Operable Breast Cancer Patients Research Articles

Disparities in quality of life among patients with breast cancer based on surgical methods: a cross-sectional prospective study

To determine the impact of breast conservation on quality of life and identify treatment-related and other demographic factors associated with post-breast cancer treatment quality of life. A prospective study was conducted on 392 women who underwent breast cancer surgery at Hangzhou Cancer Hospital from January 1, 2013, to December 31, 2022. Operable breast cancer patients who had completed all treatments except endocrine therapy were included. Patients with tumor recurrence/metastasis, bilateral or male breast cancer, and other primary malignancies were excluded. After enrollment, patients were asked to complete the BREAST-Q scale, and their pathological and medical records were reviewed. Analysis of variance was used to compare the quality of life scores among the groups. Univariate and multivariate linear regression analyses were performed to identify independent factors associated with quality of life scores in different domains. Participants completed the BREAST-Q scale at a median of 4.6 years after surgery. Quality of life scores varied based on the therapeutic strategy. Breast conservation has significant advantages over mastectomy in terms of breast satisfaction, psychosocial, and sexual well-being. Compared to oncoplastic breast-conserving surgery, mastectomy was independently associated with decreased breast satisfaction, psychosocial, and sexual well-being, while conventional breast-conserving surgery showed comparable outcomes to oncoplastic breast-conserving surgery in terms of these factors. Breast conservation leads to an improvement in quality of life compared to mastectomy. Oncoplastic breast-conserving surgery does not lead to a decrease in quality of life compared to conventional breast-conserving surgery and offers better outcomes compared to mastectomy.

Impact of the COVID-19 pandemic on breast cancer pathological stage at diagnosis in Tunisian patients.

Breast cancer (BC) patients' diagnosis and management was affected by a global reorganization after the Coronavirus disease 2019 (COVID-19). Our study aimed to assess the impact of the pandemic on the pathological stage of newly diagnosed patients with BC compared to pre-pandemic and to identify predictive factors of tumor advanced stage. Pathological records of all consecutive newly operated BC patients between March 2020 and December 2021 were reviewed retrospectively. Clinical and pathological prognostic factors of BC were collected and compared between pre-pandemic and pandemic periods. Then, predictive factors of tumor advanced stage were identified. Of the 225 cases included in the analysis, 98.7% were females and 1.3% were males. The median time from first histological diagnosis to first surgical treatment was enlarged by 42 days with a significant difference between the two periods (p = 0.002). Newly diagnosed BC patients during the COVID-19 pandemic were operated at a more advanced stage (54.1% vs 36.2%, p = 0.007), had a greater lymphovascular invasion (p = 0.002), lymph node metastasis (p = 0.015) and are more commonly of IBC NST histological type (p = 0.005). Moreover, multivariate analyses showed that the pandemic period (AOR = 2.28; p = 0.016) and the lympho-vascular invasion (p < 0.001) were independently associated with advanced stage of tumors. Our findings proved an increase in alarming rates of advanced stage BC associated with the COVID-19 crisis. These findings support recommendations for a quick restoration of BC screening at full capacity, with adequate prioritization strategies to mitigate harm.

A prospective audit to assess the feasibility of sentinel lymph node biopsy and/or low axillary sampling in clinicoradiologically node-negative axilla for early breast carcinoma

Background: Sentinel lymph node (SLN) dissection was designed to minimize side effects of lymph node surgery but still offer outcomes of axillary lymph node dissection. Aims and Objectives: Our study is designed to determine whether SLN resection achieves the same therapeutics outcome as complete axillary dissection but with fewer side effects for node-negative axilla in clinicoradiologically operable breast cancer patients. Materials and Methods: Duration-based prospective observational study was carried out at the General Surgery and Surgical Oncology Department at Government Medical College and Hospital, Aurangabad with a duration of 2 ½ years from July 2019 to January 2022. A total of 36 patients of breast cancers with stages T1-T2, N0 with clinically and radiologically negative axilla from July 2019 to January 2022 duration were included in our study. Results: When the histopathological status of axillary lymph nodes was compared to the histopathology of SLNs it was seen that out of 36 patients, the histopathology of sentinel node was positive in 10 patients (10/36) however the rest of the axilla was positive in 6 cases and negative in 4 cases and the histopathology sentinel node was negative in 26 patients out of 36 cases (26/36) however the rest of the axilla was also negative in 24 cases and positive in 2 cases. Conclusion: SLN biopsy using methylene blue dye alone is a highly reliable and predictable technique to stage the axilla in breast cancer patients as this study shown a low false-negative rate (7.69%). This technique may help to avoid complete axillary lymph node dissection in sentinel node-negative patients thereby minimizing the morbidity of axillary lymph node dissection. This study demonstrates that sentinel node localization is possible with methylene blue dye alone.

