bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel imaging marker for low- and mid-recurrence score patients at risk for recurrence.
Authors: Peterson Joseph R , Antony Anu K. , Team The SimBioSys , Cole John A.
Published: June 2022

e12565

Background: The 21-gene (Oncotype DX) recurrence score (RS) has been utilized as a prognostic assay in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer. The results stratify patients into low-, mid- and high-risk of disease recurrence. Patients with a low recurrence score tend to have lower recurrence rates and are less responsive to chemotherapy. On the other hand, patients with high-recurrence scores are more likely to respond to chemotherapy. While for patients at the high end of the RS spectrum it is apparent that chemotherapy carries benefit, distinguishing chemotherapy benefit for low- and mid-recurrence score (RS-low/-mid) patients is less clear. Methods: To address this, we used a novel 2-paramenter pharmacokinetic modeling framework that allows biosignatures to be extracted from dynamic contrast enhanced (DCE) magnetic resonance imaging (MRI) studies that contain 3-6 timepoints spaced 60-90 seconds apart. These parameters, referred to as P1 and P2, represent leakiness from vessels to the extravascular space and vice versa. Results: Using this model, we performed a study in a cohort of 111 breast cancer patients with 21-gene assay RS and DCE-MRIs available. P1 and P2 were extracted from patient standard clinical DCE-MRIs. We performed univariate (Kaplan-Meier) survival analyses to test the prognostic value of the parameters covariate in predicting recurrence free survival (RFS). A pre-specified value of the median P1 and P2 across the patient population was used for stratifying patients into “low” and “high” groups, representing patients with “low” or “high” vessel leakiness. We analyzed patients according to RS. Low P1 showed better outcomes in RS-low and RS-mid patients (n=88, p≤0.028; log-rank test). Patients with a high P1 had a 20.2% chance recurrence at six years. The same trend was observed when considering just RS-mid patients only (n=23, p≤0.058). No recurrences were observed in patients with low P1 in either the RS-low or RS-mid categories. Additionally, there were no recurrences in the high P1, RS-low/-mid category that received chemotherapy, suggesting that chemotherapy could be beneficial in this category of patients, although the trend was not statistically significant (n=10, p=0.46). Similar results were seen for P2. Conclusions: Overall, we demonstrate how our prognostic imaging marker can identify a subset of patients with low-/mid-recurrence scores that could benefit from chemotherapy. This new prognostic approach has the potential to optimize treatment and improve personalized care by providing clarity on the use of chemotherapy in low-/mid-recurrence score patients.[Table: see text]
Tumor copy number alterations were associated with primary endocrine resistance in ER+ breast cancer.
Authors: Lu Qianyi , Xu Fei , Wang Shusen , Wang Na , Shao Yang , Ouyang Yuming
Published: June 2022

e12567

Background: Several studies has showed alterations in genes were associated with endocrine resistance in breast cancer. Nevertheless, genomic landscape in primary endocrine-resistant breast cancer has not been thoroughly reported. Whether the genomic landscape of primary endocrine-resistant breast cancer is different from that of secondary endocrine-resistant breast cancer is unknown. Methods: We analyzed the genomic landscape of primary tumor of consecutive patients with estrogen-receptor positive (ER+) breast cancer in real-world clinical practice in our center between September, 2019 to December, 2020. According to the duration of endocrine treatment, we classified them into primary endocrine resistance group and secondary endocrine resistance group. Results: A total of 41 tumor samples of which 25 cases in primary endocrine resistance and 16 cases in secondary endocrine resistance were included for analysis. TP53 (65.9%, 27/41), PIK3CA (46.3%, 19/41), MYC (36.6%, 15/41), MCL1 (31.7%, 13/41), CCND1 (31.7%, 13/41) were the most frequently altered genes in all 41 BCs. Copy number amplification of MYC was common in primary endocrine resistant group (48.0%, 12/25), while lower in secondary endocrine resistant group (18.8%, 3/16, P = NS). Copy number alteration (CNA) of CCND1, MCL1, FGF19, ZNF217, ZNF703 and FGFR1 were commonly observed in primary endocrine resistance group. Percentage of CNA in all mutation types was significant increased in primary endocrine resistance group than in secondary resistance group (33.0% vs. 21.0%, P = 0.03). Then we further analyzed and found CNA burden, which was defined as number rather the percentage of the CNA event, was associated with the prognosis in ER+ breast cancer. When defining 6 as the cut-off value of CNA-High, DFS, PFS and OS were practically poorer in patients with CNA-High than those with CNA-Low. Conclusions: Copy number alterations were more commonly seen in primary endocrine-resistant breast cancer and associated with prognosis in ER+ breast cancer. This founding urged to further investigate the prognostic value of CNA burden in predicting the effectiveness of endocrine therapy.
Investigate the accuracy and economic value of the upstaging prediction model for ductal carcinoma in situ.
Authors: Chiu Ching-Wen , Tam Ka-Wai , Shih Shen Liang Jerry
Published: June 2022

