bluuebunny/crossref_metadata_2025 huggingface dataset:
Trends in location of death for individuals with pediatric cancer in the United States.
Authors: Jain Urvish , Mathew Angelin , Jain Bhav , Feliciano Erin Jay Garbes , Dee Edward Christopher Christopher , Wolden Suzanne L.
Published: May 2024

1591

Background: Children and adolescents with cancer face unique symptomatic, psychosocial, and existential challenges at the end of life (EOL). Premature death alongside severe pain and complex symptoms is distressing for the patients and families. Location of death is an important clinical and psychosocial decision for many patients. Therefore, we explored differences in location of death amongst pediatric patients with cancer using a large, national US database. Methods: We performed multinomial logistic regressions and analyzed trends in place of death for children and adolescents (ages 0 to 19) diagnosed with cancer from 2003-2019 using the Centers for Disease Control and Prevention Wide-Range Online Data for Epidemiologic Research database (CDC WONDER). We studied associations in place of death with essential decedent characteristics (age, sex, and race) for ICD10 codes C00-C96 and D00-D49, which encompass the most common causes of cancer death in children and adolescents. Results: Of 1,910 pediatric oncology decedents, 910 died in a hospital, 794 died at home, 12 died in nursing facilities, 59 in hospice, and 135 in outpatient facilities. Over time, death at home decreased by 50%. Death in the hospital increased by 64% and death in hospice increased by 200%. Children 10-19 years-of-age were more likely to die in hospice than children younger than 4 and children between 5-9 years-of-age. Additionally, they were less likely to die in outpatient medical facilities and ED. 1,388 decedents were White, 411 were Black, 18 were American Indian, and 93 were Asian. Children of racial and ethnic minorities were significantly more likely to die in hospitals than White children with cancer (Black: 1.81 [1.44-2.28], Asian: 1.57 [1.03-2.41], and Hispanic: 1.60 [1.26-2.04]). Black children with cancer were also more likely (1.67 [1.11-2.53]) to die in outpatient facilities compared to White children. Asian children & Black children were less likely to die at home (0.48[0.38-0.61] and 0.55 [0.35-0.86] respectively). Conclusions: In contrast to the adult population that has demonstrated steady increases in deaths at home, for children with cancer, relative rates of death at home decreased while death in the hospital increased, with distinct differences among race/ethnic groups. Adequate education and support are needed to facilitate both autonomy and symptom palliation at EOL. Future work must explore underlying reasons for differences in place of death across time and demographic groups, so as to identify and alleviate any potential barriers, and to promote equitable access to a good death for each individual.
Racial, ethnic, and regional influences on national patterns of mammographic screening for breast cancer.
Authors: Buchholz Thomas A. , Soriano Emily C. , Mesko Shane , Xavier Marin Feldman , Fortmann Adelaide L , Philis-Tsimikas Athena , Bagsic Samantha R.
Published: May 2024

1600

Background: Racial, ethnic, and geographic factors can affect disparities in medical care. Mammographic screening has been demonstrated to reduce the risk of breast cancer death for appropriate subsets of women and accordingly is an accepted standard recommendation. Herein, we studied the utilization in screening mammography in patients who have access to primary care physicians according to race, ethnicity, and United States geographic region. Methods: We queried the Cosmos Epic national database to ascertain mammographic screening rates for women aged 50 to 65 who had 1 or more encounters with a primary care physician. Patients with a previous breast cancer and/or ductal carcinoma in situ history and those with missing race or ethnicity data were excluded. Results: The COSMOS database was queried for the period of 11/9/2020 – 11/8/2023. A total of 7,837,164 individuals met our study criteria. The overall rate of positive mammographic screening was 63.8%. Because of the large sample size, small differences in screening rates according to analyzed variables reached statistically significant differences. Accordingly, we defined a clinically relevant low rate of mammography screening for a specific variable as a utilization rate of less than 60%. Using this methodology, there were no differences noted according to race. Both Black/African American and Asian groups had a slightly higher screening rates than Whites. However, the data indicate that rates varied according to ethnicity. Mammographic screening was less frequent in Hispanic/Latino versus not Hispanic (58.9% vs. 64.3%). In addition, rates varied according to census US regions with the lowest rates in the West region (55.5%). Rates of mammographic screening for Blacks/African American and Whites were within 5% of one another in all four of the geographic regions. With respect to ethnicity, the South region had the only difference exceeding 5%, with respective rates of 61.8% for Not Hispanic/Latino versus 55.7% for Hispanic Latino. Conclusions: Many patients receiving health care in the United States do not undergo recommended mammogram screening. We found no clinically significant difference in screening rates according to race but identified a lower rate in Hispanic/Latino populations, particularly in the South. Targeted educational efforts and community outreach efforts in this region are warranted.
Colorectal cancer and the heart: Uncovering the beat of racial disparities in MACCE.
Authors: Uttam Chandani Kanishka , Agrawal Siddharth Pravin , Raval Maharshi , Siddiq Sajid , Nadeem Ahmed , Chintakuntlawar Ashish V.
Published: May 2024

