bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract PD8-05: Mismatch repair deficiency predicts response to HER2 blockade in HER2-negative breast cancer
Authors: Haricharan Svasti , Punturi Nindo , Seker Sinem , Devarakonda Vaishnavi , Kalra Rashi , Chen Ching-Hui , Mazumder Aloran , Li Shungqiang , Primeau Tina , Ellis Matthew , Kavuri Shyam
Published: February 2021

Estrogen receptor positive (ER+) breast cancer is a leading cause of cancer-related death globally. Resistance to standard of care endocrine treatment occurs in at least 30% of ER+ breast cancer patients resulting in ~40,000 deaths every year in the US alone. Preclinical studies strongly implicate activation of growth factor receptor, HER2 in endocrine treatment resistance of ER+ breast cancer that is HER2- at diagnosis. However, clinical trials of pan-HER inhibitors in ER+/HER2- patients have disappointed, likely due to a lack of predictive biomarkers. Here we demonstrate that loss of MLH1, a principal mismatch repair gene, causally activates HER2 in ER+/HER2- breast cancer upon endocrine treatment. Additionally, we show that HER2 activation is indispensable for endocrine treatment resistant growth of MLH1-defective cells in vitro and in vivo. Consequently, inhibiting HER2 restores sensitivity to endocrine treatment in multiple experimental models including patient-derived xenograft tumors. Patient data from multiple clinical datasets (TCGA, METABRIC, Alliance (Z1031) and E-GEOD-28826) supports an association between MLH1 loss, HER2 upregulation, and sensitivity to trastuzumab in endocrine treatment-resistant ER+/HER2- patients. These results provide strong evidence that MLH1 could serve as a first-in-class predictive marker of sensitivity to combinatorial treatment with endocrine drugs and HER2 inhibitors in endocrine treatment-resistant ER+/HER2- breast cancer patients. Implications of this study extend beyond breast cancer to Lynch Syndrome cancers.

Citation Format: Svasti Haricharan, Nindo Punturi, Sinem Seker, Vaishnavi Devarakonda, Rashi Kalra, Ching-Hui Chen, Aloran Mazumder, Shungqiang Li, Tina Primeau, Matthew Ellis, Shyam Kavuri. Mismatch repair deficiency predicts response to HER2 blockade in HER2-negative 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 PD8-05.
Abstract PS1-31: Nomogram for predicting axillary lymph node pathological response in node-positive breast cancer patients after neoadjuvant chemotherapy
Authors: Wang Xin , Wang Wenyan , Liu Jiaxiang , Meng Xiangzhi , Liu Jiaqi , Guo Changyuan , Song Ying , Cui Ningyi , Li Qiao , Xing Zeyu , Wang Jie , Zhang Menglu , Feng Kexin , Wang Pilin , Wang Xiang
Published: February 2021

Background: Pathological complete response (pCR) of axillary lymph nodes (ALNs) is frequently achieved in patients with clinically node-positive breast cancer after neoadjuvant chemotherapy (NAC). ALN status is an important prognostic factor for choosing the type of axillary lymph node surgery. Many patients with axillary pCR could replace axillary lymph node dissection (ALND) with sentinel lymph node biopsy (SLNB). Our goal is to develop a new predictive clinical model to detect axillary pCR after NAC and provide clinical clues for avoiding ALND. Methods: A retrospective series of 547 patients who had biopsy-proven positive ALNs at diagnosis from 2007 to 2014 in National Cancer Center/Cancer Hospital of Chinese Academy of Medical Sciences were involved. We analyzed the clinicopathologic features and developed a nomogram to predict the probability of ALN pCR. Univariate assessment was performed using chi-square test. A multivariate logistic regression stepwise model was used to generate a nomogram to predict ALN pCR in node positive patients. The receiver operating characteristic (ROC) curve was established and the area under the curve (AUC) was calculated to evaluate the accuracy of the model. Internal validation was estimated using 50-50 hold out validation method. Nomogram was validated externally with the prospective cohorts of 167 patients from 2016 to 2018 of Cancer Hospital of Chinese Academy of Medical Sciences and 75 patients from 2018 to 2019 of Beijing Tiantan hospital.Results: In the retrospective study, 172 (31.4%) patients achieved axillary pCR after NAC. Multivariate analysis indicated that clinical nodal (N) stage, hormone receptor (HR) status and clinical response of primary tumor after NAC were significant independent predictors for axillary pCR (P<0.05). The AUCs of the internal validation for the training and test sets were 0.719 and 0.753, respectively. The nomogram was validated in external cohorts with AUCs of 0.862 and 0.766, respectively.Conclusion: We developed a nomogram to predict axillary pCR in node positive breast cancer patients after NAC. The predictive model performed well in prospective external validation. This practical tool could provide information to surgeons about whether to avoid ALND after NAC.

