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Cancers Jan 2024Surgery, anticancer drugs (chemotherapy, hormonal medicines, and targeted treatments), and/or radiation are common treatment strategies for neoplastic diseases.... (Review)
Review
Surgery, anticancer drugs (chemotherapy, hormonal medicines, and targeted treatments), and/or radiation are common treatment strategies for neoplastic diseases. Anticancer drugs eliminate malignant cells through the inhibition of specific pathways that contribute to the formation and development of cancer. Given the ability of such pharmacological medications to combat cancerous cells, their role in the management of neoplastic diseases has become essential. However, these drugs may also lead to undesirable systemic and ocular adverse effects due to cyto/neuro-toxicity and inflammatory reactions. Ocular surface side effects are recognized to significantly impact patient's quality of life and quality of vision. Blepharoconjunctivitis is known to be a common side effect caused by oxaliplatin, cyclophosphamide, cytarabine, and docetaxel, while anastrozole, methotrexate, and 5-fluorouracil can all determine dry eye disease. However, the potential processes involved in the development of these alterations are yet not fully understood, especially for novel drugs currently available for cancer treatment. This review aims at analyzing the potential ocular surface and adnexal side effects of novel anticancer medications, trying to provide a better understanding of the underlying pharmacological processes and useful insights on the choice of proper management.
PubMed: 38254833
DOI: 10.3390/cancers16020344 -
Antioxidants (Basel, Switzerland) Jan 2024The common human coronavirus (HCoV) exhibits mild disease with upper respiratory infection and common cold symptoms. HCoV-OC43, one of the HCoVs, can be used to screen...
The common human coronavirus (HCoV) exhibits mild disease with upper respiratory infection and common cold symptoms. HCoV-OC43, one of the HCoVs, can be used to screen drug candidates against SARS-CoV-2. We determined the antiviral effects of FDA/EMA-approved drug anastrozole (AZ) on two human coronaviruses, HCoV-OC43 and HCoV-229E, using MRC-5 cells in vitro. The AZ exhibited antiviral effects against HCoV-OC43 and HCoV-229E infection. Subsequent studies focused on HCoV-OC43, which is related to the SARS-CoV-2 family. AZ exhibited anti-viral effects and reduced the secretion of inflammatory cytokines, TNF-α, IL-6, and IL-1β. It also inhibited NF-κB translocation to effectively suppress the inflammatory response. AZ reduced intracellular calcium and reactive oxygen species (ROS) levels, including mitochondrial ROS and Ca, induced by the virus. AZ inhibited the expression of NLRP3 inflammasome components and cleaved IL-1β, suggesting that it blocks NLRP3 inflammasome activation in HCoV-OC43-infected cells. Moreover, AZ enhanced cell viability and reduced the expression of cleaved gasdermin D (GSDMD), a marker of pyroptosis. Overall, we demonstrated that AZ exhibits antiviral activity against HCoV-OC43 and HCoV-229E. We specifically focused on its efficacy against HCoV-OC43 and showed its potential to reduce inflammation, inhibit NLRP3 inflammasome activation, mitigate mitochondrial dysfunction, and suppress pyroptosis in infected cells.
PubMed: 38247540
DOI: 10.3390/antiox13010116 -
JAMA Oncology Mar 2024Adding fulvestrant to anastrozole (A+F) improved survival in postmenopausal women with advanced estrogen receptor (ER)-positive/ERBB2 (formerly HER2)-negative breast... (Randomized Controlled Trial)
Randomized Controlled Trial
Endocrine-Sensitive Disease Rate in Postmenopausal Patients With Estrogen Receptor-Rich/ERBB2-Negative Breast Cancer Receiving Neoadjuvant Anastrozole, Fulvestrant, or Their Combination: A Phase 3 Randomized Clinical Trial.
IMPORTANCE
Adding fulvestrant to anastrozole (A+F) improved survival in postmenopausal women with advanced estrogen receptor (ER)-positive/ERBB2 (formerly HER2)-negative breast cancer. However, the combination has not been tested in early-stage disease.
OBJECTIVE
To determine whether neoadjuvant fulvestrant or A+F increases the rate of pathologic complete response or ypT1-2N0/N1mic/Ki67 2.7% or less residual disease (referred to as endocrine-sensitive disease) over anastrozole alone.
DESIGN, SETTING, AND PARTICIPANTS
A phase 3 randomized clinical trial assessing differences in clinical and correlative outcomes between each of the fulvestrant-containing arms and the anastrozole arm. Postmenopausal women with clinical stage II to III, ER-rich (Allred score 6-8 or >66%)/ERBB2-negative breast cancer were included. All analyses were based on data frozen on March 2, 2023.
