bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of weakly hormone receptor (HR)-positive, HER- negative breast cancer (BC) and current treatment strategies.
Authors: Poterala Johanna , Wisinski Kari Braun 
Published: May 2020

e12621 Background: HR and HER2 status is critical for determining initial management of BC. Current guidelines define estrogen receptor (ER) and progesterone receptor (PR)+ as ≥1%. Previous reports of small cohorts with low HR+/HER2- disease showed similar rates of pathologic complete response (pCR) following neoadjuvant chemotherapy (NAC) as triple negative BC (TNBC). This study aims to further characterize this group of patients (pts), focusing on modern management and breast/axillary pCR rates following NAC. Methods: Pts with newly diagnosed stage I-III, HR+/HER2- BC from 1/1/2009–4/1/2019 were found using the University of Wisconsin Hospital and Clinics Cancer Registry. Medical records were reviewed for demographics, tumor characteristics with quantification level of ER and PR ( < 33%), treatments including NAC and adjuvant chemotherapy (chemo), endocrine therapy, surgery and radiation, and follow-up clinical data. Results: Data reviewed from 2,905 pts: 2,604 (89.6%) were HR+/HER2-, 282 (9.7%) were ER+/PR-, and 19 (0.7%) were ER-/ PR+. A total of 64 pts [median age 54 (22-87), 100% female] met inclusion criteria. At diagnosis, 23 (36%) were anatomic stage 1, 30 (47%) stage II, and 11 (17%) stage III; 18 (28%) had biopsy (bx) proven nodal disease. 57 (89%) had invasive ductal carcinoma; 9 (14%) were ER+/PR+, 43 (67%) ER+/PR-, and 12 (19%) ER-/ PR+. The majority [51 (80%)] received chemo, ~ half with NAC 30 (48%), 1 pt chemo plan was unknown. NAC regimens included an anthracycline (A) and taxane (T) [26 (41%)], a sole A regimen [1 (1%)], and an A+T and platinum regimen [3 (5%)]. 4 pts received capecitabine after NAC. 50 (78%) pts had a sentinel lymph node bx, but 13 (20%) had an axillary node dissection (ALND). 10 (16%) pts did not receive any endocrine therapy, 28 (44%) got tamoxifen, 22 (34%) an aromatase inhibitor, and 4 (6%) unknown. Of 28 pts who had NAC followed by breast and axillary surgery, 12 (43%) had pCR (ypT0/Tis/ypN0). Of the 12 pts who had bx proven nodal disease at diagnosis and NAC, 7 (64%) pts had pCR at the axilla. One pt had progressive disease on NAC, 1 had local recurrence and 8 (13%) pts had distant recurrence. Median time to recurrence was 13.6 (5.6 – 48.7) months. Only 2 pts with pCR had distant recurrence. Conclusions: BC that are HER2- and weakly HR+ treated with NAC demonstrated an axillary and overall pCR rate more similar to TNBC than breast cancers with strong HR+. Neoadjuvant approaches may reduce need for ALND and pCR may provide important prognostic information. Clinical trials should be developed to focus on this unique patient cohort.
Treatment patterns and clinical outcomes of patients with early triple negative breast cancer at a tertiary medical center.
Authors: Tchou Julia C. , Burkbauer Laura , Goldbach Macy , Malinovitch Angela , Keele Luke 
Published: May 2020

e12624 Background: The clinical benefit of neoadjuvant chemotherapy in patients with early triple negative breast cancer (eTNBC), especially those with clinical stage I (cStage I) disease, remains unclear. This study aims to examine the treatment pattern and outcomes of patients with eTNBC treated at a tertiary medical center. Methods: After receiving IRB approval, clinical characteristics, treatment patterns and invasive disease-free survival (iDFS) outcomes of patients with eTNBC treated in 2009-2019 were compared between those who received adjuvant chemotherapy (AC) vs. neoadjuvant chemotherapy (NAC). Inverse probability weighting (IPW) statistical methods were used to adjust for subgroup imbalances including age, race, clinical T and N stage. Results: Study cohort (n=919) was 70% white and 25% black. Median follow-up for AC and NAC was 49+/-26 and 28+/-19 months respectively. The majority, 56% (400/717), in AC had cStage I disease while only 8% (16/202) in NAC had cStage I disease. Other clinical characteristics were summarized in Table. The most common chemotherapy regimen used in AC and NAC groups was AC-T: 58% and 79%; followed by TC: 32% and 4%; and carboplatin: 2% and 5% respectively. pCR was noted in 83 patients (41%). Multivariate analyses using IPW showed that AC conferred an improved iDFS with a gain of 18 months in those with <=cStage IIA compared to NAC with pCR (Table). Conclusions: Despite limitations including our small sample size and retrospective study design, our results showed that NAC appeared to only benefit eTNBC patients with higher disease burden (>=cStageIIB). Future work to elucidate the clinical benefits of emerging novel NAC strategies in eTNBC will be of interest. [Table: see text]
Locoregional recurrence following pathologic complete response in patients with T1-3 N0 breast cancer treated with neoadjuvant chemotherapy, breast conserving surgery and whole breast radiation: Is a trial of omission of radiation warranted?
Authors: Parvez Elena , Muanza Thierry 
Published: May 2020