Citation Format: Xin Wang, Wenyan Wang, Jiaxiang Liu, Xiangzhi Meng, Jiaqi Liu, Changyuan Guo, Ying Song, Ningyi Cui, Qiao Li, Zeyu Xing, Jie Wang, Menglu Zhang, Kexin Feng, Pilin Wang, Xiang Wang. Nomogram for predicting axillary lymph node pathological response in node-positive breast cancer patients after neoadjuvant chemotherapy [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 PS1-31.
Abstract PS1-37: Reduction mammoplasty in the setting of neoadjuvant chemotherapy
Authors: Hewitt Kelly , Wu Susan , Barnes Laura , Yang Joanna , Piper Merisa
Published: February 2021

Background: Oncoplastic reduction mammoplasty is an accepted method of breast conserving surgery that also allows for potentially improved symmetry and aesthetics compared to other techniques and allows for larger tissue volumes to be removed with acceptable cosmetic outcomes. Neoadjuvant systemic chemotherapy (NAC) is increasingly used for the treatment of patients with breast cancer. While there is some data that oncoplastic reduction may delay timing of adjuvant radiation, we sought to examine this in our patients, and specifically to compare complications and time to radiation in patients who received NAC to those that didn’t.

Methods: A retrospective analysis was done of all patients with DCIS or invasive cancer who underwent a reduction mammoplasty and received adjuvant radiation at our single institution from 2009-2018. Patients who received NAC were compared to those that did not.

Results: A total of 114 patients underwent reduction mammoplasty as part of their oncologic surgery and received adjuvant radiation at our institution. Of those, 40.4% received neoadjuvant chemotherapy and 49.1% received no neoadjuvant treatment. A total of 38 patients (33.3%) had some postoperative complication with 8.8% having a serious complication that required intervention. Adjuvant radiation started after 8 weeks in 74.6% of patients and after 12 weeks in 38.6% of patients, with the majority of these delays due to non-clinical factors. A total of 29.4% of patients had a delay due to wound healing issues. There was no association between NAC and delayed radiation due to wound healing (p=0.18).

Discussion: Oncoplastic reduction mammoplasty is a safe option for breast-conserving surgery in patients who have received NAC. The receipt of NAC in itself does not delay timing of adjuvant radiation or lead to increases in delayed wound healing. We are additionally examining other factors and their possible interaction with NAC, including diabetes, smoking, BMI and breast reduction size. In those with larger tumors receiving NAC who would otherwise not be candidates for breast conserving surgery, oncoplastic reduction should be considered as an appropriate option for surgical management. Reduction also allows for wider excision which may mitigate the impact of the longer time from surgery to radiation.

Citation Format: Kelly Hewitt, Susan Wu, Laura Barnes, Joanna Yang, Merisa Piper. Reduction mammoplasty in the setting of neoadjuvant chemotherapy [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 PS1-37.
Abstract PS1-55: Clipping of involved axillary lymph nodes before Neo adjuvant chemotherapy may improve in identification rates & staging of axilla in breast cancer
Authors: Elahi Mohammad Bilal , Bichoo Raouef Ahmed , Grover Kartikae , Khalifa Eiman , Ihsan Naila Bint , Kneeshaw Peter J , Wooler Brendan Paul , Dumitru Dorin , Roychaudhury Ronjabati , Rahman Ayesha , Mahapatra Tapan Kumar
Published: February 2021

Introduction: Neo adjuvant chemotherapy is increasingly being employed in breast cancer to reduce tumour size & down stage axilla. To reduce false negative rates in axillary lymph nodes after down staging with chemotherapy and to improve axillary conservation ultrasound guided clips were placed in involved axillary lymph nodes prior to commencement of NACT. The study aimed at whether preoperative lymph node clipping had any benefit in identification of lymph node after NACT.Methods: This is a single centre study of 55 patients (Mean age 53 years) with invasive breast cancer with biopsy proven involved lymph nodes (T1-3 N1) who underwent ultrasound guided axillary marker clip insertion before start of NACT. If Post chemotherapy imaging showed normal lymph nodes patients underwent SLNB with additional Lymph Nodes sampled to achieve a total of 4 lymph nodes. All sampled nodes were x rayed at the time of surgery to identify marker clip.Results: We had no procedure related complications with insertion of marker clip in any patients. The median number of nodes was 4.0. Average lymph nodes retrieved was 4.9. SLNB was identified in 47/55 patients (85.5%). Median number of sentinel nodes was 3.0 (Range 1-7) Marker was identified in 41/55 patients (74.5%) 30 (54.5%) patients had marker in sentinel node and 11 (20%) patients had marker in non-sentinel node. Histologically clip was reported in 21 (51.2%) patients. Overall pathological complete response (pCr) in axilla was seen 31/55 (56.45%). Tumours with Her2 over expression showed pCr in axilla 83% n=19/23 while triple negative tumours showed pCr in axilla 64% n=9/14. Er+ Her2- tumours showed low pCr rate 16.7% n=3/18. Completion axillary clearance was performed in 14/24 patients and 10/24 received radiotherapy to axilla.Conclusions: Clips in axillary lymph nodes are safe & relatively easy to deploy without any increased morbidity. Our clip identification rate (74.5%) co relates with other well-known publications (Caudel et al 80%, Z1071-76%). Our study findings validate that clip placement improves the identification of involved lymph nodes and hence improve the accuracy of limited axillary dissection in staging axilla.