INTERVENTIONS
Patients received anastrozole, fulvestrant, or a combination for 6 months preoperatively. Tumor Ki67 was assessed at week 4 and optionally at week 12, and if greater than 10% at either time point, the patient switched to neoadjuvant chemotherapy or immediate surgery.
MAIN OUTCOMES AND MEASURES
The primary outcome was the endocrine-sensitive disease rate (ESDR). A secondary outcome was the percentage change in Ki67 after 4 weeks of neoadjuvant endocrine therapy (NET) (week 4 Ki67 suppression).
RESULTS
Between February 2014 and November 2018, 1362 female patients (mean [SD] age, 65.0 [8.2] years) were enrolled. Among the 1298 evaluable patients, ESDRs were 18.7% (95% CI, 15.1%-22.7%), 22.8% (95% CI, 18.9%-27.1%), and 20.5% (95% CI, 16.8%-24.6%) with anastrozole, fulvestrant, and A+F, respectively. Compared to anastrozole, neither fulvestrant-containing regimen significantly improved ESDR or week 4 Ki67 suppression. The rate of week 4 or week 12 Ki67 greater than 10% was 25.1%, 24.2%, and 15.7% with anastrozole, fulvestrant, and A+F, respectively. Pathologic complete response/residual cancer burden class I occurred in 8 of 167 patients and 17 of 167 patients, respectively (15.0%; 95% CI, 9.9%-21.3%), after switching to neoadjuvant chemotherapy due to week 4 or week 12 Ki67 greater than 10%. PAM50 subtyping derived from RNA sequencing of baseline biopsies available for 753 patients (58%) identified 394 luminal A, 304 luminal B, and 55 nonluminal tumors. A+F led to a greater week 4 Ki67 suppression than anastrozole alone in luminal B tumors (median [IQR], -90.4% [-95.2 to -81.9%] vs -76.7% [-89.0 to -55.6%]; P < .001), but not luminal A tumors. Thirty-six nonluminal tumors (65.5%) had a week 4 or week 12 Ki67 greater than 10%.
CONCLUSIONS AND RELEVANCE
In this randomized clinical trial, neither fulvestrant nor A+F significantly improved the 6-month ESDR over anastrozole in ER-rich/ERBB2-negative breast cancer. Aromatase inhibition remains the standard-of-care NET. Differential NET response by PAM50 subtype in exploratory analyses warrants further investigation.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT01953588.
Topics: Aged; Female; Humans; Anastrozole; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Fulvestrant; Ki-67 Antigen; Neoadjuvant Therapy; Nitriles; Postmenopause; Receptor, ErbB-2; Receptors, Estrogen; Triazoles; Triple Negative Breast Neoplasms; Middle Aged
PubMed: 38236590
DOI: 10.1001/jamaoncol.2023.6038 -
Lipids in Health and Disease Jan 2024Endocrine drugs may affect lipid metabolism in breast cancer (BC) patients. This study explores lipid changes in early-stage BC patients taking different endocrine drugs.
BACKGROUND
Endocrine drugs may affect lipid metabolism in breast cancer (BC) patients. This study explores lipid changes in early-stage BC patients taking different endocrine drugs.
METHODS
The changing trend of blood lipid during endocrine therapy in 2756 BC patients from January 2013 to December 2021 was retrospectively analyzed. The changes in four lipid parameters were assessed by the Generalized Linear Mixed Model, including total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL-C), and high-density lipoprotein (HDL-C). These parameters were quantified at baseline and at 6, 12, 18, 24, 36, 48, 60, and 72 months after endocrine therapy initiation. Furthermore, a subgroup analysis according to menopausal status or medication types was conducted.
RESULTS
A total of 1201 patients taking aromatase inhibitors (AIs), including anastrozole (ANA), letrozole (LET), or exemestane (EXE), and 1555 patients taking toremifene (TOR) were enrolled. TC and TG levels showed a significantly elevated trend during 5 years of treatment (P < 0.05). HDL-C levels increased from baseline in the TOR group (P < 0.05). Compared with the postmenopausal AI group, the increasing trends of TC, TG, and LDL-C in the premenopausal AI group were more evident with the extension of time (β = 0.105, 0.027, 0.086, respectively). Within 3 years, TC, TG, and LDL-C levels in the ANA and LET groups were significantly higher than baseline (P < 0.05). Moreover, the levels of TG in the EXE group were significantly lower than that in the ANA or LET group (P < 0.05), but this significant difference disappeared after 3 years.