e12625 Background: Pathologic complete response(pCR) after neoadjuvant chemotherapy(NAC) in patients with breast cancer(BC) is associated with decreased recurrence and improved survival. In NSABP B18 and B27, 10-yr locoregional recurrence(LRR) after pCR in patients with Stage I-III BC undergoing breast conserving surgery(BCS) and whole breast RT(WBRT) was 5.2-6.9%. However, LRR may be overestimated as Her2 therapy was not used and only some eligible patients received endocrine therapy. A retrospective study using modern protocols found a 5-yr LRR of up to 2.6%. We hypothesize that LRR in N0 patients is even lower, and de-escalation of therapy should be examined. The study objective is to assess if a prospective trial of omission of WBRT after BCS in patients with N0 BC and pCR after NAC is warranted and to assess feasibility. Methods: Patients with T1-T3 N0 invasive BC diagnosed between Dec 2011-2017 treated with NAC and BCS were identified from a hospital BC registry. Health records were retrospectively reviewed to identify patients with pCR, defined as absence of residual invasive or in-situ disease(ypT0N0). Incidents of locoregional and distant recurrence were recorded. Results: Of 89 patients with T1-3 N0 invasive BC treated with NAC and BCS, 29(32.6%) had pCR. Median follow-up was 61.1 months. Median age was 55 yrs and median tumour size was 2.4cm. Receptor status was 16(55.2%) HR-Her2-, 4(13.8%) HR-Her2+, 7(24.1%) HR+Her2+ and 2(6.9%) HR+Her2-. NAC protocols consisted of an anthracycline and/or a taxane in 27(90%) patients, and 6 patients were treated on NAC trials. All patients with Her2+ disease received Her2 targeted therapy. Adjuvant endocrine therapy was taken by 8 of 9 patients with HR+ disease. All patients received WBRT without nodal RT. RT plan was available for 26(86.7%) patients. RT dose ranged from 40-50Gy, and all but 4 received tumour bed boost. There were no local or regional recurrence events at last follow-up. One patient developed brain metastases at 15.7 months. Conclusions: Over 6 years, 29 patients were identified that would be eligible for a prospective trial evaluating omission of WBRT after pCR in N0 patients treated with NAC and BCS. At median 5-yr follow-up, there were no locoregional recurrences in our cohort, demonstrating that the absolute benefit provided by WBRT is likely small. Our results indicate a prospective trial is warranted and will require multi-institution participation to accrue.
Comparing efficacy and toxicity profile of weekly paclitaxel to dose-dense paclitaxel (every two weeks) in treatment of breast cancer: A meta-analysis and systematic review.
Authors: Khan Usman , DeRosa Antonio , Xu Jiaqiong , Patel Tejal Amar 
Published: May 2020

e12634 Background: Neoadjuvant and adjuvant chemotherapy includes anthracyclines and taxanes has been used in early stage breast cancer. Studies have demonstrated superiority of weekly and dose dense Paclitaxel when compared with every 3 week regimen. Both weekly and dose dense administration of paclitaxel is an acceptable treatment as they are thought to have similar disease free and overall survival. The two regimens have clearly different toxicity profile but not many studies have compared them against each other. We conducted this analysis to compare efficacy of both regimens in terms of pCR if used in neoadjuvant setting and compared both regimen in terms of grade 3-4 neurotoxicity. Methods: Systematic literature searches were conducted in four databases for randomized controlled trials published in English. The databases searched were: (1) MEDLINE (2) Embase, (3) The Cochrane Library, and (4) Scopus. 18 studies were included in pCR data analysis. Total of 38 studies were included in this meta-analysis for the toxicity analysis. Results: Our analysis showed no significant difference in the rate of pathological complete response between weekly paclitaxel and dose dense paclitaxel (p=0.266). Meta-analysis showed the overall estimate proportion for weekly paclitaxel causing neurotoxicity was 0.04 (95% CI: 0.02-0.06) and for the dose dense paclitaxel 0.10 (95% CI: 0.05-0.17). The test for heterogeneity between two sub-groups in toxicity analysis was p=0.042. Conclusions: Our analysis showed no significant difference in rate of pCR between two regimens however rate of grade 3-4 neurological toxicity was more in dose dense paclitaxel as compared to weekly paclitaxel. This difference in neurological toxicity with no corresponding difference in rate of pathological complete response can be an important factor in deciding the chemotherapy regimen for our patients.
Correlation between HER2 amplification level and response to neoadjuvant treatment with trastuzumab and chemotherapy in HER2 positive breast cancer.
Authors: Antolin Silvia , García-Caballero Lucía , Reboredo Cristina , Molina Diaz Aurea , Mosquera Joaquín , Vázquez-Boquete Angel , Gallego Rosalía , Santiago Maria Paz , Concha Angel , Perez Maria EVA , Calvo Lourdes , García-Caballero Tomás 
Published: May 2020

