Prospective Multicenter Study Research Articles

Abstract PO4-07-08: Impact of an MRI/US fusion imaging for preoperative planning using non-wire localization technique in breast conserving surgery in patients with non-mass enhancement on MRI. A prospective multicenter study

Abstract [Background] Preoperative breast MRI is used to evaluate for additional and extent disease for newly diagnosed breast cancer patients with dense breasts. The potential benefit of preoperative MRI is still being controversial. However, when breast conserving surgery (BCS) is considered for non-mass enhancement (NME) on MRI, the precise image-guided localization is required. Although breast ultrasound (US) plays an adjunctive role in evaluation of MRI findings in preoperative planning for BCS, NME is less likely than a mass or focus to have a US correlate. Furthermore, the presence of NME increases the re-operation rate in BCS because of the difficulty in evaluating the tumor margin. An MRI/US fusion imaging has recently been developed that uses either real-time virtual sonography TM (RVS) or volume navigation TM (Vnav), and can overlay an US with the MRI image of the same site in real time by using magnetic position tracking system. The purpose of this prospective multicenter study was to evaluate the effect of MRI/US fusion imaging for preoperative planning using non-wire localization technique in BCS in patients with NME. [Methods] In 3 Japanese hospital, 13 patients who had lesions with NME that exceeded the US hypoechoic area were enrolled in this study from 2019 to 2022. Written informed consent was acquired, and then an additional supine MRI using a body surface coil was performed. During preoperative planning before BCS, RVS/Vnav was used to determine the NME enhancing area and to mark the area on the skin. Tissue markers were inserted under US at a location assessed by RVS/Vnav as the edge of extent of NME. We analyzed both the surgical margin positivity rate and the reoperation rate. [Results] The preoperative diagnosis by core needle biopsy were 6 DCIS and 7 invasive ductal carcinoma. NME distribution types were 7 segmental, 3 focal, 2 linear 4 and 1 regional. The median diameters of the NME and hypo-echoic lesions were 31 mm (range: 18–39 mm) and 16 mm (range: 9–32 mm), respectively (p = 0.0005). After confirming the localization of the tissue marker with intraoperative US, 12 lumpectomy and 1 quadrantectomy were conducted. The median specimen weight was 63g (range: 54-105g). In the final pathologic diagnosis of excised specimens were 5 DCIS and 8 IDC. In 8 cases (62%), the pathologic diameter was larger than the US diameter. All surgical margins were negative. None of the patients required additional resection. [Conclusions] The findings of study suggest that preoperative planning using non-wire localization technique under MRI/US fusion imaging for BCS in patients with NME could improve both a surgical margin positive rate and a reoperation rate. Citation Format: Shogo Nakano, Manabu Futamura, Keitaro Kamei, Takayoshi Uematsu, Miwa Yoshida, Sadako Akashi-Tanaka, Junta Sakakibara, Ichiro Isomoto, Hiroko Satake, Maiko Takahashi, Minami Hatono, Junko Araki. Impact of an MRI/US fusion imaging for preoperative planning using non-wire localization technique in breast conserving surgery in patients with non-mass enhancement on MRI. A prospective multicenter study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-07-08.

Abstract PO4-15-01: A multi-center prospective cohort study to evaluate the presence of circulating tumor cells using the Epic Sciences platform among women with metastatic breast cancer

Abstract Background: The presence of tumor cells (or their components) in the blood of women with a history of early breast cancer has the potential to herald the development of metastatic recurrence at its earliest stages. Such early detection could potentially lead to novel prevention strategies, but it requires a sensitive assay. Objective: To use the Epic Sciences platform to detect and enumerate CTCs in blood samples from patients with an established diagnosis of metastatic breast cancer (MBC), prior to initiation of 1st line systemic therapy in the metastatic setting. Methods: We conducted a multi-center prospective cohort study to evaluate the presence of CTCs using the Epic Sciences platform among patients with a new diagnosis of MBC. Men or women age 18 to 85 were included, irrespective of breast cancer subtype. Patients with a prior or concurrent malignancy whose natural history or treatment had the potential to interfere with the detection of MBC in a liquid biopsy were excluded. A one-time blood draw was performed before patients received any local or systemic therapy in the metastatic setting. In addition, those with recurrent disease must have been off any systemic adjuvant therapy for ≥3 weeks prior to blood collection. Two 5 mL blood samples were obtained for CTC identification and enumeration. CTC identification was based on immunofluorescence analysis using Epic Sciences platform as previously described (Ueno et al 2017). The presence of CTCs was correlated with clinical and pathological features, which were abstracted from medical records and pathology reports. The association between the presence of CTCs and clinical/pathologic characteristics was tested using Fisher’s exact test for categorical variables and t-test or Wilcoxon rank sum tests for numerical variables. All analyses were performed using the R software package. Results: 100 patients were recruited between February 2021 and January 2023 at five academic oncology centres in Ontario and Quebec, Canada. 95 patients had evaluable blood for analysis and 5 did not due to blood age and/or insufficient blood volume. Six patients were excluded after providing a blood sample because tissue biopsy ultimately revealed a 2nd primary tumor (n=4) or benign tissue (n=2). Hence, 89 patients with a clinical diagnosis of MBC and with evaluable blood for CTC analyses were ultimately included in our cohort. The average age of patients was 61 years. Most patients (n=49, 55%) had a prior history of early breast cancer, 38 (43%) had de-novo metastatic disease and prior breast cancer history was unknown for 2 patients. 50 (66%) of patients had visceral metastatic disease. The most common sites of metastases included bone (62%), lung (30%), liver (29%) and lymph nodes (17%). 63 of 89 patients (71%) had detectable CTCs at baseline, prior to any local or systemic treatment in the metastatic setting. The median number of detectable CTCs per 5mL sample was 2 (IQR 8.5) and the range was 0 – 12,798. Twenty nine of 89 (33%) patients had 5 or more CTCs detected per 5ml blood. The proportion of patients with detectable CTCs was numerically highest (n=39/51, 76%) among patients with hormone receptor (HR)+/HER2-ve breast cancer, followed by HER2+ (n=16/22, 73%) and triple negative (n=8/13, 62%) disease. Associations between CTC detection with prior history of early breast cancer, sites of metastatic disease and disease burden will also be presented. Conclusions: Approximately 3 in 4 women with newly diagnosed metastatic breast cancer have detectable CTCs using the Epic Sciences platform prior to initiation of first line systemic therapy. CTCs may be a promising tool for the monitoring of breast cancer recurrence and will be investigated in an ongoing Canadian prospective observational study that aims to elucidate biomarkers of late breast cancer recurrence. Citation Format: Katarzyna Jerzak, Pamela Goodwin, Marguerite Ennis, Christine Brezden-Masley, Nathaniel Bouganim, Mark Basik, Arushi Jain, Giuseppe Di Caro, Rick Wenstrup, Nadine Hartmann, Megan Slade, Ana Elisa Lohmann. A multi-center prospective cohort study to evaluate the presence of circulating tumor cells using the Epic Sciences platform among women with metastatic breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-15-01.

