bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of real-world (RW) data for metastatic breast cancer (mBC) patients (pts) with somatic BRCA1/2 (sBRCA) or other homologous recombination (HR)-pathway gene mutations (muts) treated with PARP inhibitors (PARPi).
Authors: Batalini Felipe , Madison Russell , Pavlick Dean C. , Sokol Ethan , Snow Tamara , Sondhi Arjun , Frampton Garrett M. , Jenkins Colby , Garber Judy Ellen , Wulf Gerburg M. , Venstrom Jeffrey Michael , Tung Nadine M. , Castellanos Emily , Schrock Alexa Betzig , McGregor Kimberly
Published: June 2021

10512

Background: PARPi are approved for treatment of pts w/ HER2-negative mBC and germline BRCA1/2 (g BRCA) pathogenic or likely pathogenic variants (muts); however, clinical benefit has also been demonstrated in mBC pts w/ sBRCA or other HR-pathway gene muts. Using a RW Clinico-Genomic Database (CGDB), we assessed outcomes for pts w/ gBRCA muts compared to pts w/ either s BRCA or other HR-pathway muts treated w/ PARPi. Methods: 6,329 mBC pts from ̃280 US cancer clinics were included in the Flatiron Health (FH) -Foundation Medicine (FM) CGDB, which includes comprehensive genomic profiling (CGP) linked to de-identified, electronic health record (EHR)-derived clinical data. Eligible pts had mBC, received care in the FH network from 1/1/2011-9/1/2020, and had tissue CGP by FM. Pts classified as gBRCA: positive germline result in EHR and BRCA mut predicted germline per FM’s somatic, germline, zygosity algorithm (SGZ) (Sun et al PMID 29415044). Non-g BRCA: negative germline results in EHR and a somatic BRCA (s BRCA) mut per SGZ or BRCA wild-type w/ another HR mut per CGP result. Pts w/o a documented gBRCA result in EHR, unknown FM BRCA SGZ result, or conflicting results were excluded. RW overall survival (rwOS) and RW progression-free survival (rwPFS) from start of PARPi for pts w/ gBRCA and non- gBRCA mBC were compared using Kaplan-Meier analysis and Cox regression adjusted for mBC line number, prior platinum, age at PARPi initiation, race, and receptor status. Results: Among pts who received PARPi in the mBC setting, 44 had gBRCA and 18 had non -gBRCA: 9 s BRCA (5 BRCA1, 4 BRCA2), 4 PALB2, 2 ATM, and 1 each of ATM+CDK12, BARD1+FANCF+RAD54L, and CHEK2. Of HR muts 76% were confirmed biallelic: 33/44 gBRCA (11 unknown), 8/9 sBRCA, 3/4 PALB2, and 3/5 other (1 unknown). Neither median rwPFS nor rwOS from start of PARPi were significantly different between the non-g BRCA and g BRCA cohorts (rwPFS: 7.0 [4.6-11.3] vs 5.5 [4.3-7.2] months (mos), aHR: 1.19 [0.57 – 2.43]; rwOS: 15.0 [7.95-16.3] vs 11.5 [9.46-NA] mos, aHR: 0.85 [0.36-1.98]). For 9 pts w/ sBRCA mut, median rwPFS was 7.1 mos (range 1.4-12.4) and all pts had progressed by data cut off. Conclusions: Despite small pt numbers and limitations from RW data, our results suggest that pts w/ biallelic non-g BRCA mBC may derive similar benefit from PARPi when tumor CGP detects a s BRCA mut or germline or somatic mut in other HR-pathway genes. These findings are consistent w/ the results from TBCRC-048 (Tung et al PMID 33119476) and support further randomized trials exploring the efficacy of PARPi in this population.[Table: see text]
The marginal diagnostic benefit of pancreatic cancer molecular profiling after germline testing.
Authors: Walker Evan Justin , Blanco Amie , Carnevale Julia C. , Cinar Pelin , Collisson Eric Andrew , Tempero Margaret A. , Ko Andrew H.
Published: June 2021

10513

Background: Germline genetic testing is now universally recommended for patients (pts) with pancreatic ductal adenocarcinoma (PDAC) for purposes of both familial screening and therapeutic guidance. Treatment selection can be further informed by tumor molecular profiling (TMP) to identify targetable somatic alterations in pts with advanced disease, but this is inconsistently applied. Determination of the rate of actionable findings identified with TMP after germline testing, which we term marginal diagnostic benefit, may inform practice patterns and workflow in this patient population. Methods: This retrospective analysis included all pts with PDAC who underwent germline testing and TMP at UCSF over a 4-yr period. Medical records were reviewed for demographics, disease-specific data, and germline testing/TMP clinical reports. Alterations classified as ‘pathogenic’ or ‘likely pathogenic’ were included, and were deemed ‘actionable’ if there was clinical or preclinical evidence of benefit from targeted therapy in any cancer, as previously described. Results: From 1/2016-1/2020, 144/738 (20%) UCSF pts with PDAC completed both germline testing and TMP. Germline testing identified actionable pathogenic alterations in 10 (7%). TMP confirmed 8/10 of these alterations and identified 3 additional therapeutic targets. Among the 134 pts without actionable germline findings, TMP identified 45 new therapeutic targets in 41 (31%) pts, increasing the overall rate of actionable findings from 7% to 35%. Most (35/58, 60%) actionable alterations involved genes associated with the Homologous Recombination DNA Damage Repair (HR-DDR) pathway (Table). 80% of pts with HR-DDR pathway alterations (9/10 germline, 19/25 somatic) received platinum-based chemotherapy. Four pts were treated with targeted therapy based on test results: PARP-inhibitor (n = 2, germline BRCA1 and PALB2 mutations), PARP-inhibitor + ATR inhibitor (n = 1, somatic ARID1A mutation) and mTOR inhibitor (n = 1, somatic STK11 deletion). Conclusions: In this analysis, PDAC TMP after germline testing increased the detection of actionable alterations (the marginal diagnostic benefit) by five-fold. As more somatic tumor alterations become actionable with the development of targeted therapeutics, TMP is a necessary complement to germline testing to fully inform personalized treatment decisions for all pts with PDAC.[Table: see text]
Breast cancer ER, PR, and HER2 expression variance by germline cancer predisposition genes.
Authors: Wei Grace , Rosa Marilin , Chang Maxine , Czerniecki Brian J. , Wang Xia
Published: June 2021

