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Journal of Pharmaceutical and... May 2024Aromatase inhibitors such as anastrozole, letrozole, exemestane and selective estrogen down-regulator (SERD) fulvestrant are used mostly to treat breast cancer estrogen...
INTRODUCTION
Aromatase inhibitors such as anastrozole, letrozole, exemestane and selective estrogen down-regulator (SERD) fulvestrant are used mostly to treat breast cancer estrogen receptor positive in post-menopausal women. These drugs are given either through the oral route or by intramuscular injection. They have shown great inter-individual variability with a risk of cardiometabolic disorders. Hence the importance of their therapeutic drug monitoring not only for exposure-efficacy but also exposure-toxicity. We describe here a LC-MS/MS method for the simultaneous quantification of anastrozole, letrozole, exemestane and fulvestrant in human plasma.
MATERIAL AND METHODS
Plasma samples were prepared by a single-step protein precipitation. The liquid chromatography system was paired with a triple quadrupole mass spectrometer. Quantification were achieved in Multiple Reactions Monitoring mode and the electrospray ionization was in positive mode.
RESULTS
The method demonstrated consistent analytical performance across various parameters, including linearity, specificity, sensitivity, matrix effect, upper and lower limits of quantification, extraction recovery, precision, accuracy, hemolysis effect, dilution integrity, and stability under different storage conditions, in accordance with established guidelines. The analysis time for each run was 4 min. Calibration curves exhibited linearity within the 1-100 ng/mL range, with correlation coefficients > 0.99 for the four analytes. Plasma concentrations from 42 patients were integrated into the selected calibration. Stability assessments indicated that the four drugs remained stable at - 20 °C for three months, 15 days under refrigeration, up to 7 days at room temperature, and after three freeze-thaw cycles.
CONCLUSION
We have developed and validated this quantitative method for therapeutic drug monitoring of those four hormone therapy drugs:anastrozole, letrozole, fulvestrant and exemestane. This method can be also used for future clinical pharmacokinetics /pharmacodynamics studies.
Topics: Humans; Female; Breast Neoplasms; Anastrozole; Letrozole; Chromatography, Liquid; Fulvestrant; Liquid Chromatography-Mass Spectrometry; Tandem Mass Spectrometry; Reproducibility of Results
PubMed: 38367520
DOI: 10.1016/j.jpba.2024.116032 -
Frontiers in Oncology 2024Aromatase inhibitors (AIs) are a cornerstone adjuvant treatment of many hormone receptor-positive breast cancers, and nearly half of women taking aromatase inhibitors...
Aromatase inhibitor-induced arthralgia ameliorated by Mediterranean diet and active lifestyle guided by continuous glucose monitoring: a case report and review of the literature.
Aromatase inhibitors (AIs) are a cornerstone adjuvant treatment of many hormone receptor-positive breast cancers, and nearly half of women taking aromatase inhibitors suffer from AI-induced arthralgia (AIA), also known as AI-associated musculoskeletal syndrome (AIMSS), for which there are limited evidence-based treatments. Pharmacologic management and complementary methods including supplements, exercise, physical therapy, yoga, acupuncture, and massage have all shown mixed results. Comprehensive diet and lifestyle strategies are understudied in AIA/AIMSS despite their disease-modifying effects across many chronic conditions. Here we report a case of a woman with stage 2 estrogen and progesterone receptor-positive invasive ductal carcinoma on adjuvant anastrozole whose AI-induced arthralgia was durably controlled through a Mediterranean plant-forward diet and daily physical activity guided by continuous glucose monitoring. We posit that diet and a lifestyle inclusive of daily physical activity constitute a low-cost, low-risk, and potentially high-reward strategy for controlling common AI-induced musculoskeletal symptoms and that more investigation in this arena, including well-designed randomized trials, is warranted.
PubMed: 38361780
DOI: 10.3389/fonc.2024.1189287 -
JMIR Research Protocols Feb 2024Patients with postmenopausal nonmetastatic estrogen receptor-positive breast cancer often experience a reduced quality of life after primary treatment. The disease and...
