ACS Chemical Health & Safety最新文献

{"title":"Abstract PO2-12-05: Scalp Cooling with the Capelli System to Reduce Doxorubicin-induced Alopecia in Patients with Localized Breast Cancer: A Phase 2 Randomized Controlled Trial","authors":"Carlos Paiva, Fabiola Dias, Angelo Matthes, Bianca Paiva, C. Souza, D. Lacerda, Augusto Antoniazzi, Maria Fernanda Machado, Matheus Godinho, Crislaine de Lima, Cristiane Cárcano, Marina Zorzetto","doi":"10.1158/1538-7445.sabcs23-po2-12-05","DOIUrl":"https://doi.org/10.1158/1538-7445.sabcs23-po2-12-05","url":null,"abstract":"\u0000 Introduction: Chemotherapy-induced alopecia (CIA) is a distressing side effect of breast cancer (BC) treatment. Scalp cooling (SC) devices have shown promise in reducing the severity of CIA. However, the impact of reducing alopecia occurrence on the quality of life of Brazilian patients remains unclear.\u0000 Objectives: This study aimed to assess the effectiveness of the Capelli System, a new SC device, in reducing CIA.\u0000 Methods: This was a single-center, controlled, randomized phase 2 clinical trial involving women with TNM stage I to III BC undergoing neoadjuvant or adjuvant doxorubicin-based chemotherapy (AC regimen: doxorubicin 60 mg/m² plus cyclophosphamide 600 mg/m², i.v., q21 days), with or without a taxane (paclitaxel or docetaxel). Participants were randomized in a 1:3 ratio into the scalp cooling (n = 33) or control (n = 12) groups. All participants were advised to cut their hair short and avoid heat-inducing tools or processes throughout chemotherapy, using cold or lukewarm water and wide-toothed combs for hair washing. The primary efficacy endpoint was grade 2 alopecia (>50% hair loss or hair shaving due to alopecia) after 4 cycles of AC. Secondary endpoints included measures of hair loss distress (BRHL) and body image (BRBI) from the EORTC Quality of Life Questionnaire - Breast Cancer Module (EORTC QLQ-BR23), as well as symptoms of anxiety and depression from the Hospital Anxiety and Depression Scale (HADS). Fitzpatrick phototype and hair type were assessed. Statistical analyses utilized generalized linear models and Fisher's Exact test (p-value < 0.05).\u0000 Results: Patients were enrolled from October 11, 2019, to January 17, 2022. Out of the 45 patients included, 8 were excluded: 2 due to intolerance, 1 with alopecia associated with COVID-19, and 5 who withdrew consent (2 with grade 2 headache, 3 without justification). The median age was 44.6 (min-max: 23-63) years, with 18 (40%) and 27 (60%) receiving adjuvant and neoadjuvant chemotherapy, respectively. Grade 2 alopecia or hair shaving occurred in 52% of scalp cooling patients and 100% of controls (p = 0.003), demonstrating a significant 48% reduction in alopecia. There were no significant differences in HADS-A, HADS-D, BRHL, or BRBI scores between the two groups. Alopecia occurrence did not show significant associations with skin or hair types. No serious adverse events related to the scalp cooling device were reported.\u0000 Conclusions: SC with the Capelli System significantly reduced CIA by half. Some patients experienced discomfort or headaches and discontinued device use. Further research is needed to understand why reduced alopecia rates do not correlate with improvements in body image or reduced hair loss distress.\u0000 Citation Format: Carlos Paiva, Fabiola Dias, Angelo Matthes, Bianca Paiva, Cristiano Souza, Domício Lacerda, Augusto Antoniazzi, Maria Fernanda Machado, Matheus Godinho, Crislaine de Lima, Cristiane Cárcano, Marina Zorzetto. Scalp Cooling with the Capelli System to Redu","PeriodicalId":12,"journal":{"name":"ACS Chemical Health & Safety","volume":"61 2","pages":""},"PeriodicalIF":11.2,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141022245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract PO5-15-10: Plasticity marker FOXC1 expression accurately predicts efficacy of Adjuvant Tamoxifen + Chemotherapy in reducing all-cause mortality in ER+LN- Breast Cancer: Validation in the SCAN-B Prospective Study (NCT02306096)","authors":"Partha Ray, Tania Ray, Clive Taylor, R. Hussa","doi":"10.1158/1538-7445.sabcs23-po5-15-10","DOIUrl":"https://doi.org/10.1158/1538-7445.sabcs23-po5-15-10","url":null,"abstract":"\u0000 INTRODUCTION: Despite the development and validation of multimarker gene panels like OncotypeDx®, Mammaprint® and EndoPredict®, an affordable and globally accessible biomarker approach that can predict increased risk of all-cause mortality in patients diagnosed with ER+LN- breast cancer, as well as the efficacy of adjuvant endocrine + chemotherapy in mitigating such elevated risk, continues to be an unmet medical need. Lack of such a pragmatic solution continues to be the cause of preventable recurrent/metastatic disease in patients diagnosed with ER+LN- breast cancer in resource-challenged settings around the world. We hypothesized that a predictive biomarker strategy that measures expression of the plasticity marker FOXC1, in combination with clinical parameters like tumor size (TS) and tumor grade (TG), may offer equivalent results to that of the above multimarker gene panels at a significantly lower economic cost without compromising accuracy of prediction results.