bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P2-03-04: Characteristics and clinical differences of breast cancer patients with negative or low HER2 expression
Authors: Voutsadakis Ioannis , Rosso Christopher 
Published: March 2022

Abstract
Background: High expression of HER2 receptor in Immunohistochemistry (IHC) sections or amplification of its gene in in situ hybridization (ISH) assays define a subset of breast cancers that have an aggressive natural history but respond to treatments blocking HER2. In contrast, patients with lower HER2 expression, not meeting the criteria for positivity, are currently treated similarly to completely HER2 negative patients. However, emerging data suggest that patients with low HER2 expression may derive benefit from newer antibody drug conjugates. Thus, this investigation sought to clarify the characteristics of HER2 low expressors and compare them with patients with no HER2 expression. Methods: We undertook a retrospective analysis of all breast cancer patients seen in our cancer center over a six-year period and classified as HER2 negative. Patients were categorized as HER2 negative when they had a score of 0 in IHC and as HER2 low if they had a score of 1+ or 2+ in IHC and no amplification by ISH. Characteristics of the patients and tumors in the two groups were compared. Results: A total of 391 HER2 negative and low patients have been included. Among them, 130 patients (33.2%) were HER2 negative (score 0 by IHC) and 261 patients (66.8%) were HER2 low (score 1+ and 2+ by IHC/ISH non-amplified). There were no differences in age, menopause status, mode of detection of cancer (clinical or screening) and clinical stage at diagnosis between the two groups. Patients in the HER2 low group had less commonly high-grade cancers than HER2 negative patients (25.35 versus 34.6%, x2 p=0.04).In addition, The HER2 low group had higher ER Histoscore (&gt;240) in 88.1% of cases compared with 69.2% in HER2 negative group (x2 p&lt;0.000). Similarly, a higher percentage of HER2 low cases than HER2 negative cases were expressing the progesterone receptor (PR, x2 p&lt;0.000). HER2 low patients were rarely (3.8%) classified as triple negative, while this percentage was 21.5% in HER2 negative patients. Conclusion: HER2 negative staining (IHC score 0) is associated with averse tumor characteristics compared with clinically HER2 negative patients with low HER2 expression (score 1+ and 2+/ISH non-amplified).
Citation Format: Ioannis Voutsadakis, Christopher Rosso. Characteristics and clinical differences of breast cancer patients with negative or low HER2 expression [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-03-04.
Abstract P2-04-01: Overexpressed cyclin D1 and CDK4 proteins are responsible for the resistance to CDK4/6 inhibitor in breast cancer that can be reversed by PI3K/mTOR inhibitors
Authors: Liu Qiang , Cai Zijie , Wang Jingru , Li Yudong , Wong Lok Lam 
Published: March 2022

Abstract
CDK4/6 inhibitors are now the standard treatment in advanced HR+/HER2- breast cancer patients. Nevertheless, the resistance to CDK4/6 inhibitors is inevitable, limiting its use and efficacy. The mechanisms and the strategies to overcome resistance are of great interest. Here, we show that the palbociclib-resistant breast cancer cells express significantly higher levels of Cyclin D1 and CDK4 proteins because of upregulated protein synthesis. Silencing Cyclin D1 or CDK4 directly led to cell cycle arrest while silencing Cyclin E1 or CDK2 restored the sensitivity to palbociclib in palbociclib-resistant cells. Furthermore, PI3K/mTOR pathway was hyper-activated in palbociclib-resistant cells, leading to more phosphorylated 4E-BP1 and higher levels of Cyclin D1 and CDK4 translation. Targeting PI3K/mTOR pathway with a specific PI3Kα inhibitor (BYL719) or an mTOR inhibitor (everolimus) reduced the protein levels of Cyclin D1 and CDK4, and restored the sensitivity to palbociclib in resistant cells both in vitro and in vivo. The tumors from breast cancer patients who progressed after palbociclib treatment had significantly higher protein expression of Cyclin D1, CDK4, p-AKT and p-4E-BP1 than the paired samples before palbociclib treatment. In conclusion, our findings suggest that overexpressed Cyclin D1 and CDK4 proteins lead to the resistance to CDK4/6 inhibitor and PI3K/mTOR inhibitors are able to restore the sensitivity to CDK4/6 inhibitors, which provides the biomarker and rationale for the combinational use of CDK4/6 inhibitors and PI3K/mTOR inhibitors after CDK4/6 inhibitor resistance in breast cancer.