e12577

Background: The current study aims to define the “high-risk upstaging model” in ductal carcinoma in situ (DCIS) and investigate its accuracy in order to suggest the most precise application of sentinel lymph node biopsy (SLNB). Methods: PubMed, EMBASE, and Cochrane library databases were searched. Prospective and retrospective cohort studies that evaluated the pathological outcomes of SLNB and the upstaging rate in women with DCIS were included. We analyzed factors that potentially indicate nodal involvement risk and combine the significant ones into “high-risk upstaging model”. Consecutively, we conducted a retrospective study by applying our model and NCCN guideline model into DCIS patients extracted from hospital database. Both the excess treatment rate and incomplete treatment rate of SLNB were analyzed. The diagnostic performance of the model in predicting upstaging risk was evaluated with receiver operating characteristic (ROC) curve. Results: We retrieved 43 prospective and 69 retrospective studies including 44,001 DCIS patients. The upstaging rate was significantly higher in patients with estrogen receptor-negative status, palpable mass, tumor size > 2 cm on imaging, and high-nuclear grade and those who received a preoperative diagnosis through core needle biopsy. We then collected 168 DCIS patients who entered in Shuang-Ho hospital from February 2017 to August 2021. Ninety-six patients who didn’t upstage in final pathology have received extra SLNB and two patients who upstaged in final pathology did not receive SLNB in primary surgery. The areas under the ROC curve of the model developed by multivariable logistic regression for predicting upstaging risk in the NCCN guideline group and “high-risk upstaging model” group were 0.642 and 0.706, the sensitivity at 66.0% and 83.0%, and the specificities at 62.5% and 49.2%, respectively. Conclusions: “High-risk upstaging model” shows higher areas under the ROC curve and sensitivity as well compared with current NCCN guideline. Our prediction model can provide surgeons with a more accurate and specific indications of SLNB in DCIS.
Lymphocyte populations in wound fluid in breast cancer patients after mammoplasty with textured implants.
Authors: Przhedetskiy Yuriy V. , Sagakyants Aleksandr B. , Przhedetskaya Viktoria Yu , Zlatnik Elena Yu , Bondarenko Elena S. , Shulgina Oksana G. , Zolotareva Ekaterina I. , Ulianova Elena P. , Pozdnyakova Viktoria V. , Ulianova Yulia V. , Volkova Viktoriya L. , Bauzhadze Mamuka V. , Pustovaya Irina V. , Chertova Natalia A. , Goncharova Elena G. , Maldonado Mary L.
Published: June 2022

e12588

Background: Breast reconstruction after skin-sparing mastectomy for breast cancer (BC) is an important rehabilitation stage. Its results depend on many factors, with the immune system status playing the main role. The purpose of this study was to identify characteristics of the local lymphocyte populations in patients with breast cancer in the early postoperative period after reconstructive surgery with textured implants (TI). Methods: The study included 30 patients aged 32-68 years, mean age 42.9±1.98 years, with stage I-IIb BC (monocentric nodular BC, T1N0M0 - T2N1M0). All patients underwent skin-sparing mastectomy with level II axillary lymph node dissection and immediate implant reconstruction in 2017-2019. Populations and subpopulations of lymphocytes were determined in wound fluid from the cavity with TI on days 1, 3-4 and 7 after the surgery using the FacsCanto II flow cytometer (Becton Dickinson, USA) with markers: CD3 FITC /CD15+56 PE /CD45 PerCP /CD4 PE-Cy7/CD19 APC/ CD8 APC-Cy7; CD45RA FITC /CD45RO PE /CD3 PerCP /CD8 APC; CD45RA FITC /CD62L PE /CD3 PerCP /CD4 APC; CD4 FITC /CD127 PE /CD3 PerCP / CD25 APC-Cy7; CD4 FITC /CD38PE /CD3 PerCP / HLADR APC. At least 50,000 cells were accumulated in each sample for the analysis. Results: The relative number of total lymphocytes exceeded the initial values by 3.3 (p=0.025) and 10.9 (p=0.012) times, respectively, on days 3-4 and 7 after surgery. Levels of CD3+CD4+ cells increased gradually and were 29% (p=0.042) higher by day 7, while levels of CD3+CD8+ decreased during the whole observation period. Levels of Tregs did not change, while B lymphocytes decreased by 36% (p=0.035) and 67% (p=0.026), respectively, on days 3-4 and 7. The levels of activated T lymphocytes increased by 33% (p=0.038) on days 3-4, compared with the initial values, probably due to the elevation of CD3+CD8+ levels (by 32%, p=0.037). The number of activated T lymphocytes with the CD3+CD4+ phenotype increased by 44% (p=0.024) on days 6-7. While the content of CD3+CD4+ cells with early activation markers (CD38+) significantly decreased (by 40%, p=0.031) and remained the same on days 3-4 and 7, the number of CD3+CD8+ with similar markers (CD38+) significantly increased by 28% (p=0.044) and 43%. Conclusions: TI implantation was accompanied by the activation of the cytotoxic T unit during the observation period, together with a decrease in immunosuppressive populations of lymphocytes, which may indicate a favorable development of the patient's body reaction.
Phase 2 study of anlotinib combined with taxanes and lobaplatin in the neoadjuvant treatment of triple-negative breast cancer: Efficacy, safety and biomarker analysis.
Authors: Tian Hao , Zhang Guozhi , Liang Yan , Liu Jing , Fan Linjun , Zhu Kai , Zhang Yi , Qi Xiaowei
Published: June 2022

