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Purpose: To investigate the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of inavolisib, a potent and selective small-molecule inhibitor of p110α that promotes the degradation of mutated p110α, in combination with palbociclib and endocrine therapy (ET), in a phase I/Ib study in patients with PIK3CA -mutated, hormone receptor-positive/human epidermal growth factor receptor 2-negative locally advanced/metastatic breast cancer (ClinicalTrials.gov identifier: NCT03006172)., Methods: Women ≥18 years of age received inavolisib, palbociclib, and letrozole (Inavo + Palbo + Letro arm) or fulvestrant (Inavo + Palbo + Fulv arm) until unacceptable toxicity or disease progression. The primary objective was to evaluate safety or tolerability., Results: Fifty-three patients were included, 33 in the Inavo + Palbo + Letro arm and 20 in the Inavo + Palbo + Fulv arm. Median duration of inavolisib treatment was 15.7 and 20.8 months (cutoff: March 27, 2023), respectively. Treatment-related adverse events (TRAEs) occurred in all patients; the most frequent were stomatitis, hyperglycemia, and diarrhea; grade ≥3 any TRAE rates were 87.9% and 85.0%; 6.1% and 10.0% discontinued any treatment due to TRAEs in the Inavo + Palbo + Letro and Inavo + Palbo + Fulv arms, respectively. No PK drug-drug interactions (DDIs) were observed among the study treatments when administered. Confirmed objective response rates were 52.0% and 40.0% in patients with measurable disease, and median progression-free survival was 23.3 and 35.0 months in the Inavo + Palbo + Letro and Inavo + Palbo + Fulv arms, respectively. Available paired pre- and on-treatment tumor tissue and circulating tumor DNA analyses confirmed the effects of study treatment on pharmacodynamic and pathophysiologic biomarkers of response., Conclusion: Inavolisib plus palbociclib and ET demonstrated a manageable safety profile, lack of DDIs, and promising preliminary antitumor activity.

Purpose: Novel agents such as PI3K and mTOR inhibitors (PI3K/mTORi) have expanded treatment options in metastatic breast cancer (MBC). Nevertheless, mortality rates remain disproportionately high for Black patients and patients with lower socioeconomic status. Furthermore, clinical trials for these novel agents lacked diversity, so their toxicity profile in minority populations is uncertain., Methods: We conducted a retrospective analysis of EHR-derived data from the Flatiron Health Database for patients with HR+, HER2- MBC. Multivariable logistic regression was used to evaluate factors associated with PI3K/mTORi use and toxicity outcomes., Results: A total of 9169 patients with MBC were included in our analysis, of which 1780 (19.4%) received a PI3K/mTORi. We estimated the conditional total effect of insurance through Medicaid, and found lower odds of use of PI3K/mTORi among patients on Medicaid compared to those with commercial insurance (OR 0.73, 95% CI 0.54-0.99, p = 0.049). Odds of PI3K/mTORi use were higher for patients treated at an academic center (OR 1.28, CI 1.06-1.55, p = 0.01). Modeled as a controlled direct effect, Black/African American (Black/AA) race had no impact on odds of PI3K/mTOR use. Black/AA patients had twice the odds of developing hyperglycemia on PI3K/mTORi compared to White patients (OR 2.02, CI 1.24-3.39, p < 0.01)., Conclusion: This analysis of real-world data suggests that the use of PI3K/mTORi is influenced by socioeconomic factors. We also found racial disparities in toxicity outcomes, with Black/AA patients having twice the risk of hyperglycemia. Our findings call for greater efforts to ensure access to novel treatments and improve their tolerability in diverse populations., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating adverse effect of taxane therapy. Small non-randomized studies in patients with early-stage breast cancer (ESBC) suggest both cryotherapy and compression therapy may prevent CIPN. It is unknown which is more effective., Methods: We conducted a randomized phase IIB adaptive sequential selection trial of cryotherapy vs. compression therapy vs. placebo ("loose" gloves/socks) during taxane chemotherapy. Participants were randomized in triplets. Garments were worn for 90-120 min, beginning 15 min prior and continuing for 15 min following the infusion. The primary goal was to select the best intervention based on a Levin-Robbins-Leu sequential selection procedure. The primary endpoint was a < 5-point decrease in the Functional Assessment of Cancer Therapy Neurotoxicity (FACT-NTX) at 12 weeks. An arm was eliminated if it had four or more fewer successes than the currently leading arm. Secondary endpoints included intervention adherence and patient-reported comfort/satisfaction., Results: Between April 2019 and April 2021, 63 patients were randomized (cryotherapy (20); compression (22); placebo (21)). Most patients (60.3%) were treated with docetaxel. The stopping criterion was met after the 17th triplet (n = 51) was evaluated; success at 12 weeks occurred in 11 (64.7%) on compression therapy, 7 (41.1%) on cryotherapy, and 7 (41.1%) on placebo. Adherence to the intervention was lowest with cryotherapy (35.0%) compared to compression (72.7%) and placebo (76.2%)., Conclusion: Compression therapy was the most effective intervention in this phase IIB selection trial to prevent CIPN and was well tolerated. Compression therapy for the prevention of CIPN should be evaluated in a phase III study., Clinical Trial Registration: ClinicaTrials.gov Identifier: NCT03873272., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Elderly women diagnosed with metastatic breast cancer (MBC) are living longer, however their primary care management may be sub-optimal. Influenza results in preventable hospitalizations and deaths. Guidelines recommend the influenza vaccine for those > 65 years and those with cancer but use is unknown., Methods: A retrospective analysis was conducted using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked data. Patients were included if they were diagnosed with MBC from 1/1/2008-12/31/2017 and were ≥ 65 years of age. The primary outcome was influenza vaccine use among patients surviving ≥ 3-years. We conducted multivariable analyses using demographic and clinical factors to identify