Abstract PO4-19-04: AXSANA – EUBREAST-3: An international prospective multicenter cohort study to evaluate different surgical methods of axillary staging in clinically node-positive breast cancer patients treated with neoadjuvant chemotherapy

Abstract Background The optimal surgical staging procedure of the axilla in patients who convert from a clinically positive (cN+) to a clinically negative node status (ycN0) through neoadjuvant chemotherapy is still controversial. Widely diverse techniques such as full Axillary Lymph Node Dissection (ALND), Targeted Axillary Dissection (TAD), Targeted Lymph Node Biopsy (TLNB) and Sentinel Lymph Node Biopsy (SLNB) alone are given preference in different international guidelines. So far, no comparative data on the oncological outcome or the morbidity of the different procedures are available. Further research is needed to safely de-escalate the extent of axillary surgery in this patient group. Trial design The AXSANA study is an international prospective cohort study including cN+ patients converting to ycN0 status and treated with different axillary staging techniques according to the standard at their treating institution. The study was initiated by the EUBREAST network. The trial includes patients with cT1-4c tumors, who present initially with axillary lymph node metastasis scheduled for neoadjuvant chemotherapy. According to an amendment in 2020 the inclusion of patients with highly suspicious nodes without confirmation using a minimally invasive biopsy is allowed. All patients converting to ycN0 status undergo follow-up for 5 years irrespectively of the ypN status. Primary endpoints: Invasive disease-free survival, axillary recurrence rate and health-related quality of life (HRQoL). HRQoL are evaluated using four standardized questionnaires (EORTC QLQ-C 30, EORTC QLQ-BR 23, Lymph ICF and SOC-13) at baseline and after 1, 3 and 5 years after surgery. Secondary endpoints are the feasibility and performance of different axillary staging techniques (detection rate, number of removed lymph nodes and association with complications, arm morbidity and quality of life, operating time and use of clinical and economic resources); impact of learning curve, and the detailed mapping of surgical and oncological treatment standards in different countries. The impact on different regional treatment strategies (radiotherapy, ALND) in patients with ypN0(i+), ypN1(mi) and ypN1 is assessed. Current status of the study: 4336 patients from 284 study sites and 26 countries were enrolled in the study between June 2020 and June 2023. Among 3722 patients with a defined surgical concept 1631 women were scheduled for TAD, 1483 for ALND, 469 for SLNB, 25 for TLNB and 109 for other procedures. A target lymph node was marked in 2309 patients, most frequently using clips/coils (1850, 80.1%), followed by magnetic seeds (219, 9.5%), carbon ink (171, 7.4%), radar marker (80, 3.5%), radioactive seeds (4, 0.2%) and other techniques (24, 1.0%). Funding: AGO-B, GBG, Claudia-von Schilling Foundation, Ehmann Foundation, Eugen und Irmgard Hahn Foundation, AWOgyn, Merit Medical, Endomagnetics, Mammotome Contact information: Prof. Dr. Thorsten Kühn Department of Gynecology and Obstetrics University of Ulm, Germany Baumreute 37 D-73730 Esslingen Germany E-Mail: kuehn.thorsten@t-online.de Citation Format: Thorsten Kühn, Steffi Hartmann, Elmar Stickeler, Jana de Boniface, Oreste Davide Gentilini, Sarah Fröhlich, Franziska Ruf, Marc Thill, Michael Hauptmann, Guldeniz Karadeniz Cakmak, Isabel Rubio, Maria Luisa Gasparri, Michalis Kontos, Eduard-Alexandru Bonci, Laura Niinikoski, Bilge Aktas Sezen, Rosa Di Micco, Dawid Murawa, Geeta Kadayaprath, David Pinto, Florentia Peintinger, Matilda Appelgren, Janine M. Simons, Marjolein Smidt, Ellen Schlichting, Lukas Dostalek, Elisabeth Thiemann, Markus Hahn, Michael Schrauder, Semra Gunay, Gunay Gurleyik, Nina Helidon, Hagigat Valiyeva, Ashutosh Kothari, Marian Vanhoeij, Andraz Perhavec, Tsvetomir Ivanov, Dov Zippel, Lia Rebaza, Sarun Thongvitokomarn, Sibylle Loibl, Maggie Banys-Paluchowski. AXSANA – EUBREAST-3: An international prospective multicenter cohort study to evaluate different surgical methods of axillary staging in clinically node-positive breast cancer patients treated with neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-19-04.

Abstract PO2-23-02: Results of a prospective randomised multicentre study comparing indocyanine green (ICG) fluorescence combined with a standard tracer versus ICG alone for sentinel lymph node biopsy in early breast cancer: The INFLUENCE Trial

Abstract Background: Use of fluorescence mapping for visualization of lymphatic and nodal tissue for sentinel lymph node biopsy (SNB) reveals high rates of identification (>98%). Studies combining ICG with either blue dye or radioisotope (RI) have shown high levels of concordance (>90%) and comparable performance parameters between ICG and standard tracers for SNB localization. ICG combines many advantages of blue dye and RI without the disadvantages of allergic reactions, staining of skin and surgical tissues along with handling and disposal of radioactivity materials. Moreover, magnetic tracers pose challenges of interference relating to surgical instrumentation and magnetic resonance imaging (MRI). The combination of ICG with a conventional tracer may represent a transition phase and this randomized study evaluates ICG as a sole tracer agent for SNB in early-stage breast cancer. Methods: In a prospective randomized study, 100 patients with unilateral clinically node negative tumours scheduled to undergo routine SNB for core-biopsy proven invasive breast cancer (≤5cm) were identified at multidisciplinary meetings [non-invasive tumours excluded]. All patients had pre-operative axillary ultrasound and breast conserving surgery or mastectomy. Patients were recruited in two cohorts (n=50); cohort 1 was assigned to either ICG [2ml 0.5%] alone (n=25) or combined with RI [Technetium99 nanocolloid, 20MBq] (n=25). Cohort 2 received ICG alone (n=25) or combined with blue dye for SNB localization. The number of nodes whether blue, radioactive, fluorescent or a combination thereof were recorded. Lymphatic and nodal tissue was visualized with a fluorescent camera/detection system. Sensitivity of ICG alone and/or in combination with one or another standard tracer was calculated. The main objective was to assess the performance of ICG alone compared with a standard tracer combination in terms of rates of SNB identification along with procedural node positivity rates. Statistical analysis employed Chi-Square test, Fisher’s Exact test, and logistic regression to determine differences between groups. Results: A total of 100 patients were randomized between March and December 2022 with 3 patients excluded from analysis (non-receipt of treatment allocation). Amongst evaluable patients (n=97), the overall SNB identification rate was 96.9% and by tracer category as follows: ICG alone = 97.9% (46/47); ICG + RI = 100% (25/25); ICG + blue dye = 92% (23/25). For cohort 1, the procedural node positivity rates were 17% for ICG alone and 18% for ICG + RI with corresponding figures of 12% for ICG alone and 20% for ICG + blue dye for cohort 2. Mean procedural node retrieval per case was 2.5 in ICG alone Vs ICG + Blue Dye and 2.3 in ICG alone Vs ICG/RI cohorts. There were no significant differences (p>0.05) in performance of ICG alone or combined with a standard tracer, with ICG alone being non-inferior in terms of procedural and nodal detection rates. Similar conclusions were reached from a secondary analysis adjusting for BMI, age and mode of detection (screening/symptomatic). Conclusion: ICG fluorescence imaging permits real-time visualisation of lymphatics and gives an additional dimension to SNB that appears safe versus the competitive alternatives. These results confirm high sensitivity for fluorescence localisation alone for SNB with comparable performance to combined methods with blue dye or RI. The fluorochrome ICG is reliable as a sole tracer and avoids potential drawbacks of blue dye and RI including staining, allergic reactions, availability and costs. Citation Format: Vassilis Pitsinis, Rahul Kanitkar, Alessio Vinci, Emad Elseedawy, Laura Canna, John R Benson. Results of a prospective randomised multicentre study comparing indocyanine green (ICG) fluorescence combined with a standard tracer versus ICG alone for sentinel lymph node biopsy in early breast cancer: The INFLUENCE Trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-23-02.

