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Competing Interests: Disclosure: Kelly K. Hunt reports the following: Medical Advisory Board of ArmadaHealth and AstraZenece; research funding to MD Anderson Cancer Center–Cairn Surgical, Eli Lilly & Co., and Lumicell. MC-M; consultant for the following companies: Astra Zeneca, Exact Sciences, Roche/Genentech, and Daiichi-Sankyo; and member of data safety monitoring committees for Roche/Genentech and Astra Zeneca.

Background: HER2-positive breast cancer is traditionally treated with neoadjuvant systemic therapy (NST), but optimal treatment sequencing is less clear in patients with small tumors. We investigated clinicopathologic and oncologic outcomes in early stage HER2-positive breast cancer., Patients and Methods: An institutional database was queried to identify patients with cT1-2 (≤ 3 cm) N0M0, HER2-positive breast cancer treated from 2015 to 2020 and compared upfront surgery and NST cohorts. Logistic regression was performed to identify factors predicting upstaging. Survival outcomes by group were compared using log-rank tests., Results: Of 256 patients identified, 170 (66.4%) received upfront surgery and 86 (33.6%) NST. The NST cohort was younger and had more cT2 and grade 3 tumors and negative sentinel nodes. There was no significant difference in type of breast surgery or receipt of axillary lymphadenectomy. After upfront surgery, 4 (2.4%) patients had upstaging to pT > 3 cm and 18 (10.6%) to pN1-3. No factors predicted upstaging. After NST, 47 (54.7%) achieved pathologic complete response and 3 (3.5%) had upstaging to ypN1-3 with older age (OR 1.08, p = 0.004) and hormone receptor-positive status (OR 7.07, p = 0.002) identified as predictors. At median follow-up of 3.55 years, 10 (3.9%) patients had recurrence and 5 (2.0%) patients died. There were no significant differences in oncologic outcomes between groups., Conclusions: Patients with cT1-2 (≤ 3 cm)N0 HER2-positive breast cancer selected for NST have higher-risk disease. Low rates of pathologic upstaging were observed with no difference in surgical treatments and overall excellent oncologic outcomes in both groups. These findings may guide decision-making regarding treatment sequencing for patients with early stage HER2-positive disease., (© 2024. Society of Surgical Oncology.)

Aim: To evaluate the impact of palbociclib treatment on health-related quality of life (HRQoL) in patients with hormone receptor-positive, human epidermal growth factor 2-negative advanced breast cancer (HR+/HER2- aBC) or metastatic breast cancer (mBC) in both the clinical and real-world setting. Materials & methods: A systematic literature review was conducted to identify clinical trials and real-world evidence studies up to June 2023 that reported HRQoL outcomes in patients with HR+/HER2- aBC or mBC treated with Palbociclib. Results: 15 unique studies reported across 35 records were identified. Of these, seven were randomized controlled trials (RCTs), three were single-arm clinical trials and five were real-world evidence (RWE) studies. HRQoL was generally found to be maintained in patients with HR+/HER2- aBC or mBC across RCTs, single-arm clinical trials and RWE studies. HRQoL measures across instruments, study types and line of therapy, were largely reported to be at least maintained if not improved from baseline among patients treated with palbociclib and were observed to be comparable or better in the palbociclib group versus monotherapy control arm in RCTs. Similar results were seen for treatment-related outcomes (e.g., sexual functioning, upset by hair loss, systemic therapy side effects etc.), and important individual patient outcomes, including pain, fatigue and physical functioning. Findings were also consistent across key clinical characteristics (visceral metastases, neutropenia), as well as patient populations often underrepresented in clinical trials (Asian patients, older adults). Conclusion: Overall, current evidence suggests that HRQoL is largely preserved with the addition of palbociclib to endocrine therapy in patients with HR+/HER2- aBC or mBC across study types and populations.