associations with vaccine use. We compared utilization to cancer-free controls., Results: We identified 1,970 patients with MBC that survived for ≥ 3 years. The median age at diagnosis was 73 years. Furthermore, 1,742 (88%) patients were White, and 153 (8%) patients were Black. Only 1,264 (64%) received an influenza vaccine at least one time and 51% received the vaccine at least two times. A multivariable model found lower odds of vaccine receipt for Black patients (OR = 0.48; 95% CI 0.34-0.68, p < 0.001) and higher odds for patients that saw primary care in the year prior to diagnosis (OR = 1.91, 95% CI 1.57-2.33, p < 0.001). Patients with MBC had lower odds of vaccine use compared to cancer free controls (OR = 0.85, 95% CI 0.74-0.97, p < 0.001)., Conclusion: Over 1/3 of long-term MBC survivors in our cohort did not receive the influenza vaccine. Black patients are about half as likely to be vaccinated. Given the known benefit of the vaccine, improving uptake could be an important strategy to improve outcomes., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Limited information is available for patients with breast cancer (BC) and coronavirus disease 2019 (COVID-19), especially among underrepresented racial/ethnic populations., Methods: This is a COVID-19 and Cancer Consortium (CCC19) registry-based retrospective cohort study of females with active or history of BC and laboratory-confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection diagnosed between March 2020 and June 2021 in the US. Primary outcome was COVID-19 severity measured on a five-level ordinal scale, including none of the following complications, hospitalization, intensive care unit admission, mechanical ventilation, and all-cause mortality. Multivariable ordinal logistic regression model identified characteristics associated with COVID-19 severity., Results: 1383 female patient records with BC and COVID-19 were included in the analysis, the median age was 61 years, and median follow-up was 90 days. Multivariable analysis revealed higher odds of COVID-19 severity for older age (aOR per decade, 1.48 [95% CI, 1.32-1.67]); Black patients (aOR 1.74; 95 CI 1.24-2.45), Asian Americans and Pacific Islander patients (aOR 3.40; 95 CI 1.70-6.79) and Other (aOR 2.97; 95 CI 1.71-5.17) racial/ethnic groups; worse ECOG performance status (ECOG PS ≥2: aOR, 7.78 [95% CI, 4.83-12.5]); pre-existing cardiovascular (aOR, 2.26 [95% CI, 1.63-3.15])/pulmonary comorbidities (aOR, 1.65 [95% CI, 1.20-2.29]); diabetes mellitus (aOR, 2.25 [95% CI, 1.66-3.04]); and active and progressing cancer (aOR, 12.5 [95% CI, 6.89-22.6]). Hispanic ethnicity, timing, and type of anti-cancer therapy modalities were not significantly associated with worse COVID-19 outcomes. The total all-cause mortality and hospitalization rate for the entire cohort was 9% and 37%, respectively however, it varied according to the BC disease status., Conclusions: Using one of the largest registries on cancer and COVID-19, we identified patient and BC-related factors associated with worse COVID-19 outcomes. After adjusting for baseline characteristics, underrepresented racial/ethnic patients experienced worse outcomes compared to non-Hispanic White patients., Funding: This study was partly supported by National Cancer Institute grant number P30 CA068485 to Tianyi Sun, Sanjay Mishra, Benjamin French, Jeremy L Warner; P30-CA046592 to Christopher R Friese; P30 CA023100 for Rana R McKay; P30-CA054174 for Pankil K Shah and Dimpy P Shah; KL2 TR002646 for Pankil Shah and the American Cancer Society and Hope Foundation for Cancer Research (MRSG-16-152-01-CCE) and P30-CA054174 for Dimpy P Shah. REDCap is developed and supported by Vanderbilt Institute for Clinical and Translational Research grant support (UL1 TR000445 from NCATS/NIH). The funding sources had no role in the writing of the manuscript or the decision to submit it for publication., Clinical Trial Number: CCC19 registry is registered on ClinicalTrials.gov, NCT04354701., Competing Interests: GN, SV, AK, TS, NK, DA, JA, JA, ZB, NB, TB, BB, SB, MB, PB, SB, BB, HB, CC, HC, JD, AD, NE, LF, DF, CF, MG, CG, PG, SG, MH, HH, DH, CH, CJ, SJ, MJ, VK, EK, NK, VK, AK, DK, CL, PL, KL, ML, XL, GL, GL, DM, AM, MM, SM, RM, IM, VM, RN, SN, RN, TN, TO, OP, KP, JP, KP, JP, HP, MP, YR, PR, SR, JR, DR, MR, SR, AR, LS, PS, MS, LS, MS, DS, MS, LT, MT, ST, LW, GW, MW, EW, SM, BF, JW, ML, MA, DS No competing interests declared

Purpose: Cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) with endocrine therapy (ET) improves progression-free survival (PFS) and overall survival (OS) in hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC). Although preclinical and clinical data demonstrate a benefit in changing ET and continuing a CDK4/6i at progression, no randomized prospective trials have evaluated this approach., Methods: In this investigator-initiated, phase II, double-blind placebo-controlled trial in patients with HR+/HER2- MBC whose cancer progressed during ET and CDK4/6i, participants switched ET (fulvestrant or exemestane) from ET used pre-random assignment and randomly assigned 1:1 to the CDK4/6i ribociclib versus placebo. PFS was the primary end point, defined as time from random assignment to disease progression or death. Assuming a median PFS of 3.8 months with placebo, we had 80% power to detect a hazard ratio (HR) of 0.58 (corresponding to a median PFS of at least 6.5 months with ribociclib) with 120 patients randomly assigned using a one-sided log-rank test and significance level set at 2.5%., Results: Of the 119 randomly assigned participants, 103 (86.5%) previously received palbociclib and 14 participants received ribociclib (11.7%). There was a statistically significant PFS improvement for patients randomly assigned to switched ET plus ribociclib (median, 5.29 months; 95% CI, 3.02 to 8.12 months) versus switched ET plus placebo (median, 2.76 months; 95% CI, 2.66 to 3.25 months) HR, 0.57 (95% CI, 0.39 to 0.85); P = .006. At 6 and 12 months, the PFS rate was 41.2% and 24.6% with ribociclib, respectively, compared with 23.9% and 7.4% with placebo., Conclusion: In this randomized trial, there was a significant PFS benefit for patients with HR+/HER2- MBC who switched ET and received ribociclib compared with placebo after previous CDK4/6i and different ET.

