A Cohort Study to Evaluate Genetic Predictors for Aromatase Inhibitor Musculoskeletal Symptoms (AIMSS): Results from ECOG-ACRIN E1Z11.

PURPOSE: Aromatase Inhibitor-Associated Musculoskeletal Symptoms (AIMSS) are common and frequently lead to AI discontinuation. Single nucleotide polymorphisms (SNPs) in candidate genes have been associated with AIMSS and AI discontinuation. E1Z11 is a prospective cohort study designed to validate associations between 10 SNPs and AI discontinuation due to AIMSS. PATIENTS AND METHODS: Postmenopausal women with stage I-III hormone receptor-positive breast cancer received anastrozole 1 mg daily and completed patient-reported outcomes (PRO) to assess AIMSS (Stanford Health Assessment Questionnaire; HAQ) 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 strata provided 80% power to detect an effect size of 1.5-4. SNPs were in ESR1 (rs2234693, rs2347868, rs9340835), CYP19A1 (rs1062033, rs4646), TCL1A (rs11849538, rs2369049, rs7158782, rs7159713), and HTR2A (rs2296972). RESULTS: Of 970 evaluable women, 43% developed AIMSS and 12% discontinued AI therapy within 12 months. While more Black and Asian women developed AIMSS compared to White women (49% vs 39%, p=0.017; 50% vs 39%, p=0.004, respectively), 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 odds ratio for rs2296972 (HTR2A) approached significance for developing AIMSS. CONCLUSION: We were unable to prospectively validate candidate SNPs previously associated with AI discontinuation due to AIMSS. Future analyses will explore additional genetic markers, PRO predictors of AIMSS, and differences by race.

Exploring Adolescent and Young Adult Cancer Survivors' Experience with Cancer Treatment-Related Symptoms: A Qualitative Analysis of Semi-Structured Interviews.

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.

Barriers to endocrine therapy adherence: perspectives of Black breast cancer survivors and their providers.

PURPOSE: Adherence to oral endocrine therapy (ET) remains an issue for up to half of women prescribed these medications. There is emerging data that Black breast cancer survivors (BCS) have lower rates of ET adherence. Given the disparities in breast cancer recurrence and survival for Black BCS compared to their White counterparts, the goal of this study is to better understand barriers to ET adherence among Black BCS from the patient and provider perspectives. METHODS: In this qualitative study, we conducted semi-structured interviews between October 29, 2021, and March 1, 2023. Interviews were recorded and transcribed, and coded data were organized into primary and secondary themes. Participants were recruited from a single academic cancer center. A convenience sample of 24 Black BCS and 9 medical oncology providers was included. Eligible BCS were 18 years or older, English-speaking, diagnosed with stage I-III hormone receptor-positive breast cancer, who had initiated ET. RESULTS: Mean age of the BCS was 55 years (interquartile range, IQR 17 years). About one-fourth had a high school diploma or less (26.1%) and 47% completed a college education or higher. Approximately one-third of participants had annual household incomes of $40,000 or less (30.4%) or more than $100,000 (30.4%). Forty-three percent of the patient participants had private insurance; 11% were insured through Medicaid or the federal healthcare exchange; 26.1% had Medicare; and 13% were uninsured. Of the 9 medical oncology providers interviewed, 2 were advanced practice providers, and 7 were medical oncologists. We found 3 major themes: (1) Black BCS often had concerns about ET before initiation; (2) after initiation, both BCS and providers reported side effects as the most impactful barrier to ET adherence; and (3) survivors experienced challenges with managing ET side effects. CONCLUSIONS: Our results suggest that multifaceted support interventions for managing ET-related symptoms may lead to improved adherence to ET among Black women and may reduce disparities in outcomes. IMPLICATIONS FOR CANCER SURVIVORS: Multifaceted support interventions for managing ET-related symptoms may lead to improved adherence to ET among Black breast cancer survivors.

Endocrine and Targeted Therapy for Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer-Capivasertib-Fulvestrant: ASCO Rapid Recommendation Update.

