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Background N-terminal pro–brain natriuretic peptide (NT-proBNP) is a cardiac biomarker associated with the risk of heart failure and death in the general population, but it has not been explored in cancer survivors. Methods Using a US nationally representative sample of adults 20 years of age and older from the National Health and Nutrition Examination Survey from 1999 to 2004, this study compared NT-proBNP levels between adults without cancer (n = 12 574) and adult cancer survivors (n = 787). It examined the association of NT-proBNP with all-cause and cause-specific mortality among cancer survivors. Results Cancer survivors had higher NT-proBNP levels than adults without cancer (median [interquartile range] = 125.4 pg/mL [52.4-286.0] vs 43.2 pg/mL [20.3-95.0]). In particular, survivors of breast, prostate, and colorectal cancers had higher NT-proBNP levels than adults without cancer (multivariable-adjusted P  < .05). In total, 471 survivors died (141 from cancer; 95 from cardiac disease) during a median follow-up period of 13.4 years (9393 person-years). Among cancer survivors, higher NT-proBNP levels were statistically associated with increased risks of all-cause death (hazard ratio [HR] = 1.31, 95% confidence interval [CI] = 1.18 to 1.46) and cardiac death (HR = 1.55, 95% CI = 1.21 to 2.00) but not with death from cancer (HR = 1.10, 95% CI = 0.92 to 1.32]). Higher NT-proBNP levels were associated with elevated overall mortality in survivors of prostate cancer (HR = 1.49, 95% CI = 1.22 to 1.81) and colorectal cancer (HR = 1.78, 95% CI = 1.00 to 3.16) (P  = .169 for interaction). Nonlinear dose-response relationships were observed between NT-proBNP and mortality, with statistically significant relationships emerging above 125 pg/mL. Conclusions Cancer survivors had higher NT-proBNP levels than adults without cancer, and elevated NT-proBNP levels were associated with higher risks of all-cause and cardiac mortality in cancer survivors. [ABSTRACT FROM AUTHOR]

Background: Patient-reported outcomes (PROs) are a better tool for evaluating the experiences of patients who have symptomatic, treatment-associated adverse events (AEs) compared with clinician-rated AEs. The authors present PROs assessing health-related quality of life (HRQoL) and treatment-related neurotoxicity for adjuvant capecitabine versus platinum on the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network (ECOG-ACRIN) EA1131 trial (ClinicalTrials.gov identifier NCT02445391). Methods: Participants completed the National Comprehensive Cancer Network Functional Assessment of Cancer Therapy-Breast Cancer Symptom Index (NFBSI-16) and the Functional Assessment of Cancer Therapy-Gynecologic Oncology Group neurotoxicity subscale (platinum arm only) at baseline, cycle 3 day 1 (C3D1), 6 months, and 15 months. Because of early termination, power was insufficient to test the hypothesis that HRQoL, as assessed by the NFBSI-16 treatment side-effect (TSE) subscale, would be better at 6 and 15 months in the capecitabine arm; all analyses were exploratory. Means were compared by using t-tests or the Wilcoxon rank-sum test, and proportions were compared by using the χ2 test. Results: Two hundred ninety-six of 330 eligible patients provided PROs. The mean NFBSI-16 TSE subscale score was lower for the platinum arm at baseline (p = .02; absolute difference, 0.6 points) and for the capecitabine arm at C3D1 (p = .04; absolute difference, 0.5 points), but it did not differ at other times. The mean change in TSE subscale scores differed between the arms from baseline to C3D1 (platinum arm, 0.15; capecitabine arm, -0.72; p = .03), but not from baseline to later time points. The mean decline in Functional Assessment of Cancer Therapy-Gynecologic Oncology Group neurotoxicity subscale scores exceeded the minimal meaningful change (1.38 points) from baseline to each subsequent time point (all p < .05). Conclusions: Despite the similar frequency of clinician-rated AEs, PROs identified greater on-treatment symptom burden with capecitabine and complemented clinician-rated AEs by characterizing patients' experiences during chemotherapy. [ABSTRACT FROM AUTHOR]