e12641 Background: HER2 targeted therapy in combination with chemotherapy have changed the aggressive natural history of HER2-positive tumors. To select patients to be treated with this type of agents, determination of HER2 status is usually carried out by immunohistochemistry, followed by in situ hybridization in equivocal cases (2+). There are contradictory data in literature regarding correlation between level of HER2 amplification determined by FISH and early and long-term treatment benefits. Objectives: The aim of this study was to correlate quantitative results of FISH (ratio HER2/CEN17 and number of HER2 signals/nucleus) with the grade of response to neoadjuvant treatment with trastuzumab and chemotherapy. Methods: We analyzed 100 consecutive cases of stage I-III breast carcinomas treated with trastuzumab and chemotherapy in the neoadjuvant setting at A Coruña University Hospital between 2005 and 2016. At Santiago University Hospital, 4 tissue microarrays were prepared and the IQFISH (Dako-Agilent) technique was performed using pretreatment biopsies. Results: HER2 amplification was found in 92 of 100 cases studied. Pathological Complete Response (pCR) (Miller-Payne grading system) was obtained in 58% of the patients whose tumors showed amplification. No pCR was obtained in the 8 patients whose tumors were negative by FISH (not amplified). Analysis of the quantitative results demonstrated a statistical significant direct correlation between pCR and both HER2/CEN17 ratios and HER2 gene copies/nucleus (p = 0.002 and p= 0.004, respectively). We also demonstrated an association between the HER2 amplification level (both ratios and numbers of HER2 signals) and a trend toward improved disease free survival (DFS) (p = 0.451 and p= 0.619, respectively). Conclusions: HER2 amplification level determined by FISH it is a good and available predictive factor of response and must be included in pathologic reports because it can provide valuable information to oncologists on the possibilities of achieving pCR after neoadjuvant treatment in HER2-positive breast cancer. Key words: Breast cancer, FISH, HER2 amplification, trastuzumab, neoadjuvant therapy, pathological complete response.
Translesion synthesis genes POLI and REV1 in breast tumors and response to neoadjuvant chemotherapy.
Authors: Thompson Patricia , Jones Emma V , Preece Christina , Li Jinyu , Bhalla Jigna , Cohen Jules , Baer Lea N. , Pierce Andrew , Stopeck Alison 
Published: May 2020

e12642 Background: Translesion synthesis (TLS) of DNA by specialized polymerases (POLs) and REV1, a scaffold protein that recruits other TLS DNA POLs for nascent strand extension, experimentally enable tumor cells to replicate through DNA damage. TLS POLs are hypothesized to contribute to treatment resistance. Methods: We conducted a discovery gene expression study using NanoString technology with a bespoke codeset enriched for DNA damage response genes and RNA from 12 TN, 10 HER2+ and 29 ER+/HER2- breast cancer patients before neoadjuvant chemotherapy (NACT) and when available, in the matching residual tumor. Eleven patients achieved a pathologic complete response (pCR), 12 had < 1 cm residual disease (partial responders) and 28 patients had > 1cm residual disease (non-responders). RNA counts were normalized and log-transformed for differential expression analyses corrected for false discovery. Results: DNA polymerase Iota ( POLI) was the top overexpressed gene in the pretreatment biopsy of non-responders independent of tumor subtype (p corrected = 0.0002). Expression of REV1 was also significantly higher in non-responders and positively correlated with POLI (r = 0.577, p < 0.0001). Despite a small sample size, pretreatment expression levels of POLI and REV1 were significantly higher in ER+ (n = 38) than ER- (n = 13) tumors (p = 0.0006). When restricted to ER+ tumors, POL1 and REV1 expression levels were significantly higher in pretreatment biopsy of non-responders (n = 25) than partial and complete responders (n = 13). For ER+ patients, response by median POL1/REV1 expression levels are shown in Table. Pre/post treatment POL1 and REV1 expression did not change in patients with residual disease. Conclusions: In discovery, two genes involved in TLS of DNA (POLI and REV1) were found overexpressed in pretreatment biopsies from breast cancers poorly responsive to NACT, independent of tumor subtype. Overexpression was more common among ER+ tumors, which exhibit a high inherent resistance to chemotherapy. If confirmed, expressed levels of POLI and REV1 may identify a subgroup of breast cancers resistant to NACT for which targeted inhibition of mutagenic TLS may be beneficial. [Table: see text]
Incidence of brain metastases in patients receiving neoadjuvant chemotherapy (NAC) with trastuzumab and pertuzumab (HP) in HER2-positive early breast cancer (BC).
Authors: Ferraro Emanuela , Barrio Andrea Veronica , Patil Sujata , Robson Mark E. , Dang Chau T. 
Published: May 2020