\u0000 METHODS: Pre-treatment tumor RNA data obtained from a training cohort (compendium of gene expression microarray datasets, n=2857) and a single large validation cohort (SCAN-B Prospective Multicenter Observational Study, n=3520) for patients diagnosed with ER+LN- breast cancer were analyzed for FOXC1 expression, tumor size (TS) and tumor grade (TG) and correlated with Recurrence-Free Survival (RFS) and Overall Survival (OS). Optimized biomarker cutoff values based on model area-under-curve were leave-one-out cross validated and Risk-of-Recurrence (ROR) prediction algorithm derived utilizing the (compendium) training dataset. The unmodified strategy was then validated in the independent (SCAN-B) validation dataset.\u0000 RESULTS: A predetermined High ROR score calculated using FOXC1 expression, TS and TG (trained using the compendium dataset) predicted efficacy of adjuvant endocrine + chemotherapy over that of adjuvant endocrine therapy alone in ER+LN- patients in terms of statistically significant reduction in all-cause mortality at 8-years post-diagnosis in the SCAN-B validation dataset (4.66% vs 24.06%, n=326, OR=6.48, 95%CI [2.97-14.11], p< 0.0001). OncotypeDx® (5.7% vs 14.4%, n=762, OR=2.79, 95%CI [1.37-5.67], p=0.002), Mammaprint® (5.1% vs 18.4%, n=665, OR= 95%CI [2.04-8.43], p< 0.0001) and Endopredict® (4.8% vs 15.2%, n=923, OR=3.58 95%CI [1.78-7.21], p=0.0002) were also statistically significant predictors of the same.\u0000 CONCLUSION: Pre-treatment tumor FOXC1 mRNA or protein expression (assessed using qRT-PCR or routine immunohistochemistry (IHC), respectively, when combined with TS and TG presents a unique and economical alternative solution to multimarker gene panel tests like OncotypeDx®, Mammaprint® or Endopredict®, for guiding therapy of patients diagnosed with ER+LN- breast cancer in resource challenged settings. Such an approach to identify elevated risk of recurrence in patients diagnosed with ER+LN- breast cancer and prevent the same by guiding adjuvant endocrine + chemo","PeriodicalId":12,"journal":{"name":"ACS Chemical Health & Safety","volume":"47 S2","pages":""},"PeriodicalIF":11.2,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141022306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract PO5-20-01: SENTINOT2- Use of superparamagnetic iron oxide tracer to avoid unnecessary sentinel lymph node biopsies","authors":"Mary Bajomo, Ivan Marin, Jessica Montalvan, Margarita Riojas-Barrett, Logan Healy, E. Bonefas, Stacey Carter, Alastair Thompson","doi":"10.1158/1538-7445.sabcs23-po5-20-01","DOIUrl":"https://doi.org/10.1158/1538-7445.sabcs23-po5-20-01","url":null,"abstract":"\u0000 Background/Purpose: The use of superparamagnetic nanoparticles of iron oxide tracers (Magtrace) and electromagnetometers (SentiMag) for the detection of sentinel lymph nodes (SLN) during breast cancer surgery has been demonstrated to be noninferior to traditional radioisotope (RI) and blue dye detection, with additional safety benefits. Previous work has shown that transcutaneous detection of SLN with Magtrace/Sentimag is possible for over 30 days. Because of the safety, efficacy, and long detection window of Magtrace, we aim to investigate the use of Magtrace to prevent unnecessary SLN biopsies (SLNB) in breast cancer surgery. SLNB are commonly performed during breast conserving surgeries (BCS) or mastectomy for patients with a preoperative diagnosis of ductal carcinoma in-situ (DCIS). Because metastasis is not expected in patients diagnosed with DCIS, SLNB may be unnecessary and potentially harmful. However, in 15-25% of cases, unexpected invasive carcinoma is found during the post-surgical histopathological analysis of the resected breast tissue. For these cases, if SLNB are forgone during the initial surgery, SLNB during a second (delayed) procedure is the usual standard of care to evaluate SLN for metastasis. However, potential changes to lymphatic drainage following the initial resection may affect tracer localization to SLN. Consequently, we aim to compare SLN detection rates during delayed SLNB with Magtrace administered prior to initial BCS or mastectomy and subsequent RI tracer administered prior to delayed SLNB.