bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract GS1-05: Trial Assigning Individualized Options for Treatment (TAILORx): An Update Including 12-Year Event Rates
Authors: Sparano Joseph , Gray Robert J. , Makower Della , Albain Kathy S. , Hayes Daniel F. , Geyer Charles , Dees Elizabeth , Goetz Matthew P. , Olson John A. , Lively Tracy G. , Badve Sunil , Saphner Thomas , Wagner Lynne I. , Whelan Timothy , Kaklamani Virginia , Sledge George
Published: March 2023

Background: Late recurrence of breast cancer after 5 years accounts for about 50% of recurrences in hormone receptor (HR)-positive early breast cancer (EBC). TAILORx established non-inferiority of adjuvant endocrine therapy (ET) given for at least 5 years to chemotherapy plus ET (CET) in EBC and a 21-gene recurrence score (RS) of 11-25, although there was some chemotherapy benefit in women

Methods: Eligibility criteria included women 18-75 years with HR-positive, HER2-negative, T1b-T2N0 EBC who agreed to have CT assigned or randomized based on the RS assay. The primary endpoint was invasive disease-free survival (iDFS) in the RS 11-25 group. The “primary analysis” refers to the original prespecified analysis for the primary IDFS endpoint (836 IDFS events at full information in the RS 11-25 group) after a median of 7.5 years. The “updated analysis” was performed after a median followup of 11.0 and 10.4 years in the randomized and overall populations, respectively.

Results:10,253 eligible women enrolled between 4/7/06-10/6/10.The updated analysis includes substantially more events that the primary analysis, including IDFS events (1819 vs. 1210), distant recurrences (561 vs. 384), locoregional +/- distant recurrences (764 vs. 543), and deaths (910 vs. 499). The table provides 5 and 12-year event rates (and standard errors) for all arms, and comparisons of the randomized arms. The primary trial conclusions remain unchanged: ET was non-inferior to CET in the randomized group with a RS 11-25. Although recurrence occurred in < 10% by 12 years for a RS 0-25, late recurrence events beyond 5 years exceeded earlier recurrence. Non-recurrence events occurred in about 13% at 12 years (~1%/year), contributing substantially to the IDFS rates. For women

Conclusions: The current updated analysis confirms findings from the original primary analysis that ET is non-inferior to CET in HR-positive, HER2-negative, node-negative EBC and a RS 11-25. As in the original primary analysis, the subgroup of women

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

Background: Recent studies suggest that enhancer reprogramming underlies heterogeneity and disease progression in estrogen receptor-positive (ER+) BC. Cell-type/state specific transcription is governed by high-order assemblies of master transcription factors (TFs) and epigenetically defined regulatory regions including super-enhancers (SEs). We previously showed that aberrant activation of the pioneer TF FOXA1 promotes enhancer and transcriptional reprogramming in endocrine-resistant BC, involving the ER and the AP-1 FRA1 and c-JUN TFs. As SEs maintain a robust cell-type/state specific core transcriptional regulatory circuitry (CRC) in developmental and tumorigenic processes, we sought to identify key additional TFs in SE/FOXA1-driven CRCs in endocrine resistance, which could serve as attractive therapeutic targets.

Methods: TF binding motif at the shared SEs (mapped by H3K27ac ChIP-seq) between MCF7-parental (P) cells with ectopic FOXA1 overexpression (OE) and the endogenous FOXA1-amplifed tamoxifen-resistant (TamR) cells was analyzed by HOMER. ER-bound SEs distinguishing TamR vs. P cells were defined by integrating the SEs with our prior ER ChIP-seq data (PMID 28507152). KLF4 motif within these ER-bound SEs was scanned using FIMO and linked to nearby genes by intersection with the previously defined promoter-tethered regions (PTRs) (PMID 24141950). Differential gene expression in MCF7-TamR cells upon KLF4 knockdown (KD) by 3 unique siRNAs was analyzed using limma from edgeR. The biological and clinical significance of the KLF4-dependent genes was analyzed using Gene Ontology and survival modeling with METABRIC and the ER+ metastatic BC cohort ( SABCS19-GS2-02 ). Cell migration was assessed by the wound-healing assay.

Citation Format: Rachel Schiff. Oncogene signal transduction and antiestrogen resistance [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr MS1-1.
Abstract MS1-3: Treatment of ER+/HER2+ breast cancer
Authors: Johnston Stephen
Published: March 2023

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

Citation Format: Stephen Johnston. Treatment of ER+/HER2+ breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr MS1-3.
Abstract OT1-03-01: XMT-1660: A Phase 1b trial of a B7-H4 targeted Antibody Drug Conjugate (ADC) in Breast, Endometrial, and Ovarian Cancers
Authors: Hamilton Erika , Chaudhry Arvind , Spira Alexander I. , Adams Sylvia , Abuhadra Nour , Giordano Antonio , Parajuli Ritesh , Han Hyo S. , Weise Amy , Marchesani Aubri , Josephs Kate , Shin Chu Ri , Kalinsky Kevin
Published: March 2023

