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

2020 ◽  
Vol 21 (16) ◽  
pp. 5625
Author(s):  
Sara Tenti ◽  
Pierpaolo Correale ◽  
Sara Cheleschi ◽  
Antonella Fioravanti ◽  
Luigi Pirtoli
Keyword(s):  
Aromatase Inhibitors ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Management Strategies ◽  
Pharmacological Treatments ◽  
Hormone Receptor Positive ◽  
Menopausal Women ◽  
Molecular Aspects ◽  
Post Menopausal ◽  
Positive Breast Cancer

Aromatase inhibitors (AIs) have radically changed the prognosis of hormone receptor positive breast cancer (BC) in post-menopausal women, and are a mainstay of the adjuvant therapy for BC after surgery in place of, or following, Tamoxifen. However, AIs aren’t side effect-free; frequent adverse events involve the musculoskeletal system, in the form of bone loss, AI-associated arthralgia (AIA) syndrome and autoimmune rheumatic diseases. In this narrative review, we reported the main clinical features of these three detrimental conditions, their influence on therapy adherence, the possible underlying molecular mechanisms and the available pharmacological and non-pharmacological treatments. The best-known form is the AIs-induced osteoporosis, whose molecular pathway and therapeutic possibilities were extensively investigated in the last decade. AIA syndrome is a high prevalent joint pain disorder which often determines a premature discontinuation of the therapy. Several points still need to be clarified, as a universally accepted diagnostic definition, the pathogenetic mechanisms and satisfactory management strategies. The association of AIs therapy with autoimmune diseases is of the utmost interest. The related literature has been recently expanded, but many issues remain to be explored, the first being the molecular mechanisms.

scholarly journals Problems with the Use of Aromatase Inhibitors in Breast Cancer

2018 ◽  
Vol 4 (1) ◽  
pp. 41-42
Author(s):  
James J Stark
Keyword(s):  
Breast Cancer ◽  
Aromatase Inhibitors ◽  
Hormone Receptor ◽  
Mineral Density ◽  
Dexa Scan ◽  
Hormone Receptor Positive ◽  
Menopausal Women ◽  
Post Menopausal ◽  
Oncology Practice ◽  
Medicare Database

The use of Aromatase Inhibitors (AI’s) in the adjuvant therapy of operable breast cancer is ubiquitous. All guidelines in widespread use advocate their use in hormone-receptor-positive breast cancer in post-menopausal women. Premenopausal hormone-receptor-positive women who are considered at high risk of relapse are also treated with drug- or surgically-induced ovarian suppression plus an AI following chemotherapy, producing somewhat better results than those seen with chemo followed by tamoxifen [1]. A major side effect of these drugs is the accelerated loss of bone mineral density (BMD). The use of bone-sparing agents such as bisphosphonates has become widespread but not routine in these patients. Whether or not they receive bone-sparing agents, patients on AI’s should receive periodic assessment of bone density. How do doctors comply with this common-sense approach? The answer: not as often as they should. The best data on this practice was published in the Journal of Oncology Practice in May 2017 from a group of investigators at Yale [2]. Using the SEER Medicare database they identified over 135,000 women diagnosed with breast cancer from 2007 to 2010. Using robust exclusion criteria for such things as metastasis at presentation, too brief exposure to bisphosphonates, in situ only cancer, and prior diagnosis of osteoporosis, they identified 2409 women who met all entry criteria and served as the population studied. Within this group only 51% received a DEXA scan at initiation of AI and only 34% had a second scan within three years of being on therapy. What the authors were not able to ascertain was how many of these patients were placed on a prophylactic bisphosphonate or equivalent at the start of AI therapy. What was clear is that age and race had a lot to do with who received a DEXA scan. 30% of women over 85 vs. 56% ages 67-69 were scanned. 53% of causasian women were scanned vs. 33% non-caucasian. Wonen with higher stage and more comorbidities were also less likely to have been scanned.

PALOMA3: A double-blind, phase III trial of fulvestrant with or without palbociclib in pre- and post-menopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer that progressed on prior endocrine therapy.

2015 ◽  
Vol 33 (18_suppl) ◽  
pp. LBA502-LBA502 ◽  
Author(s):  
Nicholas C. Turner ◽  
Jungsil Ro ◽  
Fabrice Andre ◽  
Sherene Loi ◽  
Sunil Verma ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endocrine Therapy ◽  
Hormone Receptor ◽  
Progression Free Survival ◽  
Double Blind ◽  
Free Survival ◽  
Hormone Receptor Positive ◽  
Menopausal Women ◽  
Post Menopausal ◽  
Positive Breast Cancer