\u0000 Methods: SENTINOT2 is an ongoing international trial with BCM as the sole US site. For eligible patients with a preoperative diagnosis of DCIS, Magtrace will be administered prior to BCS or mastectomy. If invasive carcinoma is found from the post-surgical histopathological analysis, patients will receive delayed SLNB within 4 weeks of their initial surgery. Prior to delayed SLNB, patients will be randomized into two groups differing in the order of modality used for SLN detection (Magtrace or RI). Subjects with the following conditions will be excluded from the study: hypersensitivity to Magtrace, iron overload disease, pregnancy, and lactation. The total expected accrual for this study is 538 subjects globally and 50 subjects at BCM.\u0000 Results: Currently, 19 patients have been enrolled in SENTINOT2. The subject population is 11% Asian, 26% Black/African American, and 47% Caucasian with non-Hispanic ethnicity. 5% of subjects identified as Hispanic Caucasian and 11% of subjects declined to report their race or ethnicity. 79% of patients had mastectomies, while 21% had BCS. After post-surgical histopathological analysis, 21% (4/19) patients were determined to have invasive carcinoma and received delayed SLNB. 50% (2/4) of these patients were randomized to have Magtrace as their first SLN detection modality (Mag-RI) while the other 50% (2/4) had RI as their first SLN detection modality (RI-Mag). Table 1 shows comparable SLN dete","PeriodicalId":12,"journal":{"name":"ACS Chemical Health & Safety","volume":"6 1","pages":""},"PeriodicalIF":11.2,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141022320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract PO5-18-10: Omission of SLNB in triple-negative and HER2-positive breast cancer patients with radiologic and pathologic complete response in the breast after NAST: a single-arm, prospective surgical trial (EUBREAST-01 trial, GBG 104)","authors":"T. Reimer, B. Gerber, Thorsten Kuehn, Nikola Bangemann, A. Kleine-Tebbe, A. Stefek, Ulrike Doerste, Carolin Hammerle, Oliver Hoffmann, Alexander Hein, Isabel Rubio, F. Peintinger, K. Mehta, S. Loibl, E. Botteri, Oreste D Gentilini","doi":"10.1158/1538-7445.sabcs23-po5-18-10","DOIUrl":"https://doi.org/10.1158/1538-7445.sabcs23-po5-18-10","url":null,"abstract":"\u0000 Background: Currently, axillary surgery for breast cancer is considered a staging procedure that does not seem to influence breast cancer mortality since the risk of developing metastasis depends mainly on the biological behavior of the primary (seed-and-soil model). Based on this, postsurgical therapy should be considered based on biological tumor characteristics. Retrospective data of cancer registry trials showed a strong correlation between breast pathologic complete response (pCR) and nodal pCR depending on intrinsic subtypes. Improvements in systemic treatments for breast cancer have increased the rates of pCR in patients receiving neoadjuvant systemic therapy (NAST), offering the opportunity to decrease, and perhaps eliminate, surgery in patients who have a pCR. Trial design: The EUBREAST network designed a clinical trial (NCT04101851) in which only patients with the highest likelihood of having a pCR after NAST (triple-negative or HER2-positive breast cancer) will be included, and type of surgery will be defined according to the response to NAST rather than on the classical T and N status at presentation. In the ongoing trial, axillary surgery will be eliminated (no axillary sentinel lymph node biopsy [SLNB]) for initially clinical node-negative (cN0) patients with radiologic complete remission (rCR) and a breast pCR (ypT0/ypTis) as determined in the lumpectomy specimen. The trial design is a multicenter single-arm study with a limited number of patients (N=440 as the screening population with an expected 80% pCR-rate) which might give practice-changing results in a short period, sparing the time and the costs of a randomized comparison. Patients will be recruited in European countries (Austria, Germany, Italy, and Spain) over 48 months. Inclusion criteria: -Written informed consent -Histologically confirmed unilateral primary invasive carcinoma of the breast (core biopsy). Multifocal or multicentric tumors are allowed if breast-conserving surgery (BCS) is planned. -Age at diagnosis at least 18 years -imaging techniques with estimated tumor stage between cT1-T3 before NAST -triple-negative (TNBC) or HER2-positive invasive