bluuebunny/crossref_metadata_2025_split huggingface dataset:
Survival and recurrence of breast cancer patients with pathologic complete response after neoadjuvant chemotherapy.
Authors: Lee Young Joo , Ahn Sei-Hyun , Sohn Byung Ho , Lee jong Won , Chung Il Yong , Ko Beom Seok , Kim Hee Jeong , Kim Jisun , Lee Sae Byul 
Published: May 2019

e12121 Background: Patients with Pathologic complete response after neoadjuvant chemotherapy is known to have a good prognosis. However, there is a difference depending on how the complete remission is defined. Methods: We analyzed basic characteristics and outcomes of 295 patients who had pathologic complete response defined as ypT0 and ypTis after neoadjuvant chemotherapy for breast cancer at Asan Medical Center in Seoul, Korea. Results: Median follow up period was 66.5 month(6~128 month). Overall survival was 94% at 5-year and 10-year. No difference was shown in preoperative age, grade, HR/HER2 status, Ki-67 level. Clinical stage III showed worst outcome(85.8%). Survival rate between ypT0N0 (98.8%) and ypTis (89.1%, p=0.00) and between ypT0/TisN residual (85.7%, p=0.00) was shown, but no statistical difference between ypTis and ypT0/Tis with residual nodes(p=0.539). Disease free survival also showed no statistical significance between age, HR/Her2 status. But patients with low Ki-67 level(0~20%)(68.2%) at diagnosis had worse DFS compared to high Ki-67 level(>20%)(87.5%)(P=0.013). No difference between intrinsic subtypes was shown. Patients with residual nodal disease had worse DFS(66.1%) than ypN0(89.1%)(p=0.00). DFS of ypT0N0 was 92.7% and ypTisN0(75.5%), ypT0/Tis with residual metastatic nodes(71.4%). There was no significant difference in type of chemotherapy regimen. Conclusions: Overall survival and disease free survival was different in ypT0N0 with ypTis and residual nodal disease. Good prognosis of pathologic complete response should be limited to cases in which the cancer has completely disappeared.
Effect of additional administration of pertuzumab for the post-treatment in patients with HER2-positive locally advanced/metastatic breast cancer who were previously treated with pertuzumab.
Authors: Kubo Shinichiro 
Published: May 2019

e12500 Background: Currently, there are no data related to re-administering trastuzumab (T) + pertuzumab (P) beyond the second-line therapy to patients with human epidermal growth factor receptor 2-positive advanced/metastatic breast cancer (HER2-MBC) who had previously received P. The present study targeted patients with HER2-MBC who were previously treated with P and aimed to evaluate the efficacy and safety of additional administration (top-up intervention) of P post-disease progression (PD) after standard treatment with T plus chemotherapy vinorerbine(VNR) or eribulin (ERI). Methods: SBP-08 was a multicenter, collaborative, single-arm phase II study of HER2-MBC patients who had previously received P. After standard treatment with T and chemotherapy, P was additionally administered (top-up intervention) post-PD. Results: Eleven HER2-MBC patients, recruited between June 2016 and June 2018, who had previously received P participated in this study. Their mean age was 63.5 years, and 45% were estrogen receptor (ER)-negative, while 55% were ER-positive. The mean chemotherapy history was 3.6 regimens, with a median of four regimens. Previous treatment regimens with P had been effective in all patients. All patients had organ metastasis and treatment histories with TDM-1. Initially, during the two-year case collection period, registration of 30 patients was planned. However, the study was terminated because the interim analysis did not demonstrative effectiveness, and it was decided that there were no potential benefits to the patients. The overall response rate (ORR) of the standard treatment was 0%, stable disease (SD) was 36%, PD was 55%, and the clinical benefit rate (CBR) was 0%. The following combination anticancer agents were used: VNR (10 patients) and ERI (one patient). The intervention treatment (top-up with P) achieved the following: ORR 0%, SD 22%, PD 78%, and CBR 0%. PFS for the standard treatment was 1.6 months, whereas PFS for the intervention treatment was 1.3 months. In the standard treatment, febrile neutropenia was observed in two patients. No increases in adverse events were observed with the intervention treatment. Conclusions: No clinical benefit was demonstrated with the intervention treatment in the present study. Top-up with P after standard treatment with T and chemotherapy post-PD was deemed ineffective. Clinical trial information: UMIN000020837.
Monitoring treatment efficacy and resistance in breast cancer patients via circulating tumor DNA genomic profiling.
Authors: Jia Wang Xiao , Chen Zhan-Hong , Sun Tian , Yang Zi Yan , Zheng Yabing , Yu Ruoying , Wu Xue , Yan Junrong , Shao Yang , Shao Xiying , Huang Jian , Wenming Cao 
Published: May 2019

