What is hormone therapy and when is it indicated?

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The response of breast cancer to hormone therapy (HT) is directly influenced by the expressiveness of steroid hormone receptors, including the estrogen receptor (ER) and the progesterone receptor (RP); the endocrine response being uncertain when the expression of hormone receptors is quantitatively or qualitatively low (<10%).

Among the therapeutic options, Tamoxifen stands out, a selective estrogen receptor modulator (SERM) for pre- and post-menopausal women; and aromatase inhibitors (AIs) for postmenopausal women. The choice of each medication is based on different clinical criteria, such as body mass index, smoking, side effects, safety profile and menstrual status; in addition to the pattern of evolution and progression of the disease.

AIs reduce estrogen synthesis by blocking the adrenal enzymatic process. Therefore, they should not be used in women with preserved ovarian function, and if indicated for women in menacme, suppression of ovarian function is recommended. For patients who experience amenorrhea after chemotherapy, the hormonal profile should be periodically evaluated and postmenopausal status confirmed.

Hormone therapy uses medications that inhibit the action or synthesis of female hormones. This helps to stop the growth of cancer cells. If these hormones are blocked, cancer cells cannot grow. Hormone therapy is used after surgery to decrease the chances of the cancer coming back. It is also used to treat breast cancer that has spread to other parts of the body. Hormone therapy is indicated when hormone receptors are measured and it is observed that the tumor is hormone-dependent, that is, it can respond to this treatment.

Another resource to block hormones that act on the breast is the removal of the ovaries in premenopausal women. These patients are also candidates for the use of LHRH analogues, subcutaneous injections given monthly, which lead to blockage of ovarian function.

Like chemotherapy, hormone therapy can be used in adjuvant, preoperative or metastatic disease. It is generally well tolerated and in hormone-responsive cases (rich in hormone receptors) they are the drugs of choice. It should not be applied simultaneously with chemotherapy. Hormonal treatment is usually long-term and the adjuvant recommendation is 5 to 10 years.

Hormone therapy can also be used in cancer chemoprevention, that is, given to women at higher risk, it reduces the chance of developing the disease. The FDA (North American regulatory body) recommends the use of Tamoxifen in women at higher risk. Studies have shown that they have had their risk reduced by 50%.

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When is hormone therapy indicated?

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It can be indicated as neoadjuvant (preoperative), adjuvant (postoperative) or in metastatic disease.

Neoadjuvant hormone therapy reduces mastectomy rates and increases the rate of conservative surgeries, especially for unifocal tumors distant from the nipple-areola complex. In patients with luminal A tumors (ER and/or RP positive, HER2 negative and Ki67 < 14%), hormone therapy is likely to represent the best neoadjuvant therapy option, considering the adverse event profile and response rates.

In pre-menopausal women, the STAGE study evaluated the effectiveness of neoadjuvant HT, comparing the use of Anastrozole (Aromatase Inhibitor) or Tamoxifen, both in association with Goserelin (LHRH analogue). In that study, Anastrozole was superior to tamoxifen at all objective response rates.

In postmenopause, among the therapeutic options in neoadjuvant therapy, controversies remain regarding the comparison between Tamoxifen and AIs. Among AIs, however, there was no significant difference between the groups evaluated in the prospective study, which compared the use of Letrozole and Anastrozole and Exemestane. However, a recent meta-analysis evaluating several neoadjuvant TH regimens observed a higher rate of objective clinical response in patients using Letrozole and Everolimus, an inhibitor of the PI3K/mTOR signaling pathway. (The PI3K/mTOR pathway is known to regulate various cellular functions, such as cell cycle regulation, migration, angiogenesis, morphology and organization of the cytoskeleton).