bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract CC1-1-2: To clip or not to clip (Part 2)
Authors: Galimberti Viviana 
Published: March 2023

Abstract
Neoadjuvant chemotherapy (NAC) changed the breast surgery approach and increased indications in recent years. NAC allows to downstage the primary tumor and also may clear the axilla of lymph node metastases in some patients. In fact, NAC allows de-escalation of surgery: not only resulted in an increase in conservative surgery in 40%, which was the initial goal of chemotherapy, but in particular it allows for a reduction in axillary surgery. Furthermore, in relation to the molecular characteristics of the tumors we can have a pathological complete response (pCR) ranging from 20 to 80%. In node-positive patients who converted to cN0 different prospective studies ACOSOG Z1071, SENTINA, SN FNAC and GANEA 2, have demonstrated that the FNR of the SNB was high, more than the acceptable 10%. Therefore, strategies to reduce the FNR treatment in cN+ patients are being investigated: is to remove more than three negative axillary lymph nodes or marking of positive axillary nodes with a tattoo or clip, the so-called target axillary dissection (TAD), to document their removal. But all the effort to reduce the FNR rate do not have clinical prognostic significance. This has already been demonstrated in the literature in different randomized trials with long term follow up. The 10-year follow-up of our study confirmed our preliminary data that the use of standard sentinel node biopsy (SNB) without the use of clip is acceptable in cN1/2 patients who become cN0 after NAT and will not translate into a worse outcome. In fact, the axillary recurrences found were less than 2% in particular in the group that started from a positive axilla were 1.8 %, if we considered that 2 of them had a micrometastatic SN and refused the AD, but if we considered only those with a negative SN the percentage drops to 0.9% Similar positive data with different follow up were also confirmed by other studies that used SNB alone without TAD. All these studies data, with now comforting results on the follow up, confirm that SN surgery alone for selected patients who have an excellent response to NAC is not oncologically inferior to AD during a short- and long-term follow-up.
Citation Format: Viviana Galimberti. To clip or not to clip (Part 2) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr CC1-1-2.
Abstract ED1-1: What are PROs and evidence for benefit?
Authors: Rosenberg Shoshana 
Published: March 2023

Abstract
Patient-reported outcomes (PROs) are self-reported assessments provided directly by patients. PROs can be used for research, to tailor and improve clinical and supportive care, and for quality assessment purposes. It is well-established that PROs, rather than clinician evaluations, better capture the patient experience. Additionally, there is growing evidence supporting the routine incorporation of PROs into clinical practice. In particular, the use of PRO-based interventions is associated with improved symptom management, enhanced patient-provider communication, and better outcomes, including quality of life and survival, in patients with advanced cancer. Among patients in the post-active treatment and survivorship phase of care, PROs are critical in identifying and understanding late and long-term effects of treatment, identifying unmet needs, and determining if survivors are receiving appropriate follow-up care. There are also data in the survivorship setting demonstrating how PROs can predict other outcomes, such as adherence to aromatase inhibitors in breast cancer survivors. Careful consideration of age (e.g., pediatric vs. adult measures), race and ethnicity (e.g., was the measure validated in a diverse and representative population), language (e.g., was the measure validated in other languages), literacy level (e.g., was the measure written for individuals with low literacy levels), mode of delivery (e.g., paper vs. tablet), and participant burden (e.g., does the assessment take a reasonable amount of time) when selecting PROs is critical to ensure that the information learned is generalizable and that the benefit patients can gain through the incorporation of PROs into cancer care is equitable.
Citation Format: Shoshana Rosenberg. What are PROs and evidence for benefit? [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr ED1-1.
Abstract ED12-2: Mechanisms of sensitivity and resistance to HRD targeting agents in breast cancer – PARPi and beyond
Authors: Lord Christopher 
Published: March 2023

