Non-metastatic Breast Cancer Patients Research Articles

Evaluation of oral silymarin formulation efficacy in prevention of doxorubicin induced hepatotoxicity in patients with non-metastatic breast cancer.

Chemotherapy-induced hepatotoxicity is a common complication in breast cancer patients, especially with doxorubicin-containing regimens. Liver enzyme abnormality is reported in 34.8% of patients undergoing AC-T regimen and fatty liver is reported in 30% to 50% of cases. Antioxidant and anti-inflammatory properties of silymarin, a polyphenolic flavonoid extract derived from Silybum marianum, may be useful in preventing chemotherapy-induced hepatotoxicity. This study evaluated the effect of oral silymarin for preventing doxorubicin induced hepatotoxicity in non-metastatic breast cancer patients. In this triple-blind, placebo-controlled clinical trial, 50 patients with non-metastatic breast cancer were assigned to receive either 140 mg silymarin tablets or the placebo three times daily for 63 days and were evaluated for liver function test before the study and at the end of each chemotherapy cycle (every 3 weeks) for 4 cycles. In addition, an ultrasonography assessment was performed upon entry and the end of the study. Based on ultrasonography, the fatty liver grade was significantly higher in the placebo group at the end of the study. Moreover, the serum levels of aspartate aminotransferase (p = 0.015) and alkaline phosphatase (p = 0.004) at 6-week intervals, and the serum level of alkaline phosphatase (p = 0.002) at 9-week intervals were significantly lower in the silymarin group. Oral formulation of silymarin 420 mg/day for 63 days significantly prevented hepatotoxicity caused by doxorubicin in patients with non-metastatic breast cancer mostly based on liver ultrasonography but not laboratory parameters. Further investigations are suggested on different doses, durations and formulations of silymarin, particularly nano-formulations for increasing its oral bioavailability.

Treatment outcomes and prognostic factors in nonmetastatic metaplastic breast cancer patients: a multicenter retrospective cohort study.

Metaplastic breast carcinoma (BC-Mp) is an uncommon subtype that poses unique challenges. The limited information on patient prognosis and therapeutic strategies motivated our research initiative. We aimed to assess disease-free survival (DFS), overall survival (OS), and influential factors in patients with nonmetastatic BC-Mp. In this multicenter retrospective cohort study, clinicopathological data for nonmetastatic BC-Mp patients treated at four oncology units in Poland (2012-2022) were gathered. Among 115 women (median age 61, range: 28-91), the median tumor size was 40 mm (range 20-130); 30% of patients exhibited positive local lymph nodes. The majority of patients presented with stage II (46%) and triple-negative breast cancer (TNBC) (84%). Radiotherapy was administered to 61% of patients. Surgical procedures included breast-conserving surgery in 31% of patients and mastectomy in 68%. Eighty-three per cent of patients received chemotherapy. The median estimated DFS and OS were 59 and 68 months, respectively. Multivariable analysis revealed that tumor size influenced DFS and OS (Hazard ratios [HR] = 1.02, 95%CI 0.01-0.03 for both endpoints) and taxanes application improved DFS (HR = 0.47, 95%CI 0.24-0.93), but other factors did not. For patients receiving neoadjuvant systemic therapy (N = 51), taxanes improved DFS and OS according to univariable analysis. Our findings highlight poor DFS and OS regardless of receiving optimal treatment, emphasizing the need for tailored therapeutic strategies for BC-Mp patients. Taxanes appear promising in a neoadjuvant setting, particularly within the current standard of care for the TNBC subtype.

Symptom Monitoring and Health-Related Quality of Life in Non-metastatic Breast Cancer Patients: A Systematic Review

Abstract Purpose of Review This review aims to investigate the effect of patient-reported symptom monitoring, defined as the process of active and systematic reporting of symptoms initiated by the patient, on the health-related quality of life of breast cancer patients. Recent Findings Evidence suggests that online patient-reported symptom monitoring has the potential to positively impact the health-related quality of life of non-metastatic breast cancer patients, who are receiving systemic therapy. However, there is a lack of literature specifically addressing patient-reported symptom monitoring and HRQoL in metastatic breast cancer patients. Summary Additional research on symptom monitoring and HRQoL in breast cancer patients at all stages and during all phases in the disease trajectory, including its impact on personalized treatment, is needed before integration into routine care can be considered. Validated questionnaires and current implementation frameworks should be used to accelerate knowledge development about symptom monitoring for patients and their healthcare professionals, ultimately enhancing symptom self-management and the efficiency of breast cancer healthcare in the future.