Background: Breast cancer (BC) is the most commonly diagnosed cancer and one of the leading causes of cancer death in women. Despite significant therapeutic advances, the majority of patients with unresectable or recurrent/metastatic disease eventually develop resistance to available standard of care (SOC) therapies. B7-H4 is a poor prognostic factor and is overexpressed in several cancers including endometrial, ovarian, and breast. As a member of the CD28/B7 family of cell surface proteins, it promotes tumorigenesis by suppressing anti-tumor immunity. XMT-1660 is a B7-H4-targeted Dolasynthen antibody drug conjugate with a precise, optimized drug-to-antibody ratio and a DolaLock microtubule inhibitor payload with controlled bystander effect. In the preclinical setting, XMT-1660 has demonstrated anti-tumor activity in TNBC and ER+/HER2- patient-derived xenograft mouse models, which included tumors from heavily pre-treated patients (Collins et al, AACR 2022). Increased anti-tumor activity tended to be more frequent in models with higher B7-H4 expression, providing rationale for a Ph1 clinical trial. Methods: The Ph1 trial includes a first-in-human open-label dose escalation (DES) portion followed by dose expansion (EXP) evaluating XMT-1660 in patients with BC, EC, and OC following progression on SOC as applicable (i.e., CDK4/6i + ET; platinum-based chemotherapy). In the DES, Bayesian Optimal Interval (BOIN) design will be used to determine the MTD. Patients will receive XMT-1660 IV Q3 weeks. Primary endpoints in DES are to assess safety and determine a recommended phase 2 dose (RP2D) and assessment of preliminary efficacy as a secondary endpoint. In the EXP portion, cohorts enrolling TNBC, ER+/HER2- BC, EC/OC are planned and additional patients may be enrolled based on emerging data. The primary endpoint of EXP is to assess safety and tolerability, overall response rate, disease control rate, and duration of response. Secondary endpoints include pharmacokinetic analysis and antidrug antibodies. Patients are not selected by B7-H4 status, but baseline tumors samples are collected for retrospective tumor tissue evaluation. The trial is currently enrolling patients. NCT05377996

Citation Format: Erika Hamilton, Arvind Chaudhry, Alexander I. Spira, Sylvia Adams, Nour Abuhadra, Antonio Giordano, Ritesh Parajuli, Hyo S. Han, Amy Weise, Aubri Marchesani, Kate Josephs, Chu Ri Shin, Kevin Kalinsky. XMT-1660: A Phase 1b trial of a B7-H4 targeted Antibody Drug Conjugate (ADC) in Breast, Endometrial, and Ovarian Cancers [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT1-03-01.
Abstract OT1-12-03: Precision breast conserving surgery with the guidance of localization combined with multidetector CT 3-dimensional image reconstruction: a single center, prospective, cohort study
Authors: Xia Yiqin , Cao Da , Yang Lili , Zheng Mingjie , Weng Miaomiao , Shi Ke , Wang Ruoxi , Zhao Meng , Xie Hui , Wang Shui
Published: March 2023

Introduction: Precision breast conserving surgery (PBCS) requires doctors to precisely remove the tumor while preserving as much normal tissue as possible. The aims of this study were to determine whether wire-guided localization (WGL) combined with multidetector CT (MDCT) guided 3D reconstruction could guide PBCS.

Methods: From 2020 to 2022, 31 patients with unifocal breast cancer were enrolled for PBCS guided by WGL combined with MDCT guided 3D reconstruction. Surrounded WGL was performed under local anesthesia, followed by an immediate contrast enhanced MDCT scan. PBCS guided by MDCT guided 3D reconstruction was performed one day after the localization. Women who underwent palpation guided BCS were included as control, and logistic regression analysis was applied.

Results: PBCS were performed in 31 patients. The mean tumor size in US was 19.48±5.86mm (9-32mm). Compare with control group, a smaller specimen diameter was observed in PBCS group (P=0.005), and the rate of the largest margin greater than or equal to 20mm were significantly lower (P=0.004). The operation time of PBCS was shortened (P=0.046). Moreover, PBCS does not affect the reoperation rate (P=0.514) or the rate of positive margins (P=0.660).

Conclusion: For patients with unifocal breast cancer, WGL combined with MDCT guided 3D reconstruction could guide PBCS without affecting the safety.

Table 1. Baseline characteristics of patients in PBCS group and control group. BMI, body mass index; US, ultrasound; HR, hormone receptor.

Table 2. Surgical outcomes of patients in PBCS group and control group.

Citation Format: Yiqin Xia, Da Cao, Lili Yang, Mingjie Zheng, Miaomiao Weng, Ke Shi, Ruoxi Wang, Meng Zhao, Hui Xie, Shui Wang. Precision breast conserving surgery with the guidance of localization combined with multidetector CT 3-dimensional image reconstruction: a single center, prospective, cohort study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT1-12-03.
Abstract OT2-08-01: A prospective phase 2 study on efficacy and safety of AK105, anlotinib combined with nab-paclitaxel (nab-P) as a first-line therapy in patients(pts) with advanced triple-negative breast cancer(TNBC)
Authors: Sun Tao , Zhang Liang
Published: March 2023

