bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract PS7-78: Trends in BRCA testing among patients diagnosed with breast cancer -a retrospective analysis of a United States commercial claims database from the PRIOR-1 study
Authors: Corman Shelby , Kale Hrishikesh , Shah Pooja , Adeboyeje Gboyega
Published: February 2021

Background The use of BRCA testing to guide the course of breast cancer treatment has evolved in the last 5 years; however, little is known about the use of BRCA testing in a real-world setting. This study assessed the trend in prevalence of BRCA testing and sociodemographic and clinical predictors of receiving a BRCA test among newly diagnosed patients with breast cancer. Methods This was a retrospective study conducted using the Optum Clinformatics Datamart database. Patients newly diagnosed with breast cancer, continuously enrolled in a health plan for ≥6 months before and after diagnosis were included in the study. Claims for BRCA testing were identified after diagnosis using HCPCS, ICD-9/10 procedure, and LOINC codes. The prevalence of BRCA testing was calculated for patients diagnosed in each year from 2012-2017. Multivariable logistic regression was used to assess predictors of BRCA testing controlling for sociodemographic and clinical factors. Results From a total of 81,774 breast cancer patients included, 13,529 (16.5%) received a BRCA test after diagnosis. The prevalence of BRCA testing increased from 1,721 (11.5%) in 2012 to 2,384 (17.1%) in 2013 and remained stable over time until 2017 [2,191, (18.5%)]. Of patients receiving a BRCA test, 11,688 (86%) were tested within 1 year of diagnosis. The median time to receive a BRCA test from diagnosis was 29 days (mean: 172.7 days). Results from logistic regression indicated that diagnosis at a younger age (e.g., 18-44 years versus ≥75 years, odds ratio [OR] = 25.3), diagnosis in recent years (e.g., 2017 versus 2012, OR =1.94), having a point of service versus health maintenance organization plan type (OR = 1.10), presence of metastasis (OR = 1.62), and family history of cancer (OR = 4.98) significantly (P<0.05) increased odds for receiving a BRCA test. Female gender (OR = 0.28), living in regions other than West (e.g. South, OR = 0.86), having commercial insurance versus Medicare Advantage (OR = 0.96), Charlson comorbidity index score of ≥3 vs 0 (OR= 0.83) were significantly (P<0.05) associated with lower odds of receiving a BRCA test. Conclusions Prevalence of BRCA testing among breast cancer patients increased initially in 2013 and remained stable over time until 2017. Several demographic and clinical factors were associated with the use of BRCA testing among breast cancer patients.

Citation Format: Shelby Corman, Hrishikesh Kale, Pooja Shah, Gboyega Adeboyeje. Trends in BRCA testing among patients diagnosed with breast cancer -a retrospective analysis of a United States commercial claims database from the PRIOR-1 study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS7-78.
Abstract PS8-18: Describing the cancer spectrum in families with CHEK2 pathogenic and likely pathogenic variants by mutation type
Authors: Moroney Julia G , Basiliere Michele S
Published: February 2021

Background: Deleterious CHEK2 variants have well-defined risks for breast and colorectal cancers. Some studies have also suggested association with a variety of other cancers, including leukemia, kidney, prostate, thyroid and gastric cancers. However, most CHEK2 studies are based on European founder mutations, and there is a lack of data on non-founder mutations. Here, we describe the cancer family histories of patients with both founder and non-founder CHEK2 mutations. Methods: This is a retrospective review of patients who underwent germline testing of 31 cancer risk genes. All pathogenic (P) and likely pathogenic (LP) variants in CHEK2 were selected from our database and categorized as founder or non-founder mutations. Personal and family histories of cancer reported by the ordering provider were recorded for each case. Cancer rates were calculated as the number of patients with a personal and/or family history of each cancer divided by the total number of patients. Ethnicities in our CHEK2+ cohort and our overall database were calculated as a percentage. Results: A total of 132 patients were found to have P/LP variants in CHEK2. This CHEK2+ cohort was largely Caucasian (79.5%), despite our overall database being ethnically diverse (56% Caucasian). Nineteen different mutations were identified, 75% of which were founder and 25% were non-founder mutations. Personal histories of cancer were identified in 7% of patients. Twenty-eight different cancers were reported in patients’ personal/family histories. The rates of select cancers in the total cohort, founder mutation group and non-founder mutation group are reported in Table 1. Discussion: These findings support previous reports that prostate, gastric and kidney cancers may be part of the CHEK2 cancer spectrum, which has typically only included breast and colorectal cancer. We also identify ovarian and pancreatic cancer as potential CHEK2-associated cancers. Cancer rates are similar between CHEK2 patients with founder and non-founder mutations. Differences in cancer rates were observed between these two groups, but this cohort was too small to determine significance. Additional studies are needed to understand the overlap of cancer risk with non-founder mutations and those well-described for founder mutations.

