bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract PO2-08-05: ERBB2 mutated breast cancer detected by next generation sequencing: integrated analysis based on real-world data and The Cancer Genome Atlas
Authors: Kim Junghyun , Kook Yoonwon , Baek Seung Ho , Kim Min Ji , Moon Sohyun , Lee Seung Eun , Kim Jee Hung , Bae Soong June , Jeong Joon , Ahn Sung Gwe
Published: May 2024

Background ERBB2 mutation has been recognized as an actionable target for pan-HER tyrosine kinase inhibitors in the era of precision medicine for solid tumors. In our real-world cohort utilizing next-generation sequencing (NGS), we successfully identified cases of ERBB2-mutated breast cancer. Furthermore, we investigated the clinical and pathological characteristics of these cases by integrating our data with The Cancer Genome Atlas (TCGA). Methods Our real-world cohort with NGS included 423 breast cancer patients treated at Gangnam Severance Hospital in Seoul, Republic of Korea, between April 2017 and January 2023. Among these patients, 13 were confirmed to have ERBB2 mutation through NGS analysis. We also incorporated data from TCGA database, which included 818 cases with ERBB2 sequencing. We compared the clinical characteristics (age, sex, stage, and ER, PR, and HER2 status) between the two groups. Furthermore, we examined the frequency of two of the most common mutations, PIK3CA and TP53, in both groups. Additionally, we investigated the distribution of PAM50 subtypes in the TCGA cohort. Results This study analyzed a total of 1,244 cases with NGS data. Among these cases, 31 (2.5%) exhibited ERBB2 mutation, with 13 patients identified in our dataset and 18 in the TCGA data. Among the 31 cases with ERBB2 mutation, 21 (67.7%) had HER2-negative disease. No significant differences were observed in other clinical characteristics based on ERBB2 status. Within the group of 31 ERBB2-mutated cases, TP53 mutations were found in 12 cases (38.7%), while PIK3CA mutations were found in 12 cases (38.7%). In the TCGA dataset, 4 cases (22.2%) with ERBB2 mutation were classified as HER2-E subtype, and the rate of HER2-E subtype was significantly higher in the ERBB2-mutated group compared to the ERBB2-wild group (22.2% vs. 7.6%, p=0.024). Conversely, 14 cases (77.8%) with ERBB2 mutation exhibited a non-HER2 enriched subtype. Conclusions Consistent with previous knowledge, ERBB2 mutations can be detected in HER2-negative breast cancer, despite their rarity. Furthermore, a considerable proportion of ERBB2-mutated breast cancer may depend on various oncogenic signaling pathways other than the HER2 pathway. Further studies are warranted to optimize therapeutic strategies for ERBB2-mutated breast cancer.

Citation Format: Junghyun Kim, Yoonwon Kook, Seung Ho Baek, Min Ji Kim, Sohyun Moon, Seung Eun Lee, Jee Hung Kim, Soong June Bae, Joon Jeong, Sung Gwe Ahn. ERBB2 mutated breast cancer detected by next generation sequencing: integrated analysis based on real-world data and The Cancer Genome Atlas [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-08-05.
Abstract PO2-24-09: Prolonged Effects of Hypoxia in Luminal Breast Cancer Cells Promotes an Aggressive Phenotype
Authors: Moriarty Aidan , Iriondo Oihana , Mecenas Desirae , Li Yilin , Amzaleg Yonatan , Klotz Remi , Yu Min
Published: May 2024

Aidan Moriarty

Mentor: Dr. Min Yu Hypoxic Memory in Breast Cancer Cells Metastasis is the main cause of tumor-related mortality in breast cancer patients. Improving our understanding of the metastatic cascade is imperative to improve patient outcomes. Prior research indicates cancer cells with increased metastatic potential have acquired adaptive properties induced by factors in the tumor microenvironment (TME), including hypoxia. However, previous hypoxia research has been primarily focused on signaling changes that occur when cancer cells are in the hypoxic TME and does not account for long-term changes that may occur once cancer cells re-enter normoxia, such as when they metastasize. Our research in patient-derived circulating tumor cell (CTCs) lines and breast cancer cell lines has indicated that certain transcriptional changes are maintained after cells leave hypoxia, and that these post-hypoxic CTCs maintain a higher metastatic potential compared to cells not exposed to hypoxia. Taking an un-biased approach to define changes in hypoxia-exposed breast cancer cells upon reoxygenation, we performed bulk RNA-Seq on luminal breast cancer cell lines in various oxygen conditions over time. We found that a subset of genes that were differentially expressed in hypoxic conditions were maintained as up- or down-regulated after cells were reoxygenated, indicating a “hypoxic memory”. Additionally, a subset of genes were differentially expressed in the post-hypoxic cells compared to normoxia controls, demonstrating novel and prolonged gene expression changes induced by hypoxia exposure. We performed functional assays and observed that this post-hypoxic state is associated with a more aggressive phenotype in vitro. Current research in our lab is on-going to understand the epigenetic changes that may be responsible for this hypoxic memory to further understand the consequences of hypoxic memory in CTC biology and metastasis. Finally, we have designed a dual-reporter hypoxia-tracing system to validate our findings in vivo. This research will improve our understanding of the prolonged influence of hypoxia on metastatic potential in breast cancer cells and has the potential to inform future therapeutic strategies.

