bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P3-03-22: Use of 64Cu-DOTA trastuzumab positron emission tomography to predict pathologic complete response in locally advanced HER2 positive breast cancer
Authors: Mortimer Joanne , Rockne Russell , Liu Jessica , Yuan Yuan , Stewart Daphne , Waisman James , Frankel Paul , Kruper Laura , Adhikarla Vikram 
Published: March 2022

Abstract
Use of 64Cu-DOTA trastuzumab Positron Emission Tomography to predict pathologic complete response in locally advanced HER2 positive breast cancer. Background: We have demonstrated that 64Cu-DOTA trastuzumab is an effective PET imaging agent of HER2 positive breast cancer and correlated with HER2 status by IHC. Methods: Patients with locally advanced breast cancer were eligible if they had biopsy confirmed HER2 + disease, locally advanced disease and were to be treated with neoadjuvant therapy. Pretreatment staging included a breast MRI, 18F-FDG-PET/CT and 64Cu-trastuzumab-PET/CT (64CuT-PET). Prior to injection of 64Cu-trastuzumab, patients received 50 mg of cold trastuzumab per our previously established protocol. 64CuT-PET was obtained at 21-25 h over fields of view chosen in reference to MRI. Uptake in lesions was measured in terms of body wt-normalized SUV. Lesions with intensity &gt; adjacent tissue were considered positive on PET. Breast MRI was obtained after 4 cycles of chemotherapy and preoperatively. Response to therapy was determined on the surgical specimen. Results: Eighteen women have completed study and are evaluable for treatment response. The median age was 56 years (Range 32-62); 5 were ER- and PR-; 13 ER+/- PR+. One patient had increased 64CuT-PET uptake at T4 which was not appreciated on conventional imaging and subsequent biopsy confirmed metastatic disease. She is included in the analysis as she ultimately underwent surgical management of the breast. Complete pathologic response was seen in 14/18 patients - 11/14 ER+/- PR + and 3/4 ER-/PR-. Four patient had residual disease at surgery; 3 of 4 were HER2 negative and 1 was HER2+. Uptake on 64CuT-PET correlated with increased uptake on 18F-FDG-PET. The ratio of 64CuT-PET: 18F-FDG-PET ≥ 0.7 was associated with complete pathologic response at surgery.Conclusions: The ratio of 64CuT-PET to 18F-FDG-PET ≥ 0.7 was associated with complete pathologic response in women undergoing neoadjuvant chemotherapy for locally advanced HER2+ breast cancer. Residual disease after HER2-directed therapy was frequently HER2 negative.
Citation Format: Joanne Mortimer, Russell Rockne, Jessica Liu, Yuan Yuan, Daphne Stewart, James Waisman, Paul Frankel, Laura Kruper, Vikram Adhikarla. Use of 64Cu-DOTA trastuzumab positron emission tomography to predict pathologic complete response in locally advanced HER2 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 P3-03-22.
Abstract P3-05-04: The histone demethylase hairless functions as a tumor suppressor gene in breast cancer development
Authors: Liu Liang , Shen Yao , Singh Jasvinder , Sah Bindy , Chen Zhongming , Henzler Christine , Ha Wootae , Su Tao , Hibshoosh Hanina 
Published: March 2022

Abstract
The hairless (HR) gene encodes a transcription factor with histone demethylase activity that is essential for development and tissue homeostasis. Previous studies suggest that HR possesses antitumor activity in skin cancer models. Surveying human cancer genomics datasets identified frequent HR missense mutations or deletions in various human malignancies including breast cancers, suggesting that HR might function as a tumor suppressor in cancer development. By targeted sequencing, we identified HR mutations in approximately 29% of human breast cancer tissues (n=85), compared to 33% for BRCA2 and 17% for BRCA1 in the same sample cohort. Digital PCR assays also revealed frequent HR copy number loss across breast cancer subtypes. To further define HR’s putative tumor suppressor function in breast cancer and its mechanism of action, we reconstituted HR expression in HR-deficient human breast cancer cells. HR re-expression significantly suppressed tumor growth and metastasis in orthotopic xenograft mouse models. This antitumor activity of HR in breast cancer cells was partly associated with transcriptional activation of the CELF2 tumor suppressor gene, a new HR-regulated gene identified by RNA-seq studies. Consistent with HR’s H3K9 demethylase activity, pharmacological inhibition of H3K9 methylation inhibited HR-deficient breast cancer cell proliferation and migration. Taken together, these studies demonstrate that HR is a novel tumor suppressor, and pharmacological inhibition of H3K9 methylation may be explored to reduce HR-deficient breast cancer cell growth and survival. methylation inhibited HR-deficient breast cancer cell proliferation and migration in vitro, and tumor growth and metastasis in xenograft models. Taken together, these studies suggest that HR is a novel tumor suppressor, and pharmacological inhibition of H3K9 methylation may be explored to treat HR-deficient breast cancers.