Survival benefits of propofol-based versus inhalational anesthesia in non-metastatic breast cancer patients: a comprehensive meta-analysis

Whether the anesthesia technique, inhalational general anesthesia (IGA) or propofol-based anesthesia (PBA), influences the long-term survival of non-metastatic breast cancer (eBC) remain unclear and controversial. We carried out a literature search on 16thJuly, 2022 for studies comparing IGA and PBA in eBC undergoing standard surgery, according to PRISMA 2020. The major endpoint in our study was overall survival (OS). Seventeen studies including four randomized clinical trials and thirteen retrospective cohort studies were included in the meta-analysis. Ten studies provided data for crude OS in unweighted eBC patients (imbalance in baseline characteristics). The summarized estimate HRs of the PBA group versus the IGA group (ten studies, N = 127,774, IGA group: 92,592, PBA group: 35,182.) was 0.83 (95%CI: 0.78–0.89). Compared with IGA, PBA was associated with both better 1-year OS (two studies, N = 104,083, IGA group: 84,074, PBA group: 20,009. Pooled HR = 0.80, 0.73–0.89) and 5-year OS (six studies, N = 121,580, IGA group: 89,472, PBA group: 32,108. HR = 0.80, 0.74–0.87). Ten studies applied PSM method to balance the baseline characteristics. In these weighted patients, PBA still showed a better OS (ten studies, N = 105,459, IGA group: 79,095, PBA group: 26,364. HR = 0.93, 0.87–1.00), a better 1-year OS (two studies, N = 83,007, IGA group: 67,609, PBA group: 15,398. HR = 0.88, 0.78–0.98) and a trend towards a better 5-year OS (nine studies, N = 121,580, IGA group: 76,797, PBA group: 24,066. HR = 0.95, 0.88–1.03). Loco-regional recurrence-free survival (LRRFS) was also better in PBA group (HR = 0.73, 0.61–0.86). The present study is the first comprehensive meta-analysis to demonstrate that propofol-based anesthesia could significantly improve OS and LRRFS in non-metastatic breast cancer patients, compared with inhalational anesthesia.

A Plea for Monitoring Serum Selenium Levels in Breast Cancer Patients: Selenium Deficiency Is Rare during the First Year of Therapy, and Selenium Supplementation Is Associated with Elevated Risk of Overdosing.

(1) Background: The role of selenium in cancer biology remains poorly understood. Our aim was to study the course of selenium serum levels and the use of selenium supplements during breast cancer therapy. (2) Methods: Serum selenium levels, clinical-pathological data, selenium supplementation, and lifestyle factors were monitored quarterly over one year. (3) Results: A total of 110 non-metastatic breast cancer patients were enrolled in the prospective observational "BEGYN-1" study. At baseline, 2.9% of patients were selenium-deficient (<50 ng/mL), 1.9% were overdosed (>120 ng/mL), and 6.4% received substitution. The median selenium level was 81.5 ng/mL and ranged between 78.7 and 84.5 ng/mL within the year. A total of 25.3% of the patients received supplementation, resulting in significantly higher selenium levels (p < 0.05). A total of 8.7-28.6% of the patients using supplements were overdosed. Selenium levels strongly correlated with mushroom consumption (p = 0.003), but no association was found with therapy or clinical characteristics. (4) Conclusions: Although selenium deficiency is rare, serum selenium levels should be assessed in breast cancer patients. Mushrooms and nuts should be preferred over supplements to correct selenium deficiency. Ruling out selenium deficiency helps prevent the risk of selenosis and avoid unnecessary, costly supplementation in patients who are often financially burdened due to their disease.

Exploring the Relationship between MicroRNAs, Intratumoral Microbiota, and Breast Cancer Progression in Patients with and without Metastasis.

Breast cancer (BC) continues to pose a significant burden on global cancer-related morbidity and mortality, primarily driven by metastasis. However, the combined influence of microRNAs (miRNAs) and intratumoral microbiota on BC metastasis remains largely unexplored. In this study, we aimed to elucidate the interplay between intratumoral microbiota composition, miRNA expression profiles, and their collective influence on metastasis development in BC patients by employing 16S rRNA sequencing and qPCR methodologies. Our findings revealed an increase in the expression of miR-149-5p, miR-20b-5p, and miR-342-5p in metastatic breast cancer (Met-BC) patients. The Met-BC patients exhibited heightened microbial richness and diversity, primarily attributed to diverse pathogenic bacteria. Taxonomic analysis identified several pathogenic and pro-inflammatory species enriched in Met-BC, contrasting with non-metastatic breast cancer (NonMet-BC) patients, which displayed an enrichment in potential probiotic and anti-inflammatory species. Notably, we identified and verified a baseline prognostic signature for metastasis in BC patients, with its clinical relevance further validated by its impact on overall survival. In conclusion, the observed disparities in miRNA expression and species-level bacterial abundance suggest their involvement in BC progression. The development of a prognostic signature holds promise for metastasis risk assessment, paving the way for personalized interventions and improved clinical outcomes in BC patients.

Assessing quality of life and depression in non-metastatic breast cancer patients following surgical treatment: A cross-sectional study in Lebanon.