Background: Survival outcomes in metastatic breast cancer (MBC) have improved due to novel agents such as CDK4/6 inhibitors (CDK4/6i). Nevertheless, Black patients and patients with lower socioeconomic status (SES) continue to bear a disproportionate mortality burden., Methods: We conducted a retrospective analysis of EHR-derived data from the Flatiron Health Database (FHD). A dataset was constructed to include Black/African-American (Black/AA) and White patients with hormone receptor (HR)-positive, HER2-negative MBC. Outcomes included CDK4/6i use (overall and first-line), and rates of leukopenia, dose reduction, and time on treatment for first-line CDK4/6i. Multivariable logistic regression was used to evaluate factors associated with use and outcomes., Results: A total of 6802 patients with MBC were included, of which 5187 (76.3%) received CDK4/6i. Of those, 3186 (61.4%) received CDK4/6i first-line. Overall, 86.7% of patients were categorized as White and 13.3% as Black/AA; 22.4% were > 75 years old; 12.6% were treated at an academic site; 3.3% had Medicaid insurance. In addition to advanced age and poorer performance status, lower use of CDK4/6i was associated with Black/AA vs White race (72.9% vs 76.8%; OR 0.83, 95% CI 0.70-0.99, p = 0.04) and Medicaid vs commercial insurance (69.6% vs 77.4%; OR: 0.68, 95% CI 0.49-0.95, p = 0.02). Odds of CDK4/6i use were twofold higher for patients treated at an academic center (p < 0.001). Rates of CDK4/6i-induced leukopenia and dose reductions did not differ significantly by race, insurance type, or treatment site. Time on CDK4/6i was significantly lower among Medicaid patients (395 days) than patients with commercial insurance (558 days) or Medicare (643 days) (p = 0.03)., Conclusion: This analysis of real-world data suggests that Black race and lower SES are associated with decreased CDK4/6i use. However, among patients treated with CDK4/6i, subsequent toxicity outcomes are similar. Efforts to ensure access to these life-prolonging medications are warranted., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Sedative-hypnotic medications are used to treat chemotherapy-related nausea, anxiety, and insomnia. However, prolonged sedative-hypnotic use can lead to dependence, misuse, and increased health-care use. We aimed to estimate the rates at which patients who receive adjuvant chemotherapy for breast cancer become new persistent users of sedative-hypnotic medications, specifically benzodiazepines and nonbenzodiazepine sedative-hypnotics (Z-drugs)., Methods: Using the MarketScan health-care claims database, we identified sedative-hypnotic-naïve patients who received adjuvant chemotherapy for breast cancer. Patients who filled 1 and more prescriptions during chemotherapy and 2 and more prescriptions up to 1 year after chemotherapy were classified as new persistent users. Univariate and multivariable logistic regression analyses were used to estimate odds of new persistent use and associated characteristics., Results: We identified 22 039 benzodiazepine-naïve patients and 23 816 Z-drug-naïve patients who received adjuvant chemotherapy from 2008 to 2017. Among benzodiazepine-naïve patients, 6159 (27.9%) filled 1 and more benzodiazepine prescriptions during chemotherapy, and 963 of those (15.6%) went on to become new persistent users. Among Z-drug-naïve patients, 1769 (7.4%) filled 1 and more prescriptions during chemotherapy, and 483 (27.3%) became new persistent users. In both groups, shorter durations of chemotherapy and receipt of opioid prescriptions were associated with new persistent use. Medicaid insurance was associated with new persistent benzodiazepine use (odds ratio = 1.88, 95% confidence interval = 1.43 to 2.47) compared with commercial or Medicare insurance., Conclusions: Patients who receive sedative-hypnotic medications during adjuvant chemotherapy for breast cancer are at risk of becoming new persistent users of these medications after chemotherapy. Providers should ensure appropriate sedative-hypnotic use through tapering dosages and encouraging nonpharmacologic strategies when appropriate., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Purpose: We evaluated whether a novel, fully automated convolutional neural network (CNN)-based mammographic evaluation can predict breast cancer relapse among women with operable hormone receptor (HR)-positive breast cancer., Methods: We conducted a retrospective cohort study among women with stage I-III, HR-positive unilateral breast cancer diagnosed at Columbia University Medical Center from 2007 to 2017, who received adjuvant endocrine therapy and had at least two mammograms (baseline, annual follow-up) of the contralateral unaffected breast for CNN analysis. We extracted demographics, clinicopathologic characteristics, breast cancer treatments, and relapse status from the electronic health record. Our primary endpoint was change in CNN risk score (range, 0-1). We used two-sample t-tests to assess for difference in mean CNN scores between patients who relapsed vs. remained in remission, and conducted Cox regression analyses to assess for association between change in CNN score and breast cancer-free interval (BCFI), adjusting for known prognostic factors., Results: Among 848 women followed for a median of 59 months, there were 67 (7.9%) breast cancer relapses (36 distant, 25 local, 6 new primaries). There was a significant difference in mean absolute change in CNN risk score from baseline to 1-year follow-up between those who relapsed vs. remained in remission (0.001 vs. - 0.022, p = 0.030). After adjustment for prognostic factors, a 0.01 absolute increase in CNN score at 1-year was significantly associated with BCFI, hazard