Citation Format: Liang Liu, Yao Shen, Jasvinder Singh, Bindy Sah, Zhongming Chen, Christine Henzler, Wootae Ha, Tao Su, Hanina Hibshoosh. The histone demethylase hairless functions as a tumor suppressor gene in breast cancer development [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-05-04.
Abstract P3-09-01: A ubiquitination cascade regulating the integrated stress response and survival in carcinomas
Authors: Cervia Lisa D , Shibue Tsukasa , Gaeta Benjamin , Borah Ashir A , Leung Lisa , Li Naomi , Dumont Nancy , Gonzalez Alfredo , Bick Nolan , Kazachkova Mariya , Dempster Joshua M , Krill-Burger John M , Piccioni Federica , Udeshi Namrata D , Olive Meagan E , Carr Steven A , Root David E , McFarland James M , Vazquez Francisca , Hahn William C 
Published: March 2022

Abstract
Targeting of mutated oncogenes has led to the identification of new targeted therapies. However, druggable oncogenes do not occur in most cancers. Systematic identification of signaling pathways required for the fitness of cancer cells will facilitate the development of new cancer therapies. We used gene essentiality measurements in 793 cancer cell lines to identify selective co-essentiality modules and found that a ubiquitination ligase complex composed of UBA6, BIRC6, KCMF1 and UBR4, which encode an E1, E2 and two heterodimeric E3 subunits, respectively, is required for the survival of a subset of epithelial tumors, particularly subtypes of breast cancer. Suppressing BIRC6 in cell lines that are dependent on this complex led to a substantial reduction in cell fitness in vitro and potent tumor regression in vivo. Mechanistically, BIRC6 suppression resulted in selective activation of the integrated stress response (ISR) by stabilization and upregulation of the heme-regulated inhibitor (HRI), a direct ubiquitination target of the UBA6/BIRC6/KCMF1/UBR4 complex. These observations uncover a novel ubiquitination cascade that regulates ISR and highlight the potential of ISR activation as a new therapeutic strategy.
Citation Format: Lisa D Cervia, Tsukasa Shibue, Benjamin Gaeta, Ashir A Borah, Lisa Leung, Naomi Li, Nancy Dumont, Alfredo Gonzalez, Nolan Bick, Mariya Kazachkova, Joshua M Dempster, John M Krill-Burger, Federica Piccioni, Namrata D Udeshi, Meagan E Olive, Steven A Carr, David E Root, James M McFarland, Francisca Vazquez, William C Hahn. A ubiquitination cascade regulating the integrated stress response and survival in carcinomas [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-09-01.