Citation Format: Mohammad Bilal Elahi, Raouef Ahmed Bichoo, Kartikae Grover, Eiman Khalifa, Naila Bint Ihsan, Peter J Kneeshaw, Brendan Paul Wooler, Dorin Dumitru, Ronjabati Roychaudhury, Ayesha Rahman, Tapan Kumar Mahapatra. Clipping of involved axillary lymph nodes before Neo adjuvant chemotherapy may improve in identification rates & staging of axilla in 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 PS1-55.
Abstract PS1-60: Is immediate breast reconstruction safe in post neoadjuvant chemotherapy patients? A single centre audit
Authors: Mansour Fatima , Meilak Joseph , Kabeer Kirti , Gowda Manoj , Jafferbhoy Sadaf , Marla Sekhar , Gopalan Vallipuram , Narayanan Sankaran , Soumian Soni
Published: February 2021

Introduction: Neoadjuvant chemotherapy (NACT) is increasingly utilised in the treatment of aggressive breast cancers. There are concerns that this could impact patient recovery following extensive oncoplastic procedures. The literature regarding this is limited and conflicting. We aimed to assess the impact of neoadjuvant chemotherapy on patients undergoing immediate breast reconstructions.

Method: A 5-year retrospective single centre audit of prospectively collected data on patients undergoing immediate breast reconstruction following NACT, was completed. The oncoplastic procedures performed included myocutaneous and perforator flaps, therapeutic mammoplasty and implant based reconstruction. Demographic data, length of stay, biochemical measurements, rates of wound infection, haematoma, explantation rates and return to theatre, were collected. For comparison a matched cohort of patients who underwent primary reconstruction without NACT, during the same period, was selected.

Results: One hundred and fourteen patients were included in the study (52 post NACT vs 62 controls). There were 52% that underwent implant based reconstruction, 33% flaps and 15% mammoplasties. Overall, the NACT group appeared to have slightly improved outcomes including lower complication rates (19% vs 23%, p= 0.042) and length of stay (1.45 vs 1.59 days, p>0.05). Hypoalbuminemia (25.0%) and low WCC (65.2%) were significantly higher in the NACT group but this was not associated with increased complication rates. Conclusion: Our audit suggests that NACT does not cause a significant increase in post-operative morbidity. Further studies with larger numbers will be required to validate these results.

Citation Format: Fatima Mansour, Joseph Meilak, Kirti Kabeer, Manoj Gowda, Sadaf Jafferbhoy, Sekhar Marla, Vallipuram Gopalan, Sankaran Narayanan, Soni Soumian. Is immediate breast reconstruction safe in post neoadjuvant chemotherapy patients? A single centre audit [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 PS1-60.
Abstract PS1-66: Current practice in implant-based breast reconstruction: A french long-term follow-up study
Authors: Pauly Lea , Couturaud Benoit , Reyal Fabien
Published: February 2021

Background: There is a lack of data on the use of breast implants and the path of patients reconstructed after breast cancer in France. This study aims to identify the paths of patients reconstructed by breast implant in France and assess their impact on survival, but also estimate the quality of the reconstruction, determined by early removal or replacement of implants.Methods : We performed a multicentric retrospective cohort study on women who underwent immediate or delayed implant-based reconstruction after curative or prophylactic mastectomy between 2002 and 2010 in three French private health institutions of public interest.Results : We identified 9 care pathways according to the type of disease, the type of surgery, the addition or not of adjuvant radiotherapy, and the timing of reconstruction. Theses courses concern 2,499 patients, and 3,191 breasts on which at least one implant has been placed. Five implant brands were mainly used during this period: PIP, Mentor, Allergan, Sebbin, and Perthese - with a total of 4,106 implants. The median of follow-up is 6 years [0 ;12 ;1]. The number of implants per breast is significantly different according to the reconstruction pathways (p<0.001). The overall survival and removal incidence of implants are significantly different according to the differents profiles of reconstruction (Log-Rank test: p <0.001).Conclusion : The profiles of patients reconstructed by implants are very heterogeneous, according to their disease, their surgery, the adjunction of adjuvant radiotherapy, and the reconstruction time. This leads to very differents overall survival and breast implants removal rates. By identifying specific pathways despite the heterogeneity of the population, this study makes it possible to identify patients at risk more precisely and to have a more global vision on implant reconstruction in France in the 2000s, over a decade of PIP breast implant use.

Citation Format: Lea Pauly, Benoit Couturaud, Fabien Reyal. Current practice in implant-based breast reconstruction: A french long-term follow-up 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 PS1-66.
Abstract PS11-22: Lipophilic statins for prolonging dormancy and overall survival: A real-world retrospective investigation
Authors: Marti Juan Luis Gomez , Wells Alan
Published: February 2021

Background: Micrometastases from breast cancer (BC) might undergo quiescence following adjuvant therapies. Oftentimes they reactivate, prompting metastatic relapse and aggressive, uncurable disease. It is necessary to find alternative, safe therapies that could be used as adjuvants for delaying the dormancy process and reduce metastatic breast cancer (MBC) progression. Prior epidemiological studies found prolonged overall survival from chronic statin use. However, the effectiveness of statin use through different stages of progression, including advanced MBC, has not yet been defined. Methods: A real-world, retrospective analysis of 1,016 deceased patients with MBC treated from 1999-2019 at the University of Pittsburgh Medical Center (UPMC). Lipophilic statin (atorvastatin and simvastatin) use and dosing were retrieved from medical records through an IRB-approved R3 request and merged with already available clinical variables. A total of 122 patients were included in the analysis as the statin use group. This included patients who were prescribed statins through the course of their breast cancer. For measuring time to relapse, only patients with statin prescription before being diagnosed with MBC were selected. Log-ranks were used to compute survival. Uni- and multi-variate Cox hazard models were also applied. Statistical analysis was computed using the package ggpubr on R v3.6.3.Results: Women who used statins were older at the time of detection of primary (60 vs 52 years of age, respectively) and MBC (66 vs 56 years of age, respectively). An almost 2-fold reduction was found in the onset of liver metastasis as first relapse in the statin group, compared to general population (5.7% vs 10.4%, respectively). Increased overall survival (OS) was found among statin users who had ER (+) (p<0.05), and HER2 (-) (p<0.05) BC. Statins were associated with an increase in time from diagnosis until relapse, in ER (+) (p=0.03) and HER2(-) (p=0.02) patients with BC. Patients with ER (-), HER2 (-) MBC also seemed to partially benefit from statin use (p=0.09). Multivariate analysis adjusted for age, ER-status, statin use, and adjuvant chemotherapy also predicted increased OS for patients using statins. No differences in survival were seen when measuring time from metastatic diagnosis to death, suggesting that statins may be effective in prolonging dormancy but lack benefit against relapsing MBC.Conclusion: Lipophilic statins may prolong dormancy and overall survival but not slow the progression of relapsing metastatic breast cancer.