ASCO Rapid Recommendation Updates highlight revisions to select ASCO guideline recommendations as a response to the emergence of new and practice-changing data. The rapid updates are supported by an evidence review and follow the guideline development processes outlined in the ASCO Guideline Methodology Manual. The goal of these articles is to disseminate updated recommendations, in a timely manner, to better inform health practitioners and the public on the best available cancer care options. Guidelines and updates are not intended to substitute for independent professional judgment of the treating provider and do not account for individual variation among patients. See appendix for disclaimers and other important information (Appendix 1 and Appendix 2, online only).

ctDNA transiting into urine is ultrashort and facilitates noninvasive liquid biopsy of HPV+ oropharyngeal cancer.

BACKGROUNDTransrenal cell-free tumor DNA (TR-ctDNA), which transits from the bloodstream into urine, has the potential to enable noninvasive cancer detection for a wide variety of nonurologic cancer types.MethodsUsing whole-genome sequencing, we discovered that urine TR-ctDNA fragments across multiple cancer types are predominantly ultrashort (<50 bp) and, therefore, likely to be missed by conventional ctDNA assays. We developed an ultrashort droplet digital PCR assay to detect TR-ctDNA originating from HPV-associated oropharyngeal squamous cell carcinoma (HPV+ OPSCC) and confirmed that assaying ultrashort DNA is critical for sensitive cancer detection from urine samples.ResultsTR-ctDNA was concordant with plasma ctDNA for cancer detection in patients with HPV+ OPSCC. As proof of concept for using urine TR-ctDNA for posttreatment surveillance, in a small longitudinal case series, TR-ctDNA showed promise for noninvasive detection of recurrence of HPV+ OPSCC.ConclusionOur data indicate that focusing on ultrashort fragments of TR-ctDNA will be important for realizing the full potential of urine-based cancer diagnostics. This has implications for urine-based detection of a wide variety of cancer types and for facilitating access to care through at-home specimen collections.FundingNIH grants R33 CA229023, R21 CA225493; NIH/National Cancer Institute grants U01 CA183848, R01 CA184153, and P30CA046592; American Cancer Society RSG-18-062-01-TBG; American Cancer Society Mission Boost grant MBGI-22-056-01-MBG; and the A. Alfred Taubman Medical Research Institute.

Attempted replication of pharmacogenetic association of variants in PPP1R14C and CCDC148 with aromatase inhibitor-induced musculoskeletal symptoms.

Third-generation aromatase inhibitors (AI) are the standard treatment for patients with hormone receptor positive (HR+) breast cancer. While effective, AI can lead to severe adverse events, including AI-induced musculoskeletal syndrome (AIMSS). Genetic predictors of AIMSS have the potential to personalize AI treatment and improve outcomes. We attempted to replicate results from a previous genome-wide association study that found a lower risk of AIMSS in patients carrying PPP1R14C rs912571 and a higher risk in patients carrying CCDC148 rs79048288. AIMSS data were collected prospectively from patients with HR+ breast cancer prior to starting and after 3 and 6 months of adjuvant AI via the Patient-Reported Outcome Measurement Information System and Functional Assessment of Cancer Therapy-Endocrine Symptom. Germline genotypes for PPP1R14C rs912571 and CCDC148 rs79048288 were tested for a similar association with AIMSS as previously reported via $2 tests. Of the 143 patients with AIMSS and genetics data were included in the analysis. There was no association identified between PPP1R14C rs912571 and AIMSS risk (P > 0.05). Patients carrying CCDC148 rs79048288 variant alleles had lower AIMSS incidence in a secondary analysis (P = 0.04); however, this was in the opposite direction of the previous finding. The study did not replicate previously reported associations with AIMSS risk for genetic variants in PPP1R14C and CCDC148 and AIMSS risk. Further research is needed to discover and validate genetic predictors of AIMSS that can be used to personalize treatment in patients with HR+ breast cancer.

Polypharmacy, over-the-counter medications, and aromatase inhibitor adherence in early-stage breast cancer.