Abstract P3-12-03: Pre-diagnostic plasma 25-hydroxyvitamin D and mortality among women with breast cancer in the nurses’ health study cohorts
Authors: Holder Etienne 
Published: March 2022

Abstract
Background: Sufficient levels of vitamin D are critical for optimal health. 25-hydroxyvitamin D (25(OH)D) is an essential steroid hormone, derived from sun exposure, diet, and supplement use, that is hypothesized to influence breast cancer prognosis by inhibiting breast tumor growth. While this has been observed in laboratory-based studies, findings from observational studies are inconclusive. We examined the association between pre-diagnostic 25(OH)D concentrations and both breast cancer-specific and overall mortality to explore the potential effects of vitamin D, a modifiable exposure. Methods: We evaluated the association between pre-diagnostic plasma 25(OH)D concentrations and breast cancer-specific and total mortality among 1,300 women diagnosed with invasive, non-metastatic breast cancer enrolled in the Nurses’ Health Study 1 (NHS1) and Nurses’ Health Study 2 (NHS2) cohorts. In this analysis, women provided a blood sample from 1989-1990 and a second blood sample in 2000-2001 (NHS1) or a blood sample from 1996-1999 (NHS2). Women were diagnosed with breast cancer after blood collection up through 2016 (NHS1) and 2017 (NHS2) and censored at end of study (2016 NHS1; 2017 NHS2) or death, whichever came first. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (95%CI) for mortality after adjustment for tumor characteristics, type of cancer treatment, and lifestyle factors. For women with two blood samples, most recent exposure status was used in the analyses. Results: A total of 396 total deaths and 145 breast cancer-specific deaths occurred during follow-up through 2017. We observed a non-statistically significant 25% lower breast cancer-specific mortality rate among those with the highest, versus lowest, quartile of pre-diagnostic 25(OH)D levels (HRQ4vsQ1 0.75, 95%CI 0.45-1.25; p for trend=0.32), that did not vary significantly by estrogen receptor status of the tumor (p for interaction=0.61). Women in the highest vs. lowest quartile of plasma 25(OH)D experienced a 31% lower overall mortality rate (HRQ4vsQ1 0.69, 95%CI 0.51-0.93; p for trend=0.03). In cause-specific mortality analyses among non-breast cancer deaths, non-statistically significant decreases were observed for other cancer deaths and cardiovascular disease deaths. Conclusion: Pre-diagnostic plasma 25(OH)D levels were not significantly associated with lower breast cancer-specific mortality among women with breast cancer. However, significant inverse associations were observed for total mortality, which supports a potential benefit of vitamin D among these women.
Citation Format: Etienne Holder. Pre-diagnostic plasma 25-hydroxyvitamin D and mortality among women with breast cancer in the nurses’ health study cohorts [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-12-03.
Abstract P3-12-14: Attenuated negative prognostic effect of progesterone receptor negativity in postmenopausal ER+ breast cancer with normal BMI (&lt;25): A nation-wide study in Korean Breast Cancer Society and the institutional cohort
Authors: Bae Soong June , Hwang Jawon , Lee Janghee , Ji Jung Hwan , Chu Chihhao , Kim Jee Hung , Ahn Sung Gwe , Jeong Joon 
Published: March 2022

Abstract
Purpose Loss of progesterone receptor (PR) expression is a poor prognostic factor in ER+/HER2- breast cancer. A growing body of evidence suggests that PR expression is affected by endogenous estrogen level and modulated by body mass index (BMI). Using Korean Breast Cancer Society Registry (KBCSR) and institutional database, we evaluated survival outcome by PR expression in the postmenopausal groups stratified by BMI. Moreover, we investigated 21-gene recurrence score to assess intrinsic tumor biology. Method Data from the KBCSR for patients diagnosed with invasive breast cancer when aged over 50 years were reviewed, and 33,314 with BMI were included. Of these, we investigated overall survival (OS) of women at age of 60 and older with a median follow-up of 56 months (n=9,492). In the institutional cohort with ER+HER2- breast cancer women at age of 50 and older (n=703), the landmark survival analyses were performed to address the 5-years recurrence-free survival (RFS). In the subset of the institutional cohort, 21-gene recurrence scores were identified in individuals (n=470). Normal weight is defined as BMI less than 25kg/m2. Result Among the postmenopausal women from the KBCSR, the PR- was significantly associated with adverse OS (hazard ratio [HR], 1.39; 95% CI, 1.16-1.67; p&lt;0.001) in high BMI group (≥25) whereas in normal BMI group (&lt;25) did not (HR, 1.07; 95% CI, 0.89-1.29; p=0.498) (interaction p=0.046). In the institutional cohort with ER+/HER2- postmenopausal women (age&gt;50), RFS was superior in the PR+ than in the PR- in the postmenopausal with high BMI (≥25). In contrast, RFS was not separated by PR in the normal BMI group (&lt;25). When we compared the 21-gene recurrence score according to PR, the scores were significantly lower in the PR+ than in the PR- regardless of BMI. Conclusion In ER+/HER2- aged postmenopausal breast cancer women with normal BMI who have low estrogen environment, negative prognostic effect of absence of PR expression is attenuated. Bad tumor biology of PR- cancer is conserved irrespective of BMI. We support the hypothesis that weight control to reduce endogenous estrogen produced by adipose tissue is beneficial for postmenopausal women with ER+ breast cancer.
