Use of non steroidal aromatase inhibitors in treatment of patients with early invasive hormone-dependent breast cancer in everyday clinical practice

Background: In spite of the availability of various treatment approaches including surgery, radiotherapy, and hormonal therapy, the steroidal aromatase inhibitors (SAIs) play a significant role as chemotherapeutic agents for the treatment of estrogen-dependent breast cancer with the benefit of reduced risk of recurrence. However, due to greater toxicity and side effects associated with currently available anti-breast cancer agents, there is emergent requirement to develop target-specific AIs with safer anti-breast cancer profile. Methods: It is challenging task to design target-specific and less toxic SAIs, though the molecular modeling tools viz. molecular docking simulations and QSAR have been continuing for more than two decades for the fast and efficient designing of novel, selective, potent and safe molecules against various biological targets to fight the number of dreaded diseases/disorders. In order to design novel and selective SAIs, structure guided molecular docking assisted alignment dependent 3D-QSAR studies was performed on a data set comprises of 22 molecules bearing steroidal scaffold with wide range of aromatase inhibitory activity. Results: 3D-QSAR model developed using molecular weighted (MW) extent alignment approach showed good statistical quality and predictive ability when compared to model developed using moments of inertia (MI) alignment approach. Conclusion: The explored binding interactions and generated pharmacophoric features (steric and electrostatic) of steroidal molecules could be exploited for further design, direct synthesis and development of new potential safer SAIs, that can be effective to reduce the mortality and morbidity associated with breast cancer.

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Steroidal aromatase inhibitors inhibit growth of hormone-dependent breast cancer cells by inducing cell cycle arrest and apoptosis

APOPTOSIS ◽

10.1007/s10495-013-0879-6 ◽

2013 ◽

Vol 18 (11) ◽

pp. 1426-1436 ◽

Cited By ~ 12

Author(s):

Cristina Amaral ◽

Carla Varela ◽

Margarida Borges ◽

Elisiário Tavares da Silva ◽

Fernanda M. F. Roleira ◽

...

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Cell Cycle Arrest ◽

Cancer Cells ◽

Aromatase Inhibitors ◽

Breast Cancer Cells ◽

Cycle Arrest ◽

Steroidal Aromatase Inhibitors

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Relevance of Aromatase Inhibitors in Breast Cancer Treatment

Current Topics in Medicinal Chemistry ◽

10.2174/1568026621666210701143445 ◽

2021 ◽

Vol 21 ◽

Author(s):

Ankita Sood ◽

Damanpreet Kaur Lang ◽

Rajwinder Kaur ◽

Balraj Saini ◽

Sandeep Arora

Keyword(s):

Breast Cancer ◽

Aromatase Inhibitors ◽

Breast Tissue ◽

Positive Impact ◽

Treatment Options ◽

Living Standards ◽

Efficacious Treatment ◽

Clinical Resistance ◽

Steroidal Aromatase Inhibitors ◽

Near Future

: Efficacious treatment for breast cancer is still a challenge despite the presence of various treatment options. Aromatase enzyme present in the breast tissue is responsible for estrogen formation from androgens. Aromatase inhibitors manifest remarkably ameliorated therapeutic efficacy as compared to the current therapeutic options available and exhibit a better safety profile as compared to the other drugs. Clinical resistance to aromatase inhibitors is perceived as a lack of growth inhibition by aromatase inhibitors treatment and cancer therapy becomes ineffective in causing a decrease in the size of the tumor. Naturally extracted aromatase inhibitors have a huge positive impact on vitality and living standards. This review article highlights the particulars about the currently approved steroidal and non-steroidal aromatase inhibitors for clinical use, adverse effects associated with their use and approach to tackling the problem, various strategies to overcome aromatase inhibitors resistance, information on the synthesis of various peculiar aromatase inhibitors which can prove as highly efficient and potent drugs in the near future and the drugs of natural and semi-synthetic origin which can demonstrate to be more efficient, potent and less-toxic than conventional therapy.

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Using a New Marker Clip System in Breast Cancer: Tumark Vision® Clip - Feasibility Testing in Everyday Clinical Practice

Breast Care ◽

10.1159/000486388 ◽

2018 ◽

Vol 13 (2) ◽

pp. 114-118 ◽

Cited By ~ 4

Author(s):

Anna Marlene Rüland ◽

Friederike Hagemann ◽

Mattea Reinisch ◽

Johannes Holtschmidt ◽

Aylin Kümmel ◽

...

Keyword(s):

Breast Cancer ◽

Clinical Practice ◽

Lymph Nodes ◽

Axillary Dissection ◽

Axillary Lymph ◽

Breast Cancer Patients ◽

Everyday Clinical Practice ◽

3 Dimensional ◽

Promising Tool ◽

Tumor Region

Background: This study presents first feasibility experiences with a new 3-dimensional (3D) marker clip system in clinical practice. The rate of clinical complete responses in the treatment of breast cancer patients is increasing; additionally, a change to targeted axillary dissection is being considered after neoadjuvant chemotherapy (NACT). Consequently, marker clips are needed which are reliable and easy to handle even in the axillary lymph node system. Methods: A total of 50 patients from the Breast Care Unit of the Kliniken Essen Mitte were included. Clip marking of all 50 primary breast cancer lesions as well as 23 lymph nodes was performed using the Tumark Vision® clip. Following application, the position and visibility of the marker clip were monitored and documented in 2 axes. Results: The feasibility of the Tumark Vision clip was excellent in everyday clinical practice as none of the markers dislocated. After clip marking of the tumor region and/or suspicious lymph nodes, all Tumark Vision clips could be detected in both axes. The 3D shape could be observed in all cases after application. Conclusion: The new 3D-shaped marker clip seems to be a promising tool for marking breast cancer lesions and even lymph nodes before NACT. As there are many studies ongoing to prove the feasibility of a shift from standard axillary dissection after NACT towards targeted axillary dissection, the Tumark Vision clip seems to provide good visibility even in lymph nodes after NACT. Further studies are warranted.