Analysis of neoadjuvant chemotherapy for breast cancer: a 20-year retrospective analysis of patients of a single institution

BackgroundNeoadjuvant chemotherapy (NAC) has been widely applied in operable breast cancer patients. This study aim to identify the predictive factors of overall survival(OS) and recurrence free survival (RFS) in breast cancer patients who received NAC from a single Chinese institution.Patients and MethodsThere were 646 patients recruited in this study. All the patients were treated at department of Surgical Oncology, Sir Run Run Shaw Hospital between February 25, 1999 and August 22, 2018. The relevant clinicopathological and follow-up data were collected retrospectively. RFS and OS were assessed using the Kaplan-Meier method. Multivariate Cox proportional hazards model was also employed. Multi-variate logistic regression model was simulated to predict pathologic complete response (pCR).ResultsIn total, 118 patients (18.2%) achieved pCR during NAC. The 5-year OS was 94.6% versus 78.1% in patients with and without pCR, respectively (P < 0.001). The 5-year RFS was 95.3% and 72.7%, respectively (P < 0.001). No difference was detected among molecular subtypes of 5-year RFS in patients obtained pCR. Factors independently predicting RFS were HER2-positive subtype (hazard ratio(HR), 1.906; P = 0.004), triple-negative breast cancer (TNBC) (HR,2.079; P = 0.003), lymph node positive after NAC(HR,2.939; P < 0.001), pCR (HR, 0.396;P = 0.010), and clinical stage III (HR,2.950; P = 0.016). Multi-variate logistic regression model was simulated to predict the pCR rate after NAC, according to clinical stage, molecular subtype, ki-67, LVSI, treatment period and histology. In the ROC curve analysis, the AUC of the nomogram was 0.734 (95%CI,0.867–12.867).ConclusionsFollowing NAC, we found that pCR positively correlated with prognosis and the molecular subtype was a prognostic factor.

The Effect of Art Therapy on Pain, Emesis, Anxiety, and Quality of Life in Operated Breast Cancer Patients: Randomized Control Trials.

Background: Breast cancer symptoms related to the disease nature and treatments develop and the quality of life of patients is impacted. Art therapy improves the quality of life by increasing symptom control and treatment compliance. This study aimed to determine the effect of art therapy on pain, emesis, anxiety, and quality of life in operated breast cancer patients. Methods: This experimental research was carried out with a total of 60 patients, 30 in the intervention group (IG) and 30 in the control group (CG), who received treatment in the Oncology Center of Sivas Cumhuriyet University Practice and Research Hospital. A Personal Information Form, the Pain Intensity-Visual Analog Scale, the Rhodes Index of Nausea, Vomiting, and Retching, the Beck Anxiety Inventory, and the Functional Assessment of Cancer Therapy Scale-General (FACT-G) were used to collect research data. Within the scope of the research, IG received chemotherapy sessions for 10 weeks (five sessions) with 2-week intervals by an art specialist in marbling, accompanied by ney music. CG received no intervention. The obtained data were uploaded to the SPSS (22.0) program and statistical analysis was performed. Results: The decrease in the pain, nausea-vomiting, and anxiety levels of the patients in IG and the increase in their quality of life after the art therapy accompanied by ney music were statistically significant compared with the first follow-up (p < 0.05). There was no statistically significant change in the quality of life of the patients in the CG, whereas their pain, nausea-vomiting, and anxiety scores increased. According to the comparison between IG and CG, there was a significant difference in favor of IG in terms of pain severity, quality of life, emesis, and anxiety levels (p < 0.05). Conclusions: The art of marbling with ney was effective in operated breast cancer patients experiencing pain, emesis, and anxiety and improved their quality of life. Clinical Trial Registration: NCT05666583.