Breast cancer is a global health concern that significantly impacts the quality of life (QOL) of individuals. This study aims to comprehensively examine the interplay between QOL and depression among nonmetastatic breast cancer patients in Lebanon, a region with limited research in this context. A cross-sectional study was conducted at Hammoud Hospital-University Medical Center from January 2018 to January 2023. Data was collected through a self-administered questionnaire distributed as Google Forms via WhatsApp. A total of 193 patients had non-metastatic breast cancer. Out of these, 81 valid responses were obtained. The Patient Health Questionnaire and Quality of Life Scale were used to assess depression and QOL, respectively. A total of 81 patients were included with mean age 54.4 years. Results revealed that 77.8% of patients experienced provisional depression, with 35.8% meeting criteria for major depressive disorder. Financial status and chronic diseases were associated with the likelihood of developing major depressive disorder. The mean QOL score was 81.14, lower than the average for healthy individuals. Educational level and presence of chronic diseases were significant factors influencing QOL. Postsurgical depression prevalence is substantial, underscoring the importance of integrating mental health care. Economic status and comorbidities are influential factors, necessitating targeted interventions. Breast cancer's impact on QOL is profound, falling below that of other chronic conditions. Education empowers coping, while comorbidities impact QOL. Our findings emphasize the multidimensional nature of breast cancer care, advocating for holistic support and addressing emotional well-being.

Correlation of stress, depression, sleep, and pain with race and body mass index (BMI): Secondary analysis from Alliance A011502.

e23171 Background: A011502 is a phase 3 trial that randomized high-risk nonmetastatic breast cancer (BC) patients (pts) to aspirin 300 mg daily vs. placebo. Obesity and Black race have been shown to be associated with worse clinical outcomes. We studied the association of stress, depression, sleep and pain with each other, and with BMI and race. Methods: At baseline, 2735, 2610, 2720, and 2422 pts completed Perceived Stress Scale (PSS), Center for Epidemiologic Studies Depression Scale Revised (CESD-R), Brief Pain Inventory (BPI), and Pittsburgh Sleep Quality Index (PSQI) respectively. Stress was categorized with PSS scores: low (0-13), moderate (14-26) or high (27-40). Depression was categorized with CESD-R scores: no depression (0-15) or depression (≥16). Pain was categorized with BPI scores: none/mild (0-3) or moderate/severe (≥4). Sleep quality was categorized with PSQI scores: good (0-5) or poor ( &gt; 5). Associations of measures by race and BMI were analyzed using chi-square test. Results: There was a statistically significant association among stress, depression, pain, and sleep quality (p &lt; 0.01 for all). Compared to pts with BMI &lt; 25, overweight and obese women reported higher stress (2.9%, 2.3% vs. 1.7%, p = 0.04), depression (13.4%, 18% vs. 9.6%, p &lt; 0.01), moderate/severe pain (16.5%, 20.3% vs. 12%, p &lt; 0.01), and poor sleep (64.9%, 71.5% vs. 60.4%, p &lt; 0.01). Black women reported more moderate/severe pain compared to White women or other races (32.9% vs. 14.2% vs. 27.8%, p &lt; 0.01). There was no association of other symptoms with race (Table 1). Conclusions: Obesity was associated with higher stress, depression, poor sleep and pain among BC pts from A011502. Black women reported higher pain compared to other races. Future studies are warranted that determine causal associations, how symptoms may relate to outcome disparities, and develop approaches to address them. U10CA180821, U10CA180882, UG1CA233196; https://acknowledgments.alliancefound.org . Clinical trial information: NCT02927249 . [Table: see text]

Association of higher baseline stress and pain with clinical outcomes: Secondary analysis from Alliance A011502.

11016 Background: A011502 is a phase 3 randomized double-blind clinical trial that enrolled high-risk nonmetastatic breast cancer (BC) patients (pts) and randomized pts to aspirin 300 mg daily vs. placebo. There was no significant difference in invasive disease-free survival (iDFS) between the two arms. A secondary objective was to determine the association of inflammation-affiliated factors (stress, depression, poor sleep quality and pain) with iDFS and overall survival (OS). We hypothesized that these baseline factors are associated with worse clinical outcomes. Methods: At baseline, 2735, 2720, 2422 and 2610 pts completed Perceived Stress Scale (PSS), Brief Pain Inventory (BPI), Pittsburgh Sleep Quality Index (PSQI) and Center for Epidemiologic Studies Depression Scale Revised (CESD-R) respectively. Stress was categorized with PSS scores: low (0-13), moderate (14-26) or high stress (27-40). Pain was categorized with BPI scores: none/mild (0-3) or moderate/severe (≥4). Sleep quality was categorized with PSQI scores: good (0-5) or poor ( &gt; 5).Depression was categorized with CESD-R scores: no depression (0-15) or depression (≥16). Associations between the measures of interest and outcomes were performed with multivariable Cox models controlling for age, body mass index, time since diagnosis, race, ethnicity, hormone receptor status and treatment arm. Results: Median follow up was 35 months. The associations from multivariable Cox model are shown in Table 1. Pts who reported high PSS had significantly worse iDFS and (non-significant) worse OS. Moderate/severe average (avg) pain was significantly associated with worse iDFS and OS. Poor sleep quality and depression were associated with worse iDFS and OS but not statistically significant. Conclusions: Pts reporting higher stress and pain at baseline had worse outcomes. We acknowledge that both pain and stress may be related to other non-cancer issues (chronic comorbidities). Our study highlights the need for clinical trials to consider including questionnaires to assess pt-reported outcomes. Future studies are warranted to determine if measures to decrease pain and stress would improve BC outcomes. U10CA180821, U10CA180882, UG1CA233196; https://acknowledgments.alliancefound.org . NCT02927249: Clinical trial information: NCT02927249 . [Table: see text]