Background: Despite lower chemotherapy use in older triple-negative breast cancer (TNBC) patients, their outcomes match younger counterparts. We compared outcomes in early-stage TNBC patients by age receiving chemotherapy at a major cancer center with a national TNBC database., Methods: Retrospective study using institutional data on stage I-III TNBC (ER/PR < 10%) women with neoadjuvant/adjuvant chemotherapy. Based on their ages at diagnosis, patients were stratified into four categories: ≤40, 41-59, 60-69, and ≥ 70 years. Demographic and clinical characteristics recorded included race, disease stage, ER/PR positivity, treatment regimen, lymphatic or vascular invasion (LVI), histologic grade, Ki-67 level, body mass index (BMI), and pathologic complete response (pCR) following neoadjuvant treatment and are summarized using descriptive statistics. The primary endpoints were overall survival (OS), disease-free survival (DFS), and distant disease-free survival (DDFS); all were estimated using the Kaplan-Meier method. Both univariate and multivariate (MV) Cox regressions were applied to evaluate the impact of important covariates on these time-to-event endpoints., Results: Of the 2336 patients studied, 492 (21.1%) were ≤ 40 years old, 1239 (53.1%) were 41-59, 461 (19.7%) were 60-69, and 144 (6.2%) were ≥ 70. In the univariate regression model of OS/DFS/DDFS, age ≥ 70 was significantly associated with worse OS (p = 0.0217); other factors associated with worse OS were non-anthracycline-based chemotherapy, higher tumor stage, and neoadjuvant chemotherapy. The multivariate Cox regression model, adjusted for race and stage, showed no significant effects of age on OS; however, patients ≥ 70 years old who received non-anthracycline treatment combinations had worse DFS (hazard ratio = 0.349 vs. 1.049, p = 0.0293) and DDFS (hazard ratio = 0.317 vs. 1.016, p = 0.0251) than patients ≤ 40 years old. DFS from MV model after adjusting for age, race, and disease stage, the hazard ratio between anthracycline + taxane treatments and anthracycline + other treatments in patients ≥ 70 years old was statistically significantly lower than in patients ≤ 40 years old (hazard ratios [HRs] = 0.349 vs. 1.049, p = 0.0293)., Conclusions: Our findings indicate that outcomes such as DFS are less favorable in older compared to younger patients with early-stage TNBC, primarily in those who did not receive an anthracycline based chemotherapy regimen., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) is the most frequently diagnosed metastatic breast cancer (mBC) subtype. Combinations of endocrine therapy (ET) with cyclin-dependent kinase 4/6 inhibitors (CDK4 & 6is) improve outcomes compared with ET alone. The efficacy and safety of abemaciclib among patients with HR+/HER2- mBC has been demonstrated in the MONARCH clinical trials; however, there is a paucity of real-world evidence, particularly in older patients., Methods and Materials: This retrospective cohort study analyzed the electronic medical record data/charts of adult patients with HR+/HER2- mBC receiving abemaciclib in US-based community oncology settings (1 September 2017 to 30 September 2019). Patients with other primary malignancies, clinical trial enrollment, and incomplete charts were excluded. Patient characteristics, treatment attributes and patterns, and real-world outcomes (clinical benefit rate [CBR] and stable disease among patients with response data available, time to chemotherapy [TTC], time to treatment discontinuation [TTD], and progression-free survival [PFS]) were summarized. Multivariable models evaluated the association between demographic/clinical characteristics and outcomes., Results: Of the 448 final patients, 99% were female, with a median age of 67 years (25% were ≥ 75 years) and median follow-up of 11 months; most (60%) initiated abemaciclib within 2 years of mBC diagnosis. Patients received a median of 1 (P25 = 0, P75 = 3) prior line of therapy for mBC before abemaciclib, including other CDK4 & 6is (48%) and prior chemotherapy (31%); most (57%) had visceral disease. The CBR for the overall population was 53%, with 48% achieving stable disease. The median TTC was not reached; median TTD was 249 days (95% confidence interval [CI]: 202, 304). The median PFS was 329 days (95% CI 266, 386). The discontinuation rate of abemaciclib owing to adverse events (30%) trended higher with age (years) (P = 0.027): 18-49 (n = 42; 19%), 50-64 (n = 155; 25%), 65-74 (n = 138; 32%), 75-84 (n = 82; 37%), ≥ 85 (n = 31; 49%); only 23% of patients overall had a dose hold or reduction prior to discontinuation., Conclusions: These patients were older than those in the MONARCH studies with substantial visceral disease, and prior chemotherapy and CDK4 & 6i use. Discontinuation rates were higher than in previous real-world studies (11.9%), highlighting the need for proactive management to optimize outcomes, particularly in older patients with mBC., (© 2023. The Author(s).)