Does Dual Anti-HER2 Therapy Increase Early Cardiac Toxicity in Comparison with Trastuzumab Alone in Breast Cancer Patients Receiving Adjuvant Radiotherapy? A Multicenter Retrospective Study

Adjuvant trastuzumab in combination with RT has proved its safety in terms of cardiac events. Dual anti-HER2 therapy with pertuzumab is currently standard adjuvant therapy in N+ and high-risk N0 early breast cancer (BC) patients. Our study aims to find if it increases early cardiac toxicity compared with trastuzumab alone in BC patients receiving adjuvant radiotherapy. Operable BC patients who received adjuvant radiotherapy (RT) and trastuzumab with or without pertuzumab between January 2017 and September 2020 in 7 Chinese centers were retrospectively reviewed. The cardiac examination included ultrasonography, electrocardiogram (ECG), NT-proBNP, and cTnI before RT and during follow-up. The cardiac event was any new-onset symptomatic heart disease or abnormality in the cardiac examination after RT. In total, 711 patients with a median age of 52 years were included, of whom 567 (79.7%) patients were treated with trastuzumab-only and 144 (20.3%) patients received dual anti-HER2 therapy. Adjuvant RT was given concurrently in 140/144 (97.2%) of dual anti-HER2 therapy and 562/567 (99.1%) of trastuzumab alone, respectively. With a median follow-up of 11 months, no patients developed symptomatic heart diseases. Among patients with normal baseline, 17 (2.4%), 86 (12.1%), 18 (2.5%) and 14 (7.3%) developed new-onset diastolic dysfunction, left ventricular ejection fraction (LVEF) decline, abnormal ECG, and abnormal NT-proBNP, respectively. No significant difference was found between the trastuzumab-only and dual anti-HER2 cohort in the incidence of all kinds of new-onset cardiac events (all p > 0.1). Multivariate analysis showed that left-sided (vs right-sided) RT significantly increased the risk of ECG abnormality (HR = 2.32, 95% CI 1.62-3.32, p<0.001). Increased age was an independent risk factor for diastolic dysfunction (HR = 1.1, 95% CI 1.02-1.18, p = 0.0098). Dosimetric analysis showed that patients who developed any cardiac events had increased mean heart dose (397.67±251.08 vs 344.87±236.75 cGy, p = 0.032). A significant increase in risk of cardiac events was found in patients with mean heart dose > 450 cGy (HR = 1.55, 95% CI 1.17-2.05, p = 0.0024), V5 > 26% (HR = 1.51, 95% CI 1.09-2.09, p = 0.013), and V30 > 5.5% (HR = 1.49, 95% CI 1.09-2.04, p = 0.0117), respectively. Further analysis was done in the subgroup of patients treated with left-sided RT, internal mammary nodes RT, or anthracyclines, no difference in risk of cardiac events was found between trastuzumab alone and dual anti-HER2 therapy in concurrent with RT (all p > 0.05). Compared with trastuzumab-only, dual anti-HER2 therapy does not increase early cardiac toxicity in combination with adjuvant RT in BC patients. Cardiac radiation exposure remains the primary risk factor associated with early cardiac toxicity.

Abstract OT1-09-01: Axillary surgery de-escalation after neoadjuvant chemotherapy in breast cancer patients with initially involved node: the GANEA 3 trial

Abstract Background: In breast cancer patients, neoadjuvant chemotherapy (NAC) allows to obtain pathological complete response (pCR). In case of initially involved node before NAC, pCR after NAC could make it possible to avoid axillary surgery. The aim of our study was to address parameters to build a tool able to accurately select patients at a high probability of axillary pCR after NAC. Method: GANEA 3 was a French prospective multi institutional cohorts of breast cancer patients with a proven axillary involved node treated with NAC (NCT03630913). Initially involved node was clipped before treatment. Each patient received, before and after NAC, a bilateral mammography, a Magnetic Resonance Imaging (MRI), an axillary sonography. After NAC breast, conservative or radical, and axillary surgery, were performed. Breast surgery allowed to measure breast tumor residual and to perform a Sataloff classification. Targeted axillary detection (TAD) was defined as the combination of the resection of the clipped node and SLN dissection. Axillary clipped node, sentinel lymph node (SLN) and axillary lymph node dissection (ALND) were always performed. ALND allowed to assess the false negative rate (FNR) of axillary clipped node and SLN dissection. A total of 500 included patients is planned to close this still ongoing trial. Results : From January 2019 to March 2022, 405 patients were included from 18 institutions. We present here the results of the 260 first patients, who experienced a complete treatment with NAC courses and post NAC breast and axillary surgery. Among these patients, SBR grade was III in 52%, OR and PR were positive in 59% and 46% respectively, HER2 was overexpressed in 40%, 26% were triple negative and pCR was present in 28%. FNR of the SLN detection was 21.1%, 9% for the clipped node alone and 6% for the TAD. Histopronostic grading, progesteron receptors, HER2 expression, MRI results and Sataloff grading of breast residual tumor were indepently linked with global pCR (breast and axilla) in multivariate analysis. The Area Under the Curve (AUC) model was 0.91 with 82% correctly patients classified. The false negative rate of no pCR classified patients was 14%. Conclusion : Intermediate results of Ganea 3 trial showed that operable breast cancer patients with an initially involved axillary node treated with NAC, showed that TAD allows to reduce the FNR of axillary surgery. Patients with histopronostic grade 3, negative progesteron receptors, HER2 overexpression, a normal MRI after NAC and a breast Sataloff A, have a low risk of axillary tumour residual burden and could be safely spare from any axillary surgery. Large prospective trials are needed to confirm the safety of this surgical de-escalation. Citation Format: Céline Renaudeau, Pierre Gimbergues, Eugénie Guillot, Marie-Pierre Chauvet, Marian Gutowski, Eva Jouve, Philippe Rauch, Monique Cohen, Christelle Faure, Marie-Martine Padeano, Vivien Ceccato, Catherine Uzan, Anne-Sophie Bats, Hélène Charitansky, Pierre-François Dupré, Augustin Reynard, Séverine Alran, Cécile Bendavid-Athias, Loïc Campion, Isabelle Doutriaux, Jean-Marc Classe. Axillary surgery de-escalation after neoadjuvant chemotherapy in breast cancer patients with initially involved node: the GANEA 3 trial [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT1-09-01.