10526

Background: The association between breast cancer characteristics and survival with estrogen receptor (ER) and progesterone receptor (PR) expression has been primarily studied via binomial categories, ER-positive and ER-negative. In order to better characterize germline genetic influences on these markers, we investigated their IHC expression semi-quantitatively in cancer predisposition germline pathogenic variant (PV) carriers of the following genes: BRCA1, BRCA2, PALB2, TP53, PTEN, CDH1, ATM, CHEK2, and Lynch syndrome genes. The HER2 expression was also analyzed. Methods: We conducted a retrospective chart review of patients with germline panel genetic testing for cancer predisposition genes at Moffitt Cancer Center’s GeneHome clinic. Inclusion criteria included 1) women ≥18 years old, 2) breast cancer diagnosis, 3) cancer predisposition germline panel genetic test results, 4) available ER and PR expression levels, and 5) available HER expression and/or amplification status. ER, PR, and HER2 status were compared between PV carriers and non-PV carriers via Mann-Whitney U at p>0.05. Results: A total of 847 cases were reviewed for the study. Among 658 patients with a breast cancer diagnosis and complete ER PR data, 365 cases (55.5%) were non-PV carriers and 293 cases (44.5%) carried a PV in at least one of the genes listed above. Among 635 cases with available HER2 expression/amplification status, 355 (55.9%) cases were non-PV carriers and 288 (45.4%) cases were PV-carriers. When compared with non-PV carrier controls, BRCA1 PV carriers’ breast tumors had significantly lower ER and/or PR expression. Further, BRCA2 and TP53 PV tumors also displayed moderately lower ER expression. Contrarily, CHEK2 tumors displayed higher ER and PR expression compared to controls. Further, BRCA1 and BRCA2 PV carriers were more likely to have HER2- breast cancers. Conclusions: Differences in ER, PR, HER2 expression levels were observed in germline PV carrier breast cancers, signaling differential impacts by germline PVs on the tumor evolution process. It is likely that tumor differences in PV carriers influence responses to therapies, including hormone therapy, anti-HER2 therapy, and subsequent survival.[Table: see text]
Differential effects of the 2015 American Cancer Society guidelines on screening mammography exams based on socioeconomic status.
Authors: Capaccione Kathleen M. , Huang Sophia , West Elizabeth , Deng Aileen , Salvatore Mary M. , Desperito Elise
Published: June 2021

10539

Background: Guidelines for screening mammography have changed several times since initiation of regular screening mammography in the 1970’s. Most recently, in 2015, the American Cancer Society (ACS) revised their screening guidelines, recommending that a patient discuss screening mammography with her primary care doctor (PCP) between the ages of 40-44 and should begin yearly screening at age 45; after age 54, ACS recommended screening every other year. Prior to this, from 2003-2015, ACS had recommended screening mammography every year beginning at the age of 40. We hypothesized that these guidelines were adopted to varying degrees in different patient populations and may have disproportionately reduced screening mammography utilization in socioeconomically disadvantaged populations. Methods: Here, we analyzed monthly screening mammography rates over time in two large New York City hospitals, one in a socioeconomically advantaged area and the other in a socioeconomically disadvantaged area. Using our radiology records query system, we searched for monthly screening mammography numbers for women by decade from 2012 to 2018. We performed statistical analysis to evaluate changes in number of exams over time. Student’s t-tests were used to evaluate for significant differences. Results: In both groups of 40-49 year old patients, monthly mammograms increased from 2012-2016. In the socioeconomically advantaged group, this increase continued until 2018 resulting in an overall 400% increase in screening mammograms over time. The change in ACS screening guidelines had no effect on the rate of screening mammography in this group. Conversely, after the revision of the ACS guidelines in 2015, there was a marked decline in screening mammography in the 40-49 year old group in the socioeconomically disadvantaged population. By 2018, there was a statistically significant difference in women screened in all age groups (40-49, p<.0001; 50-59, p<.0001; 60-69, p<.01; 70-79, p<.0001; 80+, p<.0001) between these two patient populations. Conclusions: These data suggest that implementation of the 2015 ACS screening guidelines had a disproportionate effect on patients from socioeconomically disadvantaged areas and that these effects have led to significant disparities in screening mammography trends over time. We postulate that lower levels of health literacy may have contributed to misunderstanding of the screening guidelines. More research is needed to elucidate the underlying etiology of these disparities and ensure that women from all socioeconomic backgrounds receive appropriate screening mammography. Over time, this may result in disproportionate breast cancer morbidity and mortality in populations not receiving appropriate screening.
Risk factors for early-onset colorectal cancer in China.
Authors: Pan Zhe , Huang Junfeng , Huang Mingkai , Yao Zhiyuan , Huang Jiongqiang , Chen Jingsong , Wang Rongchang
Published: June 2021

