ABSTRACT
PURPOSE: We previously reported that postmenopausal women with estrogen receptor-α-positive breast cancer receiving adjuvant anastrozole 1 mg/day (ANA1) with estrone (E1) ≥1.3 pg/mL and estradiol (E2) ≥0.5 pg/mL [inadequate estrogen suppression (IES)] had a threefold increased risk of a breast cancer event. The objective of this study was to determine if increasing anastrozole to 10 mg/day (ANA10) could result in adequate estrogen suppression (AES: E1 <1.3 pg/mL and/or E2 <0.5 pg/mL) among those with IES on ANA1. PATIENTS AND METHODS: Postmenopausal women with estrogen receptor-α-positive breast cancer planning to receive adjuvant ANA1 were eligible. E1 and E2 were assessed pre- and post-8 to 10 weeks of ANA1. Those with IES were switched to 8- to 10-week cycles of ANA10 followed by letrozole 2.5 mg/day. E1 and E2 were assessed after each cycle. Anastrozole concentrations were measured post-ANA1 and post-ANA10. Primary analyses included patients who documented taking at least 80% of the planned treatment (adherent cohort). RESULTS: In total, 132 (84.6%) of 156 eligible patients were ANA1 adherent. IES occurred in 40 (30.3%) adherent patients. Twenty-five (78.1%) of 32 patients who began ANA10 were adherent, and AES was achieved in 19 (76.0%; 90% confidence interval, 58.1%-89.0%) patients. Anastrozole concentrations post-ANA1 and post-ANA10 did not differ by estrogen suppression status among adherent patients. AES was maintained/attained in 21 (91.3%) of 23 letrozole-adherent patients. CONCLUSIONS: Approximately 30% of ANA1-adherent patients had IES. Among those who switched to ANA10 and were adherent, 76% had AES. Further studies are required to validate emerging data that ANA1 results in IES for some patients and to determine the clinical benefit of switching to ANA10 or an alternative aromatase inhibitor.
Subject(s)
Anastrozole , Breast Neoplasms , Nitriles , Postmenopause , Triazoles , Humans , Anastrozole/administration & dosage , Anastrozole/therapeutic use , Anastrozole/adverse effects , Female , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Middle Aged , Aged , Triazoles/administration & dosage , Triazoles/adverse effects , Nitriles/administration & dosage , Nitriles/adverse effects , Estrogens/administration & dosage , Neoplasm Staging , Antineoplastic Agents, Hormonal/administration & dosage , Antineoplastic Agents, Hormonal/adverse effects , Antineoplastic Agents, Hormonal/therapeutic use , Prospective Studies , Estradiol/administration & dosage , Estrone/blood , Estrone/administration & dosage , Aromatase Inhibitors/administration & dosage , Aromatase Inhibitors/adverse effectsABSTRACT
BACKGROUND: In MONARCH 2, the addition of abemaciclib to fulvestrant significantly improved both progression-free survival (PFS) and overall survival (OS) in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) with disease progression on prior endocrine therapy. In MONARCH 3, the addition of abemaciclib to a nonsteroidal aromatase inhibitor (NSAI) as initial therapy for HR+, HER2- ABC significantly improved PFS. Here, we present the prespecified final OS results for MONARCH 3. PATIENTS AND METHODS: MONARCH 3 is a randomized, double-blind, phase III study of abemaciclib plus NSAI (anastrozole or letrozole) versus placebo plus NSAI in postmenopausal women with HR+, HER2- ABC without prior systemic therapy in the advanced setting. The primary objective was investigator-assessed PFS; OS was a gated secondary endpoint, and chemotherapy-free survival was an exploratory endpoint. RESULTS: A total of 493 women were randomized 2 : 1 to receive abemaciclib plus NSAI (n = 328) or placebo plus NSAI (n = 165). After a median follow-up of 8.1 years, there were 198 OS events (60.4%) in the abemaciclib arm and 116 (70.3%) in the placebo arm (hazard ratio, 0.804; 95% confidence interval 0.637-1.015; P = 0.0664, non-significant). Median OS was 66.8 versus 53.7 months for abemaciclib versus placebo. In the subgroup with visceral disease, there were 113 OS events (65.3%) in the abemaciclib arm and 65 (72.2%) in the placebo arm (hazard ratio, 0.758; 95% confidence interval 0.558-1.030; P = 0.0757, non-significant). Median OS was 63.7 months versus 48.8 months for abemaciclib versus placebo. The previously demonstrated PFS benefit was sustained, and chemotherapy-free survival numerically improved with the addition of abemaciclib. No new safety signals were observed. CONCLUSIONS: Abemaciclib combined with an NSAI resulted in clinically meaningful improvement in median OS (intent-to-treat population: 13.1 months; subgroup with visceral disease: 14.9 months) in patients with HR+ HER2- ABC; however, statistical significance was not reached.