Citation Format: Juan Luis Gomez Marti, Alan Wells. Lipophilic statins for prolonging dormancy and overall survival: A real-world retrospective investigation [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 PS11-22.
Abstract PS11-23: Current landscape in phase 3 trials in breast cancer at major oncology conferences
Authors: Bretas Gustavo Oliveira , Bines José , Saad Everardo Delforge
Published: February 2021

Background: The oral presentation of studies at conferences may impact treatment practice even before the publication or regulatory approval. Methodological aspects and reporting patterns are evolving, and an assessment of these features may help understand the current landscape and the way forward. Methods: We analyzed the characteristics of primary analyses of phase 3 trials from oral sessions presented at ASCO, ESMO and SABCS 2017-19 and the timing of their subsequent publications. We excluded non-inferiority trials and duplicate presentations within the period. Results: Of 36 unique trials, 19/10/7 had a first author from Europe/United States/Asia or elsewhere, and 21/15 were in the (neo)adjuvant/palliative settings. All but one trial had 2 arms. The number of patients enrolled ranged from 226 to 4884 (median, 646). All but 2 trials were on systemic therapy, with 16 dedicated exclusively to hormone-receptor+, 8 to HER2+ and 6 to triple-negative disease. According to the authors, 23 (63.9%, 95% CI, 46.2 to 79.2%) trials were positive, and 13 were negative. For only 2 of the negative trials was the conclusion not entirely consistent with results. When sponsor information was available, 18/21 industry vs 4/14 academic trials were positive (P=0.002). Paradoxically, negative trials were larger than positive trials (medians of 2639 and 585 patients; P=0.002), perhaps because all but one of 13 negative trials were in the (neo)adjuvant setting, vs 9/23 among positive trials (P=0.004). The time to publication was significantly shorter for positive than negative trials (medians of 215 vs 785 days; HR=0.32; P=0.013). Of 30 trials with time-to-event endpoints, the ratio between observed:expected HR could be computed for 24: the mean was 0.88 for 15 positive and 1.43 for 9 negative trials (P=0.004; 1.09 overall). Conclusion: In recent phase 3 trials in breast cancer, positive trials are more likely than negative trials to be industry-sponsored, to assess the metastatic setting, and to be published earlier. These results also suggest that the treatment effect has been underestimated in positive trials. Research is ongoing to elucidate potential determinants of the latter hypothesis.

Citation Format: Gustavo Oliveira Bretas, José Bines, Everardo Delforge Saad. Current landscape in phase 3 trials in breast cancer at major oncology conferences [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 PS11-23.
Abstract PS11-31: Survival among female breast cancer patients who have survived a previous cancer
Authors: Pruitt Sandi L , Zhu Hong , Heitjan Daniel , Gerber David E , Maddineni Bhumika , Xiong Danyi , Halm Ethan , Murphy Caitlin
Published: February 2021

Background A growing number of women newly diagnosed with breast cancer have survived a previous cancer. Although little is known about their prognosis, this population is frequently excluded from clinical trials. Additional evidence about the survival of this population is needed, so that trial sponsors and investigators can create evidence-based trial eligibility criteria. Among women newly diagnosed with breast cancer, we examined the impact of previous cancer on overall and cancer-specific survival. Methods This population-based cohort study included patients age ≥66 years and diagnosed with breast cancer between 2005-2015 in linked SEER-Medicare data. Separately by breast cancer stage, we estimated overall survival using Cox regression and cause-specific survival using competing risk regression for women with and without previous cancer, adjusting for numerous covariates and competing risk of death from previous cancer, other causes, or the incident breast cancer. Results Of 138,576 women diagnosed with incident breast cancer, 10,822 (8%) had a previous cancer of another organ site. Many of these (n=5,014, 46.3%) were diagnosed ≤5 years of breast cancer. For all breast cancer stages except IV in which there was no significant survival difference, women with vs. without previous cancer had worse overall survival. This survival disadvantage was driven by deaths due to the previous cancer and other causes. In contrast, women with previous cancer generally had favorable breast-cancer specific survival; however this varied somewhat by stage and over time. Conclusions Many women newly diagnosed with breast cancer are already cancer survivors. These women had generally worse overall survival, worse survival from other causes, but their disease-specific survival varied depending on their breast cancer stage and over time.