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Effects of new C6-substituted steroidal aromatase inhibitors in hormone-sensitive breast cancer cells: Cell death mechanisms and modulation of estrogen and androgen receptors

The Journal of Steroid Biochemistry and Molecular Biology ◽

10.1016/j.jsbmb.2019.105486 ◽

2019 ◽

Vol 195 ◽

pp. 105486 ◽

Cited By ~ 6

Author(s):

Tiago V. Augusto ◽

Cristina Amaral ◽

Carla L. Varela ◽

Fernanda Bernardo ◽

Elisiário Tavares da Silva ◽

...

Keyword(s):

Breast Cancer ◽

Cell Death ◽

Cancer Cells ◽

Aromatase Inhibitors ◽

Breast Cancer Cells ◽

Androgen Receptors ◽

Hormone Sensitive ◽

Cell Death Mechanisms ◽

Steroidal Aromatase Inhibitors

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Primary Therapy of Early Breast Cancer: Evidence, Controversies, Consensus

Geburtshilfe und Frauenheilkunde ◽

10.1055/a-0897-6457 ◽

2019 ◽

Vol 79 (06) ◽

pp. 591-604 ◽

Cited By ~ 8

Author(s):

Michael Untch ◽

Christoph Thomssen ◽

Ingo Bauerfeind ◽

Michael Braun ◽

Sara Y. Brucker ◽

...

Keyword(s):

Breast Cancer ◽

Risk Assessment ◽

Clinical Practice ◽

Consensus Conference ◽

Evidence Based ◽

Primary Therapy ◽

Therapeutic Decision ◽

Everyday Clinical Practice ◽

S3 Guideline ◽

Benefit Risk Assessment

AbstractThe results of the international St. Gallen Consensus Conference for the treatment of patients with primary breast cancer were discussed this year by a working group of leading breast cancer experts in view of the therapy recommendations for everyday clinical practice in Germany. Three of the breast cancer experts are also members of this yearʼs St. Gallen panel. The comparison of the St. Gallen recommendations with the annually updated treatment recommendations of the AGO 2019 as well as the S3 guideline is useful, since the recommendations of the St. Gallen panel represent the opinions of experts from various countries and disciplines. The recommendations of the S3 guideline and AGO are based on evidence-based research of the literature. This yearʼs 16th St. Gallen conference featured the motto “Magnitude of clinical benefit”. In addition to the evidence-based data, each therapeutic decision must also undergo a benefit/risk assessment of the patientʼs individual situation and be discussed with the patient.

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Real-world efficacy and safety of eribulin in advanced and pretreated HER2-negative breast cancer in a Spanish comprehensive cancer center

BMC Pharmacology and Toxicology ◽

10.1186/s40360-019-0367-x ◽

2019 ◽

Vol 20 (1) ◽

Cited By ~ 1

Author(s):

Milana Bergamino Sirvén ◽

Adela Fernández-Ortega ◽

Agostina Stradella ◽

Idoia Morilla ◽

Catalina Falo ◽

...

Keyword(s):

Breast Cancer ◽

Central Nervous System ◽

Nervous System ◽

Clinical Practice ◽

Objective Response ◽

Comprehensive Cancer Center ◽

Special Focus ◽

Efficacy And Safety ◽

Everyday Clinical Practice ◽

Prognosis Factors

Abstract Background Eribulin improves survival in pre-treated HER2-negative advanced breast cancer (ABC). However, limited data exist on co-morbidities and central nervous system (CNS) efficacy. The purpose of this study was to review eribulin’s efficacy and safety in everyday clinical practice with special focus on age, body mass index (BMI) and central nervous system (CNS) activity. Methods An observational study was conducted in a series of HER2-negative ABC patients treated from January’14-December’17 outside a clinical trial. Objective Response Rate (ORR), Progression Free Survival (PFS), Overall Survival (OS), and association of clinical and pathological variables with outcome were evaluated. Results Ninety-five women were treated with at least one cycle of eribulin. Median age was 57 (33–83), and 18% were obese. Median number of prior chemotherapies for ABC was 3 (2–5) and 76% of patients had visceral metastases, including 21% with CNS involvement. Most tumors were estrogen receptor-positive (79%). ORR and stable disease (SD) at 6 months were 26.2 and 37.5%, respectively. Remarkably, relevant CNS efficacy was observed with eribulin: 20% of patients obtained partial response and 25% SD. Treatment was generally well tolerated and manageable, with 29% grade 3 and 10.9% grade 4 toxicities. Median PFS and OS were 4.1 months (CI95% 3.2–4.9) and 11.1 months (CI95% 9.5–14.7), respectively. Triple-negative disease, > 2organs involved and being younger than 70 years old were independent prognosis factors for worse OS in multivariate analysis. Most patients (75%) progressed in pre-existing metastases sites. Conclusion In everyday clinical practice, eribulin’s efficacy seems similar to pivotal trials. CNS-efficacy was observed. TNBC, > 2 organs involved and being younger than 70 years old were independent prognosis factors for worse OS. Remarkably, less incidence of grade 4-toxicity compared to previous studies was found.

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