Background: PD-1/PD-L1 inhibitor plus chemotherapy have shown tolerability and significant clinical benefits in pts with advanced TNBC. As antiangiogenic agent could remodel tumor blood vessels and increase the response to immune-checkpoint inhibitors (ICIs), we designed an investigator initiated trial (IIT) to investigate the efficacy and safety of AK105 (anti-PD-1 antibody), anlotinib (antiangiogenic, multi-target tyrosine kinase inhibitor) combined with nab-P as a first-line therapy in pts with advanced TNBC. Method: In this multicenter, prospective, single arm, phase 2 study, eligible pts were female aged 18-75 years, with ECOG PS 0-1, who had locally advanced or recurrent/metastatic triple-negative (estrogen receptor-, progesterone receptor- and HER2-) breast cancer. The main exclusive criteria were previous use of PD-1/PD-L1 antibody, cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) antibody or antiangiogenic agent, and central nervous system (CNS) metastases. Eligible pts were treated with intravenous AK105(200mg on day 1), oral anlotinib(12mg once daily on days 1-14) and intravenous nab-P (125mg/m2 on days 1 and 8). The triplet combination regimen repeated every 21 days until disease progression, death or intolerable toxicity. The primary endpoint is overall response rate (ORR), and the secondary endpoints are disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety. Simon’s two-stage design were used to calculate the sample size assuming ORR is improved from 45.9% (nab-P alone) to 65% (AK105, anlotinib combined with nab-P) with the power (1-β) taken as 0.80 and the type I error (α) taken as 0.05 (two-sided). Enrollment began in June 2022 with a total goal of 42 pts at 7 sites in China. Clinical trial information: NCT05244993. Research Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Citation Format: Tao Sun, Liang Zhang. A prospective phase 2 study on efficacy and safety of AK105, anlotinib combined with nab-paclitaxel (nab-P) as a first-line therapy in patients(pts) with advanced triple-negative breast cancer(TNBC). [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT2-08-01.
Abstract OT2-18-01: Nab-paclitaxel followed by dose-dense epirubicin/cyclophosphamide in neoadjuvant chemotherapy for triple-negative breast cancer: an open-label, single-arm phase II study
Authors: Liu Yin , Fan Lei , Shao Zhi-Ming , Wang Zhong-Hua
Published: March 2023

Purpose: The anti-tumor activity of nab-paclitaxel followed by epirubicin/cyclophosphamide (EC) as neoadjuvant chemotherapy (NAC) in Asian patients remains unclear, particularly in the aggressive subtype triple-negative breast cancer (TNBC). This study aimed to evaluate the efficacy and safety of this NAC regimen in TNBC. Methods: In this Simon’s two-stage, phase II study, treatment-naïve patients with resectable unilateral primary invasive TNBC were enrolled. Eligible patients received nab-paclitaxel 125 mg/m2 weekly on day 1 for 12 weeks, followed by dose-dense EC (epirubicin 90 mg/m2; cyclophosphamide 600 mg/m2) on day 1 for four 2-week cycles. The primary endpoint was the total pathological complete response (tpCR, ypT0/is ypN0) rate. Secondary endpoints included breast pathological complete response (bpCR, ypT0/is) rate, objective response rate (ORR), the proportion of patients requiring breast-conserving surgery, and safety. Results: 55 eligible patients were enrolled and treated. After neoadjuvant therapy, tpCR and bpCR were respectively observed in 43.1% (95% CI, 29.3%-57.8%) and 49.0% (95% CI, 3)4.8%-63.4%) of 51 evaluable patients for pathological response evaluation. 44 had an ORR as their best response (80.0%; 95% CI, 67.0%-89.6%). No correlations between clinicopathological variables and pathological/clinical response were observed. Grade 3 or more AEs occurred in 63.6% of 55 patients. The most frequent AEs were alopecia. No treatment-related surgical delay or death occurred. Conclusions: Nab-paclitaxel followed by dose-dense EC as NAC demonstrates promising anti-tumor activity and acceptable tolerability for patients with TNBC.

Citation Format: Yin Liu, Lei Fan, Zhi-Ming Shao, Zhong-Hua Wang. Nab-paclitaxel followed by dose-dense epirubicin/cyclophosphamide in neoadjuvant chemotherapy for triple-negative breast cancer: an open-label, single-arm phase II study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT2-18-01.
Abstract P1-01-01: The Role of Adjuvant Chemotherapy for Elderly Women with Triple-Negative Breast Cancer
Authors: Lan Tian , Guo Qiusheng , Lu Yunyan , Gu Junwei , Shao Xiying , Xu Haibin , Hu Zujian
Published: March 2023

