or any estrogen containing medicine such as hormone replacement therapy