scholarly journals Aromatase inhibitors and their use in the sequential setting.

1999 ◽  
pp. 259-263 ◽  
Author(s):  
R C Coombes ◽  
C Harper-Wynne ◽  
M Dowsett
Keyword(s):  
Clinical Practice ◽  
Endocrine Therapy ◽  
Aromatase Inhibitors ◽  
Mechanism Of Action ◽  
Hormone Receptor ◽  
Second Generation ◽  
Third Generation ◽  
Optimal Sequence ◽  
The Past ◽  
Hormone Receptor Positive

Over the past decade several novel aromatase inhibitors have been introduced into clinical practice. The discovery of these drugs followed on from the observation that the main mechanism of action of aminogluthemide was via inhibition of the enzyme aromatase thereby reducing peripheral levels of oestradiol in postmenopausal patients. The second-generation drug, 4-hydroxyandrostenedione (formestane), was introduced in 1990 and although its use was limited by its need to be given parenterally it was found to be a well-tolerated form of endocrine therapy. Third-generation inhibitors include vorozole, letrozole, anastrozole and exemestane, the former three being non-steroidal inhibitors, the latter being a steroidal inhibitor. All are capable of inhibiting aromatase action by >95% compared with 80% in the case of 4-hydroxyandrostenedione. The sequential use of different generations of aromatase inhibitors in the same patients is discussed. Studies suggest that an optimal sequence of these compounds may well result in longer remission in patients with hormone receptor positive tumours.

scholarly journals Fulvestrant in advanced breast cancer: evidence to date and place in therapy

2017 ◽  
Vol 9 (7) ◽  
pp. 465-479 ◽  
Author(s):  
Katalin Boér
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Postmenopausal Women ◽  
Endocrine Therapy ◽  
Aromatase Inhibitors ◽  
Hormone Receptor ◽  
Single Agent ◽  
Advanced Breast ◽  
Hormone Receptor Positive ◽  
Metastatic Setting

Breast cancer is a classical hormone-dependent tumour; therefore, endocrine therapy is the mainstay of treatment for hormone receptor-positive, human epidermal growth factor 2-negative advanced breast cancer. Until recently, classical endocrine agents such as tamoxifen, steroidal and nonsteroidal aromatase inhibitors and fulvestrant have been widely used in postmenopausal patients to treat locally advanced or metastatic disease. However, for patients with this subtype of breast cancer, the landscape of endocrine therapy is rapidly changing. Therapies targeting oestrogen modulation have evolved in recent years following the introduction of targeted agents, mTOR and CDK 4/6 inhibitors that are administered in combination with hormone therapy. As a result, options for endocrine therapy have expanded in recent years, and a variety of single-agent or combinations of targeted drugs and endocrine therapies are accepted. Fulvestrant is a selective oestrogen receptor downregulator (SERD) which was introduced to clinical practice in 2002, initially with the indication to treat postmenopausal women with hormone-receptor-positive advanced breast cancer as second-line therapy postdisease progression after aromatase inhibitors or tamoxifen. Additionally, fulvestrant has also been shown to be active in patients previously untreated with endocrine therapy, either both in the neoadjuvant and the metastatic setting, alone or in combination with other targeted therapies. Currently, the standard dose is 500 mg, which is administered with a loading dose. Fulvestrant received a new FDA indication in December 2016, in combination with palbociclib, both in pre/peri/postmenopausal women with breast cancer progressing after endocrine therapy. This manuscript aims to give an overview of new efficacy data and the current role of fulvestrant in the systemic therapy of hormone-receptor-positive advanced breast cancer, in the context of other available therapeutic modalities.

scholarly journals Current Landscape of Targeted Therapy in Hormone Receptor-Positive and HER2-Negative Breast Cancer

2021 ◽  
Vol 28 (3) ◽  
pp. 1803-1822
Author(s):  
Samitha Andrahennadi ◽  
Amer Sami ◽  
Mita Manna ◽  
Mehrnoosh Pauls ◽  
Shahid Ahmed
Keyword(s):  
Breast Cancer ◽  
Targeted Therapy ◽  
High Risk ◽  
Endocrine Therapy ◽  
Aromatase Inhibitors ◽  
Hormone Receptor ◽  
Early Stage ◽  
Treatment Options ◽  
Mtor Inhibitors ◽  
Hormone Receptor Positive

Background: Hormone receptor-positive and HER2-negative breast cancer (HR + BC) is the most prevalent breast cancer. Endocrine therapy is the mainstay of treatment, however, due to the heterogeneous nature of the disease, resistance to endocrine therapy is not uncommon. Over the past decades, the emergence of novel targeted therapy in combination with endocrine therapy has shown improvement in outcomes of HR + BC. This paper reviews available data of targeted therapy and the results of pivotal clinical trials in the management of HR + BC. Methods: A literature search in PubMed and Google Scholar was performed using keywords related to HR + BC and targeted therapy. Major relevant studies that were presented in international cancer research conferences were also included. Results: Endocrine therapy with tamoxifen and aromatase inhibitors are backbone treatments for women with early-stage HR + BC leading to a significant reduction in mortality. They can also be used for primary prevention in women with a high risk of breast cancer. Preliminary data has shown the efficacy of adjuvant cyclin-dependent kinase (CDK) 4/6 inhibitor, abemaciclib, in high-risk disease in combination with aromatase inhibitors. For most women with advanced HR + BC, endocrine therapy is the primary treatment. Recent evidence has shown that the use of CKD 4/6 inhibitors, mTOR inhibitors, and PI3K inhibitors in combination with endocrine therapy has been associated with better outcomes and delays initiation of chemotherapy. Several novel agents are under study for HR + BC. Discussion: Targeted treatment options for HR + BC have evolved. The future of overcoming resistance to targeted therapy, novel compounds, and predictive markers are key to improving HR + BC outcomes.