10542

Background: The incidence of colorectal cancer among persons aged < 50 years (early-onset colorectal cancer, EOCRC) has increased since the early 1990s. However, the risk factors contributing to this trend remain largely unknown. Methods: We conducted a retrospective study of participants who were aged < 50 years and without a previous cancer history, using the China Kadoorie Biobank cohort study. We analyzed data related to demographics, lifestyle habits, family history, and comorbidities of EOCRC cases with participants without colorectal cancer in this age group (controls). Univariate and multivariate-adjusted cox regression models were used to estimate the associations with risk factors. Results: We identified 225 EOCRC cases and 88842 controls that include the final analyses. Of the 225 EOCRC patients, 105 (46.7%) were colon cancers and 120 (53.3%) were rectum cancers. EOCRC cases were older, have more intake of fish and eggs, have higher BMIs, diabetes, and family history of cancer compared with controls (P < 0.05). After adjustment for potential confounding factors, increasing age (HR 2.18, 95%CI 2.05-2.31), BMI (HR 1.06, 95%CI 1.01-1.11), family history of cancer (HR 1.41, 95%CI 1.00-1.98), and more intake of fish (HR 1.54, 95%CI 1.09-2.19) were significantly associated with a higher risk of EOCRC. In sensitivity analyses stratified by cancer site (colon and rectum), the results remained consistent. Conclusions: Based on the large Chinese cohort study, we found increasing age, higher BMI or obesity, family history of cancer, and more intake of fish were independent risk factors for EOCRC. Further studies are needed to identify factors that cause the increasing incidence of EOCRC in China and other countries, and explore the potential mechanism behind.[Table: see text]
Efficacy of HPV vaccination among seropositive, DNA negative cohorts.
Authors: Mac Eochagain Colm , Power Robert , Parker Imelda
Published: June 2021

10552

Background: Prophylactic HPV vaccination of naïve cohorts is known to be highly effective in the prevention of incident HPV infection and HPV-associated cervical premalignancy. Conversely, vaccination of women with active (DNA+) HPV infections has been demonstrated to be ineffective. Vaccine efficacy among previously exposed, but currently uninfected women, i.e. those who have serological evidence of a prior HPV infection without corresponding detectable HPV DNA, remains incompletely defined. This meta-analysis assessed the serotype-specific efficacy of prophylactic HPV vaccination against HPV16/18 persistent infection (PI) and cervical intraepithelial neoplasia (CIN) among seropositive, DNA negative (SPDN) women enrolled to RCTs of HPV L1-based vaccines. Methods: The study protocol was prospectively registered on PROSPERO (CRD42020206888). Searches were conducted on 08/16/20 on MEDLINE, EMBASE, SCOPUS and CENTRAL. RCTs of L1-based prophylactic bivalent or quadrivalent HPV vaccines, reporting serotype-specific clinical efficacy endpoints in the HPV16/18 seropositive, DNA-negative populations were included. Two authors independently screened studies, extracted data and assessed for bias. Data for SPDN women were extracted from subgroup analyses within primary and secondary publications, publication supplements, and manufacturers' clinical study reports. Relative risks (RR) of 6-month persistent infection (6mPI), 12-month persistent infection (12mPI), CIN1+ and CIN2+ were pooled using a random-effects model. Results: A total of 1727 citations were reviewed. 8 studies, with a total of 9569 SPDN participants, met all eligibility criteria. The relative risk of 6mPI (RR: 0.22, 95% CI 0.08-0.61, p = 0.018), 12mPI (RR: 0.20, 95% CI 0.05-0.80, p = 0.035), CIN1+ (RR:0.13, 95% CI 0.05-0.30, p = 0.003) and CIN2+ (RR: 0.15, 95% CI 0.04-0.59, p = 0.022) was significantly reduced in the vaccinated compared to the unvaccinated group. The number needed to vaccinate (NNV) to prevent one case of CIN1+ and CIN2+ was 152 and 208 respectively. Conclusions: Our findings suggest high serotype-specific efficacy for HPV vaccination among cohorts of women with evidence of prior HPV 16/18 infections. Women without DNA evidence of active infection may be seronegative, implying naïve status and > 99% efficacy; or seropositive, implying SPDN status and 87% efficacy against CIN1+ for HPV 16/18. Women without DNA evidence of HPV 16/18 infection should be offered prophylactic HPV vaccination regardless of prior exposure history.
Socioeconomic background in relation to stage at diagnosis in women with breast cancer.
Authors: Ariza Juan Manuel , Cowppli-Bony Anne , Billon Solenne , Ayrault-Piault Stephanie , Blanc-Lapierre Audrey , Florence Molinie Florence
Published: June 2021