Purpose: Neoadjuvant anti-PD-(L)1 therapy improves the pathological complete response (pCR) rate in unselected triple-negative breast cancer (TNBC). Given the potential for long-term morbidity from immune-related adverse events (irAEs), optimizing the risk-benefit ratio for these agents in the curative neoadjuvant setting is important. Suboptimal clinical response to initial neoadjuvant therapy (NAT) is associated with low rates of pCR (2-5%) and may define a patient selection strategy for neoadjuvant immune checkpoint blockade. We conducted a single-arm phase II study of atezolizumab and nab-paclitaxel as the second phase of NAT in patients with doxorubicin and cyclophosphamide (AC)-resistant TNBC (NCT02530489)., Methods: Patients with stage I-III, AC-resistant TNBC, defined as disease progression or a < 80% reduction in tumor volume after 4 cycles of AC, were eligible. Patients received atezolizumab (1200 mg IV, Q3weeks × 4) and nab-paclitaxel (100 mg/m 2 IV,Q1 week × 12) as the second phase of NAT before undergoing surgery followed by adjuvant atezolizumab (1200 mg IV, Q3 weeks, × 4). A two-stage Gehan-type design was employed to detect an improvement in pCR/residual cancer burden class I (RCB-I) rate from 5 to 20%., Results: From 2/15/2016 through 1/29/2021, 37 patients with AC-resistant TNBC were enrolled. The pCR/RCB-I rate was 46%. No new safety signals were observed. Seven patients (19%) discontinued atezolizumab due to irAEs., Conclusion: This study met its primary endpoint, demonstrating a promising signal of activity in this high-risk population (pCR/RCB-I = 46% vs 5% in historical controls), suggesting that a response-adapted approach to the utilization of neoadjuvant immunotherapy should be considered for further evaluation in a randomized clinical trial., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Breast cancer in males constitutes approximately 1% of all breast cancer cases globally. Despite extensive treatment experience with abemaciclib in women with metastatic breast cancer (MBC), real-world evidence in male MBC is lacking., Methods: This analysis was a part of a broader, retrospective study that analyzed electronic medical records and charts of 448 men and women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) MBC who initiated an abemaciclib-containing regimen from January 2017 through September 2019. Data were collected from the Florida Cancer Specialists & Research Institute and the Electronic Medical Office Logistics Health Oncology Warehouse Language™ databases and summarized descriptively. Real-world best response was described: complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD)., Results: Data for six male patients with MBC who were treated with abemaciclib in combination with an aromatase inhibitor (AI) or fulvestrant are presented. Four patients were aged ≥ 75 years, and four patients had ≥ 3 metastatic sites, including visceral involvement. Abemaciclib was initiated in/after third-line (≥ 3L) in four patients, and patients had history of treatment with AI (n = 4), chemotherapy (n = 3), and/or prior cyclin-dependent kinase 4 and 6 inhibitors (n = 2) in the metastatic setting. Abemaciclib + fulvestrant was the most common abemaciclib-containing regimen (n = 4). Best response was documented in four patients: 1 each with CR, PR, SD, and PD., Conclusion: Prevalence of male MBC in this dataset was consistent with expected prevalence in the broader population. Most male patients received an abemaciclib-containing regimen in ≥ 3L, with anti-cancer activity observed despite heavy metastatic burden and prior treatments in a metastatic setting., (© 2023. The Author(s).)

Objective: In the PALOMA-2 trial, palbociclib in combination with letrozole prolonged progression-free survival (PFS) and exhibited an acceptable safety profile in patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer (ABC). This post hoc analysis of PALOMA-2 evaluated the efficacy and safety of palbociclib plus letrozole in patients with preexisting conditions grouped by Medical Dictionary for Regulatory Activities (MedDRA) System Organ Class (SOC)., Methods: Postmenopausal patients without prior treatment for ABC were randomized 2:1 to receive palbociclib (125 mg/d on a 3 weeks on/1 week off schedule) plus letrozole (2.5 mg/d, continuous) or placebo plus letrozole. Patients were grouped by the following MedDRA SOC preexisting conditions: gastrointestinal, musculoskeletal, metabolic, and vascular/cardiac. Median PFS was estimated by the Kaplan-Meier method, and treatment emergent adverse events (AEs) were compared between treatment arms within each preexisting condition subgroup., Results: At baseline, 276 (41.4 %) patients had preexisting gastrointestinal disorders, 390 (58.6 %) had musculoskeletal disorders, 259 (38.9 %) had metabolic disorders, and 382 (57.4 %) had vascular/cardiac disorders. Baseline characteristics were similar between subgroups and between each arm within subgroups. Regardless of baseline preexisting condition, palbociclib plus letrozole prolonged PFS compared with placebo plus letrozole. Treatment-emergent AEs associated with palbociclib plus letrozole and dose modifications due to AEs were similar across preexisting condition subgroups., Conclusion: This post hoc analysis of PALOMA-2 demonstrated a favorable effect of palbociclib on PFS and a safety profile consistent with previous observations, regardless of underlying preexisting condition. Pfizer Inc (NCT01740427)., Competing Interests: Declaration of competing interest K Gelmon has received consulting/advisory fees from Pfizer Inc, Novartis, AstraZeneca, NanoString Technologies, and Merck. JM Walshe has received consulting/advisory fees and fees for non-CME services from Roche, Genomic Health, and Pfizer Inc. R Mahtani has received research funding from Agendia, Amgen, AstraZeneca, Biotheranostics, Daiichi, Eisai, Genentech, Immunomedics, Lilly, Merck, Novartis, Pfizer, Puma, Sanofi, and SeaGen. AA Joy has received consulting/advisory fees from Mylan, Teva, Purdue, BMX, BI, Genomic Health, PUMA, Pfizer Inc, Roche, AstraZeneca, Novartis, and Lilly. M Karuturi has received consulting/advisory fees from Pfizer Inc. DR Lu, S Kim, P Schnell, and E Bananis are employees of and own stock in Pfizer Inc., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Standard-of-care treatment for metastatic hormone receptor-positive (HR + ), HER2-negative (HER2 - ) breast cancer includes endocrine therapy (ET) combined with a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i). Optimal treatment after progression on CDK4/6i is unknown. The TRINITI-1 trial investigated ribociclib, a CDK4/6i that has recently demonstrated significant overall survival benefit in two phase III trials, in combination with everolimus and exemestane in patients with HR + , HER2 - advanced breast cancer (ABC) after progression on a CDK4/6i., Patients and Methods: This multicenter, open-label, single-arm, phase I/II study included patients with locally advanced/metastatic HR + /HER2 - breast cancer. The primary endpoint was clinical benefit rate (CBR) at week 24 among patients with ET-refractory disease with progression on a CDK4/6i. Other endpoints included safety and biomarker analysis., Results: Of 104 patients enrolled (phases I and II), 96 had prior CDK4/6i. Recommended phase II doses (all once daily days 1-28 of 28-day cycle) were ribociclib 300 mg, everolimus 2.5 mg, and exemestane 25 mg (group 1) and ribociclib 200 mg, everolimus 5 mg, and exemestane 25 mg (group 2). CBR among 95 efficacy-evaluable patients (phases I and II) at week 24 was 41.1% (95% confidence interval, 31.1-51.6), which met the primary endpoint (predetermined threshold: 10%). Common adverse events included neutropenia (69.2%) and stomatitis (40.4%). No new safety signals were observed; no grade 3/4 QTc prolongation was reported., Conclusions: Preliminary TRINITI-1 safety and efficacy results support further investigation of CDK4/6 blockade and targeting of the PI3K/AKT/mTOR signaling pathway in patients with ET-refractory HR + /HER2 - ABC after progression on a CDK4/6i., (©2021 American Association for Cancer Research.)