e12605

Background: Pathological complete response (pCR) is associated with improved prognosis in triple-negative breast cancer (TNBC). Anlotinib, a novel multi-target tyrosine kinase inhibitor that effectively inhibits VEGFR, FGFR, c-KIT, c-MET, and RET, monotherapy has been proven effective in HER-2 negative metastatic breast cancer, but its efficacy in early-stage TNBC is unknown. This phase 2 study aims to evaluate the efficacy and safety of adding anlotinib to neoadjuvant chemotherapy in patients (pts) with primary TNBC. Methods: Pts with clinical stage II/III TNBC were to be treated with 5 cycles of anlotinib (12mg, d1-14, q3w) plus 6 cycles of taxanes (docetaxel 75 mg/m2 or nab-paclitaxel 260 mg/m2, d1, q3w) and lobaplatin (30 mg/m2, d1, q3w), followed by surgery. The primary endpoint was the total pCR (tpCR; ypT0/is ypN0). A Simon’s two-stage optimum design was used, and ＞5 of 11 pts were required to achieve tpCR in the first stage, with a pre-specified tpCR rate of 54.5% before proceeding to the second stage. A total of 31 participants was required for the study. Results: Six out of 11 pts achieved tpCR in the first stage, reaching the threshold for the second stage. From Jan 2021 to Jan 2022, a total of 22 pts were enrolled and 12 received surgery after the completion of neoadjuvant therapy, but a total of 2 pts withdrew from the study due to the COVID-19 pandemic or serious adverse events. Of the 22 eligible pts, the median age was 49 years (range, 29-64), 64% were postmenopausal, and 73% were nodal involved. At the time of surgery, 58.3% (7/12) achieved tpCR. Of the 9 pts with the node-positive disease at diagnosis, 88.9% (8/9) became ypN0. The results of FUSCC TNBC classification (IHC-based) revealed the tpCR rates were 57.1% (4/7), 100% (3/3), and 0% (0/2) for BLIS subtype, IM subtype and LAR/unknown subtypes, respectively. Biomarker analysis showed the tpCR rates were 100% (3/3) and 100% (4/4) in patients with gBRCA1 mutation and MYC amplification, respectively. The most common grade 3 or 4 treatment-related adverse events were leucopenia (6/22, 27%), neutropenia (6/22, 27%), anemia (5/22, 23%), decreased appetite (5/22, 23%), hypertension (2/22, 9%), ALT increased (1/22, 5%) and oral mucositis (1/22, 5%). No treatment-related deaths occurred. The trial is ongoing. Conclusions: The addition of anlotinib to neoadjuvant chemotherapy showed manageable toxicity and promising antitumor activity for patients with early-stage TNBC. Clinical trial information: ChiCTR2100043027.
Fragement C Gamma receptor IIIa polymorphism is predictive of trastuzumab efficacy in the neoadjuvant setting of HER2-positive breast cancer patients.
Authors: Lee Kaping , Luo Rongzhen , Wang Shusen , Xu Fei
Published: June 2022

e12607

Background: Antibody-dependent cell-mediated cytotoxicity (ADCC) is one of the most important mechanisms of Trastuzumab. Fragement C Gamma receptor (FcγR) IIA and IIIA polymorphisms influence the affinity of immunoglobin G (IgG). Recently, FcγRIIA and FcγRIIIA polymorphisms have identified with the efficacy of trastuzumab. However, whether FcγR polymorphisms are associated with the efficacy of trastuzumab in the neoadjuvant setting was unclear. Methods: We retrospectively enrolled 101 patients with HER2-positive breast cancer receiving chemotherapy plus trastuzumab as neoadjuvant therapy and mastectomy in Sun Yat-sen university cancer center from May 2015 to March 2021. Among them, twenty patients were excluded because lacking of blood samples. Clinical and pathological characteristics, treatments and outcomes of patients were collected. We purified the genomic DNA from peripheral blood samples, performed nested polymerase chain reaction (PCR) and sanger sequencing to identify the polymorphisms of FcγRIIA(rs1801274) and FcγRIIIA(rs396991). Results: Patient samples (n=81) were successfully detected. No significant differences between FcγRIIA/FcγRIIIA genotypes and clinical characteristics, including age, clinical stage, menstrual status, molecular subtyping, treatment and pathological complete response (pCR) rate. In subgroup analyses, FcγRIIIA polymorphism was significantly correlated with pCR rate in the population who received paclitaxel plus trastuzumab therapy (n=34, P<0.05). The Kaplan-Meier analyses showed that no significant difference in disease-free survivals (DFS) between FcγRIIA-131 H/H and R carriers genotype groups ( P=0.24), either that in the FcγRIIIA-158 F/F and V carriers genotype groups ( P=0.60). But the DFS in FcγRIIIA-158 V carriers genotype group were significant longer than that in FcγRIIIA-158 F/F genotype group in subgroup who received paclitaxel plus trastuzumab therapy (n=34, P=0.036), while that was not significant difference in patients with anthracycline-based treatment (n=47, P=0.248). DFS has not yet been reached. Conclusions: FcγRIIIA polymorphism is predictive of trastuzumab efficacy in the neoadjuvant setting of HER2-positive breast cancer patients who received paclitaxel plus trastuzumab therapy. Anthracycline-based treatment may improve the outcomes of HER2 positive breast cancer patients with FcγRIIIA-158 F/F genotype.[Table: see text]
Influencing factors of the recurrence after neoadjuvant therapy in HER2-positive breast cancer.
Authors: Morales Murillo Serafin , Gasol Cud"S Ariadna , Tuset Der-abrain Noemí , Rodriguez Alvaro , Velasco Sanchez Ana , Vilardell Felip , Sanchez Guzman Douglas , Canosa Morales Carles , Olivé Jordi Melé
Published: June 2022

