bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract ES2-1: Everything you always wanted to know about AI but were afraid to ask
Authors: Barzilay R 
Published: March 2022

Abstract
In this talk, I will introduce the audience to the foundations of artificial intelligence and its application to breast cancer diagnostics and care. By nature, many of the traditional clinical tasks such as risk assessment, prediction of treatment efficacy and forecasting patient trajectory can be thought of as prediction problems. Given sufficient amounts of patient data with outcomes, a machine learning model can make predictions which often exceed in accuracy human experts. However, to make these tools more applicable in the clinical setting, we need to augment AI models with the ability to explain their decisions to humans, and assess their uncertainty. In my talk, I will give multiple examples of deployed AI applications, analyzing their strengths and weaknesses. First, I will describe a natural language processing system for extracting tumor information from pathology reports. Next, I will talk about image-based AI models for risk assessment and early detection of breast cancer. Finally, I will summarize AI drug discovery methods for personalized medicine.
Citation Format: R Barzilay. Everything you always wanted to know about AI but were afraid to ask [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 ES2-1.
Abstract ES6-2: CDK4/6 for ER+
Authors: Mayer IA 
Published: March 2022

Abstract
Hormone receptor positive (HR+) breast cancer is the most common subtype of breast cancer. A reasonable proportion of HR+ tumors recur during or following adjuvant endocrine therapy, and late recurrences (beyond 10 years from diagnosis) are not uncommon. The CDK4/6 inhibitors palbociclib, ribociclib and abemaciclib were approved in combination with endocrine therapy for the treatment of first and second-line metastatic HR+ breast cancer, based on impressive improvements in progression-free survival and overall survival. Therefore, transitioning these drugs to the adjuvant setting in high-risk patients made sense, to further prevent short and long-term metastatic recurrence of HR+ breast cancer. To date, 3 of the 4 phase III clinical trials with CDK4/6 inhibitors in the adjuvant setting have been reported, with mixed results. Penelope-B and PALLAS, both exploring the use of palbociclib for 1 and 2 years, respectively, along with endocrine therapy in patients with high-risk clinical characteristics failed to demonstrate a benefit in 4-years and 2-years disease-free survival (DFS), despite an early signal of benefit in the Penelope-B trial at 2-years. The Monarch-E trial, using abemaciclib for 2 years along with endocrine therapy for patients with very high anatomical and biologic recurrence risk, has shown a 3% higher 2-years DFS than endocrine therapy alone, but follow-up is quite short (19 months), and it is unclear if it will be maintained over time. The NATALEE trial, using ribociclib for 3 years with endocrine therapy is expected to yield results in 2025. These data highlight several questions that remained unanswered. Are the CDK4/6 inhibitors different from each other despite an identical mechanism of action? Does duration of treatment matter? Does disease biology matter? Discontinuation rates, albeit different between these trials, seems to be an unlikely answer for the discrepant results. Fortunately, all these adjuvant trials have collected a rich biorepository of tissue and blood, which allows the investigators to better ellucidate unique biomarkers that may predict individual benefit for each of the approved CDK4/6 inhibitors, that will hopefully guide optimal patient selection and treatment combinations. Till then, longer follow-up on the Monarch-E and NATALEE trials are necessary to explore if CDK4/6 inhibitors should or not be incorporated to endocrine therapy in the adjuvant setting for patients at high-risk of metastatic recurrence.
Citation Format: IA Mayer. CDK4/6 for ER+ [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 ES6-2.
Abstract MS1-2: Genomics of DNA repair defects in breast cancer
Authors: Nik-Zainal S 
Published: March 2022

Abstract
While driver mutations in cancer genomes were the focus of cancer research for a long time, passenger mutational signatures - the imprints of DNA damage and DNA repair processes that have been operative during tumorigenesis - are also biologically informative. In this lecture, I provide an update of what has been uncovered in breast cancers in relation to genomic imprints of DNA repair defects and showcase how we have developed computational applications that we hope to translate toward clinical utility.
Citation Format: S Nik-Zainal. Genomics of DNA repair defects 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 MS1-2.
Abstract OT1-14-02: Phase 3 study of trastuzumab deruxtecan (T-DXd) with or without pertuzumab vs a taxane, trastuzumab and pertuzumab in first-line (1L), human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (mBC): DESTINY-Breast09
Authors: Tolaney Sara M , Barroso-Sousa Romualdo , Jiang Zefei , Park Yeon Hee , Rimawi Mothaffar , Saura Cristina , Schneeweiss Andreas , Toi Masakazu , Yu Tinghui , Shetty Jagdish , Herbolsheimer Pia , Loibl Sibylle 
Published: March 2022