ratio = 1.05 (95% Confidence Interval 1.01-1.09, p = 0.011)., Conclusion: Short-term change in the CNN-based breast cancer risk model on adjuvant endocrine therapy predicts breast cancer relapse, and warrants further evaluation in prospective studies., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Diagnosis of LM is limited by low sensitivity of cerebrospinal fluid (CSF) cytopathology. Detecting tumor cells in CSF (CSF-TCs) might be more sensitive. We evaluated if CNSide (CNSide), a novel assay for tumor cell detection in CSF, can detect CSF-TCs better than conventional CSF cytology., Methods: We enrolled adults with metastatic breast cancer and clinical suspicion for LM to undergo lumbar puncture (LP) for CSF cytopathology and CNSide. CNSide captured CSF-TCs using a primary 10-antibody mixture, streptavidin-coated microfluidic channel, and biotinylated secondary antibodies. CSF-TCs were assessed for estrogen receptor (ER) expression by fluorescent antibody and HER2 amplification by fluorescent in situ hybridization (FISH). CSF cell-free DNA (cfDNA) was extracted for next-generation sequencing (NGS). Leptomeningeal disease was defined as positive CSF cytology and/or unequivocal MRI findings. We calculated sensitivity and specificity of CSF cytology and CNSide for the diagnosis of LM., Results: Ten patients, median age 51 years (range, 37-64), underwent diagnostic LP with CSF evaluation by cytology and CNSide. CNSide had sensitivity of 100% (95% Confidence Interval [CI], 40%-100%) and specificity of 83% (95% CI, 36%-100%) for LM. Among these patients, concordance of ER and HER2 status between CSF-TCs and metastatic biopsy were 60% and 75%, respectively. NGS of CSF cfDNA identified somatic mutations in three patients, including one with PIK3CA p.H1047L in blood and CSF., Conclusions: CNSide may be a viable platform to detect CSF-TCs, with potential use as a diagnostic tool for LM in patients with metastatic breast cancer. Additional, larger studies are warranted., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: To update recommendations of the American Society of Clinical Oncology (ASCO)-Ontario Health (Cancer Care Ontario [CCO]) adjuvant bone-modifying agents in breast cancer guideline., Methods: An Expert Panel conducted a systematic review to identify new, potentially practice-changing data., Results: Four articles met eligibility criteria and form the evidentiary basis for revision of the previous recommendations., Recommendations: Adjuvant bisphosphonate therapy should be discussed with all postmenopausal patients (natural or therapy-induced) with primary breast cancer, irrespective of hormone receptor status and human epidermal growth factor receptor 2 status, who are candidates to receive adjuvant systemic therapy. Adjuvant bisphosphonates, if used, are not substitutes for standard anticancer modalities. The benefit of adjuvant bisphosphonate therapy will vary depending on the underlying risk of recurrence and is associated with a modest improvement in overall survival. The NHS PREDICT tool provides estimates of the benefit of adjuvant bisphosphonate therapy and may aid in decision making. Factors influencing the decision to recommend adjuvant bisphosphonate use should include patients' risk of recurrence, risk of side effects, financial toxicity, drug availability, patient preferences, comorbidities, and life expectancy. When an adjuvant bisphosphonate is used to prevent breast cancer recurrence, the therapeutic options recommended by the Panel include oral clodronate, oral ibandronate, and intravenous zoledronic acid. The Panel supports starting bisphosphonate therapy early, consistent with the points outlined in the parent CCO-ASCO guideline; this is a consensus recommendation. The Panel does not recommend adjuvant denosumab to prevent breast cancer recurrence, because studies did not show a consistent reduction of breast cancer recurrence in any subset of those with early-stage breast cancer.Additional information can be found at www.asco.org/breast-cancer-guideline., Competing Interests: Andrea EisenOther Relationship: Cancer Care Ontario Melissa K. AccordinoHonoraria: Sermo (I), M3 (I), Charter Oak Research, ExpertConnect, Medscape, Deerfield Management, Incrowd, Massive BioOther Relationship: Onclive Mark J. ClemonsHonoraria: PfizerConsulting or Advisory Role: Cornerstone Research Group, ApotexTravel, Accommodations, Expenses: Pfizer Sukhbinder Dhesy-ThindHonoraria: PfizerConsulting or Advisory Role: Novartis Canada Pharmaceuticals Inc, Seattle Genetics Melissa S. DillmonStock and Other Ownership Interests: Johnson & Johnson (I), Bristol Myers Squibb (I)Consulting or Advisory Role: Puma Biotechnology Elizabeth S. FrankHonoraria: AstraZenecaTravel, Accommodations, Expenses: Roche Sigrun HallmeyerLeadership: Association of Community Cancer Centers (ACCC)Honoraria: Cardinal HealthConsulting or Advisory Role: Bristol Myers Squibb, Cardinal Health, Array PharamceuticalSpeakers' Bureau: Bristol Myers SquibbTravel, Accommodations, Expenses: Cardinal Health, Bristol Mers SquibbUncompensated Relationships: Society for Immunotherapy of Cancer Beverly MoyConsulting or Advisory Role: MOTUS (I)Research Funding: Puma Biotechnology (Inst) Alia ThawerHonoraria: Knight Pharmaceuticals, Novartis Canada Pharmaceuticals Inc, Pfizer, GlaxoSmithKline Canada, AbbVie, AstraZeneca CanadaConsulting or Advisory Role: Ipsen, Amgen, Novartis, Lilly, Sandoz-Novartis, Pfizer, EisaiResearch Funding: Novartis, AstraZeneca Joy Y. WuResearch Funding: Radius Health Catherine H. Van PoznakResearch Funding: Bayer (Inst)Patents, Royalties, Other Intellectual Property: UpToDateNo other potential conflicts of interest were reported.