Purpose: There is little evidence determining whether elderly patients (from 70 to 90 years old) with triple-negative breast cancer (TNBC) could benefit from adjuvant chemotherapy (AC). The objective of this study was to explore the effect of AC in these population following surgery. Methods: A total of 4610 patients were identified in the Surveillance, Epidemiology, and End Results database (2010-2018). Inverse probability of treatment weighting (IPTW) was used to reduce the selection bias. IPTW-adjusted Kaplan-Meiers survival analysis and Cox proportional hazards models were performed to compare breast cancer specific survival (BCSS) and overall survival (OS) in the two different treatment groups. Results: All eligible patients were divided into two groups, the chemotherapy (n=1989) and the observation (n=2621) groups. The percentage of patients receiving AC versus observation increased significantly from 2010 to 2018 (estimated annual percentage change, 1.49%; 95%CI, 0.75-2.16%, p=0.002). The 5-year IPTW-adjusted rates of BCSS and OS in AC group were better than that in observation group (BCSS: 82.32% vs. 78.42%, p=0.010; OS: 75.54% vs. 64.65%, p< 0.001). In IPTW-adjusted Cox proportional hazards regression analysis, elderly patients could benefit from AC (BCSS: HR, 0.77, 95%CI, 0.62-0.94, p=0.012; OS: HR, 0.66, 95%CI, 0.57-0.78, p< 0.001). AC was associated with a significant outcome benefit across year at diagnosis, marital status, stage, lymph node, surgery and radiation subgroups (all p< 0.05). Patients with T1ab could not benefit from AC. Conclusions: We show a BCSS and OS benefit from AC in old patients with TNBC. AC may remain a reasonable treatment approach in these specific patients. For the patients with T1ab, de-escalated treatment should be administrated with caution. It requires further randomized controlled trial to ensure the AC effectiveness for elderly TNBC patients.

Citation Format: Tian Lan, Qiusheng Guo, Yunyan Lu, Junwei Gu, Xiying Shao, Haibin Xu, Zujian Hu. The Role of Adjuvant Chemotherapy for Elderly Women with Triple-Negative Breast Cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-01-01.
Abstract P1-03-03: Real-World Treatment Patterns and Clinical Outcomes in Patients Treated with Eribulin After Prior PI3K Inhibitor Therapy for Metastatic Breast Cancer
Authors: Goyal Ravi K. , Zhang Jingchuan , Davis Keith L. , Kaufman Peter A.
Published: March 2023

Background: Eribulin has been used in the treatment of metastatic breast cancer (MBC) following approval in 2010 in the United States (US). Recently, several new therapeutic classes have been approved for patients with MBC, including the phosphoinositide 3-kinase (PI3K) inhibitor alpelisib. This study aimed to assess the treatment patterns and clinical outcomes in patients with MBC treated with eribulin following alpelisib in US clinical practice. Methods: A retrospective, noninterventional medical chart review study was performed to obtain de-identified patient data via participating oncologists. Study population included adult female patients with a diagnosis of MBC who initiated eribulin therapy between March 1, 2019, and September 30, 2020, following prior therapy with alpelisib. Eribulin treatment parameters and patient characteristics were captured. Progression-free survival (PFS) and overall survival (OS) since eribulin initiation was assessed using Kaplan-Meier methods. Results: This interim analysis included 47 eligible patients (median age 62 years at eribulin initiation; 77% Caucasian). The majority (91.5%) of this cohort had HR+/HER2– MBC; 72.3% had a known PIK3CA mutation. Eribulin was classified as 2nd line, 3rd line, and 4th line or later in 34%, 47%, and 19% of patients, respectively, in regard to the line of therapy in the metastatic setting. At last follow-up, eribulin treatment was ongoing for 34% of patients. The median treatment duration was 5.2 months (q1, q3: 3.9, 7.1) among those who had discontinued eribulin, and 11.3 months (q1, q3: 10.0, 13.7) among those who were still on treatment. At last follow-up, 72.3% of patients were alive. The estimated PFS rate at 12 months was 57.1% (95% CI: 40.0-70.9). Median was not reached for OS after initiation of eribulin; the estimated OS rates at 12 and 24 months were 80.2% (95% CI: 65.3-89.2) and 61.8% (95% CI: 37.2-79.2), respectively. Conclusion: Among patients with MBC who initiated eribulin following prior treatment with a PI3K inhibitor, over 60% were estimated to survive for at least 2 years. Future studies to confirm these results are warranted.

Citation Format: Ravi K. Goyal, Jingchuan Zhang, Keith L. Davis, Peter A. Kaufman. Real-World Treatment Patterns and Clinical Outcomes in Patients Treated with Eribulin After Prior PI3K Inhibitor Therapy for Metastatic Breast Cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-03-03.
Abstract P1-09-02: Oncological, Cosmetic and Quality of life outcomes following breast conservation surgery in patients presenting after non-oncological excsion of breast primary: A prospective follow up study
Authors: IRRINKI R N NAGA SANTOSH , KHARE SIDDHANT , Singh gurpreet , laroiya ishita , mishra aniket
Published: March 2023

Background For early-stage breast cancer BCS followed by radiation therapy has been validated as safe alternative to Radical Mastectomy. One peculiar problem faced in developing countries is patients in whom primary tumor has been excised elsewhere. There is a lack of clear treatment history and pre-operative examination and imaging in such patients, which makes accurate staging and planning for definitive surgery much more challenging. We did this retrospective analysis to assess clinical, cosmetic and QOL outcomes in the above-mentioned group of patients. Methods Patients between 18 and 80 years diagnosed with biopsy proven carcinoma breast that had the primary tumor excised outside and underwent BCS at our institute were included. They were subjected to routine history and physical examination as per the institute standard of care. Overall survival was estimated using Kaplan Meier curve. Expected 4 years survival was calculated using percentage of people who were alive out of those patients whose follow up was known at the end of 4 years. Cosmetic outcome was assessed using patient reported BCTOS 12 scores whereas quality of life outcome was assessed using patient reported EORTC and SF 36 questionnaire scores. Results Twenty-two patients were enrolled. Overall survival at 4 years was 72% comparable in NACT and No NACT (p< 0.29). 5.45% patients had local recurrence. Cosmetic outcome was excellent to good in 90% patients, similar between NACT and No NACT (p 0.69). Quality of life was excellent-good in 65% patients (EORTC) which was significantly higher in No NACT group (p 0.05) Conclusion BCS after scar excision following non oncological resection of breast primary may be an acceptable modality of treatment with good cosmetic and Quality of life outcomes.