BACKGROUND
Patients with postmenopausal nonmetastatic estrogen receptor-positive breast cancer often experience a reduced quality of life after primary treatment. The disease and treatment trajectory consists of surgery followed by chemotherapy or radiation therapy. Upon this, maintenance hormone therapy with an aromatase inhibitor can result in several physical and psychosocial symptoms. Optimal symptom control during maintenance therapy is central to maintaining the patient's quality of life.
OBJECTIVE
This study aims to (1) develop an electronic symptom management tool for patients with postmenopausal early breast cancer receiving maintenance aromatase inhibitors with an endocrine aspect and (2) assess the feasibility, acceptability, and usability of the pilot version of the Bone@BC app. Furthermore, longitudinally, symptom prevalence and quality of life for patients with postmenopausal nonmetastatic estrogen receptor-positive breast cancer will be explored.
METHODS
This study follows a multistage research plan. In stage 1, a systematic literature review to establish an overview of aromatase inhibitor-related symptoms reported by postmenopausal women with nonmetastatic estrogen receptor-positive breast cancer will be completed. In stage 2, a comprehensive overview of symptoms related to aromatase inhibitors (letrozole, exemestane, and anastrozole) will be performed (eg, by reviewing medical leaflets and guidelines). In stage 3, an electronic app with a user-friendly Patient Concern Inventory list to comprise symptoms and concerns will be developed. Last, in stage 4, a convergent mixed methods feasibility study of the pilot version of the Bone@BC app will be conducted. A total of 45 patients with postmenopausal nonmetastatic estrogen receptor-positive breast cancer will use the app daily for symptom identification and respond to 6 serial patient-reported outcome measurements for 12 weeks. Finally, semistructured interviews will be performed. The primary outcome includes consent rate, attrition rate, retention rates, technical issues, and adherence, assessed using preestablished criteria on feasibility and a mixed methods approach for exploring acceptability. A patient advisory board consisting of 5 women with breast cancer is recruited to include their perspectives and experiences in the planning, organization, implementation, and dissemination of the research throughout the project.
RESULTS
At the time of submitting this paper (January 2024), a total of 23 patients have been included in the stage 2 medical audit over the recruitment period of 3 months (November 2022 to February 2023), and 19 patients have been enrolled in stage 2, the semistructured patient interviews.
CONCLUSIONS
This protocol describes a study investigating the feasibility, acceptability, and usability of the symptom management tool Bone@BC developed for patients with breast cancer with an endocrine aspect.
TRIAL REGISTRATION
ClinicalTrails.gov NCT05367830; https://clinicaltrials.gov/ct2/show/NCT05367830.
INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID)
DERR1-10.2196/49549.
PubMed: 38358787
DOI: 10.2196/49549 -
Journal of Chromatography. A Mar 2024Herein, we have developed a novel method of aqueous-sample dispersive liquid-liquid microextraction (AqS-DLLME) followed by sweeping micellar electrokinetic...
Dispersive liquid-liquid microextraction followed by sweeping micellar electrokinetic chromatography-tandem mass spectrometry for determination of six breast cancer drugs in human plasma.
Herein, we have developed a novel method of aqueous-sample dispersive liquid-liquid microextraction (AqS-DLLME) followed by sweeping micellar electrokinetic chromatography-tandem mass spectrometry (MEKC-MS/MS) for simultaneous determination of breast cancer drugs letrozole, anastrozole, palbociclib, ribociclib, abemaciclib, and fulvestrant in human plasma. Coupling of MEKC to MS was possible due to the use of ammonium perfluorooctanoate (APFO) as a volatile surfactant. The MEKC and MS conditions were optimized to achieve a fast, sensitive, selective, and green analysis enabling full separation of the analytes within 16 min. Electrophoretic buffer was 125 mM APFO at apparent pH 10.5 in 32 % MeOH, while sheath liquid was 70 % MeOH with 0.2 % formic acid, delivered at 10 µL/min. Excellent extraction recoveries from plasma ranging from 89.4 to 104.9 % were obtained with a combination of protein precipitation and DLLME. The developed method was validated according to the ICH guidelines. Remarkable selectivity, accuracy (bias < 6.7 %), precision (RSD < 15.8 %), and stability (bias < 10.4 %) with insignificant matrix effect (RSD < 14.0 %) and no carry-over were obtained over a wide range of concentrations. Linearity with inter-day slope RSD lower than 8.7 % was demonstrated. With this method, very low concentrations could be detected after the injection of only 68.7 nL of the sample. The method was applied to plasma samples from six women currently receiving breast cancer treatment. Determined concentrations of the drugs of interest agreed with concentrations found in clinical studies, thus proving the suitability of the developed method for therapeutic drug monitoring as a superior alternative to published LC-MS methods.