Purpose: This phase I study (RAD1901-005; NCT02338349) evaluated elacestrant, an investigational oral selective estrogen receptor degrader (SERD), in heavily pretreated women with estrogen receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer, including those with estrogen receptor gene alpha ( ESR1 ) mutation. The primary objective was to determine the maximum tolerated dose and/or recommended phase II dose (RP2D)., Methods: The study consisted of a 3 + 3 design (elacestrant capsules) followed by expansion at RP2D (400-mg capsules, then 400-mg tablets) for the evaluation of safety and antitumor activity. Elacestrant was taken once daily until progression or intolerability., Results: Of 57 postmenopausal women enrolled, 50 received RP2D (400 mg once daily): median age, 63 years; median three prior anticancer therapies, including cyclin-dependent kinase 4,6 inhibitors (CDK4/6i; 52%), SERD (52%), and ESR1 mutation (circulating tumor DNA; 50%). No dose-limiting toxicities occurred; the most common adverse events at RP2D (400-mg tablet; n = 24) were nausea (33.3%) and increased blood triglycerides and decreased blood phosphorus (25.0% each). Most adverse events were grade 1-2 in severity. The objective response rate was 19.4% (n = 31 evaluable patients receiving RP2D), 15.0% in patients with prior SERD, 16.7% in patients with prior CDK4/6i, and 33.3% in patients with ESR1 mutation (n = 5/15). The clinical benefit rate (24-week) was 42.6% overall (n = 47 patients receiving RP2D), 56.5% (n = 23, ESR1 mutation), and 30.4% (n = 23, prior CDK4/6i). Elacestrant clinical benefit was associated with decline in ESR1 mutant allele fraction., Conclusion: Elacestrant 400 mg orally once daily has an acceptable safety profile and demonstrated single-agent activity with confirmed partial responses in heavily pretreated patients with estrogen receptor-positive metastatic breast cancer. Notably, responses were observed in patients with ESR1 mutation as well as those with prior CDK4/6i and prior SERD. A phase III trial investigating elacestrant versus standard endocrine therapy is ongoing., Competing Interests: Aditya BardiaConsulting or Advisory Role: Novartis, Genentech, Pfizer, Spectrum Pharmaceuticals, BioTheranostics, Merck, Radius Health, Inc., Immunomedics, Genentech/Roche, Innocrin Pharma, Sanofi, Puma Biotechnology, Daiichi Sankyo/AstraZenecaResearch Funding: BioTheranostics Virginia KaklamaniHonoraria: Celgene, Eisai, Genentech, Novartis, Pfizer, Genomic Health, Puma Biotechnology, AstraZeneca, Seattle Genetics, Daiichi SankyoConsulting or Advisory Role: Amgen, Eisai, Puma Biotechnology, Celldex, AstraZeneca, AthenexSpeakers' Bureau: Eisai, Genentech, Celgene, Novartis, Genomic Health, Puma Biotechnology, PfizerResearch Funding: Eisai Sharon WilksHonoraria: Seattle GeneticsConsulting or Advisory Role: Seattle GeneticsResearch Funding: Seattle Genetics Donald RichardsConsulting or Advisory Role: Ipsen, Taiho Pharmaceutical, Seattle Genetics/Astellas, Mirati Therapeutics Wael HarbResearch Funding: AI Therapeutics Cynthia OsborneHonoraria: Agendia, Guardant Health, Breast Cancer Index, Seattle Genetics, ImmunomedicsSpeakers' Bureau: Novartis, LillyTravel, Accommodations, Expenses: Novartis, Lilly Robert WesolowskiConsulting or Advisory Role: Puma Biotechnology, Pfizer, Roche DiagnosticsResearch Funding: Acerta PharmaTravel, Accommodations, Expenses: Puma Biotechnology, Pfizer, Roche Diagnostics Meghan KaruturiConsulting or Advisory Role: Pfizer, MD Anderson Physician's Network Paul ConklingEmployment: Virginia Oncology AssociatesResearch Funding: Bristol-Myers Squibb, EMD Serono, Arcus Biosciences, Aptose Biosciences, Janssen, Pfizer, Bayer, Astex Pharmaceuticals Rebecca G. BagleyEmployment: Radius Health, Inc. Yamei WangEmployment: Radius Health, Inc.Stock and Other Ownership Interests: RDUS Maureen G. ConlanEmployment: Radius Health, Inc.Stock and Other Ownership Interests: Radius Health, Inc. Peter KabosConsulting or Advisory Role: LillyResearch Funding: Radius Health, Inc., Lilly, Pfizer, AstraZeneca, Sanofi, Genentech, AngiochemNo other potential conflicts of interest were reported.