CINDERELLA clinical trial: Using artificial intelligence–driven healthcare to enhance breast cancer locoregional treatment decisions.

TPS621 Background: Breast cancer treatments often pose challenges in balancing efficacy with quality of life. The CINDERELLA Project pioneers an artificial intelligence (AI)-driven approach (CINDERELLA APP) for shared decision-making process, aiming to harmonise locoregional therapeutic interventions with breast cancer patients' expectations about aesthetic outcomes. The CINDERELLA clinical trial aims to establish a new standard in patient-centred care by bridging the gap between clinical treatment options and patient expectations through innovative technology. The trial focuses on evaluating the effectiveness of the CINDERELLA APP in improving patient satisfaction regarding locoregional treatment aesthetic outcomes, aligning patient expectations with real-world results, and assessing its impact on overall quality of life and psychological well-being. Methods: Trial design and statistical methods: This international multicentric interventional randomised controlled open-label clinical trial will recruit and randomise patients into two groups: one receiving standard treatment information and the other using the AI-powered CINDERELLA APP. The primary objective is to assess the levels of agreement among patients' expectations regarding the aesthetic outcome before and 12 months after locoregional treatment. The trial will also evaluate the aesthetic outcome level of agreement between the AI evaluation tool and self-evaluation. The impact of the intervention on aligning expectations with outcomes will be evaluated using the Wilcoxon signed-rank test. The improvement in classification of aesthetic results post-intervention will be measured by calculating the Weighted Cohen's kappa. Outcomes across different groups will be compared using statistical tests and bootstrap methods. CANKADO functions as the base system, allowing doctors to supervise APP content for patients and handle data gathering, while upholding principles of privacy, data security, and ethical AI practices. Intervention planned: Using the CINDERELLA APP, the patient will have access to supervised medical information approved by breast cancer experts, and the AI system will match patient's information to pictures showing the potential aesthetic outcome (spectrum of good-poor) according to different locoregional approach. Major eligibility criteria: Non-metastatic breast cancer patients eligible for either breast-conserving surgery or mastectomy with immediate reconstruction. Current enrollment: Recruitment is currently open at six study sites. The recruitment started on 8 August 2023, aiming to enroll at least 515 patients/arm. As of January 26, 2024, clinical study sites have successfully randomised 177 patients. Clinical trial information: NCT05196269 .

The role of obesity in the clinicopathologic variables and treatment of early stage breast cancer.

e12555 Background: Breast cancer (BC) is the second most common cancer among women in the United States. Studies have found obesity to be a key risk factor for BC, in which obese patients have higher recurrence and mortality. With 40% of the United State population being obese, we studied the differences in clinicopathological variables and treatment of normal-weight (NW) and obese patients with BC in a community-based cancer center within Florida. Methods: In this retrospective study, 535 patients with non-metastatic breast cancer (NMBC) diagnosed between January 1st, 2015 and December 31st, 2021 were identified. A Two Proportion Z test was done to evaluate the association between body mass index (BMI) groups of NW (BMI &lt;25) and obese (BMI &gt;30) patients amongst several independent variables. Variables included are histology, grade, estrogen and progesterone receptor status (ER/PR), human epidermal growth factor receptor 2 (HER2) status, chemotherapy, and surgical modality. Results: Results demonstrated that only Grade 2 histology was statistically more prevalent in NW vs obese patients (p &lt; 0.01). 218 patients underwent mastectomy with 54% in the obese BMI. 317 patients were treated with lumpectomy with 65% in the obese BMI. Of the 211 NW patients, 97% were HER2 negative or low compared to 96% in the obese group. Only 3% and 4% of patients were HER2 positive in NW and obese groups, respectively. Of the obese patients, 40% were treated with neoadjuvant/adjuvant chemotherapy compared to 33% of NW patients (p=0.05). Factors such as mean age, smoking status and other demographic information were not statistically different between the groups. Conclusions: This study demonstrates that obese NMBC patients required chemotherapy more often than NW patients and that histologic characteristics cannot explain this difference in treatment. Factors such as stage at diagnosis or BC prognostic scores may contribute to the increased use of chemotherapy in obese patients. A limitation of this study is that the stage of disease at diagnosis was not abstracted, as a new staging system for BC was implemented in 2018. Furthermore, studies have suggested that, in obese patients, difficulty in identification of a mass in clinical or self -breast exam and poor compliance with screening guidelines may delay diagnosis of BC at an earlier stage. Obesity has many negative health effects, and with the increased use of novel weight loss medications, it will be important in the future to study the impact this may have on breast cancer development, histopathologic features, and treatment of patients with breast cancer. [Table: see text]

Pleiotrophin serum level and metastasis occurrence in breast cancer patients.