Abstract PO3-19-04: The CROWN STUDY: A multicenter prospective cohort study of cardiovascular outcomes in premenopausal women with hormone receptor positive breast cancer treated with ovarian suppression and an aromatase inhibitor

Abstract Background: Treatment for premenopausal women with high or intermediate risk hormone receptor (HR)+ breast cancer (BC) includes the concurrent use of ovarian function suppression (OFS) and an aromatase inhibitor (AI) to induce near complete estrogen deprivation (NCED). The long-term cardiovascular (CV) sequela for women treated with NCED is unknown. Premature menopause in non-cancer populations is associated with CV disease. The CROWN study (CaRdiac Outcomes With Near complete estrogen deprivation) will use sophisticated imaging assessments of cardiac dysfunction to understand the evolution of CV injury, as well as biomarker and demographic correlates, with the goal of developing tools to assess and mitigate CV risk. Methods: This is a NIH funded prospective cohort study conducted at 3 regional NCI-supported Cancer Centers (Atrium Health Wake Forest Baptist, Virginia Commonwealth and Duke) that will include premenopausal women, age ≤ 55, with Stage I-III BC following completion of planned chemotherapy, surgery and radiation with an ECOG 0-1. HR+ BC patients will receive an AI and OFS. Women with HR- BC are included as comparators. CV imaging and biomarkers will be obtained at baseline, 1 year and 2 years (Table 1). These assessments will include serial cardiac magnetic resonance (CMR) and coronary computed tomography angiography (CCTA) imaging as well as laboratory measurements, including exploratory biomarkers. The primary objective is to determine the 24-month difference in stress myocardial blood flow as measured by adenosine CMR imaging in both groups. We will correlate CMR imaging with CCTA to provide complementary detail of coronary plaque changes. The study will also assess the relevance of pre-existing risk factors on study outcomes, including an emphasis on racial disparities, and dynamic change in modifiable and treatment related risk factors. We plan to enroll 90 women, 67 in the NCED group and 23 in the HR-group, allowing for a 10% drop out rate. There are two primary types of statistical analyses. The first includes testing hypotheses between group (NCED vs HR-) and within group (longitudinal changes within the NCED group). The second analyses, involve developing predictive equations utilizing a stepwise linear regression approach to determine if patient demographics, clinical parameters and serum biomarkers are associated with cardiovascular changes over time. A total of 17 patients are enrolled as of 07/2023. NCT05309655 Study Procedures XX- XX Citation Format: Susan Dent, Emily Douglas, Sarah Hatcher, Katherine Ansley, Carolyn Park, Nathaniel O'Connell, Mary Hackney, Ralph D'Agostino, Rani Bansal, Renee Avecilla, Monica Brown, Kacey Clayton-Stiglbauer, Igor Klem, Jennifer Jordan, Alexandra Thomas. The CROWN STUDY: A multicenter prospective cohort study of cardiovascular outcomes in premenopausal women with hormone receptor positive breast cancer treated with ovarian suppression and an aromatase inhibitor [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-19-04.

Abstract PO2-22-12: Patient-reported outcomes 3 and 18 months after prepectoral implant-based breast reconstruction: Results from the UK Pre-BRA multicentre prospective cohort study

Abstract Background: Prepectoral implant-based reconstruction (PPBR) with and without mesh is becoming the standard of care for prosthetic reconstruction in the UK. In addition to being easier and quicker to perform, the procedure is perceived to be associated with better patient-centred outcomes including decreased post-operative pain, avoidance of animation deformity and improved cosmesis. Evidence to support these benefits, however, is lacking. The UK PreBRA prospective multicentre cohort study (ISRCTN11898000) aimed to assess patient-reported outcomes (PROs) before and 3 and 18 months following PPBR to provide much needed evidence to support the effectiveness of the technique. Methods: Women aged 18 or over undergoing mastectomy for breast cancer or risk-reduction who opted to have PPBR between July 2019 and December 2020 were eligible to participate in the study. Demographic, operative, oncology and three-month complication data were collected. Participants were asked to complete the validated BREAST-Q questionnaire at before surgery and at 3 and 18 months following the procedure. Questionnaires were scored according to the developers’ instructions and scores compared over time. Exploratory analysis of covariance, adjusting for baseline scores was performed to explore factors impacting PROs following PPBR. Results: 347 women underwent PPBR at 40 centres across the UK. Of these, 334 (96.3%) completed PROMs at baseline with 237 (68.3%) completing at least two of the three main BREAST-Q scales at both 3 and 18 months. The median age of the cohort was 49 (range 23-74). Most women (n=291, 87.1%) had mastectomy for malignancy with a quarter (n=82, 24.6%) undergoing bilateral surgery. Approximately a fifth (n=68, 20.4%) had a body mass index >30 and 12% (n=40) were active smokers at the time of surgery. At 3 months, 68 (20.4%) had experienced a complication requiring readmission and/or re-operation and 27 (8.1%) experienced an implant loss. In the cohort overall, women undergoing PPBR reported slight increases in their ‘Satisfaction with Breasts’ scores from baseline to 3 months after surgery but by 18 months, their scores had fallen below baseline values (Table 1). ‘Physical well-being’ scores decreased from baseline to 3 months but then remained stable. No changes were seen in ‘Psychosocial well-being’ scores across the three timepoints. At 18 months, after adjusting for baseline BREAST Q scores, women having surgery for risk-reduction reported scores that were 10-16 points lower than those having surgery for malignancy across all four main domains for the BREAST-Q. This exceeded the minimum clinically meaningful difference and was highly statistically significant. Women with high mastectomy weights ( >600g) reported lower scores for ‘Physical’, ‘Psychosocial’ and ‘Sexual’ well-being but not ‘Satisfaction with Breasts’. Smoking adversely impacted ‘Psychosocial well-being’ and ‘Satisfaction with Breasts’ and women with BMI >30 reported lower ‘Physical well-being’ scores at 18 months. Having a major complication requiring readmission/re-operation did not affect BREAST-Q scores, but when considered separately, implant loss dramatically impacted all BREAST-Q domains Conclusions: Women having PPBR report short-term improvements in ‘Satisfaction with Breasts’ scores but these are not maintained over time and decrease to below baseline 18 months after surgery. ‘Physical well-being’ also decreased after PPBR despite no disruption to the pectoralis muscle. Women having surgery for risk-reduction reported the worse PROs. Further work is needed to establish the long-term patient-reported outcomes of PPBR and factors impacting these. Citation Format: Leigh Johnson, Kate Harvey, Parisa Sinai, Nicola Mills, Paul White, Chris Holcombe, Shelley Potter. Patient-reported outcomes 3 and 18 months after prepectoral implant-based breast reconstruction: Results from the UK Pre-BRA multicentre prospective cohort study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-22-12.

Abstract PO3-23-06: Short-term clinical and patient-reported outcomes of oncoplastic breast conserving surgery and mastectomy with and without immediate breast reconstruction: The UK ANTHEM multicentre prospective cohort study