PURPOSE: Polypharmacy is associated with negative health outcomes and decreased medication adherence. Polypharmacy is common in cancer populations, but few studies have evaluated the relationship between polypharmacy and aromatase inhibitor (AI) adherence. No studies have evaluated the relationship between over-the-counter (OTC) supplements and AI adherence. Our primary hypothesis was that polypharmacy would be associated with increased risk of premature AI discontinuation. METHODS: This exploratory analysis used data from the Exemestane and Letrozole Pharmacogenetics (ELPh) trial, a prospective, multicenter, randomized controlled trial that enrolled participants from 2005 to 2009. Included patients were female, postmenopausal, with stage 0-III breast cancer, who had completed indicated chemotherapy, surgery, and radiation. Participants were randomized to adjuvant exemestane or letrozole and completed serial clinical examinations and questionnaires for two years. Concomitant medication data were collected prospectively. Cox proportion models were used for statistical analysis of the relationship between polypharmacy, OTCs, medication class, and AI adherence. RESULTS: In the 490 analyzed participants, use of any prescription medications at baseline was associated with decreased risk of premature AI discontinuation (HR 0.56, p = 0.02). Use of selective serotonin reuptake inhibitors (SSRIs) or selective serotonin and norepinephrine reuptake inhibitors (SNRIs) at baseline was associated with decreased risk of premature AI discontinuation (HR 0.67, p = 0.04). Use of any OTCs was not associated with AI discontinuation. CONCLUSION: Baseline use of prescription medications but not OTCs was associated with increased AI persistence. Future research is needed to understand how this can be utilized to promote AI adherence.

Risk of Toxicity From Topical 5-Fluorouracil Treatment in Patients Carrying DPYD Variant Alleles.

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.

Vitamin D Insufficiency as a Risk Factor for Paclitaxel-Induced Peripheral Neuropathy in SWOG S0221.

BACKGROUND: Prior work suggests that patients with vitamin D insufficiency may have a higher risk of chemotherapy-induced peripheral neuropathy (CIPN) from paclitaxel. The objective of this study was to validate vitamin D insufficiency as a CIPN risk factor. METHODS: We used data and samples from the prospective phase III SWOG S0221 (ClinicalTrials.gov identifier: NCT00070564) trial that compared paclitaxel-containing chemotherapy regimens for early-stage breast cancer. We quantified pretreatment 25-hydroxy-vitamin D in banked serum samples using a liquid chromatography-tandem mass spectrometry targeted assay. We tested the association between vitamin D insufficiency (≤20 ng/mL) and grade ≥3 sensory CIPN via multiple logistic regression and then adjusted for self-reported race, age, body mass index, and paclitaxel schedule (randomization to weekly or every-2-week dosing). We also tested the direct effect of vitamin D deficiency on mechanical hypersensitivity in mice randomized to a regular or vitamin D-deficient diet. RESULTS: Of the 1,191 female patients in the analysis, 397 (33.3%) had pretreatment vitamin D insufficiency, and 195 (16.4%) developed grade ≥3 CIPN. Patients with vitamin D insufficiency had a higher incidence of grade ≥3 CIPN than those who had sufficient vitamin D (20.7% vs 14.2%; odds ratio [OR], 1.57; 95% CI, 1.14-2.15; P=.005). The association retained significance after adjusting for age and paclitaxel schedule (adjusted OR, 1.65; 95% CI, 1.18-2.30; P=.003) but not race (adjusted OR, 1.39; 95% CI, 0.98-1.97; P=.066). In the mouse experiments, the vitamin D-deficient diet caused mechanical hypersensitivity and sensitized mice to paclitaxel (both P<.05). CONCLUSIONS: Pretreatment vitamin D insufficiency is the first validated potentially modifiable predictive biomarker of CIPN from paclitaxel. Prospective trials are needed to determine whether vitamin D supplementation prevents CIPN and improves treatment outcomes in patients with breast and other cancer types.

Effects of CYP3A4 and CYP2C9 genotype on systemic anastrozole and fulvestrant concentrations in SWOG S0226.