Abstract
Background: A combination of a taxane, trastuzumab, and pertuzumab (THP) is the standard-of-care (SOC) 1L treatment for patients (pts) with HER2+ mBC; THP demonstrated median progression-free survival (mPFS) of 18.7 mo and overall survival (OS) of 56.5 mo (Swain et al. N Engl J Med. 2015;372:724-734). However, pts eventually develop resistance to treatment. Novel treatment options are necessary in order to delay the emergence of resistance and provide better clinical outcomes, improve quality of life (QOL), and prolong survival in the 1L setting. T-DXd has demonstrated efficacy in pts with heavily pretreated HER2+ mBC, with an objective response rate (ORR) of 61.4%, duration of response (DOR) of 20.8 mo, and mPFS of 19.4 mo (Modi et al. Cancer Res. 2021. Abstract PD3-06). Data from DESTINY-Breast01 supported global approvals of T-DXd in HER2+ mBC. Here we describe a phase 3 trial evaluating the efficacy and safety of T-DXd ± pertuzumab compared with THP in the 1L treatment of HER2+ mBC. Trial design: DESTINY-Breast09 (NCT04784715) is a global, multicenter, randomized, phase 3 trial assessing the efficacy and safety of T-DXd with or without pertuzumab compared with SOC THP as 1L treatment in pts with HER2+ (IHC 3+ or ISH+ assessed locally per ASCO-CAP guidelines and centrally confirmed) advanced or mBC. This study consists of 3 treatment arms: arm A (T-DXd + placebo), arm B (T-DXd + pertuzumab), and arm C (THP). Randomization is 1:1:1 and pts will be stratified by prior treatment status (de novo vs recurrent), hormone receptor status (positive vs negative), and PIK3CA mutation status (detected vs not detected). Pts (N≈1134) must have had no prior chemotherapy or HER2-targeted therapy for advanced or mBC (1 prior line of endocrine therapy is allowed for mBC). The primary endpoint is PFS by blinded independent central review. Secondary endpoints include PFS by investigator assessment, OS, ORR, DOR, PFS2, health-related quality of life (QOL), pharmacokinetics, immunogenicity, and safety.
Citation Format: Sara M Tolaney, Romualdo Barroso-Sousa, Zefei Jiang, Yeon Hee Park, Mothaffar Rimawi, Cristina Saura, Andreas Schneeweiss, Masakazu Toi, Tinghui Yu, Jagdish Shetty, Pia Herbolsheimer, Sibylle Loibl. Phase 3 study of trastuzumab deruxtecan (T-DXd) with or without pertuzumab vs a taxane, trastuzumab and pertuzumab in first-line (1L), human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (mBC): DESTINY-Breast09 [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 OT1-14-02.
Abstract OT1-16-01: A multicenter phase II study of vaccines to prevent recurrence in patients with HER-2 positive breast cancer
Authors: Han Hyo S , Disis Mary , Wesolowski Robert , Fisher Carla , Gandhi Shipra , Chan Nancy , Gwin William , Gogineni Keerthi , Mick Rosemarie , Rodriguez Christina Sierra , Hogue Deanna , Liu Hien , Costa Ricardo , Czerniecki Brian 
Published: March 2022