Introduction The addition of taxanes to anthracycline-based chemotherapy is considered standard of care in the treatment of breast cancer. However, there are insufficient data regarding the safety of taxanes during pregnancy. The aim of this study was to describe the incidence of obstetric and neonatal adverse events associated with the use of taxane-containing chemotherapy regimens for the treatment of breast cancer during pregnancy. Methods This is a multicenter, international cohort study of breast cancer patients treated with taxanes during pregnancy. A descriptive analysis was undertaken to synthetize available data. Results A total of 103 patients were included, most of whom were treated with paclitaxel and anthracyclines given in sequence during gestation (90.1%). The median gestational age at taxane initiation was 28 weeks (range = 12-37 weeks). Grade 3-4 adverse events were reported in 7 of 103 (6.8%) patients. The most common reported obstetric complications were intrauterine growth restriction (n = 8 of 94, 8.5%) and preterm premature rupture of membranes (n = 5 of 94, 5.3%). The live birth rate was 92 of 94 (97.9%), and the median gestational age at delivery was 37 weeks (range = 32-40 weeks). Admission to an intensive care unit was reported in 14 of 88 (15.9%) neonates, and 17 of 70 (24.3%) live births resulted in small for gestational age neonates. Congenital malformations were reported in 2 of 93 (2.2%). Conclusion Obstetric and neonatal outcomes after taxane exposure during pregnancy were generally favorable and did not seem to differ from those reported in the literature with standard anthracycline-based regimens. This study supports the use of taxanes during gestation when clinically indicated. [ABSTRACT FROM AUTHOR]

Background The expansion of hematopoietic stem cells carrying recurrent somatic mutations, termed clonal hematopoiesis (CH), is common in elderly individuals and is associated with increased risk of myeloid malignancy and all-cause mortality. Though chemotherapy is a known risk factor for developing CH, how myelosuppressive therapies affect the short-term dynamics of CH remains incompletely understood. Most studies have been limited by retrospective design, heterogeneous patient populations, varied techniques to identifying CH, and analysis of single timepoints. Methods We examined serial samples from 40 older women with triple-negative or hormone receptor–positive breast cancer treated on the prospective ADjuVANt Chemotherapy in the Elderly trial to evaluate the prevalence and dynamics of CH at baseline and throughout chemotherapy (6 and 12 weeks). Results CH was detected in 44% of patients at baseline and in 53% at any timepoint. Baseline patient characteristics were not associated with CH. Over the course of treatment, mutations exhibited a variety of dynamics, including emergence, expansion, contraction, and disappearance. All mutations in TP53 (n = 3) and PPM1D (n = 4), genes that regulate the DNA damage response, either became detectable or expanded over the course of treatment. Neutropenia was more common in patients with CH, particularly when the mutations became detectable during treatment, and CH was significantly associated with cyclophosphamide dose reductions and holds (P  = .02). Conclusions Our study shows that CH is common, dynamic, and of potential clinical significance in this population. Our results should stimulate larger efforts to understand the biological and clinical importance of CH in solid tumor malignancies. Trial Registration ClinicalTrials.gov (https://clinicaltrials.gov/ct2/show/NCT03858322). Clinical trial registration number: NCT03858322. [ABSTRACT FROM AUTHOR]

Opinion statement: For high-risk early-stage hormone-receptor-positive, HER2-negative breast cancer (HR + /HER2 − EBC), short- and long-term recurrence risks remain substantial despite local control with surgery and radiation and systemic treatment with chemotherapy and endocrine therapy (ET). Recent trials have provided new strategies for reducing recurrence. The monarchE trial demonstrated that adding 2 years of adjuvant abemaciclib to ET improves invasive disease-free survival (iDFS) and distant recurrence-free survival (DRFS). In the OlympiA trial for high-risk disease in patients with germline BRCA1/BRCA2 mutations, adding 1 year of olaparib to ET improved iDFS, DRFS, and overall survival (OS). In addition, for premenopausal women with high-risk tumors, long-term follow-up of the SOFT, ASTRRA, TEXT, ABCSG-12, and HOBOE trials supports the role of ovarian function suppression (OFS), in combination with adjuvant tamoxifen or aromatase inhibition (AI). For postmenopausal women with high-risk tumors, extended-duration AI for at least 7 years should be used with zoledronic acid. Given the remaining recurrence risk even with these interventions and with the ongoing development of new strategies for HR + disease, patients with high-risk EBC should be encouraged to participate in clinical trials, such as trials of immunotherapy, novel oral estrogen receptor alpha (ERα)-targeting agents, antibody–drug conjugates (ADCs), and trials guided by measurements of minimal residual disease (MRD). [ABSTRACT FROM AUTHOR]