Abstract
Although PARP inhibitors (PARPi) deliver significant and sustained anti-tumour responses in those with HR defective cancers, PARPi resistance is a common clinical phenomenon and limits the overall effectiveness of these agents. I will discuss how reversion mutations in BRCA1 and BRCA2 cause PARPi resistance and how the emergence of reversions might be targeted by immune responses against the neopeptides caused by reversion mutations. I will also discuss how other mechanisms of PARPi resistance such as 53BP1/Shieldin complex dysfunction could be targeted by evolutionary “double binds” using drugs such as Pol-theta inhibitors that exploit new vulnerabilities put in place by emerging PARPi resistance mechanisms
Citation Format: Christopher Lord. Mechanisms of sensitivity and resistance to HRD targeting agents in breast cancer – PARPi and beyond [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr ED12-2.
Abstract ED2-1: Cancer risks in patients with moderate penetrance gene mutations
Authors: Shah Payal 
Published: March 2023

Abstract
The genetic landscape of inherited breast cancer is broad, spanning from high and moderate penetrance pathogenic variants in breast cancer susceptibility genes, to polygenic risk associated with the cumulative impact of single nucleotide polymorphisms (SNPs). This educational session will review the landscape of inherited breast cancer. The discussion will then focus on breast cancer susceptibility genes associated with moderately elevated risks of breast cancer including PALB2, ATM, CHEK2 and others. Recent data informing quantitative and qualitative cancer risk estimates, management recommendations, therapeutic implications, and reproductive considerations will be reviewed. Emerging issues and treatment strategies under investigation will also be discussed.
Citation Format: Payal Shah. Cancer risks in patients with moderate penetrance gene mutations [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr ED2-1.
Abstract ED3-1: Updates in the pathology of PABC
Authors: Siziopikou Kalliopi 
Published: March 2023

Abstract
Updates in the Pathology of Pregnancy Associated Breast Cancer (PABC)
Pregnancy associated breast cancer is defined as a breast cancer diagnosed during gestation, lactation and within 1 to 5 years postpartum. While the development of malignancy during pregnancy is rare, the incidence is increasing; breast cancer is one of the most common cancers diagnosed during pregnancy and the postpartum period occurring in up to 1 in 3000 deliveries. Of interest, breast cancer is the leading cause of cancer death in US women age 15-29. Pregnancy has a dual effect on breast cancer development: on one hand cancer protective and on the other cancer promoting. While a number of hypotheses have been proposed over the years to explain these effects, the most likely hypothesis for the development of PABC is the involution hypothesis. This hypothesis proposes that the involution pathways activated during pregnancy and the immediate postpartum period are remodeling programs similar to wound healing and inflammation that may be associated with tumor development and progression. Although PABCs can be any subtype of breast carcinomas, they are usually invasive ductal carcinomas of high tumor grade and large tumor size with higher stage at presentation and higher rates of lymph node involvement. Most PABCs are hormone receptor negative tumors with high Ki-67 proliferation rates; most frequently, they are either triple negative or HER2-positive carcinomas. A number of studies have shown that PABCs have different genomic signatures than the non-PABC tumors with PABCs having an increased expression of immune response mediators. Better understanding of the molecular pathways of tumor initiation and progression and prompt diagnosis and state-of-art treatment protocols in PABC is expected to lead to better outcomes for these young breast cancer patients.
Citation Format: Kalliopi Siziopikou. Updates in the pathology of PABC [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr ED3-1.
Abstract ED4-3: Inflammatory Breast Cancer
Authors: Lynce Filipa 
Published: March 2023

Abstract
Inflammatory Breast Cancer (IBC) has an incidence of 1-5% among all breast cancers diagnosed within the USA, yet it accounts for a disproportionately high rate of mortality, leading to up to 10% of all breast cancer related deaths. Although IBC can present with any receptor status in terms of estrogen, progesterone, and human epidermal growth factor 2 (HER2), there is a higher proportion of HER2 positive cases compared to non-IBC. Given the distinct difference in outcome, it is important to differentiate IBC from more indolent locally advanced non-IBC with secondary inflammatory features. Despite ongoing efforts to identify molecular markers specific for IBC, the underlying tumor biology and genomic drivers of progression remain largely unknown. In this session we will review tumor-intrinsic signaling pathways, the role of the tumor microenvironment and clinical trials with combination therapies to inform future biomarkers of disease progression in IBC.
Citation Format: Filipa Lynce. Inflammatory Breast Cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr ED4-3.
Abstract ED7-2: Multiplex spatial proteomic profiling
Authors: Rimm David 
Published: March 2023