Breast cancer (BC) cases in Makassar, Indonesia, are on the rise, with 2723 cases recorded in 2018. Tumor cells in the blood indicate metastasis, emphasizing the need for early diagnosis and monitoring. Pleiotrophin (PTN) is associated with various human malignancies, and recent studies suggest a correlation between PTN expression and advanced BC stages; therefore, PTN could serve as an independent predictor of metastasis. This study aimed to determine the correlation between serum PTN level, histopathological grading, and metastasis occurrence in BC patients in Makassar, Indonesia. This study used an observational cross-sectional design. Pleiotrophin serum levels were examined using enzyme-linked immunosorbent assays. This study used a t-test and ROC curve analysis for the statistical tests. Of the 64 samples used in this study, metastasis was present in 26 cases and absent in 38 samples. The mean PTN serum levels in metastatic and non-metastatic breast cancer patients were 4.311 and 1.253, respectively. The PTN receiver operating characteristic curve showed an area under the curve of 2.47 ng/dL, which was statistically significant (p < 0.001). A significant relationship was found between PTN level and metastasis (p < 0.001). The correlation coefficient was 0.791, indicating a positive correlation. This study revealed that the serum PTN level among breast cancer patients had a cut-off value of 2.47 ng/dL. The research established a clear correlation between PTN level and metastasis occurrence in breast cancer patients, indicating a higher likelihood of distant metastasis with elevated PTN concentration.

Abstract PO5-23-11: Elevated linoleic acid levels in red blood cells membrane predicts response to neoadjuvant chemotherapy in breast cancer patients

Abstract Introduction: Fatty acids (FA) consumed in the diet have been implicated in increasing the risk of breast cancer (BC). Humans have a wide variety of FAs, including saturated (SFA), monounsaturated (MUFA), and polyunsaturated (PUFA) FAs. PUFAs can be further classified into omega-3 (n-3) and omega-6 (n-6) PUFAs. While n-3 has been associated with reducing inflammation and promoting apoptosis in BC cells, n-6 has been linked to increased inflammation, oxidative stress, and the promotion of BC cell proliferation and treatment resistance. In healthy women, the n-3 content in mammary tissue correlates with n-3 content in red blood cells (RBCs). The FA profile of the RBC membrane provides an unbiased option to assess lipid intake and composition, reflecting long-term FA intake and providing an objective and sensitive measure of lipid intake and body fat deposits. Notably, BC patients have been found to display a high n-6:n-3 ratio in RBCs, which is associated with inflammatory and oxidative stress biomarkers. The neoadjuvant chemotherapy treatment (NACT) model presents a unique opportunity to study resistance mechanisms in non-metastatic BC patients. In this approach, the absence of tumor (pathologic complete response: pCR, or Residual Cancer Burden (RCB) = 0) after NACT indicates treatment sensitivity and better overall survival (OS). Objective: The objective of this study is to determine whether differences in FA profiles determined in the RBC membrane and plasma are associated with the response to NACT in non-metastatic BC patients. Methods: A prospective study was conducted, including non-metastatic BC patients scheduled to receive NACT. Blood samples were collected before the first cycle of NACT to measure plasma and RBC FA derivatives, SFAs, MUFAs, and PUFAs. The pathological complete response (pCR) and residual cancer burden (RCB) were assessed. Results: A total of twenty-eight BC patients were included in the study. When comparing pCR vs. no-pCR using total SFA, MUFA, and PUFA plasma samples, no significant differences were observed. However, in RBC, an increase in PUFA was associated with a higher rate of no-pCR (**p&amp;lt; 0.01). Furthermore, comparing omega-6 and omega-3 (both PUFA) levels, an increase in omega-6 was associated with no-pCR (**p&amp;lt; 0.01), while no significant differences were observed with omega-3. No differences were obtained in plasma samples for either omega-6 and omega-3. To determine which specific omega-6 PUFAs were responsible for the association with no-pCR, elevated levels of linoleic acid (LA) in RBC were found to be associated with no-pCR (**p&amp;lt; 0.01). Other omega-6 PUFAs, including gamma-linolenic acid (GLA), eicosadienoic acid (EDA), dihomo-gamma linolenic acid (DGLA), and arachidonic acid (ARA), showed no significant associations. Multivariate and regression analysis confirmed LA (C18:2 n-6, LA) as the most relevant FA when assessing RCB (0-1 vs. 2-3) in RBC membranes, but not in plasma. The receiver operating characteristic (ROC) curve analyzing LA levels in RBC showed an area under the curve (AUC) of 0.855 for RCB (sensitivity: 76.9%, specificity: 92.3%). Conclusions: To the best of our knowledge, this is the first study demonstrating a clear connection between RBC membrane FA composition, specifically LA concentration, and the pathological response in BC patients after NACT. The measurements taken in plasma did not show significant associations, suggesting that RBC membrane FA profile of could serve as a relevant prognostic biomarker for studying resistance mechanisms to NACT in early BC patients Table. Measured FAs in RBC membrane and plasma by pathologic complete response *Indicates p&amp;lt;0.05; abbreviations: pCR: pathological complete response; SD: standard deviation; yr: years; BMI: body mass index; HR: hormone receptor; HER2: human epidermal growth factor receptor type-2; NLR: neutrophil to lymphocyte ratio; HG: histological grade; RCB: residual cancer burden; NA: not applicable Citation Format: Benjamin Walbaum, César Sánchez, Francisco Acevedo. Elevated linoleic acid levels in red blood cells membrane predicts response to neoadjuvant chemotherapy in breast cancer patients [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-23-11.