Purpose: Prolonged use of controlled substances can place patients at increased risk of dependence and complications. Women who have mastectomy and reconstructive surgery (M + R) may be vulnerable to becoming new persistent users (NPUs) of opioid and sedative-hypnotic medications., Methods: Using the MarketScan health-care claims database, we identified opioid- and sedative-hypnotic-naïve women who had M + R from 2008 to 2017. Women who filled ≥ 1 peri-operative prescription and ≥ 2 post-operative prescriptions within one year after surgery were classified as NPUs. Univariate and multivariable logistic regression analyses were used to estimate rates of new persistent use and predictive factors. Risk summary scores were created based on the sum of associated factors., Results: We evaluated 23,025 opioid-naïve women and 25,046 sedative-hypnotic-naïve women. We found that 17,174 opioid-naïve women filled a peri-operative opioid prescription, and of those, 2962 (17.2%) became opioid NPUs post-operatively. Additionally, 9426 sedative-hypnotic-naïve women filled a peri-operative sedative-hypnotic prescription, and of those, 1612 (17.1%) became sedative-hypnotic NPUs. Development of new persistent sedative-hypnotic use was associated with age ≤ 49 [OR 1.77 (95% CI 1.40-2.24)] and age 50-64 [1.60 (1.27-2.03)] compared to age ≥ 65; Medicaid insurance [2.34 (1.40-3.90)]; southern residence [1.42 (1.22-1.64)]; breast cancer diagnosis [2.24 (1.28-3.91)]; and chemotherapy [2.17 (1.94-2.42)]. Risk of NPU increased with higher risk score. Women with ≥ 3 of these risk factors were three times more likely to become sedative-hypnotic NPUs than patients with 0 or 1 factors [2.94 (2.51-3.43)]. Comparable findings were seen regarding new persistent opioid use., Conclusion: Women who have M + R are at risk of developing both new persistent opioid and new persistent sedative-hypnotic use. A patient's risk of becoming an NPU increases as their number of risk factors increases. Non-pharmacologic strategies are needed to manage pain and anxiety following cancer-related surgery., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Diffuse optical tomography breast imaging system (DOTBIS) non-invasively measures tissue concentration of hemoglobin, which is a potential biomarker of short-term response to neoadjuvant chemotherapy. We evaluated whether DOTBIS-derived measurements are modifiable with targeted therapies, including AKT inhibition and endocrine therapy., Methods: We conducted a proof of principle study in seven postmenopausal women with stage I-III breast cancer who were enrolled in pre-surgical studies of the AKT inhibitor MK-2206 (n = 4) or the aromatase inhibitors exemestane (n = 2) and letrozole (n = 1). We performed DOTBIS at baseline (before initiation of therapy) and post-therapy in the affected breast (tumor volume) and contralateral, unaffected breast, and measured tissue concentrations (in μM) of total hemoglobin (ctTHb), oxyhemoglobin (ctO 2 Hb), and deoxyhemoglobin (ctHHb), as well as water fraction (%)., Results: We found consistent decreases in DOTBIS-measured hemoglobin concentrations in tumor volume, with median percent changes for ctTHb, ctHHb, ctO 2 Hb, and water fraction for the entire cohort of - 27.1% (interquartile range [IQR] 37.5%), - 49.8% (IQR 29.3%), - 33.5% (IQR 47.4%), and - 3.6% (IQR 10.6%), respectively. In the contralateral breast, median percent changes for ctTHb, ctHHb, ctO 2 Hb, and water fraction were + 1.8% (IQR 26.7%), - 8.6% (IQR 29.3%), + 6.2% (IQR 29.5%), and + 1.9% (IQR 30.7%), respectively., Conclusion: We demonstrated that DOTBIS-derived measurements are modifiable with pre-surgical AKT inhibition and endocrine therapy, supporting further investigation of DOTBIS as a potential imaging assessment of response to neoadjuvant targeted therapies in early stage breast cancer., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: COVID-19 has altered healthcare delivery. Previous work has focused on patients with cancer and COVID-19, but little has been reported on healthcare system changes among patients without COVID-19., Methods: We performed a retrospective study of patients with breast cancer (BC) in New York City between February 1, 2020, and April 30, 2020. New patients were included as were patients scheduled to receive intravenous or injectable therapy. Patients with COVID-19 were excluded. Demographic and treatment information were obtained by chart review. Delays and/or changes in systemic therapy, surgery, radiation, and radiology related to the pandemic were tracked, along with the reasons for delay and/or change. Univariate and multivariable analysis were used to identify factors associated with delay and/or change., Results: We identified 350 eligible patients, of whom 149 (42.6%) experienced a delay and/or change, and practice reduction (51.0%) was the most common reason. The patients who identified as Black or African American, Asian, or Other races were more likely to experience a delay and/or change compared with White patients (Black, 44.4%; Asian, 47.1%; Other, 55.6%; White, 31.4%; P = .001). In