Citation Format: Qiang Liu, Zijie Cai, Jingru Wang, Yudong Li, Lok Lam Wong. Overexpressed cyclin D1 and CDK4 proteins are responsible for the resistance to CDK4/6 inhibitor in breast cancer that can be reversed by PI3K/mTOR inhibitors [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-04-01.
Abstract P2-11-14: Pathology AI features and immune biomarkers of postpartum involution: Implications for postpartum breast cancer
Authors: Ogony Joshua Were , De Bel Thomas , Radisky Derek , VanderLaak Jeroen , Sherman Mark 
Published: March 2022

Abstract
Breast cancer risk is increased in parous women in the period following childbirth, peaking at five years. After weaning or in the absence of lactation, the breast undergoes postpartum involution (PPI), a process characterized by epithelial cell death and tissue remodeling that returns the mammary gland to a baseline state, and has previously been associated with increased inflammation and breast cancer development and progression in preclinical models. Features of PPI and determinants of related inflammation have been incompletely characterized among women. In this study, we performed visual and AI analysis of 725 digitized H&E images of normal breast tissues donated to the Komen Tissue Bank (KTB) by parous and nulliparous women ≤45 years, and further investigated the immune microenvironment in specimens from 23 women (also from KTB, 13 parous, 10 nulliparous) using NanoString RNA immuno oncology (IO) 360 panels and immune protein biomarkers by NanoString GeoMx Digital Spatial Profiling (DSP). We found that recently parous women (≤5 years of a last birth) had higher numbers of terminal duct lobular units (TDLUs), immune cells, and plasma cells as compared with nulliparous women, and that beyond 5 years of a last birth, TDLU numbers were still higher in parous women, but the immune and plasma cell content of the breast of parous and nulliparous women were not significantly different. Our gene expression analysis revealed differential expression of genes that clustered according to parity status, with interferon stimulated genes; STAT1 and IFITM1, and interferon alpha receptor 1 (IFNAR1), and MHC class II genes (HLA-DMA, HLA-DPA,HLA-DPB1, and HLA-DRA) elevated in parous women. Our DSP analysis revealed that immune biomarkers with immunosuppressive functions, including ARG1, VISTA, CTLA-4, and CD68 were significantly higher in parous women as compared with nulliparous women. Breast tissues of parous women show lobular expansion and alterations in immune cell components compared with nulliparous tissues. Further research is needed to assess how these alterations may impact risk.
Citation Format: Joshua Were Ogony, Thomas De Bel, Derek Radisky, Jeroen VanderLaak, Mark Sherman. Pathology AI features and immune biomarkers of postpartum involution: Implications for postpartum breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-11-14.
Abstract P2-12-19: Platinum is essential in neoadjuvant treatment of triple negative breast cancer: A network meta-analysis
Authors: Li Junjie , Chen Li , Tan Wei , Qi Fang , Zhang Yang , Wang Zhonghua , Shao Zhimin 
Published: March 2022

Abstract
Background: Due to the heterogeneity of triple negative breast cancer (TNBC) and variety of neoadjuvant regimen, the best way to provide optimal neoadjuvant regimen in early-stage TNBC is still a challenge. However, the preferred regimen, especially when combining target therapy such as bevacizumab, Poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors (PARPi), and PD-1/PD-L1 inhibitor, is still not clear. Methods: Medline, EMBASE, Cochrane Library, and Web of Science were searched in May 2020 to identify randomized controlled trials (RCTs). We conducted a fixed-effect network meta-analysis (NMA) with a Bayesian framework to assess the efficacy and safety of different neoadjuvant regimens for patients with early or locally advanced TNBC. (Registration: PROSPERO CRD42020223012). Results: A total of 35 RCTs involving 8424 participants were included, of which, 22 RCTs with 5203 patients were included in this NMA focusing on pathologic complete response (pCR). Compared to anthracycline-taxane based regimen (AT), an improvement in pCR was observed for anthracycline-taxane based combined platinum (ATP) (odds ratio [OR]=2.04, 95% credible interval [CrI]: 1.69, 2.48), TCb (T= docetaxel; Cb= carboplatin; OR=2.16, 95%CrI: 1.20, 3.91). Combining target therapy (including bevacizumab [Bev], veliparib, atezolizumab, or pembrolizumab) with AT or ATP also improved pCRs. Eleven RCTs reported serious adverse events (SAEs), and five RCTs were included in NMA. TCb was associated with less serious adverse events than AT. However, ATP, AT+Bev, ATP+Bev, ATP+Veliparib and ATP+Pembro were associated with more serious AEs than AT. Conclusions: Platinum-based neoadjuvant regimens increased pCRs in TNBC patients, among which TCb was preferred with less SAEs. Platinum-based regimens should also be considered a preferred option when combining target therapy such as Bev, PARPi, and PD-1/PD-L1 inhibitor.