1611

Background: Due to its high prevalence, colorectal cancer (CRC) forms a considerable burden on the healthcare system. Advancements in treatment modalities like immunotherapy have led to significant improvement in the 5-year survival. This, along with the cardiotoxic therapy regimens results in a remarkable incidence of major cardiovascular and cerebrovascular events (MACCE). Thus, it becomes imperative to address the intricacies of factors including racial disparities in MACCE, as these aid with facilitating equitable management of all CRC patients. Methods: Using ICD-10 codes, patients with CRC were identified from National Inpatient Sample 2019 database. We included all-cause in-hospital mortality (ACIHM), acute myocardial infarction (AMI), atrial fibrillation (AF), cerebrovascular accident (CVA), and sudden cardiac death (SCD) as MACCE for the outcomes. Baseline characteristics including demographics, comorbidities; and MACCE outcomes were studied using chi-square for categorical or ANOVA for continuous data (statistical significance determined as p-value < 0.05) and results were stratified based on patient’s races. Results: A total sample patient population of 171,695 patients with a diagnosis of CRC were identified of which 70.71% (121,410) were White, 13.85% (23,790) were Black, 9.15% (15,720) were Hispanic, 3.23% (5,555) were Asian/Pacific Islander, 0.5% (840) were Native American, and 2.55% (4380) belonged to Other races. Substantial differences in the prevalence of comorbidities were noted with hypertension (46.32%) and renal failure (24.74%) being more common in Black patients, diabetes mellitus (37.5%) in Native American patients, and dyslipidemia (37.89%) in White patients. Upon comparison with White patients, the ACIHM was higher in Black patients with adjusted odds ratio (aOR) of 1.23 (95% CI 1.057-1.432, p = 0.007) and Asian/Pacific Islander patients with aOR of 1.359 (1.014-1.823, p = 0.04). While AMI was found to be lower in all races, as compared to White patients, AF was remarkably higher in all races. CVA was higher in Black patients as compared to White patients with aOR of 1.626 (95% CI 1.401-1.886, p < 0.001). SCD was substantially higher in Black patients with aOR 2.059 (95% CI 1.478-2.869, p < 0.001), and in Hispanic patients with aOR 1.743 (95% CI 1.1-2.761, p = 0.018), when compared to White patients. Conclusions: The study noted higher prevalence of MACCE across the board with poorer outcomes in non-White populations, which highlights the urgent need for resource allocation to improve outcomes. This has to be done in pre and post cancer treatment patients, especially in high risk populations. Additionally, the role of cardio-oncology service at every stage of management of CRC appears to be crucial.
Predicting therapeutic clinical trial enrollment for underrepresented patients in neuro-oncology using supervised machine learning.
Authors: Mehari Mulki , Warrier Gayathri , Dada Abraham , Kabir Aymen , Chukwueke Ugonma Nnenna , Porter Alyx B. , Hervey-Jumper Shawn L.
Published: May 2024

1614

Background: Despite the unique ability of machine learning (ML) techniques to uncover complex interactive effects in datasets, studies exploring predictors of clinical trial enrollment have largely used standard statistical methods to discern associations. Furthermore, there have been limited applications of ML to close existing disparities in clinical trial enrollment of underrepresented patients in neuro-oncology. This study aims to use supervised machine learning to define and validate primary contributors of therapeutic clinical trial enrollment for a) all patients, b) women and c) NIH-designated minority patients with low- and high-grade glioma. Methods: Adult glioma patients who received care from the UCSF Brain Tumor Center between 1997- 2017 were identified in a prospective registry. Bootstrap forest (BF) and Recursive Partitioning (RP) models were created by randomly dividing patients in a 70/30 split into development (DEV) and validation (VAL) cohorts among all patients, women, and NIH-designated minority patients, separately. Model performance was assessed using the area under the curve (AUC) in the DEV and VAL cohorts. Results: Among 1042 patients, 350 patients (33.6%) enrolled in a therapeutic clinical trial. There were 445 women (42.7%), of which 144 (32.4%) enrolled, and 141 minority patients (13.5%), of which 39 (27.7%) enrolled. For all patients, in order of decreasing influence, the BF model selected median neighborhood household income, age, neighborhood poverty level, distance from hospital, tumor location, tumor volume, treatment with chemotherapy, occupation, KPS, insurance status, employment status, seizure at presentation, and volumetric extent of resection (EOR) to predict trial enrollment (DEV AUC: 0.984; VAL AUC: 0.746). For women, the BF model selected distance from hospital, age, household income, neighborhood poverty level, tumor location, treatment with chemotherapy, and KPS for trial prediction (DEV AUC: 0.972; VAL AUC: 0.746), whereas for minority patients, the BF model selected neighborhood poverty level, age, occupation, distance from hospital, tumor volume, insurance status, employment status, and EOR to predict trial enrollment (DEV AUC: 0.9830; VAL AUC: 0.769). The RP model for women designated those with non-White race as less likely to enroll (DEV AUC: 0.735; VAL AUC: 0.665) while the RP model for minority patients characterized those who preferred a non-English language or who were divorced or widowed as less likely to enroll (DEV AUC: 0.775; VAL AUC: 0.601). Conclusions: Supervised machine learning models achieved similar predictive performance among patient subgroups, while uncovering interactions between gender identity, minority status, and sociodemographic variables. These findings can guide targeted recruiting efforts to advance equitable trial enrollment for women and minorities.
Diagnostic test use and time to cancer diagnosis in Medicare recipients.
Authors: Chung Karen , Epstein Andrew J. , Kim Michelle K. , Karlitz Jordan J.
Published: May 2024