breast cancer -TNBC is defined by: ER-negative (< 10% positive cells in IHC) and PgR-negative (< 10% positive cells in IHC), HER2-negative -clinically and sonographically tumor-free axilla before core biopsy (cN0/iN0) -in cases with cN0 and iN+, a negative core biopsy or fine-needle aspiration biopsy of the sonographically suspected lymph node is required -no evidence for distant metastasis (M0) -standard NAST with rCR -planned BCS with postoperative external whole-breast irradiation (conventional fractionation or hypofractionation) Primary objective: 3-year rate of axillary recurrence-free survival (ARFS) after BCS Statistics: The calculated total case number for per-protocol analysis is N=350, and the expected total number of screened patients is N=440. The assumption for acceptable 3-year ARFS ≥98.5% in the experime","PeriodicalId":12,"journal":{"name":"ACS Chemical Health & Safety","volume":"4 6","pages":""},"PeriodicalIF":11.2,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141022328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract PO1-07-10: Blood Based Early Cancer Detection Assay","authors":"Andrew Carson, Michael Wang, Bryan Leatham, Kristin Fathe, Eun-Hae Cho, Tae-Rim Lee, Junnam Lee, J. Ahn, Dasom Kim, Byung In Lee","doi":"10.1158/1538-7445.sabcs23-po1-07-10","DOIUrl":"https://doi.org/10.1158/1538-7445.sabcs23-po1-07-10","url":null,"abstract":"\u0000 Background: Breast cancer screening programs utilizing mammography have been shown to be highly effective in identifying breast cancer in women over the age of 40. High breast density is an independent risk factor for breast cancer and makes mammograms more difficult to interpret, decreasing their sensitivity. In the spring of 2023, the FDA, who certifies all mammography facilities under the Mammography Quality Standards Act, updated its regulations to require that breast density status be reported to all individuals receiving a mammogram. The new guidelines now require individuals with dense breast tissue be notified of this status. The guidelines also recommend these women discuss additional screening options with their healthcare providers1. These additional screening options may include breast tomosynthesis, breast MRI, breast ultrasound, and/or molecular breast imaging. Many of these options require additional exposure to radiation, are expensive, and are not equitably available across the country. In addition, they all require a follow-up appointment. Compliance can be challenging given the top barriers to mammography cited include the need for transportation, child-care, and the ability to take time off from work2. Genece Health is developing a simpler and less expensive screening solution that identifies the presence of early to late-stage breast cancer using cfDNA from a single blood draw. The Genece Health assay utilizes an algorithm that leverages Artificial Intelligence and Machine Learning to analyze fragment size and end motif patterns in cfDNA as well as regional mutational density to detect presence of ctDNA originating from breast cancer. This algorithm provides highly sensitive and specific results in a preliminary data set. Methods: The preliminary data set, presented herein, is a cohort of over 50 retrospective breast cancer plasma samples and over 100 presumed normal samples. The breast cancer samples were collected at all stages of progression, from stage 0, or ductal carcinoma in situ (DCIS), through stage IV. The majority ( >50%) were from stage I breast cancer. 400 µL of double spun plasma, collected in Streck BCT devices, was processed to purify and isolate cfDNA. cfDNA was used to create WGS libraries that were sequenced on a NovaSeq 6000. Sequence data were analyzed using a bioinformatics pipeline that yields an ensemble probability that correlates to the presence or absence of ctDNA from breast cancer. Results: The Genece Health assay and algorithm performed with a specificity greater than 85%. With this specificity, the assay had a sensitivity greater than 85% in samples from stages II to IV and a slightly lower sensitivity in stage 0 and I samples. Follow-up analyses were conducted to stratify performance based on breast cancer type (e.g. invasive ductal carcinoma vs invasive lobular carcinoma) and HR, PR, and HER2 status (e.g. HER2-negatives vs HER2-positives). Conclusions: The presented preliminary data indicate","PeriodicalId":12,"journal":{"name":"ACS Chemical Health & Safety","volume":"12 3","pages":""},"PeriodicalIF":11.2,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141022378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract PO3-20-10: Case Series: Invasive Secretory Carcinoma","authors":"Lauren Geisel, Hemanth Venkatesh, Alyssa Obermiller, Quyen Chu, Jessica Gielow, Danielle Henry","doi":"10.1158/1538-7445.sabcs23-po3-20-10","DOIUrl":"https://doi.org/10.1158/1538-7445.sabcs23-po3-20-10","url":null,"abstract":"\u0000 Secretory variant invasive ductal carcinoma is not well described in the literature but is defined by its unique histopathology. These tumors stain positive for S100 and are typically triple negative hormonal cancers with an overall good prognosis. There is speculation that secretory carcinoma in adults is more aggressive with a greater likelihood for tumor recurrence. We present two case studies of this rare histopathologic diagnosis. First, a 76-year-old female with a recurrent secretory variant, invasive ductal carcinoma of the left breast. Second, a 68-year-old male who presented with invasive and in situ secretory carcinoma.\u0000 A thorough chart review of all available institutional and outside institution records was performed from initial diagnosis to current treatment. Background information and de-identified patient information was summarized for this case series.\u0000 This is a 76-year-old female who presented to her physician in 2011 with a palpable left breast and axillary mass. Her workup demonstrated ER+/PR+/HER2- invasive ductal carcinoma with lobular features of the left breast measuring 2.3 cm, along with a 1.5 cm malignant axillary lymph node. She underwent a left breast lumpectomy with axillary dissection. She underwent adjuvant whole breast radiation, axillary nodal radiation, and was placed on anastrozole therapy for 5 years. Seven years later a recurrence was noted in the superior aspect of the left breast. MRI guided biopsy revealed recurrent left breast cancer with pathology of invasive ductal carcinoma, secretory variant. She elected to undergo lumpectomy alone. Final pathology demonstrated invasive ductal carcinoma, secretory variant, ER negative (0%), PR negative (0%), HER2 negative (0%), pT1bNx. She underwent accelerated adjuvant partial breast radiation. Follow up and surveillance with bilateral breast MRI two years later demonstrated a new left breast mass, found to be triple negative, recurrent secretory variant invasive ductal carcinoma. She underwent definitive treatment with a left skin sparing mastectomy, right sentinel lymph node biopsy, and a latissimus dorsi flap with implant placement. Final pathology demonstrated multifocal recurrent secretory carcinoma, two foci measuring 6 and 11 mm.\u0000 Our second patient was a 68-year-old male who initially presented to the clinic for evaluation of a ventral incisional hernia. During his initial assessment, a palpable retro-areolar nodule was noted on physical exam. Subsequent mammography demonstrated a hypoechoic mass with irregular margins measuring 2.8 x 2.3 x 1.7 cm along with increased vascularity and calcifications. An ultrasound guided biopsy demonstrated invasive secretory carcinoma. Initial pathologic testing of the tumor demonstrated ER positive (5%), PR positive (1%), and HER2 negative. The patient was taken to the operating room for a total mastectomy with sentinel lymph node biopsy. His postoperative pathology demonstrated negative margins, and invasive secretory c","PeriodicalId":12,"journal":{"name":"ACS Chemical Health & Safety","volume":"34 5","pages":""},"PeriodicalIF":11.2,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141022407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract PO1-10-01: Racial/Ethnic Disparities in Rates of Pathological Complete Response and Survival in Patients with Inflammatory Breast Cancer","authors":"Rebecca Zasloff, Samantha Thomas, Kendra M Parrish, Astrid Botty Van Den Bruele, G. DiLalla, Maggie DiNome, Laura Rosenberger, Hannah Woriax, E. S. Hwang, Jennifer Plichta, Akiko Chiba","doi":"10.1158/1538-7445.sabcs23-po1-10-01","DOIUrl":"https://doi.org/10.1158/1538-7445.sabcs23-po1-10-01","url":null,"abstract":"\u0000 Radiation Therapy Toxicities and Survival Outcomes in Monoallelic ATM Variant Carriers with Non-Metastatic Breast Cancer: A Retrospective Analysis Rayan Bensenane1 MD, Arnaud Beddok1,2,3 MD, Nadine Andrieu4 PhD, Fabienne Lesueur4 PhD, Eve Cavaciuti 4 MSc, Dorothee Le Gal4 MSc, Eon-Marchais Severine4 PhD, Dominique Stoppa Lyonnet 5MD PhD, Youlia Kirova1 MD 1. Institut Curie, PSL Research University, Radiation Oncology Department, Paris/Saint-Cloud/Orsay, France. 