Citation Format: Aidan Moriarty, Oihana Iriondo, Desirae Mecenas, Yilin Li, Yonatan Amzaleg, Remi Klotz, Min Yu. Prolonged Effects of Hypoxia in Luminal Breast Cancer Cells Promotes an Aggressive Phenotype [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-24-09.
Abstract PO2-25-05: Spatial multiplexing of protein biomarkers for immune cell profiling of the tumor microenvironment with ChipCytometry
Authors: Berigan Benton
Published: May 2024

Understanding the spatial distribution of key immune cell populations is critical in advancing our understanding of cancer and the development of novel therapeutics. Historically, the spatial analysis of the tumor microenvironment (TME) has been limited to relatively low-plex immunohistochemical (IHC) or immunofluorescent (IF) assays, which were inadequate for deep immune cell profiling of the TME. Here, we present the analysis of fresh-frozen human breast tissue using spatial multiplexing technology called ChipCytometry, which combines iterative immuno-fluorescent staining using open-source antibodies for quantitative measure of virtually unlimited protein biomarkers on the same sample and high dynamic range imaging to facilitate quantitative phenotyping with single-cell resolution. In addition to traditional pathology review of the high-plex dataset, subsequent image analysis can be done using open-source or commercial software for advanced spatial analyses, including cluster analysis, neighborhood analysis and advanced data visualization. The results show precise expression levels for each of the protein biomarkers in the assay for each individual cell within the sample while maintaining spatial information about each cell. Dozens of immune cell subtypes were identified and quantified based on protein expression profiles. Spatial analysis of the samples revealed quantifiable heterogeneity of immune cell infiltration within the tumor samples, demonstrating the utility of the ChipCytometry platform for in-depth immune profiling in clinical samples. The ChipCytometry platform enables simultaneous detection of multiple protein biomarkers on a single tissue section for deep immune cell profiling in the TME. Combined with the single-cell spatial information, such datasets provide an opportunity for the discovery of new complex multiplexed biomarker signatures to inform therapeutic development and personalized medicine.

Citation Format: Benton Berigan. Spatial multiplexing of protein biomarkers for immune cell profiling of the tumor microenvironment with ChipCytometry [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-25-05.
Abstract PO2-27-07: The Role of HCMV Infection in Facilitating Brain Metastasis through the Creation of a Suppressive Tumor Microenvironment in Breast Cancer Patients
Authors: Dong Wenjuan , Wang Xin , Han Kun , Puri Akshjot , Irfan Amna , Qian Wei , Guzman Liliana , Rosato Roberto , Sheng Jianting , Zhao Hong , Chang Jenny , Wong Stephen
Published: May 2024

Human Cytomegalovirus (HCMV) infection has emerged as a noteworthy factor in breast cancer patients, particularly those experiencing brain metastasis. Despite being prevalent and often asymptomatic, HCMV's contribution to tumor progression remains enigmatic. Notably, a high proportion of breast cancer patients with brain metastasis exhibit HCMV positivity in both primary tumors and metastatic lesions. This study aims to elucidate the influence of HCMV infection on brain metastasis by investigating its impact on the tumor microenvironment. Our findings reveal a distinctive immune suppressive tumor microenvironment in HCMV-positive breast cancer patients. This environment is characterized by impaired NK cell function and an elevated accumulation of TH2 cells. To comprehend the role of HCMV in promoting brain metastasis, we have developed a murine breast tumor model using MCMV, enabling us to mirror the clinical trajectory of tumor progression and metastasis. The integration of a GFP reporter gene into the MCMV genome facilitates the tracking of infected cancer cells. Within this model, we observe a significant increase in brain metastasis coupled with reduced survival rates. Single-cell sequencing analysis uncovers diminished NK cell presence and activation, along with heightened TH2 cell accumulation within the tumor microenvironment—results that parallel the clinical observations in breast cancer patients. GSEA analysis underscores the secretion of inhibitory cytokines by MCMV-infected cancer cells, contrasting with their non-infected counterparts. Collectively, our study reveals that CMV infection contributes to brain metastasis in breast cancer by generating inhibitory cytokines. This hampers the recruitment and proliferation of immune cells within the tumor microenvironment and concurrently impairs the cytotoxic capabilities of NK cells. These insights shed light on the intricate interplay between viral infection and tumor progression, offering potential avenues for therapeutic exploration.

Citation Format: Wenjuan Dong, Xin Wang, Kun Han, Akshjot Puri, Amna Irfan, Wei Qian, Liliana Guzman, Roberto Rosato, Jianting Sheng, Hong Zhao, Jenny Chang, Stephen Wong. The Role of HCMV Infection in Facilitating Brain Metastasis through the Creation of a Suppressive Tumor Microenvironment in Breast Cancer Patients [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-27-07.
Abstract PO3-08-11: Association between Histologic Variants and the Results of Multigene Testing in Patients with Hormone Receptor-positive, HER2-negative Invasive Lobular Cancer
Authors: Ahn Jee Hyun , Lee Suk Jun , Yang Seung Hye , Kim Jee Ye , Park Hyung Seok , Kim Seung Il , Park Byeong Woo , Park Seho
Published: May 2024

Invasive lobular carcinoma (ILC), which accounts for approximately 5-15% of all breast cancers, can be divided into classic type and various other variants. Multigene testing (MGT) has prognostic value in hormone receptor (HR)-positive, HER2-negative breast cancer. We aimed to investigate the association between the results of MGT and histological variation of ILC.

1582 HR-positive, HER2-negative breast cancer patients treated between January 2014 and December 2022 were reviewed. Patients were divided into three groups; ILC-favorable group, ILC-unfavorable group and invasive ductal carcinoma (IDC) group. The ILC-favorable group consisted of classic and tubulolobular types, while the ILC-unfavorable group included pleomorphic, solid, signet ring cell, florid, and alveolar types according to the reported prognosis of each ILC variant. Among the various types of MGT, the 21-gene assay (OncotypeDX), the 70-gene assay (Mammaprint), and the 12-gene assay (Endopredict) assay were used in clinical setting.

The median age of patients was 50 years (range 20-85 years). 75.5% of patients received the 21-gene assay, 12.8% received the 70-gene assay, and 11.6% received the 12-gene assay. The high-risk results in MGT were showed in 7.7% of 155 patients in ILC-favorable group, 26.1% of 23 patients in ILC-unfavorable group, and 20.9% of 1404 patients in IDC group (p-value < 0.001). In the multivariate logistic regression analysis, ILC-favorable group showed significantly lower odds of high-risk results compared to IDC group (OR=0.284, 95% CI; 0.147-0.548), while ILC-unfavorable group did not show any significant difference compared to IDC group (OR=0.797, 95% CI; 0.263-2.411).