1622

Background: In the Medicare-aged population, liver, ovarian and pancreatic cancers have an incidence of 34–73/100,000, are associated with high mortality, can often be associated with no or vague symptoms, and rely on multiple tests for diagnosis (dx). Our objective is to quantitate dx testing and time to a cancer dx in Medicare recipients. Methods: Pts with newly dx’d liver, ovarian or pancreatic cancers were identified in 100% fee-for-service (FFS) Medicare enrollment and claims data from 1 Oct 2017 - 31 Dec 2022. Dx test use was tracked for up to 24 months prior to dx; pts had to have ≥1 dx test within 60 days before the cancer dx date. Inclusion criteria also included ≥24 months of continuous enrollment in FFS Medicare prior to dx and qualification based on age ≥65. Exclusion criteria included prior cancer dx and Medicare Advantage enrollment. The start of dx workup was identified by looking back in time at the sequence of dx tests occurring before the cancer dx date and were separated by ≤60 days between consecutive tests. The earliest test in the sequence was deemed the first dx test. Index date was defined as the latest office visit date before the first dx test or date of the first dx test if no office visit met criteria. Dx tests (ie, biopsies, endoscopies, imaging, lab tests) were identified by billing/CPT codes. Dx workup duration from index to dx date and dx test types received were tracked. Results: Among 59,490 Medicare beneficiaries analyzed, mean age was 77.0 (SD 7.3), 60% were female, and 80% were non-Hispanic White. Median (25th, 75th percentile) days from index date to cancer dx was 56 (24, 109) for liver, 47 (20, 91) for ovary, and 43 (16, 89) for pancreas. Dx testing modalities utilized for each cancer type (Table) demonstrate high variability. The percentage of pts who underwent both CT and MRI to help establish a liver, ovarian and pancreatic cancer dx was 38.6%, 14.1% and 32.3%, respectively. While overall imaging use prior to dx was high, PET and PET-CT use was low (<1% PET; 1.7%–2.2% PET-CT). Conclusions: Multiple tests are utilized to establish a cancer dx in Medicare beneficiaries, including use of multiple imaging modalities in the same patient. 25% of pts required more than 89-109 days, depending on cancer type, to establish a dx. There may be opportunities to increase diagnostic efficiency and shorten time to cancer diagnosis in older individuals. [Table: see text]
Analyzing correlates for cervical cancer awareness in Mauritania, Madagascar, and Benin from the Demographic Health Survey (DHS): 2017-2022.
Authors: Olivieri Daniel J , Eastment McKenna , Mugisha Noleb Mugume , Pinder Leeya Fatima , Menon Manoj
Published: May 2024

1626

Background: Cervical cancer is the leading cause of cancer-related mortality in low- and middle-income countries (LMICs). Prior studies associate high cervical cancer awareness with reductions in cervical cancer incidence. Herein we utilize nationally representative Demographic and Health Surveys Program (DHS) to analyze correlates of cervical cancer awareness and inform global outreach strategies. Methods: All DHS surveys conducted between 2017-2022 were queried for questions on cervical cancer awareness. Socio-demographic (e.g., age, marital status), socioeconomic (e.g., education, wealth, literacy) and variables pertaining to healthcare decision making, intimate partner violence (IPV), and female genital mutilation/circumcision (FGC/M)) were extracted. Sample weights were applied, and bivariate logistic regressions were performed. Variables with p<0.20 were included in multivariate analysis. Results: Of the DHS surveys, we analyzed data from 25,239 women aged 15-49 years old living in Mauritania, Madagascar, and Benin - the only three countries which met search criteria. Cervical cancer awareness varied from 41% in Mauritania (3,283/7,290), 32% in Madagascar (3,071/9597), and 10% in Benin (783/7,712). After multivariate adjustment, age (OR=1.03 [1.02-1.04]; OR=1.04 [1.03-1.05]; OR=1.03 [1.01-1.05]), education (OR=1.21 [1.06-1.38]; OR=1.68 [1.48-1.91]; OR=1.83 [1.51-2.23]), and wealth index (OR=1.18 [1.07-1.30]; OR=1.24 [1.16-1.32]; OR=1.18 [1.07-1.30]) were associated with increased awareness across Mauritania, Madagascar, and Benin, respectively. Mobile telephone ownership was associated with increased awareness in Mauritania (OR=1.87 [1.48-2.36]) and Benin (OR=1.66 [1.27-2.19]), and internet usage was associated with increased awareness in Madagascar (OR=1.75 [1.46-2.10]) and Benin (OR=1.71 [1.33-2.31]). Women who underwent FCG/M (OR=0.81 [0.67-0.98]) were associated with decreased awareness in Mauritania. Women who experienced IPV were associated with increased awareness (OR=1.39 [1.11-1.73]) in Mauritania. Women who independently make healthcare decisions were associated with decreased awareness in Mauritania (OR=0.88 [0.83-0.95]) but increased awareness in Madagascar (OR=1.07 [1-1.15]). Rurality was associated with decreased awareness in Madagascar (OR=0.71 [0.59-0.84]). Last, less than 1% (200/25,239) of all women were screened for cervical cancer. Conclusions: Age, education, and wealth were associated with increasing awareness, while rurality and FGM/C were associated with decreased awareness in various settings. Given the known association between awareness and screening, targeted efforts to increase awareness among women with lower socioeconomic status has the potential to reduce global cervical cancer disparities.
Evaluating the utility of routine survivorship exams in breast cancer: Modality of detection of recurrence in a prospective cohort study.
Authors: Duffens Ali , Laurent Cecile , Roh Janise M. , Kushi Lawrence H. , Liu Raymond
Published: May 2024

