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HOW DOES ANASTROZOLE WORK?

Anastrozole works by reducing the amount of oestrogen made in the body.

Some breast cancers use oestrogen in the body to help them to grow. These are known as oestrogen receptor positive or ER+ breast cancers.

Anastrozole will only be prescribed if your breast cancer is ER+.

Before the menopause, oestrogen is mainly produced in the ovaries. After the menopause, the ovaries no longer produce oestrogen, but some oestrogen is made in body fat. This process involves an enzyme (a type of protein) called aromatase.

Anastrozole belongs to a group of drugs called aromatase inhibitors. Aromatase inhibitors stop the aromatase enzyme from working. This means there’s less oestrogen in the body to help breast cancer cells to grow.

Invasive breast cancers are tested to see if they are ER+ using tissue from a biopsy or after surgery.

Tests may also be done to see if your breast cancer is progesterone receptor positive (PR+). Progesterone is another hormone. The benefits of hormone therapy are less clear for people whose breast cancer is only progesterone receptor positive (PR+ and ER-). Very few breast cancers fall into this category. However, if this is the case your specialist will discuss with you whether hormone therapy is appropriate.

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Use of anastrozole in the chemoprevention and treatment of breast cancer: A literature review

Breast cancer is one of the most commonly diagnosed types of cancer in women, presenting high incidence rates in developed regions of the world compared with developing ones. Incidence rates of the disease range from 27 cases per 100,000 women in Eastern Africa to 96 cases per 100,000 women in Western Europe.1,2 Breast cancer is characterized as a multifactorial disease and its development has been reported as the result of complex interactions between an individual’s genoma and the environment.3 Prolonged exposure to estrogene plus progesterone plays a significant role in the etiology of breast carcinoma and biosynthesis pathway of estrogens is thus an important therapeutic target.

The main enzyme involved in estrogen biosynthesis is CYP19A1 or aromatase that belongs to the cytochrome P450 family and is predominantly located in the liver, adrenal glands and fatty tissue.5 However, the source of estrogen varies widely between premenopausal and postmenopausal women (Figure 1).6 In premenopausal women, the main source of estrogen is the ovary, while in postmenopausal women, estrogen is derived from the conversion of androgens into estrogens (through the aromatase enzyme). In particular, testosterone is converted into estradiol, androstenedione into estrone and 16-alpha-hydroxytestosterone into estriol (Figure 2), originating from the peripheral tissues, including the skin, fatty tissue and breast. Therefore, the aromatase enzyme directly affects estrogen biosynthesis in the breast and it is believed that this enzyme plays an important role in the progression of breast cancer.

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Anastrozole (Arimidex) – an aromatase inhibitor for the adjuvant setting?

The development of new aromatase inhibitors such as anastrozole represents a significant step forward in the clinical management of postmenopausal women with hormone-sensitive breast cancers. The evidence in support of anastrozole – a non-steroidal, orally administered aromatase inhibitor – as an effective antitumour agent is outlined here.

Anastrozole was one of the first agents to move immediately from phase I studies of clinical pharmacology into clinically evaluable phase III trials, due primarily to its proven effectiveness in reducing plasma oestrogen, a recognized surrogate marker for anti-aromatase activity. Large-scale trials have now shown that anastrozole shows significant benefits over established endocrine agents in both first- and second-line management of advanced breast cancer. Consequently, anastrozole is an effective alternative to tamoxifen for first-line treatment of advanced disease in postmenopausal women and is now available for such use in a number of different countries. Given this superior efficacy profile in the management of advanced disease, anastrozole may also provide advantages in early disease therapy, where long-term treatment may be required to prevent disease recurrence.

Since its introduction in 1973, tamoxifen has remained the endocrine therapy of choice for early breast cancer in postmenopausal patients (Early Breast Cancer Trialists’ Collaborative Group, 1992, 1998) and has provided clinicians with an effective and well tolerated treatment. However, tamoxifen has a number of limitations, based primarily on its partial oestrogen agonist activity, which contribute directly to endometrial cell proliferation and rarely endometrial cancer (Fisher et al, 1998) and breast tumour stimulation. In contrast, aromatase inhibitors act by suppressing conversion of androgen substrates into oestrogen (the primary source of oestrogen in postmenopausal women), thereby reducing the incidence of the more serious side-effects associated with tamoxifen while maintaining efficacy for the management of hormone-sensitive breast cancer. Primary prerequisites for effective alternative agents in the adjuvant or preventative settings include equivalent or superior efficacy and/or improved tolerability compared with tamoxifen, together with easy and convenient administration. Tolerability assumes a much greater importance in the adjuvant setting, where prolonged thera

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Anastrozole (Arimidex)

Anastrozole is used to treat cancer. It is given orally (by mouth).

Possible Side Effects

Nausea Swelling of your legs, ankles and/or feet

Trouble sleeping

Weakness

Headache

Depression

Inflammation of your throat

Lymphedema - swelling in your affected arm

Joint, bone, back, and general pain

Arthritis

You may develop osteoporosis (weak and brittle bones)

Risk of bone fractures (i.e., femoral, hip, vertebral) fractures

Hot flashes or sudden skin flushing may happen. You may also feel warm or red.

Cough, trouble breathing

Rash

High blood pressure

Warnings and Precautions

If you have a history of severe heart disease, this drug may increase your risk of a heart attack. Decrease in your bone mass, which may put you at risk of bone fractures, especially of your spine, hip and wrist. Your doctor may monitor your bone mineral density.

Your cholesterol level may increase.

Allergic reactions, including anaphylaxis are rare but may happen in some patients. Signs of allergic reaction to this drug may be swelling of the face, feeling like your tongue or throat are swelling, trouble breathing, rash, itching, fever, chills, feeling dizzy, and/or feeling that your heart is beating in a fast or not normal way. If this happens, do not take another dose of this drug. You should get urgent medical treatment.

Skin reactions such as rash, ulcers, or lesions/blisters

Changes in your liver function

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What is ARIMIDEX used for?

https://www.astrazeneca.ca/content/dam/az-ca/downloads/productinformation/arimidex-consumer-information-leaflet-en.pdf

ARIMIDEX is used for the treatment of postmenopausal women with hormone receptor positive breast cancer in the following conditions:

Adjuvant treatment for early breast cancer.

Advanced breast cancer.

In hormone sensitive breast cancer, estrogens stimulate tumour growth. Following menopause, estrogens continue to be produced in small amounts in other body tissues such as the breasts, muscle and fat.

ARIMIDEX belongs to a group of medicines called aromatase inhibitors. It blocks the action of aromatase, an enzyme needed in the production of estrogens. This may help reduce the growth of breast cancer and delay the breast cancer from recurring.

Medicinal ingredients: anastrozole Non-medicinal ingredients: hypromellose, lactose monohydrate, macrogol 300, magnesium stearate, povidone, sodium starch glycolate and titanium dioxide