Table 1: Select cancer rates by CHEK2 mutation typeBreast FemaleOvarianProstateColorectalPancreaticUterineGastricKidneyAll80.3%39.4%25%23.5%13.6%8.3%8.3%6.1%Founder81.8%40.4%30.3%23.2%18.2%9.1%9.1%8.1%Non-founder75.8%36.3%9.1%24.2%0%6%6%0%

Citation Format: Julia G Moroney, Michele S Basiliere. Describing the cancer spectrum in families with CHEK2 pathogenic and likely pathogenic variants by mutation type [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS8-18.
Abstract PS9-22: Supportive care needs and patient experience of women with metastatic breast cancer in a safety-net system
Authors: Buchanan Ashley , El-Mubasher Ola , Sarfo Astrid , Badr Hoda
Published: February 2021

Background: Metastatic breast cancer (MBC) is an incurable, albeit treatable cancer affecting over 150,000 women in the US. Addressing supportive care needs has become increasingly important as women are living longer with MBC due to advances in treatment. However, most supportive care programs were developed for women with early stage breast cancer. The existing literature also offers limited understanding of the needs of patients receiving care in safety net settings, which are often under-resourced and treat medically underserved populations, who are more likely to be diagnosed with MBC.

Methods: This study sought to understand the supportive care needs and experience of MBC patients receiving care in a safety net system. Semi-structured interviews were conducted with 11 patients (average age = 42.8 years, SD = 19.5) who were undergoing treatment for MBC. Questions centered on the diagnosis and treatment experience, patient-provider communication, and perceived barriers to care. Interviews were digitally audio-recorded, transcribed and coded using a Grounded Theory approach. Results: Patients noted that a lack of familiarity with medical terminology and insufficient medical knowledge made it difficult for them to evaluate treatment options, make treatment decisions, and communicate their supportive care needs. Half (n=5) did not feel their healthcare concerns were validated when expressed and some even went so far as to exaggerate reports of physical symptom severity in order to receive more timely and attentive care. Patients were dissatisfied with the timeliness of information delivery, scheduling delays, and long wait times. Some also felt that seeing different providers (e.g., residents, fellows) each time they came into the clinic interfered with the doctor-patient bond and continuity of care.

Conclusion: This study identified patient, provider, and system-level factors affecting MBC patients’ experience of care in a safety-net system. Our findings indicate a strong need for support services including outreach to address health literacy issues, treatment decision making, and symptom management concerns. They also indicate a need for improved disease and treatment information exchange between patients and healthcare providers.

Citation Format: Ashley Buchanan, Ola El-Mubasher, Astrid Sarfo, Hoda Badr. Supportive care needs and patient experience of women with metastatic breast cancer in a safety-net system [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS9-22.
Abstract PS9-35: Volumetric assessment of lymphedema with 3D sensor
Authors: Maciel-Miranda Alejandro , Otero-Hernández Miriam I , Martínez-Silva Darinka , Escrivá-Machado Jesus F
Published: February 2021

Volumetric assessment of lymphedema with 3D sensor: A new practical method Secondary lymphedema of the upper extremities is an important quality-of-life issue for around 40% of patients who were treated for breast cancer and required axillary nodal dissection and radiotherapy. Volume measurement is an important aspect of diagnosis, follow up, and evaluation after conservative or surgical treatment for lymphedema. Until now, there have been complex techniques to assess volume of affected limbs: bioimpedance, liquid-displacement volumetry, CT, MRI. There is a need for a practical method of volumen assessment in lymphedema patients. The objective of the present study is to confirm whether or not 3D scanning for volumetric assessment is useful and correlates with direct perimeter measurement and indirect volume calculation. Methods: A 3D sensor (Structure Sensor, Occipital Inc) mounted on an Ipad (Apple, Inc.) was used to make a 3D model file of the affected limb, that was later analyzed by 3DsizeME software (TechMed 3D, Inc.) in a desktop computer. 3D model analysis allows to measure perimeters and volumes. Fifteen patients were measured, lymphedema and normal limbs (30 extremities) by this technique and were also measured with tape, as traditional method; results were compared to assess correlation. Results: There were not statistical difference between the two techniques (p 0.05). Table attached. Discussion: volumetric assessment by 3D sensor allows consistent and reproducible measurements. It is practical as we only need the space of an ipad, it can be performed in the clinic visit, by any doctor, nurse or physical therapist. It is not expensive, as the software charges US$10 by each analysis. It do not expose the patient to any harmful radiation, as is obtained by and infrared camera. Allows electronic records of all measurements. Average time to capture 3D model is 5 minutes. We think this new method is a valuable tool for any lymphedema clinic as volume measurement is important for disease evaluation and now, more important, with a growing field of surgical treatment for this disease.