1629

Background: National Comprehensive Cancer Network surveillance guidelines for invasive breast cancer recommend a history and physical exam every 3-12 months for the first 5 years, followed by annually, and mammography every 12 months. However, frequent in-office visits create time toxicity for breast cancer survivors, may have low utility in recurrence detection, and can create false reassurance. This study evaluates the modality of breast cancer recurrence in an integrated health system with access to primary and specialty care. Methods: We investigated mode of detection of recurrent breast cancer in the Pathways Study, a prospective cohort study of adult women diagnosed with and treated for invasive breast cancer in Kaiser Permanente Northern California, with enrollment from 2006 to 2013, and follow-up through December 2021. In this analysis, we included 4,431 women diagnosed at Stages I-III. Cohort members were followed for recurrences, deaths, and other outcomes. Of primary interest was modality of detection of recurrence, categorized as patient-driven symptoms, surveillance mammogram, diagnostic testing (i.e., other surveillance imaging for recurrence such as PET CT or MRI), routine clinical breast exam, or incidental finding. Results: A total of 617 (13.9%) women were identified as having breast cancer recurrence. Patients with recurrence shared similar demographic characteristics to those without recurrence. The recurrence population had median age of 59.2 years, BMI of 28.2 kg/m2, and racial/ethnic composition of 63% white,13% Hispanic,12% Asian, and 10% black. The median time from diagnosis to recurrence was 4 years. Seventy percent of recurrences were found to have distant metastatic disease, of which only 6.7% had concurrent local nodal and/or breast involvement. For those without metastases, 17.7% had recurrence localized in the ipsilateral breast, 2.8% in both the breast and locoregional nodes, and 9.3% only in locoregional nodes. Most recurrences were detected by patient driven symptoms (69.4%). Among the total cases, 8.1% of patients were diagnosed by routine mammogram, 10.9% with diagnostic testing and 4.5% by incidental finding. Recurrences in 6.8% of patients were detected by routine physician exam. Overall survival for those with recurrence was 31.1% and most deaths were attributed to breast cancer (89%). Conclusions: Our study, the largest investigation of breast cancer recurrence modality of detection in a US community oncology setting with comprehensive care, revealed the majority of recurrences were identified through patient self-detection with only 6.8% detected by physician exam. Most recurrences were distant, underscoring the need for alternative screening modalities to detect metastatic recurrences earlier, especially in the context of emerging treatments and improved survival rates for oligometastatic disease.
Patient satisfaction with cancer care delivery through telemedicine at a comprehensive cancer center across three years during and after the COVID-19 pandemic.
Authors: Doshi Sahil D , Khadem Charvadeh Yasin , Seier Kenneth , Bange Erin Mary , Daly Robert Michael , Polubriaginof Fernanda C. G. , Buckley Michael T. , Kuperman Gilad , Stetson Peter D. , Schrag Deb , Morris Michael J. , Panageas Katherine
Published: May 2024

1632

Background: Telemedicine, once sparingly utilized, surged during the COVID-19 pandemic to enhance care accessibility and safety concerns. Despite initial satisfaction, its usage remains highly variable across institutions. We sought to explore patient satisfaction at a comprehensive cancer center, associations with demographic characteristics, and change over time. Methods: A survey was sent to all first-time telemedicine users at Memorial Sloan Kettering Cancer Center from September 2021 to October 2023. Adult patients who had their initial telemedicine visit, regardless of specialty, received the questionnaire. It comprised 10 general questions about the telemedicine experience and 11 questions regarding clinical trial education and informed consent. To analyze the unstructured free text responses, we employed BERTopic, a topic modeling algorithm that leverages transformer-based embeddings to facilitate the creation of easily interpretable topics within a collection of text documents. Through topic modeling with BERT embeddings, we captured subtle nuances and semantic relationships in language to identify topics more effectively. Results: A total of 15,111 patients completed 15,251 questionnaires; 140 patients completing two surveys. Patient demographics are summarized in Table 1; the median age at encounter was 66 years and 98% of patients preferred English. Satisfaction levels were high, with 92% expressing willingness for future telemedicine visits and 90% recommending it to other patients. Notably, 21% found telemedicine superior to in-person visits, while 53% considered them equal. Further, satisfaction remained consistent across six-month intervals from 2021-2023. In 1606 (11%) surveys, patients noted discussing clinical trials; 17% preferred in-person discussions for the informed consent process while most either preferred telemedicine or had no preference. Topic modeling revealed 18 topics within the unstructured dataset; key topics included comments on video & audio quality, connectivity and technology issues, convenience for patients who live outside of the city and those with physical limitations, and long wait time to see a doctor. Conclusions: Our analysis confirms high patient satisfaction with telemedicine, including discussions on clinical trial enrollment, that has remained consistent in the years following the COVID-19 pandemic. Given variability in use, it is important to identify how to better deliver telemedicine to those patients who prefer it.[Table: see text]
Oncologic outcome of response-guided axillary treatment in patients with cN1 breast cancer after primary systemic therapy.
Authors: van Hemert Annemiek , van Loevezijn Ariane , Baas Marie-Sophie , Stokkel Marcel P , Groen Emilie , van der Noort Vincent , Loo Claudette , Sonke Gabe S. , Russell Nicola , van Duijnhoven Frederieke H , Vrancken Peeters Marie-Jeanne T.F.D
Published: May 2024