e12502 Background: Circulating tumor DNA (ctDNA) from liquid biopsy provides a valuable assessment of invasive breast cancer (BC). We evaluated the utility of ctDNA to reflect the efficacy of HER2-targeted trastuzumab in treating HER2+ BC patients, as well as chemotherapy in treating HER2- BC patients, to monitor trastuzumab and chemotherapy resistance mechanisms. Methods: Targeted next-generation sequencing (NGS) of 416 cancer-relevant genes was performed in 41 plasma biopsy samples from 19 HER2+ and 12 HER2- BC patients in a retrospective study. We compared ctDNA somatic mutations and germline mutations for analyzing acquired and innate resistance, respectively. Results: ERBB2 somatic copy number of HER2+ BC patients who developed progressed diseases to HER2-target therapy was significantly higher than those benefited from HER2-target therapy. HER2+ BC patients who developed acquired resistance to trastuzumab showed frequent genomic alterations on ERBB2, TP53, EGFR, NF1 and SETD2 genes. Specifically, in longitudinal analyses, somatic mutations found in the original breast tumor can be detected in the liver metastasis and plasma ctDNA with increased allele frequencies. Newly emerged deleterious mutations occurred when the patient was benefiting from trastuzumab, predicting the poor prognosis. From these newly emerged somatic mutations, EBBB2L869R was further investigated in vitro and contributed to trastuzumab resistance. In the HER2- BC patients with chemotherapy resistance, frequently genetic alterations on TP53, PIK3CA and DNA damage repair genes were observed in ctDNA mutation profiling. Conclusions: liquid biopsy ctDNA, particularly longitudinal analyses, provides insights into targeted therapy efficacy and gene alterations underlying trastuzumab resistance and chemotherapy resistance in HER2+ and HER2- BC patients, respectively.
Changing trends in HER-2 neu positive breast cancers in women: A study by a medical student and his preceptor.
Authors: Monga Aaron , Prasad Chaya , Prasad Rama , Alcantara Rita 
Published: May 2019

e12509 Background: Breast cancer affects 3.5 million women in the United States with 155, 000 women living with metastatic breast cancer in the US with 40,290 deaths every year. In particular, HER-2 NEU positive lesions are aggressively malignant, with increased recurrence and decreased survival but good response to Herceptin. This study reviews trends of breast cancers and looks in depth into prognostic indicators, in HER-2 NEU positive breast cancers. Methods: Anonymized medical data including demographics and tumor characteristics from San Antonio Regional Hospital’s (SARH) tumor registry database were collected from 2015-2017. Inclusion criteria included female patients with a diagnosis of invasive breast cancers. Data was stratified according to age at diagnosis, race of the patient, histologic grade, size of the tumor, lymph node status, HER-2 NEU status and stage (pathologic and clinical). Results: From 2015 to 2017 we identified 371 patients with invasive breast cancers. The percentages of HER-2 NEU positive patients in these years was 15.7%, 16.0%, and 9.4% in 2015, 2016 and 2017 respectively. This represented a 6.6% drop in HER-2 NEU positive patients from 2016 to 2017. We then looked at all HER-2 NEU positive breast cancers. In 2017, 71% of patients with HER-2 NEU positive tumors presented with a low pathologic size compared to 36% in 2016 and 44% in 2015, and 29% presented with low histologic grade compared to 14% in 2016 and 12% in 2015, and 0% of patients presented with lymph node metastases compared to 18% in 2016 and 20% in 2015. Overall 100% of patients with HER-2 NEU positive tumors presented at a low stage compared to 73% in 2016 and 52% in 2015. Conclusions: Our data shows a decrease in HER-2 NEU positive cancers from 2015 to 2017. It is important to note that these HER-2 NEU lesions were associated with, smaller pathologic size, lower histologic grade, lower incidence of lymph node involvement and lower clinical stage. The identification of this subset of low grade, low stage HER-2 NEU positive tumors may be attributed to newer imaging modalities such as digital tomosynthesis and more aggressive preventive screening measures. These sensitive screening techniques may ensure a good clinical outcome.
Selected reaction monitoring mass spectrometry (SRM-MS) evaluation of HER2 equivocal breast cancer.
Authors: Edenfield William Jeffery , Merchant Krupa , Martin Julie C. , Drusbosky Leylah , Elliott Mary Helen , Reddy Sandeep K. , Szeto Christopher , Cecchi Fabiola , Schammel Christine , Schammel David P , Grinstead Rhett M , Chung Ki Y. 
Published: May 2019