Abstract
Multiplex spatial analysis is touted as a potential solution for tissue biomarkers for prognostic and companion diagnostic applications. Spatial analysis infers maintaining the location of a biomolecule so that both its amount and context can contribute to the information obtained. Immunohistochemistry (IHC) is the archetypal method of spatial profiling and the only application that has made it to the clinic. In this session, we will discuss technologies based on IHC, but that allow assessment of at least two, and as many as 100 or more proteins within the cell or molecular compartment that maintains spatial context. The simplest and most common approach is multiplex immunofluorescence, followed by a number of next generation techniques that use alternative labeling of the antibodies or cycling strategies or both to generate spatially informed data. Excluding Mass spectrometry-based methods, still in early stages, the highest “plex” method for protein is digital spatial profiling. Digital spatial profiling (DSP) uses a molecular method to define spatial compartments which is different from other high-plex methods that use cell segmentation, an image analysis method that largely depends on the presence of a cell nucleus in the image. As a result, the DSP method allows assessment of both cellular and non-cellular stromal compartments. DSP and other high-plex methods that will be discussed are thought to be best used as biomarker discovery tools, that might find biomarkers that can be measured with a more traditional approach for assessment in the clinic.
Citation Format: David Rimm. Multiplex spatial proteomic profiling [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr ED7-2.
Abstract ED9-3: Effects of age on the tumor microenvironment
Authors: McAllister Sandra 
Published: March 2023

Abstract
Dr. McAllister’s translational research group studies breast cancer as a systemic disease with an emphasis on the role of immune fitness in disease control and response to therapy. In this education session, Dr. McAllister will introduce the concept of “immunological age”. She will discuss her team’s ongoing efforts to understand how age sets the stage for triple-negative breast cancer (TNBC) progression and response to immune checkpoint blockade therapy.
Her team was the first to report that bone marrow derived immune cells from 8–10-week-old young mice promote more aggressive TNBC growth when transferred to 12–15-month-old aged mice (Marsh, et al., Cancer Research, 2016). They subsequently identified cellular and molecular mechanisms that promote aggressive disease, as typically observed in younger individuals. Likewise, her group was the first to report that immune checkpoint blockade therapy is less effective in older mice with TNBC and discovered a treatment strategy that improved outcomes in pre-clinical TNBC models (Sceneay, et al., Cancer Discovery, 2019). The same tumor cellular and molecular pathways that stratified by age in their pre-clinical models also defined age-stratified differences between younger (under 40) and older (over 65) TNBC patients in the METABRIC dataset.
She will present her team’s new work on functional aspects of immunological age in TNBC and the ongoing efforts of the Older Women with Breast Cancer Research and Treatment Team at the Dana-Farber/Brigham Cancer Center. Ultimately, she and her team wish to eliminate age- and race-based disparities in breast cancer outcomes.
Citation Format: Sandra McAllister. Effects of age on the tumor microenvironment [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr ED9-3.
Abstract F3-2: Fasting and caloric restriction mimetics stimulate anticancer immunosurveillance
Authors: Kroemer Guido 
Published: March 2023