514

Background: In breast cancer, the majority of clinically node positive (cN1) patients are treated with primary systemic treatment (PST), with increasing rates of axillary pathologic complete response (pCR). Evidence supporting tailoring axillary treatment according to the response is growing. However, it is still debatable whether ALND is beneficial in cN1 patients with residual nodal disease and if any further axillary treatment is necessary in patients achieving pCR. In this study, we present the four-year oncologic outcome of cN1 patients undergoing either axillary radiation treatment or no axillary treatment according to the ‘Marking Axillary lymph nodes with Radioactive Iodine seeds’ (MARI)-protocol. Methods: Between 2014 and 2021, we prospectively enrolled patients with node positive breast cancer and 1 - 3 involved axillary lymph nodes on FDG-PET/CT pre-PST, who were treated according to the MARI-protocol. Patients with residual disease of the MARI node (ypN1) received axillary radiotherapy (RT), while patients with a pCR of the MARI node (ypN0) received no further axillary treatment. The primary endpoint was the axillary recurrence rate. Secondary endpoints include invasive disease free survival (iDFS) and overall survival (OS), calculated using the Kaplan-Meier method. Results: Of the 367 included patients, more than half (54%, n= 198) had hormonal receptor positive (HR+)/Human Epidermal growth factor 2 negative (HER2-) breast cancer; 59 patients (16%) had HR+/HER2+; 39 patients (11%) had HR-/HER2+ and 71 patients (19%) had triple negative (TN) subtype. Median age was 49 (IQR 41 – 56) years. 231 (63%) patients who had ypN1 received RT and 136 patients (37%) who achieved ypN0 received no further axillary treatment. Median follow up was 49 (IQR 32 – 70) months. Axillary recurrence rate was 3.5% ( n= 8) in patients with ypN1 and 0.7% ( n= 1) in patients with ypN0. Most axillary recurrences ( n= 6) occurred simultaneously with distant metastases in the ypN1 group. In patients with ypN1, the iDFS was 86% and the OS 93%; in ypN0 patients, the iDFS was 93% and the OS 98%. Conclusions: Response-guided axillary treatment in patients with limited nodal disease according to the MARI protocol is associated with favorable oncologic outcome without performing ALND’s. De-escalation can therefore be considered safe. [Table: see text]
Recurrence score gene axes scores and outcomes by race and ethnicity in the RxPONDER trial.
Authors: Abdou Yara , Hoag Jess R , Barlow William E. , Gralow Julie R. , Meric-Bernstam Funda , Albain Kathy S. , Hayes Daniel F. , Lin Nancy U. , Perez Edith A. , Goldstein Lori J. , Chia Stephen K. L. , Dhesy-Thind Sukhbinder K. , Rastogi Priya , Schott Anne F. , Racz Jennifer M. , Tripathy Debashish , Hortobagyi Gabriel N. , Pusztai Lajos , Sharma Priyanka , Kalinsky Kevin
Published: May 2024

515

Background: Racial inequities in breast cancer outcomes remain a significant healthcare concern. In a previous analysis of the RxPONDER trial by race/ethnicity, we showed that non-Hispanic Black (NHB) women have worse outcomes compared to non-Hispanic Whites (NHW) despite similar 21-gene recurrence scores (RS). The RS is determined by an assay consisting of 16 cancer-related genes involved in invasion, ER and HER2 signaling, and proliferation. To provide a better understanding of the differences in underlying tumor biology amongst different racial/ethnic groups, we analyzed RS gene axes scores amongst each group and associations with outcomes. Methods: A total of 3,102 women were included: Hispanic (15.5%), NHB (4.7%), Asian (9.5%), and NHW (70.2%). The primary outcome was invasive disease-free survival (IDFS). This analysis extends median follow-up from 5 to 7 years and evaluates gene axes scores that are components of the RS by race/ethnicity. Impact of proliferation, ER, GRB7 (HER2), and invasion axes scores on IDFS was evaluated in Cox regression models. Results: There were no differences in RS distribution across racial/ethnic groups, and RS remained prognostic for each group with no significant variation in RS prognostic value. However, NHBs were noted to have significantly higher proliferation axis scores than NHWs (p<0.001); HER2 axis scores was higher for Asians than NHWs (p<0.001); and Hispanics had both higher HER2 (p=0.002) and proliferation (p=0.02) axes scores compared to NHWs. These results remained statistically significant after adjusting for age. Relative to NHWs, IDFS was worse for NHBs (HR 1.41; 95% CI 0.98-2.03) and better for Asians (HR 0.63; 95% CI 0.43-0.91) in unadjusted analysis. Adjusting for treatment arm, age, grade, menopausal status, proliferation, ER and HER2 axes scores attenuated the impact of race on IDFS for NHBs (HR 1.22; 95% CI 0.84-1.76), although the findings were unchanged for Asians (HR 0.64; 95% CI 0.44-0.93; Table). In a multivariable model, proliferation axis (HR 1.56; 95% CI 1.35-1.80) and ER axis (HR 0.81; 95% CI 0.71-0.93) were prognostic for IDFS. Conclusions: RS gene axes scores differ by race/ethnicity with higher proliferation axis scores noted in NHBs, which could partially explain their inferior outcomes noted in RxPONDER. These findings suggest that tumor biology is indeed important, however, we must dig deeper to uncover intricate factors that contribute to disparities, which is key to designing comprehensive strategies to address them. Clinical trial information: NCT01272037 . [Table: see text]
Estimating benefit from dose dense adjuvant chemotherapy for early breast cancer in the PANTHER randomized phase 3 trial.
Authors: Matikas Alexios , Gnant Michael , Johansson Hemming , Untch Michael , Tsiknakis Nikolaos , Greil Richard , Loibl Sibylle , Foukakis Theodoros , Bergh Jonas C. S.
Published: May 2024