Subject(s)
Aminopyridines , Antineoplastic Combined Chemotherapy Protocols , Aromatase Inhibitors , Benzimidazoles , Breast Neoplasms , Letrozole , Receptor, ErbB-2 , Receptors, Estrogen , Receptors, Progesterone , Humans , Female , Aminopyridines/administration & dosage , Aminopyridines/therapeutic use , Benzimidazoles/administration & dosage , Benzimidazoles/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Breast Neoplasms/mortality , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Receptor, ErbB-2/metabolism , Receptor, ErbB-2/antagonists & inhibitors , Double-Blind Method , Letrozole/administration & dosage , Letrozole/therapeutic use , Aromatase Inhibitors/therapeutic use , Aromatase Inhibitors/administration & dosage , Middle Aged , Aged , Receptors, Progesterone/metabolism , Receptors, Estrogen/metabolism , Anastrozole/therapeutic use , Anastrozole/administration & dosage , Adult , Aged, 80 and over , Progression-Free SurvivalABSTRACT
PURPOSE: Aromatase inhibitor (AI)-associated musculoskeletal symptoms (AIMSS) are common and frequently lead to AI discontinuation. SNPs in candidate genes have been associated with AIMSS and AI discontinuation. E1Z11 is a prospective cohort study designed to validate the association between 10 SNPs and AI discontinuation due to AIMSS. PATIENTS AND METHODS: Postmenopausal women with stage I to III hormone receptor-positive breast cancer received anastrozole 1 mg daily and completed patient-reported outcome measures to assess AIMSS (Stanford Health Assessment Questionnaire) at baseline, 3, 6, 9, and 12 months. We estimated that 40% of participants would develop AIMSS and 25% would discontinue AI treatment within 12 months. Enrollment of 1,000 women with a fixed number per racial stratum provided 80% power to detect an effect size of 1.5 to 4. SNPs were found in ESR1 (rs2234693, rs2347868, and rs9340835), CYP19A1 (rs1062033 and rs4646), TCL1A (rs11849538, rs2369049, rs7158782, and rs7159713), and HTR2A (rs2296972). RESULTS: Of the 970 evaluable women, 43% developed AIMSS and 12% discontinued AI therapy within 12 months. Although more Black and Asian women developed AIMSS than White women (49% vs. 39%, P = 0.017; 50% vs. 39%, P = 0.004, respectively), the AI discontinuation rates were similar across groups. None of the SNPs were significantly associated with AIMSS or AI discontinuation in the overall population or in distinct cohorts. The OR for rs2296972 (HTR2A) approached significance for developing AIMSS. CONCLUSIONS: We were unable to prospectively validate candidate SNPs previously associated with AI discontinuation due to AIMSS. Future analyses will explore additional genetic markers, patient-reported outcome predictors of AIMSS, and differences by race.
Subject(s)
Aromatase Inhibitors , Breast Neoplasms , Polymorphism, Single Nucleotide , Humans , Female , Aromatase Inhibitors/therapeutic use , Aromatase Inhibitors/adverse effects , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Middle Aged , Aged , Prospective Studies , Anastrozole/therapeutic use , Anastrozole/adverse effects , Anastrozole/administration & dosage , Cohort Studies , Postmenopause , Aged, 80 and over , Patient Reported Outcome Measures , Aromatase/geneticsABSTRACT
Occult breast cancer (OBC) is characterized by metastatic presentation of undetectable breast tumor on imaging exams. OBC is a rare disease (accounting for 0.3% to 1.0% of all breast cancers) that represents a major diagnostic challenge. The aim of this study was to report a case of OBC with primary presentation of multiple cutaneous metastases with subsequent emergence of bone metastasis. A 70-year female patient had multiple cutaneous metastatic lesions in the left cervical region, left breast, left axillary region, left subscapular region, in three chirodactylus of the right hand and three chirodactylus of the left hand. Imaging tests (mammogram, ultrasonography and magnetic resonance imaging of the breast) did not show alterations. Biopsy, histology sections and immunohistochemistry of the left cervical cutaneous lesion were compatible with OBC. After two years of anastrozole treatment (1mg/day), there was regression of all cutaneous lesions and stabilization of bone metastasis. OBC has a better prognosis. It may exhibit spontaneous regression or respond to less aggressive treatment strategies, as described in this case.
Subject(s)
Anastrozole/administration & dosage , Breast Neoplasms/diagnosis , Skin Neoplasms/diagnosis , Aged , Antineoplastic Agents, Hormonal/administration & dosage , Biopsy , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Female , Humans , Prognosis , Skin Neoplasms/drug therapy , Skin Neoplasms/secondary , Treatment OutcomeABSTRACT
BACKGROUND: For postmenopausal women with hormone-receptor-positive breast cancer, the most effective duration for adjuvant therapy with an aromatase inhibitor remains unclear. METHODS: In this prospective, phase 3 trial, we randomly assigned postmenopausal women with hormone-receptor-positive breast cancer who had received 5 years of adjuvant endocrine therapy to receive the aromatase inhibitor anastrozole for an additional 2 years (2-year group, receiving a total of 7 years) or an additional 5 years (5-year group, receiving a total of 10 years). The primary end point was disease-free survival. The primary analysis included all the patients who were still participating in the trial and who had no recurrence 2 years after randomization (i.e., when treatment in the 2-year group had ended). Secondary end points were overall survival, contralateral breast cancer, second primary cancer, and clinical bone fracture. RESULTS: Among the 3484 women who were enrolled in the trial, 3208 remained in the trial without disease progression after the first 2 years of extended anastrozole treatment following randomization. Among these women, disease progression or death occurred in 335 women in each treatment group in the primary-analysis set at 8 years (hazard ratio, 0.99; 95% confidence interval [CI], 0.85 to 1.15; P = 0.90). No between-group differences occurred in most secondary end points, and subgroup analyses did not indicate differences in any particular subgroup. The risk of clinical bone fracture was higher in the 5-year group than in the 2-year group (hazard ratio, 1.35; 95% CI, 1.00 to 1.84). CONCLUSIONS: In postmenopausal women with hormone-receptor-positive breast cancer who had received 5 years of adjuvant endocrine therapy, extending hormone therapy by 5 years provided no benefit over a 2-year extension but was associated with a greater risk of bone fracture. (Funded by AstraZeneca and the Austrian Breast and Colorectal Cancer Study Group; ABCSG-16/SALSA ClinicalTrials.gov number, NCT00295620.).