Potential Antihuman Epidermal Growth Factor Receptor 2 Target Therapy Beneficiaries: The Role of MRI-Based Radiomics in Distinguishing Human Epidermal Growth Factor Receptor 2-Low Status of Breast Cancer.

Multiparametric MRI radiomics could distinguish human epidermal growth factor receptor 2 (HER2)-positive from HER2-negative breast cancers. However, its value for further distinguishing HER2-low from HER2-negative breast cancers has not been investigated. To investigate whether multiparametric MRI-based radiomics can distinguish HER2-positive from HER2-negative breast cancers (task 1) and HER2-low from HER2-negative breast cancers (task 2). Retrospective. Task 1: 310 operable breast cancer patients from center 1 (97 HER2-positive and 213 HER2-negative); task 2: 213 HER2-negative patients (108 HER2-low and 105 HER2-zero); 59 patients from center 2 (16 HER2-positive, 27 HER2-low and 16 HER2-zero) for external validation. A 3.0 T/T1-weighted contrast-enhanced imaging (T1CE), diffusion-weighted imaging (DWI)-derived apparent diffusion coefficient (ADC). Patients in center 1 were assigned to a training and internal validation cohort at a 2:1 ratio. Intratumoral and peritumoral features were extracted from T1CE and ADC. After dimensionality reduction, the radiomics signatures (RS) of two tasks were developed using features from T1CE (RS-T1CE), ADC (RS-ADC) alone and T1CE + ADC combination (RS-Com). Mann-Whitney U tests, the least absolute shrinkage and selection operator, receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA). For task 1, RS-ADC yielded higher area under the ROC curve (AUC) in the training, internal, and external validation of 0.767/0.725/0.746 than RS-T1CE (AUC=0.733/0.674/0.641). For task 2, RS-T1CE yielded higher AUC of 0.765/0.755/0.678 than RS-ADC (AUC=0.706/0.608/0.630). For both of task 1 and task 2, RS-Com achieved the best performance with AUC of 0.793/0.778/0.760 and 0.820/0.776/0.711, respectively, and obtained higher clinical benefit in DCA compared with RS-T1CE and RS-ADC. The calibration curves of all RS demonstrated a good fitness. Multiparametric MRI radiomics could noninvasively and robustly distinguish HER2-positive from HER2-negative breast cancers and further distinguish HER2-low from HER2-negative breast cancers. 3. Stage 2.

Retrospective Study of Prognostics Factors in Operated Breast Cancer Patients in the Western Indian Population

Retrospective Study of Prognostics Factors in Operated Breast Cancer Patients in the Western Indian Population

Comprehensive liquid biopsy analysis as a tool for the early detection of minimal residual disease in breast cancer