In comparison to IDC, the variants of ILC with favorable prognosis show lower rates of high-risk results in MGT, while the variants of ILC with poor prognosis do not differ significantly from IDC. For patients who diagnosed the variants of ILC with poor prognosis, MGT could be useful for prognosis prediction or treatment decision-making.

Citation Format: Jee Hyun Ahn, Suk Jun Lee, Seung Hye Yang, Jee Ye Kim, Hyung Seok Park, Seung Il Kim, Byeong Woo Park, Seho Park. Association between Histologic Variants and the Results of Multigene Testing in Patients with Hormone Receptor-positive, HER2-negative Invasive Lobular Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-08-11.
Abstract PO4-01-01: Prognostic Impact of Adjuvant Trastuzumab for the Treatment of Localized Stage I Breast Cancer - Single Tertiary Center Experience
Authors: Sapon-Cousineau Sasha , Florescu Marie , Charpentier Danielle , Younan Rami , Patocskai Erica , Hassan Saima , Boulva Kerianne , Ayoub Jean-Pierre
Published: May 2024

Prognostic Impact of Adjuvant Trastuzumab for the Treatment of Localized Stage I Breast Cancer – Single Tertiary Center Experience

Sasha Sapon-Cousineau, Marie Florescu, Danielle Charpentier, Rami Younan, Erica Patocskai, Saima Hassan, Kerianne Boulva, Jean-Pierre Ayoub

Centre hospitalier de l’Université de Montréal, Montréal, Québec, Canada

The HER2 oncoprotein is an established therapeutic target, and the combination of adjuvant chemotherapy and targeted anti-HER2 therapy substantially reduces the risk of recurrence and death over chemotherapy alone in high-risk operable breast cancers that overexpress HER2. However, most studies demonstrating the benefits of anti-HER2 treatments have focused on cohorts at high risk of recurrence. Limited data exists for low-risk cancers to justify this treatment.

We performed a retrospective study from 263 patients treated at our oncology center at the Centre hospitalier de l’Université de Montréal between 2006 and 2019 for HER2-positive, N0 or N0(i+) and T1mic to T1c breast cancers. A total of 227 patients were included, 149 (57%) with anti-HER2 treatment and 78 (30%) without. Patients had a single site of HER2-overexpressing invasive breast neoplasia with a follow-up of at least 6 months. Primary outcome was overall survival. Secondary outcomes were disease-free survival and the impact of tumoral and demographic factors.

Median follow-up period was 6.7 years. Overall survival at 5 years was 97% (CI 94, 100) for the group with anti-HER2 treatment versus 92% (CI 85, 98) for the group without anti-HER2 treatment. The difference in overall survival between the two treatment groups increased with tumor size. Disease-free survival at 5 years was 93% (CI 88, 87) for the group with anti-HER2 treatment versus 82% (CI 74, 92) for the group without anti-HER2 treatment. In subgroup analysis, age and tumor size had a significant impact on the difference in disease-free survival between groups.

Our study demonstrates the significant impact of anti-HER2 targeted therapies on overall survival and disease-free survival for patients with small, HER2 positive localized breast cancers. Further benefit is seen in certain subgroups, such as older patients and those with tumors larger than 1.0 cm, and this should be considered when determining appropriate treatment.

Citation Format: Sasha Sapon-Cousineau, Marie Florescu, Danielle Charpentier, Rami Younan, Erica Patocskai, Saima Hassan, Kerianne Boulva, Jean-Pierre Ayoub. Prognostic Impact of Adjuvant Trastuzumab for the Treatment of Localized Stage I Breast Cancer - Single Tertiary Center Experience [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-01-01.
Abstract PO4-01-10: Multi-modal artificial intelligence models from baseline histopathology predict prognosis in HR+ HER2- early breast cancer
Authors: Kates-Harbeck Daniel , Kreipe Hans-Heinrich , Gluz Oleg , Christgen Matthias , Kuemmel Sherko , Graeser Monika , Nitz Ulrike , Mahner Sven , Mayr Doris , Wuerstlein Rachel , Mitani Akinori , Zhang Jingbin , Pinckaers Hans , Ren Yi , Wood Peter , Griffin Jacqueline , Feng Felix , Esteva Andre , Keim-Malpass Jess , Kates Ronald , Harbeck Nadia
Published: May 2024

Background: Prognostic assessment in HR+ HER2- early breast cancer (EBC) remains challenging given relatively low rates of disease progression. Nuanced risk stratification is needed for decisions regarding systemic therapy. Modern artificial intelligence (AI)-based techniques have already provided substantial medical progress, particularly in prostate cancer. Here, we leverage multi-modal artificial intelligence (MMAI) trained using digital histopathology and clinical data to evaluate whether the MMAI technology can be expanded to other disease indications by applying the technology to the WSG PlanB and ADAPT trials in HR+ HER2- EBC.

Methods: Pre-treatment breast biopsy and surgical hematoxylin and eosin (H&E) slides were digitized from the WSG PlanB and ADAPT trials for HR+ HER2- EBC patients receiving endocrine therapy +/- chemotherapy. Median follow-up in both trials exceeded 5 years. A multi-modal artificial intelligence architecture was developed and validated on predicting risk of distant recurrence (DR). Time-to-event endpoints were summarized using cumulative incidence curves. Univariable and multivariable Fine-Gray models were used to assess performance; hazard ratios were reported per standard deviation increase of the model score.

Results: A total of 5539 patients from the two trials with H&E images and available follow-up data were used for development and validation of a multi-modal artificial intelligence architecture. The MMAI score derived using the training set was significantly associated with risk of DR in a validation cohort. To put the results into the clinical context in HR+ HER2- EBC, comprehensive validation analyses are currently ongoing and will be presented at the meeting.