multivariable analysis, Medicaid compared with commercial insurance (odds ratio [OR], 3.04; 95% CI, 1.32 to 7.27) was associated with increased odds of a delay and/or change, whereas stage II or III BC compared with stage I (OR, 0.38; 95% CI, 0.15 to 0.95; and OR, 0.28; 95% CI, 0.08 to 0.092, respectively) was associated with decreased odds of a delay and/or change., Conclusion: Almost half of the patients with BC without COVID-19 had a delay and/or change. We found racial and socioeconomic disparities in the likelihood of a delay and/or change. Further studies are needed to determine the impact these care alterations have on BC outcomes., Competing Interests: Jason D. WrightConsulting or Advisory Role: Clovis OncologyResearch Funding: MerckPatents, Royalties, Other Intellectual Property: UpToDate Grace A. HillyerResearch Funding: Genentech Kevin KalinskyStock and Other Ownership Interests: Array BioPharma, Pfizer, GRAILConsulting or Advisory Role: bioTheranostics, Lilly, pfizer, Novartis, Eisai, AstraZeneca, Genentech/Roche, Immunomedics, Ipsen, Merck, Seattle GeneticsSpeakers' Bureau: LillyResearch Funding: Incyte, Novartis, Genentech/Roche, Lilly, Pfizer, Calithera Biosciences, Immunomedics, Acetylon Pharmaceuticals, Seattle Genetics, Amgen, Zeno Pharmaceuticals, CytomX TherapeuticsTravel, Accommodations, Expenses: Lilly, AstraZeneca, PfizerOther Relationship: Immunomedics, Genentech Dawn L. HershmanConsulting or Advisory Role: AIM Specialty Health Melissa K. AccordinoHonoraria: Sermo, M3, Charter Oak Research, ExpertConnect, MDoutlook, Medscape, Medscape, M3, Medsurvey, Deerfield Management, OCN, Enterprise Analysis Corporation, Medpanel, Incrowd, Massive BioResearch Funding: TrioOther Relationship: OncliveNo other potential conflicts of interest were reported.

Purpose: This study's primary objective was to evaluate the changes in optically derived parameters acquired with a diffuse optical tomography breast imaging system (DOTBIS) in the tumor volume of patients with breast carcinoma receiving neoadjuvant chemotherapy (NAC)., Experimental Design: In this analysis of 105 patients with stage II-III breast cancer, normalized mean values of total hemoglobin ([Formula: see text]), oxyhemoglobin ([Formula: see text]), deoxy-hemoglobin concentration ([Formula: see text]), water, and oxygen saturation ([Formula: see text]) percentages were collected at different timepoints during NAC and compared with baseline measurements. This report compared changes in these optical biomarkers measured in patients who did not achieve a pathologic complete response (non-pCR) and those with a pCR. Differences regarding molecular subtypes were included for hormone receptor-positive and HER2-negative, HER2-positive, and triple-negative breast cancer., Results: At baseline, [Formula: see text] was higher for pCR tumors (3.97 ± 2.29) compared with non-pCR tumors (3.00 ± 1.72; P = 0.031). At the earliest imaging point after starting therapy, the mean change of [Formula: see text] compared with baseline ([Formula: see text]) was statistically significantly higher in non-pCR (1.23 ± 0.67) than in those with a pCR (0.87 ± 0.61; P < 0.0005), and significantly correlated to residual cancer burden classification ( r = 0.448; P < 0.0005). [Formula: see text] combined with HER2 status was proposed as a two-predictor logistic model, with AUC = 0.891; P < 0.0005; and 95% confidence interval, 0.812-0.969., Conclusions: This study demonstrates that DOTBIS measured features change over time according to tumor pCR status and may predict early in the NAC treatment course whether a patient is responding to NAC., (©2021 American Association for Cancer Research.)

Background: The purpose of this study is to evaluate whether the changes in optically derived parameters acquired with a diffuse optical tomography breast imager system (DOTBIS) in the contralateral non-tumor-bearing breast in patients administered neoadjuvant chemotherapy (NAC) for breast cancer are associated with pathologic complete response (pCR)., Methods: In this retrospective evaluation of 105 patients with stage II-III breast cancer, oxy-hemoglobin (ctO 2 Hb) from the contralateral non-tumor-bearing breast was collected and analyzed at different time points during NAC. The earliest monitoring imaging time point was after 2-3 weeks receiving taxane. Longitudinal data were analyzed using linear mixed-effects modeling to evaluate the contralateral breast ctO 2 Hb changes across chemotherapy when corrected for pCR status, age, and BMI., Results: Patients who achieved pCR to NAC had an overall decrease of 3.88 μM for ctO 2 Hb (95% CI, 1.39 to 6.37 μM), p = .004, after 2-3 weeks. On the other hand, non-pCR subjects had a non-significant mean reduction of 0.14 μM (95% CI, - 1.30 to 1.58 μM), p > .05. Mixed-effect model results indicated a statistically significant negative relationship of ctO 2 Hb levels with BMI and age., Conclusions: This study demonstrates that the contralateral normal breast tissue assessed by DOTBIS is modifiable after NAC, with changes associated with pCR after only 2-3 weeks of chemotherapy.