Liquid biopsy (LB) provides a unique minimally invasive tool to follow-up cancer patients over time, to detect minimal residual disease (MRD), to study metastasis-biology and mechanisms of therapy-resistance. Molecular characterization of CTCs offers additionally the potential to understand resistance to therapy and implement individualized targeted treatments which can be modified during the disease evolution and follow-up period of a patient. In this study, we present a long-term follow-up of operable breast cancer patients based on a comprehensive liquid biopsy analysis. We performed a comprehensive liquid biopsy analysis in peripheral blood of 13 patients with early-stage operable breast cancer at several time points for a period of ten years, consisting of: (a) CTC enumeration using the CellSearch system, (b) phenotypic analysis of CTCs using Immunofluorescence, (c) gene expression analysis, in EpCAM(+) CTCs for CK-19, CD24,CD44, ALDH1, and TWIST1, (d) analysis of PIK3CA and ESR1 mutations in EpCAM(+) CTCs and corresponding plasma ctDNA and (e) DNA methylation of ESR1 in CTCs. 10/13 (77%) patients were found negative for LB markers in PB during the whole follow-up period, and these patients did not relapse during the follow-up. However, 3/13(18%) patients that were positive for at least one LB marker relapsed within the follow-up period. The molecular characteristics of CTCs were highly different even for the same patient at different time points, and always increased before the clinical relapse. Our results indicate that liquid biopsy can reveal the presence of MRD at least 4 years before the appearance of clinically detectable metastatic disease demonstrating that a comprehensive liquid biopsy analysis provides highly important information for the therapeutic management of breast cancer patients.

Effects of Regular Exercise, Arts (Origami), and Group Psychotherapy on the Quality of Life, Anxiety, Depression, Patient Satisfaction, and Hope in Cancer Patients in Remission: A Prospective Study

Background: Cancer is a critical public health problem worldwide. Some studies found that group psychotherapy, when applied to cancer patients as a psychiatric approach, also decreases the existing psychopathological symptoms. Objectives: This study aimed to determine the effects of a Quality-of-Life Support Program (QOLSP) for cancer patients in remission. Methods: Twenty-six cancer patients who were monitored while in remission were included in this study. During the eight-week prospective study, a QOLSP was implemented weekly. The patients’ hope, anxiety, depression, and quality of life (QoL) were assessed using different scales. Additional questionnaires assessed the status of program satisfaction and the arm utilization angle of the breast cancer patients (n=20). Results: The total mean score on the hope scale was initially 25.6±3.9 and increased to 29.7±1.9 post-QOLSP (P˂0.001). Additionally, the total mean score on the EORTC QLQ-C30 scale was initially 68.9±4.9 and increased to 92.6±2.2 post-QOLSP (P˂0.001). Moreover, the total mean anxiety and depression scores on the Hospital Anxiety and Depression Scale (HADS) decreased (P&lt;0.001) post-QOLSP. Factors affecting the hope score differences, including the hope pre-score and the sap score (Loss of Appetite), in the EORTC QLQ-C30 symptom scale were significant (P&lt;0.001 and P=0.01, respectively). Factors affecting the anxiety and depression score differences were the HADS anxiety (P=0.001) and depression (P&lt;0.001) pre-scores, in descending order. Moreover, the factor affecting the sql2 score, evaluating General Health Status on the EORTC QLQ-C30, was the sql2 pre-score (P&lt;0.001). All 26 patients were “very satisfied” with the program, and the arm usage angle of the 20 operated breast cancer patients improved. Conclusion: Facilities that can provide a multidisciplinary QOLSP throughout treatment and follow-up will favorably affect QoL, anxiety, depression, hope, and satisfaction among cancer patients.

Grading Evaluation of Cardiotoxicity in Patients with Breast Cancer Treated with Adjuvant Paclitaxel Anthracycline/Cyclophosphamide Chemotherapy: A Meta-Analysis.

Objective The cardiac safety of concurrent treatment with anthracycline (A), cyclophosphamide (C), and paclitaxel (T) in an adjuvant BC treatment regimen is still under debate. In this study, we aimed to determine cardiotoxicity events following ACT chemotherapy among operable breast cancer patients without HER2-positive. Methods We searched PubMed and the Cochrane Library for RCTs prior to July 2019 evaluating the cardiac impairment of ACT chemotherapy regimens in BC patients. The search terms were “BC,” “chemotherapy,” “docetaxel or “doxorubicin,” “paclitaxel,” and “cyclophosphamide.” Cardiotoxic events included LVEF decline ≥ 10 points, congestive heart failure (CHF), and cardiac death. Results In total, 12 studies with 4032 subjects were included in this meta-analysis, and all patients received ACT regimen. The analysis results indicated that LVEF decrease ≥ 10 points was the most common cardiotoxic event (16%; (95% CI (8%–24%)) with χ2 = 95.75, P < 0.001, I2 = 95.8%). CHF showed the lowest rate (1%; (95% CI (0%–1%)) with χ2 = 8.00, P = 0.433, I2 = 0.0%). Subgroup analysis demonstrated that the incidence of CHF due to A → C → T chemotherapy regimen was lower than that of other events, however, without significance. No significant difference was observed in the occurrence of cardiac death. Conclusion The ACT regimen in patients with HER2-negative BC was associated with an increased risk of adverse cardiactoxic events.