Citation Format: R N NAGA SANTOSH IRRINKI, SIDDHANT KHARE, gurpreet Singh, ishita laroiya, aniket mishra. Oncological, Cosmetic and Quality of life outcomes following breast conservation surgery in patients presenting after non-oncological excsion of breast primary: A prospective follow up study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-09-02.
Abstract P1-09-11: Impact of breast surgical procedure on survival in BRCA mutated patients with invasive breast cancer: mastectomy versus conservative treatment
Authors: JANKOWSKI CLEMENTINE , Mahiou Katia , Laura Vincent , Costaz Hélène , padéano Marie-Martine , Causeret Sylvain , Mamguem Ariane , Dabakuyo Sandrine , COUTANT CHARLES
Published: March 2023

Introduction: Patients with BRCA1/2 mutations have a higher risk of developing breast cancer compared to the wild-type population. For patients with a BRCA mutation, there are no specific recommendations for surgical management. The aim of this study was therefore to retrospectively investigate overall survival (OS) and recurrence-free survival (RFS) of BRCA mutated patients with localized invasive breast cancer, by comparing conservative surgery versus mastectomy. Methods: This study was based on data from the Côte d’Or breast and gynecological cancer registry. Data from patients with a constitutional BRCA1/2 mutation who presented with invasive breast cancer were collected retrospectively from 1998 to 2018. The Kaplan-Meier method was used to describe RFS and OS. Results:A total of 104 patients were included in the analysis, of whom 69 had conservative surgery and 35 underwent mastectomy. Regarding survival, there was no significant difference in OS (HR =1.49; 95% confidence interval (CI) [0.76-2.93], p=0.25). Similarly, there was no significant difference in RFS (HR =1.40; 95% CI [0.81-2.40], p=0.22), survival without homolateral recurrence (HR =0.88; 95% CI [0.30-2.61], p=0.89), without contralateral recurrence (HR =1.50; 95% CI [0.55-4.09], p=0.42), or without distant metastatic recurrence (HR =1.42, 95% CI [0.69-2.90], p=0.33). Conclusion: In invasive breast cancer in a patient with a germline BRCA1/2 mutation, conservative surgery, when possible, appears to be a feasible option over total mastectomy, with no difference in overall survival. However, the patient should be informed of the aggressive nature of recurrence in this population requiring chemotherapy in most cases.

Citation Format: CLEMENTINE JANKOWSKI, Katia Mahiou, Vincent Laura, Hélène Costaz, Marie-Martine padéano, Sylvain Causeret, Ariane Mamguem, Sandrine Dabakuyo, CHARLES COUTANT. Impact of breast surgical procedure on survival in BRCA mutated patients with invasive breast cancer: mastectomy versus conservative treatment [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-09-11.
Abstract P1-10-03: Ultra-hypofractionated Radiotherapy for Breast Cancer: A Brazilian Single-Institutional Series
Authors: de Brito Leticia Hernandes , Restini Felipe Cicci Farinha , Starling Maria Thereza Mansur , de Siqueira Gabriela Silva Moreira , Marta Gustavo Nader , Carvalho Heloisa de Andrade , Hanna Samir Abdallah
Published: March 2023

INTRODUCTION Extreme hypofractionation in patients with early-stage breast cancer has been studied in randomized phase III non-inferiority trials. There is scarce data on this strategy in Latin American patients. OBJECTIVES To describe the profile of patients diagnosed with breast cancer treated with radiotherapy with an ultra-hypofractionated regimen (5 fractions of 5.2 Gy, in one week), as well as the dosimetric aspects and acute toxicity related to the treatment. METHOD Retrospective cohort through a Brazilian uni-institutional series, with analysis of pathological, dosimetric, and toxicity variables. RESULTS Between May 2020 and March 2022, 67 patients were included, with a median age at diagnosis of 71 years (41-93). Regarding staging, 25.8% had in situ tumors, 60.6% of patients were IA, and only 3% were stage IIA. Nineteen percent of patients had histological grade 3; 24.6%, had nuclear grade 3. Hormone receptors were positive in 92.1% of patients. The mean ki67 was 19%, and HER2 was negative at 84.5%. All patients underwent conservative surgery, and 5 underwent reconstruction with autologous flaps. Fifty-one patients underwent hormone therapy and only 2 underwent adjuvant chemotherapy. All but two patients were treated with the conformal technique (VMAT was used due to unfavorable anatomy). The mean volume of the irradiated breast was 926 cm3 (ranging from 920 to 932 cm3). Regarding the constraints of the organs at risk, the average V8Gy of the ipsilateral lung was 11.4%, ranging from 0 to 24%. In the heart, the average volumes receiving 1.5Gy and 7Gy were, respectively, 9.2% and 0.7%. No patient had acute toxicity greater than grade 2. The effects on the skin appeared on average 20 days after the end of treatment, with resolution in a maximum of 3 months. The median follow-up time was 10 months (3 - 26). We did not observe any case of local-recurrence, of breast-cancer-related death. CONCLUSION Although our follow-up time is premature, we have found that ultra-hypofractionated radiotherapy was feasible, tolerable, and safe, for patients with early breast cancer. Also, the constraints on the organs at risk were respected. There were no high-grade acute toxicities. Besides convenience, ultra-hypofractionation can improve access to radiotherapy in resource-scarce settings.

