Aromatase inhibitors in the treatment of advanced breast cancer

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PantherMedia / Tomas Anderson

In breast cancer, new, malignant tissue starts growing in a mammary (breast) gland. The tumor first develops in the breast, and the cancer cells may later spread to other parts of the body.

In advanced breast cancer, the cancer can no longer be completely removed through surgery – for instance, because too much of the breast tissue is affected or because it has entered nearby lymph nodes. It is also described as advanced breast cancer if the cancer cells have spread to other parts of the body, forming metastases. Distant metastases can occur in organs such as the lungs or liver, or in bones. Breast cancer is also considered to be at an advanced stage if it comes back after previous treatment.

Women who have advanced breast cancer have several treatment options, depending on the type of tumor, their general health and their personal circumstances. The standard treatment is to try to surgically remove as much of the tumor as possible. Additional (adjuvant) therapy – in the form of radiation, hormone therapy or chemotherapy – can be used to try to kill any remaining cancer cells.

About two thirds of all women with breast cancer have a hormone-sensitive tumor. This means that like estrogen influence how fast the cancer cells grow. If the cancer cells have receptors that the can attach to, the tumor is called hormone-receptor-positive breast cancer (HR-positive or HR+). This type of breast cancer can be treated with hormone therapy, which aims to slow down tumor growth.

Hormone therapy can work in several ways, including the following:

  • By blocking hormone receptors on the cancer cells: The drug tamoxifen is similar to estrogen. When it is used, it blocks certain hormone receptors that are also found on the cancer cells, so that the natural estrogen in the body can no longer attach to them.
  • By inhibiting estrogen production: After menopause, most of the estrogen in women's bodies is produced in the adrenal glands and in muscle and fat tissue. For the estrogen to be made there, an enzyme called aromatase is needed. Drugs such as anastrozole, extemestane and letrozole block aromatase, thereby preventing the production of estrogen in the body. That is why they are called aromatase inhibitors. Before menopause, estrogen is mainly produced in the ovaries. The aromatase inhibitors don't have this effect there. So women who have not yet reached menopause are first given the drug tamoxifen.

In 2016, the Institute for Quality and Efficiency in Health Care (IQWiG, Germany) looked into how treatment with aromatase inhibitors compares with no treatment, a placebo (fake) treatment, or other hormone therapies, such as tamoxifen. The Institute also looked for differences between different aromatase inhibitors.

They found suitable data on first-line treatment with aromatase inhibitors. First-line treatment is the first treatment that is used in advanced breast cancer.

The aromatase inhibitors anastrozole and letrozole have been approved for this purpose in Germany. IQWiG found five studies that compared anastrozole or letrozole with a standard first-line treatment such as tamoxifen: Four studies (with a total of 1,290 women) compared anastrozole with tamoxifen. Another study (with a total of 939 women) compared letrozole with tamoxifen. The results are described below.

What are the pros and cons of aromatase inhibitors?

Overall, aromatase inhibitors weren't found to have any proven advantages or disadvantages compared with tamoxifen. The studies either didn't find any differences between aromatase inhibitors and tamoxifen, or there wasn't enough suitable data for an assessment.

No difference

There was no difference between first-line treatment with aromatase inhibitors and first-line treatment with tamoxifen regarding a number of issues: For instance, about the same number of women stopped their treatment due to side effects. What's more, about the same number of women developed a cardiovascular (heart and blood vessel) disease as a result of the treatment.

What remains unanswered?

There wasn't enough data to answer other questions about first-line treatment with these drugs. For example, it's not clear how aromatase inhibitors affect life expectancy when used as a first-line treatment. Different studies came to different conclusions here. Also, the studies didn't provide any suitable data on the influence of aromatase inhibitors on life without recurrences, breast-cancer-related symptoms or various severe side effects of treatment. They didn't look into how aromatase inhibitors affect the women's quality of life either.

No suitable data was available for the following treatment approaches using aromatase inhibitors:

  • Second-line treatment: If the first treatment that is used in advanced breast cancer isn't successful, a different treatment (known as a second-line treatment) is usually considered. This is often a different drug or a different treatment approach, such as another aromatase inhibitor or hormone therapy.
  • Third-line treatment: This is a treatment that is used if a second-line treatment wasn't successful. It is still not clear whether aromatase inhibitors have any pros or cons when used in these two treatment approaches.

Institute for Quality and Efficiency in Health Care (IQWiG, Germany). Aromatase inhibitors in female breast cancer: Final report; Commission A10-03. September 20, 2016. (IQWiG reports; Volume 437).

IQWiG health information is written with the aim of helping people understand the advantages and disadvantages of the main treatment options and health care services.

Because IQWiG is a German institute, some of the information provided here is specific to the German health care system. The suitability of any of the described options in an individual case can be determined by talking to a doctor. can provide support for talks with doctors and other medical professionals, but cannot replace them. We do not offer individual consultations.

Our information is based on the results of good-quality studies. It is written by a team of health care professionals, scientists and editors, and reviewed by external experts. You can find a detailed description of how our health information is produced and updated in our methods.

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Updated on July 12, 2017
Next planned update: 2021


Institute for Quality and Efficiency in Health Care (IQWiG, Germany)

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