Subject(s)
Anastrozole/administration & dosage , Aromatase Inhibitors/administration & dosage , Breast Neoplasms/drug therapy , Neoplasm Recurrence, Local/prevention & control , Administration, Oral , Aged , Anastrozole/adverse effects , Antineoplastic Agents, Hormonal/administration & dosage , Antineoplastic Agents, Hormonal/therapeutic use , Aromatase Inhibitors/adverse effects , Breast Neoplasms/mortality , Breast Neoplasms/surgery , Chemotherapy, Adjuvant , Disease-Free Survival , Fractures, Bone/epidemiology , Fractures, Bone/etiology , Humans , Kaplan-Meier Estimate , Middle Aged , Postmenopause , Prospective Studies , Receptors, Estrogen , Receptors, Progesterone , Tamoxifen/therapeutic useABSTRACT
Thromboembolic complications are a leading cause of morbidity and mortality in cancer patients. Cancer patients often present with an increased risk for thrombosis including hypercoagulation, so the application of antiplatelet strategies to oncology warrants further investigation. This study investigated the effects of anastrozole and antiplatelet therapy (aspirin/clopidogrel cocktail or atopaxar) treatment on the tumour responses of luminal phenotype breast cancer cells and induced hypercoagulation. Ethical clearance was obtained (M150263). Blood was co-cultured with breast cancer cell lines (MCF7 and T47D) pre-treated with anastrozole and/or antiplatelet drugs for 24 h. Hypercoagulation was indicated by thrombin production and platelet activation (morphological and molecular). Gene expression associated with the epithelial-to-mesenchymal transition (EMT) was assessed in breast cancer cells, and secreted cytokines associated with tumour progression were evaluated. Data were analysed with the PAST3 software. Our findings showed that antiplatelet therapies (aspirin/clopidogrel cocktail and atopaxar) combined with anastrozole failed to prevent hypercoagulation and induced evidence of a partial EMT. Differences in tumour responses that modulate tumour aggression were noted between breast cancer cell lines, and this may be an important consideration in the clinical management of subphenotypes of luminal phenotype breast cancer. Further investigation is needed before this treatment modality (combined hormone and antiplatelet therapy) can be considered for managing tumour associated-thromboembolic disorder.
Subject(s)
Anastrozole/adverse effects , Antineoplastic Agents, Hormonal/adverse effects , Blood Coagulation , Breast Neoplasms/drug therapy , Epithelial-Mesenchymal Transition , Platelet Aggregation Inhibitors/adverse effects , Thrombophilia/prevention & control , Adult , Anastrozole/administration & dosage , Anastrozole/therapeutic use , Antineoplastic Agents, Hormonal/administration & dosage , Antineoplastic Agents, Hormonal/therapeutic use , Aspirin/administration & dosage , Aspirin/adverse effects , Aspirin/therapeutic use , Breast Neoplasms/complications , Cells, Cultured , Clopidogrel/administration & dosage , Clopidogrel/adverse effects , Clopidogrel/therapeutic use , Drug Interactions , Female , Humans , Imines/administration & dosage , Imines/adverse effects , Imines/therapeutic use , MCF-7 Cells , Platelet Aggregation Inhibitors/administration & dosage , Platelet Aggregation Inhibitors/therapeutic use , Pyridines/administration & dosage , Pyridines/adverse effects , Pyridines/therapeutic use , Thrombin/metabolism , Thrombophilia/drug therapy , Thrombophilia/etiologyABSTRACT
Breast cancer remains the most common cancer in women in the United States. For certain women at high risk for breast cancer, endocrine therapy (ET) can greatly decrease the risk. Tools such as the Breast Cancer Risk Assessment Tool (or Gail Model) and the International Breast Cancer Intervention Study risk calculator are available to help identify women at increased risk for breast cancer. Physician awareness of family history, reproductive and lifestyle factors, dense breast tissue, and history of benign proliferative breast disease are important when identifying high-risk women. The updated US Preventive Services Task Force and American Society of Clinical Oncology guidelines encourage primary care providers to identify at-risk women and offer risk-reducing medications. Among the various ETs, which include tamoxifen, raloxifene, anastrozole, and exemestane, tamoxifen is the only one available for premenopausal women aged 35 years and older. A shared decision-making process should be used to increase the usage of ET and must be individualized. This individualized approach must account for each woman's medical history and weigh the benefits and risks of ET in combination with the personal values of the patient.
Subject(s)
Anastrozole/administration & dosage , Breast Neoplasms/prevention & control , Estrogen Antagonists/administration & dosage , Health Personnel/education , Preventive Medicine/education , Raloxifene Hydrochloride/administration & dosage , Selective Estrogen Receptor Modulators/administration & dosage , Tamoxifen/administration & dosage , Adult , Aged , Aged, 80 and over , Breast Neoplasms/epidemiology , Curriculum , Decision Making, Shared , Education, Medical, Continuing , Female , Humans , Male , Middle Aged , Preventive Medicine/methods , Risk Assessment , Risk Factors , United States/epidemiologyABSTRACT
This post hoc analysis of MONARCH 2 and MONARCH 3 assesses the efficacy, safety, and pharmacokinetics (PK) of abemaciclib in combination with endocrine therapy (ET) in East Asian patients with hormone receptor positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer. MONARCH 2 and MONARCH 3 are global, randomized, double-blind, phase 3 studies of abemaciclib/placebo + fulvestrant and abemaciclib/placebo + nonsteroidal aromatase inhibitor (NSAI, anastrozole or letrozole), respectively. The East Asian population comprised 212 (31.7%) of the 669 intent-to-treat (ITT) population in the MONARCH 2 trial and 144 (29.2%) of the 493 ITT patients in the MONARCH 3 trial. In the East Asian population, median progression-free survival (PFS) was significantly prolonged in the abemaciclib arm compared with placebo in both MONARCH 2 (hazard ratio [HR], 0.520; 95% confidence interval [CI], 0.362 to 0.747; P < .001; median: 21.2 vs 11.6 months) and MONARCH 3 (HR, 0.326; 95% CI, 0.200 to 0.531, P < .001; median: not reached vs 12.82 months). Diarrhea (MONARCH 2: 90%; MONARCH 3: 88%) and neutropenia (MONARCH 2: 68%; MONARCH 3: 58%) were the most frequent adverse events observed in the East Asian populations. Abemaciclib exposures and PK were similar in East Asians and the non-East Asian populations of both trials. Abemaciclib in combination with ET in the East Asian populations of MONARCH 2 and MONARCH 3 provided consistent results with the ITT populations, demonstrating improvements in efficacy with generally tolerable safety profiles for patients with HR+, HER2- advanced breast cancer.