Abstract Background: Oncoplastic breast conserving surgery (OPBCS) may allow women with early breast cancer to avoid mastectomy leading to fewer complications and better quality of life. High quality comparative evidence, however, is lacking. The UK ANTHEM study (ISRCTN18238549) aimed to explore the feasibility of undertaking a large-scale multicentre study comparing the clinical and patient reported outcomes (PROs) of OPBCS as an alternative to mastectomy +/- immediate breast reconstruction (IBR) in women offered both options. Methods: Women aged 18 and over with invasive breast cancer or DCIS not suitable for standard breast conserving surgery, who were offered OPBCS as an alternative to mastectomy +/- IBR were eligible to participate in the study. Demographic, operative, oncological data were collected and the numbers of women experiencing complications at 3 months following surgery compared by procedure type. Participants completed the validated BREAST-Q at baseline and 3 months post-operatively. Questionnaires were scored according to the developers’ instructions and scores compared across timepoints by procedure group. Analysis of covariance, adjusting for baseline scores was used to explore factors influencing patient-reported outcomes after surgery. Results: 361 women from 32 UK centres participated in the study. When offered both options, the majority (n=284, 78.7%) elected to undergo OPBCS with either a therapeutic mammaplasty (TM) (n=207, 57.3%) or a chest wall perforator flap (CWPF) (n=77, 21.3%). The remaining 77 (21.3%) women chose mastectomy with (n=40, 11.1%) or without IBR (n=37, 10.3%). Women having mastectomy + IBR were significantly younger than those choosing other procedure types (p=0.002) and those choosing TM had higher BMIs (P=0.008), but there were no other differences between the groups. By 3 months post-operatively, 23.0% (n=83) women had experienced at least one complication, but there were no differences between the groups (p=0.50). The BREAST-Q was completed by 329 (91.1%) and 282 (78.1%) women at baseline and 3 months respectively. Although their scores were initially the lowest, women undergoing TMs reported clinically meaningful and statistically significant increases in ‘Satisfaction with Breasts’ (baseline 53.7 [95% confidence interval [CI] 50.4-57.0] to 3 months 68.9 [95% CI 65.5-72.2], p< 0.001) and ‘Psychosocial Well-being’ scores (baseline 62.1 [95% CI 59.2-65.0] to 3 months 70.4 [95% CI 66.9-73.8] p< 0.001) from baseline to 3 months. Women having CWPF and mastectomy +/- IBR did not report any significant changes in either ‘Satisfaction with Breasts’ or ‘Psychosocial Well-being’ scores over time. ‘Physical Well-being’ scores significantly decreased from baseline to three months in all treatment groups (p< 0.001) but were lowest after mastectomy only (56.5 [95% CI 47.4-65.5]) and highest in the TM group (68.6 [95% CI 65.9-71.3], p< 0.001). ‘Sexual Well-being’ decreased in all groups except for women having mastectomy + IBR. Adjusting for baseline, women undergoing OPBCS with TM (13.2, 95% CI 4.2-22.2, p< 0.001) or CWPF (11.4, 1.6-21.2, p=0.02) reported significantly higher ‘Satisfaction with Breasts’ scores at 3 months than those undergoing mastectomy. Receipt of IBR did not appear to lead to significantly higher scores compared with mastectomy alone (6.47, 95% CI -6.19 to 19.12, p=0.32). Women undergoing TM reported significantly higher ‘Psychosocial’ and ‘Physical well-being’ at 3 months compared with those having other procedure types. Experiencing a post-operative complication resulted in significant decreases in all BREAST-Q domains. Conclusions: When offered OPBCS as an alternative to mastectomy, most women choose breast conservation. This option is safe and appears to be associated with improved short-term PROs, particularly in the TM group. Further work is needed to establish the long-term outcomes of these techniques to support informed decision-making. Citation Format: Charlotte Davies, Leigh Johnson, Carmel Conefrey, Nicola Mills, Patricia Fairbrother, Chris Holcombe, Lisa Whisker, William Hollingworth, Joanna Skillman, Paul White, Douglas MacMillan, Charles Comins, Shelley Potter. Short-term clinical and patient-reported outcomes of oncoplastic breast conserving surgery and mastectomy with and without immediate breast reconstruction: The UK ANTHEM multicentre prospective cohort study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-23-06.

CXCL13 as a biomarker in the diagnostics of European lyme Neuroborreliosis - A prospective multicentre study in Austria.

'Definite Neuroborreliosis (NB)' is diagnosed with the presence of NB-specific symptoms, cerebrospinal fluid (CSF) pleocytosis and an elevated Borrelia Burgdorferi antibody index. However, some diagnostic uncertainties exist. The B-cell chemokine CXCL13 represents an emerging biomarker for the diagnosis and treatment of NB because its intrathecal concentration rises prior to the Borrelia antibody index and drops rapidly after antibiotic therapy. Nevertheless, due to lacking prospective data, a definite CXCL13 cut-off for the diagnosis of NB is still pending. Definition of a CSF CXCL13 cut-off for the diagnosis of acute and untreated NB in a prospective study setting. This multicentre prospective study involved 6 neurological departments treating patients in the Lower Austria district (1.7 million inhabitants). The controls were patients scheduled for a spinal tap but not clinically diagnosed with NB. Demographic data, clinical characteristics and blood counts, as well as inflammatory CSF values and CSF CXCL13-concentration were analysed. We recruited 440 adult patients, of whom 42 have been diagnosed as having an acute and untreated 'definite NB'. Three hundred ninety-eight patients were assigned to the control group. The median intrathecal CXCL13 concentration was 2384 pg/ml for patients with NB and 0 pg/ml for controls. The difference was highly statistically significant (P ≤ .001). A CSF CXCL13 cut-off of 271 pg/ml resulted in a sensitivity of 95.2% and a specificity of 97.2% for the confirmation or exclusion of NB. Based on our results, we propose a CSF CXCL13 cut-off of 271 pg/ml with Euroimmun-Elisa for the diagnosis of acute and untreated NB. Due to its high sensitivity and specificity, CXCL13 is a strong candidate biomarker for routine NB assessment, especially in clinically unclear cases.

Abstract PO4-18-12: MELODY: A prospective non-interventional multicenter cohort study to evaluate different imaging-guided methods for localization of malignant breast lesions (EUBREAST-4/iBRA-NET, NCT 05559411)

Abstract Background: In the last decades, the proportion of breast cancer patients receiving breast-conserving surgery has increased, reaching 70-80% in developed countries. In case of non-palpable lesions, surgical excision requires some form of breast localization. While wire-guided localization has long been considered gold standard, it carries several limitations, including logistical difficulties, the potential for displacement and patient discomfort, and re-excision rates reaching 21%. Other techniques (radioactive seed or radio-occult lesion localization, intraoperative ultrasound, magnetic, radiofrequency and radar localization) have been developed with the aim of overcoming these disadvantages. However, comparative data on the rates of successful lesion removal, negative margins and re-operations are limited. In the majority of studies, the patient’s perspective with regard to discomfort and pain level has not been evaluated. The aim of MELODY (MEthods for LOcalization of Different types of breast lesions) is to evaluate different imaging-guided localization methods with regard to oncological safety, patient-reported outcomes, and surgeon and radiologist satisfaction. Methods: The EUBREAST and the iBRA-NET have initiated the MELODY study to assess breast localization techniques and devices from several perspectives (NCT05559411, http://melody.eubreast.com). MELODY is a prospective intergroup cohort study which enrolls female and male pts. requiring breast-conserving surgery and imaging-guided localization for invasive breast cancer or DCIS. Multiple or bilateral lesions and neoadjuvant chemotherapy are allowed. Primary outcomes are: 1) Intended target lesion and/or marker removal, independent of margin status on final histopathology, and 2) Negative resection margin rates at first surgery. Secondary outcomes are, among others: rates of second surgery and secondary mastectomy, Resection Ratio (defined as actual resection volume divided by the calculated optimum specimen volume), duration of surgery, marker dislocation rates, rates of marker placement or localization failure, comparison of patient-reported outcomes, rates of “lost markers” and diagnostician/radiologist’s and surgeon’s satisfaction as well as the health economic evaluation of the different techniques. Target accrual: 7,416 patients. Enrollment started in January 2023. The study will be conducted in 30 countries and is supported by the Oncoplastic Breast Consortium (OPBC), AWOgyn, AGO-B and SENATURK. Financial support will be provided by Endomag, Merit Medical, Sirius Medical and Hologic. Citation Format: Maggie Banys-Paluchowski, Thorsten Kühn, Yazan Masannat, Nina Ditsch, Antonio Esgueva, Neslihan Cabıoğlu, Dawid Murawa, Nuh Zafer Canturk, Isabel Rubio, Jana de Boniface, Andreas Karakatsanis, Rajiv Dave, Shelley Potter, Ashutosh Kothari, Oreste Davide Gentilini, Walter Weber, Natalia Krawczyk, Steffi Hartmann, Guldeniz Karadeniz Cakmak, Markus Hahn, Michael P. Lux, Tove Tvedskov, Lina Pankratjevaite, Michalis Kontos, Florentia Peintinger, Aoife Lowery, Marjolein Smidt, Lia Rebaza, Maria Vasconcelos, Bahadir M. Gulluoglu, Bilge Aktas Sezen, Rosa Di Micco, Sarah Nietz, Francois Malherbe, Maria Luisa Gasparri, Séverine Alran, SVS Deo, Mah Muneer Khan, James Harvey. MELODY: A prospective non-interventional multicenter cohort study to evaluate different imaging-guided methods for localization of malignant breast lesions (EUBREAST-4/iBRA-NET, NCT 05559411) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-18-12.