Citation Format: Sandi L Pruitt, Hong Zhu, Daniel Heitjan, David E Gerber, Bhumika Maddineni, Danyi Xiong, Ethan Halm, Caitlin Murphy. Survival among female breast cancer patients who have survived a previous 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 PS11-31.
Abstract PS11-41: A spatially resolved single cell atlas of the human breast
Authors: Kessenbrock Kai
Published: February 2021

The human breast consists of lobules connected to an intricate network of ducts that are surrounded by fatty tissues, designed to produce and transport milk to nourish offspring. Histopathology has identified 10 major cell types based on morphological features but have provided limited information on cell states - the transcriptional programs of cell types that reflect different biological functions. In this study we have generated an unbiased ‘cell atlas’ of the normal human breast to define the cell types and cell states using single cell RNA sequencing and spatial transcriptomics methods. We performed 3’ microdroplet based single cell and nuclei RNA sequencing of 248,687 stromal cells and 89,301 nuclei from 35 women with pathologically normal breast tissues that were collected from mastectomies and reduction mammoplasties. Unbiased expression analysis identified four major cell types: adipocytes, epithelial cells (luminal and basal), fibroblasts and endothelial cells and defined their transcriptional programs. Additionally, 8 minor cell types were identified in the breast, including macrophages, T-cells, natural killer cells, mast cells, pericytes, apocrine cells, neurons and smooth muscle cells. Our data revealed hundreds of novel markers of these cell types and defined their transcriptional programs and cell states. Most cell types had multiple transcriptional programs including luminal epithelial cells (hormone receptor positive and secretory), basal epithelial cells (myoepithelial or basal), endothelial cells (E1, E2, E3), myeloid cells, T-cells and fibroblasts (F1-F4) and provided insight into developmental lineages. We further delineated the spatial organization of these cell types and cell states within the tissue architecture via a 34 antibody CODEX ultra-high plex immunofluorescence imaging experiment. Antibodies were targeted against epithelial, endothelial and immune cells and imaging data were acquired at single cell resolution from breast tissues measuring up to 35mm2. Cell phenotypes were independently clustered, correlated to transcriptomic data and cellular neighborhoods were mapped using nearest neighbor approximations. The breast cell atlas data provides an invaluable normal reference for the research community to understand how normal cell types are reprogrammed in diseases such as breast cancer.

Citation Format: Kai Kessenbrock. A spatially resolved single cell atlas of the human breast [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 PS11-41.
Abstract PS12-22: Maintenance therapy with everolimus plus aromatase inhibitors vs aromatase inhibitors as after first-line chemotherapy in HR+/HER2- metastatic breast cancer: Updated analyses of the phase III randomized MAIN-A trial
Authors: Guarneri Valentina , Cinieri Saverio , Dieci Maria Vittoria , Bengala Carmelo , Mariani Gabriella , Bisagni Giancarlo , Frassoldati Antonio , Zamagni Claudio , Orlando Laura , Giorgi Carlo Alberto , De Salvo Gian Luca , Conte PierFranco
Published: February 2021

Background Despite endocrine therapy is the mainstay of treatment for HR+/HER2- metastatic breast cancer (MBC), patients with high disease burden or those at risk of visceral crisis are still offered first-line chemotherapy (CT). Chemotherapy is generally followed by maintenance hormonal therapy. The MAIN-A study is an investigator-driven, randomized phase III trial designed to compare maintenance everolimus (EVE) combined with aromatase inhibitors (AI) versus AI alone in pts with disease control after first-line CT.Methods Postmenopausal pts achieving disease control (stable disease, partial response or complete response) after first-line CT were randomly assigned to EVE 10 mg po daily plus AI or to AI alone. Primary aim was PFS in the ITT. We present here overall survival (OS) results and the impact of tumor characteristics on PFS.Results 110 pts were randomized to EVE+AI (n=52) or to AI (n= 58). Primary aim results have been already presented (Guarneri V, ESMO Breast 2019), showing a non-significant prolongation of median PFS in the ITT population for EVE+AI (9.9 mos vs 7.2 mos, HR 0.764, 95% CI 0.501-1.164. Patients with visceral metastases tended to experience shorter PFS as compared with patients with patients with bone/soft tissues metastases (median 11.1 mos vs 6.4 mos, p=0.0746). The levels of estrogen receptor expression (>or< 50%) did not impact PFS, overall and by treatment arm. At the time of this writing, a total of 61 death events have been recorded. No difference in OS was observed between the two arms (median 33.9 mos for EVE+AI vs 33.5 mos for AI, HR 0.97, 95% CI 0.59-1.61).Conclusions Maintenance EVE+AI did not significantly impact on the outcome of metastatic breast cancer patients deemed suitable for first line chemotherapy.