521

Background: Adjuvant dose dense chemotherapy for early breast cancer improves patient outcomes across all subgroups compared with standard interval treatment. However, the effect of dose dense treatment based on individual patient risk and over time, and the performance of the PREDICT model at this setting are not well-studied. Methods: This is an exploratory analysis from the phase 3 PANTHER trial (NCT00798070) that compared adjuvant sequential epirubicin/cyclophosphamide (EC) and docetaxel (D) administered in either tailored dose dense (tDD EC/D, every 2 weeks) or standard interval schedule (FEC/D, every 3 weeks) to patients with high-risk resected early breast cancer. Dose tailoring in the experimental arm was performed according to a predefined algorithm based on hematologic and non-hematologic toxicity. We evaluated the performance of PREDICT in terms of calibration and discrimination in the entire cohort and subgroups of interest, conducted a subpopulation treatment effect pattern plot (STEPP) analysis and observed the relative treatment effect over time. Results: The intention-to-treat population consists of n=2003 randomized patients. Median follow-up was 10.3 years (interquartile range, 9.1 – 10.5 years). PREDICT consistently underestimated 5-year (absolute difference 1.4%) and 10-year overall survival (absolute difference 6.6%) in the entire population and across all subgroups, but mostly so in the highest risk patients where the difference between observed and predicted 10-year survival reached 20.4% for patients with tumors larger than 5 cm. Discriminatory accuracy was lower for 10-year than for 5-year survival (AUC 0.728 and 0.786, respectively), although the difference in model performance between the two treatment groups was small. In STEPP analysis, absolute benefit from tDD EC/D in the primary endpoint of breast cancer relapse free survival was stable across risk-defined overlapping subpopulations and ranged from 3.8% in the lowest risk patients to 3.6% in the highest risk ones. There was no evidence of differential treatment effect through time (pinteraction >0.1 for all time-to-event endpoints). Conclusions: In this largely node-positive population, PREDICT consistently overestimated risk for death in all patient subgroups. We could not reliably identify any subgroup not benefiting from dose dense treatment, which should be the standard of care for primary resected high-risk breast cancer. Clinical trial information: NCT00798070 .
Patient-reported provider communication skills and adherence to recommended treatment in breast cancer.
Authors: Chino Fumiko , Chino Junzo P. , Thom Bridgette , Meske Sam , Ganz Patricia A. , Weiss Marisa C.
Published: May 2024

537

Background: Effective communication is essential to build trust and improve patient understanding of cancer diagnosis and treatment. Little is known about patient comprehension of provider explanations and whether better communication influences adherence to recommended treatment especially in breast cancer (BC) which may require years of adjuvant treatment. Methods: Between 7/2023-8/2023, active patients and survivors were recruited from Breastcancer.org and consented to participate in an anonymous online survey in English or Spanish. Eligibility included: US resident, age ≥18, and diagnosed with BC within the past 10 years. Survey assessed patient-reported overall communication, side effect communication, and treatment adherence. Multivariate analysis (MVA) assessed relationship of patient-reported understanding and treatment adherence after controlling for gender, age, stage, race, ethnicity, and education. Results: Of 1266 screened, 997 met eligibility and participated. 98.2% identified as women, 81.2% White, 4.8% Black, and 4.2% Hispanic. Median age was 62 (interquartile range IQR 53-69) and median time since diagnosis 2.1 years (IQR 1-5.1). 6.5% had metastatic disease. 77.3% had a college degree. 93.4% participants reported their doctors “usually” or “always” explained things in a way they could understand. On MVA, there was a trend for minoritized groups (Black, Hispanic, Indigenous patients) to report their doctors were less likely to explain things well (OR 0.57, 95%CI 0.30-1.06, p=0.08) but there were no significant differences. Most felt their doctors “definitely” (45.8%) or “to some extent” (10.3%) explained possible short-term side effects. One-third (35.2%) stated their doctors explained “to some extent” and that they also did their own research to fully understand short-term side effects; 6.1% stated that their own research was the only thing that helped them understand as their doctors did not explain. Less than one-third (27.9%) felt their doctors “definitely” explained possible long-term side effects. 7.7% participants took less medication that their doctors prescribed due to treatment side effects, 15.1% stopped taking a medication or treatment altogether. Patients who reported that their doctors were “sometimes” or “never” understandable were more likely to reduce or stop their treatment (44.4% vs 21.3%, p<0.001). This held true on MVA: patients reporting poor communication were less likely to adhere to recommended treatment (OR 0.36, 95%CI 0.21-0.62, p<0.001). Conclusions: Surveyed patients with BC report good provider communication skills overall but note that side effect profiles are not always well-explained, especially for long-term side effects. More than 1 in 5 did not follow some aspect of BC treatment as recommended, and those who reported poor communication with their providers were 64% less likely to be adherent to recommended care.
Long-term oncologic outcome of breast-conserving surgery in breast cancer with BRCA 1/2 mutation (ON-BRCA II, KoREa-BSG 06).
Authors: Lee Janghee , Ryu Jai Min , Kim Hong-Kyu , Park Hyung Seok , Kang Byeongju , Ahn Sung Gwe , Chung Min Sung , Shin Seon-Hi , Go Junwon , Kim Sanghwa , Kim Eun Young , Kang Young-Joon , Min Sun Young , Lee Moo Hyun , Shin Eunju , Shin Jisoo , Lee Sae Byul , CHA CHIHWAN
Published: May 2024