Topics: Humans; Female; Tandem Mass Spectrometry; Breast Neoplasms; Chromatography, Micellar Electrokinetic Capillary; Liquid Phase Microextraction; Micelles; Caprylates; Fluorocarbons
PubMed: 38354504
DOI: 10.1016/j.chroma.2024.464698 -
BMC Health Services Research Feb 2024The effectiveness of anastrozole for breast cancer prevention has been demonstrated. The objective of this study was to evaluate the cost-effectiveness of anastrozole...
PURPOSE
The effectiveness of anastrozole for breast cancer prevention has been demonstrated. The objective of this study was to evaluate the cost-effectiveness of anastrozole for the prevention of breast cancer in women with a high risk of breast cancer and to determine whether anastrozole for the primary prevention of breast cancer can improve the quality of life of women and save health-care resources.
METHODS
A decision-analytic model was used to assess the costs and effects of anastrozole prevention versus no prevention among women with a high risk of breast cancer. The key parameters of probability were derived from the IBIS-II trial, and the cost and health outcome data were derived from published literature. Costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were calculated for the two strategies,One-way and probabilistic sensitivity analyses were performed.
RESULTS
In the base case, the incremental cost per QALY of anastrozole prevention was £125,705.38/QALY in the first 5 years compared with no prevention in the UK, above the threshold of WTP (£3,000/QALY),and in the 12-year period, the ICER was £8,313.45/QALY, less than WTP. For the US third-party payer, ICER was $134,232.13/QALY in the first 5 years and $8,843.30/QALY in the 12 years, both less than the WTP threshold ($150,000/QALY).
CONCLUSION
In the UK and US, anastrozole may be a cost-effective strategy for the prevention of breast cancer in high-risk postmenopausal women. Moreover, the longer the cycle of the model, the higher the acceptability. The results of this study may provide a scientific reference for decision-making for clinicians, patients, and national medical and health care government departments.
Topics: Humans; Female; Anastrozole; Breast Neoplasms; Cost-Effectiveness Analysis; Postmenopause; Quality of Life; Nitriles; Triazoles; Cost-Benefit Analysis; United Kingdom; Quality-Adjusted Life Years
PubMed: 38350960
DOI: 10.1186/s12913-024-10658-0 -
International Journal of Molecular... Jan 2024The triple-negative breast cancer (TNBC) subtype is characterized by the lack of expression of ERα (estrogen receptor α), PR (progesterone receptor) and no...
The triple-negative breast cancer (TNBC) subtype is characterized by the lack of expression of ERα (estrogen receptor α), PR (progesterone receptor) and no overexpression of HER-2. However, TNBC can express the androgen receptor (AR) or estrogen receptor β (ERβ). Also, TNBC secretes steroid hormones and is influenced by hormonal fluctuations, so the steroid inhibition could exert a beneficial effect in TNBC treatment. The aim of this study was to evaluate the effect of dutasteride, anastrozole and ASP9521 in in vitro processes using human TNBC cell lines. For this, immunofluorescence, sensitivity, proliferation and wound healing assays were performed, and hormone concentrations were studied. Results revealed that all TNBC cell lines expressed AR and ERβ; the ones that expressed them most intensely were more sensitive to antihormonal treatments. All treatments reduced cell viability, highlighting MDA-MB-453 and SUM-159. Indeed, a decrease in androgen levels was observed in these cell lines, which could relate to a reduction in cell viability. In addition, MCF-7 and SUM-159 increased cell migration under treatments, increasing estrogen levels, which could favor cell migration. Thus, antihormonal treatments could be beneficial for TNBC therapies. This study clarifies the importance of steroid hormones in AR and ERβ-positive cell lines of TNBC.