10574

Background: Breast cancer (BC) has been associated with socioeconomic deprivation and rural residence. However, it’s still unclear how these factors interplay to affect the frequency and incidence of early and advanced BC. Methods: Taking advantage of the Loire-Atlantique/Vendée cancer registry (France), we investigated the association between early (TNM stage < 2) and advanced (TNM stage ≥2) BC and the socio-economic background (SB) of women diagnosed in the study region from 2008 to 2015. Socioeconomic status was studied using the residence information of every patient linked to the European Deprivation Index (EDI), an ecological index constructed to reflect individual deprivation experienced at the smallest geographical unit of France (IRIS = 2000 inhabitants). To investigate SB, we created a composite variable using the EDI and the urban/rural context information, to define 4 categories: affluent-urban, affluent-rural, deprived-urban, and deprived-rural. Two statistical approaches were implemented: i) mixed-effects logistic regression models to examine the likelihood (relative risk, RR) of being diagnosed with advanced BC, and ii) Poisson regression for modeling incidence rates of early and advanced stages. Analyses were stratified by age ( < 45, 45 to 74, > 75 years) with a random intercept at the IRIS level. For the strata 45 to 74, the models were adjusted for organized screening. Results: During the study period, 14,542 BC cases were recorded. Compared to the women diagnosed in the most affluent-urban areas, a higher proportion of cancer diagnosed at an advanced stage was observed in the women living in more deprived-rural areas (aged < 45 years, RR = 1.48 95% CI 1.17 - 1.73; aged 45 to 74 years, RR = 1.22, 95% CI 1.02-1.42; aged > 74 years, RR = 1.08, 95% CI 0.85-1.27). Furthermore, while in the population under 74 years, incidence rates of early BC in deprived-rural women were reduced by 25-85 % in comparison to affluent-urban women (IRR: 0.33 to 0.97 95% CI 0.16 -0.98), the rates of advanced BC were unaffected by deprivation-rurality (Deprived rural vs Affluent urban, IRR: 1.06 to 1.13 95% CI 0.79 -1.72). For the population over 74 years, we were unable to detect any associations between SB and BC incidence by stage at diagnosis. Conclusions: Advanced stage at diagnosis was more frequent among deprived–rural women aged under 74 years and coincided with the low incidence rates of early stages in this population. No disparities in the incidence rates of advanced BC were detected according to their SB in any age classes, suggesting other factors may be stronger contributors to the advanced stage at diagnosis. Future research should investigate whether screening practices may influence the disparities in the early stage at diagnosis for women under 74.
A comprehensive literature review and meta-analysis on prevalence of BRCAm, HRRm and HRD+ across tumor types.
Authors: Shao Changxia , Wan Jun , Tang Huilin , Marley Andrew , Miller Chelsey , Brown Madeline , Song Yiqing , Han Jiali , Adeboyeje Gboyega
Published: June 2021

10589

Background: Poly (ADP-ribose) polymerase inhibitor (PARPi) may have broad application in the treatment of cancer patients with mutations in BRCA (BRCAm) or other homologous recombination repair genes (HRRm) or with homologous recombination deficiency positive (HRD+). A literature review and meta-analysis were conducted to evaluate the prevalence of BRCAm, HRRm, and HRD+ across tumor types. Methods: Comprehensive searches for eligible studies in Ovid MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Cochrane reviews were performed in May 2020 to capture studies published in English, within 10 years for manuscripts and 3 years for abstracts across geographic regions. A weighted summary estimate was calculated for BRCAm. A summary estimate with corresponding 95% CI was calculated using random-effects models for HRD+ and HRRm. Results: A total of 342 eligible studies with at least 100 samples were included in the review of BRCA1/2m prevalence, containing a total of over 469,000 samples across 24 tumor types. The most frequent indications examined in the included studies were breast (study number n = 144), ovarian (53), prostate (17) and pancreatic (11) cancers. The prevalence of germline BRCA1m (gBRCA1m) and gBRCA2m was 5% and 4% for breast, 12% and 5% for ovarian, 1% and 3% for prostate, and 1% and 4% for pancreatic cancer, respectively. The prevalence of somatic BRCA1m (sBRCA1m) and somatic BRCA2m (sBRCA2m) was 3% and 3% for breast, 7% and 5% for ovarian, 3% and 5% for prostate, and 1% and 3% for pancreatic cancer, respectively. Few studies evaluated endometrial, lung and colon cancers, the prevalence of gBRCA1m or gBRCA2m was generally less than 1%, and the prevalence of sBRCA1m and sBRCA2 ranged 1 to 3%. Seven publications were identified where HRD+ was defined by either BRCAm or genomic instability score (GIS) ≥ 42 across breast, ovarian and pancreatic cancers. The overall HRD+ prevalence was 56% (95%CI: 48, 64), with similar prevalence observed across the 3 tumor types and was 50% (34, 66) for the 3 studies only counting GIS≥ 42. 194 studies across 26 tumor types were identified that examined HRRm as mutations in one or more HRR genes other than BRCA1/2m. The definitions of HRRm varied substantially across the studies, and ATM (2.8%), CHEK2 (1.6%), and PALB2 (1.6%) accounted for most of the observed mutations among HRR genes. Conclusions: Prevalence of BRCAm, HRRm and HRD+ varied by cancer type. This comprehensive meta-analysis enriches the knowledge in this field and demonstrates the need to standardize the measurement of HRRm and HRD.Understanding the prevalence of these biomarkers could have important clinical implications.
Distribution of BRCA1/2 germline and somatic alterations across cancer type.
Authors: Chen Jingde , Quan Ming , Yan Zhengqing , Chen Shiqing , Huang Mei , Cui Jiujie , Chen Zhiqin , Gao Yong
Published: June 2021