Abstract
Background: HER2-positive breast cancer patients are commonly treated with neoadjuvant therapy including HER2-targeted therapy. Patients who have residual invasive disease have less favorable outcomes with an increased risk of recurrent disease than patients with complete pathologic response (pCR). It has also been observed that these non-pCR patients have low or absent anti-HER-2 CD4 Th1 responses. We hypothesized that correcting the anti-HER-2 CD4 Th1 response using vaccines will increase interferon gamma production which we have shown is a potent inducer of apoptosis and senescence in HER2-positive breast cancer. This study will be evaluating safety and immunogenicity of two vaccines (multivalent anti-oncodriver DNA vaccine (WOKVAC) or HER-2-pulsed dendritic cell vaccine (DC1)). Methods: This is a multi-center, phase 2, randomized study to determine the safety and tolerability of HER2 vaccines (DC1 and WOKVAC), assess immunogenicity, and evaluate recurrence free survival. Patients with HER2-positive early breast cancer (stage I-III) are eligible if they have residual invasive disease in the breast or axilla at surgery after receiving neoadjuvant chemotherapy plus HER2 -targeted therapy. Patients are randomly assigned in a 1:1 ratio to receive 1 of 2 adjuvant HER2 vaccines, either DC1 or WOKVAC for 1 year. A permuted-block randomization scheme was used with stratification according to residual cancer burden (RCB) (1+2 vs 3). The primary end points are safety and immunogenicity (immune response rate measured by ELISPOT). Each treatment arm will be assessed separately. Any statistical comparison between arms is purely exploratory, as this study is neither designed nor powered for comparative hypotheses. Secondary endpoints include recurrence-free survival. Exploratory analyses include the assessment of prognostic and predictive biomarkers including circulating tumor cells, serum HER2 levels, and other immune markers. The enrollment began in 2018 and we plan to accrue the total of 110 patients. ClinicalTrials.gov Identifier: NCT03384914
Citation Format: Hyo S Han, Mary Disis, Robert Wesolowski, Carla Fisher, Shipra Gandhi, Nancy Chan, William Gwin, Keerthi Gogineni, Rosemarie Mick, Christina Sierra Rodriguez, Deanna Hogue, Hien Liu, Ricardo Costa, Brian Czerniecki. A multicenter phase II study of vaccines to prevent recurrence in patients with HER-2 positive 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 OT1-16-01.
Abstract P1-05-08: Targeting tumor heterogeneity and breast cancer metastasis through the metastatic microenvironment mediated epigenetic reprogramming
Authors: Yang Li , So Jae Young , Skrypek Nicolas , Merchant Anand , Nelson George , Yang Howard , Lee Maxwell 
Published: March 2022

Abstract
Targeting tumor heterogeneity and breast cancer metastasis through the metastaticmicroenvironment mediated epigenetic reprogrammingLi Yang and Jae Young So, Nicolas Skrypek, Anand Merchant, George Nelson, Howard H.Yang, Maxwell P. LeeNational Cancer Institute, National Institutes of Health, Bethesda, MD 20892Current cancer treatments are largely based on the genetic characterization of primarytumors and are ineffective for metastatic disease. There is lack of mechanistic understanding ashow cancer cells are selected and evolved to establish distant metastatic colonies. In addition,tumor heterogeneity and biomarker identification remain to be some of the most difficultchallenges in cancer treatment. In the current study, we discovered an increased DNAmethyltransferase 3B (DNMT3B) in metastatic nodules and in tumor cells with epithelia tomesenchymal (EMT) phenotype. Of great interest, high levels of DNMT3B were correlated withpoor clinical outcomes in multiple human breast cancer datasets. Mechanistically, DNMT3Balters multiple pathways including STAT3, NFkappaB, PI3K/Akt, beta-catenin, Notch signalingas well as EMT, which are critical for cancer cell survival, apoptosis, proliferation, invasion, andcolonization. We further identified PGE2 and IL6 as critical inflammatory mediators inDNMT3B induction. Importantly, targeting IL6 or PGE2 production reduced DNMT3Bexpression and improved chemo treatment or PD1 immune therapy. Furthermore, perioperative(surgical removal of primary tumors) targeting DNMT3B in combination with chemotherapymarkedly suppressed tumor recurrence and metastasis in preclinical mouse models for triplenegative breast cancer. Our studies identify DNMT3B as an important mechanism fortranscription regulation in tumor heterogeneity that is critical for tumor invasion and metastasis,thus suggesting a validated target for treating metastatic disease.
Citation Format: Li Yang, Jae Young So, Nicolas Skrypek, Anand Merchant, George Nelson, Howard Yang, Maxwell Lee. Targeting tumor heterogeneity and breast cancer metastasis through the metastatic microenvironment mediated epigenetic reprogramming [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 P1-05-08.
Abstract P1-09-06: Insulinemic potential of diet and risk of total and subtypes of breast cancer among US women
Authors: Romanos-Nanclares Andrea , Willett Walter C. , Rosner Bernard A. , Tamimi Rulla M. , Tabung Fred K. , Holmes Michelle D. , Chen Wendy Y , Eliassen A. Heather 
Published: March 2022

