bluuebunny/crossref_metadata_2025 huggingface dataset:
Patterns of ovarian cancer care in an elderly population in Australia: A prospective cohort study from the National Gynaecology Oncology Registry (NGOR).
Authors: Naidoo Mahendra , Scott Clare L. , McNally Orla , Rome Rob , Perera Sharnel , Zalcberg John Raymond ,   NGOR Steering Committee & Ovarian, Tubal and Peritoneal (OTP) Cancer Working Group
Published: June 2023

5572

Background: Elderly women with ovarian cancer are often undertreated in comparison to best practice. The National Gynae-Oncology Registry (NGOR) is Australia’s first country-wide clinical quality registry (CQR) measuring compliance with optimal care defined by a set of clinical quality indicators (CQIs). Objectives: To assess compliance with a predefined set of CQIs for elderly women with newly diagnosed ovarian cancer aged > 75 compared to non-elderly women aged <75 years of age from the NGOR sites. Methods: All women with newly diagnosed ovarian cancer from May 2017 – July 2022 were eligible for inclusion. Data were collected from medical records and relevant hospital linked databases by expert data managers. Results: A total of 1590 women were eligible for inclusion from 21 hospitals across 5 Australian states. The CQI data were subsequently aggregated and are summarised in the table. The proportion of elderly women receiving first-line chemotherapy with a platinum and taxane doublet was significantly lower compared to non-elderly (60% vs 89%, p < 0.001). The proportion of women with sub-optimally debulked or Stage IV cancer who received first-line chemotherapy with a platinum/taxane doublet and bevacizumab was significantly lower in elderly women compared to non-elderly (10% vs 30%, p < 0.001) . Enrolment in clinical trials or translational research was significantly lower in elderly women compared to non-elderly (13% vs 21%, p=0.002). The remaining CQIs showed no significant differences between the age groups. Conclusions: In this cohort, most measures of best practice were not significantly different between elderly and non-elderly women, with the exception of elderly women receiving less first line doublet chemotherapy, less doublet chemotherapy with bevacizumab in sub-optimally debulked or Stage IV cancer, and less likely to be enrolled in clinical trials or translational research. While these 3 CQIs represent a minority of the overall list of CQIs, such lack of compliance may result in significant differences in quality of life and overall survival for elderly women with ovarian cancer. Subsequent investigation is therefore warranted to confirm and explain these findings. [Table: see text]
Response to subsequent platinum-based chemotherapy post PARP inhibitor in recurrent epithelial ovarian cancer.
Authors: MacAulay Vacheresse Genevieve , Sabri Elham , Domingo Sheryl , Le Tien
Published: June 2023

5578

Background: Maintenance therapy with PARP inhibitors (PARPi) can increase progression free survival (PFS) for recurrent or metastatic platinum-sensitive epithelial ovarian cancer (EOC). Little is known about disease trajectory following treatment with these agents, though some evidence suggests a decreased response to subsequent platinum-based chemotherapy. This retrospective cohort study assessed real-world response rates to platinum-based chemotherapy for recurrent high grade EOC following treatment with a PARPi. Methods: All patients prescribed a PARPi as maintenance therapy for recurrent or metastatic EOC at the Ottawa Regional Cancer Center (ORCC) from September 2017 to May 2022 were included. PFS following penultimate therapy (line of therapy preceding PARPi initiation) as well as the PFS following subsequent platinum-based chemotherapy in patients with disease progression more than 6 months after penultimate therapy were calculated. Incidence of platinum resistance in patients with disease progression following PARPi therapy was determined. Results: 91 patients were included in the analysis including 54 patients on niraparib and 36 patients on olaparib. Follow-up after initiation of PARPi ranged from 4.6 months to 62.0 months with a median of 16.3 months. 54 (59.3%) of patients experienced disease progression after initiation of PARPi therapy, including 10 (11.0%) who progressed within 6 months of their penultimate therapy. Of the 44 patients who experienced disease progression more than 6 months following penultimate therapy, 32 (72.7%) were rechallenged with platinum-based chemotherapy. Of these, 16 (50.0%) experienced further disease progression with 14 (43.8%) progressing within 6 months of their platinum rechallenge. Median PFS following platinum rechallenge was 4.4 months (from 0.8 months to 34.9 months), significantly lower than previous reports. Conclusions: Patients who experienced disease progression following PARPi therapy showed a poor response to subsequent platinum-based chemotherapy, even when progression occurred more than 6 months after completion of their penultimate platinum-based chemotherapy. This supports the theory that PARPi resistance may be a surrogate for platinum resistance and raises concern for possible contribution of PARPi in the induction of platinum resistance in recurrent EOC.
Molecular and immune profiling of TP53-mutated ovarian cancers with non-BRCA1/2 homologous recombination gene alterations.
Authors: Strickland Kyle C. , Previs Rebecca A. , Wallen Zachary D , Nesline Mary K , Ko Heidi Chwan , Pabla Sarabjot , Hastings Stephanie , Jensen Taylor J. , Reddy Prasanth , Severson Eric A , Ramkissoon Shakti
Published: June 2023