e12608

Background: HER2-positive breast cancer is the more suitable subtype to perform a neoadjuvant therapy with chemotherapy and antiHER2 therapy because a high pathologic response and significance survival. However, despite this high percentage of pathological responses, there are still recurrences that can affect survival. Methods: We analyze a cohort of 287 HER-2 positive breast cancer treated with neoadjuvant chemotherapy and antiHER2 therapy according to current guidelines, to find the factors that could induce a recurrence. Results: Median age was of 56 (28-89), median tumor size of 37 mm (12-140), 145 (50%) had nodal involvement, estrogen receptor positive in 152 patients (53%) and median ki67 expression of 41% (3-95). HER2 expression by inmunohistochemistry was 2+ in 83 patients (29%) and 3+ in 204 (71%). A total of 50% complete pathological response (pCR) rate was detected and 54 (18,8%) relapsed. 17 patients with pCR (12%) and 37 patients without pCR (25%) had a recurrence (OR 4,31, p: 0,003). The factors that most influenced the relapse in the group of patients with pCR were: the initial size (greater than 5 cm) 30% of relapses, the initial axillary involvement (19%) and the cases with HER2 +3 expression and estrogen receptor negative (17%). In the group without pCR, the relapse was more frequent in patients with HER2 +2 expression and estrogen receptor negative (40%), HER2 +3 expression and estrogen receptor negative (43%), initial tumor size greater than 5 cm (38%) and axillary involvement (38%). Conclusions: Although pCR continues to be the most important factor to avoid relapse, there are other factors that must be considered as determinants of relapse despite achieving a pCR. Initial size greater than 5 cm is a poor prognostic factor despite reaching a pCR with up to 30% relapses, so other adjuvant interventions should be considered after initial neoadjuvant treatment.
Clinical N3 as an independent risk factor of recurrence for breast cancer patients achieving pathological complete response and near-pathological complete response after neoadjuvant chemotherapy.
Authors: Qian Xiaoyan , Zhang Pin , Xiu Meng , Li Qing , Wang Jiayu , Fan Ying , Luo Yang , Cai Ruigang , Li Qiao , Yuan Peng , Ma Fei , Xu Binghe
Published: June 2022

e12619

Background: Although achieving pathological complete response (pCR) and near-pathological complete response (near-pCR) after neoadjuvant chemotherapy (NAC) in breast cancer predicts a better outcome, some patients still experience recurrence. The aim of our study was to analyse the predictive factors of recurrence in the pCR and near-pCR population. Methods: We reviewed 1209 breast cancer patients treated with NAC. A total of 292 patients achieving pCR and near-pCR between January 2010 and April 2021 in the Cancer Hospital, Chinese Academy of Medical Sciences (CHCAMS) were included in our analysis. pCR was defined as ypT0N0/ypTisN0. Near-pCR was defined as ypT1mi/1a/1bN0 or ypT0/isN1mi. The Kaplan-Meier method with the log rank test was used to estimate recurrence analysis. Results: Of the 292 patients,173 were pCR and 119 were near-pCR. The median age was 46 years (range 23-75 years). The predominant tumor subtype was human epidermal growth factor receptor type 2 (HER2) positive (49.0%) and triple-negative breast cancer (TNBC) (30.8%). The median duration of follow-up was 53 months (range 9-138 months). A total of 16 (8.9%) patients developed recurrence, with 9 (5.2%) in the pCR group and 16 (13.4%) in the near-pCR group. The vast majority of recurrence occurred within 36 months from onset of NAC. The 5-year recurrence-free survival (RFS) rate of patients achieving pCR was significantly higher than that of patients achieving near-pCR (94.6% vs.85.6%, P=0.008). Clinical N3 (cN3) before NAC was an independent factor of higher risk for recurrence in patients who achieved pCR ( P=0.003) and near-pCR ( P=0.036). Tumor size before NAC, subtype of breast cancer and chemotherapy regimens showed no significant association with RFS both for patients who achieved pCR and near-pCR ( P ≥0.05). Conclusions: cN3 before NAC was an independent factor of higher risk for recurrence in patients who achieved pCR and near-pCR. It is worthwhile to monitor closely for patients with cN3, especially in the first 3 years.
Lactate dehydrogenase as a surrogate marker for both PCR and survival in breast cancer patients who underwent neoadjuvant chemotherapy.
Authors: Lee In Hee , Chae Yee Soo , Lee Jeeyeon , Park Ho Yong , Jung Jin Hyang , Park Ji-young , Park Jee-Young
Published: June 2022

e12621

Background: Glucose metabolism in cancer cells produces various glycolytic metabolites, which can affect cancer progression and treatment outcome. Herein we evaluated the association of glucose transporters and enzymes involved in glucose metabolism with clinic-pathological factors and outcomes in breast cancer patients who underwent neoadjuvant chemotherapy(NAC). Methods: We selected 7 target transporters and enzymes(GLUT1, hexokinase 2, lactate dehydrogenase, MCT1, MCT4, IGF1RA, and IGF1RB) involved in glucose metabolism. Their tumoral expressions were scored both quantitively and qualitatively based on tissue microarrays and immunohistochemistry as previously described (Pinheiro et al, 2010) and then evaluated in relationships with pretreatment clinical/pathological characteristics and treatment outcomes including findings of 18F-FDG PET/CT,pathologic complete response(pCR), and relapse in breast cancer(stage IIA-IIIC) patients who underwent anthracycline or taxane-based NAC. Results: Of the 236 enrolled patients, 145(61.4%), 44(18.6%), and 47(19.9%) were luminal, HER2-enriched, and TNBC subtypes. Pathologic CR was determined 50(21.2%) and 57(24.2%) relapses, 42(17.8%) distant relapses, and 28 deaths were observed during median follow-up duration of 64.0 (32.3-114.9) months. The expression rates of the target molecules were 76.0, 31.1, 42.1, 54.9, 67.9, 78.4, and 49.8% for GLUT1, hexokinase 2 (HK2), lactate dehydrogenase(LD), MCT1, MCT4, IGF1RA, and IGF1RB, respectively. Among target molecules in glucose metabolism, LD was significantly associated with pCR(OR = 0.251; p- = 0.016) and distant disease-free survival (HR = 2.29; P = 0.019). Plus, LD expression shows a trend for a high SUVmax of primary tumor 18F-FDG PET/CT(OR = 1.797 P = 0.060). Conclusions: Tumoral expression of lactate dehydrogenase can be considered as a predictive marker for pCR to NAC and plus prognostic marker for survival in patients with breast cancer.
Neutrophil-lymphocyte ratio and prediction of pathological complete response to neoadjuvant treatment in breast cancer.
Authors: Clarke Rachel , Lucas Mairi , Ryan Niamh , Walsh Siun , Mahon Sarah , Kelly Catherine Margaret
Published: June 2022