Folate receptor alpha (FRα) has been reported to be expressed in up to 80% of triple-negative breast cancers (TNBC) with limited expression in normal tissues, making it a promising therapeutic target. Mirvetuximab soravtansine (mirvetuximab-s) is an antibody drug conjugate which has shown promise in the treatment of FRα-positive solid tumors in early phase clinical trials. Herein, are the results of the first prospective phase II trial evaluating mirvetuximab-s in metastatic TNBC. Patients with advanced, FRα-positive TNBC were enrolled on this study. Mirvetuximab-s was administered at a dose of 6.0 mg/kg every 3 weeks. 96 patients with advanced TNBC consented for screening. FRα staining was performed on tumor tissue obtained from 80 patients. The rate of FRα positivity by immunohistochemistry was 10.0% (8/80). Two patients were treated on study, with best overall responses of stable disease in one and progressive disease in the other. Adverse events were consistent with earlier studies. The study was terminated early due to the low rate of FRα positivity in the screened patient population and lack of disease response in the two patients treated. The observed rate of FRα positivity was considerably lower than previously reported and none of the patients had a partial or complete response. Treatment with mirvetuximab-s should only be further explored in TNBC if an alternate biomarker strategy is developed for patient selection on the basis of additional preclinical data.

Background: Adjuvant chemotherapy benefits early-stage breast cancer (BC) patients. Older women receive guideline-adherent treatment less frequently and experience treatment delays more frequently. We evaluated factors associated with delaying adjuvant chemotherapy and the delays' survival impact in a large population-based cohort of elderly BC patients., Methods: Patients age >66 years diagnosed 2001-2015 with localized or regional BC were identified in the SEER-Medicare and Texas Cancer Registry-Medicare databases. Time from surgery to chemotherapy (TTC) was categorized into four groups: 0-30, 31-60, 61-90, and >90 days. We identified predictors of delays, estimated overall (OS) and BC-specific (BCSS) survival, and determined the association between TTC and outcome adjusting for other variables., Results: Among 28,968 women (median age 71 years), median TTC was 43 days. 10.7% of patients experienced TTC >90 days. Older age, Black or Hispanic race/ethnicity, unmarried status, more comorbidities, hormone receptor-positivity, mastectomy, Oncotype DX testing, and full state buy-in were associated with increased risk of delay. Five-year OS estimates by TTC group were 0.82, 0.81, 0.80, and 0.74, respectively (p<.001). BCSS demonstrated a similar trend (p<.001). Chemotherapy delay was associated with worse OS (HR=1.33, 95%CI 1.25-1.40) and BCSS (HR=1.39, 95%CI 1.27-1.53). In subgroup analysis, delayed chemotherapy was associated with worse OS and BCSS among patients with hormone receptor-positive (HR=1.56, 95%CI 0.97-2.51), HER2-positive (HR=1.99, 95%CI 1.04-3.79), and triple-negative (HR=2.15, 95%CI 1.38-3.36) tumors., Conclusion: Chemotherapy delays are associated with worse survival in older BC patients. Providers should avoid delays and initiate chemotherapy ≤90 days after surgery regardless of patients' BC subtype or age., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Importance: Breast cancer risk and comorbidities increase with age. Data are lacking on the association of adjuvant chemotherapy with survival in elderly patients with multiple comorbidities and node-positive breast cancer., Objective: To examine the association of chemotherapy with survival in elderly patients with multiple comorbidities and estrogen receptor-positive, node-positive breast cancer., Design, Setting, and Participants: This retrospective cohort study included patients in the US National Cancer Database who were 70 years or older; had a Charlson/Deyo comorbidity score of 2 or 3; had estrogen receptor-positive, ERBB2 (formerly HER2 or HER2/neu)-negative breast cancer; and underwent surgery for pathologic node-positive breast cancer from January 1, 2010, to December 31, 2014. Propensity scores were used to match patients receiving adjuvant chemotherapy with those not receiving adjuvant chemotherapy based on age, comorbidity score, facility type, facility location, pathologic T and N stage, and receipt of adjuvant endocrine and radiation therapy. Data analysis was performed from December 13, 2018, to April 28, 2020., Exposures: Chemotherapy., Main Outcomes and Measures: The association of adjuvant chemotherapy with overall survival was estimated using a double robust Cox proportional hazards regression model., Results: Of a total of 2 445 870 patients in the data set, 1592 patients (mean [SD] age, 77.5 [5.5] years; 1543 [96.9%] female) met the inclusion criteria and were included in the initial nonmatched analysis. Of these patients, 350 (22.0%) received chemotherapy and 1242 (78.0%) did not. Compared with patients who did not receive chemotherapy, patients who received chemotherapy were younger (mean age, 74 vs 78 years; P < .001), had larger primary tumors (pT3/T4 tumors: 72 [20.6%] vs 182 [14.7%]; P = .005), and had higher pathologic nodal burden (75 [21.4%] vs 81 [6.5%] with stage pN3 disease and 182 [52.0%] vs 936 [75.4%] with stage pN1 disease; P < .001). More patients who received chemotherapy also received other adjuvant treatments, including endocrine therapy (309 [88.3%] vs 1025 [82.5%]; P = .01) and radiation therapy (236 [67.4%] vs 540 [43.5%]; P < .001). In the matched cohort, with a median follow-up of 43.1 months (95% CI, 39.6-46.5 months), no statistically significant difference was found in median overall survival between the chemotherapy and no chemotherapy groups (78.9 months [95% CI, 78.9 months to not reached] vs 62.7 months [95% CI, 56.2 months to not reached]; P = .13). After adjustment for potential confounding factors, receipt of chemotherapy was associated with improved survival (hazard ratio, 0.67; 95% CI, 0.48-0.93; P = .02)., Conclusions and Relevance: This cohort study found that in node-positive, estrogen receptor-positive elderly patients with breast cancer and multiple comorbidities, receipt of chemotherapy was associated with improved overall survival. Despite attempts to adjust for selection bias, these findings suggest that physicians carefully selected patients likely to derive treatment benefit from adjuvant chemotherapy based on certain unmeasured variables. A standardized, multidisciplinary approach to care may be associated with long-term treatment outcomes in this subset of the population.