2. Gordon Center for Medical Imaging, Massachusetts General Hospital, Harvard Medical School, 125 Nashua St., Boston, MA, 02114, USA 3. Institut Curie, PSL Research University, University Paris Saclay, Inserm LITO U1288 Orsay, France 4. Inserm, U900, Institut Curie, PSL Research University, Mines ParisTech, Paris, France 5.Department of Genetics, Institut Curie; Inserm U830, Institut Curie; Paris-Cité University Abstract (characters: 2952; max 3400 characters, not include spaces) Background: The Ataxia-Telangiectasia Mutated (ATM) gene, involved in the repair of DNA double-strand breaks, can contribute to radiosensitivity when a bi-allelic variant is present and lead to Ataxia-Telangiectasia syndrome. Moreover, monoallelic ATM pathologic variant (PV) carriers, especially women, has an estimated occurrence rate of 0.5-1% globally and face a 2 to 3-fold increased risk of developing breast cancer. Despite evidence of in vitro radiosensitivity in cells derived from monoallelic variant carriers, there is a dearth of patient studies examining the risk of radiation-induced toxicity. This study aims to explore radiation therapy (RT) toxicities in non-metastatic breast cancer women carrying a germline monoallelic ATM variant, compared to non-carriers. Methods: A retrospective study was conducted on patients treated at Institut Curie, Paris from 1999 to 2014 and participating to CoF-AT (a French national study) and GENESIS database. ATM variant screenings encompassed both PV and non-PV, with toxicities evaluated using CTCAE v.5. Variants were classified as pathogenic, variant of unknown significance (VUS), or benign. Follow-up started from age/date at breast cancer to acute, late toxicities, disease recurrence or last news. Survival and toxicity comparisons were made using Kaplan-Meier survival analysis and Chi-square tests, respectively, with a significance level of α set at 0.05. Results: Among 50 patients, nine were ATM variant carriers (3 PV/5 VUS/1 benign), and 41 were non-carriers. Most patients had no smoking history (68%), and invasive ductal carcinoma was the predominant diagnosis (82%). The majority underwent breast-conservative surgery (80%), and the dominant RT techniques were 3D-Conformational Radiation Therapy (70%) and Isocentric Lateral Decubitus (30%). The median RT dose was 50 Gy over an average period of 36.5 days. With a median follow-up of 12 years post-diagnosis, no significant difference in acute dermatitis, esophagitis, lymphedema, cutaneous fibrosis, telangiectasia, or hea","PeriodicalId":12,"journal":{"name":"ACS Chemical Health & Safety","volume":"33 2","pages":""},"PeriodicalIF":11.2,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141022416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract PO1-03-08: Association of patient-reported triple-negative breast cancer (TNBC) knowledge with clinical trial participation","authors":"Megan Tesch, N. Graham, Sean J. Ryan, Melissa Hughes, E. Wrabel, N. Tung, Steve Lo, Thomas Fynan, Meredith Faggen, Natalie Sinclair, Maria Constantinou, Sarah Sinclair, N. Tayob, Nancy Lin, Ann Partridge, Eric P. Winer, S. Tolaney, A. Garrido-Castro","doi":"10.1158/1538-7445.sabcs23-po1-03-08","DOIUrl":"https://doi.org/10.1158/1538-7445.sabcs23-po1-03-08","url":null,"abstract":"\u0000 Background: Patients with TNBC are highly encouraged to participate in clinical trials given the lack of targeted treatment options for this breast cancer subtype. Yet little is known regarding barriers to trial participation in this population, including the impact of patients’ understanding about TNBC biology. We examined whether disease knowledge and other patient-level factors were associated with TNBC patients’ participation in trials. Methods: From a multicenter, prospective cohort study of patients enrolled from 2019-present with newly diagnosed TNBC (ER/PR ≤10% also eligible), we identified those with stage I-III tumors who completed at least one survey. Surveys assessed demographics, TNBC knowledge, risk perceptions, and participation in clinical trials. Patients were assigned to Cohort A if surgery was the first intervention and Cohort B if neoadjuvant therapy was given. Medical records were reviewed to verify the accuracy of tumor characteristics reported by patients. Data was summarized with descriptive statistics and logistic regression was used to identify factors associated with trial participation. Results: Of the 137 patients included, median age was 56 years (IQR 46-63), 104 (82%) were non-Hispanic White, 10 (8%) Black, 5 (4%) Hispanic. and 110 (86%) had at least some college education. Overall, 55 (41%) had stage I tumors, 65 (48%) stage II, and 14 (10%) stage III. Among 116 patients with available clinical trial participation data, 55 (47%) reported trial participation, 