Abstract PO3-12-11: A phase-3 randomized controlled study to evaluate the role of hydroxyprogesterone in prevention of chemotherapy induced neurotoxicity in women with breast cancer

Abstract Introduction Chemotherapy induced peripheral neuropathy (CIPN) is seen in 60% breast cancer patients who receive paclitaxel-based chemotherapy with no conclusively known pathophysiology. Hydroxyprogesterone is known to have neuroprotective and neuro-regenerative potential. We conducted a randomized controlled trial assessing the role of hydroxyprogesterone in reducing the incidence and severity of CIPN. Methodology Histologically proven, post-menopausal, non-metastatic breast cancer patients without pre-existing neuropathy, planned to receive paclitaxel (with or without trastuzumab) in the adjuvant or neoadjuvant setting were screened and consented. They were randomized to receive depot hydroxyprogesterone injection 500 mg followed by 250 mg injection every 2 weekly (trial arm) versus 1 ampoule (2 ml) of vitamin-B complex (B1-100mg, B6-100mg and B12-1000µg) injection every 2 weekly (control arm) during the entire course of paclitaxel-based chemotherapy. The primary end point was cumulative incidence of grade II-IV CIPN, at the last cycle of chemotherapy as assessed by CTCAE-V4. Secondary end point was EORTC-QLQ-CIPN20 assessment 8 weeks after last cycle of chemotherapy. Patients were stratified for stage, diabetes mellitus, and frequency of paclitaxel administration. Sample size was calculated for a 20% reduction in CIPN from 60% with α-0.05 and power of 80%, for 2-sided significance of p-0.05, with a drop-out rate of 10%. Results A total of 240 patients were randomized between November 2015 and February 2023- 120 each on the trial and control arm. The median age was 54 (43-73) and 55 (43-74) years; 35% and 31.7% patients were early breast cancer (cT1-2, N0-1) in the trial and control arms respectively. The median pT size was 2.6 cm and 65% patients were node positive overall. The incidence of grade II-IV CIPN (motor and/or sensory) at the end of chemotherapy was 55.9% and 56.8% in the trial and control arms respectively (p=0.90, 95%CI-0.12-0.13). Overall, chemotherapy related adverse events (CTCAE-V4) were seen in 41.39 and 39.9% in trial and control arms respectively. The average EORTC-QLQ-CIPN20 score at 8 weeks after last cycle of chemotherapy for motor neuropathy was 11.18 (0-70) and 13.53 (0-74), for sensory neuropathy was 8.51 (0-76) and 9.27 (0-81) and that for autonomic neuropathy was 4.94 (0-67) and 4.65 (0-67) in the trial and control arms respectively (p=NS). Conclusion Hydroxyprogesterone did not reduce the incidence of paclitaxel related CIPN when assessed immediately post-chemotherapy. The absolute incidence of CIPN (any grade) was 61% in our study which is like that reported in literature. Long term follow-up of these patients will assess the recovery of CIPN and long-term impact of the study interventions on CIPN. The study was approved by Institutional Review Board and Drug Controller General of India (CTRI/2015/11/006381). Citation Format: Rajendra Badwe, Shalaka Joshi, Rohini Hawaldar, Tejal Panhale, Nita Nair, Sandesh Sawant, Vaibhav Vanmali, Mitchelle Engineer, Anuradha Daptardar, Vani Parmar, Seema Gulia, Sudeep Gupta. A phase-3 randomized controlled study to evaluate the role of hydroxyprogesterone in prevention of chemotherapy induced neurotoxicity in women with 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 PO3-12-11.