Chemotherapy-related cognitive impairment and associated brain changes may reflect accelerated brain aging; however, empirical evidence for this theory is limited. The purpose of this study was to measure brain aging in newly diagnosed patients with breast cancer treated with chemotherapy (n = 43) and compare its longitudinal change to that of controls (n = 50). Brain age indices, derived from cortical measures, were compared between women with breast cancer and matched healthy controls across 3 timepoints (time 1: pre-surgery, time 2: 1 month following chemotherapy completion, and time 3: 1-year post-chemotherapy). The breast cancer group showed a significant decrease in cortical thickness across the 3 timepoints (p < .001) and a trend towards significant increase in predicted brain age especially from pre-treatment (time 1) to post-chemotherapy (time 2) compared to controls (p = 0.08). Greater increase in predicted brain age was related to several clinical factors (HER-2 status, surgery type, and history of neoadjuvant chemotherapy) and greater decrease in cortical thickness was associated with greater decrease in performance on a verbal learning task from time 1 to time 3 (r = - 0.48, p < .01). This study demonstrated evidence of increased cortical brain aging in middle-aged patients with breast cancer following chemotherapy treatment that was associated with decreased verbal memory performance.

Purpose and Introduction: A growing number of cancer patients are older adults aged 65 years and older. Patients with cancer are at increased risk for developing osteoporosis, falls, and fractures. We sought to identify the incidence of fractures in older adults who underwent cancer care between January 2013 and December 2015., Methods: A comprehensive geriatric assessment was performed, and bone densitometry was measured at baseline, with a 2-year follow-up., Results: In this study, among 304 patients with gastrointestinal, urologic, breast, lung, and gynecologic cancers we evaluated, and who completed the bone density testing (n = 199), 80% had osteoporosis or low bone mass (osteopenia). There was a higher prevalence of osteoporosis in cancer patients (40 vs. 16%, p = 0.05) than in population studies. Vitamin D insufficiency (< 30 ng/ml) was identified in 49% of tested cases (n = 245). Risk factors for low bone mass or osteoporosis were advanced age (p = 0.05), malnutrition (p = 0.04), and frailty (p = 0.01). Over the following 2 years (median follow-up 18 months), there was an incidence of fractures of 110 per 1000 person-years, or 2.8 times higher than reported in individuals without cancer. Risk factors for fractures included advanced age (70-79 vs. 60-69 years, p = 0.05) and frailty (p = 0.03)., Conclusion: Most older cancer patients studied have osteoporosis or low bone mass, resulting in an almost 3-fold increase in fracture risk as compared to epidemiologic studies. Bone health issues are commonly seen in older cancer patients, we recommend universal bone density testing. The initiation of antiresorptive treatment when findings are of osteopenia or osteoporosis will reduce the risk of fractures.