Citation Format: Alejandro Maciel-Miranda, Miriam I Otero-Hernández, Darinka Martínez-Silva, Jesus F Escrivá-Machado. Volumetric assessment of lymphedema with 3D sensor [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS9-35.
Abstract PS9-63: Real world data on the adoption of trastuzumab biosimilars in the treatment of HER2-positive breast cancer
Authors: Flood William A , Avery Tiffany , Kozlovsky Vlad , Margolis Neil , Reddy Sandeep
Published: February 2021

Background: Biosimilars for trastuzumab were introduced into the US market for the treatment of HER2-positive breast cancer in 2019, with the goal of providing the clinical benefit of the brand product at a lower price (increased value). Adoption of trastuzumab biosimilars may be affected by multiple factors, including physician confidence in biosimilar efficacy and efficacy across stages, practice reimbursement, payer medical policy/redirection. To look at the adoption of trastuzumab biosimilars in the US medical oncology community, we queried a database of submitted treatment plans for patients with breast cancer. Methods: Data from a pre-authorization platform used by multiple commercial insurance companies in the US (NantHealth Eviti) was analyzed. Cases were identified from approved treatment plans for patients with breast cancer by inclusion of brand trastuzumab or trastuzumab + hyaluronidase-oysk, or trastuzumab biosimilars. Results: As of July 1, 2020, 10,557 treatment plans trastuzumab-based therapy were submitted, 1740 (16.5%) of which used a trastuzumab biosimilar. Adoption of trastuzumab biosimilars increased over time, from 1.6% (27/1676) treatment plans in Q3-2109 to 43.3% (753/1736) in Q2-2020. No clear differences were observed between use in stage 0-IIIc disease (17.4%) vs stage IV/recurrent disease (14.5%). Using the July 1, 2020 CMS pricing for these drugs at normalized dose of 440 mg for trastuzumab/trastuzumab biosimilars or 600 mg of trastuzumab + hyaluronidase, the average cost/cycle/patient for brand therapy and biosimilar therapy is $4502 and $3618, respectfully, representing a savings of $1,374,620/cycle across the biosimilar-treated population. Additional analyses to be presented will include Q3 2020 utilization and patterns of utilization across payers with/without medical policy favoring biosimilars. Conclusions: Adoption of trastuzumab biosimilars in this commercial population has been rapid since their introduction. Use of these drugs provides a substantial opportunity for societal savings in the treatment of HER2-positive breast cancer.

Citation Format: William A Flood, Tiffany Avery, Vlad Kozlovsky, Neil Margolis, Sandeep Reddy. Real world data on the adoption of trastuzumab biosimilars in the treatment of HER2-positive breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS9-63.
Abstract SP113: The making of an ADC
Authors: Parren PWHI
Published: February 2021

Targeted treatment using antibody therapeutics has proved successful for the development of meaningful treatments in diverse therapeutic areas. However, despite strong advances, many patients still fail to respond or become resistant to targeted treatment and novel innovative approaches to improve therapy are therefore required. Genetic and chemical engineering of antibodies, fueled by recent molecular insights, is providing important opportunities for the development of more potent antibody therapeutics.

Antibody-drug conjugates (ADC), which combine the tumor-targeting capacity of monoclonal antibodies with the antitumor activity of cytotoxic agents, received much attention. In the road-map to developing an ADC, understanding target biology and selecting the most optimal antibody, linker and toxic payload represent critical parameters. This talk will provide an overview of this thought process in the context of the development of two ADCs currently in the clinic, tisotumab vedotin and enapotamab vedotin.

Citation Format: PWHI Parren. The making of an ADC [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr SP113.
Abstract SP012: Convergent evolution of resistance pathways during early stage breast cancer treatment with combination cell cycle (CDK) and endocrine signaling inhibitors
Authors: Griffiths JI , Chen J , Cosgrove PA , O'Dea A , Sharma P , Ma CX , Trivedi M , Kalinsky K , Wisinski KB , O'Reagan R , Makhoul I , Spring LM , Bardia A , Adler FR , Cohen AL , Chang JT , Khan QJ , Bild AH
Published: February 2021

Combining cyclin-dependent kinase (CDK) inhibitors with endocrine therapy improves outcomes for metastatic estrogen receptor positive (ER+), HER2 negative, breast cancer patients. However, the value of this combination in potentially curable earlier stage patients is not clear. Using single cell transcriptomic profiling, we examined the evolutionary trajectories of early stage breast cancer tumors using serial tumor biopsies from a clinical trial of preoperative endocrine therapy alone (letrozole) or in combination with the cell cycle inhibitor ribociclib. Applying hierarchical regression and Gaussian process mathematical modelling, we classified each tumor by whether it shrinks or persists with therapy and determined cancer phenotypes related to evolution of resistance and cell cycle transcriptional rewiring. We found that all patients’ tumors undergo subclonal evolution during therapy, irrespective of the clinical response. However, tumors subjected to endocrine therapy alone showed reduced diversity over time, those facing combination therapy exhibited increased diversity. Despite different diversity, single nuclei RNA sequencing uncovered common phenotypic changes in tumor cells that persist following treatment. In these tumors, accelerated loss of estrogen signaling is convergent with up-regulation of the JNK pathway, while persistent tumors that maintain estrogen signaling during therapy show potentiation of CDK4/6 activation consistent with ERBB4 and ERK signaling up-regulation. Cell cycle reconstruction identified that these tumors can rebound during combination therapy treatment, indicating stronger selection and promotion of a proliferative state. These results indicate that combination therapy in early stage ER+ breast cancers with ER and CDK inhibition drives rapid evolution of resistance via a shift from estrogen signaling to alternative growth factor receptor mediated proliferation and JNK signaling activation, concordant with a bypass in the G1 checkpoint.