5579

Background: Molecular alterations in homologous recombination (HR) pathway genes lead to HR deficiency (HRD) in ~50% of high grade serous ovarian carcinomas (HGSOC). The immune microenvironment of BRCA1/2-mutated HGSOC has been extensively characterized, in contrast to tumors with mutations in other HR genes. We evaluated a cohort of epithelial ovarian cancers (EOC) enriched for HGSOC and compared molecular and immune signatures of tumors with BRCA1/2 mutations ( BRCAm) to those with non-BRCA1/2 HR gene mutations (NBHRD). Methods: We characterized 173 EOC by comprehensive genomic and immune profiling (CGIP) using panel-based next-generation DNA (523 genes) and RNA sequencing (384 genes), respectively. We enriched for HGSOC by selecting for TP53 mutations and excluding tumors with non-serous histology or any mutation in POLE, MLH1, PMS2, MSH2, MSH6, or nucleotide excision repair genes. Tumors lacking BRCA1/2-mutations were classified as NBHRD if a reportable mutation was present in canonical HR genes. Mutational burden (TMB, mut/Mb) was estimated from detected SNV/indels. We calculated immune-related expression signatures, including tumor immunogenicity score (TIGS), cellular proliferation (CP), and cancer testis antigen burden (CTAB). PD-L1 expression was assessed by tumor proportion score (TPS) following 22C3 immunohistochemistry. Differences in TMB, TIGS, CP, CTAB, PD-L1 and gene expression rank were tested for using Wilcoxon rank-sum test. Results: Of 173 EOC, 84 cases had complete CGIP, including 11 (13%) BRCAm, 7 (8%) NBHRD (Table), and 66 (79%) lacking HR gene alterations. On average, NBHRD tumors harbored lower TMB (4.1±2.3 vs. 6.6±2.3 vs. p=0.03) and elevated TIGS (59.1±16.2 vs. 41.7±16.2 p=0.044) compared to BRCAm tumors. We found no difference in PD-L1 (p=0.21), CP (p=0.26), or CTAB (p=0.48). Expression changes were identified in 32 immune genes, of which 31 (97%) were substantially up-regulated (1.3-3.3 fold) in NBHRD compared to BRCAm tumors. Conclusions: Our findings showed our cohort of NBHRD tumors were more immunogenic but less mutagenic than BRCAm tumors, implying enhanced immunogenicity unrelated to neoantigen load. Given that immune checkpoint inhibitors have shown limited efficacy in ovarian cancer, our data suggest NBHRD tumors may have stronger and possibly distinct immune escape mechanisms compared to BRCAm tumors. [Table: see text]
Exploring the significance of PARP inhibitor therapy after first-line chemotherapy in patients with homologous recombination proficient ovarian cancer: An extracted individual patient data and trial-level meta-analysis.
Authors: Cunha Mateus Trinconi , Lazar Neto Felippe , Estevez-Diz Maria Del Pilar , Bonadio Renata Colombo
Published: June 2023

5580

Background: The use of poly (ADP-ribose) polymerase inhibitors (PARPi) as maintenance therapy in advanced epithelial ovarian cancer (EOC) patients (pts) has shown to delay cancer progression among patients with mutated BRCA (mBRCA) or homologous recombination deficiency (HRD), with debatable and divergent benefit among the subgroup of patients with homologous recombination proficiency (HRP). We aimed to further clarify the efficacy of PARPi after first-line chemotherapy (1L CT) in patients with HRP EOC. Methods: A systematic literature search of PubMed, Embase, The Cochrane Library until February 9th was conducted to identify articles or presentations of phase III clinical trials (P3CT) evaluating PARPi maintenance therapy after 1L CT in ovarian cancer. Individual patient data was reconstructed from Kaplan-Meier plots of progression-free survival (PFS) among pts with mBRCA, HRD and HRP through WebPlotDigitizer and R package IPDfromKM and futher combined. We also performed trial-level meta-analysis with a random effects model. Comparisons were made with Cox proportional hazards. Clinical benefit for each sub-group was accessed with the ESMO Magnitude of Clinical Benefit Formulary 2b (ESMO MBCS). Results: The literature search resulted in 513 items. After screening, 6 P3CT (SOLO1, PRIMA, VELIA, PAOLA, PRIME, and ATHENA-MONO) were selected, and the longer follow-up data of each trial was used. A total of 3205 pts were included in the analysis (2090 in PARPi arms, 1115 in control arms). HRP was associated with worse PFS regardless of the treatment arm (HRP vs mBRCA in PARPi arms: HR 1.92, 95% CI 1.62 – 2.21, P < 0.001). Compared to control treatment arm, PARPi therapy was associated with a improved PFS in all subgroups, although the magnitude of benefit decreased from mBRCA to HRD and HRP (Table). Trial-level meta-analysis yielded similar results. PARPi therapy summed 4 out of 4 possible points at ESMO MBCS for mBRCA and HRD, but only 2 points among HRP pts, confirming a lower clinical benefit in this subgroup. Conclusions: This meta-analysis included additional P3CT recently presented and new data of subgroup analysis of previous studies. Results confirm a statistically significant benefit of PARPi maintenance after 1L CT for HRP EOC. Nevertheless, the relative and absolute gain in PFS is modest (9% in 2 years), while mBRCA and HRD subgroups have a substantial benefit. The worse prognosis of HRP pts, in addition to the small clinical benefit of PARPi therapy, highlights the need for new treatment strategies for this subgroup. [Table: see text]
Healthcare access dimensions and uterine cancer survival: A National Cancer Database study.
Authors: Anastasio Mary Katherine , Gupta Anjali , Akinyemiju Tomi F. , Previs Rebecca A.
Published: June 2023