Citation Format: Leticia Hernandes de Brito, Felipe Cicci Farinha Restini, Maria Thereza Mansur Starling, Gabriela Silva Moreira de Siqueira, Gustavo Nader Marta, Heloisa de Andrade Carvalho, Samir Abdallah Hanna. Ultra-hypofractionated Radiotherapy for Breast Cancer: A Brazilian Single-Institutional Series [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-10-03.
Abstract P1-10-14: Higher radiation dose to the heart in left sided breast cancer; anatomy versus dosimetry
Authors: El-Din Mohamed Alm , Niemierko Andrzej , Taghian Alphonse
Published: March 2023

Abstract: Background: There is assumption that omitting the internal mammary chain radiotherapy (IMC RT) in patients with breast cancer (BC) will significantly reduce the cardiac exposure for all patients regardless the cardiac anatomy of each patient. Aim: to evaluate the impact of IMC RT on the dose received by the heart and its chambers in patients with favorable versus unfavorable cardiac anatomy. Patients and methods: CT scans were obtained of 20 patients with left-sided BC, 10 with favorable and 10 with unfavorable cardiac anatomy. Three plans were generated for each patient, one treating only the breast with tangents, and one treating the breast and IMC with wide photon tangents, and one treating the breast and IMC to 50Gy with photon tangent fields and a matching medial electron field. Dose volume histograms (DVHs) were generated for the heart and chambers. The equivalent uniform doses (EUDs) were calculated for each DVH, and the mean EUDs for plans with unfavorable and favorable cardiac anatomy were compared using a two-sided two-sample T-test Results: The mean dose received by the heart from plans with tangents plus IMC fields in patients with favorable cardiac anatomy was significantly lower than that received from plans with tangents only or wide tangents in patients with unfavorable anatomy (P < .0001). The average EUD for plans with tangents and IMC fields in the favorable group was 16 Gy (SD = 4.5) as compared to 36 Gy (SD = 3.6) and 37 Gy (SD = 5.1) for plans with tangents only and wide tangents in the unfavorable group, respectively ((P < .0001). The doses to the right ventricle were not significantly different. Conclusions: Ttreatment plans should be individualized based on the cardiac anatomy of each patient.

Citation Format: Mohamed Alm El-Din, Andrzej Niemierko, Alphonse Taghian. Higher radiation dose to the heart in left sided breast cancer; anatomy versus dosimetry [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-10-14.
Abstract P1-10-15: Concious sparing of contralateral thyroid lobe in Ca Breast patients receiving post mastectomy radiotherapy by IMRT technique – A single institution dosimetric study
Authors: Chomal Manish , Iyer Minaal , Kalimurthy Ananth , Sahay Joshua , Banik Sushanta
Published: March 2023

Purpose/Objective(s): The purpose of this paper is to report the dosimetric effects of conscious sparing of contralateral lobe of thyroid gland in carcinoma breast patient receiving locoregional radiation by tangential beam Intensity Modulated radiotherapy technique.

Materials/Methods: Treatment plans of 20 Ca Breast patients, who received post mastectomy adjuvant locoregional radiotherapy, were evaluated. Since October 2021 we adopted a department protocol of conscious sparing of contralateral thyroid in breast radiotherapy. 10 of these had conscious sparing of contralateral thyroid (group A) whereas 10 of old plans were evaluated when C/L thyroid were not given constraints & are being passively spared due to location on contralateral/non treatment side of neck (group B). Treatment planning was done using tangential beam (6 MV) IMRT in Eclipse 13.7 TPS in all of these patients. All of these patients received treatment to chest wall & SCF. RTOG contouring guidelines were followed in all the patients. Prescription Dose was 40Gy in 15# for both groups. The best treatment plans were selected ensuring 95% PTV dose coverage and acceptable dose to OARs. Uniform contouring, plan optimization & evaluation protocols were followed for all of these patients.

Results: The mean thyroid volume in group A is 4.30cc & in group B is 3.99cc which is not statistically different (P value -0.639) The mean dose of thyroid in group A is 7.98Gy whereas in group B it is 17.00Gy which is spastically significant (P value – 0.000003). Comparison of mean dose to contralateral lobe (in Gy) between the two groups

Groups No. Mean ± SD ‘t’ value P value

Thyroid dose with constraint 10 7.98±1.46 -6.702, df=18 0.000003*

Thyroid dose without constraint 10 17.00±3.99

Unpaired ‘t’ test applied. P value = 0.000003, Significant

Conclusion: OARs present on contralateral side are passively spared due to the location. This often results in a tendency of not actively prescribing constraints to these. This study emphasizes that conscious sparing of contralateral Thyroid lobe can further reduce the dose to significant levels. This reduction can preserve thyroid function further. Further clinical trials are required to corroborate this dosimetric gain with clinical thyroid function preservation.