We aimed to determine if resting state functional magnetic resonance imaging (fMRI) acquired at pre-treatment baseline could accurately predict breast cancer-related cognitive impairment at long-term follow-up. We evaluated 31 patients with breast cancer (age 34-65) prior to any treatment, post-chemotherapy and 1 year later. Cognitive testing scores were normalized based on data obtained from 43 healthy female controls and then used to categorize patients as impaired or not based on longitudinal changes. We measured clustering coefficient, a measure of local connectivity, by applying graph theory to baseline resting state fMRI and entered these metrics along with relevant patient-related and medical variables into random forest classification. Incidence of cognitive impairment at 1 year follow-up was 55% and was predicted by classification algorithms with up to 100% accuracy ( p < 0.0001). The neuroimaging-based model was significantly more accurate than a model involving patient-related and medical variables ( p = 0.005). Hub regions belonging to several distinct functional networks were the most important predictors of cognitive outcome. Characteristics of these hubs indicated potential spread of brain injury from default mode to other networks over time. These findings suggest that resting state fMRI is a promising tool for predicting future cognitive impairment associated with breast cancer. This information could inform treatment decision making by identifying patients at highest risk for long-term cognitive impairment.

Background: CDK 4 and 6 inhibitors (CDK4/6i), which arrest unregulated cancer cell proliferation, show clinical efficacy in breast cancer. Unexpectedly, a patient treated on a CDK4/6i-based trial, as first-line therapy in metastatic breast cancer, developed rapid disease progression following discontinuation of study drug while receiving standard second-line therapy off trial. We thus sought to expand this observation within a population of patients treated similarly at The University of Texas MD Anderson Cancer Center. Methods: Using an IRB-approved protocol, 4 patients previously enrolled on CDK4/6i trials were analyzed for outcomes after discontinuing study drug. These patients were treated on a randomized trial of first-line endocrine therapy +/- a CDK4/6i. Rapid disease progression was defined as progression occurring within 4 months of CDK4/6i discontinuation. Results: In total, 4 patients developed rapid disease progression and died; 2 of whom died within 6 months of CDK4/6i discontinuation. Conclusion: This case series suggests a potential for rapid disease progression following CDK4/6i discontinuation. However, the clinical course following progression must be validated in large CDK4/6i clinical trials and standard-of-care cohorts. If confirmed, such observations may alter the algorithm for subsequent therapy in patients with disease progression on CDK4/6i. Nevertheless, the need remains to define a mechanistic basis for this rapid progression and formulate alternative therapeutic strategies., Competing Interests: Competing Interests: All authors, Sami I. Bashour, Iman Doostan, Khandan Keyomarsi, Vicente Valero, Naoto T. Ueno, Powel H. Brown, Jennifer K. Litton, Kimberly B. Koenig, Meghan Karuturi, Sausan Abouharb, Debasish Tripathy, Stacy L. Moulder-Thompson, and Nuhad K. Ibrahim, have no conflicts of interest or competing interests to declare.

Deregulation of the cell cycle machinery is a hallmark of cancer. While CDK4/6 inhibitors are FDA approved (palbociclib) for treating advanced estrogen receptor-positive breast cancer, two major clinical challenges remain: (i) adverse events leading to therapy discontinuation and (ii) lack of reliable biomarkers. Here we report that breast cancer cells activate autophagy in response to palbociclib, and that the combination of autophagy and CDK4/6 inhibitors induces irreversible growth inhibition and senescence in vitro, and diminishes growth of cell line and patient-derived xenograft tumours in vivo. Furthermore, intact G1/S transition (Rb-positive and low-molecular-weight isoform of cyclin E (cytoplasmic)-negative) is a reliable prognostic biomarker in ER positive breast cancer patients, and predictive of preclinical sensitivity to this drug combination. Inhibition of CDK4/6 and autophagy is also synergistic in other solid cancers with an intact G1/S checkpoint, providing a novel and promising biomarker-driven combination therapeutic strategy to treat breast and other solid tumours.

Cancer and neurocognitive disorders, such as dementia and delirium, are common and serious diseases in the elderly that are accompanied by high degree of morbidity and mortality. Furthermore, evidence supports the under-diagnosis of both dementia and delirium in older adults. Complex questions exist regarding the interaction of dementia and delirium with cancer, beginning with guidelines on how best measure disease severity, the optimal screening test for either disorder, the appropriate level of intervention in the setting of abnormal findings, and strategies aimed at preventing the development or progression of either process. Ethical concerns emerge in the research setting, pertaining to the detection of cognitive dysfunction in participants, validity of consent, disclosure of abnormal results if screening is pursued, and recommended level of intervention by investigators. Furthermore, understanding the ways in which comorbid cognitive dysfunction and cancer impact both cancer and non-cancer-related outcomes is essential in guiding treatment decisions. In the following article, we will discuss what is presently known of the interactions of pre-existing cognitive impairment and delirium with cancer. We will also discuss identified deficits in our knowledge base, and propose ways in which innovative research may address these gaps., (Copyright © 2016. Published by Elsevier Ltd.)