Citation Format: Valentina Guarneri, Saverio Cinieri, Maria Vittoria Dieci, Carmelo Bengala, Gabriella Mariani, Giancarlo Bisagni, Antonio Frassoldati, Claudio Zamagni, Laura Orlando, Carlo Alberto Giorgi, Gian Luca De Salvo, PierFranco Conte. Maintenance therapy with everolimus plus aromatase inhibitors vs aromatase inhibitors as after first-line chemotherapy in HR+/HER2- metastatic breast cancer: Updated analyses of the phase III randomized MAIN-A trial [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 PS12-22.
Abstract PS13-12: Apatinib combined with taxanes and platinum neoadjuvant chemotherapy for patients with triple-negative and HER2-positive breast cancer: A multicenter, randomized, open-label, phase II trial
Authors: Liu Yunjiang , Zhang Xiangmei , Wang Li , Cao Miao , Zhang Shuo , Zhang Hui , Zhou Yarong , Wang Jintian
Published: February 2021

Background: Apatinib, a tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor 2 (VEGFR2), has demonstrated a promising efficacy in patients with metastatic breast cancer. For triple-negative and HER2-positive subtypes, increasing the pathological complete response (pCR) of neoadjuvant therapy may benefit their clinical outcomes. Here, we assessed whether the combination of Apatinib with neoadjuvant chemotherapy elevate the pCR rate in locally advanced breast cancer. Method: In this multicenter, open-label trial, we randomized 53 patients into TP neoadjuvant chemotherapy (docetaxel 75 mg/m2 or nab-paclitaxel 260 mg/m2 or paclitaxel liposome 175 mg/m2 day 1, and carboplatin AUC=6 or cisplatin 75 mg/m2 or lobaplatin 30 mg/m2 day 1), or combined with apatinib (500mg day 1-21) . Trastuzumab was added to neoadjuvant therapy in HER2-positive subtype. Six cycles were repeated every 3 weeks. Results: In total patients with stage IIb-IIIc triple-negative and HER2-positive breast cancer, the addition of apatinib to TP neoadjuvant chemotherapy (Apa+TP) significantly increased the pCR rate (70.8%, 17/24), compared with TP along (41.4%, 12/29), P=0.032. When separating patients into triple-negative (Apa+TP 66.7% (8/12) vs. TP 42.9% (3/7)) and HER2-positve (Apa+TP 75% (9/12) vs. TP 40.9% (9/22)) subtypes, the effect of apatinib on pCR was also improved though no significant differences were found (P=0.377; P=0.080 separately) compared with control group. The most common Grade 3-4 adverse events (AE) included hypertension (Apa+TP 12.5% vs. TP 0%, P=0.173), hand-foot syndrome (Apa+TP 8.3% vs. TP 0%, P=0.389) and erythra (Apa+TP 4.2% vs. TP 0%, P=0.924). No significant differences of toxic effects were found between Apa+TP and control group. Conclusion: Apatinib combined with TP neoadjuvant chemotherapy significantly increased the pCR rate in patients with locally advanced triple-negative and HER2-positive breast cancer, indicating an applicable strategy in the future.

EfficacyTriple-negative breast cancer efficacyHer2-positive breast cancer efficacySafety

Citation Format: Yunjiang Liu, Xiangmei Zhang, Li Wang, Miao Cao, Shuo Zhang, Hui Zhang, Yarong Zhou, Jintian Wang. Apatinib combined with taxanes and platinum neoadjuvant chemotherapy for patients with triple-negative and HER2-positive breast cancer: A multicenter, randomized, open-label, phase II trial [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 PS13-12.
Abstract PS13-36: Prevention of chemotherapy-induced alopecia: A prospective study in breast and ovarian cancer patients
Authors: Papadopoulos Lia A , Chua Susan , Goss Geraldine , Johnson Jane , Ling Aaron , Devitt Bianca
Published: February 2021

Background: Scalp cooling minimises chemotherapy-induced alopecia (CIA) which may reduce distress, improve quality of life and body image. This study assesses scalp-cooling efficacy in women receiving chemotherapy for early and advanced breast and ovarian cancer. Methods: Women with breast or ovarian cancer undergoing chemotherapy and scalp cooling at two intuitions were enrolled prospectively. Data collected included demographics, chemotherapy agent(s), hair loss and reasons for discontinuing scalp cooling. Successful hair preservation (SHP) was defined as Dean’s scale grade 0-2 (<!–=50%) hair loss without desire for head-cover use at the completion of chemotherapy. Results were analysed using descriptive statistics. Results: 188 patients were enrolled, mean age 54 [28-83] . 90 women (48%) achieved SHP. 120 (64%) completed scalp cooling. Reasons for discontinuation included: intolerance 34 (49%), perceived loss of hair in 28 (41%) and extra chair time in 6 (9%). 14% continued scalp cooling despite significant hair loss (>50%) SHP was significantly higher in non-anthracycline regimens; 62% (70/112) compared with anthracycline-containing regimens; 24% (18/74), p<0.0001. Single-agent taxane regimen achieved highest SHP in 70% (31/44)and in carboplatin/Paclitaxel regimen; 80% (16 of 20). SHP was lower in Docetaxel-Cyclophosphamide; 48% (21/44), in FEC-D; 27% (20/74) and in AC-T; 26% (16 of 62). SHP rates did not differ between ethnicities; 47% (15/32) in Asian and 47% (75/156) of non-Asian ethnicities, p=0.90. In non-anthracycline regimens SHP was numerically, but non-significantly higher in younger age (<65) 65% (52/81) compared with older age (>/=65) 57% (17/29). Conclusion: Among women receiving chemotherapy for early or advanced breast and ovarian cancer, scalp cooling offers a chance to prevent CIA with most success in taxane +/- carboplatin regimens.

Further study is warranted into patients views on the trade-off of benefits and costs in this limited, resource intensive intervention.

