- Radiation-induced morphea-a rare but severe late effect of adjuvant breast irradiation : Case report and review of the literature. [Journal Article]
- SOStrahlenther Onkol 2018; 194(11):1060-1065
- CONCLUSIONS: Little is known about risk factors and pathogenesis of RIM. Here we describe the first case of RIM following immunotherapy. The diagnosis is based on clinical appearance and histopathological examination. Treatment should be initiated in the inflammatory stage in order to prevent or delay irreversible fibrosis and atrophy of the breast.
- Integration of Clinical Variables for the Prediction of Late Distant Recurrence in Patients With Estrogen Receptor-Positive Breast Cancer Treated With 5 Years of Endocrine Therapy: CTS5. [Journal Article]
- JCJ Clin Oncol 2018 Jul 01; 36(19):1941-1948
- Purpose Estimating risk of late distant recurrence (DR) is an important goal for managing women with hormone receptor-positive breast cancer after 5 years of endocrine treatment without recurrence. W...
Purpose Estimating risk of late distant recurrence (DR) is an important goal for managing women with hormone receptor-positive breast cancer after 5 years of endocrine treatment without recurrence. We developed and validated a simple clinicopathologic tool (Clinical Treatment Score post-5 years [CTS5]) to estimate residual risk of DR after 5 years of endocrine treatment. Patients and Methods The ATAC (Arimidex, Tamoxifen, Alone or in Combination) data set (N = 4,735) was used to create a prognostic score for post-5-year risk of DR. Validity of CTS5 (ATAC) was tested in the BIG 1-98 data set (N = 6,711). Time to late DR, 5 years after finishing scheduled endocrine therapy, was the primary end point. Cox regression models estimated the prognostic performance of CTS5 (ATAC). Results CTS5 (ATAC) was significantly prognostic for late DR in the ATAC cohort (hazard ratio, 2.47; 95% CI, 2.24 to 2.73; P < .001) and BIG 1-98 validation cohort (hazard ratio, 2.07; 95% CI, 1.88 to 2.28; P < .001). CTS5 (ATAC) risk stratification defined in the training cohort as low (< 5% DR risk, years 5 to 10), intermediate (5% to 10%), or high (> 10%) identified 43% of the validation cohort as low risk, with an observed DR rate of 3.6% (95% CI, 2.7% to 4.9%) during years 5 to 10. From years 5 to 10, 63% of node-negative patients were low risk, with a DR rate of 3.9% (95% CI, 2.9% to 5.3%), and 24% with one to three positive nodes were low risk, with a DR rate of 1.5% (95% CI, 0.5% to 3.8%). A final CTS5 for future use was derived from pooled data from ATAC and BIG 1-98. Conclusion CTS5 is a simple tool based on information that is readily available to all clinicians. CTS5 was validated as highly prognostic for late DR in the independent BIG 1-98 study. The final CTS5 algorithm identified 42% of women with < 1% per-year risk of DR who could be advised of the limited potential value of extended endocrine therapy.
- Bioequivalence of Oral Formulations of Anastrozole in Healthy Chinese Male Volunteers: A Randomized, Single-Dose, Two-Period, Two-Sequence Crossover Study. [Journal Article]
- CPClin Pharmacol Drug Dev 2018 Apr 16
- Anastrozole is currently used as first-line treatment in locally advanced or metastatic breast cancer. A generic anastrozole tablet was developed to offer an alternative to the marketed tablet formul...
Anastrozole is currently used as first-line treatment in locally advanced or metastatic breast cancer. A generic anastrozole tablet was developed to offer an alternative to the marketed tablet formulation. The aim of the current study was to evaluate the bioequivalence between the test and reference formulations of anastrozole in a single-dose, 2-period, 2-sequence crossover study with a 14-day washout interval. A total of 20 healthy male Chinese volunteers were enrolled and completed the study, after oral administration of a single dose of 1.0-mg test and reference formulations of anastrozole. The blood samples were collected at different times and were determined by a fully validated high-pressure liquid chromatography-tandem mass spectrometry method. The evaluated pharmacokinetic parameters, including Cmax , AUC0-t , and AUC0-∞ , were assessed for bioequivalence based on current guidelines. The observed pharmacokinetic parameters of anastrozole of the test drug were similar to those of the reference formulation. The 90% confidence intervals of test/reference ratios for Cmax , AUC0-t , and AUC0-∞ were within the bioequivalence acceptance range of 80%-125%. The results obtained from these healthy Chinese subjects in this study suggest that the test formulation of anastrozole 1.0-mg tablet is bioequivalent to the reference formulation (Arimidex 1.0-mg tablet).
- Tracking evolution of aromatase inhibitor resistance with circulating tumour DNA analysis in metastatic breast cancer. [Journal Article]
- AOAnn Oncol 2018 Jan 01; 29(1):145-153
- CONCLUSIONS: Cancers progressing on the first-line AI show high levels of genetic heterogeneity, with frequent sub-clonal mutations. Sub-clonal KRAS mutations are found at high frequency. The genetic diversity of AI resistant cancers may limit subsequent targeted therapy approaches.