Citation Format: Soong June Bae, Jawon Hwang, Janghee Lee, Jung Hwan Ji, Chihhao Chu, Jee Hung Kim, Sung Gwe Ahn, Joon Jeong. Attenuated negative prognostic effect of progesterone receptor negativity in postmenopausal ER+ breast cancer with normal BMI (&lt;25): A nation-wide study in Korean Breast Cancer Society and the institutional 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 P3-12-14.
Abstract P3-12-22: Socioeconomic position and prognosis in premenopausal breast cancer: A population-based cohort study in Denmark
Authors: Hjorth Cathrine , Damkier Per , Ejlertsen Bent , Lash Timothy L , Sørensen Henrik T , Cronin-Fenton Deirdre 
Published: March 2022

Abstract
Background: To investigate how socioeconomic position (SEP) influences the effectiveness of cancer-directed treatment in premenopausal breast cancer patients in terms of breast cancer recurrence and mortality.Methods: Our cohort included all premenopausal women aged 18-55 years diagnosed with non-metastatic breast cancer and prescribed docetaxel-based chemotherapy in Denmark during 2007-2011. Population-based administrative registries provided data on SEP: marital status (married including registered partnership or single including divorced or widowed), cohabitation (cohabiting or living alone), education (low, intermediate or high), income (low, medium or high), and employment status (employed, unemployed or health-related absenteeism). For each SEP measure, we computed incidence rates, cumulative incidence proportions (CIPs) and used Poisson regression to compute incidence rate ratios and 95% confidence intervals (95% CIs) of recurrence and death. We stratified on ER status/tamoxifen to evaluate interaction.Results: Our cohort included 2,616 women; 286 (CIP: 13%) experienced recurrence and 223 (CIP: 11%) died during follow-up (median 6.6 and 7.2 years, respectively). Single women had both increased risks of recurrence (IRR: 1.45, 95% CI: 1.11-1.89) and mortality (IRR: 1.83, 95% CI: 1.32-2.52). Furthermore, we observed increased mortality in women with low education (IRR: 1.49, 95% CI: 0.95-2.33), low income (IRR: 1.37, 95% CI: 0.83-2.28), unemployment (IRR: 1.61, 95% CI: 0.83-3.13) or health-related work absenteeism (IRR: 1.80, 95% CI: 1.14-2.82), but smaller or no increased risk of recurrence. These findings were especially evident among women with ER+ tumors prescribed tamoxifen.Conclusions: Low SEP in premenopausal women with non-metastatic breast cancer was associated with increased mortality, but not always recurrence. This suggests underdetection of recurrences in certain groups. Poor prognosis in women with low SEP, especially single women, may partly be explained by tamoxifen adherence.
Citation Format: Cathrine Hjorth, Per Damkier, Bent Ejlertsen, Timothy L Lash, Henrik T Sørensen, Deirdre Cronin-Fenton. Socioeconomic position and prognosis in premenopausal breast cancer: A population-based cohort study in Denmark [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-12-22.