Atrial fibrillation incidence after coronary artery bypass graft surgery and percutaneous coronary intervention: the prospective AFAF cohort study

Objectives. Atrial fibrillation is a common arrhythmia in patients with ischemic heart disease. This study aimed to determine the cumulative incidence of new-onset atrial fibrillation after percutaneous coronary intervention or coronary artery bypass grafting surgery during 30 days of follow-up. Design. This was a prospective multi-center cohort study on atrial fibrillation incidence following percutaneous coronary intervention or coronary artery bypass grafting for stable angina or non-ST-elevation acute coronary syndrome. Heart rhythm was monitored for 30 days postoperatively by in-hospital telemetry and handheld thumb ECG recordings after discharge were performed. The primary endpoint was the cumulative incidence of atrial fibrillation 30 days after the index procedure. Results. In-hospital atrial fibrillation occurred in 60/123 (49%) coronary artery bypass graft and 0/123 percutaneous coronary intervention patients (p < .001). The cumulative incidence of atrial fibrillation after 30 days was 56% (69/123) of patients undergoing coronary artery bypass grafting and 2% (3/123) of patients undergoing percutaneous coronary intervention (p < .001). CABG was a strong predictor for atrial fibrillation compared to PCI (OR 80.2, 95% CI 18.1–354.9, p < .001). Thromboembolic stroke occurred in-hospital in one coronary artery bypass graft patient unrelated to atrial fibrillation, and at 30 days in two additional patients, one in each group. There was no mortality. Conclusion. New-onset atrial fibrillation during 30 days of follow-up was rare after percutaneous coronary intervention but common after coronary artery bypass grafting. A prolonged uninterrupted heart rhythm monitoring strategy identified additional patients in both groups with new-onset atrial fibrillation after discharge.

Abstract GS03-01: Magnetic Resonance Imaging and a 12-Gene Expression Assay to Optimize Local Therapy for Ductal Carcinoma In Situ: 5-year clinical outcomes of E4112

Abstract BACKGROUND. Advanced diagnostics such as magnetic resonance imaging (MRI) and gene-expression profiles are potentially useful to guide treatment in patients with ductal carcinoma in situ (DCIS). To evaluate these tests, we performed a prospective single arm multicenter study. We have previously reported the impact of MRI on surgical management of DCIS patients, and the effect of a 12-gene DCIS Score (DS) on radiotherapy (RT) use after wide local excision (WLE). We now report a pre-planned analysis of ipsilateral breast events (IBE) at 5-years. METHODS. Adult women with a core needle biopsy diagnosis of DCIS and eligible for WLE based on conventional imaging were registered following consent. All registered patients underwent breast MRI. Those still eligible, and willing, to receive WLE after appropriate follow-up biopsies underwent resection to free margins. DCIS sections were submitted to Exact Sciences for DS. Those with a low DS (&amp;lt; 39) were advised to omit RT; those with intermediate/high (inter/hi) DS (≥39) were advised to receive RT. All participants were monitored at 6-month intervals for any breast cancer event, and for survival. An IBE was defined as the first DCIS or invasive recurrence in the ipsilateral breast following the final WLE. Participants without IBE were censored by date of last contact or date of death for those who died. Follow-up was truncated at 5 years from WLE. Using data available as of 07-06-2023, Kaplan-Meier (K-M) curves were constructed to estimate the time-to-event distributions for subjects who received RT and for those who did not. The 5-year IBE rates and 95% confidence intervals (CIs) were estimated from K-M curves for all subjects with a DS (analogue of Intention to Treat [ITT] analysis), and for the subset who were compliant with their DS-based RT recommendation (Per Protocol analysis). The analyses were repeated for subgroups based on age at DCIS diagnosis (&amp;lt; 50 vs. ≥ 50). RESULTS. Of 339 women evaluable for the previously reported primary analysis (PMID 30653209), 171 (50.4%) underwent WLE with free surgical margins and had DS available for RT recommendations (ITT population). Of these, 7/82 low DS patients underwent RT, and 5/89 inter/hi DS patients declined RT; thus, the adherence to DS-based RT recommendations was 93%. At a median of 5 years of follow-up from final WLE, the ITT population experienced a total of eight IBE events (4.8%, 95% CI 2.4, 9.4) with 5-year IBE rates that were similar for participants with a low DS and for those with a inter/hi DS: 5.1% (95% CI: 1.9, 12.9) and 4.5% (95% CI 1.7, 11.7), respectively. Stratification by age did not alter these results: among women aged &amp;lt; 50 years (n=33), the IBE rate was 6.7% (95% CI 1.0, 38.7) for low DS and 5.6% (95% CI 0.8, 33.4) for inter/hi DS. Among women aged ≥ 50 years (n=138), the IBE rate was 4.7% (95% CI 1.5, 13.8) for low DS and 4.3% (95% CI 1.4, 12.7) for inter/hi DS. In the per-protocol analysis (N=159 adherent to RT recommendations), IBE rates were also similar for participants who had a low DS and no RT [5.5% (95% CI 2.1, 14.1)] and for those with inter/hi DS who received RT [4.8% (95% CI: 1.8% to 12.3%)]. Again, there was no discernible influence by age as categorized above. CONCLUSION. We report the first prospective data on use of DCIS Score for RT decisions, and 5-year IBE rates. We find that DS-based recommendations are followed by &amp;gt;90% of patients. Although the sample size is limited, the data are reassuring in that the IBE rate is similar between the low DS group treated with WLE alone and the inter/hi DS group treated with WLE and radiation, whereas prior studies have shown a marked difference in IBE rates by DS with excision alone. Therefore, this prospective trial provides strong evidence to support the omission of RT after surgery in DCIS patients with low DS, and its use in patients with intermediate/high DS. Citation Format: Seema Khan, Justin Romanoff, Constantine Gatsonis, Habib Rahbar, Ruth Carlos, Sunil Badve, Jean Wright, Constance Lehman, Worta McCaskill-Stevens, Ralph Corsetti, Derrick Spell, Kenneth Blankstein, Linda Han, Jennifer Sabol, John Bumberry, Ilana Gareen, Bradley Snyder, Lynne Wagner, Kathy Miller, Joseph Sparano, Christopher Comstock. Magnetic Resonance Imaging and a 12-Gene Expression Assay to Optimize Local Therapy for Ductal Carcinoma In Situ: 5-year clinical outcomes of E4112 [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr GS03-01.