Purpose: The incidence and predictors of diabetes (DM) in patients with breast cancer (BC) were evaluated. We compared DM incidence and physician access in BC patients to matched controls., Methods: We identified women with stage I-III BC diagnosed from 2005 to 2013 in the SEER-Medicare database, with ≥ 2 years of follow-up after diagnosis, without previous DM claims. Incident DM was determined by ≥ 1 DM claims after BC diagnosis. Multivariable analysis was used to identify factors associated with incident DM. Age- and race-matched non-cancer controls were obtained from a 5% random sample and assigned an index date. Physician and PCP visits per-patient-per-year were compared between cases and controls in the two-year period prior to and after the index date., Results: Among 14,506 eligible BC patients, 3234 (22.3%) developed DM versus 16.5% of controls. Among BC patients, factors associated with incident DM included race (Black OR 1.63 95% CI 1.39-1.93, Hispanic OR 3.03 95% CI 1.92-4.81; vs. Caucasians), SES (Quintile 0 vs. Quintile 4 OR 1.55 95% CI 1.33-1.78), and receipt of chemotherapy (vs. none OR 1.19 95% CI 1.08-1.31). Among cases and controls, respectively, median physician visits per-patient-per-year were 19 and 17 prior to the index date, and 46 and 19 after the index date; median PCP visits were 2 for both groups in both periods., Conclusion: About 22% of BC patients developed DM, more than controls in the same period. While there were differences in healthcare access, there weren't differences in PCP access between groups. This represents an opportunity for better comorbidity management in BC patients.

Background: Cardiovascular disease (CVD) is the leading cause of death among patients with early-stage breast cancer (BC), but adherence to cardiovascular disease risk factor (CVD-RF) medications is reported to be poor in BC survivors. The objective of the current study was to determine the association between nonadherence to CVD-RF medications and cardiovascular events in BC survivors., Methods: The authors included patients with stages I to III BC from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database who had Medicare part D coverage and who were taking at least 1 CVD-RF medication prior to their BC diagnosis (2008-2013). Logistic regression was performed to define factors associated with nonadherence. Cox regression was used to calculate the association between nonadherence and new cardiac events after treatment., Results: Among 15,576 patients included in the current analysis, 4797 (30.8%) were nonadherent to at least 1 category after the initial BC treatment period. Black race, greater comorbidity burden, more advanced cancer stage, hormone receptor-negative status, and receipt of chemotherapy were found to be associated with nonadherence. Nonadherence after treatment demonstrated a trend toward an increased risk of a subsequent cardiac event (hazard ratio [HR], 1.15; 95% CI 1.00-1.33 [P = .06]). This effect size increased with nonadherence to a greater number of medications (P < .01). There was an increased risk of experiencing a cardiac event noted with becoming nonadherent to hypertension medications (HR, 1.33; 95% CI, 1.18-1.51 [P < .0001]), hyperlipidemia medications (HR, 1.21; 95% CI, 1.05-1.40 [P = .009]), and diabetes medications (HR, 1.31; 95% CI, 1.10-1.56 [P = .003])., Conclusions: Nonadherence to CVD-RF medications after treatment of BC is associated with an increased risk of a cardiac event. Improving outcomes and reducing morbidity after a diagnosis of BC requires attention to non-BC conditions., (© 2020 American Cancer Society.)

Purpose: Multidisciplinary care (MDC) encourages multiple specialists to formulate a unified treatment plan. We sought to determine the frequency and predictors of MDC and assess the association between MDC and nationally-recognized quality metrics in patients with breast cancer. Methods: We used the surveillance, epidemiology, and end results-medicare dataset to evaluate patients diagnosed with stages I-III breast cancer who underwent breast-conserving surgery between 2002 and 2011 with follow-up to 2012. We defined MDC as a visit claim from a surgeon, radiation oncologist and medical oncologist within 12 months of diagnosis. We used multivariable regression analysis to determine the association between demographic and clinical variables and MDC, and to assess the association between MDC and three nationally-recognized quality indicators (adjuvant hormone therapy for hormone receptor-positive tumors, chemotherapy for hormone receptor-negative cancer, and radiation after lumpectomy). Results: Of the 61,039 patients in our initial cohort, 53,849 (88.2%) saw a medical oncologist, 46,521 (76.2%) saw a radiation oncologist, and 43,280 (70.9%) were evaluated by all three providers the first year after diagnosis. MDC use was higher in patients with the highest socioeconomic status compared with the lowest [odds ratio (OR) 1.74, 95% CI 1.63-1.86], in patients diagnosed in later years, and those with stage III disease compared to stage I [OR 1.29, 95% CI 1.19-1.41]. Patients older in age (≥80 vs. 65-69 years, OR 0.33, 95% CI 0.31-0.34), patients with more comorbidities, those who lived in a rural setting compared to urban (OR 0.61, 95% CI 0.57-0.64), and unmarried patients (OR 0.79, 95% CI 0.76-0.82) were less likely to see all three providers. In a multivariable analysis, MDC use was associated with increased likelihood of meeting each quality metric. Conclusion: Early stage breast cancer patients were evaluated by a surgeon, radiation oncologist and medical oncologist less than 75% of the time. Enhanced coordination of care and navigation programs may improve the quality of care delivered.