Abstract
Background: Insulin resistance and hyperinsulinemia play important roles in the progression of multiple chronic disease and conditions. Diet modulates insulin response; however, evidence is limited regarding whether diet with higher insulinemic potential is associated with invasive breast cancer risk.Objectives: We prospectively evaluated the association between adherence to a food-based empirical dietary index for hyperinsulinemia (EDIH) and the incidence of invasive breast cancer.Methods: We prospectively followed 76,595 women from the Nurses’ Health Study (NHS, 1984-2016) and 93,295 women from the Nurses’ Health Study II (NHSII, 1991-2017). Diet was assessed by food frequency questionnaires every 4 years. The insulinemic potential of diet was evaluated using the EDIH that was pre-defined based on circulating C-peptide concentrations. Higher scores indicate higher insulinemic potential, while lower scores indicate lower insulinemic potential.Results: During 4,215,162 person-years of follow-up, we documented 10,595 breast cancer cases (6,639 NHS; 3,914 NHSII). Being in the highest, compared with the lowest, EDIH quintile was associated with higher breast cancer risk (HRQ5vsQ1 1.18; 95% CI 1.10, 1.27; P-trend&lt;0.01). The association was suggestively strongest among women with current BMI&lt;25 kg/m2 (HRQ5vsQ1 1.20; 95% CI 1.08, 1.34; P-trend&lt;0.01; P-interaction=0.06) compared to overweight/obese women. Although heterogeneity by estrogen receptor (ER) status was non-significant (P=0.17), the strongest association between EDIH and breast cancer was observed with ER-negative tumors (HRQ5vsQ1 1.26; 95% CI 1.04, 1.51; P-trend&lt;0.01). Among tumor molecular subtypes, the strongest associations were observed with HER2-enriched tumors (HRQ5vsQ1 1.75; 95% CI 1.08, 2.82; P-trend=0.01).Conclusions: A dietary pattern contributing to hyperinsulinemia was associated with greater breast cancer risk in women from the NHS/NHSII. In particular, a more hyperinsulinemic diet was associated with higher risk of breast cancer among lean women when compared to overweight or obese women. Moreover, the hyperinsulinemic diet showed a stronger positive association with ER-negative breast tumors, independent of adiposity. Our findings suggest that dietary interventions to reduce insulinemic potential may have a role in breast cancer prevention.
Citation Format: Andrea Romanos-Nanclares, Walter C. Willett, Bernard A. Rosner, Rulla M. Tamimi, Fred K. Tabung, Michelle D. Holmes, Wendy Y Chen, A. Heather Eliassen. Insulinemic potential of diet and risk of total and subtypes of breast cancer among US women [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 P1-09-06.
Abstract P1-13-07: De-escalation of five-year adjuvant endocrine therapy in patients with ER-low positive breast cancer: Propensity-matched analysis from a prospectively maintained cohort
Authors: Yu Keda , Cai Yuwen , Shao Zhiming 
Published: March 2022

Abstract
Background The standard 5 years of endocrine therapy has shown additional benefits when compared with short-term 2-3 years of treatment in patients with estrogen receptor (ER)-positive breast cancer; however, whether the long-term treatment is still necessary for ER-low positive (1%-10% by immunohistochemistry) breast cancer is unclear. Methods The prospectively maintained Breast Surgery Database of Fudan University Shanghai Cancer Center was used for this propensity-matched analysis. The primary endpoint was disease-free survival (DFS). Multivariate Cox regression and propensity score matching methods were performed to minimize bias. Hazard ratio (HR) with 95% confidence interval (CI) was calculated. All statistics were 2-sided. Results From 2012 to 2017, there were 22768 consecutive women with pathologically confirmed early-stage breast cancer and 1013 (4.45%) were identified as ER-low positive. Among them, 634 cases met the inclusion criteria and were divided into three groups: received no endocrine therapy (n=89); received 2-3 years of endocrine therapy (n=185); and received approximately 5 years of endocrine therapy (n=360). At a median follow-up of 65 months, there was no significant difference in DFS between patients who received 2-3 years and 5 years of endocrine therapy (HR, 0.82; 95% CI: 0.51-1.33; P=0.43). In the multivariate Cox regression analysis of the propensity score-matched samples, the DFS was not significantly better for patients who received 5 years of endocrine therapy than those receiving 2-3 years of treatment (HR, 0.74; 95% CI: 0.41-1.31; P=0.30). Conclusion Short-term 2-3 years of endocrine therapy might be an alternative for ER-low positive breast cancer instead of standard 5 years.
Citation Format: Keda Yu, Yuwen Cai, Zhiming Shao. De-escalation of five-year adjuvant endocrine therapy in patients with ER-low positive breast cancer: Propensity-matched analysis from a prospectively maintained cohort [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 P1-13-07.
Abstract P1-16-07: A synthetic lethality treatment strategy for p53 mutant breast cancer
Authors: Bakin Andrei , Zonneville Justin , Wang Moyi , Alruwaili Mohammed , Eng Kevin , Iyer Renuka , Park Ben , Fountzilas Christos 
Published: March 2022