552

Background: Among patients with sporadic breast cancer, it is well known that prognoses are similar following breast-conserving surgery (BCS) versus mastectomy. However, previous data assessing oncologic outcomes between BCS and mastectomy in patients with BRCA mutation are limited and inconsistent. Thus, this study aims to compare the oncologic outcomes including locoregional recurrence (LRR), distant recurrence (DR), and overall survival (OS) among this population. Methods: Patients with BRCA mutation and index breast cancer who underwent BCS or mastectomy between January 2008 and December 2015 were retrospectively screened from 13 institutions. We included patients aged from 20-80 with invasive breast cancer (pT1-3 N0-3). Patients with de novo metastasis were excluded. To minimize selection bias from retrospective nature, the propensity score matching (PSM) with Greedy nearest neighbor method was performed for covariates including age, molecular subtype, and tumor stage. Results: A total of 553 patients with BRCA mutation were identified. Among them, 367 (66.2%) patients received BCS and 186 (33.8%) were treated with mastectomy. After 1:1 PSM, there was no significant differences in age, molecular subtype, tumor size, nodal status, and histologic tumor grade between patients undergoing BCS versus mastectomy. At 8.3 years of median follow up, LRR, DR, and OS rates did not differ between groups (all p > 0.05). On multivariate analysis, type of breast surgery (BCS vs. mastectomy) was not significantly associated with the oncologic outcomes after adjusting covariates including age, molecular subtype, tumor stage, and histologic grade (all p > 0.05). Additionally, we performed subgroup analysis in matched patients based on tumor size, LN metastasis, HG, and subtype. In all subgroup, the type of breast surgery was not a significant risk factor influencing disease recurrence. Conclusions: Our findings suggest that there was no difference in oncologic outcomes among BRCA mutation carriers who underwent BCS or mastectomy. Breast conservation with close surveillance is a reasonable treatment option for BRCA mutation carriers. Further studies combined with prospectively collected data are warranted to validate our findings.
Radiogenomics of homologous recombination deficiency (HRD) in breast cancer: Radiomics-based image biomarker for HRD.
Authors: Lim Joonoh , Paik Pill Sun , Lee Jeongmin , Oh Brian Baek-Lok , Kim Ryul , Ju Young Seok , Lee Jeong Seok , Kwon Minsuk , Lee Sangmoon , Lee Won-Chul
Published: May 2024

554

Background: Homologous recombination deficiency (HRD) in breast cancer is an actionable target, with treatment efficacy potentially linked to timely detection. Notably, BRCA1 and BRCA2 are key genes implicated in HRD, and their pathogenic germline mutations are crucial criteria for the use of poly (ADP-ribose) polymerase inhibitors (PARPi). Although germline BRCA1/2 mutations are detectable in only a small fraction (1-5%) of breast cancers, recent whole-genome sequencing (WGS) studies have revealed that up to 22% of breast cancers also exhibit HRD-like genomic characteristics, suggesting a broader potential for HRD-targeted therapy. This has spurred the development of genomic-feature-based HRD identification methods. However, the invasive and costly nature of these methods poses a challenge. This has prompted our investigation into non-invasive image biomarkers for HRD identification. Methods: Invasive breast cancer patients were recruited from March 2021 to August 2022. Eligibility criteria included availability of fresh-frozen tumor tissue for WGS and suitability for dynamic contrast-enhanced (DCE) MRI to facilitate radiomics analysis. The association between HRD and radiomic features as well as clinicopathologic factors was investigated through rigorous genomic and statistical analysis. Results: This study encompassed 145 patients aged 20 to 69 years, of whom 16.6% (24 out of 145) were genomically identified as HRD. All patients harboring pathogenic germline mutations in BRCA1 (n=3) or BRCA2 (n=2), along with concomitant somatic LOH, exhibited HRD. A comprehensive analysis of 214 radiomic features revealed that tumor sphericity, informational measure of correlation 1 (IMC1), size-zone non-uniformity normalized (SZNN), and small area emphasis (SAE) derived from subtracted early dynamic T1-weighted imaging were significantly correlated with HRD. Moreover, these radiomic features demonstrated substantial diagnostic value, as evidenced by their ROC-AUC and PR-AUC performance against baseline models: Sphericity (ROC: 0.62, p=0.055; PR: 0.22, p=0.053), SAE (ROC: 0.63, p=0.052; PR: 0.32, p=0.007), SZNN (ROC: 0.63, p=0.04; PR: 0.30, p=0.007), and IMC1 (ROC: 0.62, p=0.067; PR: 0.29, p=0.02). Additionally, our findings suggest that these radiomic features are more directly related to HRD than to the triple-negative phenotype, which is commonly linked to HRD. Conclusions: We found that four radiomic features from MRI have significant predictive value for identifying HRD in breast cancer. Given their fair predictability and immediate availability, these features are ideally suited for a screening approach, potentially identifying more patients eligible for targeted treatment. This finding represents a significant advancement in the fields of radiology and precision oncology, opening new avenues for patient-specific treatment strategies.
Postpartum breast cancer: Analysis of factors related to pregnancy and identification of differential prognostic markers.
Authors: García Cesteros Natalia , López-Herrero López María , Guevara Madrid Geraldina , Mora Martin Fernando , Teso Martín Beatriz , De La Fuente Dominguez Iciar , Guil Luna Silvia , Aranda Aguilar Enrique , De La Haba Juan
Published: May 2024