e12627

Background: Pathological complete response (pCR) after neoadjuvant therapy in breast cancer is an important prognostic indicator for improved disease free survival. High tumour grade, low ER-status, HER2-positivity predict higher likelihood of a pCR however better predictive biomarkers are needed. The role of the immune system and specifically the presence of tumour infiltrating lymphocytes in increasing response to chemotherapy has been extensively studied across cancer subtypes2. We sought to determine if neutrophil-to-lymphocyte ratio (NLR) as a marker of immune inflammatory response could be informative in predicting likelihood of pCR. Methods: We identified a cohort of patients who had received neoadjuvant chemotherapy between 2012 to 2018. We extracted clinical, pathological and laboratory data for each case. A pretreatment peripheral blood test was used to calculate a neutrophil-to-lymphocyte ratio. We used R-studio to analyse our data. The primary objective was to determine if there was an association between NLR and pCR. Statistical analysis was performed to assess whether NLR ratio correlated with pCR. Results: We identified 107 patients who had received NAC for early stage breast cancer during our study period. The mean NLR in the cohort was 2.95 (range 0.76-11.9). 35 (32.7%) patients achieved a pCR. There was no statistically significant different in NLR in those who achieved pCR (n=35) and those who did not (n=72) (p value= 0.75). Patients with triple negative breast cancer (TNBC) had a higher rate of pCR (45.1%), compared to HER2-positive (42.1%) and ER-positive HER2-negative (25.4%). The NLR was not significant in predicting pCR within the separate histological cohorts. Conclusions: NLR did not predict for pathological complete response in our cohort. Further studies into the predictive value of NLR in this setting with larger cohorts are needed. Investigation into the dynamic changes of NLR both pre, post during treatment may provide further insights as may larger cohorts for analysis in each histological subtype.
Prognostic value of molecular response via ctDNA measurement in predicating response of systemic therapy in patients with advanced solid cancer.
Authors: Esmail Abdullah , Guan Jian , Xu Jiaqiong , Al-Rawi Hadeel , Parks Bethany , Al Saadi Noor , Khan Tanya , Madoux Laura , Taha Marwa , Abdelrahim Maen
Published: June 2022

e13001

Background: Molecular profiling of cancer can guide treatment decision, monitor response and predict clinical outcome in the era of precision medicine and individualized treatment. Emerging evidence has suggested that ctDNA change correlates with treatment response and predates radiological relapse. Thus, we aim to provide real-world data regarding the dynamic changes of ctDNA level measured via Guardant 360 Response in advanced solid cancer correlates with clinical outcome. Methods: We retrospectively reviewed data of patients with advanced solid cancer and had at least 2 timepoints of Guardant 360 Response test at Houston Methodist Cancer center from 1/1/2014- 2 /1/2022. Data collected included age, gender, type of solid cancer, mutational values, treatment started date and type of systemic therapy. Personalized mutational profiles derived from tumor tissue via whole-exome sequencing were used to design patient-specific ctDNA assays for variant detection in plasma samples. Blood samples taken at baseline and 8 weeks were analyzed to a 70-gene next-generation sequencing panel. On-therapy changes in circulating tumor DNA levels (molecular response) were measured using a ratio computation, with response defined as a decrease in mean variant allele fraction of 50% or more. Apart from ctDNA analysis, patients were also monitored using tumor markers and radiological imaging. Results: : Of 267 patients, only 93 were met the inclusions criteria with age 58.66 (±12.95) and female were the most with 77 (82.80%). Patients with breast cancer were the dominant with 62 (66.67%), Lung adenocarcinoma 20 (21.51%), Uveal Melanoma 4 (4.30%), Colorectal Cancer and Lung Squamous Cell Carcinoma 2 (2.15 %) each, Large Cell Lung Carcinoma, Sarcoma and Thymic Carcinoma were 1(1.07%) each. Patients who received Chemotherapy /Immunotherapy were 38 (41.30%), Chemotherapy/Immunotherapy/Radiation therapy were 29 (31.52%), Immunotherapy 9 (9.78%), Chemotherapy/Immunotherapy/Targeted Therapy 2 (2.17%) and Targeted Therapy /Chemotherapy 3 (3.26%).Patients samples who correlated with clinical data were 89 (95.70%) and only 4 (4.30%) were not .Follow-up time 2.15 (interquartile range: 1.10-4.12) years, patients who still alive are 24 (25.81%), median survival time 2.4 (95% CI: 1.78-2.76) years. Conclusions: Our data demonstrated that molecular response evaluation using circulating tumor DNA as a noninvasive predictor of response to systemic therapy in addition to standard of care imaging in some solid cancer. Further prospective studies are needed to confirm the validation.
Integrated analysis of pivotal biomarker, immune cell infiltration, and therapeutic drugs for LSM1-mutated in breast cancer.
Authors: Tzeng Yen-Dun Tony , Sheu Jim Jinn-Chyuan , Li Chia-Jung
Published: June 2022