Abstract PO5-04-01: Inetetamab combined with sirolimus and chemotherapy in HER2 positive metastatic breast cancer patients with abnormal activation of Pi3k/Akt/mTOR pathway after trastuzumab treatment

Abstract Objective: To explore the efficacy and safety of Inetetamab Combined with Sirolimus and Chemotherapy in the treatment of human epidermal factor receptor 2 (HER2) positive metastatic breast cancer patients with abnormal activation of Pi3k/Akt/mTOR (PAM) pathway after Trastuzumab treatment. Methods: This prospective multicenter clinical study enrolled HER2 positive metastatic breast cancer patients at the National Cancer Center in China from July 2021 to September 2022 with PAM pathway mutation confirmed by histology or peripheral blood genetic testing. The inclusion criteria included: 1) Recurrent and metastatic breast cancer patients with HER2 positive confirmed histologically; 2) ECOG PS score ≤ 2; 3) Patients who have progressed after previous treatment with Trastuzumab; 4) Patients with PAM pathway mutation confirmed by Genetic testing; 5) Patients' cardiac, pulmonary, liver and bone marrow functions are basically normal; 6) Patients voluntarily sign informed consent forms. The exclusion criteria included: 1) Patients previously treated with mTOR inhibitors or pyrotinib; 2) Patients who have used chronic Corticosteroid for more than 3 months or used Immunosuppressive drug within 4 weeks; 3) Patients with symptomatic central nervous system metastasis; 4) Patients with left ventricular Ejection fraction&amp;lt; 50% or clinical manifestations of obvious arrhythmia, myocardial ischemia, severe atrioventricular block, cardiac insufficiency, and severe valvular disease; 5)Diagnosed with other malignant tumors within five years. Patients were randomly divided into trial group and control group. The patients in the trial group received inetetamab combined with sirolimus and chemotherapy, and control group received pyrotinib and chemotherapy. RECISTv1.1 standard was used to evaluate the efficacy of patients. Descriptive statistics are used to summarize clinical pathological features. Kaplan Meier method was used to draw survival curves. Log-rank test was used to compare progression free survival (PFS) differences between groups. P&amp;lt; 0.05 was considered statistically significant. Results:A total of 59 HER2 positive metastatic breast cancer patients with abnormal activation of PAM pathway were included, of which 37 patients received the treatment of inetetamab group and 22 patients received the treatment of pyrotinib group. The median follow-up time was 5.33 months. In the intent-to-treat set, the median PFS of patients in the inetetamab group was 4.64 months, which was shorter than 5.69 months in the pyrotinib group. There was no statistically significant difference between the two groups (P=0.51; HR=0.41; 95% CI, 0.12-1.45). The objective response rate (ORR) of the inetetamab group and the pyrotinib group were 28.1% and 29.4%, respectively. In terms of safety, the incidence of adverse events (AE) in the experimental group was (33/37) 89.1%, while (16/21) 76.2% in the control group. The incidence of AE above level 3 in the inetetamab group and pyrotinib group were (13/37) 35.1% and (3/21) 14.3%, respectively. Conclusion:For the metastatic HER2 positive breast cancer patients with abnormal activation of PAM pathway treated with trastuzumab previously, the combination of inetetamab with sirolimus and chemotherapy regimen are equivalent to the combination of pyrotinib and chemotherapy regimen. It demonstrated that combination of inetetamab with sirolimus and chemotherapy could be one of the treatment options for the metastatic HER2 positive breast cancer patients. Citation Format: Qiao Li, Dan Lv, Xiaoying Sun, Mengyuan Wang, Li Cai, Feng Liu, Chenghui Li, Jiuda Zhao, Jing Sun, Yehui Shi, Fei Ma. Inetetamab combined with sirolimus and chemotherapy in HER2 positive metastatic breast cancer patients with abnormal activation of Pi3k/Akt/mTOR pathway after trastuzumab treatment [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-04-01.

Treatment of newly diagnosed moderate or severe chronic graft-versus-host disease with prednisone and everolimus (PredEver first): a prospective multicenter phase IIA study.

Although most patients with chronic graft-versus-host disease (cGVHD) show initial response to first-line therapy, long-term clinically meaningful success of first-line treatment remains rare. In a prospective multicentre phase II trial in 6 German centers, patients with newly diagnosed moderate or severe cGVHD received prednisone and everolimus for 12 months followed by a 1-year follow-up period. Primary endpoint was treatment success (TS) at 6 months defined as patient being alive, achieving PR or CR of cGVHD, having no relapse of underlying disease and requiring no secondary treatment for cGVHD. Of the 34 patients evaluable for efficacy, 19 (56%) had TS at 6 months with 22 and 52% of the patients in a CR and PR respectively. Overall 30 patients (88%) had a CR or PR as best response, nearly all responses (29/30) occurring within the first 6 weeks of treatment. The cumulative incidence of treatment failure at 1 year was 63%, corresponding to 37% TS. Predefined safety endpoint (thrombotic microangiopathy, pneumonitis, and avascular necrosis) were not observed in any patient. Addition of everolimus to prednisolone is well tolerated and may improve long-term treatment success. Larger studies are necessary to ascertain the possible role of everolimus in first-line treatment of cGVHD.

Abstract PO3-15-01: Overexpression of N-glycosylation related gene OST4 promotes chemotherapy resistance in triple-negative breast cancer

Abstract Triple-negative breast cancer (TNBC) is one of the most aggressive subtypes of breast cancer, with high malignancy and poor outcome. Resistance to chemotherapy leads to treatment failure. How to overcome drug resistance is the key point in TNBC treatment. Previously, we initiated a prospective multicenter single-arm NeoPath clinical study (ClinicalTrial.gov identifier: NCT03907800) to assess the efficacy and safety of nab-paclitaxel combined with carboplatin in the neoadjuvant therapy of triple negative and HER2-positive early breast cancer. A total of 99 TNBC patients were enrolled and the pCR rate in TNBC was 33.78%. Samples before and after treatment were collected. RNA-sequencing results showed that OST4 was of high-expression in drug-resistant TNBC tumor tissues compared with chemo-sensitive samples. To verify the clinical significance of OST4 expression levels in TNBC, we tested the expression of OST4 by immunohistochemical technique on a tissue microarray including 87 TNBC cases treated with chemotherapy. We found that high expression of OST4 was associated with poor tumor differentiation, and patients with high OST4 expression had more relapse after chemotherapy. Ex-vivo proliferation assay and foci formation assay further confirmed that over-expression of OST4 promoted chemo-resistance, whereas down-regulating OST4 could reverse resistance in TNBC cell lines. As an oligosaccharyltransferase, it is reported that OST4 played parts in N-glycosylation. So we try to elucidate the relationship between N-glycosylation and drug resistance. Glycoproteomics results verified the existence of differential N-glycosylation atlas in drug-resistant tumor tissues compared with drug sensitive samples. NGS1 was identified as a potential target of OST4 by co-immunoprecipitation and mass spectrometry. In conclusion, high expression of OST4 could promote chemotherapy resistance in TNBC trough N-glycosylation regulation. Targeting OST4 may help reverse drug-resistance and improve therapeutic effect in TNBC. Citation Format: Wei Wang, Deyue Liu, Shuning Ding, Yan Fang, Jiayi Wu, Li Zhu. Overexpression of N-glycosylation related gene OST4 promotes chemotherapy resistance in triple-negative breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-15-01.

Abstract PS01-01: Feasibility and oncological safety of targeted axillary dissection or sentinel lymph node biopsy in patients with clinically node-positive disease after neoadjuvant chemotherapy in the prospective MF-1803 NEOSENTITURK-study

Abstract PS01-01: Feasibility and oncological safety of targeted axillary dissection or sentinel lymph node biopsy in patients with clinically node-positive disease after neoadjuvant chemotherapy in the prospective MF-1803 NEOSENTITURK-study

Safety, Efficacy, and Cost-effectiveness of Organ Suspension in Laparoscopic Gynecologic Surgery. A Retrospective Cohort Study to Validate an Innovative Technique: Laparoscopic Organ Suspension sec. Angioni.