Definitive radiotherapy with stereotactic or IMRT boost with or without radiosensitization strategy for operable breast cancer patients who refuse surgery.

For breast cancer (BC) patients who refused surgery, we developed a definitive treatment employing modern sophisticated radiation techniques. Thirty-eight operable BC patients were treated by conventionally fractionated whole-breast (WB) radiotherapy in combination with stereotactic (for primary tumor) or intensity-modulated (for primary tumor with/without regional lymph nodes [LN]) radiotherapy (IMRT) boost. Standard doses were 50Gy/25 fractions, 21Gy/3 fractions and 20Gy/8 fractions, respectively, for the three radiation modalities. Disease stages were 0 (ductal carcinoma in situ [DCIS]) in seven patients, I in 12, II in 16 and III in three. In 26 patients, intratumoral hydrogen peroxide injection or hyperthermia with oral tegafur-gimeracil-oteracil potassium (S-1) was also used to sensitize the tumors to radiation. Hormonal and standard systemic therapy were administered in 25 and 13 patients, respectively. Complete and partial responses were obtained in 19 patients each; in patients with partial response, no further regrowth of the residual mass was observed, except for two patients who developed local recurrence. During a follow-up of 8-160months (median, 50months for living patients), two, one and two patients developed local relapse, sub-clavicular node metastasis and distant metastasis, respectively. The 5-year rates for overall, progression-free and local relapse-free survival were 97.2, 90.9 and 93.4%, respectively. Fourteen patients developed Grade 3 radiation dermatitis but all recovered after treatment. In 47%, the affected breast became better-rounded, and the nipple of the irradiated breast became higher by ≥1cm than the contralateral nipple. Our method might be a treatment option for operable BC patients.

Influence of alcohol sensitivity on bone metastases and skeletal-related events in primary operable breast cancer: A retrospective cohort study.

BackgroundBone metastases in breast cancer patients are a common concern for medical doctors and dentists. Bone-modifying agents, which are necessary to prevent skeletal-related events (SREs), are associated with osteonecrosis of the jaw as an adverse side effect. Hypersensitivity to alcohol is an unfavorable response caused by deficiency of aldehyde dehydrogenase-2 (ALDH2) activity. Inactive ALDH2 is associated with osteoporosis, but its influence on bone metastases is unclear. The aim of our study was to evaluate the effects of alcohol sensitivity on bone metastases and SREs in primary operable breast cancer patients.MethodsWe retrospectively analyzed patients who were administered docetaxel, an anti-tumor agent, for histologically diagnosed breast cancer between April 2004 and September 2015. Alcohol sensitivity was assessed based on medical records of hypersensitivity to alcohol. The primary endpoint was time to bone metastases and the secondary endpoint was time to first SRE from the initial docetaxel administration. Data were stratified by alcohol sensitivity and tumor stages, and differences were estimated by the Kaplan-Meier method. Prognostic risk factors were analyzed by the multivariate Cox proportional hazards model.ResultsThe median follow-up period of patients with high sensitivity to alcohol (n = 45) was 54 months and that for those with low sensitivity (n = 287) was 64 months. Stratification by alcohol sensitivity revealed that tumor stage exhibited significant correlations with the cumulative incidence of bone metastases in low-sensitivity patients; however, no differences were found in high-sensitivity patients. In multivariate analysis, alcohol sensitivity was a significant prognostic risk factor for bone metastases (HR 2.721, 95% CI 1.268–5.841, P = 0.010).ConclusionAlcohol sensitivity may be a prognostic risk factor for bone metastases. More detailed genetic investigations and metabolic analyses are needed.

28-gene classifier model for prediction of local recurrence and distant metastasis risk in HER-2 positive operable breast cancer.

e13018 Background: Accurate prediction of postoperative recurrence risk is very important for the formulation of appropriate treatment for breast cancer patients. However, traditional clinicopathological indicators cannot accurately assess the recurrence risk of patients. We aimed to build a novel gene-clinical variable model, which included 28 genetic profiles and clinical variable information, to assess the risk of recurrence in a more individualized and accurate manner. Methods: We retrospectively included a cohort of operable HER-2 positive breast cancer patients treated in Cancer Hospital of the Chinese Academy of Medical Sciences from 2010 to 2016. The genetic and clinical data were used to train and validate the 28-gene classifier model in predicting local recurrence and distant metastasis risk. Results: A total of 260 HER-2 positive breast cancer patients were Included in the study. All patients received standard adjuvant chemotherapy and routine targeted therapy after mastectomy. All patients were followed up for a median of 60.4 months for disease recurrence. Among them, 21 patients had distant metastasis events and 18 patients had local recurrence events. We used the 28 gene-clinical variable model to classify 260 patients into high- and low-risk groups. Kaplan-Meyer survival curves were used to compare the prognostic difference of DFS into high- and low- risk groups. Conclusions: 28 gene-clinical variable model may be a reliable toll to predict local recurrence and distant metastasis risk in HER-2 positive operable breast cancer.