Conclusions: We have successfully developed a multiple-instances, learning-based deep neural network for outcome prediction using H&E-stained images. This study provides important evidence that MMAI technology can further personalize breast cancer management by adding standardizable information.

Citation Format: Daniel Kates-Harbeck, Hans-Heinrich Kreipe, Oleg Gluz, Matthias Christgen, Sherko Kuemmel, Monika Graeser, Ulrike Nitz, Sven Mahner, Doris Mayr, Rachel Wuerstlein, Akinori Mitani, Jingbin Zhang, Hans Pinckaers, Yi Ren, Peter Wood, Jacqueline Griffin, Felix Feng, Andre Esteva, Jess Keim-Malpass, Ronald Kates, Nadia Harbeck. Multi-modal artificial intelligence models from baseline histopathology predict prognosis in HR+ HER2- early breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-01-10.
Abstract PO4-08-08: Is it time for a European BRCA Mutation Registry? An Italian experience
Authors: De Matteis Elisabetta , Ciccarese Mariangela , Tarantino Paolo , Grassi Tiziana , Bagordo Francesco , Rizzo Emanuele , Tumolo Maria Rosaria , Ronzino Graziana , De Giorgio Maria Rita , Mauro Salvatore , Renzo Nicola Di
Published: May 2024

Background: Knowledge of BRCA 1/2 mutation plays an important role in cancer care.

The National Plan to improve BRCA detection in order to increase access to target agents and ameliorate the prevention strategy has several implementations in the Italian regions. Recent guidelines are considering extending genetic testing to a larger population, regardless of family history. We present our experience in Apulia Region on the detection of BRCA 1/2 and its clinical implication at the regional level, to underline the importance of spreading the extension of BRCA detection at the regional level and to propose the creation of a European register for BRCA patients, based on population-based BRCA 1/2 testing.

Methods: This is an observational study conducted at a Familiar Cancer Service of the Lecce Hospital. Participants completed a questionnaire (socio-demographic epidemiology of cancer and lifestyle factors), genetic counseling and BRCA testing. Notably, genetic testing for BRCA mutations was carried out based on family cancer history since 2018, according to the Italian cancer guidelines (AIOM) and related updates in 2019 and 2023. A mutational analysis of exons and adjacent intronic regions of BRCA1/BRCA2 genes was performed by Sanger sequencing and MiSeq Illumina NGS platform.

Results:

Between 2014 and May 2023 a total of 4365 patients were enrolled in the study, of whom 2426 (56%) was evaluable for BRCA detection, 18% men (n=440) and 82% female (n=1986). Median age at diagnosis was 57 yrs. 65% of patients had a cancer diagnosis (n=1575) and 35% were healthy carriers (n=851). In particular, breast cancer (BC) was present in 63% of patients (n=1048), ovarian cancer (OC) in 21% (n=352), pancreatic cancer in 5% (n=85), prostate cancer in 4% (n=65), melanoma in 1% (n=13), and other cancers in 6% (n=92).

The table 1 (uploaded) shows the results of patients with BC (n=1048)

The presence of BRCA mutation is observed in 20.52% of BC patients (1:4.87).

Conclusion

These data confirm that BRCA mutation detection is an emerging need to improve prevention and early diagnosis according to the European Beating Cancer Plan. Therefore, it is crucial to improve this topic at regional level until the creation of a shared BRCA registry among European countries.

Table.

Citation Format: Elisabetta De Matteis, Mariangela Ciccarese, Paolo Tarantino, Tiziana Grassi, Francesco Bagordo, Emanuele Rizzo, Maria Rosaria Tumolo, Graziana Ronzino, Maria Rita De Giorgio, Salvatore Mauro, Nicola Di Renzo. Is it time for a European BRCA Mutation Registry? An Italian experience [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-08-08.
Abstract PO4-23-07: Impact of distance between tumor and nipple on locoregional recurrence in breast cancer
Authors: Cheun Jong-Ho , Kang Eunhye , Kim Hong-Kyu , Lee Han-Byoel , Moon Hyeong-Gon , Han Wonshik , Hwang Ki-Tae
Published: May 2024

Introduction: Mastectomy is usually recommended for centrally located tumors due to the risk of nipple invasion. While it is well known that there is no significant difference in survival outcomes according to tumor location, central tumors have a higher likelihood of main lactiferous duct invasion, which can result in the migration of tumor cells to the periphery. Therefore, we conducted an investigation specifically focusing on locoregional recurrence (LRR) rates based on the tumor-to-nipple distance (TND).

Method: We retrospectively collected the data of patients who underwent breast cancer surgery between 2004-2018 from two institutions. Patients who underwent neoadjuvant chemotherapy were excluded. TND information was obtained from preoperative MRI records.

Results: A total of 9,014 patients were included in the study, and the median tumor-to-nipple distance (TND) was 3.4 (0.0-15.0) cm. For all patients, the restricted cubic spline curve analysis showed that the hazard risk of LRR increased with shorter TND. The pattern was more pronounced in the breast-conserving surgery (BCS) group, whereas the mastectomy group showed a relatively constant risk regardless of TND. Thus, we conducted survival analysis for 5,455 patients who underwent BCS. We set the cutoff for TND as 2.5cm as it showed the lowest p-value for LRR rate. Compared to those with TND >2.5cm, patients with TND≤2.5cm showed significantly lower LRR (HR,1.83;95%CI,[1.37-2.46],p< 0.001) and distant metastasis(DM) (HR,1.53;95%CI,[1.16-2.02],p=0.002) rates. Overall survival was not different between two groups (p=0.405). Cox-regression analysis revealed that TND still impacts LRR (HR,1.52;95%CI,[1.11-2.09],p=0.010) but not DM. Importantly, TND still remained significant factor affecting LRR when analyzed as continuous variable (HR,1.04; 95%CI,[1.02-1.06],p< 0.001). The prognostic impact of TND was particularly evident in patients with high mammographic density.