scholarly journals Adjuvant Endocrine Therapy in Hormone Receptor-Positive Postmenopausal Breast Cancer: Evolution of NCCN, ASCO, and St Gallen Recommendations

2006 ◽  
Vol 4 (10) ◽  
pp. 971-979 ◽  
Author(s):  
Robert W. Carlson ◽  
Clifford A. Hudis ◽  
Kathy I. Pritchard
Keyword(s):  
Breast Cancer ◽  
Postmenopausal Women ◽  
Endocrine Therapy ◽  
Aromatase Inhibitors ◽  
Hormone Receptor ◽  
Randomized Clinical Trials ◽  
Adjuvant Endocrine Therapy ◽  
Axillary Lymph ◽  
Primary Therapy ◽  
Hormone Receptor Positive

Endocrine therapy has a firm role in adjuvant treatment of women with hormone receptor–positive invasive breast cancer. Until recently, tamoxifen was the most commonly used adjuvant endocrine therapy in premenopausal and postmenopausal women. Several randomized clinical trials have studied the third-generation selective aromatase inhibitors (AIs) (anastrozole, letrozole, and exemestane) as adjuvant endocrine therapy in postmenopausal women. These studies compared therapy with an AI alone versus tamoxifen alone; 2 to 3 years of tamoxifen followed by switching to an AI versus continuation of tamoxifen; or extended therapy with an AI after approximately 5 years of tamoxifen therapy. No statistically significant differences in overall survival were observed. A single trial using extended treatment with an adjuvant AI suggests a small, statistically significant survival advantage in women with axillary lymph node–positive disease while showing no statistically significant decrease in survival with the use of an AI. The toxicities of the AIs are generally acceptable, with fewer endometrial cancers, gynecologic complaints, and thromboembolic events, but more bone fractures and arthralgias compared with tamoxifen alone. Three widely disseminated treatment guidelines, the National Comprehensive Cancer Network Breast Cancer Clinical Practice Guidelines in Oncology, the American Society of Clinical Oncology Technology Assessment on the Use of Aromatase Inhibitors, and the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer, now incorporate AIs in the adjuvant therapy of postmenopausal women with estrogen receptor–positive breast cancer.

scholarly journals Endocrine Therapy for Hormone Receptor-Positive Advanced Breast Cancer: A Nation-Wide Multicenter Epidemiological Study in China

2021 ◽  
Vol 10 ◽  
Author(s):  
Yun Wu ◽  
Yiqun Han ◽  
Pei Yu ◽  
Quchang Ouyang ◽  
Min Yan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Practice ◽  
Advanced Breast Cancer ◽  
Endocrine Therapy ◽  
Real World ◽  
Hormone Receptor ◽  
Treatment Patterns ◽  
Advanced Breast ◽  
First Line ◽  
Hormone Receptor Positive

BackgroundClinical guidelines generally recommend endocrine therapy (ET) as first-line treatment of hormone receptor-positive advanced breast cancer (HR+ ABC) whereas chemotherapy (CT) should be considered in the presence of life-threatening disease or limited clinical benefit after three sequential ET regimens. However, it is unclear if real-world clinical practice is in accordance with the current guidelines. This study was to present the real-world treatment patterns and ET regimens among HR+ ABC patients in China.MethodsUsing data from the Nation-wide Multicenter Retrospective Clinical Epidemiology Study of Female Advanced Breast Cancer in China (ClinicalTrials.gov identifier: NCT03047889), we investigated the clinicopathological characteristics, clinical profiles, and treatment patterns of HR+ ABC patients from January 2012 to December 2014.ResultsA total of 2,342 patients with HR+ ABC were included in this study. Our findings revealed that, in comparisons with those receiving initial CT (n = 1445), patients initiated ET (n =402) were significantly older, later recurrent after adjuvant treatment, with a lower rate of visceral involvement and a decreasing quantity of metastatic sites. A total of 1,308 patients received palliative ET while only 18.9% patients (n = 247) reached three lines of ET. Among patients completing more than one line of ET, the median treatment duration was 8 months for the first line, 6 months for the second line, and 3 months for the third line for patients receiving ET. In the advanced setting, the choices of palliative ET regimens were diverse, yet aromatase inhibitor (AI) monotherapy was still the overall mainstay of ET; in contrast, patients were less accessible to everolimus plus AI regimen in this population.ConclusionsLess than one quarter of patients initiated palliative ET for HR+ ABC in routine clinical practice. Patients who received multi-lines of ET experienced successive shorter durations following each line of therapy. This real-life data provides a solid overview of ET for HR+ ABC from China, indicating unmet need for treatment options that improve the effectiveness of endocrine therapy.

Sign in / Sign up

Export Citation Format

Share Document