Abstract
Fasting and caloric restriction induce metabolic and neuroendocrine changes that have major anti-inflammatory and immunostimulatory effects. Some of these effects are mediated by a raise of ketone bodies (such as 3-hydroxybutyrate) and a decrease in circulating insulin-like growth factor-1 (IGF1), meaning that administration of 3-hydroxybutyrate and pharmacological inhibition of IGF1 receptor can mimic some of the beneficial effects of fasting on anticancer immunosurveillance. "Caloric restriction mimetics" (CRMs) are small molecules that induce autophagy through the same pathways that are activated by fasting, including the reduction of cytoplasmic protein acetylation. We have accumulated evidence that CRMs can stimulate anticancer immunosurveillance either as single agents (for the prevention of malignant disease) or in combination with chemotherapy and/or immune checkpoint blockade (for the treatment of established cancers). In preclinical experiments, fasting and CRMs have also been used for the prevention or treatment of hormone-induced breast cancer, and these effects are coupled to an increase in the T lymphocyte-mediated anticancer immune response. We have developed an in vitro screening assay to identify novel pharmacological agents that act as CRMs. Such neo-CRMs can be successfully employed to improve anticancer immunosurveillance in preclinical experiments.
Citation Format: Guido Kroemer. Fasting and caloric restriction mimetics stimulate anticancer immunosurveillance [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr F3-2.
Abstract GS1-05: Trial Assigning Individualized Options for Treatment (TAILORx): An Update Including 12-Year Event Rates
Authors: Sparano Joseph , Gray Robert J. , Makower Della , Albain Kathy S. , Hayes Daniel F. , Geyer Charles , Dees Elizabeth , Goetz Matthew P. , Olson John A. , Lively Tracy G. , Badve Sunil , Saphner Thomas , Wagner Lynne I. , Whelan Timothy , Kaklamani Virginia , Sledge George 
Published: March 2023

Abstract
Background: Late recurrence of breast cancer after 5 years accounts for about 50% of recurrences in hormone receptor (HR)-positive early breast cancer (EBC). TAILORx established non-inferiority of adjuvant endocrine therapy (ET) given for at least 5 years to chemotherapy plus ET (CET) in EBC and a 21-gene recurrence score (RS) of 11-25, although there was some chemotherapy benefit in women
Methods: Eligibility criteria included women 18-75 years with HR-positive, HER2-negative, T1b-T2N0 EBC who agreed to have CT assigned or randomized based on the RS assay. The primary endpoint was invasive disease-free survival (iDFS) in the RS 11-25 group. The “primary analysis” refers to the original prespecified analysis for the primary IDFS endpoint (836 IDFS events at full information in the RS 11-25 group) after a median of 7.5 years. The “updated analysis” was performed after a median followup of 11.0 and 10.4 years in the randomized and overall populations, respectively.
Results:10,253 eligible women enrolled between 4/7/06-10/6/10.The updated analysis includes substantially more events that the primary analysis, including IDFS events (1819 vs. 1210), distant recurrences (561 vs. 384), locoregional +/- distant recurrences (764 vs. 543), and deaths (910 vs. 499). The table provides 5 and 12-year event rates (and standard errors) for all arms, and comparisons of the randomized arms. The primary trial conclusions remain unchanged: ET was non-inferior to CET in the randomized group with a RS 11-25. Although recurrence occurred in &lt; 10% by 12 years for a RS 0-25, late recurrence events beyond 5 years exceeded earlier recurrence. Non-recurrence events occurred in about 13% at 12 years (~1%/year), contributing substantially to the IDFS rates. For women
Conclusions: The current updated analysis confirms findings from the original primary analysis that ET is non-inferior to CET in HR-positive, HER2-negative, node-negative EBC and a RS 11-25. As in the original primary analysis, the subgroup of women

Citation Format: Joseph Sparano, Robert J. Gray, Della Makower, Kathy S. Albain, Daniel F. Hayes, Charles Geyer, Elizabeth Dees, Matthew P. Goetz, John A. Olson Jr, Tracy G. Lively, Sunil Badve, Thomas Saphner, Lynne I. Wagner, Timothy Whelan, Virginia Kaklamani, George Sledge. Trial Assigning Individualized Options for Treatment (TAILORx): An Update Including 12-Year Event Rates [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr GS1-05.
Abstract MS1-1: Oncogene signal transduction and antiestrogen resistance
Authors: Schiff Rachel 
Published: March 2023