Subject(s)
Aminopyridines/administration & dosage , Aromatase Inhibitors/administration & dosage , Benzimidazoles/administration & dosage , Breast Neoplasms/drug therapy , Fulvestrant/administration & dosage , Aminopyridines/adverse effects , Aminopyridines/pharmacokinetics , Anastrozole/administration & dosage , Anastrozole/adverse effects , Anastrozole/pharmacokinetics , Aromatase Inhibitors/adverse effects , Aromatase Inhibitors/pharmacokinetics , Benzimidazoles/adverse effects , Benzimidazoles/pharmacokinetics , Breast Neoplasms/blood , Breast Neoplasms/genetics , Diarrhea/chemically induced , Diarrhea/epidemiology , Double-Blind Method , Drug Therapy, Combination , Female , Fulvestrant/adverse effects , Fulvestrant/pharmacokinetics , Humans , Letrozole/administration & dosage , Letrozole/adverse effects , Letrozole/pharmacokinetics , Neutropenia/chemically induced , Neutropenia/epidemiology , Receptor, ErbB-2/genetics , Treatment OutcomeABSTRACT
Abstract Objective The objective of the present study was to analyze the reasons that led to hormone therapies (HTs) regimen changes in women with breast cancer. Methods This was a retrospective cross-sectional study from a single-institution Brazilian cancer center with patient records diagnosed with breast cancer between January 2012 and January 2017. Results From 1,555 women who were in treatment with HT, 213 (13.7%) women had HT switched, either tamoxifen to anastrozole or vice-versa. Most women included in the present study who switched HT were > 50 years old, postmenopausal, Caucasian, and had at least one comorbidity. From the group with therapy change, 'disease progression' was reason of change in 124 (58.2%) cases, and in 65 (30.5%) patients, 'presence of side effects' was the reason. From those women who suffered with side effects, 24 (36.9%) had comorbidities. Conclusion The present study demonstrated a low rate of HT switch of tamoxifen to anastrozole. Among the reasons for changing therapy, the most common was disease progression, which includes cancer recurrence, metastasis or increased tumor. Side effects were second; furthermore, age and comorbidities are risk factors for side effects.
Resumo Objetivo O objetivo do presente estudo foi analisar os motivos que levaram às mudanças no esquema hormonioterápico (HT) em mulheres com câncer de mama. Métodos Estudo transversal retrospectivo realizado no Hospital da Mulher de Campinas e consequente pesquisa de prontuários de mulheres diagnosticados com câncer de mama entre janeiro de 2012 e janeiro de 2017. Resultados De 1.555 mulheres em tratamento com HT, 213 (13,7%) mulheres tiveram HT alterado, tamoxifeno para anastrozol ou vice-versa. A maioria das mulheres incluídas no presente estudo que tiveram mudança de HT tinha > 50 anos, estava na pós-menopausa, era caucasiana e tinha pelo menos uma comorbidade. Os principais motivos de troca de HT foram devido a 'progressão da doença', ocorrendo em 124 (58,2%) casos e a 'presença de efeitos colaterais' (n = 65; 30,5%). Das mulheres que sofreram efeitos colaterais, 24 (36,9%) apresentaram comorbidades. Conclusão O presente estudo demonstrou uma baixa taxa na alteração de tamoxifeno para anastrozol. Entre as razõesmais comuns para alterar a HT estava a progressão da doença, que inclui recorrência do câncer, metástase ou aumento do tumor. Os efeitos colaterais foram a segunda causa e, além disso, a idade e as comorbidades foram fatores de risco para efeitos colaterais.
Subject(s)
Breast Neoplasms/drug therapy , Antineoplastic Agents, Hormonal/therapeutic use , Neoplasm Recurrence, Local/drug therapy , Patient Participation , Tamoxifen/administration & dosage , Tamoxifen/adverse effects , Tamoxifen/therapeutic use , Medical Records , Cross-Sectional Studies , Retrospective Studies , Disease Progression , Antineoplastic Agents, Hormonal/administration & dosage , Antineoplastic Agents, Hormonal/adverse effects , Anastrozole/administration & dosage , Anastrozole/analogs & derivatives , Anastrozole/therapeutic useABSTRACT
BACKGROUND: Aromatase inhibitors are standard of care for low-grade endometrial stromal sarcomas (LGESS), based on very high response rates reported in retrospective studies. We evaluated the activity of anastrozole in recurrent/metastatic LGESS patients enrolled in PARAGON, a basket trial of anastrozole in estrogen receptor (ER±)/progesterone receptor (PR+) gynecological cancers. METHOD: An investigator-initiated, single-arm, prospective open-label trial of anastrozole 1 mg/day in patients with ER ± PR + ve LGESS with measurable disease, treated until progressive disease or unacceptable toxicity. Primary endpoint was clinical benefit (complete/partial response + stable disease) rate (CBR) at 3 months. Secondary endpoints include progression-free survival (PFS), quality of life and toxicity. RESULTS: 15 eligible patients were enrolled. CBR at 3 months was 73% (95% CI: 48-89.1%); unchanged at 6 months. Best response was 26.7%, including complete response in one (6.7%; 95% CI 1.2-29.8%), partial response in three (20%, 95% CI 7.1-45.2%) and stable disease in seven (46.7%). Four patients ceased treatment by 3 months due to progression. Median PFS was not reached (25th percentile: 2.9 months (95% CI: 1.2-NR)). PFS was 73.3%, 73.3% and 66% at 6, 12, and 18 months, respectively. Six patients remained on treatment for an average of 44.2 months (range 34.5-63.6) up until data cut. Toxicity was as expected, with 3 patients stopping due to adverse effects. CONCLUSION: The 26.7% objective response rate with anastrozole is lower than reported in retrospective series, but the CBR was high and durable. The results underscore the importance of prospective trials in rare cancers.