Objective & methods: This study tested associations of genotype-predicted activity of CYP3A4, other pharmacogenes, SLC28A7 (rs11648166) and ALPPL2 (rs28845026) with systemic concentrations of the endocrine therapies anastrozole and fulvestrant in SWOG S0226 trial participants. Results: Participants in the anastrozole-only arm with low CYP3A4 activity (i.e. CYP3A4*22 carriers) had higher systemic anastrozole concentrations than patients with high CYP3A4 activity (ß-coefficient = 10.03; 95% CI: 1.42, 18.6; p = 0.025). In an exploratory analysis, participants with low CYP2C9 activity had lower anastrozole concentrations and higher fulvestrant concentrations than participants with high CYP2C9 activity. Conclusion: Inherited genetic variation in CYP3A4 and CYP2C9 may affect concentrations of endocrine therapy and may be useful to personalize dosing and improve treatment outcomes.

Impact of the Integrative Oncology Scholars Program on Oncology Providers' Key Knowledge of Dietary Supplements and Antioxidants for Providing Evidence-based Oncology Care.

Dietary supplements are commonly used among cancer survivors. Oncology providers rarely receive training about dietary supplements. We evaluated whether e-learning modules could improve oncology providers' dietary supplement knowledge. Oncology providers participated in the National Cancer Institute funded Integrative Oncology Scholars (IOS) program. We used posttest readiness assurance tests (RAT) to measure knowledge acquisition from modules. One cohort completed a pre and posttest RAT to assess change in knowledge. Multivariate linear regression models adjusted for gender, race, profession, and years in practice were used to determine if these characteristics were associated with posttest RAT performance and change in pre to posttest RAT scores. Scholars (N = 101) included 86% (N = 87) females; age 44 ± 10 years; 72% (N = 73) Non-Hispanic White; years in practice mean range 11-15 ± 10. There were 37 physicians, 11 physician assistants, 23 nurses, 21 social workers, 2 psychologists, 4 pharmacists, and 2 physical therapists. The posttest dietary supplement and antioxidant RAT scores for all Scholars were 67 ± 18% and 71 ± 14%. In adjusted models there were no significant associations between dietary supplement and antioxidant posttest RAT scores with Scholar characteristics. Change in RAT scores for dietary supplement and antioxidants were 25% ± 23 and 26% ± 27 (P < 0.0001). In adjusted models, there were no significant predictors of change in dietary supplement RATs. For antioxidant RATs, profession was associated with change in scores (P = 0.021). Improvement in Scholar's test scores demonstrate the IOS program can significantly increase oncology providers' knowledge of dietary supplements and antioxidants.

Adverse Health Outcomes among Rural and Urban Breast Cancer Survivors: A Population-Based Cohort Study.

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.

Determining the association of rurality and cardiovascular disease among prostate cancer survivors.

PURPOSE: Rural disparities in prostate cancer survivorship and cardiovascular disease remain. Prostate cancer treatment also contributes to worse cardiovascular disease outcomes. Our objective was to determine whether rural-urban differences in cardiovascular outcomes contribute to disparities in prostate cancer survivorship. MATERIALS AND METHODS: Data were collected from the Utah Population Database. Rural and urban prostate cancer survivors were matched by diagnosis year and age. Cox proportional hazards models were used to estimate hazard ratios for cardiovascular disease (levels 1-3) based on rural-urban classification, while controlling for demographic and socioeconomic characteristics. We identified 3,379 rural and 16,253 urban prostate cancer survivors with a median follow-up of 9.3 years. RESULTS: Results revealed that rural survivors had a lower risk of hypertension (HR 0.90), diseases of arteries (HR 0.92), and veins (HR 0.92) but a higher risk of congestive heart failure (HR 1.17). Interactions between level 2 cardiovascular diseases and rural/urban status, showed that diseases of the heart had a distinct between-group relationship for all-cause (P = 0.005) and cancer-specific mortality (P = 0.008). CONCLUSIONS: This study revealed complex relationships between rural-urban status, cardiovascular disease, and prostate cancer. Rural survivors were less likely to be diagnosed with screen-detected cardiovascular disease but more likely to have heart failure. Further, the relationship between cardiovascular disease and survival was different between rural and urban survivors. It may be that our findings underscore differences in healthcare access where rural patients are less likely to be screened for preventable cardiovascular disease and have worse outcomes when they have a major cardiovascular event.