Breast cancer is the mostly commonly diagnosed cancer in women both in the United States and worldwide. Although advanced age at diagnosis is associated with more favorable tumor biology, mortality rates are comparatively higher in older adults, possibly attributed to advanced stage at presentation. There are minimal specific treatment-based guidelines in elderly patients with cancer, mostly attributable to their limited inclusion on clinical trials. In addition to the existing evidence from clinical trials and retrospective studies, practitioners need to take into consideration functional status, social support, patient preference, presence of comorbidities, and life expectancy when selecting optimal treatment., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: Because the cancer population is aging, interprofessional education incorporating geriatric principles is essential to providing adequate training for oncology fellows. We report the targeted needs assessment, content, and evaluation tools for our geriatric oncology curriculum at MD Anderson Cancer Center., Methods: A team comprising a geriatrician, a medical oncologist, an oncology PharmD, an oncology advanced nurse practitioner, and two oncology chief fellows developed the geriatric oncology curriculum. First, a general needs assessment was conducted by reviewing the literature and medical societies' publications and by consulting experts. A targeted needs assessment was then conducted by reviewing the fellows' evaluations of the geriatric oncology rotation and by interviewing fellows and recently graduated oncology faculty., Results: Geriatric assessment, pharmacology, and psychosocial knowledge skills were the three identified areas of educational need. Curriculum objectives and an evaluation checklist were developed to evaluate learners in the three identified areas. The checklist content was validated by consulting experts in the field. Online materials, including a curriculum, a geriatric pharmacology job aid, and pharmacology cases, were also developed and delivered as part of the curriculum., Conclusion: An interprofessional team approach was a successful method for identifying areas of learners' educational needs, which in turn helped us develop an integrated geriatric oncology curriculum. The curriculum is currently being piloted and evaluated., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Here, we present successful management of a patient with rupture of right sinus valsalva and ventricular septal defect. Aneurysm of the aortic sinus also known as sinus of valsalva (ASOV) is a rare cardiac defect which can be congenital or acquired. Right coronary sinus (most common) usually ruptures into the right ventricle causing left to right shunt as seen in our patient. Unruptured aneurysms cause obstruction to right ventricular outflow tract. A 29-year-old male patient presented with dyspnea, palpitations, easy fatigability and severe limitation of physical activity. Transthoracic echocardiography showed membranous out pouching of the right coronary cusp (RCC) into the right ventricle. Patient was medically managed with drugs. Under general anaesthesia, after instituting cardiopulmonary bypass (CPB) surgical repair with pericardial patch, closure of subpulmonic ventricular septal defect was performed. Patient vitals were stable after surgery and he was asymptomatic on the first follow-up after discharge.

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a distinct subtype of Hodgkin lymphoma that is characterized by unique clinical presentation, histological appearance, and indolent disease course. The recurrent nature of disease provides an opportunity to examine the role of stem cell transplantation in its management. We report here a single-center experience of 26 patients with relapsed NLPHL treated with high-dose chemotherapy and autologous stem cell transplantation between 1990 and 2008. With a median follow-up of 50 months (range, 2-138 months), the 5-year overall and event-free survival were 76% (SE 10%) and 69% (SE 10%), respectively. Our data suggest that high-dose chemotherapy and autologous transplantation should be considered as an option for patients with relapsed NLPHL., (Copyright © 2013 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Post-transplant lymphoproliferative disorder (PTLD) is a serious complication of organ transplantation. Although PTLD typically has a B-cell histology, an uncommon variant, plasmacytic PTLD can present as a monoclonal plasma cell proliferation similar to plasmacytomas seen in multiple myeloma. A retrospective analysis was performed on nine patients at our center with plasmacytic PTLD as characterized by plasmacytic histology with the presence of CD138 and lack of CD20. Of the 210 adult solid organ transplant PTLD patients diagnosed between 1988 and 2012, 9 (4%) had a histological appearance consistent with plasmacytic PTLD. The median time from transplant to diagnosis was 3.7 years (range 8 months-24 years). All patients presented with extranodal and often subcutaneous solid tumors. Laboratory features included elevated LDH and beta-2 microglobulin levels, monoclonal gammopathy, and EBV positivity of the tumor. Unlike conventional multiple myeloma, patients had normal calcium levels and only mild anemia. Six patients who have completed treatment achieved complete responses with radiation therapy and/or reduction in immunosuppression with two patients now greater than 5 years in continuous complete response. Plasmacytic PTLD, despite its plasmacytic histology, is responsive to conventional therapies used for B-cell PTLD including reduction in immunosuppression and radiation therapy., (© 2013 The Authors Transplant International © 2013 Steunstichting ESOT. Published by Blackwell Publishing Ltd.)