CONCLUSIONS
AIs significantly influenced lipid profiles more than TOR. AIs had a greater effect on blood lipids in premenopausal patients. Steroidal AIs (EXE) may affect lipid levels less than nonsteroidal AIs (ANA and LET).
Topics: Humans; Female; Breast Neoplasms; Cholesterol, LDL; Retrospective Studies; Letrozole; Toremifene; Triglycerides
PubMed: 38191454
DOI: 10.1186/s12944-024-02002-6 -
European Review For Medical and... Dec 2023In patients with breast cancer and positive hormone receptors, aromatase inhibitors are effective in reducing the risk of recurrences and are active in progressing the...
OBJECTIVE
In patients with breast cancer and positive hormone receptors, aromatase inhibitors are effective in reducing the risk of recurrences and are active in progressing the disease in this setting. On the other hand, fatigue and painful musculoskeletal side effects can significantly reduce treatment compliance. With no further treatment options to control these symptoms, non-pharmaceutical interventions, such as oxygen-ozone therapy, may play a role in managing rheumatologic symptomatology inasmuch. We have previously reported evidence on the effectiveness of oxygen-ozone in the treatment of pain and fatigue in chronic fatigue syndrome and fibromyalgia patients and in oncological patients as well.
PATIENTS AND METHODS
In this study, we reported 6 cases of patients (mean age 64 yrs, all Caucasian females) with breast cancer upon treatment with anastrozole (Arimidex®), suffering from musculoskeletal pain, weakness and fatigue, and therefore treated with oxygen-ozone major autohemotherapy according to the Italian Scientific Society of Oxygen Ozone Therapy (SIOOT) protocol. Pain was measured with a 10-item Numerical Rating Scale (NRS) and fatigue with a 7-item Fatigue Scoring Scale (FSS).
RESULTS
A reduction of at least 66% of pain (from 9.43 ±0.54 SD to 2.36 ±1.32 SD, p<0.001) and 66.26% of fatigue were obtained for all the cases. Pain and fatigue disappeared within one month from ozone therapy, and a healthy painless state lasted for many months following the oxygen-ozone therapy.
CONCLUSIONS
The oxygen-ozone therapy is a sound opportunity for breast cancer patients to reduce anti-aromatase-induced pain, fatigue, and musculoskeletal symptoms.
Topics: Female; Humans; Middle Aged; Aromatase Inhibitors; Breast Neoplasms; Musculoskeletal Pain; Ozone; Quality of Life; Oxygen; Anastrozole
PubMed: 38095411
DOI: 10.26355/eurrev_202312_34602 -
The Lancet. Oncology Jan 2024An increased risk of breast cancer is associated with high serum concentrations of oestradiol and testosterone in postmenopausal women, but little is known about how... (Randomized Controlled Trial)
Randomized Controlled Trial
Effect of baseline oestradiol serum concentration on the efficacy of anastrozole for preventing breast cancer in postmenopausal women at high risk: a case-control study of the IBIS-II prevention trial.
BACKGROUND
An increased risk of breast cancer is associated with high serum concentrations of oestradiol and testosterone in postmenopausal women, but little is known about how these hormones affect response to endocrine therapy for breast cancer prevention or treatment. We aimed to assess the effects of serum oestradiol and testosterone concentrations on the efficacy of the aromatase inhibitor anastrozole for the prevention of breast cancer in postmenopausal women at high risk.
METHODS
In this case-control study we used data from the IBIS-II prevention trial, a randomised, controlled, double-blind trial in postmenopausal women aged 40-70 years at high risk of breast cancer, conducted in 153 breast cancer treatment centres across 18 countries. In the trial, women were randomly assigned (1:1) to receive anastrozole (1 mg/day, orally) or placebo daily for 5 years. In this pre-planned case-control study, the primary analysis was the effect of the baseline oestradiol to sex hormone binding globulin (SHBG) ratio (oestradiol-SHBG ratio) on the development of all breast cancers, including ductal carcinoma in situ (the primary endpoint in the trial). Cases were participants in whom breast cancer was reported after trial entry and until the cutoff on Oct 22, 2019, and who had valid blood samples and no use of hormone replacement therapy within 3 months of trial entry or during the trial. For each case, two controls without breast cancer were selected at random, matched on treatment group, age (within 2 years), and follow-up time (at least that of the matching case). For each treatment group, we applied a multinominal logistic regression likelihood-ratio trend test to assess what change in the proportion of cases was associated with a one-quartile change in hormone ratio. Controls were used only to determine quartile cutoffs. Profile likelihood 95% CIs were used to indicate the precision of estimates. A secondary analysis also investigated the effect of the baseline testosterone-SHBG ratio on breast cancer development. We also assessed relative benefit of anastrozole versus placebo (calculated as 1 - the ratio of breast cancer cases in the anastrozole group to cases in the placebo group). The trial was registered with ISRCTN (number ISRCTN31488319) and completed recruitment on Jan 31, 2012, but long-term follow-up is ongoing.
