Potential biomarkers in breast cancer drug development: application of the biomarker qualification evidentiary framework.

Breast cancer treatments have evolved rapidly, and clinically meaningful biomarkers have been used to guide therapy. These biomarkers hold utility within the drug development process to increase the efficiency and effectiveness. To this purpose, the US FDA developed an evidentiary framework. Literature searches conducted of literature published between 2016 and 2022 identified biomarkers in breast cancer. These biomarkers were reviewed for drug development utility through the biomarker qualification evidentiary framework. In the breast cancer setting, several promising biomarkers (ctDNA, Ki-67 and PIK3CA) were identified. There is a need for increased transparency regarding the requirements for qualification of specific biomarkers and increased awareness of the processes involved in biomarker qualification.

Elderly patients with acute myeloid leukemia who only receive supportive care in the Surveillance, Epidemiology and End Results-Medicare database: demographics, treatment patterns and outcomes.

Aim: Elderly acute myeloid leukemia (AML) patients are often not treated with antileukemic therapy due to their poor overall health condition, leaving supportive care as the sole treatment option. Objective: To evaluate patient characteristics, treatment patterns and outcomes of elderly patients with AML who are treated with supportive care only. Methods: A retrospective analysis of elderly AML patients included in the Surveillance, Epidemiology and End Results-Medicare database from 2008 to 2015. Results: Of elderly patients with AML (n = 7665), 3209 (41.9%) received supportive care only. Their mean age was 79 years, 50.5% were males; 48.2% died during the first 3 months and 67.3% died during the first 6 months. 82.2% died within the first year; only 13.2% survived >12 months. 77.9% patients died due to leukemia. Conclusion: In elderly AML patients treated with supportive care only, older age, concurrent hypertension, chronic obstructive pulmonary disease, chronic kidney disease and acute myocardial infarction were identified as prognostic factors associated with decreased likelihood of survival. Ideally, these patients should be treated with antileukemic therapy in addition to supportive care, as most of them die from disease progression.

This study analyzed data on elderly patients with acute myeloid leukemia (AML) who were only treated with supportive care. The source of this data was the Surveillance, Epidemiology and End Results (SEER)-Medicare database. Of the 7665 patients diagnosed with AML during 2008­2015, 3209 (41.9%) received supportive care only. Their mean age at index date was 79 years; slightly more than half of these were males (50.5%). Almost half of these patients (48.2%) died within the first 3 months and approximately two-thirds (67.3%) died within the first 6 months. Only a small proportion (13%) of these patients were alive after 1 year. These patients who were alive after one were likely to be in remission (there was decrease in the signs and symptoms of AML). The results of this study showed that elderly AML patients who only received supportive care were more likely to die early if they also had chronic kidney disease, chronic obstructive pulmonary disease, history of acute myocardial infarction or hypertension. As elderly AML patients may be in poor general health and have other diseases (comorbidities), this could be the reason why they may not be treated with antileukemic therapy. Instead of treatment with supportive care only, these patients should ideally receive antileukemic therapy in addition to supportive care. More research should be done to find alternate treatments for these elderly AML patients.

Health-related Quality of Life in Hormone Receptor-Positive Early Breast Cancer: Analyses From the Surveillance, Epidemiology, and End Results Medicare Health Outcomes Survey.

This study describes health-related quality of life (HRQoL) among older Medicare beneficiaries with hormone receptor-positive (HR+) early breast cancer (eBC). Women aged ≥65 years diagnosed with stage I-III HR+ eBC between 1997 and 2014 using the Surveillance, Epidemiology, and End Results Medicare Health Outcomes Survey Data Resource were included. HRQoL was measured using the Short Form Health Survey including physical/mental component summary (PCS/MCS) scores and subscales. Patient surveys ≤ 24 months post-diagnosis were matched to non-cancer controls. Mean differences in HRQoL were compared using analysis of covariance. Among 1880 HR+ eBC patients versus 5640 matched non-cancer controls, eBC patients surveyed ≤ 6 months post-diagnosis (n = 530) scored lower on component scores (PCS mean difference = 1.6 [95%CI: 0.6-2.6]; MCS mean difference = 2.0 [95%CI: 1.0-3.0]) and multiple subscales. Among women surveyed 19 to 24 months post-diagnosis (n = 402), mean differences in HRQoL were modest (PCS: 1.2 [95%CI: 0.1-2.4]; MCS: -1.5 [95%CI: -2.7 to -0.3]). Most differences in HRQoL following diagnosis of eBC did not indicate statistical significance or minimally important difference, emphasizing that preservation of HRQoL is an important and realistic goal among patients with eBC.