Abstract
Breast carcinomas commonly carry mutations in the tumor suppressor p53, while therapeutic efforts to target mutant p53 were largely unfruitful. Here we report preclinical data supporting a novel combination therapy strategy for treatment of p53-mutant cancers. Genomic data revealed a high expression activity of Base-Excision Repair (BER) pathways in p53-mutant breast cancers. We designed a new methodology for testing BER in live cells. The BER studies revealed a significant dysregulation in BER-mediated repair in p53-mutant cancer cells. Taken advantage in the BER defect, we developed a novel treatment strategy that specifically targets p53-mt cancers. We found that treatment with deoxyuridine analogues induced accumulation of DNA damage selectively in p53-mutant cells. Further, inhibitors of poly (ADP-ribose) polymerase (PARPi) greatly enhanced this response and increased cell death, although PARPi as a single agent was not effective. In contrast, normal cells responded to PARPi with activation of the p53-p21 axis and cell cycle arrest. Inactivation of p53 in p53 wild-type cell lines conferred the p53-mutant phenotype. Preclinical breast cancer studies revealed that the combination of deoxyuridine analogue with PARPi was more effective in inhibition of tumor growth and metastases than either drug alone. This work illustrates a novel combination therapy strategy that may improve survival rates and outcomes for thousands of breast cancer patients.
Citation Format: Andrei Bakin, Justin Zonneville, Moyi Wang, Mohammed Alruwaili, Kevin Eng, Renuka Iyer, Ben Park, Christos Fountzilas. A synthetic lethality treatment strategy for p53 mutant 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 P1-16-07.
Abstract P1-24-05: Breast conserving surgery for non-metastatic inflammatory breast cancer: A National Cancer Database (NCDB) study
Authors: Angarita Fernando A. , Edge Stephen B. , Attwood Kristopher , Takabe Kazuaki , Young Jessica 
Published: March 2022

Abstract
Background: Single center studies have suggested breast conserving surgery (BCS) as treatment for inflammatory breast cancer (IBC). Given its infrequency, a multi-hospital database study is useful. This study reports the characteristics, outcomes, and prognostic factors of women with non-metastatic IBC who underwent BCS. Methods: The National Cancer Database (NCDB) was queried for women ≥18 years old with cT4dN0-3M0. Outcomes were compared between treatment groups. A Cox proportional hazards model assessed the relationship of variables and the overall survival (OS). Results: A total of 12,223 women were treated as follows: no surgery (12.8%), BCS (3.3%), and mastectomy (83.9%). BCS was significantly more common in academic/research institutions, South and North-East hospitals, no special type histology, triple negative breast cancer, single quadrant tumors, and node-negative tumors. Most patients who underwent BCS received chemotherapy (86.2%) and radiation therapy (61.9%), while hormonal therapy was infrequent (37.1%). Mortality was higher with BCS than mastectomy at 30 (1.3% versus 0.3%, p&lt;0.001) and 90 (6.8% versus 1.5%, p&lt;0.001) days post-surgery. Three- and five-year OS post-BCS was lower compared to mastectomy but higher than no surgery. Prognostic factors of OS for patients who underwent surgery included academic/research institutions, income ≥$63,000, hormone positive tumors, and receipt of chemotherapy and radiation therapy. Conclusion: BCS is offered to select women with non-metastatic IBC across NCDB participating hospitals. Caution is necessary while studying if surgery can be de-escalated in IBC. Standardized multidisciplinary care along with mastectomy remains the norm for patients with non-metastatic IBC.
Citation Format: Fernando A. Angarita, Stephen B. Edge, Kristopher Attwood, Kazuaki Takabe, Jessica Young. Breast conserving surgery for non-metastatic inflammatory breast cancer: A National Cancer Database (NCDB) study [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 P1-24-05.