5594

Background: Racial disparities persist throughout the continuum of care for Black patients with uterine cancer. Few studies have evaluated how multiple dimensions of healthcare access (HCA) contribute to these disparities in patients who present at an advanced stage and meet criteria for adjuvant therapy. Methods: Patients with Stage III-IV uterine cancer between 2004-2015 who received adjuvant therapy with complete sociodemographic and other relevant covariate data were identified in the National Cancer Database (NCDB). Race and ethnicity were defined as non-Hispanic (NH)-Black, Hispanic, and NH-White. Healthcare access dimensions of affordability, availability and accessibility were measured using variables defined in the NCDB. Overall survival was analyzed using Kaplan-Meier curves, log-rank test, and multivariable Cox proportional hazard models. Results: The study cohort included 43,134 patients: 78.8% NH-White, 15.3% NH-Black, and 5.9% Hispanic. Compared to NH-White and Hispanic patients, NH-Black patients were more likely to have Type II (75.6% vs. 53.9% and 55.4%) and Stage IV disease (40.8% vs. 30.7% and 32.3%). NH-Black patients were more likely to receive chemotherapy alone (53.5% vs. 43.1% and 46.2%) compared to NH-White and Hispanic patients. NH-Black patients were the most likely to have government funded insurance (58.6% vs. 50.3% and 50.4%) and live in the lowest income quartile (46.4% vs. 14.2% and 29.9%) compared to NH-White and Hispanic patients. NH-Black patients had a significantly higher risk of death than NH-White patients when adjusting for demographic/clinical characteristics and all three healthcare access dimensions (HR 1.29; 95% CI 1.24, 1.34). Conclusions: Healthcare access affordability predicts survival but does not fully explain racial disparities in survival rates of patients with advanced stage uterine cancer. NH-Black patients are more likely to have aggressive disease, receive chemotherapy alone, and have worse survival than NH-White patients regardless of pathogenic subtype. Investigating additional healthcare access dimensions may be critical to addressing disparities in uterine cancer.
Preliminary results of a phase II trial with sacituzumab govitecan-hziy in patients with recurrent endometrial carcinoma overexpressing Trop-2.
Authors: Santin Alessandro , McNamara Blair , Siegel Eric R. , Harold Justin , Mutlu Levent , Altwerger Gary , Huang Gloria S. , Andikyan Vaagn , Clark Mitchell B. , Ratner Elena , Azodi Masoud , Dottino Peter , Schwartz Peter E. , Bellone Stefania
Published: June 2023

5599

Background: Despite recent advances, there remains a significant need for targeted, efficacious treatments for advanced and recurrent endometrial carcinoma (EC). Trop-2 has been demonstrated to be overexpressed in several EC including grade 3 endometrioid adenocarcinoma (96%), and uterine serous carcinoma (65%). Trop-2 overexpression has been found to confer a worse prognosis and predicts disease recurrence. Sacituzumab govitecan-hziy (SG) is an antibody-drug conjugate comprised of a humanized anti-Trop-2 antibody conjugated with the active metabolite of irinotecan, a topoisomerase-I inhibitor. SG is currently FDA-approved for use in metastatic urothelial cancer and metastatic triple-negative breast cancer. Methods: We report results from the stage 1 of an open-label non-randomized phase 2 trial (NCT04251416) established to evaluate the clinical activity of SG in patients with persistent or recurrent EC of epithelial origin with Trop-2 overexpression. Criteria for study participation included radiographically confirmed and measurable persistent or recurrent EC, progression after or during platinum-based chemotherapy, and at least 2+ staining of Trop-2. One target lesion by RECIST v1.1 and adequate bone marrow, renal, and hepatic function were required. Patients were at least two weeks beyond prior treatment, major surgery, or high dose systemic corticosteroid use. Patients were given 10mg/kg of SG administered as an intravenous infusion once weekly on days 1 and 8 of 21-day treatment cycles. This 3-week cycle was continued without rest until disease progression or unacceptable toxicity. Results: Twenty-one patients were enrolled into stage 1. Ten patients (48%) had uterine serous carcinoma, seven (33%) had endometrioid adenocarcinoma, three (14%) had carcinosarcoma, and one patient had mixed serous and clear cell histology. All patients received at least one prior line of chemotherapy, (median 3 lines, range 1-6). At the time of submission, 20 patients were response-evaluable (Table); seven (35%) achieved objective response (5 out of 7 confirmed). Eighteen patients were evaluable for durable disease control; 7 (39%) achieved it. Follow-up durations had a median (IQR) of 15.6 (5.7–22.5) months. Median OS was 22.5 months, and median PFS was 5.7 months. The treatment was well-tolerated with no new or unexpected safety signals reported. Conclusions: Sacituzumab govitecan shows remarkable clinical activity against some of the most historically challenging and chemotherapy-resistant endometrial pathologies and demonstrates a favorable safety profile. With these promising results, we will begin the stage 2 expansion of this phase 2 trial. Clinical trial information: NCT04251416 . [Table: see text]
Influence of ovarian function supression on quality of life in breast cancer survivors during adjuvant endocrine therapy.
Authors: Dedic Plavetic Natalija , Dugonjic Okrosa Ana , Silovski Tajana , Jovic Zlatovic Josipa , Jajac Brucic Lana , Skelin Marko , Mucalo Iva
Published: June 2023