FINDINGS
3864 women were recruited into the trial between Feb 2, 2003, and Jan 31, 2012, and randomly assigned to receive anastrozole (n=1920) or placebo (n=1944). Median follow-up time was 131 months (IQR 106-156), during which 85 (4·4%) cases of breast cancer in the anastrozole group and 165 (8·5%) in the placebo group were identified. No data on gender, race, or ethnicity were collected. After exclusions, the case-control study included 212 participants from the anastrozole group (72 cases, 140 controls) and 416 from the placebo group (142 cases, 274 controls). A trend of increasing breast cancer risk with increasing oestradiol-SHBG ratio was found in the placebo group (trend per quartile 1·25 [95% CI 1·08 to 1·45], p=0·0033), but not in the anastrozole group (1·06 [0·86 to 1·30], p=0·60). A weaker effect was seen for the testosterone-SHBG ratio in the placebo group (trend 1·21 [1·05 to 1·41], p=0·011), but again not in the anastrozole group (trend 1·18 [0·96 to 1·46], p=0·11). A relative benefit of anastrozole was seen in quartile 2 (0·55 [95% CI 0·13 to 0·78]), quartile 3 (0·54 [0·22 to 0·74], and quartile 4 (0·56 [0·23 to 0·76]) of oestradiol-SHBG ratio, but not in quartile 1 (0·18 [-0·60 to 0·59]).
INTERPRETATION
These results suggest that serum hormones should be measured more routinely and integrated into risk management decisions. Measuring serum hormone concentrations is inexpensive and might help clinicians differentiate which women will benefit most from an aromatase inhibitor.
FUNDING
Cancer Research UK, National Health and Medical Research Council (Australia), Breast Cancer Research Foundation, and DaCosta Fund.
Topics: Female; Humans; Anastrozole; Breast Neoplasms; Aromatase Inhibitors; Estradiol; Case-Control Studies; Postmenopause; Nitriles; Triazoles; Double-Blind Method; Testosterone
PubMed: 38070530
DOI: 10.1016/S1470-2045(23)00578-8 -
International Journal of Analytical... 2023The main challenges faced by medical researchers while producing novel drugs are time commitment, amplified costs, creating a safety profile for the medications, reduced...
The main challenges faced by medical researchers while producing novel drugs are time commitment, amplified costs, creating a safety profile for the medications, reduced solubility, and a lack of experimental data. Chemical graph theory makes an important theoretical contribution to drug development and design by investigating the structural properties of molecules. To improve drug research and assess the effectiveness of treatments, topological indices aim to provide a mathematical representation of molecular structures. In this study, the author examined a number of recently used drugs, including tamoxifen, mesterolone, anastrozole, and letrozole which are used to treat infertility. We compute the topological descriptors with the limiting behaviors associated with these pharmaceutical drugs and offer degree-based topological parameters for them. We conducted a QSPR investigation on the prospective degree-based topological descriptors using quadratic, cubic, exponential, and logarithmic regression models.
PubMed: 38045557
DOI: 10.1155/2023/6928167 -
Cureus Oct 2023Anastrozole is an endocrine-modifying agent used in the treatment of estrogen-sensitive breast cancer in the postmenopausal breast cancer population. Anastrozole is...
Anastrozole is an endocrine-modifying agent used in the treatment of estrogen-sensitive breast cancer in the postmenopausal breast cancer population. Anastrozole is known for its side effect profile which includes an increased risk of osteoporosis. However, emerging evidence in the literature in the form of case studies demonstrates several potential ocular side effects due to the use of the medication. In our study, a 66-year-old female using anastrozole suffered severe bilateral papilledema that resolved after cessation of the medication. There is a growing body of evidence demonstrating the use of anastrozole and its impact on ocular health leading to deleterious side effects, such as papilledema.