e13011

Background: The discovery of early diagnosis and prognostic markers for breast cancer can significantly improve survival and reduce mortality. LSM1 is known to be involved in the general process of mRNA degradation in complexes containing LSm subunits, but the molecular and biological functions in breast cancer remain unclear. Methods: In the present study, we investigated the expression profiles, prognostic roles, and genetic alterations of LSM1 in patients with breast cancer through several public databases, containing Oncomine and Gene Expression Profiling Interactive Analysis, Human Protein Atlas, Kaplan–Meier plotter and cBioPortal. Then, we constructed the protein-protein interaction networks of LSM1 proteins and their interactors by using the String database and Cytoscape software. In addition, we performed the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichmente. Finally, we explored the mechanisms underlying LSM1 involvement in BRCA by using gene set enrichment analysis. Results: We found that functional LSM1 inactivation caused by mutations and profound deletions predicted poor prognosis in BRCA patients. LSM1 was highly expressed in both BRCA tissues and cells compared to normal breast tissues/cells. High LSM1 expression is associated with poorer overall survival and disease-free survival. The association between LSM1 and immune infiltration of breast cancer was assessed by TIMER and CIBERSORT algorithms. LSM1 showed a strong correlation with various immune marker sets. Most importantly, pharmacogenetic analysis of BRCA cell lines revealed that LSM1 inactivation was associated with increased sensitivity to refametinib, and trametinib. However, both drugs could mimic the effects of LSM1 inhibition and their drug sensitivity was associated with MEK molecules. Therefore, we investigated the clinical application of LSM1 to provide a basis for sensitive diagnosis, prognosis and targeted treatment of breast cancer. Conclusions: In brief, our finding may contribute to increasing currently limited prognostic biomarkers and treatment options for breast cancer.
Downregulation of ATP binding cassette subfamily a member 10 acts as a prognostic factor associated with immune infiltration in breast cancer.
Authors: Tzeng Yen-Dun Tony , Sheu Jim Jinn-Chyuan , Li Chia-Jung
Published: June 2022

e13012

Background: The human ATP binding cassette (ABC) family of transporter proteins plays an important role in the maintenance of homeostasis in vivo. The aim of this study is to evaluate the potential diagnostic, prognostic, and therapeutic value of the ABCA10 gene in BRCA. Methods: In this study, a multi-step process was used to construct an immune-related genes (IRGs) based signature leveraging the expression profiles and clinical characteristics of BRCA from the Gene Expression Omnibus (GEO) database and the Cancer Genome Atlas (TCGA) database. An integrated immunogenomic analysis was performed to determine the association between IRGs with prognostic significance and cancer genotypes in the tumor immune microenvironment (TIME). Moreover, we performed a comprehensive in silico therapeutics screening to identify agents with subclass-specific efficacy. Results: We found that ABCA10 expression was downregulated in different subgroups of breast cancer and strongly correlated with pathological stage in BRCA patients. Low expression of ABCA10 was associated with BRCA patients showing shorter overall survival (OS). ABCA10 expression may be regulated by promoter methylation, copy number variation (CNV) and kinase, and is associated with immune infiltration. Our study also demonstrated the potential role of ABCA10 modifications in tumor microenvironment (TME) cellular infiltration. Nevertheless, the regulatory mechanism remains unknown and immunotherapy is marginal in BRCA. We demonstrate the expression of different ABCA10 modulators in breast cancer associated with genetic variants, deletions, tumor mutation burden (TMB) and TME. Mutations in ABCA10 are positively associated with different immune cells in six different immune databases. Mutations in ABCA10 and immune cell infiltration play an important role in breast cancer. Conclusions: Overall, this study provides evidence that ABCA10 could become the potential targets for precision treatment and new biomarkers in the prognosis of breast cancer.
Safety and efficacy of monoclonal antibodies and tyrosine kinase inhibitors in advanced breast carcinoma.
Authors: Akbar Usman Ali , Vorla Mounica , Ashraf Aqsa , Poladi Keerthi , Qazi Shaheryar , Dab Ammar Yaser , Ijaz Hafsah , Azhar Ali Sibtain , Manahil Haider Jeoffrey Syeda , Akhtar Muhammad Ali Ali , Momin Ali
Published: June 2022

e13017

Background: Novel drugs that target HER2 receptors have shown promise in the treatment of Advanced breast carcinoma (BC). We study here the safety and efficacy of select monoclonal drugs (Mab) and tyrosine kinase inhibitors (TKIs) in the treatment of advanced BC. Methods: Following the PRISMA guidelines, we searched the literature on PubMed, Cochrane, Embase & clinicaltrials.gov. A total of 1054 articles were screened, and 6 studies were included. Results: In a phase III trial comparing Margetuximab (MAR) vs Trastuzumab (TRA), the overall survival (OS) and Progression free survival (PFS) was superior for MAR (21.6m Vs 19.8m & 5.7m Vs 4.4m respectively). However, the side effect profile is comparable for both drugs.Neutropenia (50 %) was a key problem in an ongoing trial including Zenocutuzumab (ZENO), resulting in dosage reduction. Similarly, phase III trials incorporating TKIs such as Neratinib (NER) and Tucatinib (TUC), there was improved OS (21m Vs 18.7, 24.7m Vs 19.2m respectively) as compared to Standard of care and chemotherapy. Regarding safety profile, these therapies are generally well tolerated with manageable side effects as listed in the table. Conclusions: Both monoclonal antibodies and tyrosine kinase inhibitors show clinically significant benefits in advanced HER2 positive breast carcinoma. However, more evidence and randomized clinical trials are needed to further establish their role in this rapidly evolving field.[Table: see text]
HERibuline: Eribulin mesylate and Trastuzumab in pretreated HER2-positive advanced breast cancer—A report of region’s practice.
Authors: Gassian Noemie , Paget-Bailly Sophie , Djoumakh Oum El Kheir , Mansi Laura , Dobi Erion , Bazan Fernando , Curtit Elsa , Chaigneau Loic , Meneveau Nathalie , Paillard Marie-Justine , Selmani Zohair , Viot Julien , Borg Christophe , Meynard Guillaume
Published: June 2022