560

Background: Adding ovarian function suppression to adjuvant endocrine therapy (AET) lowers the disease recurrence rates among premenopausal women with hormone receptor-positive (HR+) early breast cancer (EBC). However, a detrimental effect on endocrine symptoms burden (ESB) is expected. Therefore, this study aimed to investigate differences in Quality of life (QoL) and endocrine symptoms in premenopausal women prescribed AET, with/without gonadotropin-releasing hormone agonist (GnRH). Methods: This cross-sectional study included women, with HR+ EBC, premenopausal at diagnosis, treated with AET for more than 3 months, with and without GnRH. The research was conducted with institutional Ethics Committee approval at the University Hospital Centre Zagreb, General Hospital Šibenik, and with online survey. A validated instrument, the Functional Assessment of Cancer Therapy - Endocrine Symptoms (FACT-ES), was used. The collected data were analysed using SPSS v. 29 (p≤0.05). Results: Overall, 314 eligible BC survivors with a median age of 45 years (22-65) and a median duration of AET of 2 years (3 months -12 years) responded to FACT-ES and were included in the analysis. Altogether 45.2% (n=142) of participants were prescribed tamoxifen (TAM), 25.8% (n=81) GnRH+TAM, and 29% (n=91) GnRH+aromatase inhibitor (AI); exemestane (9%), letrozole (13.6%) and anastrozole (6.4%). The total QoL (FACT-ES) score was higher in patients treated with TAM as opposed to patients treated with AI+GnRH (p=0.01). Adding GnRH to TAM did not significantly change QoL when compared to TAM alone or AI+GnRH. In addition, patients on AI+GnRH had lower physical well-being (PWB) score than patients on TAM+GnRH (p=0.03) or TAM alone (p=0.05) and lower endocrine subscale score (ESS-19) than patients on TAM (p=0.01), indicating more endocrine symptoms in premenopausal women treated with AI+GnRH. Among patients treated with AI+GnRH letrozole had lower PWB (p=0.03) and ESS-19 score (p=0.01) than exemestane. Conclusions: This study showed that GnRH+AI in premenopausal women with HR+ EBC results in greater ESB and lower QoL compared to patients treated with TAM or GnRH+TAM. Therefore, interventions helping decrease the ESB in patients treated with AI+GnRH should be explored and developed to help patients adhere to and persist in AET. [Table: see text]
Racial and ethnic disparities in quality of diagnostic evaluation for uterine cancer among Medicare patients.
Authors: Xu Xiao , Chen Ling , Wright Jason Dennis
Published: June 2023

5600

Background: Uterine cancer is the most common gynecologic malignancy. As there is no routine screening for uterine cancer, appropriate evaluation of presenting symptoms is crucial for early diagnosis. We examined racial/ethnic disparities in the quality of diagnostic evaluation received by Medicare patients with uterine cancer. Methods: Using the Surveillance, Epidemiology and End Results (SEER)-Medicare database, we identified patients ≥65 years with uterine cancer diagnosed in 2008-2017 who presented with abnormal uterine bleeding (AUB, the most common symptom of uterine cancer). Patients with other cancer or unknown race/ethnicity were excluded. Race/ethnicity was categorized as White, Black, Hispanic, or Other (including American Indian/Alaska Native and Asian/Pacific Islander). Quality of diagnostic evaluation was measured by: 1) not receiving guideline-recommended diagnostic procedures (yes/no), and 2) number of days between AUB presentation and first diagnostic procedure. We compared these measures across racial/ethnic groups using multivariable regressions adjusting for patient sociodemographic characteristics, comorbid conditions, histology, and tumor grade. We further examined racial/ethnic differences in stage at diagnosis before vs. after accounting for these quality indicators. Results: The sample included 23,017 patients. Compared to White patients, Black, Hispanic, and Other patients were younger; more likely to reside in a metropolitan area, lack preventive care in the past year, or have comorbidities; and tended to have uterine cancer of non-endometrioid types and higher grade (p<0.001 for all). A larger proportion of Black than White patients did not receive guideline-recommended diagnostic procedures (Black: 9.6% vs. White: 5.0%, p<0.001; adjusted odds ratio [aOR] = 1.45, 95% CI: 1.20-1.74). Time from AUB presentation to first diagnostic procedure was longer for Black than White patients (90th percentile: 34 vs. 21 days, p<0.001; adjusted mean ratio = 1.38, 95% CI: 1.21-1.57). Black patients were more likely than White patients to be diagnosed at regional (aOR = 1.18, 95% CI: 1.04-1.33) or distant stage (aOR = 1.27, 95% CI: 1.06-1.52), rather than localized stage, even after adjusting for other characteristics. Further adjusting for quality of diagnostic evaluation slightly reduced Black-White differences in stage at diagnosis (regional: aOR = 1.16, 95% CI: 1.03-1.32; distant: aOR = 1.23, 95% CI: 1.03-1.48). Hispanic and Other patients also experienced delay in time to first diagnostic procedure, but they did not differ from White patients in receipt of guideline-recommended diagnostic procedures or stage at diagnosis. Conclusions: There were racial/ethnic disparities in the quality of diagnostic evaluation received by Medicare patients with uterine cancer, which may partially explain Black-White differences in their stage at diagnosis.
Efficacy and safety of anlotinib in overall and disease-specific advanced gynecological cancer: A real-world study.
Authors: Hong Xinyi , Qiu Shanhu , Wu Xia , Chen Sizhen , Chen Xiaoxiang , Zhang Bei , He Aiqin , Zhou Ying , Xu Yun , Wang Jianqing , Gao Yingchun , Xu Xizhong , Sun Li , Zhang Yang , Xiang Libing , Zhou Jundong , Guan Qun , Chen Bingwei , Shen Yang
Published: June 2023

5608

Background: Anlotinib is a novel oral small-molecule multi-target tyrosine kinase inhibitor that has been approved for treating non-small cell lung cancer. However, its efficacy and safety among patients with advanced gynecological cancer. We conducted this study to address this issue in the real-world setting. Methods: Data from patients treated with anlotinib for persistent, recurrent or metastatic gynecological cancer including cervical, endometrial, and ovarian cancer were collected from 17 centers from August 2018. The database lock-time was on March 2022. Anlotinib was administered orally on days 1–14 every 3 weeks until disease progression, severe toxicity occurred, or death. The outcomes included objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS). Results: A total of 249 patients were analyzed, with a median follow-up of 14.46 months. The overall ORR and DCR were 28.1% (95% CI 22.6% to 34.1%), and 80.7% (95% CI 75.3% to 85.4%), respectively. Specifically, the ORR varied from 19.7% to 34.4% and the DCR differed from 81.7% to 90.0% in disease-specific advanced gynecological cancer. The median PFS was 6.1 months and ranged from 5.6 to 10.0 months in the overall and disease-specific advanced gynecological cancer, respectively. Larger cumulative dosage of anlotinib (>700 mg) was in general associated with longer PFS in the overall and disease-specific advanced gynecological cancer. The most common adverse event related to anlotinib use was pain/arthralgia (18.3%). Conclusions: In conclusion, anlotinib holds promise in treating patients with advanced gynecological cancer, such as cervical, endometrial, and ovarian cancer, with reasonable efficacy and tolerable safety.
Do HER2 low tumors have a distinct clinicopathologic phenotype?
Authors: Polidorio Natália , Veeravalli Srinivasa Sevilimedu , Montagna Giacomo , Le Tiana , Morrow Monica
Published: June 2023