- HER2 status predicts for upfront AI benefit: A TRANS-AIOG meta-analysis of 12,129 patients from ATAC, BIG 1-98 and TEAM with centrally determined HER2. [Meta-Analysis]
- EJEur J Cancer 2017; 79:129-138
- CONCLUSIONS: A patient-level data meta-analysis demonstrated a significant interaction between HER2 status and treatment with AI versus tamoxifen in the first 2-3 years of adjuvant endocrine therapy. Patients with HER2-ve cancers experienced improved outcomes (distant relapse) when treated with upfront AI rather than tamoxifen, whilst patients with HER2+ve cancers fared no better or slightly worse in the first 2-3 years. However, the small number of HER2+ve cancers/events may explain a large degree of heterogeneity in the HER2+ve groups across all 3 trials. Other causes, perhaps related to subtle differences between AIs, cannot be excluded and warrant further exploration.
- Extended Adjuvant Endocrine Therapy in Breast Cancer: Evidence and Update - A Review. [Review]
- BJBreast J 2017; 23(6):694-705
- The optimal duration and treatment strategies involving adjuvant endocrine therapy in early breast cancer remained largely undetermined. As data emerge on the various modalities of treatment in both ...
The optimal duration and treatment strategies involving adjuvant endocrine therapy in early breast cancer remained largely undetermined. As data emerge on the various modalities of treatment in both pre- and postmenopausal groups, debates, and discussions continue. Most studies to date focused on the 5-year duration of treatment consisting of mainly tamoxifen. The Arimidex, Tamoxifen, Alone or in Combination (ATAC) study demonstrated that anastrozole is superior to tamoxifen and has become the mainstream treatment in postmenopausal women with early breast cancer, although the duration was arbitrarily set for 5 years, analogous to tamoxifen treatment. Several clinical trials, however, have emerged to support extended endocrine therapy as it becomes clear that the recurrence risk of breast cancer does not decrease beyond the initial 5 years of treatment. The advent of molecular signatures also plays an important role in the breast cancer profiling, and where available should be incorporated in the overall decision-making. Furthermore, side effects and noncompliance pose another issue in achieving an optimal treatment benefit. The decision-making as regards to extended endocrine treatment should therefore focus not only on the cancer biology alone but also include treatment side effects, assessment of risk of recurrence and patients' preference. In this review, we present an overview of the published studies to date as well as ongoing studies on the topic to better refine the options for adjuvant hormonal therapy.
- Plasma ESR1 Mutations and the Treatment of Estrogen Receptor-Positive Advanced Breast Cancer. [Randomized Controlled Trial]
- JCJ Clin Oncol 2016 Sep 01; 34(25):2961-8
- CONCLUSIONS: ESR1 mutation analysis in plasma after progression after prior AI therapy may help direct choice of further endocrine-based therapy. Additional confirmatory studies are required.
- Aromatase inhibitor associated arthralgia: the importance of oncology provider-patient communication about side effects and potential management through physical activity. [Journal Article]
- SCSupport Care Cancer 2016; 24(6):2643-50
- CONCLUSIONS: Breast cancer survivors who are prescribed an AI as part of their adjuvant treatment want ongoing communication with their oncology provider about the potential for joint pain side effects and how these symptoms may be managed through regular physical activity. The prescription of an AI presents a "teachable moment" for oncologists to recommend and encourage their patients to engage in regular physical activity.
- Validation of the IHC4 Breast Cancer Prognostic Algorithm Using Multiple Approaches on the Multinational TEAM Clinical Trial. [Randomized Controlled Trial]
- APArch Pathol Lab Med 2016; 140(1):66-74
- CONCLUSIONS: The use of the IHC4 algorithm was validated on the TEAM trial for predicting residual risk in patients with breast cancer. These data support the use of the IHC4 algorithm clinically, but quantitative and standardized approaches need to be used.
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- Benefit/risk for adjuvant breast cancer therapy with tamoxifen or aromatase inhibitor use by age, and race/ethnicity. [Meta-Analysis]
- BCBreast Cancer Res Treat 2015; 154(3):609-16
- In early adjuvant breast cancer trial reports, aromatase inhibitors more effectively reduced breast recurrence with lower risk of thromboembolic events and endometrial cancer than tamoxifen, while ar...
In early adjuvant breast cancer trial reports, aromatase inhibitors more effectively reduced breast recurrence with lower risk of thromboembolic events and endometrial cancer than tamoxifen, while aromatase inhibitors had higher fracture and cardiovascular disease risk. We used data from updated patient-level meta-analyses of adjuvant trials in analyses to summarize the benefits and risks of these agents in various clinical circumstances. Baseline incidence rates for health outcomes by age and race/ethnicity, absent aromatase inhibitor, or tamoxifen use were estimated from the Women's Health Initiative. Aromatase inhibitor and tamoxifen effects on distant recurrence were obtained from a meta-analysis of the Arimidex, Tamoxifen, Alone or in Combination (ATAC) and Breast International Group (Big-1-98) clinical trials. Impact on other health outcomes were obtained from meta-analyses of randomized trials comparing aromatase inhibitor to tamoxifen use and from placebo-controlled chemoprevention trials. All health outcomes were given equal weight when modeling net benefit/risk for aromatase inhibitor compared to tamoxifen use by breast cancer recurrence risk, age (decade), race/ethnicity, hysterectomy (yes/no), and by prior myocardial infarction. Over a 10-year period, the benefit/risk index was more favorable for aromatase inhibitor than for tamoxifen as adjuvant breast cancer therapy in almost all circumstances regardless of patient age, race/ethnicity, breast cancer recurrence risk, or presence or absence of a uterus. Only in older women with prior myocardial infarction and low recurrence risk was an advantage for tamoxifen seen. Using a benefit/risk index for endocrine adjuvant breast cancer therapy in postmenopausal women, benefit was higher for aromatase inhibitor use in almost all circumstances.