59 (51%) reported no trial participation, and 2 (2%) were unsure. The majority (36/55, 65%) of trial participants were in Cohort B. Among 129 patients with TNBC knowledge data, 82 (64%) and 73 (57%) correctly reported their tumor stage and grade, respectively. Most (104/129, 81%) knew TNBC was defined as ER/PR/HER2-negative, but only 16% (21/128) knew the ER/PR-negative cut off was ≤1%. Of 98 patients with risk perception data, 30 (31%) estimated their likelihood of recurrence within the next 5 years as 0%, 60 (61%) between 10-50%, and 8 (8%) between 60-100%. When asked if TNBC patients who remain cancer-free after 3 years will most likely not experience recurrence, 44 (45%) said “True,” 13 (13%) said “False,” and 40 (41%) were unsure. On univariate analysis, trial participation was less likely in Cohort A patients (OR 0.42, 95% CI 0.20 – 0.89, P=0.02) and more likely in stage II patients (vs. stage I, OR 2.43, 95% CI 1.09 – 5.39, P=0.03). On multivariable analysis, patients with at least some college education had higher odds of trial participation compared to patients with a college degree or higher (OR 3.21, 95% CI 1.11 – 9.28, P=0.03). No associations were found for other factors, including TNBC knowledge. Conclusions: About half of TNBC patients surveyed reported participating in clinical trials. Most of these patients were undergoing neoadjuvant therapy, likely reflective of greater study availability in this setting. While TNBC knowledge was not signif","PeriodicalId":12,"journal":{"name":"ACS Chemical Health & Safety","volume":"31 3","pages":""},"PeriodicalIF":11.2,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141022441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract GS03-02: Mammographic surveillance in early breast cancer patients aged 50 years or over: results of the Mammo-50 non-inferiority trial of annual versus less frequent mammography","authors":"Janet Dunn, Peter Donnelly, Nada I. Elbeltagi, Andrea Marshall, Alastair Thompson, Riccardo Audisio, Sarah Pinder, David Cameron, Amy Campbell, Sue Hartup, Lesley Turner, Annie Young, Helen B Higgins, Eila Watson, S. Gasson, Peter Barrett-Lee, Claire Hulme, Bethany Shinkins, Peter Hall, Andy Evans","doi":"10.1158/1538-7445.sabcs23-gs03-02","DOIUrl":"https://doi.org/10.1158/1538-7445.sabcs23-gs03-02","url":null,"abstract":"\u0000 Introduction:\u0000 Annual surveillance mammograms for an unspecified period, after treatment for early breast cancer, are widely practised in USA and Europe and represent a significant healthcare cost. Current UK guidelines recommend annual mammograms up to 5 years, then reverts to 3 year screening without specified risk stratification. Further evidence is needed to determine the optimum frequency and duration of mammographic surveillance.\u0000 Methods:\u0000 A multi-centre, randomised controlled, phase III trial of annual mammography versus 2-yearly for conservation surgery and 3-yearly mammograms for mastectomy patients up to 9 years. Women were eligible if aged 50 years or over at initial diagnosis of breast cancer (invasive or DCIS), and recurrence free 3 years post curative surgery.\u0000 Primary outcome was breast cancer specific survival (BCSS). Secondary outcomes include recurrence free interval (RFI) and overall survival (OS). BCSS event was defined as deaths from breast cancer and RFI as any locoregional or distant invasive recurrence or new breast primary. 5000 women were needed to detect a 3% absolute non-inferiority (NI) margin for BCSS with 2.5% one-sided alpha and at least 85% power. Analyses were carried out on intention-to-treat basis.\u0000 Results:\u0000 5235 women were randomised between April 2014 and September 2018. 4347 (83%) women were aged 55-75 years, 4203 (80%) had undergone conservation surgery, 4564 (87%) had invasive disease, 1162 (22%) had node positive disease, 4330 (83%) had ER positive tumours and 3812 (73%) were taking hormone therapy at the time of randomisation. Patient characteristics were balanced across arms.\u0000 With a median of 5.4 years follow-up (interquartile range 4.6-5.9), 319 women have died; 104 of breast cancer (53 on annual arm; 51 on less frequent arm). BCSS at 5 years was 98.2% (95% CI 97.5-98.6%) on annual arm and 98.3% (95% CI 97.7-98.8%) on less frequent arm. Hazard ratio (HR) was 1.04 (95% CI 0.71 -1.54), demonstrating non-inferiority of less frequent mammograms at the 3% margin (NI p< 0.0001; critical value 2.71) and the 1% margin (NI p=0.02; critical value 1.56).