e13020

Background: Until 2020, in human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer (ABC), the two first lines of metastatic treatment were well defined but after, many options were possible, most often combining targeted therapy plus chemotherapy. Eribulin mesylate is indicated for the treatment of patients with ABC previously treated by anthracycline and taxane regimens in the advanced setting. Here, we present the results of eribuline and trastuzumab (E/T) combination in HER2-positive ABC previously treated. Methods: Patients with HER2-positive ABC treated with the E/T combination from our region cancer institute were included in this retrospective study. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), overall response rate (ORR), clinical benefit rate (CBR) and safety. Results: Between November 2013 and July 2019, a total of 34 consecutive patients with HER2-positive ABC were included. The median number of previous lines for advanced setting was 4 (range 2-7). Patients treated by taxanes and anthracyclines represented 91% and 47% respectively; 50%, 79% and 62% were previously treated with pertuzumab, trastuzumab emtansine and lapatinib respectively. After a median follow up of 24.8 months, median PFS was 6.2 months (95% CI [3.35-7.13]) and median OS was 12.6 months (95% CI [7.13-18.56]). The ORR and CBR were 38% and 53%, respectively. No unexpected adverse event was observed. The most frequent grade 3-4 toxicity was hematologic (44.1%). Conclusions: Recently, new therapies have revolutionized the management of HER2-positive ABC and patients benefit from a prolonged overall survival associated with a maintained performance status. However, in pretreated and advanced metastatic setting, there are few scientific evidence to guide the choice of treatments. A combination of E/T could be an effective option in patients with good performance status and willing to receive treatment.
Clinical characteristics and real-world progression-free survival (rwPFS) of patients with HER2-positive and hormone receptor (HR)-positive metastatic breast cancer (MBC) initiating endocrine therapy (ET) in combination with the first line of treatment: An analysis of electronic health records in the United States.
Authors: Sanglier Thibaut , Shim Jinjoo , Eiger Daniel , Poppe Raf , Restuccia Eleonora
Published: June 2022

e13028

Background: Dual HER2 blockade with pertuzumab (P) + trastuzumab (H), combined with taxane induction therapy, is the standard of care for the first-line treatment of patients with HER2-positive MBC. In clinical practice, after achieving clinical benefit with approximately 4–6 cycles of PH + taxane induction, maintenance therapy is continued with PH only until disease progression or unmanageable toxicity. Approximately 50–60% of patients with HER2-positive MBC also have concurrent HR expression and may receive ET in combination with PH. This study investigated the clinical characteristics and outcomes of patients initiating ET combined with PH as maintenance therapy after completion of PH + taxane induction. Methods: We conducted a retrospective cohort study using a nationwide US electronic health record-derived de-identified database (Flatiron Health). Patients with HER2-positive and HR-positive MBC who initiated an ET between Jan 1, 2012 and Feb 28, 2021 with concomitant PH after receiving at least four cycles of first-line PH + taxane induction were included. The index date was the date of ET initiation. Progression data were abstracted from the medical charts. Mortality data were abstracted and combined with patient-level structured data (obituaries and Social Security Death Index). rwPFS was defined as the time from index date until first progression event > 14 days after the index date, or date of death; otherwise, patients were censored on the date of last clinical note abstraction. Baseline characteristics were described using summary statistics, and rwPFS in the maintenance setting was described using a Kaplan–Meier estimator from the index date. Results: Of 24,690 patients diagnosed with MBC in the database, 252 (1%) met the eligibility criteria. All patients were female. The median age was 56.6 years; 149 patients (59%) were diagnosed with de novo MBC; 248 (98%), with estrogen receptor-positive disease; and 182 (72%), with progesterone receptor-positive disease. One hundred ninety-three patients (77%) received an aromatase inhibitor as ET. The median number of taxane cycles received prior to the index date was six. Median maintenance rwPFS was 21.4 months (95% confidence interval = 16.1, 25.3). Conclusions: Given the therapeutic opportunity presented by HER2/HR co-expression and the favorable maintenance rwPFS shown here with PH + ET following taxane induction, the investigation of more potent ETs combined with PH is justified in order to further improve outcomes in first-line HER2-positive/HR-positive MBC.
Quality of life in patients with de novo metastatic breast cancer undergoing locoregional surgery: A prospective observational study.
Authors: Chongxi Ren , Jianna Sun , Lingjun Kong , Kun Mu , Reize Ren
Published: June 2022

e13044

Background: Breast cancer remains the most frequent type of cancer in women, with de novo metastatic breast cancer (dnMBC) accounting for approximately 10% of patients. Advances in diagnosis and treatment of breast cancer have led to an increase in cancer survival, resulting in quality of life (QoL) improvement. However, there are few reports on whether local treatment improves quality of life for de novo metastatic breast cancer (dnMBC). Aim: To evaluate QoL in dnMBC patients since randomization using scores from the FACT-B health survey. Settings and design: This study was designed as a prospective observational research project and was approved by the Ethics Committee of the Ethics Committee of Cangzhou Clinical College of Integrated Traditional Chinese and Western Medicine of Hebei Medical University (NO.20200212). Methods: Eighty-six patients with dnMBC were randomised to surgery of the primary tumor followed by systemic therapy (surgery group) or to primary systemic therapy without surgery (non-surgery group). QoL analyses covering the results at baseline, 6,12,18,24 and 30 months follow up of 81 (94%) patients, was assessed with the Functional Assessment of Chronic Illness Therapy General Questionnaire, including Breast Cancer Supplement (FACT-B) questionnaires. Inclusion criteria were: did not meet the diagnostic criteria of de novo metastatic breast cancer and patients could not cooperate QoL was assessed by FACT-BTOI variables evaluated at 6 time point. Average FACT-B TOI score was measured by the prorated aggregate score of 37 items from the FACT-B. The Wilcoxon rank sum test was used to compare the differences at each time point. The level for significance was set at p<0.05.All analyses were performed with STATA 16. Results: From 2019 to 2021,a total of 86 dnMBC patients were selected and recruited in Department of breast surgery of our hospitals. Among them, 81 completed FACT-B questionnaires and their data were analyzed. Forty-one (95%) patients in the surgery group and 40 (93%) in the non-surgery group were included in the QoL analyses. A total of 362 QoL questionnaires were analyzed, 81(100%) at baseline, and 73(90%), 64(79%), 58(72%), 47(58%), 39(48%) at 6,12,18,24, and 30 months, respectively. The average FACT-B TOI scores showed no statistically significant difference between the two groups at each time point, with a P value of 0.09 at baseline, and 0.47,0.67,0.36,0.45,0.34 at 6,12,18,24, and 30 months, respectively. No significant difference was found in QOL evaluation between the two groups. Conclusions: Our prospective randomized trial showed that compared with non-surgery counterparts, locoregional surgery does not improve QoL of patients with dnMBC. Clinical trial information: 20200212.
The modified glasgow prognostic score (MGPS) and the mortality prediction MODEL II (MPM II) CAN predict mortality in patients with breast cancer admitted to intensive care: A retrospective cohort study.
Authors: Olmez Omer Fatih , Tunay Burcu , Bilici Ahmet , Bayramgil Ayberk , Çavuşoğlu Güneş Dorukhan , Oz Huseyin
Published: June 2022