Adverse health outcomes among rural prostate cancer survivors: A population-based study.

INTRODUCTION: Rural cancer survivors experience considerable health disparities compared to urban cancer survivors for cancer treatment and survival. The objective of our study was to investigate the risk of developing diseases for rural compared to urban prostate cancer survivors in Utah. METHODS: We identified a cohort of 3575 rural prostate cancer survivors and 17,778 urban prostate cancer survivors from the Utah Cancer Registry. The Fine-Gray subdistribution hazards model was used to estimate hazard ratios and 95 % confidence intervals for diseases in major body systems among rural compared to urban prostate cancer survivors at > 1-5 years and > 5 years after prostate cancer diagnosis. RESULTS: Rural residence was associated with an increased risk of diseases of the respiratory system at > 5 years (HR: 1.16, 95 % CI: 1.01-1.32) after cancer diagnosis compared to urban residence among prostate cancer survivors in Utah. Decreased risks were observed in infectious and parasitic diseases, diseases of the blood and blood-forming organs, diseases of the nervous system and sense organs, and diseases of the skin and subcutaneous tissue for rural prostate cancer survivors between 1 and 5 years after cancer diagnosis. CONCLUSIONS: Rural prostate cancer survivors in Utah were somewhat healthier compared to urban prostate cancer survivors. Further studies are needed to confirm whether these associations are also supported for rural prostate cancer survivors in other regions of the U.S.

Confirmatory DPYD Testing in Patients Receiving Fluoropyrimidines Who are Suspected DPYD Variant Carriers Based on a Genetic Data Repository.

Using pharmacogenetics (PGx) to inform clinical decision making can benefit patients but clinical use of PGx testing has been limited. Existing genetics data obtained in the course of research could be used to identify patients who are suspected, but have not yet been confirmed, to carry clinically actionable genotypes, in whom confirmatory genetic testing could be conducted for highly efficient PGx implementation. Herein, we demonstrate that it is regulatorily and technically feasible to implement PGx by identifying suspected carriers of actionable genotypes within an institutional genetics data repository and conduct confirmatory PGx testing immediately prior to that patient receiving the PGx-relevant drug, using a case study of DPYD testing prior to fluoropyrimidine chemotherapy. In 2 years since launching this program, ~ 3,000 suspected DPYD carriers have been passively monitored and one confirmed DPYD carrier was prevented from receiving unacceptably toxic fluoropyrimidine treatment, for minimal cost and effort. Now that we have demonstrated the feasibility of this strategy, we plan to transition to PGx panel testing and expand implementation to other genes and drugs for which the evidence of clinical benefit of PGx-informed treatment is high but PGx testing is not generally conducted. This highly efficient implementation process will maximize the clinical benefits of testing and could be explored at other institutions that have research-only genetic data repositories to expand the number of patients who benefit from PGx-informed treatment while we continue to work toward wide-scale adoption of PGx testing and implementation.

Breast cancer survivorship and sexual dysfunction: a population-based cohort study.

BACKGROUND: Breast cancer is the most common non-skin cancer in women and an increasing number of people are living as breast cancer survivors. While the prognosis of breast cancer continues to improve, the rates of sexual dysfunction and the risk related to cancer treatments have not been well characterized in a population-based study. METHODS: We identified a cohort of 19,709 breast cancer survivors diagnosed between 1997 and 2017 from the Utah Cancer Registry, and 93,389 cancer-free women who were matched by age and birth state from the Utah Population Database. Sexual dysfunction diagnoses were identified through ICD-9 and ICD-10 codes from electronic medical records and statewide healthcare facilities data. Cox proportional hazard models were used to estimate hazard ratios for risk of sexual dysfunction. RESULTS: Breast cancer survivors were at higher risk of sexual dysfunction diagnosis (9.1% versus 6.9%, HR 1.60, 95% CI 1.51-1.70) compared to the general population. This risk increased 2.05-fold within 1 to 5 years after cancer diagnosis (95% CI 1.89-2.22) and 3.05-fold in individuals diagnosed with cancer at < 50 years of age (95% CI 2.65-3.51). Cancer treatments including endocrine therapy, chemotherapy and radiation therapy were associated with an increased risk of sexual dysfunction among breast cancer survivors. CONCLUSIONS: Risk of sexual dysfunction in breast cancer survivors is higher than in the general population, but may be underdiagnosed in the clinical setting. Health care professionals should be encouraged to address the topic of sexual health early on in the treatment of breast cancer, and routinely screen patients for symptoms of sexual dysfunction.