Citation Format: Junjie Li, Li Chen, Wei Tan, Fang Qi, Yang Zhang, Zhonghua Wang, Zhimin Shao. Platinum is essential in neoadjuvant treatment of triple negative breast cancer: A network meta-analysis [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-12-19.
Abstract P2-13-37: A prospective, open, multi-center clinical study of pyrotinib combined with trastuzumab and nab-paclitaxel in neoadjuvant treatment for stage II-III HER2-positive breast cancer patients
Authors: Shao Bin , Yu Zhengyan , Wang Yu , Zhao Guangcai , Zhou Fei , Wei Ranmei 
Published: March 2022

Abstract
Background: Targeted therapy has significant efficacy in adjuvant and advanced treatment of HER2-positive breast cancer, and it has also promoted its development in neoadjuvant therapy. For HER2-positive breast cancer, chemotherapy with anthracyclines and taxanes combined with trastuzumab targeted therapy is currently the standard regimen for adjuvant or neoadjuvant therapy. On the basis of the preliminary clinical trials, we carried out this study to confirmed efficacy and safety of pyrotinib combined with trastuzumab and nab-paclitaxel as neoadjuvant treatment regimen in patients(pts) with stage II- III HER2-positive breast cancer. Method: In this multicenter, single arm, prospective, open-label phase II study, 46pts with stage II-III HER2-positive breast cancer will be enrolled (in Simon twostages model, 16 pts will be enrolled in the first stage) to receive pyrotinibcombined with trastuzumab and nab-paclitaxel. The inclusion criteria are asflows. (1) female aging from 18 to 75; (2) Eastern Cooperative Oncology Group(ECOG) performance score of 0-1; (3) Life expectancy is no less than 12weeks;(4) Pathologically confirmed HER-2 positive breast cancer;(5) earlystage (T2-3, N0-1, M0) or locally advanced (T2-4, N2, or N3), with tumor sizeno less than 2cm in diameter. All pts will receive pyrotinib (400mg qd) andtrastuzumab: 8 mg/kg for cycle 1 and 6 mg/kg for cycles 2-6, intravenousinfusion, 21 days for 1 cycle, a total of 6 cycles and nab-paclitaxel: 260mg/m2,intravenous infusion, 21 days as a cycle, a total of 6 cycles. The primaryendpoint is pathological complete response rate (pCR: ypT0/is, ypN0), and thesecondary endpoints are disease-free survival time (DFS), objective responserate (ORR), and survival time without distant metastasis (DDFS). Findings: From Nov 2020 to May 2021, a total of 11 pts were enrolled, 4 pts havecompleted surgery and 6 pts could be evaluated for ORR. The pCR rate was50%, ORR was 100% (5 PR, 1CR). Adverse events (AEs) of any garde werediarrhea 11 (100.0%), anorexia and vomiting 8 (72.7%) and rash 4 (36.4%).Garde 3 AEs were diarrhea 3 (27.3%), and there was no grade 4 AEs. Conclusion: Pyrotinib combined with trastuzumab and nab-paclitaxel in neoadjuvanttreatment for pts with stage II-III HER2-positive breast cancer showedacceptable toxicity and promising efficacy.
Citation Format: Bin Shao, Zhengyan Yu, Yu Wang, Guangcai Zhao, Fei Zhou, Ranmei Wei. A prospective, open, multi-center clinical study of pyrotinib combined with trastuzumab and nab-paclitaxel in neoadjuvant treatment for stage II-III HER2-positive breast cancer patients [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-13-37.