Subject(s)
Anastrozole/administration & dosage , Endometrial Neoplasms/drug therapy , Endometrial Stromal Tumors/drug therapy , Aged , Anastrozole/adverse effects , Antineoplastic Agents, Hormonal/administration & dosage , Antineoplastic Agents, Hormonal/adverse effects , Aromatase Inhibitors/administration & dosage , Aromatase Inhibitors/adverse effects , Endometrial Neoplasms/metabolism , Endometrial Neoplasms/pathology , Endometrial Stromal Tumors/metabolism , Endometrial Stromal Tumors/pathology , Female , Humans , Middle Aged , Neoplasm Grading , Progression-Free Survival , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolismSubject(s)
Humans , Female , Adult , Young Adult , Breast Neoplasms/drug therapy , Antineoplastic Agents, Hormonal/therapeutic use , Neoplasm Recurrence, Local/drug therapy , Patient Participation , Tamoxifen/administration & dosage , Tamoxifen/adverse effects , Tamoxifen/therapeutic use , Medical Records , Cross-Sectional Studies , Retrospective Studies , Disease Progression , Antineoplastic Agents, Hormonal/administration & dosage , Antineoplastic Agents, Hormonal/adverse effects , Anastrozole/administration & dosage , Anastrozole/adverse effects , Anastrozole/therapeutic useABSTRACT
OBJECTIVE: The objective of the present study was to analyze the reasons that led to hormone therapies (HTs) regimen changes in women with breast cancer. METHODS: This was a retrospective cross-sectional study from a single-institution Brazilian cancer center with patient records diagnosed with breast cancer between January 2012 and January 2017. RESULTS: From 1,555 women who were in treatment with HT, 213 (13.7%) women had HT switched, either tamoxifen to anastrozole or vice-versa. Most women included in the present study who switched HT were > 50 years old, postmenopausal, Caucasian, and had at least one comorbidity. From the group with therapy change, 'disease progression' was reason of change in 124 (58.2%) cases, and in 65 (30.5%) patients, 'presence of side effects' was the reason. From those women who suffered with side effects, 24 (36.9%) had comorbidities. CONCLUSION: The present study demonstrated a low rate of HT switch of tamoxifen to anastrozole. Among the reasons for changing therapy, the most common was disease progression, which includes cancer recurrence, metastasis or increased tumor. Side effects were second; furthermore, age and comorbidities are risk factors for side effects.
OBJETIVO: O objetivo do presente estudo foi analisar os motivos que levaram às mudanças no esquema hormonioterápico (HT) em mulheres com câncer de mama. MéTODOS: Estudo transversal retrospectivo realizado no Hospital da Mulher de Campinas e consequente pesquisa de prontuários de mulheres diagnosticados com câncer de mama entre janeiro de 2012 e janeiro de 2017. RESULTADOS: De 1.555 mulheres em tratamento com HT, 213 (13,7%) mulheres tiveram HT alterado, tamoxifeno para anastrozol ou vice-versa. A maioria das mulheres incluídas no presente estudo que tiveram mudança de HT tinha > 50 anos, estava na pós-menopausa, era caucasiana e tinha pelo menos uma comorbidade. Os principais motivos de troca de HT foram devido a 'progressão da doença', ocorrendo em 124 (58,2%) casos e a 'presença de efeitos colaterais' (n = 65; 30,5%). Das mulheres que sofreram efeitos colaterais, 24 (36,9%) apresentaram comorbidades. CONCLUSãO: O presente estudo demonstrou uma baixa taxa na alteração de tamoxifeno para anastrozol. Entre as razões mais comuns para alterar a HT estava a progressão da doença, que inclui recorrência do câncer, metástase ou aumento do tumor. Os efeitos colaterais foram a segunda causa e, além disso, a idade e as comorbidades foram fatores de risco para efeitos colaterais.
Subject(s)
Antineoplastic Agents, Hormonal/therapeutic use , Breast Neoplasms/drug therapy , Neoplasm Recurrence, Local/drug therapy , Adult , Anastrozole/administration & dosage , Anastrozole/adverse effects , Anastrozole/therapeutic use , Antineoplastic Agents, Hormonal/administration & dosage , Antineoplastic Agents, Hormonal/adverse effects , Cross-Sectional Studies , Disease Progression , Female , Humans , Medical Records , Patient Participation , Retrospective Studies , Tamoxifen/administration & dosage , Tamoxifen/adverse effects , Tamoxifen/therapeutic use , Young AdultABSTRACT
BACKGROUND: Anastrozole has been associated with substantial accelerated bone mineral density (BMD) loss during active treatment. METHODS: One thousand four hundred and ten women were included in a BMD substudy and stratified into three strata according to their baseline T-score at spine or femoral neck. The primary objective of this analysis was to investigate whether DXA BMD at the spine and hip changed two years after treatment cessation (between years 5 and 7) in those who did not receive risedronate. RESULTS: Five- and seven-year BMD data were available for a total of 528 women who did not receive risedronate. In women with normal BMD at baseline, an increase in BMD at the lumbar spine after anastrozole withdrawal was observed 1.25% (95% CI 0.73 to 1.77) (P = 0.0004), which was larger than in those on placebo (0.14% (-0.29 to 0.56))). At the hip, BMD remained unchanged between years 5 and 7 for those previously on anastrozole but continued to a decrease in those who had been randomised to placebo (-1.35% (-1.70 to -0.98)). CONCLUSIONS: These are the first results reporting BMD changes after stopping anastrozole in a breast cancer prevention setting. Our results show that the negative effects of anastrozole on BMD in the preventive setting are partially reversible.