This study aims to evaluate the safety, efficacy, and cost-effectiveness of the Laparoscopic Organ Suspension sec. Angioni, an innovative approach to transient organ suspension (OS) in laparoscopic gynecological procedures. Recognizing the need to enhance surgical site access and overcome limitations of existing organ retraction methods, the study investigates a novel, in-theatre constructed OS device. This retrospective observational study was conducted from March 2019 to May 2021 and included 330 patients who underwent multiport or single-site-port laparoscopic surgery employing Angioni's Technique for transient pelvic organ suspension. Participants included individuals undergoing surgery for conditions such as endometriosis, ovarian cancer, endometrial cancer, pelvic prolapse, and benign ovarian cysts. The Laparoscopic Organ Suspension sec. Angioni utilizes a segment of a Foley catheter connected to a Polyglactin suture to provide adjustable tension, minimizing the need for reconfiguration during surgery. The application of this OS technique resulted in an average suspension time of 1.9 minutes, with no significant difference between senior and junior surgeons. The method proved more time-efficient for posterior peritoneum suspension than other published methods and showed no additional risks of organ damage, bleeding, conversion to laparotomy, or OS-related complications. The secondary outcomes revealed reduced hospital stays and minimal blood loss, highlighting the procedure's overall efficiency. Given its retrospective and single-center nature, the study's results may not be widely generalizable. Prospective multicentric comparative studies are recommended to to further validate the Angioni's Technique. Laparoscopic Organ Suspension sec. Angioni is introduced as a straightforward, safe, and cost-effective method that significantly streamlines the surgical process. Its adaptability and ease of use suggest that it could be a valuable addition to current gynecological surgical practices, with potential implications for increasing efficiency and reducing procedural costs. Future studies are required to confirm these results across diverse clinical environments.

Abstract PO2-22-11: 'A sledgehammer to crack a nut' or 'the safer option'? Understanding decision making for and against oncoplastic breast conserving surgery as an alternative to mastectomy in women with early breast cancer: The UK ANTHEM study

Abstract Background: Oncoplastic breast conserving surgery (OPBCS) may allow women with breast cancer to avoid mastectomy, but many women continue to choose more extensive surgery even when breast conserving options are offered. Reasons for women’s procedure choices are unclear. The UK prospective multicentre ANTHEM study (ISRCTN18238549) aimed to explore the feasibility of undertaking a large-scale multicentre study comparing the clinical and patient-reported outcomes of OPBCS as an alternative to mastectomy in women offered both options. The qualitative phase of the study aimed to use semi-structured interviews to explore women’s perceptions of choice and to understand factors influencing decision making for and against OPBCS in early breast cancer. Methods: Women offered OPBCS as an alternative to mastectomy were eligible to participate in the ANTHEM study. Participants underwent their surgical procedure of choice and were followed up for 12 months. Semi-structured interviews were conducted with a purposive sample of women who elected to undergo either OPBCS or mastectomy with or without immediate breast reconstruction (IBR) at multiple UK centres to explore perceptions of choice, rationale for decision-making, and factors influencing procedure choice. Thematic analysis was used to explore the qualitative interview data. Sampling, data collection and analysis were undertaken concurrently and iteratively until data saturation was achieved. Results: Twenty-seven women from 12 UK breast units were interviewed. Of these, 12 elected to have OPBCS with volume displacement (n=7) or replacement procedures (n=5) and 15 chose mastectomy with (n=10) or without (n=5) IBR. Overwhelmingly, women’s decisions were guided by their surgical teams and their understanding and interpretation of the information they received from them. Indeed, although provision of choice was a pre-requisite for study entry, almost a third of women didn’t feel they had been offered meaningful choice as their surgeon recommended either OPBCS or mastectomy for them. Several women described how choice was unexpected as they had automatically assumed that they would need a mastectomy and expressed delight at being offered OPBCS as an alternative. Having choice and needing to make a decision about surgery, however, was a difficult experience for some women who reported finding the process challenging. Decision-making for and against OPBCS was underpinned by women’s perceptions of three key inter-related factors based on the information they received from their surgical teams: i) the effectiveness of OPBCS at removing all the cancer; ii) perceived longer term oncological safety and iii) practical issues. Almost all women described concerns about whether all the cancer would be removed by OPBCS, the need for further surgery for involved surgical margins and anxieties about cancer recurrence over time. Women who felt reassured that OPBCS was oncologically safe were happy to accept this option. Women who remained very anxious about incomplete excision and cancer recurrence were more likely to opt for mastectomy as a ‘safer’ option. Practical issues such as the perceived magnitude of the surgery and duration of the recovery were also important with many women choosing OPBCS as a less invasive or radical option than mastectomy. While many women described preferring to keep their breast and maintaining their femininity, only a minority of women referred to the cosmetic benefits of OPBCS as influencing their decision-making. Conclusions: Women’s decision-making for OPBCS vs mastectomy for breast cancer is complex and heavily influenced by the attitudes and beliefs of their surgical team. Adequate, high-quality, accurate information about surgical options including appropriate reassurance about the short- and long-term oncological safety of OPBCS is vital if women are to make fully informed decisions and feel confident avoiding mastectomy if this is an option for them. Citation Format: Charlotte Davies, Carmel Conefrey, Nicola Mills, Patricia Fairbrother, Chris Holcombe, Lisa Whisker, Joanna Skillman, Paul White, Douglas MacMillan, Charles Comins, William Hollingworth, Shelley Potter. 'A sledgehammer to crack a nut' or 'the safer option'? Understanding decision making for and against oncoplastic breast conserving surgery as an alternative to mastectomy in women with early breast cancer: The UK ANTHEM study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-22-11.

Abstract PO2-09-12: The magnitude and temporal variations of socioeconomic inequalities in quality of life after early breast cancer: results from the multicentric French CANTO cohort