e12653 Background: The addition of pertuzumab in the neoadjuvant setting has become a standard of care in stage II-III HER2-positive BC. In the Katherine study the incidence of brain metastases (BM) at the follow-up of 3-years was 5.9 % in patients (pts) with residual disease who received TDM1. The aim of this study was to assess the incidence of BM in pts who received NAC with HP at a single center who were found to have pathological complete response (pCR) (ypT0/is ypN0) versus non-pCR at the time of surgery. Methods: Chart review on HER2-positive pts treated with NAC and HP between September 1, 2013 to May 1, 2018 was conducted. Only surgical specimens of pts whose pre-NAC specimens were internally reviewed for HER2 status by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) were included in this analysis. Data on BM as component of distant recurrence along with invasive disease-free (IDFS) and overall survival (OS) were collected. Results: 540 pts were identified. Cases with no internally verified-HER2 status (387), equivocal status (10) and discordant internal assessment (13) were excluded. 130 pts with preoperative HER2 status confirmed by dedicated breast pathologists were included. Clinicopathological features are described in Table. pCR was achieved in 77/130 (60%) of cases, residual disease in 53/130 (40%). The median follow-up was 2.83 (0.35-5.3) years. The rate of BM as first presentation of distant disease was 3.8 % (3/77) and 3.7 % (2/53) in pts with pCR and non-pCR, respectively. Median time to development BM was 35 (13-58) months and 11.7 (9-14) months in the pCR group and non-pCR, respectively. Conclusions: In our cohort, the combination of HP was associated with a high pCR rate. At a median follow-up of 2.8 years, the incidence of BM appeared to be similar in pts who achieved pCR versus non-pCR. The data of IDFS and OS will be reported. Further data are needed to validate our findings before designing clinical trials to test prophylactic strategies to prevent BM. [Table: see text]
Assessment of PD-L1 expression in circulating tumor cells in patients with breast cancer.
Authors: Chen Junqing , Chen Zhanhong , Wang Xiaojia 
Published: May 2020

e13001 Background: Evidence is accumulating that the immune checkpoint blockade targeting the programmed death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) axis has improved progression-free and overall survival of advanced breast cancer patients. PD-L1 tumor expression is emerging as a potential biomarker in PD-1/PD-L1 checkpoint blockade therapies. However, PD-L1 expression on tumor tissue is limited by the temporal and spatial heterogeneity as well as insufficient tumor tissue samples. PD-L1 expression in circulating tumor cells (CTCs) might overcome the limitation. We investigated the utility of CTCs as a noninvasive method to evaluate PD-L1 status in breast cancer patients. Methods: 46 breast cancer patients including 42 metastatic breast cancer patients and four early breast cancer patients were enrolled. CTCs were collected from peripheral blood samples using a microfluidic-based CTC separator. A novel staining procedure which included fluorescent glucose analog staining and immunostaining targeting CD45, vimentin and PD-L1 were analyzed. PD-L1 expression level was analyzed as the fraction of PD-L1 positive CTCs among total CTCs. Results: 46 breast cancer patients all had detected CTCs, ranging from 12 to 110. The fraction of PD-L1 positive CTCs varied from 2.08% to 85.69%. PD-L1 expression was obviously higher in triple negative breast cancer (TNBC) patients as compared with non-TNBC patients (47.16% vs 26.23%, P < 0.01). Interestingly, we observed that PD-L1 positive CTCs were also detected in four early TNBC patients. No significant association was found between PD-L1 expression and mesenchymal CTC phenotype. Conclusions: These data suggest that assessment of PD-L1 expression in CTCs from breast cancer patients is feasible. PD-L1 expression in CTCs might serve as a complementary tool for PD-L1 expression analysis in breast cancer patients.
Using novel biomarkers to predict chemotherapy-induced cardiovascular toxicity in patients with breast cancer.
Authors: Krishnarao Krithika , Fairweather DeLisa , Bruno Katelyn , Douglass Erika , Geiger Xochiquetzal , Tan Winston , Cornell Lauren , Yamani Mohamad 
Published: May 2020

