Fulvestrant: The Second Line Of Treatment In Breast Cancer

Fulvestrant is a pure estrogen receptor antagonist drug used as a second line of treatment in metastatic breast cancer.

It is indicated in postmenopausal women with disease progression after having previously been treated with other antiestrogenic therapy.

In addition to being indicated in the treatment of metastatic breast cancer, it is also used in women in adolescence with precocious puberty.

What is breast cancer?

Breast cancer develops when cells in the breast begin to grow and divide uncontrollably. When growing in this way, the cells form a tumor that can be palmarized on examination and can be seen on x-ray.

Breast cancer can form in different parts of the breast structure, however, most begin in the ductal ducts, which are the ones that carry milk from the glands to the nipple.

Almost any cell in the body can become cancerous  and spread to other parts of the body. When this happens, we speak of metastasis. This disease is more typical in women than in men, but people of this gender can also suffer from it.

Evil or benign?

It is important to differentiate the malignant tumor from the benign one. In many cases, women have lumps in the breasts that are abnormal growths but do not spread, therefore they do not endanger the life of the person. These tumors are benign tumors.

Any mass or change that you can see in the breast is important to be studied by a specialized person to be able to distinguish it as benign or malignant. Although it is benign, it can increase the risk of suffering the opposite.

The most common symptom of breast cancer is a new lump appearing. This lump is characterized by being non-painful, hard and with irregular edges, but this is not always the case and that is why it should always be checked by the doctor. Other possible symptoms can be:

• Skin irritation or dimpling.
• Chest or nipple pain
• Contraction of the nipples.
• Swelling of all or part of the breast.
• Nipple discharge other than breast milk.

Once we have known in general terms the disease for which fulvestrant is indicated, we can more easily understand the following aspects of it:

• Mechanism of action.
• Adverse reactions.
• Pharmacokinetics.

Mechanism of action of fulvestrant

Estrogens enter breast cells and form a complex with their steroid-like receptor. This complex can form both in the cytoplasm and in the nucleus. However, even if it is formed in the cytoplasm or in the nucleus, the complex must occupy a specific place in that nucleus.

Once inside, a specific protein will be transcribed. The formation of this complex is essential for estrogens to develop their functions.

Fulvestrant prevents the formation of this complex by reversibly and competitively inhibiting the estrogen receptor. Therefore it prevents the actions of estrogens from taking place by inhibiting their dependent transcription.

Adverse reactions

The most frequently reported adverse reactions for fulvestrant were, first and foremost, injection site pain, as it is an intramuscular drug as we will see later.

In addition, many patients have suffered from nausea and bone pain as frequent adverse reactions. Other symptoms may also appear, although less frequently, such as:

• Headache and fatigue
• Hot flushes
• Vomiting
• Loss of appetite
• Cough and dyspnea (choking sensation)
• Constipation

Pharmacokinetics

Fulvestrant is a drug that, as we have mentioned before, requires intramuscular administration, being one of the most painful injections for the patient, which is why it is inconvenient.

After administration, it is absorbed slowly and maximum concentrations in plasma can be found past 1 to 5 days.

One thing to keep in mind is that fulvestrant is highly bound to plasma proteins. This is why caution should be exercised if you are being medicated at the same time with another drug that also binds to plasma proteins in a high proportion.

It can happen that the other drug displaces the estrogen antagonist, increasing its free levels in plasma and can produce toxic effects in the patient.

It undergoes hepatic metabolism and, above all, the cytochrome P-450 3A4 isoenzyme is involved in the oxidation reactions that the drug undergoes. Once metabolized, it is eliminated by the hepatobiliary route and excreted in the faeces.