Citation Format: Manish Chomal, Minaal Iyer, Ananth Kalimurthy, Joshua Sahay, Sushanta Banik. Concious sparing of contralateral thyroid lobe in Ca Breast patients receiving post mastectomy radiotherapy by IMRT technique – A single institution dosimetric study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-10-15.
Abstract P1-11-03: VRN101099, Brain Permeable HER2 Kinase Inhibitor, Shows the Anti-tumor Activity in Preclinical Models of HER2-positive Cancers
Authors: Ko Yikyung , yoo Jihye , Jung Hong-ryul , Lim Hyerim , Lee YeongDeok , Kim Se Hyuk , Shin Dong Guk , Cho Serin , hoe Heo Myung , Kim Haelee , Cho Ha Yeon , Han Ah Reum , Ko Eunhwa , Choi Hwan Geun , Kim Deakwon , Kim Sunghwan
Published: March 2023

The brain is a common target organ for breast cancer metastasis, and the risk of brain metastasis is usually high for patients with HER2-positive breast cancer. While T-DXd showed positive results in HER2-positive breast cancer brain metastasis (BCBM), its activity and blood-brain barrier (BBB) permeability in active BCBM need to be further validated (TUXEDO-1 included 15 patients with active brain metastasis). Tucatinib plus Trastuzumab and Capecitabine triplet showed efficacy in patients with brain metastasis, but Tucatinib alone has poor BBB penetration. There is still an unmet medical need for active HER2-positive BCBM. VRN101099 is a highly selective kinase inhibitor of HER2 (Eurofins scanMAX Kinase Profiling, S-score (35) of 0.01). VRN101099 has single- to double-digit nanomolar (IC50) cellular potency in HER2-dependent cancer cells, and Ba/F3 cells expressing HER2 wild type or mutations with selectivity over wildtype EGFR. VRN101099 inhibited proliferation of BT474 with 3.6 nM IC50 but HaCaT with 829.2 nM IC50. VRN101099 binds HER2 kinase by forming a covalent bond to the Cys805 and its irreversible inhibition resulted in a longer target resident time than Tucatinib, confirmed by in vitro washout experiments. Robust in vivo activity of VRN101099 was observed in HER2-positive BT474 xenograft models. Moreover, once daily oral administration of VRN101099 significantly regressed intracranial BT474 tumor, demonstrating greater efficacy than twice daily oral administration of Tucatinib. These results were well explained by the superior brain to plasma exposure of VRN101099 to Tucatinib. Also, VRN101099 showed high exposure in the target organ, the fat pad, which potentiated better clinical translation. These anti-tumor efficacies are correlated with pharmacodynamic responses, as confirmed by decreased HER2, AKT, and ERK phosphorylation. In summary, VRN101099 is a brain penetrant, orally bioavailable, irreversible, and highly selective inhibitor of HER2 with therapeutic potential in HER2-positive BCBM. These data support the clinical development of VRN101099 in HER2-driven cancers.

Citation Format: Yikyung Ko, Jihye yoo, Hong-ryul Jung, Hyerim Lim, YeongDeok Lee, Se Hyuk Kim, Dong Guk Shin, Serin Cho, Myung hoe Heo, Haelee Kim, Ha Yeon Cho, Ah Reum Han, Eunhwa Ko, Hwan Geun Choi, Deakwon Kim, Sunghwan Kim. VRN101099, Brain Permeable HER2 Kinase Inhibitor, Shows the Anti-tumor Activity in Preclinical Models of HER2-positive Cancers [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-11-03.
Abstract P1-11-06: Multi-omics profiling of HER2-low breast cancer reveals clinically relevant subgroups and therapeutic pathways
Authors: Chen Lie , Liu Cui-Cui , Ge Jing-Yu , Shao Zhi-Ming , Yu Ke-da
Published: March 2023

The current HER2 testing algorithm can distinguish tumors that are completely negative for HER2 (IHC 0, HER2-zero) from HER2-low tumors [low (IHC 1+) or moderate expression (IHC 2+, ISH-)]. Because HER2-zero cases have often been combined with HER2-low cases, the clinical and biological understanding of HER2-low tumors is limited. To provide complementary information and shed light on the molecular characteristics and therapeutic insights of HER2-low breast cancer, we performed this multi-omics study of hormone receptor (HR)-negative and HER2-low breast cancer, also known as HER2-low triple-negative breast cancer (TNBC), and identified three subgroups: basal-like (BSL), receptor tyrosine kinase relevant (TKR), and mesenchymal stem-like (MSL). These three subgroups had distinct features and potential therapeutic targets and were validated in external datasets. Interestingly, the TKR subgroup (which exists in both HR-positive and HR-negative breast cancer) had activated HER2 and downstream MAPK signaling. In vitro and in vivo patient-derived xenograft experiments revealed that pretreatment with tyrosine kinase inhibitor (Lapatinib or Tucatinib) could inhibit HER2-signaling and induce accumulated expression of nonfunctional HER2 via a feedback loop, resulting in increased sensitivity to sequential HER2-targeting antibody-drug conjugate DS-8201. Our findings identify clinically relevant subgroups and provide potential therapeutic strategies for the previously targetless HER2-low TNBC subtype.