Impact of time to distant recurrence on breast cancer-specific mortality in hormone receptor-positive breast cancer.

Women with hormone receptor (HR)-positive early-stage breast cancer (BC) have five-year survival rates of > 90% but remain at serious risk for developing distant metastases beyond five years from diagnosis. This retrospective cohort study used data from the Surveillance, Epidemiology, and End Results (SEER) registries to examine associations between distant recurrence-free interval (DRFI) and risk of BC-specific mortality following distant relapse. The analysis includes 1,057 women with second primary stage IV BC who were initially diagnosed with AJCC stages I-III HR-positive BC between1990 and 2016. Overall, 65% of women had a preceding DRFI of ≥ 5 years. Five-year BC-specific survival following development of distant recurrence was 52% for women with DRFI ≥ 5 years compared to 31% in women with DRFI of < 5 years. In multivariable analyses, risks of cancer-specific mortality following distant recurrence were lower in women with DRFI of 5 years or more (subdistribution hazard ratio = 0.72, 95% CI 0.58-0.89, p = 0.002). The results of this study may inform patient-clinician discussions surrounding prognosis and treatment selection among HR-positive patients who develop a distant recurrence of disease.

Population-based recurrence rates among older women with HR-positive, HER2-negative early breast cancer: Clinical risk factors, frailty status, and differences by race.

BACKGROUND: Multiple independent risk factors are associated with the prognosis of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer (BC), the most common BC subtype. This study describes U.S. population-based recurrence rates among older, resected women with HR+/HER2- early BC. METHODS: We conducted a retrospective cohort study of older women diagnosed with incident, invasive stages I-III HR+/HER2- BC who underwent surgery to remove the primary tumor using the Surveillance, Epidemiology, and End Results (SEER)-Medicare Linked Database (2007-2015). SEER records and administrative health claims data were used to ascertain patient and tumor-specific characteristics, treatment, and frailty status. Cumulative incidences of BC recurrence were estimated using a validated algorithm for administrative claims data. Multivariable Fine-Gray competing risk models estimated adjusted subdistribution hazards ratios and 95 % confidence intervals for associations with BC recurrence risk. RESULTS: Overall, 46,027 women age ≥65 years were included in our analysis. Over a median follow up of 7 years, 6531 women experienced BC recurrence with an estimated 3 and 5-year cumulative incidence rates of 10 % and 16 %, respectively. Higher 3- and 5-year cumulative incidences were observed in women with larger tumor size (5+ cm, 21 % and 28 %), lymph node involvement (4+ nodes, 27 % and 37 %), and with frail health status at diagnosis (13 % and 20 %). Independent of these clinical risk factors, Black, Hispanic and American Indian/Alaskan Native women had significantly increased BC recurrence risks. CONCLUSIONS: Rates of recurrence in HR+/HER2- early BC differs by several patient and clinical factors, including high-risk tumor characteristics. Racial differences in BC outcomes deserve continued attention from clinicians and policymakers.

Risk of recurrence among patients with HR-positive, HER2-negative, early breast cancer receiving adjuvant endocrine therapy: A systematic review and meta-analysis.

BACKGROUND: A systematic review and meta-analysis was conducted to assess breast cancer (BC) outcomes among patients with early-stage hormone receptor positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) BC, receiving adjuvant endocrine therapy. METHODS: Randomized controlled trials (RCTs) and real-world evidence (RWE) studies were identified using Ovid MEDLINE®, Embase, and Evidence-Based Medicine Reviews. Clinical and methodological similarities including alignment of outcome definitions with standardized definitions for efficacy endpoints criteria were assessed to evaluate feasibility of conducting a meta-analysis. Where feasible, 5-year probabilities of BC recurrence or death were estimated using a Bayesian hierarchical arm-based model. RESULTS: Of 21 included studies, 8 RCTs and 4 RWE studies reported outcome data of interest. There was heterogeneity in outcome reporting, as well as variation in recurrence risk amongst studies with aligned reporting. Of the 12 studies, 10 were considered for inclusion in a meta-analysis of BC recurrence or death. Only a subgroup analysis of node-positive patients (3 studies; n = 7307) was deemed feasible. The 5-year probability of BC recurrence or death was 17.2% (95% credible interval: 14.6%-20.3%). CONCLUSION: Although studies reporting recurrence outcomes were limited, there remains a high risk of BC recurrence, especially among node-positive patients. Approximately 1 in 6 women with node-positive HR+/HER2- early-stage BC receiving endocrine therapy experience recurrence or death within 5-years of initiating treatment, suggesting a need for novel treatments for this population.