Abstract Objective Previous studies showed that various outcomes in patients with early breast cancer (EBC), from incidence to survival, were influenced by social factors. However, there is limited research on the socioeconomic inequalities in quality of life (QoL) after treatment for EBC, and the magnitude and changes over time of these inequalities have not been quantified. This study examines the socioeconomic inequalities in QoL and their time trends among a large cohort of patients with EBC. Methods We conducted a comprehensive longitudinal analysis using data from the prospective multicentric CANTO study (CANcer TOxicity, NCT01993498), which included participants with EBC enrolled between 2012 and 2018. QoL was assessed using the summary score of the EORTC QLQ-C30 questionnaire at the time of diagnosis and 1 and 2 years post-diagnosis. We included patients with complete QoL data at diagnosis and 2 years post-diagnosis. Analyses were conducted for three indicators of socioeconomic status separately: self-reported financial difficulties, household income and educational level. We first analyzed trajectories of QoL by socioeconomic status from diagnosis to Year 1 and Year 2. Then, social inequalities in QoL were estimated using the regression-based slope indexes of inequality (SII) and compared across the follow-up periods. The SII represents the absolute change in the QLQ-C30 summary score along the two extremes of the socioeconomic gradient, taking into account the intermediate groups and their relative sizes. The analyses were adjusted for age at diagnosis, Charlson comorbidity index, disease stage, use and type of endocrine therapy, use and type of chemotherapy, breast surgery, radiotherapy use, and lymph node management. Results In the 5915 analyzed patients, compared to those with higher socioeconomic status, those reporting a high level of financial difficulty, lower income, or lower education were younger, most often premenopausal, with comorbidities, diagnosed with stage III BC, and treated with mastectomy and axillary lymph node dissection. There were no differences between socioeconomically-defined groups concerning BC histology, grade and IHC-defined subtype. Social inequalities in QoL at baseline were statistically significant for all socioeconomic status indicators (SIIfinancial difficulties = -7.6 [-8.9;-6.2], SIIincome= -4.0 [-5.2;-2.8]) and SIIeducation= -1.9 [-3.1;-0.7]). In multivariable analyses, social inequalities significantly increased (interaction p&amp;lt; 0.05) in Year 1 (SIIfinancial difficulties = -11.1 [-12.8;-9.4], SIIincome= -6.5 [-8.0;-5.0] and SIIeducation= -5.0 [-6.6;-3.5]) and Year 2 (SIIfinancial difficulties = -10.7 [-12.2;-9.1], SIIincome= -6.7 [-8.0;-5.3] and SIIeducation= -4.7 [-6.1;-3.3]) suggesting a widening socioeconomic gap in QoL outcomes irrespective of pre-diagnosis health, tumor characteristics and treatment. Similar results were observed in subgroups defined by menopausal status (pre/postmenopausal) and type of systemic treatment (chemotherapy, endocrine therapy). Conclusion Our study highlights and quantifies the association of several individual socioeconomic indicators with the QoL of patients with EBC in France. The magnitude of socioeconomic inequalities in QoL increased over time after EBC diagnosis in a country with a strong welfare system and universal healthcare coverage. In the era of precision medicine, these results underscore the importance of developing interventions to improve precision care, considering the conditions in which people are born, grow, work, live and age and the wider set of forces and systems shaping the conditions of daily life. Citation Format: José Luis Sandoval, Antonio Di Meglio, Arlindo Ferreira, Maria Alice Franzoi, Fabrice André, Barbara Pistilli, Christelle Jouannaud, Marion Fournier, Philippe Rouanet, Asma Dhaini Mermeche, Paul Cottu, Sibille Everhard, Anne-Laure Martin, Silvia Stringhini, Idris Guessous, Ines Vaz Luis, Gwenn Menvielle. The magnitude and temporal variations of socioeconomic inequalities in quality of life after early breast cancer: results from the multicentric French CANTO cohort [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-09-12.

Adverse outcomes in patients hospitalized with pneumonia at age 60 or more: A prospective multi-centric hospital-based study in India.

Limited data exists regarding risk factors for adverse outcomes in older adults hospitalized with Community-Acquired Pneumonia (CAP) in low- and middle-income countries such as India. This multisite study aimed to assess outcomes and associated risk factors among adults aged ≥60 years hospitalized with pneumonia. Between December 2018 and March 2020, we enrolled ≥60-year-old adults admitted within 48 hours for CAP treatment across 16 public and private facilities in four sites. Clinical data and nasal/oropharyngeal specimens were collected by trained nurses and tested for influenza, respiratory syncytial virus (RSV), and other respiratory viruses (ORV) using the qPCR. Participants were evaluated regularly until discharge, as well as on the 7th and 30th days post-discharge. Outcomes included ICU admission and in-hospital or 30-day post-discharge mortality. A hierarchical framework for multivariable logistic regression and Cox proportional hazard models identified risk factors (e.g., demographics, clinical features, etiologic agents) associated with critical care or death. Of 1,090 CAP patients, the median age was 69 years; 38.4% were female. Influenza viruses were detected in 12.3%, RSV in 2.2%, and ORV in 6.3% of participants. Critical care was required for 39.4%, with 9.9% in-hospital mortality and 5% 30-day post-discharge mortality. Only 41% of influenza CAP patients received antiviral treatment. Admission factors independently associated with ICU admission included respiratory rate >30/min, blood urea nitrogen>19mg/dl, altered sensorium, anemia, oxygen saturation <90%, prior cardiovascular diseases, chronic respiratory diseases, and private hospital admission. Diabetes, anemia, low oxygen saturation at admission, ICU admission, and mechanical ventilation were associated with 30-day mortality. High ICU admission and 30-day mortality rates were observed among older adults with pneumonia, with a significant proportion linked to influenza and RSV infections. Comprehensive guidelines for CAP prevention and management in older adults are needed, especially with the co-circulation of SARS-CoV-2.

Abstract PO4-23-06: Outcomes and experiences of women denied immediate breast REconstruction after maSTectOmy for bREast cancer during the COVID-19 pandemic - The RESTORE C19 Study

Abstract Introduction 40% of women diagnosed with breast cancer in the UK each year undergo mastectomy and immediate breast reconstruction (IBR) is routinely offered to improve quality of life. During COVID19, this offer was withdrawn to prioritise frontline and emergency services. The RESTORE C19 study aimed to use mixed methods to explore the outcomes, lived experiences and views of women denied IBR during the pandemic. Methods Women not offered IBR between March &amp; October 2020, were identified via B-Map-C, a UK prospective multicentre cohort study documenting changes in breast cancer treatment decisions during the pandemic. All patients were followed up between December 2021 &amp; July 2022 (21-28 months following mastectomy) to explore their ongoing management including whether they had undergone, were awaiting, or had decided against delayed breast reconstruction (DBR) and the procedures performed. Descriptive statistics were used to summarise results. Semi-structured qualitative interviews were undertaken to explore the experiences of this group in more depth. Women were purposively sampled based on treatment centre, age, decision regarding DBR, and procedure performed. A topic guide was developed to explore experiences of breast cancer care; feelings about not having been offered IBR and factors influencing subsequent surgical decision-making. Interviews were transcribed in full and analysed thematically, with data collection and analysis undertaken concurrently and iteratively until saturation was achieved. Full ethical approval was obtained: IRAS 302580, Wales REC 4 21/WA/0347. Results Some 366 women were identified as not having been offered IBR in the B-MaP-C study for whom follow up data was available for 311 (85.0%) from 55 centres. The median age was 50 (range 27-83 years). Most women presented with symptomatic breast cancer (n=239, 76.8%), were fit with no significant comorbidities, had T1 or 2 tumours (n=215, 69.1%) and were node negative (n=186, 59.6%). Almost a fifth (n=58, 18.6%) of women had decided against breast reconstruction completely. Of the remainder, just under 60% (n=149/253), had attended a surgical consultation to discuss DBR and only a third (n=91/253, 36%) had been referred to plastic surgical services to discuss autologous procedures. Only 21 women (6.8%) had received DBR; (16 free flaps, 4 implants, 1 pedicled flap+/-implant). Interviews were performed with 18 women from 5 centres with a median age of 49 years (range 34-67): n=5 women had either received/were awaiting DBR; n=4 had undergone/were awaiting contralateral symmetrising mastectomy and n=9 had decided against/were undecided about further surgery. Whilst all women reported feeling ‘grateful’ for their breast cancer treatment, some felt ‘abandoned’ by healthcare professionals, others that they needed to chase breast surgical teams for care, advice, and support. Partners were also impacted by their experiences with some women describing lasting effects on their relationships. Many women described how their desire for symmetry, either by breast reconstruction or symmetrising mastectomy, had “paled into insignificance” in the months and years following treatment. Conclusions The impact of COVID19 continues to be felt by women treated for breast cancer in the UK. Most women not offered IBR are either still awaiting DBR almost three years after their initial mastectomy or have decided against further surgery. The interviews highlight the trauma many women experienced receiving breast cancer treatment during the pandemic and ongoing issues that, for some, are yet to be fully addressed. There is a need for individualised support to provide women with equitable and timely access to DBR and/or symmetrising mastectomy depending on patient preference to help them move on with their lives. Citation Format: Katherine Fairhurst, Rajiv Dave, Baek Kim, Rachel O'Connell, Raghavan Vidya, P.G. Roy, Stuart McIntosh, Patricia Fairbrother, Jo Skillman, Leila Rooshenas, Shelley Potter. Outcomes and experiences of women denied immediate breast REconstruction after maSTectOmy for bREast cancer during the COVID-19 pandemic - The RESTORE C19 Study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-23-06.