Sentinel node biopsy and regional recurrence following neoadjuvant chemotherapy in patients with isolated tumor cells: A rare event.

e12581 Background: Lack of consensus exists regarding the optimal surgical axillary management of breast cancer patients treated with neoadjuvant therapy followed by sentinel node biopsy (SNB) with only isolated tumor cells (ITCs) identified in the sentinel node (SN). Few studies with limited patients have addressed this. A prospectively maintained database was reviewed to identify residual nodal metastatic burden and outcomes for patients with SN ITCs. Methods: Operable breast cancer patients treated with neoadjuvant therapy followed by breast surgery with SNB were identified who had only ITCs in the SN. Patients were excluded who had recurrent breast cancer, metastatic disease at time of operation, or who had an operation performed at another institution. Residual burden of axillary metastatic disease in patients who underwent completion axillary dissection and locoregional recurrence were examined. All SNs were examined with both hematoxylin and eosin stains as well as well as immunohistochemical stains. Results: 875 patients underwent neoadjuvant therapy followed by breast surgery and SNB from July 2007 to November 2021. Seventeen patients (1.9%) had only ITCs in the SN. The mean patient age of these 17 patients was 55.6 years (range 31-83 years). The majority had invasive ductal carcinoma (n = 15, 88.2%). Fourteen patients (82.4%) had ER+ tumors, 11 (64.7%) PR+ tumors, 2 patients (11.7%) had HER2+, and 3 patients (17.6%) had triple negative cancers. All patients had clinical T1 to T3 tumors and clinical N0 (n = 11, 64.7%), N1 (n = 5, 29.4%), or N2 (n = 1, 5.9%) disease. Two patients had isolated tumor cells identified on frozen section. Both of these patients underwent axillary dissection during the index operation and had further nodal disease identified (1 patient with ITCs only and 1 patient with macrometastasis). Fourteen patients had SN tumor free frozen sections but ultimately had ITCs identified with H&amp;E. Five of these patients underwent a completion axillary dissection. Three of the 5 patients (60%) had additional ITCs identified after completion ALND. Fourteen patients had nodal irradiation. The three patients who did not receive irradiation did not undergo ALND. All patients with ER+ tumors received adjuvant endocrine therapy, the 2 patients with HER2+ cancers received adjuvant targeted HER2 therapy, and 4 patients received adjuvant chemotherapy. At a mean follow-up of 21.8 months (range 2-63 months), no locoregional recurrences occurred in any patient. Conclusions: ITCs in the SN after neoadjuvant therapy is a rare finding and are unlikely to be associated with regional recurrence.

Effectiveness of the Sanyin Formula Plus Chemotherapy on Survival in Women With Triple-Negative Breast Cancer: A Randomized Controlled Trial.

PurposeTo evaluate the efficacy of the Sanyin formula (SYF) plus conventional standard chemotherapy in operable triple-negative breast cancer (TNBC) patients, a randomized controlled trial was implemented at 5 hospitals and cancer centers in China between May 23, 2016, and October 31, 2019.Materials and MethodsFemale patients aged 18 to 80 years with operable TNBC after definitive surgery were screened and enrolled. The exclusion criteria included metastatic disease, other tumors, or locally advanced disease. Patients were randomly divided into groups SYF plus conventional standard chemotherapy and placebo plus conventional standard chemotherapy at a ratio of 1:1. The primary endpoint of the investigation was disease-free survival (DFS), and secondary endpoints included overall survival (OS) and toxicity.ResultsA total of 252 operable female TNBC patients were randomized to receive SYF plus conventional standard chemotherapy (N = 127) or a placebo plus conventional standard chemotherapy (N = 125). At a median follow-up of 51 months, 5-year DFS time was longer in those assigned to SYF plus conventional standard chemotherapy compared with placebo plus conventional standard chemotherapy (94.2%vs 85.5%, hazard ratio [HR] = 0.40; 95%CI, 0.17-0.97; P = 0.034). The absolute benefit for 5-year DFS was 8.7% in the SYF plus conventional standard chemotherapy group. No statistically significant difference was observed in OS between the two groups (P = 0.23). Patients with negative node status benefited more from SYF plus conventional standard chemotherapy treatment (HR = 0.21, P-interaction = 0.013) in accordance with the exploratory subgroup analyses of DFS.ConclusionsThe results of the present study suggest that the traditional Chinese medicine SYF plus conventional chemotherapy regimens is an effective alternative adjuvant chemotherapy strategy for female operable TNBC patients.Clinical Trial Registrationhttps://www.chictr.org.cn/searchproj.aspx, identifier ChiCTR-IPR-16008590.