Citation Format: JI Griffiths, J Chen, PA Cosgrove, A O'Dea, P Sharma, CX Ma, M Trivedi, K Kalinsky, KB Wisinski, R O'Reagan, I Makhoul, LM Spring, A Bardia, FR Adler, AL Cohen, JT Chang, QJ Khan, AH Bild. Convergent evolution of resistance pathways during early stage breast cancer treatment with combination cell cycle (CDK) and endocrine signaling inhibitors [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr SP012.
Abstract SP121: Personalized treatment for early stage HER2-positive breast cancer
Authors: Prat A
Published: February 2021

In my presentation, I will review the main clinical questions to be addressed in early-stage HER2+ disease, including the latest results from clinical trials as well as biomarker studies. Overall, the objective of my presentation is to dissect how personalized treatment of HER2+ early breast cancer has evolved in the last decade, and how is becoming a reality in particular settings, such as residual disease following standard neoadjuvant anti-HER2 therapies or in stage 1 disease. Moreover, I will discuss how the field is evolving to improve personalization of therapies and/or approaches even more in the upcoming years.

Citation Format: A Prat. Personalized treatment for early stage HER2-positive breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr SP121.
Abstract SP143: Advancing Cancer Research During Challenging Times
Authors: Sharpless N
Published: February 2021

The impact of the COVID-19 pandemic on care for people with cancer and the conduct of cancer research have been significant and will be evident for many years to come. While the National Cancer Institute (NCI) has brought to bear considerable expertise and capabilities to respond to the pandemic, our top priority remains advancing cancer research. The NCI budget, activities in response to the pandemic, breast cancer research advances, and the vision for cancer clinical trials will be discussed.

Citation Format: N Sharpless. Advancing Cancer Research During Challenging Times [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr SP143.
Abstract SP147: Aging
Authors: Stratton M
Published: February 2021

As for most human cancer types we now have substantial understanding of the landscape of somatic mutations in breast cancer. However, there is relatively little knowledge of the somatic mutations present in normal breast epithelium. This may potentially be instructive in identifying the earliest stages of breast neoplasia and in understanding why the risk of breast cancer is high compared to other tissues of the body. By sequencing laser capture microdissected elements of normal breast epithelium from healthy women, women with breast cancer and women with breast cancer predisposition we are able to provide the first comprehensive insights into somatic mutagenesis in normal breast and compare these with other normal human tissues.

Citation Format: M Stratton. Aging [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr SP147.
Abstract SP020: Beyond Hormones: Newer Pharmacologic Approaches
Authors: Brown P
Published: February 2021

It is now possible to prevent many breast cancers inhigh-risk women using anti-estrogen hormonal drugs. Several Phase III breast cancer preventiontrials demonstrated that hormonal drugs such as the “selective estrogenreceptor modulators” tamoxifen and raloxifene, and aromatase inhibitors preventthe development of 50% of ER-positive breast cancers in women. However, mostwomen at high risk of breast cancer do not use these cancer preventive drugsdue to concerns about their side effects. To overcome this problem, recent studies havefocused on testing novel approaches for the prevention of breast cancer. Results of preclinical and clinical studiestesting targeted drugs and vaccines for breast cancer prevention show that itis possible to prevent breast cancer with reduced toxicity. Studies seeking to prevent all forms ofbreast cancer, including ER-positive, HER2-positive, and “triple-negative”breast cancer, will be presented and discussed. Novel approaches testing targeted therapies including signalinginhibitors, combinations of preventive agents, and vaccines, will be presented. Many of these interventions prevent breastcancer in animal models, and are now being tested in human clinicaltrials. Results from studies testing novel drugdelivery approaches will also be discussed. Topical gels containing anti-estrogen drugs are being used to reducebreast cell growth and mammographic density in Phase II clinical trials. This topical approach has the potential toprevent ER-positive breast cancers without the toxicity of oral hormonaldrugs. All of these novel preventive measuresoffer great promise to effectively prevent all forms of breast cancer withminimal toxicity.

Citation Format: P Brown. Beyond Hormones: Newer Pharmacologic Approaches [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr SP020.
Abstract SP022: Special topics in early stage ER+ breast cancer
Authors: Cameron D
Published: February 2021