570

Background: Clinicopathologic features of breast cancer subtypes defined by hormone receptor (HR) and HER2 status differ. These analyses classified HER2 IHC <3+ with negative FISH as HER2-. With the recognition of the clinical relevance of HER2 low, there is debate as to whether this is a distinct subtype. We sought to determine if features of HER2 low tumors differ from HER2- and HER2+ after controlling for HR status. Methods: Patients undergoing upfront surgery from 1998 to 2010 were identified from a prospectively maintained institutional database. HER2 status was classified by IHC/FISH analysis as HER2-, HER2 low (IHC 1+ or 2+ with negative FISH), and HER2+ (IHC 3+ or FISH +) and stratified by HR status. Univariable (UVA) and multivariable multinomial logistic regression analysis (MVA) were performed to determine associations among variables and subtypes. Results: 11,323 tumors from 11,072 patients were included. 5,104 (45%) were HER2 low, 41.2% were HER2- and 13.6% were HER2+. On MVA stratified by HER2 status only, compared to HER2- tumors, HER2 low was associated with LVI (OR 1.2 [95% CI 1.06-1.36]; p=.003), multifocality (OR 1.26 [95% CI, 1.12-1.42]; p<.001), nodal micrometastasis (OR 1.15 [95% CI, 1.02-1.31]; p=.024), and lower rates of <3 positive nodes (OR 0.77 [95% CI, 0.66-0.90], p=.001). HER2+ was associated with younger age, high grade, multifocality, extensive intraductal component (EIC), and pN2/3 nodal stage. Clinicopathologic features stratified by HR and HER2 status are shown in the table. On UVA, in both HR+ and HR– tumors, age and multifocality were associated with HER2 low, and LVI, multifocality, and EIC with HER2+ compared to HER2- tumors. On MVA, no variables were independently associated with both HR+ and HR-/HER2 low tumors compared to HER2-. In contrast, HER2+ tumors regardless of HR status were significantly associated with multifocality and EIC. Conclusions: HER2 low breast cancer features seem to be driven by HR status and HER2 overexpression. We do not have enough evidence to support the interpretation of HER2 low as a distinct subtype. [Table: see text]
Clinical meaning of stromal tumor infiltrating lymphocytes (sTIL) in luminal early breast cancer.
Authors: García-Torralba Esmeralda , Ivars-Rubio Alejandra , Perez-Ramos Miguel , Navarro Manzano Esther , Blaya-Boluda Noel , de la Morena Barrio Pilar , Garcia-Garre Elisa , Marin Zafra Gema , Martinez-Diaz Francisco , Gomez Martinez Francisco , Lopez-Robles Javier , Alvarez Abril Beatriz , Garcia Martinez Elena , Ayala Francisco
Published: June 2023

572

Background: Luminal breast cancer (BC) is associated with lower immune activation. Although stromal tumor infiltrating lymphocytes (sTIL) are a marker of better prognosis and response in hormone receptor (HR) negative tumors, sTIL predictive and prognostic implications are less clear in luminal BC. Further insights on the clinical correlations of immune microenvironment in luminal disease may facilitate therapeutic improvement and prognostic stratification in these patients. Methods: Observational and single-center cohort of 345 women with early luminal (HR positive, HER2 negative) BC (2012-2020) treated with chemotherapy. Pre-treatment sTIL were determined in the diagnostic biopsy following validated standard methods. The correlation between sTIL and other tumor characteristics were analyzed (Spearman's Rho and Chi-squared tests). Association of sTIL with pathologic complete response (pCR) in patients treated with neoadjuvant chemotherapy (nCT) was evaluated with logistic regression models. Prognostic value of sTIL for overall (OS) or relapse free interval (RFI) was analyzed by Cox regression models. Results: Median age: 50 (range: 24-89); 48.1% premenopausal; 91.3% infiltrating ductal carcinoma; 30.1% grade 3; 87.2% progesterone receptor (PgR)+; 67.5% treated with nCT and 32.8% with adjuvant CT (aCT); 47.6% N0, 32.8% N1, 19.6% N2-3; median ki67: 30% (82.7% >10%). A 29% of patients showed sTIL=0%. Median sTIL infiltration was 5 (Q1-Q3 range [IQR], 0-10), with higher values in premenopausal (p<0.001), grade 3 (p<0.001), N+ (p<0.001) and luminal B tumors (defined as PgR- and/or grade 3 and/or Ki67>15%) (p<0.001). Ki67 was significantly correlated with sTIL (ρ:0.39; p<0.001). The percentage of sTIL was associated with pCR after nCT (OR: 1.045, 95%Ci 1.02-1.07, p=0.001). No prognostic impact of sTIL for OS or RFI was found in luminal A tumors. In luminal B cases (n=286), any grade of lymphocytic infiltration (defined as sTIL > 0%) was associated with a shorter RFI both in univariate (p=0.01) and multivariate Cox models (HR: 4.83, 95%CI 1.28-18.21, p=0.02), with a non-significant trend for poorer OS (p=0.06). Conclusions: In luminal BC, an increased level of sTIL is associated with luminal B subtype characteristics such as higher proliferation, higher tumor grade and nodal involvement. Lymphocytic infiltration has been found to be a predictor of pCR after nCT, but, in contrast with hormone receptor-negative BC, it is also associated with a poorer prognosis for recurrence and a trend towards worse overall survival in luminal B tumors. [Table: see text]
10-year mastectomy trends among breast cancer phenotypes: A national cohort study.
Authors: Pierotti Matthew Lewis , Cruz Pico Christian X. , Hasler Jill S , Williams Austin David , Handorf Elizabeth A. , Aggon Allison A. , Pronovost Mary , Porpiglia Andrea S , Vasigh Mahtab , Bleicher Richard J.
Published: June 2023