e13055

Background: We aimed to examine whether inflammatory markers and various risk scoring systems could be utilized to predict the prognosis of breast cancer patients hospitalized in the intensive care unit. Methods: In this retrospective cohort study, we evaluated 71 breast cancer patients followed and treated by the Medical Oncology Department of Medipol University Faculty of Medicine who were admitted to the intensive care unit at any stage of their treatment between 2014 and 2020. In addition to scoring systems developed to assess prognosis in the ICU, we recorded and calculated various inflammation-related markers. All data were compared between groups formed according to survival status. Results: The median age was 58 (range: 33-90) years. Thirty-seven (52.1%) patients had died and 34 (47.9%) patients had survived. Neutrophil lymphocyte ratio (p = 0.021), Modified Glasgow prognostic score (p < 0.001), APACHE II score (p < 0.001) and MPM II (admission) (p < 0.001) were significantly higher in the exitus group than in the survivors. Lymphocyte monocyte ratio (p = 0.030) and prognostic nutritional index (p = 0.004) were significantly higher in the discharged group than in the exitus group. When we evaluated performance of the prognostic scores to predict mortality, we found APACHE II score (AUC: 0.939, 95% CI: 0.888 - 0.990), MPM II-Admission (AUC: 0.936, 95% CI 0.880 - 0.992) and mGPS (AUC: 0.727, 95% CI: 0.600 - 0.854) had the highest area under curve values. Multivariable regression revealed that longer chemotherapy duration (≥2 weeks), having an mGPS score of 2 points, and high MPM-II (≥36 points) were independently associated with mortality. Conclusions: Among the inflammatory markers and scores examined, mGPS and MPM-II were found to be independently associated with mortality in breast cancer patients hospitalized in the intensive care unit. In addition, patients with longer chemotherapy duration had a higher risk of mortality, but this result was limited by various possible confounders.
Institutional review of African American (AA) patients with metastatic triple-negative breast cancer.
Authors: Vobugari Nikitha , Chitalia Ami
Published: June 2022

e13059

Background: Atezolizumab+ Abraxane (Ate+Abx) was approved as 1st line treatment in metastatic TNBC based on IMPASSION (IM) 130 trial and was subsequently withdrawn per IM131 trial. Treatment of mTNBC remains challenging. Pembrolizumab with chemotherapy received accelerated approval based on Keynote-355. Poor outcomes among AA patients (pts) are linked to biological differences, BRCA1/2 mutations, obesity, and socioeconomic barriers. In TNBC clinical trials, AA pts continue to be underrepresented, e.g., 5.8% (26) in IM130 and 4.9% (21) in IM131. Our cancer center sees over 300 new BC pts a year, and at least 50% identify as AA. Here we examine our institutional experience. Methods: IRB-approved retrospective database search was conducted between 01/01/2019- 04/16/2021 to identify 11 pts treated with Ate+Abx for mTNBC at Medstar Washington Hospital Center, DC. Demographic variables manually extracted were age, BMI, insurance type and outcomes. Results: 10/11 (91%) pts were AA with lines of therapy ranging 1-6. 20% (2/10) showed partial response (PR) on 3-month (M) interval imaging per the RECIST 1.1 scoring. PD occurred in 6/10 (60%) of pts, although PD-L1 was positive in 90% (9/10) pts. Time to progression (TTP) was 1-7 M (median 3M) compared to TTP of 5.59 to 7.46M (median 7.16M) for all races in the IM130 study. Autoimmune colitis, peripheral neuropathy, and fatigue were notable adverse effects (AEs). 2/10 (20%) pts discontinued treatment due to AEs. Colitis and neuropathy in IM130 were <1%. Mean age at drug initiation was 52.2 vs. 55 years in IM130, indicating earlier onset of mTNBC in the AA population. Conclusions: Trends of higher PD and earlier TTP were noted in our AA pts. Young age at metastasis, high number of previous lines of therapy, high number of metastatic sites, and obesity were noted amongst our AA mTNBC pts. Positive PD-L1, BRCA mutations, metastatic sites, BMI, or insurance type did not correlate with outcomes. Pts with PR vs. PD were not different in terms of insurance, metastasis sites, and BMI. Differences in AEs are noted; however, the small pt population size and lack of a control group are limitations. While the FDA has withdrawn Ate from trials for mTNBC, this study suggests a need for more AA pts to be included in clinical trials for TNBC. Lack of health care access, insufficient education, inadequate recruitment, and distrust of the medical system are contributing factors that require continued efforts.[Table: see text]