ER+ve HER2-ve breast cancer, also known as luminal breast cancer, is the commonest form of early breast cancer, and the commonest cause of breast cancer death. It is defined pathologically in terms of significant levels of expressesion of hormone receptors without over-amplified HER2: but like all other subtypes of breast cancer is not just one disease. The majority of these tumours are sensitive to endocrine therapy, and also benefit from the other standard interventions, such as chemotherapy, surgery, radiotherapy and the use of bisphosphonates: all of the curative benefits of these treatments (bar surgery) having been confirmed in individual patient meta-analyses. So what is there to say apart from exploring the mechanisms of resistance to therapy and the biologically-driven new therapeutic approaches which will be covered by the two other speakers in this session? Firstly, a review of these important data: exploration of the key questions such as choice of, and duration of, adjuvant endocrine therapy in both pre- and post-menopausal women (and in brief, men); discussion of the pattern of relapse including the almost linear risk of relapse per year for at least 10 years (unlike other subtypes of breast cancer), and the implications of that pattern for patients, clinicians and trialists. In particular the presenter will consider the SOFT/TEXT studies, the data from the meta-analyses of the adjuvant endocrine and bisphosphonate therapy studies and the very significant issues of adherence and toxicity for women. Secondly a brief look at the data on bio-markers used to suggest certain cancers don’t benefit from the use of adjuvant chemotherapy, noting the distinction between prognostic and predictive, and the challenge at times of separating these effects in women with a good prognosis, and can thus be used to offer women the possibility of avoiding chemotherapy. How to approach the pre-menopausal woman to maximise her chance of cure whilst making life tolerable and helping her “normalise” any plans she may have to have children. Third, looking at the newer therapies entering clinical trials, and in particular consideration of the emerging data on the use of CDK 4/6i in early breast cancer and what this may mean for both clinical trial design and clinical practice. But perhaps most importantly, this talk will identify pitfalls in interpretation of data, the need for long-term outcome data to truly understand what trials tell us, and what they don’t: and pointers to the future of where we may be able to further improve the lot of women with the commonest and ultimately most fatal of the main breast cancer subtypes.

Citation Format: D Cameron. Special topics in early stage ER+ breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr SP022.
Abstract SP037: New insights to cancer-associated systemic inflammation
Authors: de Visser KE
Published: February 2021

The occurrence of distant metastases accounts for over 90% of breast cancer deaths. Despite these devastating effects, metastatic disease is poorly understood and incurable. Clearly, there is an urgent need for novel therapeutic strategies that prevent and/or cure metastatic disease. For successful dissemination and metastasis, cancer cells must evade detection and destruction by the immune system and adapt to a foreign tissue environment. This process is enabled by factors secreted by the primary tumor that shape both the intratumoral microenvironment and the systemic immune landscape. By manipulating systemic immune responses and creating conditions of chronic inflammation, tumors can have a long-distance reach and transform distant tissues that are intrinsically hostile to metastatic colonization into niches that are more hospitable for metastatic lesions to grow out. Key feature of this systemic process - often referred to as pre-metastatic niche formation- is the mobilization and polarization of (immature) myeloid immune cells from the bone marrow to the circulation, tumor and distant organs. We and others have used preclinical tumor models to demonstrate that these tumor-mobilized myeloid cells, including neutrophils and macrophages, contribute to a systemic immunosuppressive environment that inhibits anti-tumor immune responses and fosters metastasis formation. The pro-metastatic function of systemic inflammation is supported by clinical observations demonstrating that neutrophil accumulation in blood of cancer patients is strongly associated with poor survival and increased risk for metastasis. Targeting pro-metastatic inflammation represents an attractive strategy to prevent or treat metastatic disease. Importantly, the oncology field can benefit from compounds that have already been developed for the treatment of inflammatory diseases.

In this Educational Session talk, I will discuss current insights into how tumors engage the immune system systemically, how systemic inflammation impacts disease progression and therapy response and how we can utilize these insights for the design of novel therapeutic opportunities. A great challenge in the field of immuno-oncology is the unexplained inter-patient heterogeneity in the intratumoral and systemic composition and functional state of the immune system. I will share some of our recent insights into how cancer cell-intrinsic mechanisms lie at the basis of this heterogeneity in the immune milieu of breast cancer, which may set the stage for personalized immune-intervention strategies.

Citation Format: KE de Visser. New insights to cancer-associated systemic inflammation [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr SP037.
Abstract SP059: Toxicities of breast cancer treatment
Authors: Henry N
Published: February 2021

Advances in screening and treatment of breast cancer have led to reductions in breast cancer recurrence and mortality. However, systemic therapies can cause long-term and late effects that negatively impact the quality of life of patients with breast cancer. It is important for patients to be aware of the potential risks, and for providers to be knowledgeable about symptom management options. For example, taxane chemotherapies reduce the risk of disease recurrence but can cause long-lasting neuropathy that interferes with activities of daily living. Unfortunately, few effective interventions for preventing or treating neuropathy have thus far been identified. Similarly, endocrine therapies significantly reduce the risk of recurrence of hormone receptor positive breast cancer. However, tamoxifen and the aromatase inhibitors can cause menopausal symptoms and arthralgias that affect survivors of breast cancer of all ages. Interventions that can effectively treat these symptoms in some, but not all, patients have been identified. In this educational session, prevention and treatment approaches for key long-term and late effects in patients with breast cancer will be discussed.