Discussion: BCS can be performed for centrally located tumors, as it offers considerable oncologic safety compared to mastectomy. However, for patients who have a fear of recurrence and are reluctant to undergo re-operation, mastectomy would be a good choice.

Citation Format: Jong-Ho Cheun, Eunhye Kang, Hong-Kyu Kim, Han-Byoel Lee, Hyeong-Gon Moon, Wonshik Han, Ki-Tae Hwang. Impact of distance between tumor and nipple on locoregional recurrence in breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-23-07.
Abstract PO5-11-01: Audit of multidisciplinary team meetings for improving breast cancer care
Authors: Sharma Kanika , Puri Gopal
Published: May 2024

Introduction: Multidisciplinary team (MDT) meeting is a well-established method of optimising care for breast cancer patients. However, its effectiveness has not been proven yet. The present study aims to audit the functioning of MDT at a tertiary care hospital in a low-middle income country. Methods: This study examines the prospectively maintained database of patients being discussed in MDT meetings occurring from August 2018 till June 2023. The MDT was suspended for few months in between owing to the COVID pandemic. The analysis was done in terms of indications of discussion, referring department, modification in the pre-MDT plan, new investigation advised, radiological and pathological concordance, significant change in management strategy and interesting cases. The analysis is both qualitative and quantitative. Quantitative analysis involves percentages, mean and median. Results: MDT at our institute was conducted every Saturday at 12 noon as an in-person meeting. The MDT was suspended from May 2020 till June 2021 in view of the pandemic. It was restarted in July 2021, on an online platform and is continued as such. A total of 473 cases were discussed with 181 (38.2%) benign causes and rest were malignant. The most common indication of discussion for malignant cases was feasibility of breast conservation (59.9%) followed by ruling out recurrence/residual disease (17.4%). The indication for benign cases was rad-path concordance and ruling out phyllodes in a case of fibroepithelial lesion. In 31.4% of the cases the plan was modified from the pre-MDT plan and there was improved care. 34.7% cases were advised to get a new investigation done in form of contrast enhanced mammogram or MRI. Seventy nine percent cases were feasible for BCS, and it was done involving few complex surgeries as well. The most common indication for deferring BCS was extensive DCIS. The total number of man hours spent in preparation as well as MDT were analysed with improved clinical care and revealed the MDT to be a time intensive exercise with poor efficacy in terms of hours spent per patient. The time to decision making was increased at an average of 7.5 days for these patients. Conclusion: MDT helps to achieve goals of superior clinical care for both benign and malignant breast disorders at the cost of increased time to decision. It is labour intensive with capability of changing decision in one third of the cases. However, MDT needs regular audit to ensure optimum care with available resources.

Citation Format: Kanika Sharma, Gopal Puri. Audit of multidisciplinary team meetings for improving breast cancer care [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-11-01.
Abstract PO5-15-03: Neutrophil-lymphocyte ratio and absolute lymphocyte count, inflammatory markers, may predict lymph node metastasis in elderly patients with operable breast cancer
Authors: Tokuda Emi , Morita Midori , Shimomura Akihiko , Horimoto Yoshiya , Kawamura Yukino , Ishizuka Yumiko , Sekine Katsutoshi , Obayashi Sayaka , Kojima Yuki , Higuchi Toru
Published: May 2024

Background: Blood-derived systemic inflammatory markers such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR) and absolute lymphocyte count (ALC) have been demonstrated as predictive markers of recurrence and prognosis in several malignancies. Increased chronic inflammation with aging has been reported to be involved in cancer cells and their microenvironment. Several studies have also reported a close relationship between inflammatory markers and cancer grade and prognosis in the elderly. In this study, we retrospectively examined the relationship between lymphocyte-related inflammatory markers and prognosis in elderly breast cancer patients. Method: We included 602 patients diagnosed with primary invasive breast cancer at 8 institutions between 2008 and 2013, all of whom were older than 70 years old and had undergone breast cancer surgery. Preoperative blood collection data were used to analyze the relationship between NLR, PLR, LMR, ALC and clinicopathological data including recurrence. Results: The pathological stages of the 602 patients were Stage I: 275, Stage II: 276, and Stage III: 51, with median NLR, PLR, LMR, and ALC values of 2.21, 134.51, 6.76, and 1840, respectively. The mean age of the patients was 75.3 years. The median follow-up was 72.8 months. 76 patients relapsed, and the mean time to relapse was 42.7 months. Lymphocyte-associated inflammatory markers and Li Sheng pathological characteristics showed no significant differences in stage, presence or absence of recurrence, or form of recurrence, but lymph node metastasis on surgical pathology showed significant differences between cases with and without lymph node metastasis in NLR and ALC (P< 0.05). Conclusions: LMR and ALC were considered useful biomarkers that can be easily measured to predict lymph node metastasis in operable elderly breast cancer

Citation Format: Emi Tokuda, Midori Morita, Akihiko Shimomura, Yoshiya Horimoto, Yukino Kawamura, Yumiko Ishizuka, Katsutoshi Sekine, Sayaka Obayashi, Yuki Kojima, Toru Higuchi. Neutrophil-lymphocyte ratio and absolute lymphocyte count, inflammatory markers, may predict lymph node metastasis in elderly patients with operable breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-15-03.
Abstract PS15-08: Final Overall Survival (OS) analysis of the SAKK 21/12 trial. CR1447 in HR+/HER2- metastatic breast cancer and androgen receptor positive triple negative breast cancer
Authors: Vetter Marcus , Lisa Holer , Rothgiesser Karin , Schönfeld Wolfgang , Riniker Salome , von Moos Roger , Torjan Andreas , Kralidis Elena , Rabaglio Manuela , Fehr Mathias K. , Müller Andreas , Thürlimann Beat
Published: May 2024

Introduction:

CR1447 (4-Hydroxytestosteron) is a compound with aromatase inhibitor and anti-androgen receptor activity and is applied transdermally. We assessed its activity and safety in metastatic breast cancer (mBC). The primary endpoint (disease control rate at week 24) was reported in 2019. We now present the final overall survival (OS) analysis of the trial.