584

Background: Breast cancer tumor phenotype has prognostic value with triple negative (TN) cancers having higher rates of distant metastases early. While tumor phenotypes are prognostic, published data demonstrates that the choice of local therapy does not affect this predisposition or affect survival. This study was performed to determine whether mastectomy is being performed more frequently for TN or HER2+ phenotypes, relative to hormone receptor positive (HR+) phenotypes despite the lack of benefit this should provide. Methods: Data from the National Cancer Database (NCDB) was analyzed from 2010 through 2019 to assess mastectomy trends and associations with patient and tumor characteristics. Women with invasive breast cancer were included. Women with Stage IV disease were excluded. Patients were categorized as mastectomy or breast conservation surgery. Patient and tumor characteristics were compared across groups using chi-square and Wilcoxon rank sum tests, and a multivariable logistic regression model was fit to assess the association between mastectomy and tumor phenotype controlling for patient and tumor characteristics. Results: 543,590 patients were evaluated. 173,380 (31.9%) patients underwent mastectomy, and 370,210 (68.1%) patients underwent breast conservation surgery. Mean age at diagnosis was 56. There were 425,174 HR+, 64,960 HER2+, and 53,456 TN tumors. The proportion of patients undergoing mastectomy peaked in 2013 at 36.14% before declining. Compared to HR+, HER2+ patients were more likely to undergo mastectomy, OR 1.39 p < 0.0001 (95% CI 1.35 – 1.43); however, there was no significant difference in mastectomy between HR+ patients and TN patients. Compared to whites, black patients were less likely to undergo mastectomy, OR 0.71 p < 0.0001 (95% CI 0.69 – 0.74), and individuals of Hispanic ethnicity less likely to undergo mastectomy, OR 0.92 p < 0.0001 (95% CI 0.89 – 0.95). Compared to private insurance, Medicare had a greater association with mastectomy, OR 1.2 p < 0.0001 (95% CI 1.18 – 1.23). There was no significant difference between other forms of insurance (Medicaid, other government insurance, no insurance) and private insurance. Education and income were not associated with different frequencies of mastectomy. Patients with higher comorbidity scores were more likely to undergo mastectomy. Conclusions: Mastectomy rates have been declining since 2013 at CoC centers. While TN breast cancer is not associated with increased mastectomy percent, mastectomy continues to be performed more frequently for HER2+ positive phenotype when adjusting for tumor and patient characteristics. These data suggest a need for education about HER2 positive phenotype due to a possible lack of understanding about the why such tumors pose a risk, and the role of local therapy in treating them.
Racial/ethnic and socioeconomic differences in breast cancer surgery performed and delayed surgical treatment: Mediating impact on mortality.
Authors: Bangolo Ayrton , Fwelo Pierre , Nwosu Kenechukwu O.S. , Adekunle Toluwani E. , Afolayan Oladipo , Ahaiwe Onyekachi , Ojaruega Akpevwe A. , Nagesh Vignesh , Jarri Amer , Dey Shraboni , Chacko Angel Ann , Gupta Bhavna , Atoot Adam
Published: June 2023

585

Background: Breast cancer is the most common malignancy affecting women of all racial and ethnic backgrounds in the United States (US). Although Socioeconomic status (SES), race/ethnicity, and surgical type/delays are associated with breast cancer mortality outcomes, studies on these associations have been contrasting. This study examined the racial/ethnic and SES differences in surgical treatment types and delays. Also, we quantified the extent to which these differences explained the racial/ethnic disparities in breast cancer mortality. Methods: We studied 290,066 women 40+ years old diagnosed with breast cancer between 2010 and 2017 identified from the Surveillance, Epidemiology, and End Results database. We performed logistic regression models to examine the association of SES and race/ethnicity with surgical treatment type and delays. We performed mediation analysis models to quantify the extent to which mortality differences were mediated by treatment, sociodemographic, and clinicopathologic factors. The study subjects were de-identified, and there was no patient contact; thus, the study was exempted from an Institutional Review Board's (IRB) approval. A p-value less than 0.05 indicated significant associations for the descriptive statistics, logistic and Cox proportional hazard regressions, and mediation analysis. We used Stata 17 to perform the analyses. Results: Non-Hispanic (NH) Black [Odds ratio (OR) = 1.16, 95% CI: 1.13-1.19] and Hispanic women [OR = 1.27, 95% CI: 1.24-1.31] were significantly more likely to undergo mastectomy compared to NH White women. Similarly, NH Black and Hispanic women had higher odds of delayed surgical treatment than NH Whites. Patients in the highest SES quintile, compared to those in lowest the lowest, were less likely to experience breast cancer-specific mortality (BCSM). Variations in treatment, SES, and clinicopathological factors significantly explained 70% of the excess BCSM among NH Blacks compared to their NH White counterparts. Conclusions: In conclusion, health disparity continues to be a major societal concern in the US. It affects people of all ages, socioeconomic classes, and ethnic/racial backgrounds. The findings of this study showed that racial and ethnic minorities, the majority of whom have a lower socioeconomic position, are significantly disadvantaged regarding the evaluation, quality, cost, and duration of medical care. Future studies can assess the multifactorial effects of sociodemographic factors like SES, access to health care assessment, and educational background amidst other variables as a multidimensional predictor of treatment delay and overall survival of breast cancer and other health issues among minoritized populations.
Disease outcomes by race in patients with high-risk triple negative breast cancer with residual disease after neoadjuvant chemotherapy: A post-hoc analysis of the EA1131 randomized clinical trial.
Authors: Kantor Olga , Newman Lisa A. , Anderson Lauren K , Glass Charity , Mayer Erica L. , Ogayo Esther R. , Chavez-MacGregor Mariana , Freedman Rachel A. , King Tari A. , Mittendorf Elizabeth A.
Published: June 2023