Citation Format: N Henry. Toxicities of breast cancer treatment [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr SP059.
Abstract SP068: The unique epigenetic state of invasive lobular breast cancers
Authors: Jeselsohn R
Published: February 2021

Although the majority of invasive lobular breast cancers (ILC) are strongly hormone receptor positive and are rarely high-grade, they present a number of unique clinical problems compared with invasive ductal cancer (IDC). These include challenges for early detection, decreased response to chemotherapy and evidence of relative resistance specifically to adjuvant tamoxifen treatment. In addition to uniform loss of e-cadherin, ILCs possess genetic alterations that are suggestive of a unique estrogen receptor axis, including an increase in the frequency of FOXA1 mutations and decrease in GATA3 mutations. In this study we performed a comprehensive analysis of the estrogen receptor axis in pre-clinical models and clinical samples of ILC and IDC. We found that ILC has a unique chromatin state that stems from gained FOXA1 chromatin binding and leads the remodeling of ER chromatin binding. We demonstrated that FOXA1 recruitment can classify primary hormone receptor positive breast cancers to ILC and IDC histological subtypes. Moreover, we show that gained FOXA1 recruitment leads to the transcription of a gene signature associated with resistance to adjuvant tamoxifen in estrogen receptor positive breast cancers and is a mechanism for the divergent pattern of response to specific endocrine treatments in ILC. Collectively, these studies unveil key insights to the fundamental biology unique to ILC, set the stage for precision endocrine treatment in estrogen receptor positive breast cancer, and offer potential treatment targets to improve outcomes for patients with ILC.

Citation Format: R Jeselsohn. The unique epigenetic state of invasive lobular breast cancers [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr SP068.
Abstract SS2-03: Patterns of medical behavior in the management of breast cancer during COVID-19. Mexican Experienc
Authors: Valencia Ricardo Villalobos , Rivera Samuel Rivera
Published: February 2021

Objective. This survey was conducted with medical oncologists treating breast cancer and explores how the COVID-19 pandemic has impacted their approach to managing breast cancer.Method. A questionnaire of ten questions was sent electronically to 123 medical oncologists throughout the Mexican Republic from June 25 to 29, 2020, a critical moment in our patient with the highest reports of new cases of patients with COVID-19.Results. Of the respondents, 47.1% work in a public and private hospital, 21.9% and 30.0% exclusively in the public and private respectively. Modification of treatment schemes due to the pandemic is reported in 42.5% (51) and 34.1% (41) occasionally. The dose modification has occurred mainly in the palliative context 71.3%. The modification of intravenous to oral chemotherapy was confirmed in 78.2% of the respondents, but this was in less than 30% of the patients. Only 27.1% of doctors have prolonged their chemotherapy schedules. To the question of postponing visits in patients under surveillance or in adjuvant with endocrine therapy, 80% of the doctors answered confirmatory. Private online consultation has been implemented in 57.8% of doctors. When asked to have patients with breast cancer and a positive test for COVID-19, 37% (43 doctors) confirmed having had patients. Delays in diagnostic protocols for breast cancer were reported in 74.5% (85). Finally 37.7% reported that less than 25% of their patients did not attend their scheduled appointment and 32.4% of the doctors reported that between 25% to 50% of their patients postponed the medical visit. (See images of results).Conclusion. In Mexico, like many countries, the treatment and follow-up of patients with breast cancer has been affected by the pandemic, a factor that impacts the results is that in our country we have a shortage of oncological drugs for more than a year, including sometimes cyclophosphamide, anthracyclines and taxanes that are essential for this disease. Management and diagnosis protocols have been delayed since medical care has been prioritized for patients with COVID-19. Unfortunately, there is no national registry of cancer patients, much less the association of cancer with COVID-19. The study, however, reflects similarity of results with other countries in medical behavior.

Citation Format: Ricardo Villalobos Valencia, Samuel Rivera Rivera. Patterns of medical behavior in the management of breast cancer during COVID-19. Mexican Experienc [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr SS2-03.
Monitoring Ponatinib in a Child with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia
Authors: Tanimura Kazuki , Yamasaki Kai , Okuhiro Yuki , Hira Kota , Nitani Chika , Okada Keiko , Fujisaki Hiroyuki , Matsumoto Kana , Hara Junichi
Published: February 2021

Ponatinib is a third-generation tyrosine kinase inhibitor (TKI) reported to show a higher efficacy for adult Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) than other TKIs. However, few studies describe ponatinib for pediatric Ph+ALL; therefore, the efficacy, safety, and optimal dosage have not been determined. Here, we report a 3-year-old girl with Ph+ALL treated by a ponatinib-containing regimen with therapeutic drug monitoring in the plasma and cerebrospinal fluid (CSF). In our case, a ponatinib-containing regimen was able to keep minimal residual disease negative, and the pharmacokinetics (PKs) of plasma ponatinib resembled that previously reported in adults. Penetration to the CSF was extremely limited. Thus, ponatinib was feasible and effective for a child with Ph+ALL, although the plasma concentration of ponatinib varied significantly throughout the treatment. The appropriate dosage should be confirmed in a prospective trial, including a detailed PK study.
A 56-Year-Old Woman with Recurrent Strokes: A Clear Case with a Therapeutic Dilemma
Authors: Miller Eric S. , Hussein Haitham M. , Gertner Elie
Published: February 2021