10590

Background: PARP inhibitors (e.g. Olaparib or niraparib) have been approved by FDA as a targeted therapy for many tumors harboring germline or somatic BRCA1/2 (g or sBRCA1/2), including ovarian cancer, prostate cancer, breast cancer and pancreases cancer. It is imperative to study the distribution of BRCA1/2 across cancer type. In this study, we aim to assess the landscape of BRCA1/2 alterations in solid tumors and evaluate the feasibility of circulating tumor DNA (ctDNA) tested by next-generation sequence (NGS) as a tool to detect BRCA1/2 alterations. Methods: For tissue specimen, genomic DNA from formalin fixed paraffin-embedded (FFPE) tumor specimens or fresh tumor tissues was used for sequence analysis. Genomic DNA (gDNA) from white blood cells was extracted using the QIAamp DNA Mini Kit (Qiagen). For ctDNA, cell-free DNA libraries were prepared using the KAPA Hyper Prep Kit following the manufacturer’s protocol. The captured libraries were loaded onto a NovaSeq 6000 platform (Illumina) for 100bp paired-end sequencing. The testing was performed in the College of American Pathologists (CAP) and Clinical Laboratory Improvement Amendments (CLIA) -certified 3D Medicines Library. Results: A total of 27, 835 patients were tested using tumor tissue during Jan. 1th 2017 to June 1th 2020, including 43% (N = 12089) of non-small cell lung cancer, 19% (N = 5357) of colorectal cancer, 8% (N = 2181) of liver cancer, 6% (N = 1621) of gastric cancer, 5% (N = 1479) of biliary tract cancer, 4% (N = 1084) of kidney cancer, 4% (N = 1045) of pancreas cancer, 3% (N = 689) of breast cancer and 2% (N = 599) of ovarian cancer. Across all tumor types, the known or likely deleterious BRCA1/2 alterations were identified in 2147 (7.7%) patients. Ovarian cancer had the highest frequency of BRCA1/2 alteration (23.4%), followed by endometrial cancer (12.7%) and breast cancer (10.6%). BRCA1/2 alteration was found in 8.8% prostate cancer and 4.2% pancreas cancer respectively. Across all tumor types, the known or likely deleterious gBRCA1/2 alterations were identified in 369 (1.3%) patients. Notably, ovarian cancer had the highest frequency of gBRCA1/2 alteration (13.9%), followed by breast cancer (7%), prostate cancer (4.4%) and endometrial cancer (4.1%). No clear hotspot mutations and mutated codons were spread throughout g or sBRCA1/2 mutations. Additionally, among 15699 patients who suffered ctDNA sequencing, any known or likely deleterious sBRCA1/2 alterations were identified in 358 (2%) patients. Similar to the results of tissue sequencing, ovarian cancer had the highest frequency of sBRCA1/2 alteration (16.67%), followed by endometrial cancer (9.68%), prostate cancer (7.18%) and breast cancer (5.58%) in the blood cohort. Conclusions: BRCA1/2 alterations existed across tumor types and the landscape of g or sBRCA1/2 alterations varied according to cancer type. Furthermore, ctDNA can be used as a potential tool to detect BRCA1/2 alterations.
Racial disparities in genetic testing of breast cancer patients.
Authors: Bayard Solange , Chen Yalei , Fasano Genevieve A. , Davis Melissa , Walker Eleanor M. , Bensenhaver Jessica Miley , Petersen Lindsay , Marti Jennifer , Simmons Rache M. , Swistel Alexander J. , Newman Lisa A.
Published: June 2021

10591

Background: TNBC is disproportionately prevalent in African American (AA) populations and in women with BRCA-1 germline mutations. BRCA mutation carriers are candidates for targeted therapy with PARP-inhibitors, and testing results may influence risk-reducing surgery choice. Methods: We evaluated genetic testing patterns and outcomes for TNBC patients treated in the prospectively maintained databases of academic cancer programs in two metropolitan cities in the Northeast (New York City, NYC) and Midwest (Detroit, Det), 1998-2018. Median follow up was 3.73 years. Testing patterns were also analyzed by time, comparing pts diagnosed before versus after the mid-2013 Supreme Court ruling that expanded testing availability by banning gene patenting. Results: Of 810 pts, 600 were from NYC and 200 from Det; 202 were AA and 488 WA. Pts undergoing genetic testing were younger (median age 50 vs 62; p < 0.0001). Compared to WA, AA pts were less likely to undergo genetic testing overall (23.8% vs 42.0%; p < 0.0001) and within site (NYC: 25.6% vs 42.8%, p = 0.008; Det: 22.3% vs 38.6%, p = 0.025). No significant differences were seen in frequency of pathogenic BRCA mutations (AA-14.6%; WA-29.3%) or VUSs (AA-6.3%; WA- 4.9%); p = 0.20. Genetic testing disparities were reduced among pts diagnosed after mid-2013 (AA-31.4% vs WA-44.0%; p = 0.01) compared to pre-mid-2013 (AA-18.3% vs WA-40.7%; p < 0.0001). No differences were seen in local or distant recurrence free survival between patients with BRCA, BRCA variants of uncertain significance, non-BRCA mutations, and patients without genetic mutations (local recurrence p = 0.827; distant recurrence p = 0.574). This outcome equivalence was consistent when stratified by WA vs AA identity. Conclusions: Genetic testing has increased for TNBC pts following the mid-2013 Supreme Court ban on gene patenting, but race-associated disparities persist. Pts undergoing genetic testing are more likely to undergo risk-reducing mastectomy, but testing results do not affect survival outcomes, regardless of race. Addressing genetic testing disparities will become increasingly important as mutation-associated targeted therapies are identified through advances in precision medicine.
Perpetrators of workplace bullying and gender discriminations experienced by women gynecologic oncologists.
Authors: Hong Linda , Rubinsak Lisa , Benoit Michelle F. , Teoh Deanna Gek Koon , Ioffe Yevgenia , Chandavarkar Uma , Brockmeyer Amy , Stevens Erin E. , Temkin Sarah Madhu
Published: June 2021