e12510 Background: Human epidermal growth factor receptor type 2 (HER2) is a significant driver of breast oncogenesis and has been found to be amplified in one-fifth of all breast cancers. Identification of cell surface over-expression of HER2 can be completed using immunohistochemistry (IHC), while amplification of the gene can be detected using fluorescence in situ hybridization (FISH) or differential polymerase chain reaction (PCR). Definitive diagnostic standards for each detection method are established, however approximately 5-10% of breast cancer patients have a HER2 status of “double equivocal,” offering little guidance to directing therapy. Previously, selected reaction monitoring mass spectrometry (SRM-MS) illustrated the dynamic range of HER2 positive protein expression by IHC or amplified FISH to have a threshold determination of 740amol.We hypothesized that this method could delineate which ‘double equivocal’ patients may indeed express enough HER2 to be candidates for targeted therapy. Methods: Overall, 76 invasive breast cancer samples identified as equivocal by IHC and FISH between 1/1/2010 and 12/31/2017 were evaluated. Typical demographic and clinicopathologic data were collected to include age, race, histology, size, hormone receptor status, treatments and outcomes. HER2 levels in each equivocal sample were quantitated using SRM-MS. Data were analyzed using Fisher’s t-tests, chi-square and ANOVA (p < 0.05). Results: Using the 740 amol/ng as the SRM-MS cut-off for HER2 positivity, the group was divided into two cohorts. No significant differences were found for demographic or pathologic variables. While identified HER2 levels were between 209.1-1286.6amol, 18 patients had SRM-MS results above the threshold but outcomes were not correlated with treatment received. Conclusions: We report the largest series of doubly equivocal HER2 patients evaluated with SRM-MS. For patients with invasive ductal carcinoma, SRM-MS was not able to identify patients for whom HER2 directed therapy would be a benefit. Future plans include an assessment of this cohort with an RNA seq algorithm given the high degree of accuracy we have shown with known HER2 positives and negatives.
Novel tetravalent bispecific T-cell engaging antibodies for cancer immunotherapy.
Authors: Lakshmikanthan Sribalaji , Wyant Timothy , Pandian Swarna , Murphy Shaun , Chen Yangde 
Published: May 2019

e12513 Background: Current immunotherapy involves redirection of T cells against tumor either by chimeric antigen receptors (CAR-T) or bispecific T-cell engagers (BiTEs). These T cell-engaging technologies have been enabled by engineering single-chain variable fragment (scFv). Most BiTEs are designed as heterodimers, with monovalent binding to tumor cell surface antigens and to CD3+ T cells. Here, we describe a novel tetravalent bispecific (TetraBi) platform: a tumor associated antigen specific, T-cell engaging antibody that provides significant advantages over traditional BiTEs. Specifically, we showcase three unique TetraBi antibodies targeted for various cancers. Methods: ABP-100 was engineered by fusing CD3-binding scFv to the c-terminus of anti-HER2 IgG1 light chain, resulting in two binding sites each for HER2 and CD3. In preclinical studies, ABP-100 was compared with a clinical-stage heterodimeric antibody that is monovalent for HER2 and CD3. We also built TetraBi for anti-Glypican 3 (GPC3, ABP-110) and Claudin 18.2 (CLDN18.2, ABP-150) for gastric cancer therapy. Results: We observed bivalent binding to the tumor antigens (HER2, GPC3, CLDN18.2) on tumor cells like the monoclonal antibodies do. Interestingly, the CD3-binding domains in our TetraBi format showed functionally monovalent binding to CD3. ABP-100 displayed comparable cytokine release to the heterodimer molecule both in vitro and in vivo. In HER2+ cancer models, ABP-100 showed highly potent antitumor activity, resulting in complete responses in tumor bearing mice at doses as low as 0.1 mg/kg with no evidence of tumor relapse. ABP110 and ABP-150 also demonstrated potent cancer cell killing in vitro. Conclusions: This novel TetraBi antibody format enables concurrent bivalent and monovalent co-engagement of distinct target antigens in tumor microenvironment with promising therapeutic implications. Furthermore, it provides a potentially larger therapeutic index than more traditional bispecific formats that feature monovalent recognition of tumor antigens.
Risk stratification based on a prognostic factor index among patients with HR+, HER2- MBC.
Authors: Vidal Gregory A. , Cuyun Carter Gebra , Gilligan Adrienne , Saverno Kim , Zhu Yajun Emily , Price Gregory L , Deluca Angelo , Nash Smyth Emily Nash , Koustenis Andrew G. , Huang Yujing , Schwartzberg Lee S. 
Published: May 2019