A 56-year-old woman with a history of cerebral amyloid angiopathy (CAA) complicated by prior intracranial hemorrhage (ICH) was evaluated for an asymptomatic ischemic stroke discovered on screening brain MRI. On echocardiogram, she was found to have a mass on her mitral valve and strongly positive antiphospholipid antibodies. She was diagnosed with nonbacterial thrombotic (Libman-Sacks) endocarditis associated with the primary antiphospholipid syndrome (APS). The treatment decision was complicated by the history of CAA with ICH within the last year with very high risk for bleeding complications if on anticoagulation. A multidisciplinary decision was made to initiate a trial of warfarin for 3 months. She fared well and warfarin was continued. She has not had any further bleeding or ischemic events over the subsequent 1.5 years and remains on warfarin for her APS.
BUB1B Overexpression Is an Independent Prognostic Marker and Associated with CD44, p53, and PD-L1 in Renal Cell Carcinoma
Authors: Sekino Yohei , Han Xiangrui , Kobayashi Go , Babasaki Takashi , Miyamoto Shunsuke , Kobatake Kohei , Kitano Hiroyuki , Ikeda Kenichiro , Goto Keisuke , Inoue Shogo , Hayashi Tetsutaro , Teishima Jun , Sakamoto Naoya , Sentani Kazuhiro , Oue Naohide , Yasui Wataru , Matsubara Akio
Published: February 2021

Introduction: BUB1 mitotic checkpoint serine/threonine kinase B encoded by BUB1B gene is a member of the spindle assembly checkpoint family. Several reports have demonstrated that overexpression of BUB1B is associated with cancer progression and prognosis. Objective: This study aims to clarify the expression and function of BUB1B in renal cell carcinoma (RCC). Methods: The expression of BUB1B was determined using immunohistochemistry and bioinformatics analysis in RCC. The effects of BUB1B knockdown on cell growth and invasion were evaluated. We analyzed the interaction between BUB1B, cancer stem cell markers, p53, and PD-L1 in RCC. Results: In 121 cases of RCC, immunohistochemistry showed that 30 (25%) of the RCC cases were positive for BUB1B. High BUB1B expression was significantly correlated with high nuclear grade, T stage, and M stage. A Kaplan-Meier analysis showed that the high expression of BUB1B was associated with poor overall survival after nephrectomy. High BUB1B expression was associated with CD44, p53, and PD-L1 in RCC. Knockdown of BUB1B suppressed cell growth and invasion in RCC cell lines. Knockdown of BUB1B also suppressed the expression of CD44 and increased the expression of phospho-p53 (Ser15). In silico analysis showed that BUB1B was associated with inflamed CD8+, exhausted T-cell signature, IFN-γ signature, and the response to nivolumab. Conclusion: These results suggest that BUB1B plays an oncogenic role and may be a promising predictive biomarker for survival in RCC.
Pru p 3 Sublingual Immunotherapy in Patients with Lipid Transfer Protein Syndrome: Is It Worth?
Authors: Beitia Juan María , Vega Castro Arantza , Cárdenas Remedios , Peña-Arellano Maria Isabel
Published: February 2021

Background: Lipid transfer proteins (LTPs) syndrome is an important cause of multiple plant food allergy in the Mediterranean area. The effectiveness of sublingual immunotherapy (SLIT) with the LTP Pru p 3 extract has been little investigated in the real-world setting. This study aimed to investigate the outcome of Pru p 3 SLIT in real-life patients with LTP syndrome with/without concurrent reactions to peanut and/or nuts. Methods: This was a prospective real-life study including all patients diagnosed with LTP allergy and treated with Pru p 3 SLIT between 2011 and 2018 in a tertiary hospital in Spain. Patients underwent open oral food challenge (OFC) tests for unpeeled peach and nuts/peanuts 1 year after the treatment started to assess food tolerance. A control group of patients diagnosed with LTP allergy who refused treatment with immunotherapy were included. Severity of symptoms and diet avoidance was recorded in both groups. Results: Twenty-nine patients with a median age of 24.7 years (range 5.5–43.1) were included: 100% were allergic to fruit; 72%, to peanut and/or nuts; 19 had a history of severe systemic reactions. Seven patients discontinued therapy; 3 (10%), due to adverse events. One year after SLIT start, 16 (73%) patients had negative OFC to peach; 95%, after 2 years; 69% had negative OFC to nuts/peanuts. The control group included 13 patients: 53.8% experienced reactions with new foods; severity of symptoms increased significantly (p < 0.001), and diet restrictions were maintained in this group. Conclusions: SLIT with Pru p 3 shows a good safety profile, and avoid dietary restrictions in patients with LTP syndrome treated in the real-life setting.
CD34-Positive Blast Count and p53 Expression in Bone Marrow Biopsies of Patients with Low-Risk Myelodysplastic Syndromes: Potential Predictive Tools of Response to Erythropoietin Stimulating Agents
Authors: Boggio Francesca , Del Gobbo Alessandro , Barella Marco , Croci Giorgio , Cassin Ramona , Reda Gianluigi , Pettine Loredana , Bandiera Laura , Bonoldi Emanuela , Riva Marta , Gianelli Umberto
Published: February 2021