Subject(s)
Anastrozole/administration & dosage , Aromatase Inhibitors/administration & dosage , Breast Neoplasms/prevention & control , Femur Neck/diagnostic imaging , Spine/diagnostic imaging , Absorptiometry, Photon , Aged , Anastrozole/adverse effects , Aromatase Inhibitors/adverse effects , Bone Density/drug effects , Case-Control Studies , Double-Blind Method , Female , Femur Neck/drug effects , Humans , Middle Aged , Postmenopause , Spine/drug effectsABSTRACT
OBJECTIVES: Based on our previous findings that postmenopausal women with estrone (E1) and estradiol (E2) concentrations at or above 1.3 pg/ml and 0.5 pg/ml, respectively, after 6 months of adjuvant anastrozole therapy had a three-fold risk of recurrence, we aimed to identify a single-nucleotide polymorphism (SNP)-based model that would predict elevated E1 and E2 and then validate it in an independent dataset. PATIENTS AND METHODS: The test set consisted of 322 women from the M3 study and the validation set consisted of 152 patients from MA.27. All patients were treated with adjuvant anastrozole, had on-anastrozole E1 and E2 concentrations and genome-wide genotyping. RESULTS: SNPs were identified from the M3 genome-wide association study. The best model to predict the E1-E2 phenotype with high balanced accuracy was a support vector machine model using clinical factors plus 46 SNPs. We did not have an independent cohort that is similar to the M3 study with clinical, E1-E2 phenotypes and genotype data to test our model. Hence, we chose a nested matched case-control cohort (MA.27 study) for testing. Our E1-E2 model was not validated but we found the MA.27 validation cohort was both clinically and genomically different. CONCLUSIONS: We identified a SNP-based model that had excellent performance characteristics for predicting the phenotype of elevated E1 and E2 in women treated with anastrozole. This model was not validated in an independent dataset but that dataset was clinically and genomically substantially different. The model will need validation in a prospective study.
Subject(s)
Anastrozole/adverse effects , Breast Neoplasms/genetics , Genetic Predisposition to Disease , Neoplasm Recurrence, Local/genetics , Adult , Anastrozole/administration & dosage , Aromatase Inhibitors/administration & dosage , Aromatase Inhibitors/adverse effects , Breast Neoplasms/blood , Breast Neoplasms/chemically induced , Breast Neoplasms/pathology , Estradiol/blood , Estrone/blood , Female , Genome, Human/genetics , Genome-Wide Association Study , Humans , Middle Aged , Neoplasm Proteins/genetics , Neoplasm Recurrence, Local/blood , Neoplasm Recurrence, Local/pathology , Polymorphism, Single Nucleotide/geneticsABSTRACT
OBJECTIVE: The objective of the present study is to observe the frequency and severity of urinary symptoms in women with breast cancer (BC) being treated with oral hormone therapy, associating them to drug adherence. METHODS: The participants were interviewed once from June to October 2016. The evaluation of urinary symptoms was performed by two questionnaires: International Consultation on Incontinence Questionnaire - Short Form (ICIQ-SF) and International Consultation on Incontinence Questionnaire Overactive Bladder Module (ICIQ-OAB). Adherence was evaluated by the Morisky-Green method. Statistical analysis was performed by the Mann-Whitney test, linear regression, and Spearman correlation. RESULTS: Fifty-eight women were interviewed: 42 treated with tamoxifen and 16 with aromatase inhibitor. Twenty-seven women (46.5%) presented urinary incontinence symptoms and 15 (25.8%) presented stress urinary incontinence (SUI). Fourteen (24.1%) women had symptoms of overactive bladder (OAB). There was no statistical difference in symptoms between both treatments and duration of treatments. Higher scores in the ICIQ-SF questionnaire were associated with low/medium adherence and advanced age. Higher scores in the ICIQ-OAB questionnaire were associated with low/medium adherence. CONCLUSION: The present study showed a high prevalence of urinary symptoms, such as urinary incontinence and OAB, associated with low/medium adherence and older age in women with BC being treated with oral hormone therapy. Health professionals should be alert to these symptoms since it could influence life quality and adherence to treatment.
OBJETIVO: O objetivo do presente estudo foi observar a frequência e a gravidade dos sintomas urinários em mulheres com câncer de mama em uso de terapia hormonal oral, associando estes com a adesão ao tratamento. MéTODOS: As pacientes foram entrevistadas uma única vez, entre junho e outubro de 2016. A avaliação dos sintomas urinários foi realizada por dois questionários: International Consultation on Incontinence Questionnaire - Short Form (ICIQ-SF, na sigla em inglês) e o Questionário Sobre Bexiga Hiperativa (ICIQ-OAB, na sigla em inglês). A adesão foi avaliada pelo método Morisky-Green. A análise estatística foi realizada pelo teste de Mann-Whitney, regressão linear e correlação de Spearman. RESULTADOS: Foram entrevistadas 58 mulheres: 42 tratadas com tamoxifeno e 16 com inibidor de aromatase. Vinte e sete mulheres (46,5%) apresentaram sintomas de incontinência urinária (IU) e 15 (25,8%) apresentaram incontinência urinária por estresse (IUS). Quatorze (24,1%) das mulheres tinham sintomas de bexiga hiperativa. Não houve diferença estatística nos sintomas entre os tratamentos e a duração dos tratamentos. Os escores mais elevados no questionário ICIQ-SF estiveram associados à baixa/média adesão e à idade avançada. Os escores mais elevados no questionário da ICIQ-OAB foram associados à baixa/média adesão. CONCLUSãO: O presente estudo mostrou alta prevalência de sintomas urinários, como IU e bexiga hiperativa, associadas à baixa/média adesão e à idade mais avançada em mulheres com câncer de mama em tratamento com hormonioterapia oral. Os profissionais de saúde devem estar atentos a esses sintomas, pois eles podem influenciar a qualidade de vida e a adesão ao tratamento.