GRAPH ABSTRACT

Highlights of characteristics of HR-negative and HER2-low breast cancer subgroups

Table S1. Highlights of characteristics of HR-negative and HER2-low breast cancer subgroups.

Citation Format: Lie Chen, Cui-Cui Liu, Jing-Yu Ge, Zhi-Ming Shao, Ke-da Yu. Multi-omics profiling of HER2-low breast cancer reveals clinically relevant subgroups and therapeutic pathways [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-11-06.
Abstract P1-11-16: Treatment with tyrosine kinase inhibitors (TKIs) in HER2-positive metastatic breast cancer after trastuzumab emtansine (T-DM1) failure: A real-world study
Authors: Yin Yongmei , Li Wei , huang Xiang , Sun Chunxiao , Hua Yijia , Jin Nan , Wu Xinyu
Published: March 2023

Background Trastuzumab emtansine (T-DM1) has shown great effectiveness in treating HER2-positive metastatic breast cancer, but therapies subsequent to T-DM1 failure remain controversial. Here, we investigated efficacy and safety of tyrosine kinase inhibitors (TKIs) based therapy in T-DM1 resistant HER2-positive metastatic breast cancer. Methods From August 2019 to April 2022, 53 HER2-positive metastatic breast cancer patients received TKIs-based therapy after T-DM1 failure in Jiangsu Province Hospital. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR), and safety profiles were reported. Results 53 patients received TKIs-based therapies as a second or later line therapy. 51 (96.2%) patients received a combined therapy, including TKIs plus capecitabine, vinorelbine or trastuzumab. 2 (3.7%) patients received TKIs alone. The median follow-up time was 19.7 months (95%CI 15.4-24.0). The median PFS was 11.9 months (95%CI 7.9-15.9). OS has not reached. ORR was 19.6% and CBR was 72.5%. For patients who had brain metastasis (n=12), the median PFS was 10.5 months (95%CI 7.5-13.5) and intracranial ORR was 33.3%. Compared with lapatinib (n=30), pyrotinib (n=21) provided a better PFS after T-DM1 progression (8.0 months vs. 19.0 months, P=0.033). The most common adverse events were thrombocytopenia (12, 23.6%), diarrhea (8, 15.7%), leucopenia (8, 15.7%) and hand-foot syndrome (8, 15.7%). Conclusion TKIs-based therapy could prolong the survival of HER2-positive metastatic breast cancer patients after T-DM1 failure, including those with brain metastases. Compared with lapatinib, pyrotinib might provide better outcomes for overcoming T-DM1 resistance.

Citation Format: Yongmei Yin, Wei Li, Xiang huang, Chunxiao Sun, Yijia Hua, Nan Jin, Xinyu Wu. Treatment with tyrosine kinase inhibitors (TKIs) in HER2-positive metastatic breast cancer after trastuzumab emtansine (T-DM1) failure: A real-world study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-11-16.
Abstract P1-13-01: Targeting RRM2 for the treatment of palbociclib resistant breast cancer
Authors: Sultana Nahid , Elford Howard L. , Faridi Jesika S.
Published: March 2023

Hormone receptor (HR) positive breast cancer (BC) is a prevalent disease accounting for almost 2 million new cases globally. Almost 70-80% of breast cancer patients are women with a positive score for the estrogen receptor (ER). HR positive BCs of all stages are selectively treated with endocrine therapy targeting ER activity. Intrinsic and acquired resistance are common phenomena, impacting patient outcomes negatively. Palbociclib is an FDA approved checkpoint inhibitor for the treatment of HR+/HER2- breast cancer in combination with aromatase inhibitors or selective estrogen receptor degraders. However, patients responding well to the therapy in the beginning, lose sensitivity to palbociclib with time. Ribonucleotide reductase (RR) is a rate limiting enzyme in DNA synthesis consisting of two subunits RRM1 and RRM2. In our previous study, we have shown that RRM2 is upregulated in ER positive tamoxifen resistant BC. Previously, we have also reported that didox (DDX) which is a unique RRM2 enzyme inhibitor can significantly halt malignant breast cancer cell division in combination with an anthracycline drug doxorubicin by targeting RRM2, mutant p53 and NFkB regulatory proteins. In this study, we target palbociclib resistant BC with DDX to circumvent palbociclib resistance. For this purpose, we have developed palbociclib resistant ER positive MCF7 and ER negative MDA-MB-468 breast cancer cell lines. Here, we report morphological changes in parental as compared to palbociclib resistant cells after treatment with palbociclib alone, DDX alone or with palbociclib as compared to non-treated cells. Cell proliferation studies confirm the synergistic combinatorial effect of palbociclib and DDX compared to palbociclib or DDX alone. We also report that DDX alone or in combination with palbociclib downregulates cell cycle and NFkB proteins in palbociclib resistant ER positive MCF7 and ER negative MBA-MB-468 breast cancer cell lines.

Citation Format: Nahid Sultana, Howard L. Elford, Jesika S. Faridi. Targeting RRM2 for the treatment of palbociclib resistant breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-13-01.