PubMed: 38034139
DOI: 10.7759/cureus.47925 -
Cureus Oct 2023Precocious puberty (PP) means the appearance of secondary sexual characters before the age of eight years in girls and nine years in boys. Puberty is indicated in girls... (Review)
Review
Precocious puberty (PP) means the appearance of secondary sexual characters before the age of eight years in girls and nine years in boys. Puberty is indicated in girls by the enlargement of the breasts (thelarche) in girls and in boys by the enlargement of the testes in either volume or length (testicular volume = 4 mL, testicular length = 25 mm, or both). Two types of PP are recognized - namely central PP (CPP) and peripheral PP (PPP). This paper aims to describe the clinical findings and laboratory workup of PP and to illustrate the new trends in the management of precocious sexual maturation. Gonadotropin-releasing hormone (GnRH)-independent type (PPP) refers to the development of early pubertal maturation not related to the central activation of the hypothalamic-pituitary-gonadal (HPG) axis. It is classified into genetic or acquired disorders. The most common forms of congenital or genetic causes involve McCune-Albright syndrome (MAS), familial male-limited PP, and congenital adrenal hyperplasia. The acquired causes include exogenous exposure to androgens, functioning tumors or cysts, and the pseudo-PP of profound primary hypothyroidism. On the other hand, CPP is the most common and it is a gonadotropin-dependent form. It is due to premature maturation of the HPG axis. CPP may occur as genetic alterations, such as MKRN3, DLK1, or KISS1;as a part of mutations in theepigenetic factors that regulate the HPG axis, such as Lin28b and let-7; or as a part of syndromes, central lesions such as hypothalamic hamartoma, and others. A full, detailed history and physical examination should be taken. Furthermore, several investigations should be conducted for both types of PP, including the estimation of serum gonadotropins such as luteinizing and follicle-stimulating hormones and sex steroids, in addition to a radiographic workup and thyroid function tests. Treatment depends on the type of PP: Long-acting GnRHa, either intramuscularly or implanted, is the norm of care for CPP management, while in PPP, especially in congenital adrenal hyperplasia, the goal of management is to suppress adrenal androgen secretion by glucocorticoids. In addition, anastrozole and letrozole - third-generation aromatase inhibitors - are more potent for MAS.
PubMed: 38021712
DOI: 10.7759/cureus.47485 -
JNCI Cancer Spectrum Oct 2023Obesity has been associated with an adverse prognosis and reduced efficacy of endocrine therapy in patients with hormone receptor-positive (HR+) breast cancer (BC). This... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Obesity has been associated with an adverse prognosis and reduced efficacy of endocrine therapy in patients with hormone receptor-positive (HR+) breast cancer (BC). This study determines the prognostic and predictive effect of body mass index (BMI) on the disease-free survival (DFS) of postmenopausal HR+ BC patients.
METHODS
Patients were identified from the DATA study (NCT00301457), a randomized controlled trial evaluating the efficacy of 6 vs 3 years of anastrozole after 2 to 3 years of adjuvant tamoxifen in postmenopausal women with HR+ BC. Patients were classified as normal weight (BMI: 18.5-24.9 kg/m2), overweight (25.0-29.9 kg/m2), or obese (≥30.0 kg/m2). The primary endpoint was DFS, evaluated from randomization (prognostic analyses) or 3 years after randomization onwards (predictive analyses; aDFS) using multivariable Cox regression analyses. P-values were 2-sided.
RESULTS
This study included 678 normal weight, 712 overweight, and 391 obese patients. After a median follow-up of 13.1 years, overweight and obesity were identified as negative prognostic factors for DFS (hazard ratio (HR) = 1.16; 95% confidence interval (CI) = 0.97 to 1.38 and HR = 1.26; 95% CI = 1.03 to 1.54, respectively). The adverse prognostic effect of BMI was observed in women aged younger than 60 years, but not in women aged 60 years or older (P-interaction = .009). The effect of extended anastrozole on aDFS was similar in normal weight (HR = 1.00; 95% CI = 0.74 to 1.35), overweight (HR = 0.74; 95% CI = 0.56 to 0.98), and obese patients (HR = 0.97; 95% CI = 0.69 to 1.36) (P-interaction = .24).
CONCLUSION
In this study among 1781 HR+ BC patients, overweight and obesity were adverse prognostic factors for DFS. BMI did not impact the efficacy of extended anastrozole.
Topics: Humans; Female; Breast Neoplasms; Anastrozole; Body Mass Index; Prognosis; Overweight; Obesity
PubMed: 37991939
DOI: 10.1093/jncics/pkad092