Topics: Humans; Androgens; Receptors, Estrogen; Triple Negative Breast Neoplasms; Estrogen Receptor beta; Cell Line, Tumor; Estrogens; Receptors, Androgen; Steroids; Estrogen Receptor alpha; Cell Proliferation
PubMed: 38338747
DOI: 10.3390/ijms25031471 -
JAMA Network Open Feb 2024Pathogenic variants (PVs) in BRCA1, BRCA2, PALB2, RAD51C, RAD51D, and BRIP1 cancer susceptibility genes (CSGs) confer an increased ovarian cancer (OC) risk, with BRCA1,...
IMPORTANCE
Pathogenic variants (PVs) in BRCA1, BRCA2, PALB2, RAD51C, RAD51D, and BRIP1 cancer susceptibility genes (CSGs) confer an increased ovarian cancer (OC) risk, with BRCA1, BRCA2, PALB2, RAD51C, and RAD51D PVs also conferring an elevated breast cancer (BC) risk. Risk-reducing surgery, medical prevention, and BC surveillance offer the opportunity to prevent cancers and deaths, but their cost-effectiveness for individual CSGs remains poorly addressed.
OBJECTIVE
To estimate the cost-effectiveness of prevention strategies for OC and BC among individuals carrying PVs in the previously listed CSGs.
DESIGN, SETTING, AND PARTICIPANTS
In this economic evaluation, a decision-analytic Markov model evaluated the cost-effectiveness of risk-reducing salpingo-oophorectomy (RRSO) and, where relevant, risk-reducing mastectomy (RRM) compared with nonsurgical interventions (including BC surveillance and medical prevention for increased BC risk) from December 1, 2022, to August 31, 2023. The analysis took a UK payer perspective with a lifetime horizon. The simulated cohort consisted of women aged 30 years who carried BRCA1, BRCA2, PALB2, RAD51C, RAD51D, or BRIP1 PVs. Appropriate sensitivity and scenario analyses were performed.
EXPOSURES
CSG-specific interventions, including RRSO at age 35 to 50 years with or without BC surveillance and medical prevention (ie, tamoxifen or anastrozole) from age 30 or 40 years, RRM at age 30 to 40 years, both RRSO and RRM, BC surveillance and medical prevention, or no intervention.
MAIN OUTCOMES AND MEASURES
The incremental cost-effectiveness ratio (ICER) was calculated as incremental cost per quality-adjusted life-year (QALY) gained. OC and BC cases and deaths were estimated.
RESULTS
In the simulated cohort of women aged 30 years with no cancer, undergoing both RRSO and RRM was most cost-effective for individuals carrying BRCA1 (RRM at age 30 years; RRSO at age 35 years), BRCA2 (RRM at age 35 years; RRSO at age 40 years), and PALB2 (RRM at age 40 years; RRSO at age 45 years) PVs. The corresponding ICERs were -£1942/QALY (-$2680/QALY), -£89/QALY (-$123/QALY), and £2381/QALY ($3286/QALY), respectively. RRSO at age 45 years was cost-effective for RAD51C, RAD51D, and BRIP1 PV carriers compared with nonsurgical strategies. The corresponding ICERs were £962/QALY ($1328/QALY), £771/QALY ($1064/QALY), and £2355/QALY ($3250/QALY), respectively. The most cost-effective preventive strategy per 1000 PV carriers could prevent 923 OC and BC cases and 302 deaths among those carrying BRCA1; 686 OC and BC cases and 170 deaths for BRCA2; 464 OC and BC cases and 130 deaths for PALB2; 102 OC cases and 64 deaths for RAD51C; 118 OC cases and 76 deaths for RAD51D; and 55 OC cases and 37 deaths for BRIP1. Probabilistic sensitivity analysis indicated both RRSO and RRM were most cost-effective in 96.5%, 89.2%, and 84.8% of simulations for BRCA1, BRCA2, and PALB2 PVs, respectively, while RRSO was cost-effective in approximately 100% of simulations for RAD51C, RAD51D, and BRIP1 PVs.