Abstract P3-01-09: Mri in the pre-operative workup of breast cancer patients
Authors: Bayard Solange , Fasano Genevieve , Chen Yalei , Marti Jennifer , Simmons Rache , Swistel Alexander , Drotman Michelle , Davis Melissa , Newman Lisa 
Published: March 2022

Abstract
PurposeThe utility of pre-operative MRI (preop MRI) for patients with a new breast cancer diagnosis is controversial. Recently there has been increased use of routine MRI during preoperative workup to evaluate for areas necessitating additional biopsy and planning of operative resection extent; however, these practices carry the risk of delaying treatment, and subjecting patients to unnecessary biopsies and overly extensive resections. Triple negative breast cancer (TNBC) is more difficult to detect on mammography compared to non-TNBC, and patients with TNBC do not receive the chemoprevention benefits of adjuvant endocrine therapy; preop breast MRI to detect mammographically occult foci of disease may therefore be more relevant for patients with TNBC. MethodsOutcomes were evaluated for TNBC patients treated in the prospectively-maintained database of an academic cancer program in a metropolitan city of the Northeast, 1998-2018. ResultsOf 428 TNBC cases, 35.7% (153) had pre-op MRI. 43.6% (61) of 140 TNBC cases ≤50 years old had pre-op MRI compared to 31.9% of 288 TNBC cases &gt;50 years old (p=0.016). There were no differences in race, or stage at presentation between those who had pre-op MRI and those who did not. 34% (52) of pre-op MRI TNBC cases underwent additional biopsies versus 0.43% (1) of TNBC patients who did not have pre-op MRI (p&lt;0.0001). Average time to treatment was 29.5 days for pre-op MRI TNBC cases compared to 25 days for TNBC patients who did not have pre-op MRI (p=0.0026). 9.8% (15) of pre-op MRI TNBC cases underwent re-excisions versus 17.7% (41) of TNBC patients who did not have pre-op MRI (p=0.076). Of those who had mastectomies, patients who had pre-op MRI were more likely to have bilateral mastectomies (21.6% (33) pre-op MRI TNBC v 12.9% (30) of TNBC patients who did not have pre-op MRI (p=0.0471)). Five-year overall survival was no different between patients who had pre-op MRI and those who did not (95.2% vs 95.3% respectively; p=0.79). Among patients undergoing breast conserving surgery, there were no significant differences in the rates of local recurrence between patients that had preop MRI compared to those that did not (13.1% vs 9.1% p=0.392). ConclusionOur data demonstrated that preop MRI in TNBC patients was associated with additional biopsies, more extensive breast surgery, and longer time to treatment. Preop MRI had no impact on survival or local recurrence among patients undergoing breast conserving surgery.
Citation Format: Solange Bayard, Genevieve Fasano, Yalei Chen, Jennifer Marti, Rache Simmons, Alexander Swistel, Michelle Drotman, Melissa Davis, Lisa Newman. Mri in the pre-operative workup of breast cancer patients [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-01-09.
Abstract P3-01-14: A model incorporating axillary tail position on mammography for preoperative prediction of non-sentinel lymph node metastasis in patients with initial cN+ breast cancer after neoadjuvant chemotherapy
Authors: Wang Kun , Zhu Teng , Zhang Tingfeng 
Published: March 2022

Abstract
Background and Objectives: Few models with good discriminative power have been constructed to predict the risk of non-sentinel lymph node (NSLN) metastasis in breast cancer prior to breast surgery after neoadjuvant chemotherapy (NAC). This study aimed to develop a new model for the prediction of NSLN metastasis in patients with initial clinical node positivity (cN+).Methods: The present study reviewed a total of 257 patients (179 in the training set and 78 in the testing set) with cN+ breast cancer who underwent both sentinel lymph node biopsy (SLNB) and axillary lymph node dissection (ALND) following NAC. Univariate and multivariate analyses were used to select clinical factors affecting NSLN metastasis prior to breast surgery. A logistic regression model was developed based on these factors and the results of post-NAC axillary tail position on mammography (AT) and ultrasound (AUS).Results: Four factors with p&lt;0.05 in the univariate analysis, including ycT0 (odds ratio [OR]: 4.84, 95% confidence interval [CI]: 2.13-11.91, p&lt;0.001), clinical stage before NAC (OR: 2.68, 95% CI: 1.15-6.58, p=0.025), estrogen receptor (ER) expression (OR: 3.29, 95% CI: 1.39-8.39, p=0.009), and Her2 status (OR: 0.21, 95% CI: 0.08-0.50, p=0.001), were independent predictors of NSLN metastases. The clinical model based on the above data resulted in an AUC of 0.82 (95% confidence interval [CI]: 0.76-0.88) in the training set and 0.83 (95% CI: 0.74-0.92) in the validation set. The results of the post-NAC AUS and. AT were added to the clinical model to construct a clinical imaging model for the prediction of NSLN metastasis with an area under the curve of 0.87 (95% confidence interval [CI]: 0.81-0.93) in the training set and 0.89 (95% CI: 0.82-0.96) in the validation set.Conclusions: The present study incorporated the results of post-NAC AT and AUS with other clinal factors to develop a new model for the prediction of NSLN metastasis in patients with initial cN+ prior to breast surgery. This model performed excellently, allowing physicians to select patients for whom unnecessary ALND could be omitted after NAC.