Introduction: The first-line therapy for patients with low-risk myelodysplastic syndromes (MDSs) commonly consists of erythropoietin stimulating agents (ESAs), with a response rate ranging from 34 to 62%. For nonresponder patients, outside clinical trials, blood transfusions are the most frequent therapeutic option, with detrimental effect on the quality of life and with risks of iron-overload. Since no studies have been yet conducted on this topic, we investigated the potential predictive role of bone marrow (BM) histological evaluation in patients treated with ESAs. Materials and Methods: We performed a morphological and immunohistochemical retrospective analysis of BM biopsies of 96 patients with low-risk MDSs subsequently treated with ESAs. Results: In our series, substantial morphological overlap was found between responder and nonresponder patients. On the contrary, patients with a percentage of CD34-positive blasts >3% or with p53 protein expression <1% responded with a significantly higher frequency to ESAs. Conclusions: Our study reinforces the role of BM biopsy as diagnostic tool in MDSs, being also able to supply information related to response to ESAs and to its loss over time.
The Impact of Shampoo Wash Frequency on Scalp and Hair Conditions
Authors: Punyani Supriya , Tosti Antonella , Hordinsky Maria , Yeomans Dawn , Schwartz James
Published: February 2021

Background: How frequently should the scalp and hair be cleansed? A dearth of objective data has led to confusion both among lay people and experts. Each extreme has potential detrimental effects: overcleaning may lead to surface damage while undercleaning may lead to buildup of harmful stimuli. This situation is complicated because both objective and subjective criteria are relevant to assess optimal cleaning. Objectives: The objective of this work was to combine epidemiological and treatment data with both objective and subjective end points to yield clear data to guide both the consumer and expert as to optimal scalp and hair cleaning practices. Methods: Two studies were conducted with Asian populations without any specific scalp pathologies. An epidemiological study was conducted as a function of natural wash frequency. This was combined with a controlled wash frequency study. In both cases, objective measures of hair and scalp condition were assessed. These were combined with self-assessments of all participants. Results: In the epidemiological study, it was observed that overall satisfaction with hair and scalp condition was achieved when washing 5–6 times per week. This was consistent for both objective and subjective end points. Controlled treatment likewise showed that a daily wash regimen was superior to once per week cleansing for all end points. No objective detrimental effects to hair at this level of cleansing were observed. Conclusions: Two different studies led to the same conclusion: higher wash frequency is both beneficial and more preferred to lower wash frequency among the Asian populations studied. Concerns related to “overcleaning” were unfounded both objectively and subjectively.
Role of Upper Respiratory Microbiota and Virome in Childhood Rhinitis and Wheeze: Collegium Internationale Allergologicum Update 2021
Authors: Tay Carina Jing Xuan , Ta Le Duc Huy , Ow Yeong Yu Xiang , Yap Gaik Chin , Chu Justin Jang Hann , Lee Bee Wah , Tham Elizabeth Huiwen
Published: February 2021

There is emerging evidence that the respiratory microbiota influences airway health, and there has been intense research interest in its role in respiratory infections and allergic airway disorders. This review aims to summarize current knowledge of nasal microbiome and virome and their associations with childhood rhinitis and wheeze. The healthy infant nasal microbiome is dominated by Corynebacteriaceae and Staphylococcaceae. In contrast, infants who subsequently develop respiratory disorders are depleted of these microbes and are instead enriched with Proteobacteria spp. Although human rhinovirus and human respiratory syncytial virus are well-documented major viral pathogens that trigger rhinitis and wheezing disorders in infants, recent limited data indicate that bacteriophages may have a role in respiratory health. Future work investigating the interplay between commensal microbiota, virome, and host immunological responses is an important step toward understanding the dynamics of the nasal community in order to develop a strategical approach to combat these common childhood respiratory disorders.
CSF Oculorrhea Presenting as “Tearing” following the Repair of Fronto-Ethmoidal Encephalocele
Authors: Goyal Nishant , Patil Aditya , Vathulya Madhubari , Kumawat Devesh , Bhatia Riti , Agrawal Sanjay
Published: February 2021

Introduction: Cerebrospinal fluid (CSF) oculorrhea is extremely rare, and very few cases have been reported mostly following trauma. There is only 1 case in the published literature where oculorrhea occurred following the repair of fronto-nasal encephalocele. Case Description: A six-year-old girl presented with gradually increasing fronto-ethmoidal encephalocele with secondary papulo-nodular changes. She underwent bi-frontal craniotomy with excision of encephalocele sac and herniated gliotic brain followed by dural closure using peri-cranial graft. One month later, she presented again with swelling over the operative site and “tearing” from both her eyes. She was diagnosed with CSF oculorrhea. After failing conservative management, lumbar drain was inserted and kept on continuous drainage. Oculorrhea stopped with lumbar drain but restarted with its removal. Therefore, theco-peritoneal shunt was placed, following which oculorrhea stopped. She is doing well at 5 months’ follow-up. Conclusion: CSF oculorrhea must be considered by the pediatric neurosurgeons in any patient who presents with “tearing” following the repair of an anterior encephalocele.