ESR1 mutation (ESR1m) is a frequent cause of acquired resistance to aromatase inhibitor (AI) plus cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i), which is a first-line therapy for hormone-receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC). Camizestrant is a next-generation oral selective estrogen receptor degrader (SERD) that in a phase II study significantly improved progression-free survival (PFS) over fulvestrant (also a SERD) in ER+/HER2- ABC. SERENA-6 (NCT04964934) is a randomized, double-blind, phase III study evaluating the efficacy and safety of switching from an AI to camizestrant, while maintaining the same CDK4/6i, upon detection of ESR1m in circulating tumor DNA before clinical disease progression on first-line therapy for HR+/HER2- ABC. The aim is to treat ESR1m clones and extend the duration of control of ER-driven tumor growth, delaying the need for chemotherapy. The primary end point is PFS; secondary end points include chemotherapy-free survival, time to second progression event (PFS2), overall survival, patient-reported outcomes and safety. Why will we perform this study? Patients with advanced breast cancer in which the cancer cells have the receptor for the hormone estrogen and/or progesterone are typically treated with an aromatase inhibitor, a hormone therapy that decreases estrogen being made in the body, together with an inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6), a drug that blocks the growth of cancer cells. Although cancers usually respond to treatment initially, the cancer cells eventually change, so the drug combination no longer works. For example, mutation of the estrogen receptor (referred to as ESR1m) can stop aromatase inhibitors from working. Camizestrant is an investigational drug that blocks estrogen receptors, including mutated receptors, reducing the growth and spread of cancer. Here we describe the SERENA-6 clinical trial, which is testing camizestrant as a treatment for patients with breast cancer with ESR1m. How will we perform this research? The phase III SERENA-6 trial will use blood tests to monitor if patients with breast cancer develop ESR1m while being treated with an aromatase inhibitor and a CDK4/6 inhibitor. If ESR1m is detected, yet the disease is stable, participants will be randomly assigned to either continue with the same aromatase inhibitor or switch to camizestrant while continuing with the same CDK4/6 inhibitor. The study will assess whether switching to camizestrant prolongs the time before the cancer grows, spreads or worsens. It will also assess the length of time that participants live for versus those who continue with an aromatase inhibitor. Clinical Trial Registration:NCT04964934 (ClinicalTrials.gov) SERENA-6 (NCT04964934) is an ongoing randomized, double-blind, phase III trial of camizestrant + CDK4/6i in ESR1-mutant HR+/HER2-negative advanced breast cancer during first-line treatment. [ABSTRACT FROM AUTHOR]