Methods

In cohort A (ER+/HER2-negative metastatic disease), one prior treatment line was allowed and 29 patients (ITT 21 patients) were included. In cohort B (triple negative mBC), eight patients were included. The trial was closed in 2018 due to futility (cohort A) and slow accrual (cohort B).

Results

At data cut-off on 11.04.2023 92% of all patients had died. Median OS for cohort A was 35.4 months (95% CI: 24.6-49.1) in the ITT population and 19.4 months (95% CI: 2.3-36.8) in the non-ITT population (patients with more than one line of endocrine therapy). In cohort B, median OS was 10.8 months (95% CI: 3.3-28.6). Treatment was well tolerated with no new safety signals and the majority of treatment-related adverse events (TRAE) were Grade 1 and 2. The most common TRAEs were dry skin (43%), rash (16%), fatigue (16%) and nausea (16%).

Discussion

Despite the trial being negative in terms of the primary endpoint, cohort A (ITT) had a median OS of 35.4 months. There were no new safety signals. Mutational analysis of AR/ER is ongoing to determine benefit of this treatment in specific subgroups. CR1447 might be a candidate drug to combine with other agents (CDK4/6 inhibitors or other targeted therapies).

Citation Format: Marcus Vetter, Holer Lisa, Karin Rothgiesser, Wolfgang Schönfeld, Salome Riniker, Roger von Moos, Andreas Torjan, Elena Kralidis, Manuela Rabaglio, Mathias K. Fehr, Andreas Müller, Beat Thürlimann. Final Overall Survival (OS) analysis of the SAKK 21/12 trial. CR1447 in HR+/HER2- metastatic breast cancer and androgen receptor positive triple negative breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS15-08.
Supplementary Figure S7 from Jak2V617F Reversible Activation Shows Its Essential Requirement in Myeloproliferative Neoplasms
Authors: Dunbar Andrew J. , Bowman Robert L. , Park Young C. , O'Connor Kavi , Izzo Franco , Myers Robert M. , Karzai Abdul , Zaroogian Zachary , Kim Won Jun , Fernández-Maestre Inés , Waarts Michael R. , Nazir Abbas , Xiao Wenbin , Codilupi Tamara , Brodsky Max , Farina Mirko , Cai Louise , Cai Sheng F. , Wang Benjamin , An Wenbin , Yang Julie L. , Mowla Shoron , Eisman Shira E. , Hanasoge Somasundara Amritha Varshini , Glass Jacob L. , Mishra Tanmay , Houston Remie , Guzzardi Emily , Martinez Benitez Anthony R. , Viny Aaron D. , Koche Richard P. , Meyer Sara C. , Landau Dan A. , Levine Ross L.
Published: May 2024

Differential gene expression responses of Jak2V617F deletion compared to JAK inhibitor therapy
Supplementary Figure S3 from Jak2V617F Reversible Activation Shows Its Essential Requirement in Myeloproliferative Neoplasms
Authors: Dunbar Andrew J. , Bowman Robert L. , Park Young C. , O'Connor Kavi , Izzo Franco , Myers Robert M. , Karzai Abdul , Zaroogian Zachary , Kim Won Jun , Fernández-Maestre Inés , Waarts Michael R. , Nazir Abbas , Xiao Wenbin , Codilupi Tamara , Brodsky Max , Farina Mirko , Cai Louise , Cai Sheng F. , Wang Benjamin , An Wenbin , Yang Julie L. , Mowla Shoron , Eisman Shira E. , Hanasoge Somasundara Amritha Varshini , Glass Jacob L. , Mishra Tanmay , Houston Remie , Guzzardi Emily , Martinez Benitez Anthony R. , Viny Aaron D. , Koche Richard P. , Meyer Sara C. , Landau Dan A. , Levine Ross L.
Published: May 2024

Functional characterization of Jak2RL knock-in/knock-out in vivo
Supplementary Figure S2 from Jak2V617F Reversible Activation Shows Its Essential Requirement in Myeloproliferative Neoplasms
Authors: Dunbar Andrew J. , Bowman Robert L. , Park Young C. , O'Connor Kavi , Izzo Franco , Myers Robert M. , Karzai Abdul , Zaroogian Zachary , Kim Won Jun , Fernández-Maestre Inés , Waarts Michael R. , Nazir Abbas , Xiao Wenbin , Codilupi Tamara , Brodsky Max , Farina Mirko , Cai Louise , Cai Sheng F. , Wang Benjamin , An Wenbin , Yang Julie L. , Mowla Shoron , Eisman Shira E. , Hanasoge Somasundara Amritha Varshini , Glass Jacob L. , Mishra Tanmay , Houston Remie , Guzzardi Emily , Martinez Benitez Anthony R. , Viny Aaron D. , Koche Richard P. , Meyer Sara C. , Landau Dan A. , Levine Ross L.
Published: May 2024

Functional consequences of Jak2V617F reversion ex vivo
Table S7 from Early Immune Remodeling Steers Clinical Response to First-Line Chemoimmunotherapy in Advanced Gastric Cancer
Authors: An Minae , Mehta Arnav , Min Byung Hoon , Heo You Jeong , Wright Samuel J. , Parikh Milan , Bi Lynn , Lee Hyuk , Kim Tae Jun , Lee Song-Yi , Moon Jeonghyeon , Park Ryan J. , Strickland Matthew R. , Park Woong-Yang , Kang Won Ki , Kim Kyoung-Mee , Kim Seung Tae , Klempner Samuel J. , Lee Jeeyun
Published: May 2024

