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The article focuses on the rapid guideline update for combining endocrine therapy with targeted agents for advanced breast cancer based on biomarker alterations. Topics include selecting between alpelisib and capivasertib for patients with PIK3CA mutations, the appropriateness of monotherapy with endocrine agents, and the impact of treatment toxicity and patient comorbidities on therapy decisions.

PURPOSE: Taxane-induced peripheral neuropathy (TIPN) is a dose-limiting toxicity of paclitaxel in patients with cancer. TIPN prediction is challenging although patients with higher systemic paclitaxel exposure have higher TIPN risk. This study aimed to identify protein predictors of TIPN and paclitaxel pharmacokinetics (PK). METHODS: This is a retrospective analysis of a prospective study of females with early-stage breast cancer receiving weekly paclitaxel. TIPN was assessed using the sensory subscale of the European Organisation for Research and Treatment of Cancer QLQ-Chemotherapy-Induced Peripheral Neuropathy (CIPN)20 (CIPN8). A blood sample was collected within 10 minutes before the end of the first paclitaxel infusion to measure plasma proteins using liquid chromatography-mass spectrometry and to estimate maximum systemic paclitaxel concentration (C max). A second sample was collected approximately 24 hours after the first infusion to estimate paclitaxel time above threshold (T c >0.05). Linear mixed-effect and regression models were used to identify proteins predictive of TIPN and paclitaxel PK parameters, respectively, using a Bonferroni-adjusted α =.0006. RESULTS: Data from 36 participants were included in the analysis testing associations of 83 proteins with TIPN or PK. Higher levels of complement C3 were associated with more severe TIPN trajectories (P =.0002). No proteins were associated with either C max or T c >0.05 (all P >.0006). CONCLUSION: Complement C3 concentration at the end of initial paclitaxel infusion may be useful for identifying patients with breast cancer and potentially other tumor types who could benefit from TIPN prevention strategies to improve long-term treatment outcomes. [ABSTRACT FROM AUTHOR]

Background: Aromatase inhibitors (AI) reduce hormone receptor-positive breast cancer recurrence risk by about 50%. However, half of AI-treated postmenopausal women report new or worsened musculoskeletal symptoms (AIMSS), and 20% discontinue therapy prematurely. Acupuncture is effective for reducing symptoms, but many women are not able to access acupuncture therapy. We hypothesize that self-administered acupressure will reduce AIMSS. Materials and methods: Postmenopausal women who have been receiving treatment with an AI for more than 3 weeks but less than 2 years, and who report new or worsened joint pain or myalgias since starting AI therapy with worst pain of at least 4 out of 10 on a numerical rating scale, are eligible. Fifty participants will be enrolled and randomized 1:1 to treatment with true or sham acupressure for 12 weeks. Participants will self-apply pressure for 3 minutes to each of the 9 acupoints daily. All participants will complete a pain assessment weekly, and a battery of symptom questionnaires every 6 weeks. Optional stool samples will be collected after 0 and 12 weeks of acupressure to examine changes in the gut microbiome. The primary endpoint is change in worst pain on the Brief Pain Inventory-Short Form with 12 weeks of the acupressure intervention, evaluated with generalized estimating equations. Conclusion: Determination that self-administered acupressure reduces AIMSS in this randomized phase 2 pilot trial will lead to a larger randomized phase 3 clinical trial to confirm the efficacy of self-acupressure. Reduction of AI-related arthralgias may improve persistence with breast cancer therapy, breast cancer outcomes, and quality of life for AI-treated patients. Trial registration: Clinicaltrials.gov NCT06228768. [ABSTRACT FROM AUTHOR]

Background: Annual or biennial breast cancer screenings are recommended for women 40 and older. Women residing in rural areas have worse breast cancer survival rates than urban women, but no study has focused on rural versus urban residence in Utah regarding breast cancer screening and mortality. Methods: Cases (n = 14,516) were women aged > 39 diagnosed with a first primary invasive breast cancer between 1998 and 2017 in Utah. Controls (n = 63,117) without a history of breast cancer were matched to cases by birth year and birth state. Mammography screening status was identified by Current Procedural Terminology (CPT) codes. Logistic regression was used to assess the odds of breast cancer diagnosis. The Cox proportional hazards model was used to assess survival outcomes for rural and urban breast cancer patients based on screening status. Results: Screening mammography usage among rural patients diagnosed with breast cancer was lower (17.7%) than urban usage (20.7%). Usage of screening mammograms resulted in higher odds of breast cancer diagnosis at localized stage rather than at a regional and distant stage. Rural breast cancer cases had a higher proportion of deaths, and a lower proportion screened, than urban breast cancer cases. Hazard ratios showed that screening mammography usage was associated with better survival among both rural (HR = 0.50, 95% CI = 0.44–0.57) and urban (HR = 0.56, 95% CI = 0.39–0.82) breast cancer cases. Conclusion: Screening mammography usage was associated with better overall survival regardless of place of residence. Removing barriers and improving information regarding breast cancer screenings are needed in both rural and urban settings in Utah to increase mammography usage, with the overall goal of increasing early detection and outcomes of breast cancer. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the validity of the Utah statewide All‐Payer Claims Database (APCD), we compared breast cancer‐specific treatments and dosages with gold‐standard abstraction of medical records. Study Design: In this pilot study, breast cancer treatments were abstracted by a certified tumor registrar at the Utah Cancer Registry (UCR) for patients diagnosed in 2013 with breast cancer. The abstraction of medical records was the gold standard for comparison with treatments identified in the APCD. The reliability and agreement between the treatment identified in the APCD and abstraction data were measured with sensitivity and specificity. Dose consistency was measured with the intraclass correlation coefficients (ICC). Results: Compared with the 186 abstractions, the sensitivity of the APCD to identify chemotherapy agents was high: 89% for any agent, 91% for carboplatin, 83% for docetaxel, 82% for doxorubicin, or 94.7% for biologic therapy. The consistency between the chemotherapy dosage identified in the claims and the abstraction varied from 63% to 76%. For radiotherapy, the sensitivity of the claims to identify the completed radiotherapy regimen was 66%. The ICC between radiotherapy doses identified in the claims and the abstraction was 54% (95% confidence interval [CI], 48%, 67%). Conclusions: Employing these novel methods, the claims were highly reliable in identifying cancer treatment agents overall, namely carboplatin, docetaxel, and trastuzumab. The claims were of moderate utility in capturing the treatment dose information. In addition to the APCD, the use of multiple data sources improved the completeness of cancer treatment information. [ABSTRACT FROM AUTHOR]

