Therapeutic Place of Fulvestrant in the Management of Hormone-receptor Positive Breast Cancer

Abstract

Fulvestrant is an oestrogen-receptor antagonist that exerts selective oestrogen receptor downregulation, antiproliferative activity and induction of apoptosis. It is indicated for the treatment of postmenopausal women with locally advanced or metastatic breast cancer for disease relapse or progression on or after adjuvant anti-oestrogen therapy. Fulvestrant was initially approved at a dose of 250 mg, however, the results of the CONFIRM trial led to approval of 500 mg dose (i.e. 500 mg on days 0, 14 and 28, then 500 mg every 28 days).Fulvestrant has also shown superiority over anastrozole as first-line therapy in the phase II trial. There are contrasting data for its efficacy when used in combination with anastrozole. It is well tolerated, with no significant difference with respect to the toxicity profile of other hormonal therapies. Treatment with fulvestrant is not associated with any clinically significant effects on sex hormone levels, bone-specific turnover markers or endometrial thickening. 4 Both anastrozole and letrozole have proven superior to tamoxifen as five years' primary adjuvant therapy in early breast cancer, in addition to providing a number of tolerability benefits compared with the tamoxifen. 5 The selective oestrogen receptor modulator (SERM) tamoxifen is also used widely to treat both premenopausal and postmenopausal patients with advanced breast cancer as firstline treatment. 6 Other endocrine therapies include the progestins, such as megestrol acetate, high-dose oestrogens and androgens. However, these treatment options are being used less frequently as newer, more effective and better-tolerated therapies become available. Although adjuvant endocrine therapy is an effective treatment for breast cancer, most patients with advanced disease will eventually exhibit resistance to individual therapies. Nonetheless, an initial response to endocrine treatment is generally indicative of a positive response to further alternative endocrine agents.

Retrospective Evaluation of Fulvestrant Efficacy and Clinical Results in Patients Using Fulvestrant

“…Although the use of combinations of CDK4/6 inhibitors (fulvestrant or letrozole) or fulvestrant as monotherapy in the first-line treatment of mHRPBC increases the treatment response of patients [ 11 , 19 ]. The most important problem in the treatment of mHRPBC patients is endocrine therapy resistance [ 19 ]. There is no known biomarker that predicts who has endocrine therapy resistance or who will benefit from endocrine therapy [ 19 ].…”

“…The most important problem in the treatment of mHRPBC patients is endocrine therapy resistance [ 19 ]. There is no known biomarker that predicts who has endocrine therapy resistance or who will benefit from endocrine therapy [ 19 ]. Resistance mechanisms are being overcome with the development of drugs such as CDK4/6 inhibitors (palbociclib, ribociclib, abemaciclib), everolimus (acting through inhibition of the PI3K/Akt/mTOR pathway), and combinations of these drugs with other endocrine therapy options in daily practice [ 11 , 19 ].…”

“…There is no known biomarker that predicts who has endocrine therapy resistance or who will benefit from endocrine therapy [ 19 ]. Resistance mechanisms are being overcome with the development of drugs such as CDK4/6 inhibitors (palbociclib, ribociclib, abemaciclib), everolimus (acting through inhibition of the PI3K/Akt/mTOR pathway), and combinations of these drugs with other endocrine therapy options in daily practice [ 11 , 19 ]. Since there is no biomarker that can help predict resistance to endocrine therapy and the efficacy of endocrine therapy, knowing that fulvestrant efficacy may vary according to age and BMI may help us to decide on the treatment of a specific group of mHRPBC.…”

Новые Возможности В Лечении Метастатического РГЖ В Постменопаузе: Клинический Обзор Ключевых Исследований

“…Фулвестрант также оказывает незначительное влияние на сывороточные уровни фолликулостимулирующего гормона и лютеинизирующего гормона у женщин в период постменопаузы с раком грудной железы [36,37], что свидетельствует об отсутствии клинически значимых периферических стероидных эффектов [38]. Более того, при применении фулвестранта у пациентов с раком грудной железы не было отмечено клинически значимого изменения уровней маркеров костного обмена в сыворотке крови [39,40].…”

Aromatase Inhibitors—Induced Musculoskeletal Disorders: Current Knowledge on Clinical and Molecular Aspects

“…These agents act as pure receptor antagonists with high affinity, and are able to induce downstream ER pathway inhibition and degradation of SERD-ER complex. Randomized clinical trials (RCTs) did not prove evidence that Fulvestrant exerts greater efficacy over Tamoxifen or AIs in the adjuvant setting, however, compared with these drugs, its use has been associated with a prolonged progression-free survival in patients with advanced and metastatic disease, where it is currently recommended, as first line treatment or as salvage therapy upon failure of Tamoxifen or AIs [8,9].…”