e12516 Background: Patient and tumor characteristics, such as tumor grade (TG), site of metastases, hormone receptor status, and endocrine resistance, affect the prognosis for patients (pts) with HR+, HER2- metastatic breast cancer (MBC). This study explored the impact of multiple clinical prognostic factors on pt overall survival (OS) and real-world progression-free survival (rwPFS). Methods: This retrospective study used electronic health record (EHR) data of US pts from a network of community oncology practices maintained in the Vector Oncology Data Warehouse from 1/1/2008 to 4/30/2017. Eligibility included HR+, HER2- MBC diagnosis in 2008 or later and prior systemic therapy for MBC. An index variable was created to assess the effect of multiple clinical prognostic factors collectively, including liver metastases (LM), primary endocrine resistance (PER) (Cardoso F et al. 2018), negative progesterone receptor (PR-) status, and high TG. Pts were grouped based on the number of prognostic factors present at MBC diagnosis: 0, 1, and 2+. Differences in rwPFS and OS from start of first line therapy were evaluated by Kaplan-Meier method and multivariable Cox proportional hazards regression. Results: Eligible pts (n=378) had a mean age of 60.3 years. Among these 57.1% were white, 36.5% were de novo metastatic, 22% had LM, 27.2% had high TG, and 27.1% were PR- at baseline. Among all pts, 170 (45%) had received endocrine therapy as first-line treatment, followed by chemotherapy (28%), CDK4 & 6 inhibitor (17%), or other anti-cancer treatment (9%). After adjustment, rwPFS and OS were significantly (p<.05) shorter in pts with 1 and 2+ clinical prognostic factors compared to pts with none (Table). Conclusions: Among pts with HR+, HER2- MBC, these data demonstrate the heterogeneity in pt survival outcomes depending on the presence and number of prognostic factors. Further research should explore the collective importance of these prognostic factors in treatment decisions. [Table: see text]
Acquired NF2 mutations confer resistance to HER2 targeted therapy in HER2-mutant breast cancer.
Authors: Li Xuelu , Ma Jing , Pan Bo , Zhao Zuowei , Li Man 
Published: May 2019

e12518 Background: Preclinical studies suggest that HER2 mutations lead to constitutive HER2 activation, but knowledge about effective treatment options and clinical resistance mechanisms remain uncharacterized. Methods: We performed dynamic monitoring of >300 serial plasma samples collected from 49 metastatic breast cancer patients used targeted sequencing of 425 clinically relevant genes, to detect HER2 mutations and track resistance to HER2-targeted treatments in HER2-mutant breast cancer. Results: We identified activating HER2 mutations (S310F、D769Y、V777L、778insGSP) in ctDNA and paired tissue samples from four patients with ER positive/HER2-amplification negative metastatic breast cancer, who had developed resistance to multi-line (>3) endocrine therapy. Two patients achieved a durable partial response (approximately 1 years) to trastuzumab combined with everolimus. Intriguingly however, analysis of ctDNA revealed that the NF2 mutation was acquired from a patient with HER2S310F/V777L who had developed resistance to HER2-targeted treatments. We showed that HER2S310F/D769Y/V777L/778insGSP mutations were constitutively active, and T47D and MCF7 overexpressing HER2S310F/V777L/778insGSP were sensitive to HER2 targeted therapies combined with everolimus. Consistent with our clinical findings, NF2 knockdown in HER2 S310F/V777L/778insGSP overexpressing T47D and MCF7 contributed to HER2-targeted therapy resistance. Furthermore, MEK inhibitor remarkably sensitized NF2 knockdown and HER2 mutations co-expressing T47D and MCF7 cells to trastuzumab. Conclusions: Dynamic monitoring of ctDNA could provide the candidate resistance genes for metastatic HER2-mutant breast cancer. Our findings validated NF2 mutations as a potential mechanism of resistance to HER2-targeted therapy, and the combined use of HER2 and ERK inhibitors may overcome resistance to HER2 targeted therapy in HER2-mutant breast cancer.
Fulvestrant in hormone receptor-positive advanced breast cancer: A UK retrospective multicenter study.
Authors: Keshwani Karim , lerner anna , Sanderson Benjamin , Board Ruth E. , Flynn Michael , Sharkey Elizabeth , Okines Alicia Frances Clare , Konstantis Apostolos , Roylance Rebecca , Hanna Daire , King Judy , Murphy Ravindhi , Rehman Farah , Guppy Amy Elizabeth , Westbury Charlotte , Takeuchi Elena , Spurrell Emma , Raja Fharat 
Published: May 2019