CellPhoneDB unique ligand receptor interactions
Table S3 from Early Immune Remodeling Steers Clinical Response to First-Line Chemoimmunotherapy in Advanced Gastric Cancer
Authors: An Minae , Mehta Arnav , Min Byung Hoon , Heo You Jeong , Wright Samuel J. , Parikh Milan , Bi Lynn , Lee Hyuk , Kim Tae Jun , Lee Song-Yi , Moon Jeonghyeon , Park Ryan J. , Strickland Matthew R. , Park Woong-Yang , Kang Won Ki , Kim Kyoung-Mee , Kim Seung Tae , Klempner Samuel J. , Lee Jeeyun
Published: May 2024

Detailed cell type proportions
Figure S3 from Early Immune Remodeling Steers Clinical Response to First-Line Chemoimmunotherapy in Advanced Gastric Cancer
Authors: An Minae , Mehta Arnav , Min Byung Hoon , Heo You Jeong , Wright Samuel J. , Parikh Milan , Bi Lynn , Lee Hyuk , Kim Tae Jun , Lee Song-Yi , Moon Jeonghyeon , Park Ryan J. , Strickland Matthew R. , Park Woong-Yang , Kang Won Ki , Kim Kyoung-Mee , Kim Seung Tae , Klempner Samuel J. , Lee Jeeyun
Published: May 2024

Figure S3. (A) Enrichment of gene expression signatures for TME subtypes using
bulk RNA-sequencing data for all patient samples at baseline and after
chemotherapy (follow-up 1; FU1). (B) Pathway enrichment analysis on differentially
expressed genes comparing bulk RNA-seq profiles for samples obtained pretreatment
(baseline) and samples obtained after 1 cycle of chemotherapy (FU1).
(C) Plots demonstrating change in immune related gene signatures (Treg, Treg
trafficking, Th2, immune checkpoints, M2 macrophages, pro-tumorgenic cytokines)
after chemotherapy treatment. Lines connect samples obtained from the same
patient. Statistical comparison performed using a Wilcoxon signed-rank test. (D)
Quantification of CD8+ cell abundance using immunohistochemistry (IHC) at
baseline and after chemotherapy (FU1) in 12 patient samples. Statistical
comparison performed using a Wilcoxon signed-rank test.
Figure S21 from Early Immune Remodeling Steers Clinical Response to First-Line Chemoimmunotherapy in Advanced Gastric Cancer
Authors: An Minae , Mehta Arnav , Min Byung Hoon , Heo You Jeong , Wright Samuel J. , Parikh Milan , Bi Lynn , Lee Hyuk , Kim Tae Jun , Lee Song-Yi , Moon Jeonghyeon , Park Ryan J. , Strickland Matthew R. , Park Woong-Yang , Kang Won Ki , Kim Kyoung-Mee , Kim Seung Tae , Klempner Samuel J. , Lee Jeeyun
Published: May 2024

Figure S21. (A) Change in M2 ratio from baseline to FU1 in patients with
decreased or increased stromal proportions. (B) Proportion of stromal cells in
patient samples from fast and slow progressing patients split by timepoint. (C)
UMAP embedding of single cell transcriptomes of all stromal cells obtained from all
samples in this trial. Labeled are granular stromal cell types separated by tumor v.s.
normal tissue, and by timepoint. (D) UMAP embeddings showing marker gene
expression for granular stromal cell types in (C). (E) Proportion of myofibroblasts in
patient samples from fast and slow progressing patients split by timepoint.
Supplementary Table 2 from Long-term Multimodal Recording Reveals Epigenetic Adaptation Routes in Dormant Breast Cancer Cells
Authors: Rosano Dalia , Sofyali Emre , Dhiman Heena , Ghirardi Chiara , Ivanoiu Diana , Heide Timon , Vingiani Andrea , Bertolotti Alessia , Pruneri Giancarlo , Canale Eleonora , Dewhurst Hannah F. , Saha Debjani , Slaven Neil , Barozzi Iros , Li Tong , Zemlyanskiy Grigory , Phillips Henry , James Chela , Győrffy Balázs , Lynn Claire , Cresswell George D. , Rehman Farah , Noberini Roberta , Bonaldi Tiziana , Sottoriva Andrea , Magnani Luca
Published: May 2024

Coverage data for patient profiling
Supplementary Figure S8 from Long-term Multimodal Recording Reveals Epigenetic Adaptation Routes in Dormant Breast Cancer Cells
Authors: Rosano Dalia , Sofyali Emre , Dhiman Heena , Ghirardi Chiara , Ivanoiu Diana , Heide Timon , Vingiani Andrea , Bertolotti Alessia , Pruneri Giancarlo , Canale Eleonora , Dewhurst Hannah F. , Saha Debjani , Slaven Neil , Barozzi Iros , Li Tong , Zemlyanskiy Grigory , Phillips Henry , James Chela , Győrffy Balázs , Lynn Claire , Cresswell George D. , Rehman Farah , Noberini Roberta , Bonaldi Tiziana , Sottoriva Andrea , Magnani Luca
Published: May 2024

Traditiom experimental strategy
Supplementary Figure S4 from Acquired Cross-Resistance in Small Cell Lung Cancer due to Extrachromosomal DNA Amplification of MYC Paralogs
Authors: Pal Choudhuri Shreoshi , Girard Luc , Lim Jun Yi Stanley , Wise Jillian F. , Freitas Braeden , Yang Di , Wong Edmond , Hamilton Seth , Chien Victor D. , Kim Yoon Jung , Gilbreath Collin , Zhong Jun , Phat Sarah , Myers David T. , Christensen Camilla L. , Mazloom-Farsibaf Hanieh , Stanzione Marcello , Wong Kwok-Kin , Hung Yin P. , Farago Anna F. , Meador Catherine B. , Dyson Nicholas J. , Lawrence Michael S. , Wu Sihan , Drapkin Benjamin J.
Published: May 2024