Purpose of Review: CDK4/6 inhibition (CDK4/6i) is a key component of first-line combination treatment with endocrine therapy for hormone receptor-positive, HER2-negative metastatic breast cancer (HR + /HER2 − MBC). Understanding and overcoming resistance are ongoing areas of investigation. Diverse resistance mechanisms have been uncovered in cell cycle regulators and growth factor signaling components, converging on upregulation of CDK6 or on perturbation of the cell cycle downstream of CDK4/6. In this review, we discuss studies in the past few years that add new findings to this growing knowledge base. Recent Findings: Recent work has shown that CDK6 upregulation in breast cancer cells induces INK4 family members (p18INK4C and p15INK4B), which render CDK6 (but not CDK4) resistant to CDK4/6i. CDK6 can also form a CDK4/6i-resistant complex with p27KIP1 and (unlike CDK4) can sequester p21CIP1/WAF1 away from inhibiting CDK2 in the presence of CDK4/6i. These resistant complexes may be targetable by next-generation CDK4/6i such as proteolysis targeting chimeras (PROTACs). Separately, recent work has suggested that IFN-STAT1 signaling, especially over extended durations, may be a mediator of resistance rather than efficacy of CDK4/6i in breast cancer. This is based on descriptive analyses, and experiments are required to test this hypothesis. Summary: Recent research has revealed new mechanisms of CDK4/6i resistance in HR + MBC, including CDK6 complexes with INK4 and CIP/KIP members and, controversially, IFN-STAT1 signaling. Advances in these areas will inform the development of better CDK4/6 inhibitors and new combination regimens. [ABSTRACT FROM AUTHOR]

Clinical trials and real‐world evidence (RWE) present conflicting results on the benefit of cyclin‐dependent kinase 4 and 6 inhibitors for patients with advanced hormone receptor–positive and human epidermal growth factor receptor‐2 overexpressing breast cancer. How can RWE be interpreted and used to help guide clinical decisions? [ABSTRACT FROM AUTHOR]

Breast cancer is the most common malignancy and the second leading cause of cancer-related mortality in the United States (US). Most patients are diagnosed with early-stage disease; however, there is still a need to prevent recurrences that often present as incurable metastatic disease. The treatment landscape of early-stage breast cancer is evolving rapidly. The immune checkpoint inhibitor pembrolizumab is approved in combination with neoadjuvant chemotherapy for the treatment of high-risk triple-negative breast cancer (TNBC). The cyclin-dependent kinase (CDK) 4 and 6 inhibitor abemaciclib is approved for adjuvant treatment of patients with high-risk hormone receptor (HR)-positive disease. While adjuvant olaparib has shown significant improvement in outcomes for patients with pathogenic/likely pathogenic BRCA1/2 mutations and high-risk human epidermal growth factor receptor 2 (HER2)-negative breast cancer, and is approved in this setting. For the HER2-positive subtype, the post-neoadjuvant therapy can be tailored based on the response to neoadjuvant chemotherapy and HER2-targeted agents. In this narrative review, we summarize the most recent approvals for early-stage breast cancer as well as frequently encountered clinical challenges utilizing these medications. [ABSTRACT FROM AUTHOR]

Objective  Breast cancer is one of the most frequently diagnosed cancers in pregnancy and is commonly treated with chemotherapy. To date, studies examining effects of chemotherapy during pregnancy on fetal growth have yielded conflicting results, and most are limited by small sample sizes or are nonspecific with respect to cytotoxic regimen or type of cancer treated. We sought to evaluate the effect of chemotherapy for breast cancer in pregnancy on birthweight and small for gestational age infants. Study Design  This is a retrospective cohort study of 74 women diagnosed with pathologically confirmed breast cancer during pregnancy between 1997 and 2018 at one of three academic medical centers, who had a singleton birth with known birthweight. Forty-nine received chemotherapy and 25 did not receive chemotherapy. Linear regression modeling was used to compare birthweight (by gestational age and sex-specific z -score) by chemotherapy exposure. Subanalyses of specific chemotherapy regimen and duration of chemotherapy exposure were also performed. Placental, neonatal, and maternal outcomes were also analyzed by chemotherapy exposure. Results  In the adjusted model, chemotherapy exposure was associated with lower birthweight (Δ z -score = −0.49, p  = 0.03), but similar rates of small for gestational age (defined as birthweight <10th percentile for gestational age) infants (8.2 vs. 8.0%, p  = 1.0; Fisher's exact test). Each additional week of chemotherapy (Δ z -score = −0.05, p  = 0.03) was associated with decreased birthweight, although no association was found with specific chemotherapy regimen. Chemotherapy exposure was associated with lower median placental weight percentile by gestational age (9th vs. 75th, p  < 0.05). Secondary maternal outcomes were similar between the group that did and did not receive chemotherapy. Conclusion  Chemotherapy for breast cancer in pregnancy in this cohort is associated with lower birthweight but no difference in the rate of small for gestational age infants. Key Points Chemotherapy for breast cancer in pregnancy is associated with decreased birthweight but similar rates of small for gestational age infants. Birthweight did not differ according to chemotherapy regimen. There is no difference in the rate of small for gestational age infants. [ABSTRACT FROM AUTHOR]