Citation Format: Lia A Papadopoulos, Susan Chua, Geraldine Goss, Jane Johnson, Aaron Ling, Bianca Devitt. Prevention of chemotherapy-induced alopecia: A prospective study in breast and ovarian cancer patients [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 PS13-36.
Abstract PS14-04: A picture worth a thousand words - “classic” inflammatory breast cancer (IBC) appearance associated with overall survival
Authors: Balema Wintana , Liu Diane , Shen Yu , El-Zein Randa , Kai Megumi , Overmoyer Beth , Miller Kathy D , Le-Petross Carisa , Ueno Naoto T , Woodward Wendy A
Published: February 2021

Background: IBC is considered a clinical diagnosis characterized by rapid onset of diffuse skin changes in the setting of a breast cancer diagnosis. A wide variety of visual changes are accurately diagnosed as IBC. Here, we sought to determine whether the most subjectively “classic” appearing presentation (swollen, involved breast with nipple inversion and diffuse skin change) was associated with worse outcomes.

Method: We reviewed the images and charts of patients from the prospective IBC registry from the MD Anderson IBC Clinic. Breast medical photographs were reviewed by a non-expert and the visual presentation was scored as classic (as above), not classic, and in between. Comparative analyses were used to assess differences between patient groups using Chi-squared test, or Fisher’s exact test for categorical variables. Wilcoxon rank sum test was used for continuous measures. We used the Kaplan Meier estimator and the log-rank test to investigate association between scoring and survival distributions. Cox proportional hazard regression was employed to assess the impact of important covariates on the overall survival.

Results: We analyzed 245 IBC patients with median age 55 (range, 26-81), M0 vs. M1 status (157 and 88 patients, respectively), 68 TNBC vs. 177 non-TNBC patients. The classic presentation was significantly associated with smoking, post-menopausal status, and metastatic disease at presentation (P = 0.002, 0.018, and 0.004, respectively). Presentation was significantly associated with OS in univariate analysis (P < 0.001). 10 year overall survival was 57% vs. 33% for classic (score 3) versus non-classic or in between presentation. The multivariable Cox regression model adjusting for clinical staging (P<0.001) and TNBC status (P<0.001) demonstrated classic presentation score was significantly associated with poorer OS time (HR 2.4, CI 1.6-3.6, p<0.001).

Conclusions: A visual inspection of presentation photograph for “classic” appearance, obvious swelling, skin change, and nipple inversion, independently predicted poorer OS in IBC. Further work is warranted to understand the differences in classic and non-classic presentations, and the relationship between smoking and breast cancer presentation.

Citation Format: Wintana Balema, Diane Liu, Yu Shen, Randa El-Zein, Megumi Kai, Beth Overmoyer, Kathy D Miller, Carisa Le-Petross, Naoto T Ueno, Wendy A Woodward. A picture worth a thousand words - “classic” inflammatory breast cancer (IBC) appearance associated with overall survival [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 PS14-04.
Abstract PS14-06: Changes in management of breast cancer patients during first wave of COVID19, throughout the area of Kent, United Kingdom. An audit of ESMO guideline implementation
Authors: Rodney Simon N , Abson Charlotte , Burcombe Russell , Jyothirmayi Rema , Harper-Wynne Catherine
Published: February 2021

Background: The global COVID-19 pandemic has placed unprecedented burden on individual oncology patients, oncology departments, hospitals and national health systems. In order to protect individual patients from the risk of COVID-19 infection as well as improve capacity for COVID-19 patient management, a series of national and internationally agreed measures were proposed. During the first wave of infections the virulence and effect on cancer patients was not known. It is vitally important that the measures implemented to combat these risks are assessed and evaluated in order to learn best how to manage potential future waves of known and unknown viral infections.Methods: The international ESMO COVID-19 guidelines and national (NICE) guidelines were implemented across Kent, UK. All changes to treatment regimens were audited to assess what were the most frequent changes and in which patient groups could these be implemented. Data was subdivided for both early and advanced breast cancer as well as ER+, HER2+ or triple negative disease.Results: We collected full treatment history from 1,718 breast cancer patients currently receiving active oncology treatments. We were able to change treatment regimens due to COVID19 for 32.8% of patients. Of these 27.1% were early breast cancer patients compared with 43.7% were those with advanced metastatic disease. The most common changes for neoadjuvant changes were proceeding to surgery before completion of planned chemotherapy (10.2%), switch to 3 weekly Paclitaxel (10%) and chemotherapy break (8%). For adjuvant patients the most common changes included postponement of bisphosphonates (70.8%), chemotherapy break (13.5%), and curtailment to 6 months of adjuvant Trastuzumab (10.4%). For our palliative patients the most common changes included delay CDK4/6 inhibitor treatment (79.2%), postponement of bisphosphonates (24.8%), break in HER2 antibody (9.6%) and break in chemotherapy (8%).Conclusions: A large proportion of breast cancer oncology patients were deemed suitable to have a change in original planned treatment. We are fortunate to have comparatively large number of treatment options that can be customised on a patient basis to individual reduce risk of COVID-19. Further analysis is needed over time to compare the oncological outcomes of those in whom treatment was changes from the current gold standards of care.