586

Background: Black women with breast cancer have the highest breast cancer mortality (BCM) rates of any racial and ethnic group. The higher burden of triple negative breast cancer (TNBC) in Black women contributes to disparities in BCM, but the extent to which disparate outcomes exist in patients with similar tumor biology is uncertain. The objective of this study was to examine racial differences in disease outcomes and BCM between Black and White patients in a clinical trial population of high-risk TNBC with residual disease after neoadjuvant chemotherapy (NAC). Methods: From 2015-2021, the ECOG-ACRIN EA1131 clinical trial randomized 415 clinical stage II-III TNBC patients with residual disease after NAC to either adjuvant capecitabine or platinum. For this analysis, 366 patients with known self-reported Black or White race and follow-up data were included. The aim of this unplanned exploratory analysis was to examine locoregional recurrence (LRR), distant recurrence (DR), and BCM by race using Kaplan-Meier curves for unadjusted estimates and Cox modeling for adjusted analyses. Results: Racial distribution of the analysis population included 66 (18.0%) Black and 300 (82.0%) White patients. 239 (65.3%) patients presented with clinical stage II and 127 (34.7%) with stage III disease. All patients had residual pathological disease after NAC: 86 (23.5%) stage I, 176 (48.1%) stage II, and 102 (27.9%) stage III (n=2 unknown). Median age was 49 years in Black and 54 years in White patients, p=0.003. Disease presentation, response to chemotherapy, and treatment arm were similar by race. Median follow up was 20 months. 2-year estimated LRR occurred in 31.6% of Black and 18.6% of White patients although this was not statistically significant (p=0.387), and 2-year estimated DR and BCM were similar by race. Estimated 2-year outcomes are outlined. Models adjusted for race, age, stage, grade, treatment arm, and locoregional therapy did not identify race as an independent predictor of LRR, DR, or BCM. Higher pathologic stage was the only consistent independent predictor of recurrent disease or BCM (stage III with HR 6.14 for LRR; HR 5.16 for DR; HR 6.84 for BCM; all p<0.001). Conclusions: In this population of high-risk patients with residual TNBC after NAC with similar tumor biology treated on a clinical trial, there was a trend towards increased LRR in Black patients and similar DR and BCM between Black and White patients at 2 years of follow-up. This suggests that differences in BCM in other breast cancer populations may be at least partially driven by differences in tumor biology. Clinical trial information: NCT02445391 . [Table: see text]
Association of minimizing the false negative rate of axillary staging surgery in patients with cN1 breast cancer after neoadjuvant chemotherapy with surgical overtreatment.
Authors: Laws Alison , Leonard Saskia , Vincuilla Julie , Parker Tonia , Kantor Olga , Mittendorf Elizabeth A. , Weiss Anna , King Tari A.
Published: June 2023

587

Background: Efforts to minimize the false negative rate (FNR) of axillary staging in cN1 breast cancer patients (pts) treated with neoadjuvant chemotherapy (NAC) have received much attention since the publication of ACOSOG Z1071. We first adopted sentinel node biopsy (SNB) with a requirement of retrieving ≥3 nodes, and later transitioned to targeted axillary dissection (TAD) with a requirement of retrieving the biopsy-proven clipped node (CN) and ≥3 nodes overall. Group consensus was to perform axillary lymph node dissection (ALND) if these technical requirements were not met. This study evaluates likelihood of surgical overtreatment with ALND due to technical failures of SNB or TAD in cN1 pts who converted to ypN0 status, and reports oncologic outcomes with each approach. Methods: Among 598 cN1 breast cancer pts treated with NAC from 2017-2022 in our prospective institutional database, we included 191 (31.9%) with attempted SNB or TAD and ypN0 status. We used descriptive statistics and chi-squared tests to compare technical complications of SNB vs. TAD resulting in requirement for ALND per group consensus despite ypN0 status. Kaplan Meier methods were used to determine oncologic outcomes in those treated with SNB or TAD alone. Results: Planned axillary surgery was SNB in 77 (40.3%) pts and TAD in 114 (59.7%). The CN was not visualized for seed localization in 14 pts (12.2% of planned TAD) and the seed was not found to be within the CN intra-operatively in 20 pts (20.0% of those with seed placed). Technical failures resulting in requirement of ALND per group consensus criteria occurred in 14 (18.2%) pts with planned SNB and 17 (14.9%) with planned TAD. Among planned TAD pts, the rate of not retrieving the CN did not change over time (p=0.52). Median follow-up in those treated with SNB alone (n=79) was 3.5 years with 1 (1.3%) axillary recurrence as well as 2 local and 2 distant recurrences and 1 non-breast cancer death. 3-yr recurrence-free survival was 90.4% (95%CI: 79.5-95.7%). Median follow-up in those with TAD alone (n=92) was 1.8 years with no recurrences or deaths. Conclusions: This study contributes to a growing body of literature supporting the oncologic safety of omitting ALND in cN1 ypN0 pts treated with NAC, irrespective of the axillary staging approach. Technical limitations in identifying ≥3 nodes or localizing and retrieving CNs resulted in overtreatment with ALND in a significant proportion (≥15%) of ypN0 pts, without significant differences between SNB vs. TAD approaches. These data support consideration of re-evaluating NCCN guidelines recommending retrieval of ≥3 nodes and localization of the CN to minimize risk of overtreatment. [Table: see text]
A phase II randomized clinical trial to assess toxicity and quality of life of patients with breast cancer with hypofractionated versus conventional fractionation radiotherapy with regional nodal irradiation.
Authors: Gil Gabriel Oliveira Bernardes , Andrade Warne Pedro , Costa Diniz Paulo Henrique , Cantidio Farley Soares , Vieira Gil Maria Luisa , Queiroz Izabella Nobre , Almeida Conceição Aparecida Mediros , Caldeira Paola Palmer Reis , Regalin Marcos , Silva-Filho Agnaldo Lopes
Published: June 2023