557

Background: Postpartum breast cancer (PPBC) has an increasing incidence. It is associated with a worse prognosis compared to other breast cancers diagnosed outside of this stage. Objectives: To study clinical and histopathological differences between PPBC (diagnosed within 10 years after delivery) and non-postpartum breast cancer (NPBC, diagnosed more than 10 years after delivery or in nulliparous). Analyze whether reproductive factors such as parity or lactation influence these characteristics. Methods: An observational, analytical and retrospective case-control study is carried out. For the first part, we consider those women with PPBC as case; healthy mothers as control. For the second part, we consider PPBC women as case; NPBC women as control. The data have been analyzed with SPSS v.22. Results: 2698 women under 45 years were recruited. 264 (9.8%) have breast cancer and 2434 (90.2%) are healthy women. The percentage of ex-smokers is higher in PPBC compared to healthy mothers (30.6% vs. 19.7%) (X2=9.632; p=0.022; SS). The proportion of women with previous gynecological pathology is higher in PPBC group than in the group of healthy mothers (48.9% vs. 25.7%) (X2=33.767; p<0.001; SS). The same occurs with previous breast pathology (51.9% vs. 21.7%) (X2=62.75; p<0.001; SS). Women with early PPBC (diagnosed within 5 years after delivery) have higher percentage of previous mastitis compared to the rest of groups that develop tumor beyond 5 years postpartum (20.3% vs. 3.6%) (X2=17.76; p=0.023; SS). The percentage of female pregnancies is more frequent in early PPBC (58.6%) compared to non-postpartum or late PPBC (42.4%) (X2=4.039; p=0.044; SS). The percentage of women who abruptly discontinued breastfeeding is higher in those with PPBC with 27.5% compared to healthy mothers (12.6%) (X2=18.448; p<0.001; SS) (Table). PPBC has higher percentage of stages II (63.9%), the other group of NPBC is mostly diagnosed in stage I (64.9%) (X2=9.808; p=0.002; SS). We found higher elevated expression of Ki67 in early PPBC (90.1%), compared to non-postpartum cancer or late PPBC (77%) (X2=6.252; p=0.012; SS). We observe higher proportion of negative estrogen receptors in early PPBC (36.6%) compared to late PPBC or non-postpartum cancer (13.6%) (X2=9.880; p=0.002; SS). Conclusions: Postpartum breast cancer presents different clinical and histopathological characteristics, highlighting differences in early postpartum period. PPBC has worse prognosis, it constitutes a different entity. Breastfeeding abrupt interruption is associated with development of PPBC. [Table: see text]
Association of tumor-infiltrating lymphocytes (TILs) and immune signatures with PAM50 intrinsic subtyping hormone receptor-positive (HR+)/HER2-negative (HER2-) early breast cancer (BC): A translational analysis of two multicentric neoadjuvant trials.
Authors: Griguolo Gaia , Paré Laia , Miglietta Federica , Bottosso Michele , Generali Daniele Giulio , Frassoldati Antonio , Musolino Antonino , Spazzapan Simon , Vernaci Grazia , Giarratano Tommaso , Cappellesso Rocco , Bisagni Giancarlo , Piacentini Federico , Tagliafico Enrico , Cagossi Katia , Pinato Claudia , Schiavi Francesca , Prat Aleix , Dieci Maria Vittoria , Guarneri Valentina
Published: May 2024

558

Background: HR+/HER2− BCs are generally described as immunologically cold, with low levels of TILs and PD-L1. Nevertheless, the addition of immunotherapy (ICI) to chemo has been reported to increase pCR rates in high-risk early HR+/HER2– BCs. Assessing the interaction between immune features and tumor biology may identify of a subset of patients (pts) with HR+/HER2− BC that would be the ideal candidates for the combination of chemo and ICI. Methods: Gene-expression data from two multicentric neoadjuvant phase II trials (GIADA, LETLOB) enrolling stage II-IIIA HR+HER2- BC pts was retrieved (Dieci, CCR 2022; Guarneri, JCO 2014). In the GIADA trial, 758 genes were assessed on baseline tumor samples by nCounter (N=43). In the LETLOB trial, gene-expression data (Affymetrix platform) from baseline core-biopsies was available for 66 pts. Intrinsic subtype was assigned using a research-based PAM50 predictor. TILs were evaluated following guidelines. Association of TILs and immune signatures with intrinsic subtyping was assessed by Kruskal-Wallis test. Results: PAM50 subtype distribution (N=109) was 44% Luminal B (LumB), 33% Luminal A (LumA), 18% Basal-like, 5% HER2-enriched (HER2-E). TILs were assessed on 101 samples: median 2 (range 0-100). Basal-like BCs showed higher TILs than other subtypes (p=0.008). No significant difference was observed between LumA and LumB BCs (Table). Basal-like tumors showed higher levels of previously published immune signatures associated with CD8 T-cells (p<0.001), Cytotoxic cells (p<0.001), IFN-gamma (p<0.001), and response to ICI in the GeparNuevo trial (p=0.003) (N=109). PD-1 (p=0.002), PD-L1 (p=0.001), and PD-L2 (p=0.001) genes were also more expressed in Basal-like BCs (evaluable in 43 samples). No significant difference was observed between LumA and LumB tumors. A significant weak to moderate positive correlation was observed between continuous TILs and immune signatures and basal-like PAM50 signature (p<0.001, Spearman coefficient=0.372 for TILs, from 0.354 to 0.648 for immune signatures). Conclusions: PAM50 intrinsic subtyping and TILs/immune signatures capture only partially overlapping information on the biology of HR+/HER2- BCs. Pts with HR+/HER2- BCs simultaneously showing features of biological aggressiveness and enhanced immunogenicity may represent the ideal candidates for the combination of ICI and chemo. [Table: see text]