LBA502 Background: The growth of hormone receptor (HR) positive breast cancer (BC) is dependent on the cyclin dependent kinases CDK4/6, that promote G1-S phase cell cycle progression. Resistance to endocrine treatment remains a major clinical problem for patients with hormone receptor positive breast cancer. The PALOMA3 study assessed the efficacy of palbociclib and fulvestrant in endocrine-resistant advanced breast cancer. Methods: In this double-blind phase 3 study women with HR positive/HER2 negative advanced metastatic BC whose cancer had relapsed or progressed on prior endocrine therapy, were randomized 2:1 to palbociclib (Palbo, 125 mg/d orally for 3 wk followed by 1 wk off) and fulvestrant (F, 500 mg per standard of care) or placebo (PLB) and F. Pre- and peri-menopausal women also received goserelin. One previous line of chemotherapy for metastatic disease was permitted. The primary endpoint was investigator assessed progression-free survival (PFS). Secondary endpoints included overall survival (OS), response assessment, patient-reported outcomes, and safety and tolerability. A pre-planned interim analysis was performed after 195 PFS events by an independent data monitoring committee. Results: 521 pts were randomized, 347 to receive Palbo+F and 174 to PLB+F. Baseline characteristics were well balanced. The median age was 57 and 56 years, 79% were post-menopausal, 60% had visceral disease, and 79% were sensitive to prior endocrine therapy. Prior therapy included chemotherapy for advanced disease in 33% of pts. At the time of the interim analysis the study met the primary endpoint, median PFS was 9.2 months for Palbo+F and 3.8 months for PLB+F (HR 0.422, 95% CI 0.318 to 0.560, P<0.000001). Consistent benefit from Palbo was seen in pre- and post-menopausal women. The most common adverse effects Palbo+F versus PLB+F were neutropenia (78.8% vs. 3.5%), leucopenia (45.5% vs. 4.1%), and fatigue (38.0% vs. 26.7%). Febrile neutropenia was reported in 0.6% pts on Palbo+F and 0.6% pts on PLB+F. The discontinuation rate due to adverse events was 2.0% on Palbo and 1.7% on PLB. Conclusions: Palbociclib combined with fulvestrant improved progression free survival in hormone receptor positive advanced breast cancer that had progressed on prior endocrine therapy, and can be considered as a treatment option for these patients. Clinical trial information: NCT01942135.

scholarly journals The Effect of Gut Bacteria on the Physiology of Red Palm Weevil, Rhynchophorus ferrugineus Olivier and Their Potential for the Control of This Pest

Insects ◽  
2021 ◽  
Vol 12 (7) ◽  
pp. 594
Author(s):  
Qian-Xia Liu ◽  
Zhi-Ping Su ◽  
Hui-Hui Liu ◽  
Sheng-Ping Lu ◽  
Bing Ma ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Management Strategies ◽  
Gut Bacteria ◽  
Economic Losses ◽  
Rhynchophorus Ferrugineus ◽  
Intestinal Immunity ◽  
Red Palm Weevil ◽  
Nutrient Metabolism ◽  
Palm Weevil

Red Palm Weevil (RPW), Rhynchophorus ferrugineus Olivier, is a notorious pest, which infests palm trees and has caused great economic losses worldwide. At present, insecticide applications are still the main way to control this pest. However, pesticide resistance has been detected in the field populations of RPW. Thus, future management strategies based on the novel association biological control need be developed. Recent studies have shown that the intestinal tract of RPW is often colonized by multiple microbial species as mammals and model insects, and gut bacteria have been found to promote the growth, development and immune activity of RPW larvae by modulating nutrient metabolism. Furthermore, two peptidoglycan recognition proteins (PGRPs), PGRP-LB and PGRP-S1, can act as the negative regulators to modulate the intestinal immunity to maintain the homeostasis of gut bacteria in RPW larvae. Here, we summarized the current knowledge on the gut bacterial composition of RPW and their impact on the physiological traits of RPW larvae. In contrast with metazoans, it is much easier to make genetic engineered microbes to produce some active molecules against pests. From this perspective, because of the profound effects of gut bacteria on host phenotypes, it is promising to dissect the molecular mechanisms behind their effect on host physiology and facilitate the development of microbial resource-based management methods for pest control.

scholarly journals From Theory to Practice: Bone Health in Women with Early Breast Cancer Treated with Aromatase Inhibitors

2021 ◽  
Vol 28 (2) ◽  
pp. 1067-1076
Author(s):  
Leonor Vasconcelos de Matos ◽  
Leonor Fernandes ◽  
Maria Teresa Neves ◽  
Fátima Alves ◽  
Mafalda Baleiras ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Breast Cancer ◽  
Aromatase Inhibitors ◽  
Bone Health ◽  
Disease Free Survival ◽  
Prognostic Impact ◽  
Hormone Receptor Positive ◽  
Fracture Cohort ◽  
Fracture Event ◽  
Post Menopausal

Aromatase inhibitors (AI) are extensively used as adjuvant endocrine therapy in post-menopausal women with hormone receptor-positive early breast cancer (HR+ EBC), but their impact on bone health is not negligible. This work aimed to assess bone loss, fracture incidence, and risk factors associated with these events, as well as the prognostic influence of fractures. We have conducted a retrospective cohort study of women with HR+ EBC under adjuvant therapy with AI, during a 3-year period. Four-hundred-and-fifty-one eligible women were reviewed (median age 68 years). Median time under AI was 40 months. A fracture event occurred in 8.4%, mostly in the radium and femoral neck and in older women (mean 74 vs. 68 years, p = 0.006). Age (OR 1.01, 95% CI 1.01–1.07, p = 0.024) and time under AI (OR 1.02, 95% CI 1.00–1.04, p = 0.037) were independent predictors of fracture, with a fair discrimination (AUC 0.71). Analysis of disease-free survival according to fracture event varied between groups, disfavoring the fracture cohort (at 73 months, survival 78.6%, 95% CI, 47.6–92.4 vs. 95.6%, 95% CI, 91.2–97.8, p = 0.027). The multivariate model confirmed the prognostic impact of fracture occurrence (adjusted HR of 3.17, 95% CI 1.10–9.11; p = 0.032). Bone health is often forgotten, despite its great impact in survivorship. Our results validate the pathophysiologic link between EBC and bone metabolism, which translates into EBC recurrence. Further research in this area may help refine these findings. Moreover, early identification of women at higher risk for fractures is warranted.

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