Objective: The Healthy Living and Eating After Cancer Trial demonstrated that a clinic‐based weight loss program reduced body weight, as compared with a waitlist control group, over 15 weeks. Here we report the impact of the weight loss intervention on health‐related quality‐of‐life outcomes at week 15, and maintenance of weight loss to week 30. Methods: This trial randomized cancer survivors of solid tumors and hematologic malignancies (breast cancer: 76.7%) to a 15‐week group‐based weight loss program (n = 30) or a waitlist control group (n = 30). Participants were not blinded to group assignment. Participants completed a variety of health‐related quality‐of‐life outcome measures at baseline and week 15. From week 15 to week 30, participants initially randomized to the weight loss program were followed with no additional intervention, and participants initially randomized to the waitlist control group commenced the weight loss program. Results: Over the 15 weeks, the weight loss program improved physical functioning (6.2 ± 2.9; p = 0.02; d = 0.31) and reduced insomnia symptoms (−17.1 ± 7.4; p = 0.03; d = −0.30) as measured by the EORTC QLQ‐C30, and sleep disturbance (−4.9 ± 1.6; p = 0.005; d = −0.40) as measured by PROMIS, compared to waitlist control. After a weight loss of 4.6 ± 3.9 kg, from week 15 to week 30, participants who were initially randomized to the weight loss program maintained their prior weight loss (+0.6 ± 3.5 kg) and participants who were initially randomized to the waitlist control group lost weight (−3.4 ± 2.9 kg; p < 0.001). Conclusions: In cancer survivors with overweight or obesity, a 15‐week clinic‐based weight loss program improved health‐related quality‐of‐life outcomes and produced sustained weight loss to week 30. [ABSTRACT FROM AUTHOR]

Background: Audio recordings of oncology clinic discussions can help patients retain and understand information about their disease and treatment decisions. Access to this tool relies on acceptance of recordings by oncologists. This is the first study to evaluate experience and attitudes of oncologists toward patients recording clinic visits. Methods: Medical, radiation, and surgical oncologists from 5 US cancer centers and community affiliates were surveyed to evaluate clinicians' experience, beliefs, and practices regarding patient‐initiated recordings. Results: Among 360 oncologists (69% response rate), virtually all (93%) have experienced patients seeking to record visits. Although 75% are comfortable with recording, 25% are uncomfortable and 56% report concerns ranging from less thorough discussions to legal liability. Most (85%) always agree when patients ask to record, but 15% never or selectively allow recording. Although 51% believe recording is positive for the patient‐physician relationship, a sizable minority report that it can lead to less detailed conversations (28%) or avoidance of difficult topics, including prognosis (33%). Views did not vary based on subspecialty, practice setting, or geographic region, but older age and years in practice were associated with more positive views of recording. The majority of clinicians (72%) desire institutional policies to govern guidelines about recordings. Conclusions: Most oncologists are comfortable with patient requests to record visits, but a sizable minority remain uncomfortable, and access to recording varies solely on physician preference. This difference in care delivery may benefit from institutional policies that promote access while addressing legitimate physician concerns over privacy and appropriate use of recordings. Most oncologists are comfortable with patients recording consultations; however, 25% are uncomfortable, and more than half (56%) express concerns related to legal liability and limiting transparent discussions with patients. Institutional policies are needed to address the concerns of oncologists and enhance equitable care for patients. [ABSTRACT FROM AUTHOR]