Citation Format: Simon N Rodney, Charlotte Abson, Russell Burcombe, Rema Jyothirmayi, Catherine Harper-Wynne. Changes in management of breast cancer patients during first wave of COVID19, throughout the area of Kent, United Kingdom. An audit of ESMO guideline implementation [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 PS14-06.
Abstract PS14-13: National comprehensive cancer network (NCCN) recommendations for drugs without US food and drug administration (FDA) approval in metastatic breast cancer: A cross-sectional study
Authors: Etan Tal , Amir Eitan , Tibau Adriana , Yerushalmi Rinat , Moore Assaf , Shepshelovich Daniel , Goldvaser Hadar
Published: February 2021

Background: NCCN guidelines include recommendations not approved by the FDA. We aimed to compare the NCCN recommendations for metastatic breast cancer (MBC) with the FDA approved indications and to identify characteristics that are associated with NCCN recommendations for off-label treatment. Methods: All NCCN recommendations for MBC and their supporting data were identified. Drug labels were reviewed to determine whether recommendations are FDA approved indications. Odds ratio (OR) and 95% confidence interval (CI) were calculated to compare between FDA approved and off-label recommendations for pre-specified categories including drug type, tumor subtype, level of recommendation and line of therapy. Results: Of 124 recommendations identified, 68 (55%) were off-label. Chemotherapy and human epidermal growth factor receptor 2 (HER2) targeted drugs were associated with less frequent approved indications (OR=0.28, 95% CI 0.12-0.62, p=0.001 and OR=0.29, 95% CI 0.12-0.70, p=0.005, respectively). Recommendations for endocrine therapy (OR=3.44, 95% CI 1.32-9.09, p=0.009) and non-HER2 targeted treatment (OR=10.0, 95% CI 3.03-33.33, p<0.001) were associated with FDA approved indications. Compared to combination therapies, monotherapies were more likely to be FDA approved (OR=3.45, 95% CI 1.64-7.23, p=0.001). Category 1 (OR=7.63, 95% CI 2.19-26.55, p=0.001) and preferred NCCN recommendations (OR=5.49, 95% CI 2.36-12.77, p<0.001) were more likely to be FDA-approved indications. Compared to off-label recommendations, NCCN recommendations of approved drugs were based on significantly higher sample size (mean 477 vs. 342 patients, p=0.017) and were non-

significantly associated with availability of randomized data (OR=1.92, 95% CI 0.87-4.24, p=0.10).Conclusion: More than half of all NCCN recommendations for MBC are off-label, mostly involving chemotherapy containing regimes for HER2 negative disease and combinations which include HER2 targeting drugs. The clarity of the NCCN guidelines can be improved by underlining the strength of the evidence supporting various recommendations for MBC and the hierarchy between various treatment options.

Citation Format: Tal Etan, Eitan Amir, Adriana Tibau, Rinat Yerushalmi, Assaf Moore, Daniel Shepshelovich, Hadar Goldvaser. National comprehensive cancer network (NCCN) recommendations for drugs without US food and drug administration (FDA) approval in metastatic breast cancer: A cross-sectional 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 PS14-13.
Abstract PS14-16: Novel iodine nanoparticle micro-localization and resultant radiotherapy-enhancement of triple negative human breast cancer growing in the brains of athymic nude mice
Authors: Ridwan Sharif M , Hainfeld James F , Stanishevskiy Yaroslav , Ross Vanessa , Smilowitz Henry M
Published: February 2021

About 30% of breast cancers metastasize to brain; those widely disseminated are fatal typically in 3-4 months, even with the best available surgery, drugs, and radiotherapy. To address this dire situation, we have developed iodine nanoparticles (INPs) that target brain tumors after intravenous (IV) injection. The iodine then absorbs X-rays during radiotherapy (RT), creating free radicals and local tumor damage, effectively boosting the local RT dose at the tumor. Efficacy was tested using the very aggressive human triple negative breast cancer (TNBC, MDA-MB-231 cells) growing in the brains of athymic nude mice. With a well-tolerated non-toxic IV dose of the INPs (7 g iodine/kg body weight), tumors showed a heavily iodinated rim surrounding the tumor having an average uptake of 2.9% iodine by weight (peaks at 4.5%), calculated to provide dose enhancement factors of ~5.5 (peaks at 8.0) – the highest ever reported for any radio-enhancing agents. With 15-Gy, single dose RT, all animals died by 72 days; INP pretreatment resulted in longer-term remissions with 40% of mice surviving 150 days and 30% surviving > 280 days (Hainfeld et al., 2020). Fluorescence confocal microscopy revealed most INP staining co-localized with CD31 in the tumor center and tumor periphery. Greatest INP and CD31 staining was in the tumor periphery, the region of increased Micro CT contrast. Tumor cells are seen to line irregularly-shaped spaces (ISS) with INP and CD31 staining very close to or on the tumor cell surface and with PAS stain on their boundary and may represent a unique form of CD31-expressing vascular mimicry in intracerebral 231-tumors. INP and CD31 co-staining is also seen around ISS formed around tumor cells migrating on CD31 positive blood-vessels. We hypothesize that breast cancer cells secrete a CD31 containing scaffold to which IV-injected INPs bind; tumor cells proliferate along the scaffold forming the boundaries of the ISS creating a form of vascular mimicry. The significant radiation dose enhancement to the prolific INP-binding ISS found throughout the tumor but concentrated in the tumor rim, may contribute significantly to the life extensions observed after INP-RT; vascular mimicry could represent a new nanoparticle, particularly INP, tumor-homing target.

Citation Format: Sharif M Ridwan, James F Hainfeld, Yaroslav Stanishevskiy, Vanessa Ross, Henry M Smilowitz. Novel iodine nanoparticle micro-localization and resultant radiotherapy-enhancement of triple negative human breast cancer growing in the brains of athymic nude mice [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 PS14-16.