11013

Background: A high prevalence of gender discrimination and harassment has been described among gynecologic oncologists (GOs). This study examined the work environment for women GOs and delineated the perpetrators of negative behaviors. Methods: An internet-based, IRB exempt survey of members of a 472-member Facebook group “Women of Gynecologic Oncology (WGO)” was conducted. Using REDcap survey platform, members provided demographics, practice infrastructure, personal experience with workplace bullying, gender discrimination, microaggressions, and outcomes. Demographic, practice and work environments and perpetrators of negative behaviors were summarized using descriptive statistics. Results: Between 7/20 and 8/19/2020, 250 (53%) of active WGO members participated in this survey. Most respondents were younger than 50 years old (93.6%); white (82.2%) and non-Hispanic (94.3%). A majority were married (84.7%) with children (75.2%). Practice environments included academic (152, 61.0%), private practice (31, 12.4%), and hospital employed (57, 22.9%). 89.9% supervised trainees. 130 (52.0%) respondents reported bullying, 140 (56.0%) gender discrimination, and 83% having experienced gender-based microaggressions. Age, race, ethnicity, practice setting, division director or chair gender or department reporting structure were not significantly associated with these experiences. Perpetrators of bullying, gender discrimination, and microaggressions were widely distributed (Table). Of those reporting bullying, 61 (46.6%) reported a male perpetrator, 25 (19.1%) female and 45 (34.4%) an equal gender distribution; of those reporting discrimination 105 (74.5%) reported a male perpetrator, 9 (6.4%) female and 27 (19.1%) an equal gender distribution. 32.9% of survey respondents acknowledged having been written up for speaking up in a way that would have been tolerated from a male colleague. 18.3% of respondents have changed jobs because of bullying; 13.5% because of discrimination. Conclusions: Women GOs report high rates of workplace bullying, gender discrimination, and microaggressions regardless of practice setting that often impact their careers. Perpetrators of these behaviors are multiple and varied. Proactive and deliberate interventions to improve the work environments for women GOs are urgently needed.[Table: see text]
Prevalence and risk factors of burnout among female oncology professionals from the Middle East and North Africa (MENA).
Authors: Abusanad Atlal , Bensalem Assia , Shash Emad , Mula-Hussain Layth Y.I. , Benbrahim Zineb , Khatib Sami Ahmad , Abdelhafeiz Nafisa , Ansari Jawaher , Jradi Hoda , Alkattan Khaled , Jazieh Abdul-Rahman
Published: June 2021

11016

Background: Burnout (BO) is a recognized challenge among oncology workforce. It affects both genders with a higher frequency among women. This study examined the factors contributing to the development of burnout among women in oncology from the Middle East and North Africa (MENA). Methods: An online cross-sectional survey was distributed to oncology professionals from different countries in the MENA region. The validated Maslach Burnout Inventory (MBI) of emotional exhaustion (EE), Depersonalization (DE), and Personal Achievement (PA) plus questions about demography/work-related factors and attitudes toward oncology were included. Data were analyzed to measure BO prevalence and related factors. Results: Between February 10 and March 15, 2020, 545 responses were submitted by female professionals. The responses pre-dated the COVID-19 pandemic emergence in the region. BO prevalence was 71% among female professionals. Women aged < 44 years represented 85% of the cohort. Sixty-two percent were married, 52% with children and one-third practiced a hobby. Two-thirds worked in medical oncology, worked for < 10 years and 35% worked in academia. The majority (73%) spent > 25% on administrative work daily. Nearly half of the respondents (49%) expressed a recurring thought of quitting oncology and 70% had no burnout support or education. Inability to deliver optimal care was reported as distressing for career development in 82%. Factors significantly influencing the BO risk are listed in Table. Marital status, having children, academia and years in practice did not impact the risk of BO among female oncologists form MENA. Conclusions: High BO prevalence was reported among female oncology professionals from MENA. The majority of women oncology workforce were young and early- to mid-career in this cohort. Younger age, practicing in North African countries, high administrative load and the recurring thought of quitting were associated with increased risk of burnout. Whereas, practicing a hobby and enjoying oncology communication decreased the BO risk. Burnout support and education specifically for women in oncology is needed.[Table: see text]
Impact of COVID-19 pandemic on well-being and work-related burnout among healthcare workers at an academic center.
Authors: Dawar Richa , Rodriguez Estelamari , Gawri Kunal , Kwon Deukwoo , Penedo Frank J.
Published: June 2021