Subject(s)
Breast Neoplasms/drug therapy , Medication Adherence , Urinary Bladder, Overactive/epidemiology , Urinary Incontinence/epidemiology , Administration, Oral , Anastrozole/administration & dosage , Anastrozole/adverse effects , Antineoplastic Agents, Hormonal/administration & dosage , Antineoplastic Agents, Hormonal/adverse effects , Aromatase Inhibitors/administration & dosage , Aromatase Inhibitors/adverse effects , Cross-Sectional Studies , Female , Humans , Interviews as Topic , Middle Aged , Portugal/epidemiology , Tamoxifen/administration & dosage , Tamoxifen/adverse effects , Urinary Bladder, Overactive/chemically induced , Urinary Incontinence/chemically inducedABSTRACT
Abstract Objective: The objective of the present study is to observe the frequency and severity of urinary symptoms in women with breast cancer (BC) being treated with oral hormone therapy, associating them to drug adherence. Methods: The participants were interviewed once from June to October 2016. The evaluation of urinary symptoms was performed by two questionnaires: International Consultation on Incontinence Questionnaire - Short Form (ICIQ-SF) and International Consultation on Incontinence Questionnaire Overactive Bladder Module (ICIQ-OAB). Adherence was evaluated by the Morisky-Green method. Statistical analysis was performed by the Mann-Whitney test, linear regression, and Spearman correlation. Results: Fifty-eight women were interviewed: 42 treated with tamoxifen and 16 with aromatase inhibitor. Twenty-seven women (46.5%) presented urinary incontinence symptoms and 15 (25.8%) presented stress urinary incontinence (SUI). Fourteen (24.1%) women had symptoms of overactive bladder (OAB). There was no statistical difference in symptoms between both treatments and duration of treatments. Higher scores in the ICIQ-SF questionnaire were associated with low/medium adherence and advanced age. Higher scores in the ICIQ-OAB questionnaire were associated with low/medium adherence. Conclusion: The present study showed a high prevalence of urinary symptoms, such as urinary incontinence and OAB, associated with low/medium adherence and older age in women with BC being treated with oral hormone therapy. Health professionals should be alert to these symptoms since it could influence life quality and adherence to treatment.
Resumo Objetivo: O objetivo do presente estudo foi observar a frequência e a gravidade dos sintomas urinários em mulheres com câncer de mama em uso de terapia hormonal oral, associando estes com a adesão ao tratamento. Métodos: As pacientes foram entrevistadas uma única vez, entre junho e outubro de 2016. A avaliação dos sintomas urinários foi realizada por dois questionários: International Consultation on Incontinence Questionnaire - Short Form (ICIQ-SF, na sigla em inglês) e o Questionário Sobre Bexiga Hiperativa (ICIQ-OAB, na sigla em inglês). A adesão foi avaliada pelo método Morisky-Green. A análise estatística foi realizada pelo teste de Mann-Whitney, regressão linear e correlação de Spearman. Resultados: Foram entrevistadas 58 mulheres: 42 tratadas com tamoxifeno e 16 com inibidor de aromatase. Vinte e sete mulheres (46,5%) apresentaram sintomas de incontinência urinária (IU) e 15 (25,8%) apresentaram incontinência urinária por estresse (IUS). Quatorze (24,1%) das mulheres tinham sintomas de bexiga hiperativa. Não houve diferença estatística nos sintomas entre os tratamentos e a duração dos tratamentos. Os escores mais elevados no questionário ICIQ-SF estiveram associados à baixa/média adesão e à idade avançada. Os escores mais elevados no questionário da ICIQ-OAB foram associados à baixa/média adesão. Conclusão: O presente estudo mostrou alta prevalência de sintomas urinários, como IU e bexiga hiperativa, associadas à baixa/média adesão e à idade mais avançada em mulheres com câncer de mama em tratamento com hormonioterapia oral. Os profissionais de saúde devem estar atentos a esses sintomas, pois eles podem influenciar a qualidade de vida e a adesão ao tratamento.
Subject(s)
Humans , Female , Urinary Incontinence/epidemiology , Breast Neoplasms/drug therapy , Urinary Bladder, Overactive/epidemiology , Medication Adherence , Portugal/epidemiology , Tamoxifen/administration & dosage , Tamoxifen/adverse effects , Urinary Incontinence/chemically induced , Cross-Sectional Studies , Interviews as Topic , Administration, Oral , Antineoplastic Agents, Hormonal/administration & dosage , Antineoplastic Agents, Hormonal/adverse effects , Aromatase Inhibitors/administration & dosage , Aromatase Inhibitors/adverse effects , Urinary Bladder, Overactive/chemically induced , Anastrozole/administration & dosage , Anastrozole/adverse effects , Middle AgedABSTRACT
OBJECTIVE: The S0226 trial demonstrated that the combination of half-dose fulvestrant (FUL) and anastrozole (ANA) (F&A) caused a significant improvement in overall survival (OS) versus ANA monotherapy for first-line treatment of postmenopausal women with hormone receptor-positive metastatic breast cancer (PMW-MBC (HR+)). The objective of this study was to evaluate the cost-effectiveness of F&A in the first-line treatment for PMW-MBC (HR+) in China. DESIGN: We constructed a Markov model over a life-time horizon. The clinical outcomes and utility data were obtained from published literature. Cost data were obtained from official Chinese websites. Sensitivity analyses were performed to test result uncertainty. SETTING: Chinese healthcare system perspective. POPULATION: A hypothetical cohort of adult patients presenting with PMW-MBC (HR+). INTERVENTIONS: F&A compared with full-dose FUL and ANAmonotherapy. MAIN OUTCOME MEASURES: The main outcome of this study was the incremental cost-effectiveness ratio (ICER) and quality-adjusted life-years (QALY). RESULTS: ANA was estimated to have the lowest cost and minimum life-years. The ICER of F&A versus ANA was US$15 665.891/QALY with incremental cost and QALY of US$12 401.120 and 0.792, respectively, which was less than the willingness-to-pay of US$29 383/QALY. Compared with F&A, FUL yielded a higher cost and a shorter lifetime; hence, it was identified as a dominated strategy. The univariate sensitivity analysis indicated the price of FUL was the most influential factor in our study. The probability that F&A was cost-effective at a threshold of US$29 383/QALY in China was 86.5%. CONCLUSION: F&A is a cost-effective alternative to FUL and ANA monotherapy for the first-line treatment of PMW-MBC (HR+) in China. F&A is a promising first-line treatment for PMW-MBC (HR+), and more research is needed to evaluate the economy of using F&A in other countries.