588

Background: The primary aim was comparing acute toxicity between conventional fractionated radiation therapy (CF-RT) and hypofractionated radiation therapy (HF-RT) for patients undergoing breast-conserving surgery or mastectomy with breast or chest wall and regional nodal irradiation (RNI). The secondary endpoints were acute and subacute toxicity, cosmesis, quality of life, and lymphedema features. Methods: Unblinded randomized trial with total of 86 patients treated with CF-RT (n = 33; 50 Gy/25 fractions ± sequential boost [10 Gy/5 fractions]) versus HF-RT (n = 53; 40 Gy/15 fractions ± concomitant boost [8 Gy/15 fractions]). Toxic effects and cosmesis evaluation used the Common Terminology Criteria for Adverse Events version 4.03 (CTCAE) and the Harvard/NSABP/RTOG scale. Patients-reported QoL was determined using European Organization for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ-C30) and the breast cancer-specific supplementary questionnaire (QLQ-BR23). Lymphedema determination compared volume differences between the affected and contralateral arms using the Casley-Smith volume formula. Results: Grade 2 and grade 3 skin rash dermatitis were lower with HF-RT than with CF-RT (28% vs. 52%, 0% vs. 6%; p = 0.022, respectively). HF-RT vs. CF-RT had lower rate of grade 2 hyperpigmentation (23% vs. 55%; p = 0.005). No differences in overall rates of any physician-assessed grade 2 or higher and grade 3 or higher acute toxicity between HF-RT vs. CF-RT were registered. There was no statistical difference between the CF-RT and the HF-RT regarding cosmesis, lymphedema rate (13% vs. 12% HF-RT vs. CF-RT; p = 1.000, respectively), and functional and symptom scales during irradiation and after six months of treatment. Conclusions: HF-RT showed lower rates of acute toxicity, with no changes in quality-of-life outcomes. Clinical trial information: NCT04015531 .
Use of PLR and NLR to evaluate the efficacy and prognosis of neoadjuvant chemotherapy with lobaplatin in triple-negative breast cancer.
Authors: Wang Cheng , Shi Qiyun , Zhang Guozhi , Yan Wenting , Wu Xiujuan , Wan Andi , Xiong Siyi , Yuan Long , Tian Hao , Ma Dandan , Jiang Jun , Zhang Yi , Qi Xiaowei
Published: June 2023

594

Background: Previously, we showed that addition of lobaplatin (L) to taxane (T) combined with anthracycline (E) could improve the pathological complete response (pCR) rate of neoadjuvant therapy for triple-negative breast cancer (TNBC) and lengthen long-term survival significantly, but the therapeutic markers of this regimen are not known. We investigated if the platelet/lymphocyte ratio (PLR) and neutrophil/lymphocyte ratio (NLR) could be used to predict the efficacy of the TEL regimen. Methods: Eighty-three patients with TNBC (stage I–III) who received TEL (docetaxel (T) at 75 mg/m2, epirubicin (E) at 80 mg/m2, and lobaplatin (L) at 30 mg/m2) from January 2014 to August 2019 were recruited. They received four cycles before surgery and two cycles after surgery. Patients were divided into four groups according to the mean values of the PLR (145.71) and NLR (2.74): high PLR (PLR+), low PLR (PLR−), high NLR (NLR+), and low NLR (NLR−). Differences in the total pathologic complete response (tpCR) rate, event-free survival (EFS), and overall survival (OS) were analyzed in different groups of patients using the TEL protocol. Results: The tpCR rate in the PLR− group was 49.0% (25/51), which was significantly higher than that in the PLR+ group (25.0% (8/32); odds ratio (OR) = 2.885, 95% confidence interval (CI) = 1.093–7.612, P = 0.032). The tpCR rate in the NLR− group was 49.1% (26/53), which was significantly higher than that in the NLR+ group (23.3% (7/30); OR = 3.164, 95% CI = 1.161–8.626, P = 0.024). The tpCR rate of the PLR−NLR− group was 53.7% (22/41), which was significantly higher than that of the PLR+/NLR+ group (26.1% (11/42), with a high proportion of any index (OR = 3.263, 95% CI = 1.298–8.204, P = 0.012). The median duration of follow-up was 69 months. EFS and OS in the NLR− group were significantly longer than those in the NLR+ group (hazard ratio (HR) = 5.946, 95% CI = 1.526–23.169, P = 0.010 for EFS; HR = 7.803, 95% CI = 1.565–38.907, P = 0.012 for OS). Five-year EFS was 95.1% for the PLR−NLR− group, 91.0% for the PLR+NLR− group, 76.0 for the PLR+NLR+ group, and 59.1% for the PLR−NLR+ group. Compared with the PLR+/NLR+ group, patients in the PLR-NLR- group had the longest EFS (P = 0.002). Conclusions: PLR and NLR could be used to predict the efficacy of neoadjuvant therapy with taxane, anthracycline, and lobaplatin regimen in TNBC, and the low-proportion group had a higher tpCR rate and a better long-term prognosis. Clinical trial information: ChiCTR-TRC-14005019 .