Abstract PO1-10-01: Racial/Ethnic Disparities in Rates of Pathological Complete Response and Survival in Patients with Inflammatory Breast Cancer

Abstract 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 heart disease was observed between the groups. Analysis of overall survival (OS) showed a 5-year OS of 98%, decreasing to 89% at 10 years. For ATM variant carriers, the OS at 5, 10, and 15 years was 100%, 89%, and 89%, respectively, similar to non-carriers. Kaplan-Meier analysis revealed no significant differences in 5, 10, and 15-year overall survival, progression-free survival, local failure-specific survival, and contralateral breast cancer rates between the groups. Conclusion: In non-metastatic breast cancer patients, monoallelic ATM variant carrier status does not significantly influence acute or late RT toxicities and survival outcomes. These findings, derived from a small cohort, highlight the need for prospective studies for further validation. Table: Acute and Late Toxicities Post-Radiation Therapy in Monoallelic ATM Variant Carriers vs Non-Carriers Citation Format: Rebecca Zasloff, Samantha Thomas, Kendra Parrish, Astrid Botty van de Bruele, Gayle DiLalla, Maggie DiNome, Laura Rosenberger, Hannah Woriax, E Shelley Hwang, Jennifer Plichta, Akiko Chiba. Racial/Ethnic Disparities in Rates of Pathological Complete Response and Survival in Patients with Inflammatory 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 PO1-10-01.

Abstract PO1-22-05: Radiation Therapy Toxicities and Survival Outcomes in Monoallelic ATM Variant Carriers with Non-Metastatic Breast Cancer: A Retrospective Analysis

Abstract 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 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 heart disease was observed between the groups. Analysis of overall survival (OS) showed a 5-year OS of 98%, decreasing to 89% at 10 years. For ATM variant carriers, the OS at 5, 10, and 15 years was 100%, 89%, and 89%, respectively, similar to non-carriers. Kaplan-Meier analysis revealed no significant differences in 5, 10, and 15-year overall survival, progression-free survival, local failure-specific survival, and contralateral breast cancer rates between the groups. Conclusion: In non-metastatic breast cancer patients, monoallelic ATM variant carrier status does not significantly influence acute or late RT toxicities and survival outcomes. These findings, derived from a small cohort, highlight the need for prospective studies for further validation. Table: Acute and Late Toxicities Post-Radiation Therapy in Monoallelic ATM Variant Carriers vs Non-Carriers * Pearson/Chi2 test ; NS: non significant at α=0.05; ATM +/+: wild type for ATM; ATM +/- : ATM monoallelic germline variant carrier Citation Format: Rayan BENSENANE, Youlia Kirova, Arnaud BEDDOK, Andine ANDRIEU, Fabienne Lesueur, Eve CAVACIUTI, Dorothée Le GAL, Severine EON-MARCHAIS, Dominique STOPPA LYONNET. Radiation Therapy Toxicities and Survival Outcomes in Monoallelic ATM Variant Carriers with Non-Metastatic Breast Cancer: A Retrospective Analysis [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 PO1-22-05.

Clinical Significance of Serum Cancer Antigen 15-3 (CA15-3) as Prognostic Parameter in Non-metastatic Breast Cancer Patients: is still a valid test?

Clinical Significance of Serum Cancer Antigen 15-3 (CA15-3) as Prognostic Parameter in Non-metastatic Breast Cancer Patients: is still a valid test?

Abstract 4975: Stretching the boundary of Oncotype DX testing

Abstract Background: The predictive value of Oncotype DX in early-stage breast cancer had been well established. Strongest data support the use of chemotherapy for Recurrence Score (RS) &amp;gt; 30, with 25-30 deriving some benefit. Those with intermediate RS 16-25 are thought to have a small benefit from chemotherapy, especially premenopausal patients. Tumor size &amp;gt;5 cm is viewed as a high-risk feature regardless of RS. Our goal is to investigate how patients with uncertainty regarding their anticipated recurrence risk were managed at our institution. Methods: We conducted a retrospective analysis to explore the management of non-metastatic HER-2 negative hormone sensitive breast cancer patients diagnosed between 01/2018 &amp;12/2020 stratifying them into the following study groups of interest: premenopausal (age &amp;lt;50), RS 16-25 compared to RS 26-30 and tumor size &amp;gt;5cm. Patients were compared based on whether they received adjuvant chemotherapy or not. The primary endpoint was the rate of local recurrence. Results: The results of our analysis are illustrated in the table. Studying the premenopausal group, 91.3% had RS &amp;lt; 16; yet 35% of them received chemotherapy. Patients with RS &amp;gt; 25 represented 3.2% of the premenopausal group, 12.5% of which did not receive chemotherapy. The six recurrences in the premenopausal group were all from the RS &amp;lt;16 subgroup. Comparing the RS 26-30 to the RS 16-25 group, patients were on average older with tumors being on average smaller, yet more patients were treated with chemotherapy; and there were no recurrences noted in both subgroups. Finally, in the tumor size &amp;gt;5 cm group, 91.4% had RS &amp;lt;16, almost all were premenopausal with many patients being lymph node negative, yet more than half received chemotherapy. Conclusions: In our study we demonstrate that in certain subgroups of early-stage breast cancer there is inconsistency in clinical practice when prescribing chemotherapy to patients factoring in their Oncotype DX scores. There is need for larger trials to guide clinicians on using Oncotype DX in those subgroups of patients. Characteristics, Treatment Pattern and Outcomes of Patient Groups of Interest Characteristics Premenopausal (N=506) RS 16-25 (N=28) RS 26-30 (N=36) Tumor Size &amp;gt;5 cm (N=47) Age, Mean (SD) 42.65 (5.46) 44.71 (3.85) 63.56 (9.65) 42.02 (6.14) Age, Range 19 - 49 36 - 49 45 - 79 28 - 57 Mean Tumor Size, mm (SD) 29.66 (52.21) 29.57 (33.88) 16.88 (11.19) 83.61 (37.52) Lymph Nodes Positive, n (%) 91 (18.0%) 2 (7.1%) 0 (0.0%) 16 (34.0%) Received Chemotherapy, n (%) 184 (36.4%) 7 (25.0%) 13 (36.1%) 25 (53.2%) Local Recurrence, n (%) 6 (1.2%) 0 (0.0%) 0 (0.0%) 0 (0.0%) Mean Follow- Up, months (SD) 19.28 (8.20) 19.39 (7.07) 21.21 (11.04) 19.26 (8.93) Citation Format: Zaid Al-Saheli, Vrushali Dabak. Stretching the boundary of Oncotype DX testing [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4975.