Subject(s)
Anastrozole/therapeutic use , Antineoplastic Agents, Hormonal/therapeutic use , Breast Neoplasms/drug therapy , Fulvestrant/therapeutic use , Anastrozole/administration & dosage , Anastrozole/economics , Antineoplastic Agents, Hormonal/administration & dosage , Antineoplastic Agents, Hormonal/economics , Breast Neoplasms/economics , Breast Neoplasms/pathology , Cost-Benefit Analysis , Drug Costs , Drug Therapy, Combination/economics , Drug Therapy, Combination/methods , Female , Fulvestrant/administration & dosage , Fulvestrant/economics , Health Care Costs , Humans , Markov Chains , Quality-Adjusted Life YearsABSTRACT
BACKGROUND: HER2 dual-blockade combined with aromatase inhibitors (AI) is a promising strategy to improve progression-free survival (PFS) in hormone receptor (HR) positive, metastatic breast cancer (MBC). Pyrotinib is a novel irreversible epidermal growth factor receptor/HER2 dual tyrosine kinase inhibitor. However, there is scarcity of data on the effectiveness and safety of pyrotinib combined with trastuzumab and AI as first-line treatment in a metastatic setting. METHODS/DESIGN: The present study is a prospective, randomized, open-label trial. 198 patients with HER2+/HR+ MBC will be recruited. Eligible patients will be allocated (2:1) to either an experimental group (pyrotinib + trastuzumab + AI) or a control group (trastuzumab + AI). Allocation will be stratified by 1) time since adjuvant hormone therapy (≤ 12 months/> 12 months/no prior hormone therapy); 2) lesion sites (visceral / non-visceral). The primary endpoint is PFS. DISCUSSION: To our knowledge, this is the first prospective randomized controlled trial to assess dual HER2-blockade with pyrotinib in the metastatic setting. This study will provide valuable evidence regarding the efficacy and safety of pyrotinib when combined with trastuzumab and an AI as first-line treatment for MBC. Moreover, it will also evaluate the feasibility of endocrine therapy as an alternative to chemotherapy in providing de-escalation therapy with less toxicity for advanced HR+/HER2+ patients. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03910712 . Registered on 10 Apr. 2019.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Receptor, ErbB-2/metabolism , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism , Acrylamides/administration & dosage , Adolescent , Adult , Aged , Aged, 80 and over , Aminoquinolines/administration & dosage , Anastrozole/administration & dosage , Androstadienes/administration & dosage , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Female , Follow-Up Studies , Humans , Letrozole/administration & dosage , Middle Aged , Prognosis , Prospective Studies , Trastuzumab/administration & dosage , Young AdultABSTRACT
Aromatase inhibitors (AIs) reduce breast cancer recurrence and prolong survival, but up to 30% of patients exhibit recurrence. Using a genome-wide association study of patients entered on MA.27, a phase III randomized trial of anastrozole versus exemestane, we identified a single nucleotide polymorphism (SNP) in CUB And Sushi multiple domains 1 (CSMD1) associated with breast cancer-free interval, with the variant allele associated with fewer distant recurrences. Mechanistically, CSMD1 regulates CYP19 expression in an SNP- and drug-dependent fashion, and this regulation is different among 3 AIs: anastrozole, exemestane, and letrozole. Overexpression of CSMD1 sensitized AI-resistant cells to anastrozole but not to the other 2 AIs. The SNP in CSMD1 that was associated with increased CSMD1 and CYP19 expression levels increased anastrozole sensitivity, but not letrozole or exemestane sensitivity. Anastrozole degrades estrogen receptor α (ERα), especially in the presence of estradiol (E2). ER+ breast cancer organoids and AI- or fulvestrant-resistant breast cancer cells were more sensitive to anastrozole plus E2 than to AI alone. Our findings suggest that the CSMD1 SNP might help to predict AI response, and anastrozole plus E2 serves as a potential new therapeutic strategy for patients with AI- or fulvestrant-resistant breast cancers.
Subject(s)
Anastrozole/pharmacology , Aromatase Inhibitors/pharmacokinetics , Breast Neoplasms/drug therapy , Membrane Proteins/genetics , Polymorphism, Single Nucleotide , Tumor Suppressor Proteins/genetics , Anastrozole/administration & dosage , Anastrozole/pharmacokinetics , Antineoplastic Agents, Hormonal/pharmacokinetics , Antineoplastic Agents, Hormonal/pharmacology , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Aromatase/genetics , Breast Neoplasms/genetics , Breast Neoplasms/mortality , Drug Resistance, Neoplasm/drug effects , Drug Resistance, Neoplasm/genetics , Estradiol/administration & dosage , Estradiol/pharmacology , Estrogen Receptor alpha/metabolism , Female , Genome-Wide Association Study , Humans , Pharmacogenetics , PostmenopauseABSTRACT
Chemobrain is one of the problems that may arise during or after treatment and there is currently no specific treatment for this condition. Our case was a 76-year-old female patient who presented to our clinic with complaints of forgetfulness that did not affect daily living activities for the last year. Breast cancer was diagnosed in 2013 and she has been receiving anastrozole treatment for 6 years after local mass excision surgery and radiotherapy. After a comprehensive geriatric evaluation, cognitive impairment due to systemic cancer therapy was detected and treatment was started with Theracurmin 90 mg twice a day therapy. After 3-months of Theracurmin therapy, she had no cognitive improvement during the follow-up. This case report demonstrated that Theracurmin treatment may be a new option for chemobrain.