Abstract
Background: Recent studies suggest that enhancer reprogramming underlies heterogeneity and disease progression in estrogen receptor-positive (ER+) BC. Cell-type/state specific transcription is governed by high-order assemblies of master transcription factors (TFs) and epigenetically defined regulatory regions including super-enhancers (SEs). We previously showed that aberrant activation of the pioneer TF FOXA1 promotes enhancer and transcriptional reprogramming in endocrine-resistant BC, involving the ER and the AP-1 FRA1 and c-JUN TFs. As SEs maintain a robust cell-type/state specific core transcriptional regulatory circuitry (CRC) in developmental and tumorigenic processes, we sought to identify key additional TFs in SE/FOXA1-driven CRCs in endocrine resistance, which could serve as attractive therapeutic targets.
Methods: TF binding motif at the shared SEs (mapped by H3K27ac ChIP-seq) between MCF7-parental (P) cells with ectopic FOXA1 overexpression (OE) and the endogenous FOXA1-amplifed tamoxifen-resistant (TamR) cells was analyzed by HOMER. ER-bound SEs distinguishing TamR vs. P cells were defined by integrating the SEs with our prior ER ChIP-seq data (PMID 28507152). KLF4 motif within these ER-bound SEs was scanned using FIMO and linked to nearby genes by intersection with the previously defined promoter-tethered regions (PTRs) (PMID 24141950). Differential gene expression in MCF7-TamR cells upon KLF4 knockdown (KD) by 3 unique siRNAs was analyzed using limma from edgeR. The biological and clinical significance of the KLF4-dependent genes was analyzed using Gene Ontology and survival modeling with METABRIC and the ER+ metastatic BC cohort ( SABCS19-GS2-02 ). Cell migration was assessed by the wound-healing assay.
Citation Format: Rachel Schiff. Oncogene signal transduction and antiestrogen resistance [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr MS1-1.
Abstract MS1-3: Treatment of ER+/HER2+ breast cancer
Authors: Johnston Stephen 
Published: March 2023

Abstract
Co-expression of hormone receptors (HR) and human epidermal growth factor receptor 2 (HER2) occurs in 10% of all breast cancers, and due to cross-talk mechanisms that influence cell signalling the co-expression of these receptors modulates response of these cancers to both HER2-directed and endocrine therapies. Prior to the advent of HER2 targeted therapies, patients with HR+/HER2+ breast cancer had a significantly worse prognosis compared with HR+/HER2- breast tumours, primarily related to HER2 signalling driving endocrine resistance. Likewise, prior clinical studies in the neoadjuvant setting showed that patients with HR+/HER2+ primary breast cancer had a lower pathological complete response rate to HER2-targeted therapy plus chemotherapy that those with HR-/HER2+ tumours, suggesting a different biology. As such, strategies that combine receptor blockade against HER2 and HR have been developed in metastatic breast cancer (MBC), confirming that combined blockade is better than endocrine therapy (ET) alone, and then that dual HER2 blockade + ET was superior to single HER2 therapy + ET. More recently combinations of a CDK 4/6 inhibitor with ET and HER2 therapy has shown significant clinical efficacy and survival benefit in heavily pre-treated patients, confirming the efficacy for non-chemotherapy targeted combinations in HR+/HER2+ MBC. In the early breast cancer (EBC) setting, most HER2 directed therapy is given in combination with chemotherapy in the neoadjuvant setting, while studies of combined ET and HER2 targeted strategies without chemotherapy work slower with lower pCR rates. As such, the real benefit for combined targeted therapy may be in the adjuvant setting where ET and HER2 therapy are routinely given together following completion of chemotherapy. Furthermore, extended adjuvant ET/HER2 therapy beyond completion of antibody based treatment may also provide extra benefit, and in higher risk patients longer treatment may prove an important consideration.
Citation Format: Stephen Johnston. Treatment of ER+/HER2+ breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr MS1-3.