Testing for ESR1 Mutations to Guide Therapy for Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer: ASCO Guideline Rapid Recommendation Update.

ASCO Rapid Recommendations Updates highlight revisions to select ASCO guideline recommendations as a response to the emergence of new and practice-changing data. The rapid updates are supported by an evidence review and follow the guideline development processes outlined in the ASCO Guideline Methodology Manual. The goal of these articles is to disseminate updated recommendations, in a timely manner, to better inform health practitioners and the public on the best available cancer care options. See the Appendix for disclaimers and other important information (Appendix 1 and Appendix 2, online only).

Genetic variations that influence paclitaxel pharmacokinetics and intracellular effects that may contribute to chemotherapy-induced neuropathy: A narrative review.

Taxanes, particularly paclitaxel and docetaxel, are chemotherapeutic agents commonly used to treat breast cancers. A frequent side effect is chemotherapy-induced peripheral neuropathy (CIPN) that occurs in up to 70% of all treated patients and impacts the quality of life during and after treatment. CIPN presents as glove and stocking sensory deficits and diminished motor and autonomic function. Nerves with longer axons are at higher risk of developing CIPN. The causes of CIPN are multifactorial and poorly understood, limiting treatment options. Pathophysiologic mechanisms can include: (i) disruptions of mitochondrial and intracellular microtubule functions, (ii) disruption of axon morphology, and (iii) activation of microglial and other immune cell responses, among others. Recent work has explored the contribution of genetic variation and selected epigenetic changes in response to taxanes for any insights into their relation to pathophysiologic mechanisms of CIPN20, with the hope of identifying predictive and targetable biomarkers. Although promising, many genetic studies of CIPN are inconsistent making it difficult to develop reliable biomarkers of CIPN. The aims of this narrative review are to benchmark available evidence and identify gaps in the understanding of the role genetic variation has in influencing paclitaxel's pharmacokinetics and cellular membrane transport potentially related to the development of CIPN.

Ovarian Function Suppression in Premenopausal Women With Concurrent Endocrine Therapy Use.

INTRODUCTION: Almost 20% of patients receiving ovarian function suppression (OFS) and endocrine therapy (ET) for breast cancer treatment had inadequate OFS within the first year of treatment. Few studies have explored the long-term effectiveness of OFS to maintain estrogen suppression. PATIENTS AND METHODS: This retrospective, single institution study examined premenopausal women with early-stage breast cancer undergoing treatment with OFS and ET. The primary endpoint was the percentage of patients with inadequate ovarian suppression (estradiol ≥10 pg/mL) during OFS cycle 2 or later. The secondary endpoint was the percentage of patients with inadequate ovarian suppression within the first cycle after OFS initiation. Differences in age, body mass index (BMI), and previous chemotherapy use were summarized via multivariable logistic regression. RESULTS: Of the 131 patients included in the analysis, 35 (26.7%) lacked adequate suppression during OFS cycle 2 or later cycles. Patients with adequate suppression throughout treatment were more likely to be older (odds ratio [OR] 1.12 [95% CI, 1.05-1.22], P = .02), have a lower BMI (OR 0.88 [95% CI, 0.82-0.94], P < .001), and have received chemotherapy (OR 6.30 [95% CI, 2.06-20.8], P = .002). A total of 20 of 83 patients (24.1%) had an inadequately suppressed estradiol level within 35 days of OFS initiation. CONCLUSION: This "real world" cohort demonstrates that estradiol concentrations above the postmenopausal range of the assay are frequently detected, including more than 1 year after the start of OFS. Additional research is needed to establish estradiol monitoring guidelines and optimal degree of ovarian suppression.