11019

Background: COVID-19 pandemic has not only caused an unprecedented distress in the community, but also significant physical and psychological exhaustion amongst healthcare workers (HCWs), that could lead to serious effects on our healthcare system. This study was conducted to assess burnout among oncologists and other healthcare professionals at a large academic center. Methods: An electronic 10-minute questionnaire was sent to actively employed physicians, APRNs and PAs at the University of Miami. Survey items evaluated various personal and professional characteristics including COVID related stress. Burnout was examined with Maslach Burnout Inventory (MBI), which evaluated severity across two domains: emotional exhaustion and depersonalization. The logistic regression model was used to estimate association between study variables and high burnout levels. Odds ratio (ORs) and corresponding 95% confidence interval (CI) were obtained. Continuous variables were tested using two-sample t-test by high burnout status. Results: The survey was sent to 739 HCWs, out of which 182 (24.6%) completed the entire survey; 63.7% were physicians, 8.6% fellows, and 27.4% APRN or PA. The pandemic led to rescheduling of professional activities (22.2%), increased workload (59.5%), job insecurity (28.6%), and decreased leadership opportunities (32.2%). 62.3% of respondents reported decreased exercise; 44.8% reported new sleep disorder; 56.1% reported increased home responsibilities; childcare arrangements were affected in 60.6%; 61.4% struggled to maintain work-life balance. 70 of 182 respondents were broadly from the fields of Oncology and Palliative Care. 9 out of these 70 respondents reported high depersonalization, 27 reported high emotional exhaustion, and 33 reported overall high burnout symptoms on either emotional exhaustion or depersonalization scales. Amongst physicians holding positions from PGY4 through licensed attendings with less than 5 years’ experience, 62.5% (95%CI=35.4-84.8) showed high burnout rate (10 of 16), which was not statistically different from older physicians (11 of 27=40.7% (95%CI=22.4-61.2)). No difference in burnout was seen for other study variables including gender, marital status, and race/ethnicity. Conclusions: COVID-19 pandemic has incited not only an unmatched level of practice changes, but also extraordinary psycho-social uncertainty, leading to a considerable impact on HCWs’ wellbeing. Long working hours, lack of sleep, fear of losing job, transition to tele-medicine, risk of getting infection and putting their family at risk, lack of childcare, pressure of home schooling- all seem to have caused an increased physical and psychological pressure among HCWs and warrants an examination of potential coping mechanisms. This study sets the stage for more elaborate research to illustrate and guide the development of wellness programs imperative to the well-being of HCWs.
Factors associated with open access publishing costs in oncology journals.
Authors: Koong Alex , Gardner Ulysses , Burton Jason C. , Stewart Caleb , Thompson Petria , Fuller Clifton Dave , Ludmir Ethan B. , Rooney Michael Kevin
Published: June 2021

11032

Background: The open access (OA) publishing model represents an exciting opportunity to facilitate dissemination of scientific information to global audiences. In contrast to many traditional models, which require readers to pay subscription fees or rely upon institutional subscriptions for article access, the OA model grants free access to all consumers. However, OA publication is often associated with significant article processing charges (APCs) for authors, which may thus serve as a barrier to publication. In this investigation, we aimed to identify journal-level factors associated with OA publication costs in oncology journals. Methods: We identified oncology journals using the SCImago Journal & Country Rank database. All journals under the “Oncology” category that offer an OA publishing option with APC data openly available were included. For all journals, we searched journal websites and tabulated journal characteristics, including APC amount (USD), OA model (hybrid vs full), journal 2-year impact factor (IF), H-index, number of citable documents, primary treatment modality (surgery, radiation, medical, non-specific), treatment site (e.g. breast, etc), and continent of origin. Pearson correlation was used to evaluate univariate linear relationships between variables; for variables with significant correlation, we generated a multiple regression model to identify journal characteristics independently associated with OA APC amount. Results: Of 367 oncology journals screened, 266 met final inclusion criteria. The median APC was 2810 USD (range 0 – 5200). On univariate linear correlation regression testing, journals with the full OA model (p < 0.001), higher journal IF (p < 0.001), higher H-index (p < 0.001), greater number of published articles (p < 0.001), and those from North America or Europe (p < 0.001) tended to have higher OA publishing costs. When these co-variates were analyzed in a multiple regression model, only full OA status (p < 0.001), higher IF (p < 0.001), and North American or European origin (p < 0.001) persisted as independently associated with greater OA APC. Conclusions: Large APCs may serve as a barrier to OA publication and therefore create or exacerbate disparities among scientific investigators seeking to share their research. In this investigation, we find that OA publication costs are greater in oncology journals that utilize the hybrid OA model, have higher IF, and are based in North America or Europe. These findings may inform targeted action to help the oncology community fully appreciate the benefits of open science.
Factors associated with endowed chair allocation in medical oncology divisions and departments in the United States.
Authors: Jia Lena , Rooney Michael Kevin , Jacobson Clare , Griffith Kent A. , Jagsi Reshma , Markham Merry Jennifer
Published: June 2021