Citation Format: Kun Wang, Teng Zhu, Tingfeng Zhang. A model incorporating axillary tail position on mammography for preoperative prediction of non-sentinel lymph node metastasis in patients with initial cN+ breast cancer after neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-01-14.
Abstract P3-02-06: A phase II study of 68Ga-ABY-025 PET for non-invasive quantification of HER2 expression in breast cancer
Authors: Alhuseinalkhudhur Ali , Lindman Henrik , Liss Per , Sundin Tora , Frejd Fredrik Y , Hartman Johan , Iyer Victor , Lubberink Mark , Velikyan Irina , Sörensen Jens 
Published: March 2022

Abstract
Introduction/Aim: 68Ga-ABY-025 is a small-protein HER2-binder which has shown promising results in evaluating HER2 receptor status in earlier studies in breast cancer (BC). The aim of the current study was to investigate the role of 68Ga-ABY-025 PET imaging in relation to histopathology and treatment response. Methods: This single-center Phase II study consecutively included neoadjuvant patients with stage 2/3 BC (n=22) and recurrent metastatic BC (rMBC, n=18). All patients had at least one HER2-positive/borderline biopsy before inclusion and underwent 68Ga-ABY-025 PET at baseline followed by FDG PET/CT and biopsies for pathology analysis as part of study. FDG PET/CT was repeated after 2 cycles of treatment and glycolytic tumor burden (FDG2-FDG1)/FDG1) was calculated for up to five largest lesions in each patient. A reduction in glycolytic tumor burden &gt;30% was considered good metabolic response. Uptake values (ABY-SUV) from 68Ga-ABY-025 PET in tumor lesions were compared with standard pathology analysis of tumor biopsies. Data was evaluated using regression and ROC analysis. Results: Biopsies for HER2 showed 32 positive, 3 borderline and 5 negative lesions. 68Ga-ABY-025 PET produced high-contrast images with ABY-SUV ranging from 0 to 50. Correlation of ABY-SUV and HER2 score from biopsies did not reach significance. HER2-targeted therapy in stage 2/3 BC resulted in a larger metabolic response (mean reduction of glycolytic tumor burden 70±26%) than in rMBC (mean reduction 25±61%, p&lt;0.001). ABY-SUV correlated negatively with change in glycolytic tumor burden (p&lt;0.0001) and ABY-SUV&gt;6.0 predicted good metabolic response in soft-tissue tumors (AUC 0.82, 95% confidence interval 0.75-0.89, p&lt;0.0001), corrected for neoadjuvant/recurrent setting. Using this cut-off, ABY SUV and invasive HER2 score were discordant in 12 of 40 patients (30%) - 6 with stage 2/3 BC and 6 with rMBC. Of the discordant cases, 68Ga-ABY-025 PET predicted the response correct in 7 cases (3 with stage 2/3 BC and 4 with rMBC) compared to biopsy-based pathology with correct prediction in 5 cases. Conclusion: 68Ga-ABY-025 PET is a potentially useful non-invasive indicator of in-vivo HER2 receptor status in breast cancer and might predict early response to HER2-targeted therapies. A larger multi-center study has been initiated to confirm these results.
Citation Format: Ali Alhuseinalkhudhur, Henrik Lindman, Per Liss, Tora Sundin, Fredrik Y Frejd, Johan Hartman, Victor Iyer, Mark Lubberink, Irina Velikyan, Jens Sörensen. A phase II study of 68Ga-ABY-025 PET for non-invasive quantification of HER2 expression in breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-02-06.