Aromatase inhibitors for early-stage breast cancer

(PantherMedia / Alexander Raths)

In breast cancer, new, malignant tissue starts growing in a mammary gland. If the cancer remains within a limited area around the breast and doesn't spread to other parts of the body (metastasis), it is referred to as early-stage breast cancer. Some of the breast lymph nodes may also be affected.

Women who have early-stage breast cancer have several treatment options, depending on the type of tumor, their individual health circumstances and their personal preferences. 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 hormones like estrogen influence how fast the cancer cells grow. If the cancer cells have receptors that the hormones can attach to, the tumor is referred to as hormone-receptor-positive breast cancer (HR-positive or HR+). Anti-hormone therapy is a possible treatment for hormone-receptor-positive cancer. This aims to slow down tumor growth.

Anti-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. There it is needed for the production of an enzyme called aromatase. 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 are ineffective there, though. So younger women who have not yet entered menopause are first treated with the drug tamoxifen.

Assessment of aromatase inhibitors

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

They found suitable data on the following treatments with aromatase inhibitors:

• Upfront therapy: In upfront therapy after breast surgery, tamoxifen or aromatase inhibitors are taken for five years.
• "Switch" treatment approach: In the "switch" treatment approach, the patient uses tamoxifen for two to three years, and then switches to an aromatase inhibitor. This anti-hormone treatment takes five years in total. The decision regarding whether or not to switch to an aromatase inhibitor is made after treatment with tamoxifen.
• Extended treatment approach: In the extended treatment approach, an aromatase inhibitor is taken after five years of treatment with tamoxifen.

No suitable or practice-oriented data was available for the following treatment approaches using aromatase inhibitors:

• Neoadjuvant therapy: In neoadjuvant therapy, treatment with medication is started before surgery in order to reduce the size of the tumor and make it easier to operate on.
• Sequential therapy: In sequential therapy, over the course of five years patients first take tamoxifen and then switch to an aromatase inhibitor (or take the aromatase inhibitor first and then switch to tamoxifen). The decision to switch medications is made beforehand, directly after breast surgery.

Due to the lack of data, it still isn't clear whether aromatase inhibitors have any advantages or disadvantages when used in these two treatments approaches.