Abstract P3-14-03: The DNA damage repair landscape in Black women with breast cancer
Authors: Mazumder Aloran , Jimenez Athena , Ellsworth Rachel E , George Sophia , Freedland Stephen J , Bainbridge Matthew N , Haricharan Svasti 
Published: March 2022

Abstract
Black women have 42% higher mortality rate from estrogen receptor positive (ER+) breast cancer than white women. Molecular mechanisms underlying worse outcome in black women are understudied. Recently, downregulation of specific DNA damage repair (DDR) genes was shown to causally induce resistance to standard care endocrine therapy by dysregulating cell cycle regulation, and to associate with poor outcome in white women with ER+ breast cancer. However, frequency and patterns of DDR dysregulation in Black women with ER+ breast cancer and impact on survival outcomes remains untested. By assessing RNA expression of 104 DDR genes across three tumor, and two normal breast, datasets, here, we map for the first time, global patterns of DDR gene expression regulation specific to Black women, both in tumors and in the normal breast. We identify a specific subset of 8 candidate DDR genes that are dysregulated at the RNA level in tumors from Black women. Of note, a novel DDR regulation signature where genes from the homologous recombination pathway are upregulated and genes from SSBR pathways (mainly base excision repair) are coincidently downregulated is almost uniquely detectable in tumors from Black women (8% incidence relative to 1% in tumors from white women, p=0.01). Moreover, this coincident DDR signature associates with dysregulated cell cycle gene expression (p&lt;0.001). In accordance, patients whose tumors demonstrate this coincident DDR signature also have significantly worse survival outcomes across datasets (hazard ratio of 9.5, p&lt;0.001). Overall, these results constitute the first systematic analysis of differences in DDR gene expression regulation between Black and white women and identify a specific DDR signature associated with poor outcome in tumors from Black women. These results provide new grounds for refining biomarker profiles and improving precision medicine for underserved populations.
Citation Format: Aloran Mazumder, Athena Jimenez, Rachel E Ellsworth, Sophia George, Stephen J Freedland, Matthew N Bainbridge, Svasti Haricharan. The DNA damage repair landscape in Black women with breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-14-03.
Abstract P3-14-04: Genetic testing in non-Hispanic Black women with breast cancer treated within an equal-access healthcare system
Authors: Ellsworth Rachel , Vargason Ashlee , Turner Clesson , Shriver Craig 
Published: March 2022

Abstract
Purpose: Identification of women with hereditary forms of cancer allows for use of precision medicine approaches to improve survival. Non-Hispanic Black (NHB) women in the US general population are less likely to undergo genetic testing or utilize risk-reducing strategies. Whether these disparities exist within the equal-access military healthcare system of the Department of Defense is not known. Methods: Genetic test information and surgical procedures were extracted for all NHB and Non-Hispanic Whites (NHW) with invasive breast cancer who were diagnosed and treated at the Murtha Cancer Center at Walter Reed National Military Medical Center and enrolled in the Clinical Breast Care Project. National Comprehensive Cancer Network criteria from the year of diagnosis were assessed for all patients. Data were analyzed using chi-square analysis with p&lt;0.05 defining significance. Results: NHB were significantly (p=0.009) more likely to meet criteria for genetic testing compared to NHW, however, test uptake did not differ significantly between populations (p=0.292). Pathogenic variant frequency (p=0.597), prophylactic mastectomy (p=0.915) and oophorectomy (p=0.076) did not differ significantly between populations. Conclusion: These data demonstrate that when barriers, such as cost and lack of insurance barriers were removed, NHB were as willing to pursue testing and risk-reducing strategies as their NHW counterparts. Increasing the availability of testing and clinical management for NHB with hereditary forms of cancer may help reduce disparate survival seen in the US general population. The contents of this publication are the sole responsibility of the author(s) and do not necessarily reflect the views, opinions or policies of Uniformed Services University of the Health Sciences (USUHS), The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., the Department of Defense (DoD) or the Departments of the Army, Navy, or Air Force. Mention of trade names, commercial products, or organizations does not imply endorsement by the U.S. Government.
Citation Format: Rachel Ellsworth, Ashlee Vargason, Clesson Turner, Craig Shriver. Genetic testing in non-Hispanic Black women with breast cancer treated within an equal-access healthcare system [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-14-04.