The coronavirus disease (COVID)-19 pandemic has affected graduate medical education training programs, including hematology-oncology fellowship programs, both across the United States and abroad. Within the Dana-Farber Cancer Institute/Mass General Brigham hematology-oncology fellowship program, fellowship leadership had to quickly reorganize the program's clinical, educational, and research structure to minimize the risk of COVID-19 spread to our patients and staff, allow fellows to assist in the care of patients with COVID-19, maintain formal didactics despite physical distancing, and ensure the mental and physical well-being of fellows. Following the first wave of patients with COVID-19, we anonymously surveyed the Dana-Farber Cancer Institute/Mass General Brigham first-year fellows to explore their perceptions regarding what the program did well and what could have been improved in the COVID-19 response. In this article, we present the feedback from our fellows and the lessons we learned as a program from this feedback. To our knowledge, this represents the first effort in the hematology-oncology literature to directly assess a hematology-oncology program's overall response to COVID-19 through direct feedback from fellows. [ABSTRACT FROM AUTHOR]

The incidence of breast cancer diagnosed during pregnancy is increasing. We sought to characterize patient, treatment, pregnancy and lactation factors among young women with newly diagnosed breast cancer during pregnancy in a prospective cohort study. We identified all women who were pregnant when diagnosed with invasive breast cancer among those enrolled in the Young Women's Breast Cancer Study (NCT01468246), and collected details on pregnancy, birth and lactation from surveys, and treatment information medical record review. Of 1302 enrolled participants, 976 women with invasive breast cancer completed full baseline surveys, among whom 39 (4.0%) patients reported being pregnant at diagnosis. Median age at diagnosis was 34 years (range: 25‐40), with stage distribution: I, 28%; II, 44%; III, 23%; and IV, 5%. 74% of patients (29/39) had grade 3 tumors, 59% (23/39) ER‐positive, and 31% (12/39) HER2‐positive disease. 23 (59%) had surgery during pregnancy, 4 (17%) during the first trimester. Among the women who had surgery during pregnancy, 61% (14/23) underwent lumpectomy, 35% (8/23) unilateral, and 4% (1/23) bilateral mastectomy. All patients who had chemotherapy (51%, 20/39) received it in second and third trimesters, and had ACx4. There were 31 live births, 2 spontaneous, and 5 therapeutic abortions. Among live births, 16 (41%) were before 37 weeks of gestation. Three women reported breastfeeding. Within 6 months after delivery, comprehensive staging in 13 patients showed upstaging in four patients. In a contemporary cohort of young women with breast cancer, pregnancy at diagnosis is relatively uncommon. Treatment during pregnancy can generally be consistent with standard surgical and chemotherapy approaches, with attention to timing of therapies. Longer‐term outcomes including effects of some timing issues including delayed use of anti‐HER2 therapy on patient outcomes warrant further research. [ABSTRACT FROM AUTHOR]

Purpose: Nine months after the implementation of a new electronic medical record (EMR) system at a single institution, physicians (MDs), nurse practitioners (NPs), and physician assistants (PAs) expressed frustration with its use. We aimed to test if an individually tailored training approach reduced time spent with the EMR and increased confidence. Materials and Methods: Two hours of training were conducted in a one-on-one manner with a trainer. Content was individualized according to the following: provider survey, EMR utilization profile, and shadowing in clinic. Surveys assessed confidence before training and immediately after training. Changes in time spent in various EMR activities before training and after training were compared. Results: Three trainers delivered one-on-one training to 133 MDs, 42 NPs, and 10 PAs who specialized in medical oncology. Participants reported an increase in confidence across all activities, and almost all providers (98%) who responded to our survey agreed that the training enhanced their efficiency. A non–statistically significant trend toward reduction in the overall time in the system was observed. Time in system was reduced primarily in activities such as documentation and ordering of laboratory tests, imaging, medications, and chemotherapy. Conclusion: A personalized and data-driven training approach was highly regarded by providers. EMR usage reports provided extensive data to identify and prioritize training content and were valuable to measure the impact of training on provider time in system. With the growth of EMR implementation and the reported relationship of EMR use to burnout, continuous and personalized training after EMR implementation is effective to reduce the time in system and increase confidence. [ABSTRACT FROM AUTHOR]