Purpose: Few studies have specifically targeted symptom management interventions for adolescent and young adult (AYA) cancer survivors. A greater understanding of AYA cancer survivors' experiences with cancer treatment-related symptoms would help develop age-appropriate oncology symptom management interventions. The purpose of this qualitative analysis was to explore AYA cancer survivors' experience with cancer treatment-related symptoms. Methods: Nineteen post-treatment AYA cancer survivors (18–39 years old) who self-reported moderate–severe cancer treatment-related symptom severity participated in video conferencing or telephone interviews. The questions in the interview guide queried participants to share their experience with cancer treatment-related symptoms. Inductive content analysis was used to identify themes from the interviews. Results: The themes that emerged from the interviews included (1) cancer treatment-related symptoms negatively affected AYA cancer survivors' quality of life (e.g., symptoms served as a reminder of cancer recurrence possibility); (2) AYA cancer survivors' attitudes and feelings about communicating cancer treatment-related symptom concerns to clinicians (e.g., patient–clinician communication was bolstered when AYAs perceived that symptoms were being taken seriously); (3) AYA cancer survivors are interested in oncology symptom management clinical trials, but logistical challenges are barriers to participation; and (4) AYA cancer survivors are interested in nonpharmacological treatments for symptom management. Conclusion: Results highlight the burden of cancer treatment-related symptoms on day-to-day life among post-treatment AYA cancer survivors. Future work is needed to identify nonpharmacological symptom management interventions, strategies to improve patient–clinician communication about symptoms, and strategies to increase the visibility and accessibility of symptom management clinical trials for AYA cancer survivors. [ABSTRACT FROM AUTHOR]

Patients carrying DPYD variant alleles have increased risk of severe toxicity from systemic fluoropyrimidine chemotherapy. There is a paucity of data regarding risk of toxicity from topical 5‐fluorouracil (5‐FU) treatment in these patients, leading to inconsistent guideline recommendations for pretreatment testing and topical 5‐FU dosing. The objective of this retrospective cohort study was to investigate whether DPYD variant allele carriers have increased risk of toxicity from topical 5‐FU. Treatment and toxicity data were retrospectively abstracted from the electronic medical records. Genotypes for the five DPYD variants that are associated with increased toxicity from systemic fluoropyrimidine chemotherapy (DPYD*2A, DPYD*13, DPYD p.D949V, DPYD HapB3, and DPYD p.Y186C) were collected from a genetic data repository. Incidence of grade 3+ (primary end point) and 1+ (secondary end point) toxicity was compared between DPYD variant carriers vs. wild‐type patients using Fisher's exact tests. The analysis included 201 patients, 7% (14/201) of whom carried a single DPYD variant allele. No patients carried two variant alleles or experienced grade 3+ toxicity. DPYD variant allele carriers did not have a significantly higher risk of grade 1+ toxicity (21.4% vs. 10.2%, odds ratio = 2.40, 95% confidence interval: 0.10–2.53, P = 0.19). Given the low toxicity risk in patients carrying a single DPYD variant allele, there is limited potential clinical benefit of DPYD genetic testing prior to topical 5‐FU. However, the risk of severe toxicity in patients with complete DPD deficiency remains unknown and topical 5‐FU treatment should be avoided in these patients. [ABSTRACT FROM AUTHOR]

Background: Limited population-based studies have focused on breast cancer survivors in rural populations. We sought to evaluate the risk of adverse health outcomes among rural and urban breast cancer survivors and to evaluate potential predictors for the highest risk outcomes. Methods: A population-based cohort of rural and urban breast cancer survivors diagnosed between 1997 and 2017 was identified in the Utah Cancer Registry (UCR). Rural breast cancer survivors were matched on year (±1 year) and age at cancer diagnosis (±1 year) with up to 5 urban breast cancer survivors (2,359 rural breast cancer survivors; 11,748 urban breast cancer survivors). Cox proportional hazards models were used to calculate HRs with 99% confidence intervals (CI) for adverse health outcomes overall, within 5 years, and >5 years after cancer diagnosis. Results: Compared with urban breast cancer survivors, rural breast cancer survivors had a 39% (HR, 1.39; 95% CI, 1.02-1.65) higher risk of heart failure (HF) within the 5 years of follow-up. Overall, there was no increase in the risk of other evaluated adverse health outcomes. A higher baseline body mass index and Charlson Comorbidity Index, family history of cardiovascular diseases, family history of breast cancer, and advanced cancer stage were risk factors for HF for rural and urban breast cancer survivors, with similar levels of HF risk. Conclusions: Rural residence was associated with an increased risk of HF among breast cancer survivors. Impact: Our study highlights the need for primary preventive strategies for rural cancer survivors at risk of heart failure. [ABSTRACT FROM AUTHOR]