e13002 Background: Despite improvement in survival in breast cancer patients from advanced therapies, rates of chemotherapy-induced cardiotoxicity manifesting as a decline in left ventricular ejection fraction (LVEF) have offset some of these benefits in patients receiving anthracycline-based chemotherapy followed by trastuzumab. Results suggesting clinical biomarkers predict cardiotoxicity are inconsistent. Recently, expression of angiotensin II type 1 receptor (ATR1) and endothelin 1 (ET1) has shown to play a role in breast tumor growth. We sought to evaluate whether the presence of ATR1 and ET1 in breast cancer tissue using immunohistochemistry (IHC) and qRT-PCR can predict chemotherapy-induced cardiotoxicity. Methods: We hypothesized that elevated expression of ATR1 and ET1 in tumor tissue is associated with chemotherapy-induced cardiotoxicity (LVEF < 50%) compared to tissue from controls. Preliminarily, 34 paraffin-embedded breast tissue specimens from women with breast cancer treated with anthracycline-based chemotherapy and trastuzumab were retrieved for analysis. IHC and qRT-PCR for expression of ATR1 and ET1 was performed on all specimens. Results: We found that ET1 expression was significantly increased in patients with an LVEF < 50%. In addition, we noted the lower the LVEF, the higher the ET1 expression (p = 0.03). We also found patients with a change in LVEF of greater than 10% had more ET1 expression compared to those without a change in LVEF (p = 0.05). We did not find a significant relationship between ATR1 and LVEF. Conclusions: Increased ET1 expression in breast tumor tissue may predict cardiotoxicity. Our findings may aid in future research using novel biomarkers to predict breast cancer patients at risk for developing chemotherapy-induced cardiotoxicity. In addition, targeted therapies to these biomarkers may potentially help prevent the development of cardiotoxicity.
A phase I study of safety and pharmacokinetics of A166, a novel selective inhibitor of human epidermal growth factor receptor-2 in Chinese patients with advanced solid tumors.
Authors: Liu Yongheng , Lian Wei , Zhao Xi , Qi Wei , Xu Jian , Xiao Liang , Qing Yan , Xue Tongtong , Wang Jingyi 
Published: May 2020

e13007 Background: Human epidermal growth factor receptor 2 (HER2) is an effective therapeutic target for breast and gastric cancer. A166 is an antibody-drug conjugate composed of a novel cytotoxic drug (monomethyl auristatin F derivative ) site-specifically conjugated to transtuzumab sequence via a stable protease-cleavable valine citrulline linker, which has a DAR (Drug Antibody Ratio) of Better efficacy were observed in preclinical CDX and PDX studies including HER2 low expression and T-DM1 resistant models while toxicity studies demonstrated a good safety profile in cynomolgus monkey. Methods: Patients with HER2-expressing or amplified advanced solid tumors refractory to standard therapies were recruited. A modified Fibonacci 3 + 3 dose-escalation design was employed with 7 dose levels (0.1, 0.3, 0.6, 1.2, 2.4, 3.6, and 4.8 mg/kg every 3 weeks). Safety analyses included all patients. PK and antitumor activity were also assessed. Primary objectives in dose escalation are safety and tolerability and determination of maximum tolerated dose (MTD) and recommended Phase 2 dose. Results: As of October 1, 2019 among 19 patients (breast cancer, colorectal cancer and gastric cancer)treated,no one experienced dose-limiting toxicity. No maximum tolerated dose was determined until 4.8mg/kg dose level. Grade≥3 adverse event was reported for 4 patient as neutropenia、anemia、Hyponatremia and Hypophosphatemia. Notably, 36.8% (n = 7) of patients experienced dry eye, as well as corneal epitheliopathy, and 2 patients withdraw from the study due to grade 2 corneal epitheliopathy. In 3.6 and 4.8 mg/kg groups, 6 patients were evaluable for tumor response, including 3 with partial response, 2 with stable disease. A166 exposure increased with the increase of dose, and extremely low exposure of free toxin and toxin-linker conjugates were observed; t1/2 was 8.29 days at the 4.8mg/kg. Conclusions: A166 showed an acceptable safety profile and promising anti-tumor activity in patients with HER2-expressing advanced solid tumors. Clinical trial information: CTR20181301 .