Purpose: Follow-up guidelines vary widely among national organizations for patients with early-stage breast cancer treated with curative intent. We sought to evaluate the patterns and predictors of provider follow-up care within the first 5 years after diagnosis., Methods: Using the SEER-Medicare linked data set, we evaluated patients who were diagnosed with stage I and II breast cancer who underwent breast-conserving surgery from 2002 to 2007 with follow-up until 2012. We defined discontinuation of follow-up as > 12 months from the previous physician visit without a visit claim from either a surgeon, medical oncologist, or radiation oncologist. We performed a multivariable logistic regression and Cox proportional hazards regression analysis to determine factors associated with the discontinuation of follow-up care., Results: Of the 30,053 patients enrolled in our initial cohort, 25,781 (85.8%) saw a medical oncologist and 21,612 (71.9%) saw a radiation oncologist in the first year in addition to a surgeon. Over the 5 years, 6,302 patients (21.0%) discontinued follow-up visits. Discontinuation of physician visits increased with increasing age. Women with stage II cancer ( v stage I) were less likely to discontinue follow-up visits (odds ratio, 0.78; 95% CI, 0.73 to 0.83). Time to early discontinuation was greater for patients with hormone receptor-negative tumors (hazard ratio, 1.14; 95% CI, 1.05 to 1.24). Women who were diagnosed more recently were less likely to discontinue seeing any physician., Conclusion: Twenty-one percent of patients with early-stage breast cancer discontinued seeing any oncology provider over the 5 years after diagnosis. Coordination of follow-up care between oncology specialists may reduce discontinuation rates and increase clinical efficiency.

Purpose: For women with stage IV breast cancer (BC), the association between survival time (ST) and use of aggressive end-of-life (EOL) care is unknown., Methods: We used the SEER-Medicare database to identify women with stage IV BC diagnosed 2002-2011 who died by 12/31/2012. Aggressive EOL care was defined as receipt in the last month of life: >1 ED visit, >1 hospitalization, ICU admission, life-extending procedures, hospice admission within 3 days of death, IV chemotherapy within 14 days of death, and/or ≥10 unique physician encounters in the last 6 months of life. Receipt of aggressive EOL care and hospice in the last month of life were determined using claims, and multivariable analysis was used to identify factors associated with receipt. Costs of care were also evaluated., Results: We identified 4521 eligible patients. Of these, 2748 (60.8%) received aggressive EOL care. Factors associated with aggressive EOL care were race (OR 1.45, 95% CI 1.19-1.81 for blacks compared to whites) and more frequent oncology office visits (OR 1.56, 95% CI 1.28-1.90). Patients who lived >12 months after diagnosis were less likely to receive aggressive EOL care (OR 0.44, 95% CI 0.38-0.52), and more likely to utilize hospice (OR 1.43, 95% CI 1.21-1.69) compared to patients who lived ≤6 months. Patients with a shorter ST had significantly higher costs of care per-month-alive compared to patients with longer ST., Conclusion: Patients with a shorter ST were more likely to receive aggressive EOL care and had higher costs of care compared to patients who lived longer.

Purpose: The optimal frequency of monitoring patients with metastatic breast cancer (MBC) is unknown; however, data suggest that intensive monitoring does not improve outcomes. We performed a population-based analysis to evaluate patterns and predictors of extreme use of disease-monitoring tests (serum tumor markers [STMs] and radiographic imaging) among women with MBC., Methods: The SEER-Medicare database was used to identify women with MBC diagnosed from 2002 to 2011 who underwent disease monitoring. Billing dates of STMs (carcinoembryonic antigen and/or cancer antigen 15-3/cancer antigen 27.29) and imaging tests (computed tomography and/or positron emission tomography) were recorded; if more than one STM or imaging test were completed on the same day, they were counted once. We defined extreme use as > 12 STM and/or more than four radiographic imaging tests in a 12-month period. Multivariable analysis was used to identify factors associated with extreme use. In extreme users, total health care costs and end-of-life health care utilization were compared with the rest of the study population., Results: We identified 2,460 eligible patients. Of these, 924 (37.6%) were extreme users of disease-monitoring tests. Factors significantly associated with extreme use were hormone receptor-negative MBC (odds ratio [OR], 1.63; 95% CI, 1.27 to 2.08), history of a positron emission tomography scan (OR, 2.92; 95% CI, 2.40 to 3.55), and more frequent oncology office visits (OR, 3.14; 95% CI, 2.49 to 3.96). Medical costs per year were 59.2% higher in extreme users. Extreme users were more likely to use emergency department and hospice services at the end of life., Conclusion: Despite an unknown clinical benefit, approximately one third of elderly women with MBC were extreme users of disease-monitoring tests. Higher use of disease-monitoring tests was associated with higher total health care costs. Efforts to understand the optimal frequency of monitoring are needed to inform clinical practice., Competing Interests: Authors’ disclosures of potential conflicts of interest are found in the article online at www.jco.org. Author contributions are found at the end of this article., (© 2016 by American Society of Clinical Oncology.)