11044

Background: Despite an increasing number of female physicians in the workforce, a gender disparity remains in many leadership roles in medicine. Endowed chairs can provide a multitude of research and career opportunities; thus, they are coveted positions in academic medicine. We examined factors associated with holding endowed chairs in oncology across the US, with a focus on whether a gender difference existed, as has been demonstrated in top internal medicine departments more generally. Methods: In 2019, we identified 95 academic oncology divisions/departments in the US, using the Oncology Division Chiefs & Department Chairs listing in the American Society of Clinical Oncology (ASCO) myConnection forum to define the institutions included. We requested a list of full professors and endowed chairs in those divisions/departments, relying on public data on websites when an institution did not respond. Using public data (e.g., institutional websites, NIH reporter, Scopus, state licensing boards), we collected information on gender, degree, total NIH funding as PIs, H-indices, publication and citation numbers, and graduation year for these individuals. We then created a multivariable logistic regression model to examine if, after controlling for other variables, gender was independently associated with an increased likelihood of holding an endowed chair. Results: One thousand thirty-three oncology full professors were identified, 290 (25.6%) of whom held endowed chairs. Overall, and in an adjusted model, greater research productivity (as measured through publications, citations, and h-index) and greater levels of NIH funding were significantly associated with having an endowed chair. Gender was not significantly associated with endowed chair status (21.9% [95% CI:17.2-27.3] of females and 26.8% [23.8-29.9] for males held endowed chairs; p = 0.11) on bivariable analysis, nor was it significant in the adjusted multivariable model (p = 0.50). Power to detect the observed difference given the total number of professors and their gender distribution was found to be ̃53%, suggesting a 47% chance of failing to reject the null hypothesis of equal gender distributions in endowed chairs when the observed difference is as large as estimated. Conclusions: Among oncology full professors, gender was not significantly associated with endowed chair status, although the number of professors in this field is too small to definitively rule out a modest gender difference. This finding contrasts with prior work that revealed a more substantial difference by gender that remained significant after controlling for other factors in a study, including all divisions in the Departments of Internal Medicine at top medical institutions. Further work is necessary to understand what specialty-specific and institutional cultural factors may help mitigate challenges in the pursuit of equity, diversity, and inclusion.
Long-term quality of life of cancer survivors: A case-control study.
Authors: Ponce-Zepeda Joaquin , Hoang Tuyen
Published: June 2021

12077

Background: There were extensive reports in literature about the debilitating health experienced by cancer patients during treatment. This study examined how the quality of life of cancer survivors changed over time. Methods: The National Health and Nutrition Examination Survey (NHANES) is a program of studies designed to assess the health and nutritional status of adults and children in the U.S. This study involved participants in NHANES from 2000-2020. Participants who reported having had a cancer diagnosis were matched one to one with participants who reported no cancer diagnosis by age, gender, race, year of recruitment into NHANES, and comorbidities. Quality of life measures including self-reported general/physical/mental health, examinations, and laboratory tests were compared between cancer cases and matched controls using paired t tests. Results: This study included 5,166 pairs of cancer cases and matched controls. Mean age was 66 (±15 years). Male 47% and female 53%. White 69%, Black 14%, Hispanic 12%, others 5%. Most common comorbidities were hypertension (56%), arthritis (50%), diabetes (19%), and thyroid (18%). About 38% of cancer cases had survived in 1-5 years; 22% in 6-10 years; 39% in 10+ years. Most prevalent cancers were skin (28%), breast (15%), and prostate (15%). Compared to controls, cancer cases who had survived in 1-5 years reported higher rates of poor general health (38% vs. 27%, p <.0001), hospitalizations (31% vs. 17%, p <.0001), mental health visits (9% vs. 7%, p =.0204). There were no significant differences in general health and healthcare utilization between cancer cases who survived > 5 years and controls. There were no clinically meaningful differences in laboratory tests and examinations between cancer cases and controls regardless of survival time. Conclusions: During the first 5 years after cancer diagnosis, survivors reported worse health than controls. As survival time extended, there was no difference between cancer cases and controls. The debilitating health reported during the first 5 years could not be explained by examinations and laboratory tests alone. Future research should explore neurochemical and hormonal markers to investigate adverse effects of cancer treatment on long-term quality of life.
The association of the affordable care's Medicaid expansion on survival in gynecologic cancer: A National Cancer Database study.
Authors: Smith Anna Jo , Applebaum Jeremy , Nickles Fader Amanda
Published: June 2021

1501

Background: Under the Affordable Care Act’s 2014 Medicaid expansion, more than 12 million Americans gained health insurance. Whether such gains in insurance improve survival in gynecologic cancer is unknown. This study aims to determine whether Medicaid expansion is associated with improved survival among women with gynecologic cancers. Methods: We conducted a retrospective cohort study using a difference-in-differences study design comparing insurance status, stage at diagnosis, delays in treatment, and one-year survival before and after the ACA’s Medicaid expansion in Medicaid expansion states (intervention group) compared to women in non-expansion states (control group). Using hospital-reported data from the 2010-2016 National Cancer Database, we compared outcomes overall for women ages 40-64 years old with endometrial, cervical, ovarian, or vulva/vaginal cancer and then stratified by cancer type, stage, race, and rural/urban status. We adjusted for patient (area-level income, area-level education, distance traveled for care, comorbidities), clinical (co-morbidities, grade) and hospital (academic facility) characteristics. Results: Our sample included 241,713 women with gynecologic cancer, 119,392 in expansion states and 122,321 in non-expansion states. Post-Medicaid expansion, there was a statistically significant 0.8 % increase in 1-year survival among patients in expansion states compared to non-expansion states (95% CI 0.1-1.5). There was also a significant reduction in uninsurance (-1.1%, 95%CI, --1.5, -0.7) and delays of 30+ days from diagnosis to treatment (-2.4%, 95%CI -3.4, -1.2). There was no significant change in early-stage diagnosis (0%; 95%CI -0.7-0.7). Improvements in one-year survival after Medicaid expansion were driven by ovarian cancer (difference-in-differences 2.2%, 95%CI 0.6-3.8) and in white women (difference-in-differences 0.8%, 95%CI 0.1-1.5), while there was no significant difference in one-year survival for non-white or rural women. Conclusions: The Affordable Care Act’s Medicaid expansion was significantly associated with 1-year survival and insurance access among patients with gynecologic cancer. Insurance expansion efforts in non-Medicaid expansion states may improve survival for women with gynecologic cancer.