Insights into the Crosstalk Between miR-200a/lncRNA H-19 and IL-6/SIRT-1 Axis in Breast Cancer.

Breast cancer (BC) is a highly prevalent malignancy that poses a significant threat to women's well-being. Novel biomarker identification helps to improve clinical outcomes and provide tailored treatments. Our research aims to explore the diagnostic potential of miR-200a/lncRNA H-19 and interleukin-6 (IL-6)/SIRT-1 axis crosstalk and evaluate the impact of metastasis on gene expression, which provides valuable insights into the diagnosis and treatment of BC. In this case-control study, we collected blood samples from 54 nonmetastatic breast cancer (NMBC) patients, 46 metastatic breast cancer (MBC) patients, and 50 healthy individuals. We used real time-polymerase chain reaction to measure the expression levels of lncRNA H-19 and miR-200a, whereas enzyme linked immunosorbent assay was used to determine the IL-6 levels. In addition, we evaluated SIRT-1 expression level using a Western blot assay. The levels of lncRNA H-19, miR-200a, and IL-6 were higher in BC patients, whereas SIRT-1 levels were lower. Patients with MBC had higher levels of lncRNA H-19, miR-200a, and IL-6 than those with NMBC. In addition, the expression of lncRNA H-19 and miR-200a showed a negative correlation with SIRT-1 expression, whereas the levels of lncRNA H-19 and miR-200a showed a positive correlation with IL-6 expression level. The diagnostic potential of lncRNA H-19 and miR-200a in BC is undeniable. Moreover, the robust association of IL-6/SIRT-1 with lncRNA H-19/miR-200a expression presents a promising opportunity for clinical outcomes and tailored treatments.

Translation and psychometric assessment of the mastectomy module of the BREAST-Q questionnaire for use in Nigeria

BackgroundThe majority of non-metastatic breast cancer patients in sub-Saharan Africa are recommended to have mastectomy. The impact of mastectomy on a predominantly young African patient population requires evaluation. The BREAST-Q is a validated patient-reported outcome measure of quality-of-life following breast surgery that has been translated into 30 languages-none in Africa. This study aimed to translate and assess the psychometric properties of the mastectomy module of the BREAST-Q for use in Nigeria.MethodsThe BREAST-Q mastectomy module was translated from English to Yoruba and its psychometric properties assessed using best practice guidelines. Translation was performed in 4 steps: forward translation (x2), back translation, back translation review, and cognitive interviews with post-mastectomy patients. The translated BREAST-Q instrument was administered to post-mastectomy patients (n = 21) alongside the EORTC-QLQ BR23 to evaluate construct validity. Test-retest reliability was evaluated using intraclass correlation coefficients (ICC); surveys were re-administered 4 weeks apart.ResultsThe translation process identified English phrases not amenable to direct translation, including “emotionally healthy” and descriptions of pain (“nagging,” “throbbing,” “sharp”). Translations were amended to reflect local context and question intent. During cognitive interviews, patients provided suggestions to simplify complex phrases, e.g. “discomfort in your breast area.”. Internal consistency within scales was over 0.70 for psychosocial wellbeing (α = 0.84–0.87), sexual wellbeing (α = 0.98–0.99), physical wellbeing in chest (α = 0.84–0.86), and satisfaction with care (α = 0.89–0.93). ICC for test-retest reliability was moderate (0.46–0.63).ConclusionsThe Yoruba version of the BREAST-Q mastectomy module presents a unique opportunity to adequately capture the experiences of Nigerian women post mastectomy. This instrument is being used in a pilot study of Nigerian patients to identify targets for intervention to improve the patient experience and compliance with breast cancer surgery.