Genomic analysis of chromosome 17 focal amplification in MGH1531-5BX and analysis of ecDNA junction mutations in MGH1518-3A.
Supplementary Figure S5 from Long-term Multimodal Recording Reveals Epigenetic Adaptation Routes in Dormant Breast Cancer Cells
Authors: Rosano Dalia , Sofyali Emre , Dhiman Heena , Ghirardi Chiara , Ivanoiu Diana , Heide Timon , Vingiani Andrea , Bertolotti Alessia , Pruneri Giancarlo , Canale Eleonora , Dewhurst Hannah F. , Saha Debjani , Slaven Neil , Barozzi Iros , Li Tong , Zemlyanskiy Grigory , Phillips Henry , James Chela , Győrffy Balázs , Lynn Claire , Cresswell George D. , Rehman Farah , Noberini Roberta , Bonaldi Tiziana , Sottoriva Andrea , Magnani Luca
Published: May 2024

Spatial transcriptomics of patients 2-3 (rare cohort treated with long-term ET until progression)
Supplementary Figure S13 from Long-term Multimodal Recording Reveals Epigenetic Adaptation Routes in Dormant Breast Cancer Cells
Authors: Rosano Dalia , Sofyali Emre , Dhiman Heena , Ghirardi Chiara , Ivanoiu Diana , Heide Timon , Vingiani Andrea , Bertolotti Alessia , Pruneri Giancarlo , Canale Eleonora , Dewhurst Hannah F. , Saha Debjani , Slaven Neil , Barozzi Iros , Li Tong , Zemlyanskiy Grigory , Phillips Henry , James Chela , Győrffy Balázs , Lynn Claire , Cresswell George D. , Rehman Farah , Noberini Roberta , Bonaldi Tiziana , Sottoriva Andrea , Magnani Luca
Published: May 2024

TRADITIOM WGS Coverage and CNA map
Table S17 from Large-scale Pan-cancer Cell Line Screening Identifies Actionable and Effective Drug Combinations
Authors: Bashi Azadeh C. , Coker Elizabeth A. , Bulusu Krishna C. , Jaaks Patricia , Crafter Claire , Lightfoot Howard , Milo Marta , McCarten Katrina , Jenkins David F. , van der Meer Dieudonne , Lynch James T. , Barthorpe Syd , Andersen Courtney L. , Barry Simon T. , Beck Alexandra , Cidado Justin , Gordon Jacob A. , Hall Caitlin , Hall James , Mali Iman , Mironenko Tatiana , Mongeon Kevin , Morris James , Richardson Laura , Smith Paul D. , Tavana Omid , Tolley Charlotte , Thomas Frances , Willis Brandon S. , Yang Wanjuan , O'Connor Mark J. , McDermott Ultan , Critchlow Susan E. , Drew Lisa , Fawell Stephen E. , Mettetal Jerome T. , Garnett Mathew J.
Published: May 2024

Supplementary Table 17 shows large effect size and significant Bliss and combo Emax biomarkers for selected top hits
Figure S1 from EGFR-Driven Lung Adenocarcinomas Co-opt Alveolar Macrophage Metabolism and Function to Support EGFR Signaling and Growth
Authors: Kuhlmann-Hogan Alexandra , Cordes Thekla , Xu Ziyan , Kuna Ramya S. , Traina Kacie A. , Robles-Oteíza Camila , Ayeni Deborah , Kwong Elizabeth M. , Levy Stellar , Globig Anna-Maria , Nobari Matthew M. , Cheng George Z. , Leibel Sandra L. , Homer Robert J. , Shaw Reuben J. , Metallo Christian M. , Politi Katerina , Kaech Susan M.
Published: May 2024

Figure S1: Myeloid cell regulation during lung tumorigenesis.
Data from Co-clinical Trial of Novel Bispecific Anti-HER2 Antibody Zanidatamab in Patient-Derived Xenografts
Authors: DiPeri Timothy P. , Evans Kurt W. , Wang Bailiang , Zhao Ming , Akcakanat Argun , Raso Maria Gabriela , Rizvi Yasmeen Q. , Zheng Xiaofeng , Korkut Anil , Varadarajan Kaushik , Uzunparmak Burak , Dumbrava Ecaterina E. , Pant Shubham , Ajani Jaffer A. , Pohlmann Paula R. , Jensen V. Behrana , Javle Milind , Rodon Jordi , Meric-Bernstam Funda
Published: May 2024

Abstract
Zanidatamab is a bispecific human epidermal growth factor receptor 2 (HER2)-targeted antibody that has demonstrated antitumor activity in a broad range of HER2-amplified/expressing solid tumors. We determined the antitumor activity of zanidatamab in patient-derived xenograft (PDX) models developed from pretreatment or postprogression biopsies on the first-in-human zanidatamab phase I study (NCT02892123). Of 36 tumors implanted, 19 PDX models were established (52.7% take rate) from 17 patients. Established PDXs represented a broad range of HER2-expressing cancers, and in vivo testing demonstrated an association between antitumor activity in PDXs and matched patients in 7 of 8 co-clinical models tested. We also identified amplification of MET as a potential mechanism of acquired resistance to zanidatamab and demonstrated that MET inhibitors have single-agent activity and can enhance zanidatamab activity in vitro and in vivo. These findings provide evidence that PDXs can be developed from pretreatment biopsies in clinical trials and may provide insight into mechanisms of resistance.
Significance:
We demonstrate that PDXs can be developed from pretreatment and postprogression biopsies in clinical trials and may represent a powerful preclinical tool. We identified amplification of MET as a potential mechanism of acquired resistance to the HER2 inhibitor zanidatamab and MET inhibitors alone and in combination as a therapeutic strategy.

This article is featured in Selected Articles from This Issue, p. 695