CONCLUSIONS AND RELEVANCE
In this cost-effectiveness study, RRSO with or without RRM at varying optimal ages was cost-effective compared with nonsurgical strategies for individuals who carried BRCA1, BRCA2, PALB2, RAD51C, RAD51D, or BRIP1 PVs. These findings support personalizing risk-reducing surgery and guideline recommendations for individual CSG-specific OC and BC risk management.
Topics: Female; Humans; Adult; Middle Aged; Breast Neoplasms; Cost-Benefit Analysis; Mastectomy; Ovarian Neoplasms; Salpingo-oophorectomy
PubMed: 38334999
DOI: 10.1001/jamanetworkopen.2023.55324 -
Gan To Kagaku Ryoho. Cancer &... Dec 2023The patient is a 74-year-old woman. She had breast cancer(invasive ductal carcinoma, ER[+], PgR[+], HER2[-], Ki-67: 30-40%)and primary right lung cancer with lumbar...
The patient is a 74-year-old woman. She had breast cancer(invasive ductal carcinoma, ER[+], PgR[+], HER2[-], Ki-67: 30-40%)and primary right lung cancer with lumbar metastasis, which led to the diagnosis synchronous double cancers of the breast and the lung. We decided to precede surgery for lung cancer because breast cancer was indicated hormonal receptor positive. Breast cancer is treated with anastrozole, thoracoscopic right upper lobectomy was performed for the lung cancer. Radiation therapy was performed for metastatic bone tumors. 13 months later, partial mastectomy sentinel lymph node biopsy performed. The histopathological diagnosis of breast cancer was pT2, pN0, cM0, pStage ⅡA, and histological response was Grade 2a. The remaining breast was treated radiation therapy. The breast cancer has not recurred and is doing well 6 months after surgery. As for primary lung cancer, 19 months have passed since surgery, and the patient is in complete remission without recurrence.
Topics: Female; Humans; Aged; Breast Neoplasms; Mastectomy; Sentinel Lymph Node Biopsy; Lung; Lung Neoplasms
PubMed: 38303307
DOI: No ID Found -
Gan To Kagaku Ryoho. Cancer &... Dec 2023Here we present a case of de novo Stage Ⅳ breast cancer successfully treated with surgery and multiple endocrine therapies over a long period of time. A 75-year-old...
Here we present a case of de novo Stage Ⅳ breast cancer successfully treated with surgery and multiple endocrine therapies over a long period of time. A 75-year-old female presented with a breast tumor with skin invasion and multiple lung metastases. Diagnosed with infiltrating breast cancer of Luminal A-like subtype, endocrine therapy with anastrozole was initiated. Despite initial response to the treatment in both the primary site and lung metastases, the primary tumor regrew and surgery with lumpectomy was performed. After a 3-year-treatment of tamoxifen, axillary lymphadenopathy and bone metastases developed. The patient was treated with fulvestrant for 5 years, resulting in clinical complete response. The now 88-year-old patient has been free of disease without treatment for a year and a half. Generally, primary tumor resection of Stage Ⅳ breast cancer does not improve prognosis, but in this case it provided good local control and enabled long-term endocrine therapy, resulting in prolonged disease-free survival.
Topics: Female; Humans; Aged; Aged, 80 and over; Breast Neoplasms; Anastrozole; Tamoxifen; Disease-Free Survival; Lung Neoplasms; Antineoplastic Agents, Hormonal
PubMed: 38303283
DOI: No ID Found -
Climacteric : the Journal of the... Apr 2024Anastrazole has recently been approved for the prevention of breast cancer in high-risk women in the UK. When given to high-risk women anastrazole halves the risk of...
Anastrazole has recently been approved for the prevention of breast cancer in high-risk women in the UK. When given to high-risk women anastrazole halves the risk of developing breast cancer but doesn't reduce the risk of breast cancer death and is associated with significant harms. Women need to be counselled about both the benefits and risks associated with anastrazole use to enable an informed treatment choice.
Topics: Female; Humans; Breast Neoplasms; Anastrozole; Postmenopause; Breast
PubMed: 38265057
DOI: 10.1080/13697137.2023.2297889