e12525 Background: Fulvestrant is a selective oestrogen receptor (ER) down regulator used to treat hormone receptor-positive advanced breast cancer in postmenopausal women. It is used at various time points in treatment. However, variations in funding across the UK limit universal patient access to fulvestrant. We sought to investigate its use and efficacy in UK clinical practice. Methods: Medical records of 458 patients with ER positive advanced breast cancer treated with fulvestrant between August 2011 and November 2018 at ten UK centres were reviewed. Demographics and treatment responses were recorded. Efficacy was analysed by progression free survival (PFS), clinical benefit rate (CBR) and overall survival (OS) with alive patients censored to December 2018. Results: Of the 445 patients with analysable data, median age was 70 (range 21-95). ECOG performance status was 0-1 in 70% (n = 285). Bone was most commonly involved (73%, n = 323), 307 (69%) had visceral involvement and 228 (51%) had nodal metastases. Both locally advanced and metastatic patients had received a median 2 (range 0 – 5 for all patients) prior endocrine therapy lines and 0 (range 0 – 6) prior chemotherapy lines. Fulvestrant was the first line treatment in 49 (11%). Median duration of fulvestrant use was 5 months (range 1-88). Overall, median PFS was 6 months. This increased to 7 months in absence of visceral disease, in whom 22% of patients achieved a prolonged PFS extending to 30 months. Fulvestrant produced a CBR of 41% in 355 patients assessed, of which 16% partially responded. First radiological assessment occurred at median 3 months (range 1-37). Progressive disease accounted for 82% of discontinuation compared to 4% owing solely to adverse events in 341 assessed patients. Median OS for the whole cohort was 23 months. Conclusions: This is one of the largest studied patient cohorts treated with fulvestrant. This heavily pre-treated population reflects real life fulvestrant use. Reassuringly the results confirm its clinical benefit in maintaining disease response. Given its potential synergistic action with other systemic agents, fair access to this highly active drug for all patients is as important now as ever before.
CDK4/6 plus aromatase inhibitor-induced alopecia in breast cancer patients.
Authors: Chan Donald , Freites Martinez Azael David , Goldfarb Shari Beth , Modi Shanu , Gajria Devika , Lacouture Mario E. 
Published: May 2019

e12537 Background: Cyclin-dependent kinase (CDK) 4 and 6 inhibitors are a novel therapy for metastatic breast cancer, and have shown to double the risk of alopecia. This study analyzed CDK4/6 plus aromatase inhibitor-induced alopecia (CDKIA), its impact on quality of life (QoL), and response to topical dermatologic therapy. Methods: The study analyzed a retrospective cohort of breast cancer patients diagnosed with CDKIA, evaluating clinical features, QoL, and response to therapy. CDKIA was also compared with endocrine-therapy induced alopecia (EIA). Results: 39 female CDKIA patients (median age 62 years [range 34-81]) were included, and 36 (92%) had standardized clinical images. CDKIA was most commonly attributed to a CDK inhibitor and letrozole in 23 patients (59%). CDKIA was similar to androgenetic alopecia (AGA) in every patient. Compared to EIA, CDKIA took less time to develop, was more severe, was associated with diffuse alopecia more frequently, and consisted of more vellus hairs on trichoscopy (Table). The Hairdex questionnaire, an alopecia-specific QoL survey, showed that CDKIA patients experienced worse QoL than EIA patients ( P < 0.05) and were most affected emotionally ( P < 0.01). There was a moderate to significant alopecia improvement in 11 of 13 CDKIA patients (85%) after treatment with topical minoxidil. Conclusions: CDKIA was clinically similar to AGA in association with diffuse alopecia. Patients with CDKIA had a negative emotional impact on appearance-based QoL. However, topical minoxidil may improve the severity of CDKIA. Baseline characteristics of CDKIA and EIA patients. [Table: see text]