\u0000 320 (6%) women had a new invasive breast cancer event (55 loco-regional recurrences, 85 new breast primaries, 139 distant recurrences and 41 with multiple invasive events); 164 on the annual arm compared to 156 on the less frequent arm. Five-year RFI was 94.2% (95% CI 93.2-95.1%) for the annual arm and 94.4% (95% CI 93.4-95.3%) for the less frequent arm; HR= 1.03; (95% CI 0.83-1.28) demonstrating non-inferiority at a 2% margin (NI p=0.006; critical value 1.36).\u0000 OS at 5 years was 94.9% (95% CI 93.9-95.7%) on the annual arm and 94.3% (95% CI 93.3-95.2%) on the less frequent arm. Hazard ratio (HR) was 1.18 (95% CI 0.94 -1.47), demonstrating non-inferiority of less frequent mammograms at the 3% margin (NI p=0.003; critical value 1.61) and the 2.5% margin (NI p=0.02; critical value 1.51).\u0000 A total of 14987 mammograms have been performed on the annual arm and 80","PeriodicalId":12,"journal":{"name":"ACS Chemical Health & Safety","volume":"18 2","pages":""},"PeriodicalIF":11.2,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141022463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract PO2-04-07: Efficacy and Safety of First-line Therapy in Patients with HER-2 positive Advanced Breast Cancer:A network Meta-analysis of Randomized Controlled Trials","authors":"Junxiao Wang, Yushuai Yu, Jie Zhang, Chuangui Song","doi":"10.1158/1538-7445.sabcs23-po2-04-07","DOIUrl":"https://doi.org/10.1158/1538-7445.sabcs23-po2-04-07","url":null,"abstract":"\u0000 Background: The numerous but conflicting first-line treatment regimens for Her-2 positive advanced breast cancer necessitate a comprehensive evaluation to inform clinical decision-making. In this study, we conducted a Bayesian network meta-analysis (NMA) to compare the efficacy and safety of different interventions.\u0000 Methods: We systematically searched for relevant randomized controlled trials (RCTs) in Pubmed, Embase, Cochrane Library and online abstracts published by ASCO, SABCS. NMA was performed using R software, STATA and Review Manager 5.4 to calculate and analyze the primary endpoint progression free survival (PFS), as well as the secondary endpoints of overall survival (OS), objective response rate (ORR) and adverse events (AE) higher than grade 3.\u0000 Results: Out of the 8,603 manuscripts retrieved, we included 30 RCTs involving 12,045 patients in our analysis. Regarding PFS, the combination of trastuzumab with TKI was more favorable than dual-target therapy (hazard ratio=0.54, 95% [CI]: 0.40–0.72), and combination chemotherapy was superior to monotherapy (HR=0.66, 0.53-0.83). It is important to note that the addition of anthracycline did not result in improved PFS (HR=1.27, 0.87-1.86). For the HR+HER2+ population, dual-target plus endocrine therapy was more effective than single-target plus endocrine therapy (HR=0.65, 0.53-0.80). Monotherapy combined with dual-target therapy significantly improved OS and ORR compared to monotherapy with single-target therapy (HR=0.69, 0.56-0.84; OR=1.89, 1.34-2.65). A comprehensive analysis of both PFS and AE higher than grade 3 indicated that monotherapy plus dual-target therapy struck a balanced approach between effectiveness and toxicity compared to other regimens.\u0000 Conclusions: Monotherapy plus dual-target therapy remains the optimal choice among all first-line treatment options for advanced breast cancer. The combination of trastuzumab with TKI demonstrated a significant improvement in PFS, but further data are warranted to confirm the survival benefit.\u0000 Figure 1. Network diagrams of PFS, OS, ORR and adverse events higher than grade 3 in eligible experimental arms.\u0000 Figure 2. Forest plot of PFS, OS, ORR and adverse events higher than grade 3 in eligible experimental arms.\u0000 (A): PFS of HER2+ for experimental arms. (B): PFS of HR+ and HER2+ for experimental arms. (C): OS of HER2+ for experimental arms. (D): ORR of HER2+ for experimental arms. (E): Adverse events higher than grade 3 of HER2+ for experimental arms.\u0000 Figure 3. Each endpoint ranking for experimental arms. (SUCRA, surface under the cumulative ranking)\u0000 (A): PFS ranking for experimental arms. (B): OS ranking for experimental arms. (C): ORR ranking for experimental arms. (D): Adverse events higher than grade 3 ranking for experimental arms. (E): Experimental arms ordered by their overall probability as the best treatment in terms of both\u0000 efficacy and safety\u0000 Citation Format: Junxiao Wang, Yushuai Yu, Jie Zhang, Chuangui Song. Efficacy and S","PeriodicalId":12,"journal":{"name":"ACS Chemical Health & Safety","volume":"37 1","pages":""},"PeriodicalIF":11.2,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141022624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}