Cost-Effectiveness Analysis of Two Chemotherapy Regiments FAC vs. Taxane for Operable Breast Cancer Patients in Indonesia.

Background:Breast cancer is the deadliest cancer among women worldwide including Indonesia. Both FAC and Taxane-based chemotherapies are often used for patients with early node-positive breast cancer. However, the study regarding the cost-effectiveness of those regiments is still rare. This study aims to analyze the cost-effectiveness of Taxane versus FAC in the Indonesia setting. Methods:Twenty-four patients with stage I-IIIA breast cancer who had received surgery, FAC or Taxane-based adjuvant chemotherapy, and radiation were included in this study. Health-related quality of life was assessed using INA-BCHRQoL. INA-BCHRQoL was mapped to the EuroQoL 5D (EQ-5D) index calculator to get the utility score. All direct cost was retrieved from electronic medical records and hospital information system. Whereas, a questionnaire was designed to collect information about society cost from patients. ICER was counted to summarize the cost-effectiveness of two chemotherapy regiments (Taxane versus FAC). A sensitivity analysis was done to assess the uncertainty result. Results:The results showed there was no significant difference between the score of quality of life and utility in respondents who received FAC chemotherapy and Taxane-based chemotherapy. However, in terms of cost, Taxane was 6.5 times higher than the FAC group per patient for chemotherapy drugs only. Moreover, the total cost of treatments in Taxane-based chemotherapy was approximately 3.7 times more costly than the counterpart in the FAC arm (p=0.000). Taxane-based chemotherapy dominated with ICER IDR 765.213.092 per QALY gained. Overall, FAC was found more cost-effective compared to the Taxane regiment. Conclusion:FAC represents the value of money compared to Taxane-based for breast cancer patients with stage I-IIIA in Indonesia.

Evaluation of KISS1 Receptor Gene Expression in Egyptian Female Patients with Breast Cancer.

Objective:Breast cancer is the second most common cancer in the world. Many metastasis suppressor genes were identified, including the KISS1 gene which encodes for a 145 amino acid protein (kisspeptin-145), which undergoes proteolytic cleavage resulting in kisspeptin-14, -13 and -10. All of these proteins can activate KISS1 receptor (KISS1R). The role of KP/KISS1R signaling in breast cancer remains controversial. The present study aimed to measure mRNA gene expression of KISS1 receptor in healthy and cancerous breast tissue and to evaluate the association of its level with the available molecular subtypes and the traditional clinico-pathological variables. Methods:The study was done on 41 operable primary breast cancer patients. Biopsies from both tumor tissue and surrounding healthy mammary tissue were taken from all patients. KISS1R mRNA expression level was measured using a quantitative real time PCR. Results:KISS1R mRNA expression was significantly higher in stage III patients compared to stage II patients. At a cut-off value for KISS1R mRNA expression of 1.75, stage II was discriminated from stage III. A significant positive correlation was found between KISS1R mRNA expression and tumor size as well as lymph nodes metastasis. KISS1R mRNA was highly expressed in ER negative cases compared to ER positive ones, and in PR negative cases compared to PR positive ones. There was a statistically significant difference in KISS1R mRNA expression levels and different molecular subtypes being over-expressed in HER2 and triple negative cancer cases. Conclusion:This study supports other studies suggesting that KISS1/KISS1R may not be acting as a metastasis suppressor in breast cancer. KISS1R mRNA is over expressed in advanced stages of breast cancer and hence it can be used as a prognostic marker for aggressiveness of breast cancer. Also being over expressed in triple negative patients, KISS1R could represent a promising therapeutic target in triple negative cases.

Abstract P2-08-02: Virtual replication of the NeoSphere trial using SimBioSys TumorScope: Associating standard of care data with clinical outcomes in HER2 positive breast cancer patients to garnish novel insights in silico

Abstract Background Clinical trials can be logistically burdensome, financially expensive, and potentially detrimental to patient outcomes. The NeoSphere study, which investigated the efficacy of docetaxel (T), pertuzumab (P), and trastuzumab (H) in combination with one another, was performed recently over an eight year stretch with n=254 operable breast cancer patients distributed across four study arms. Given the inherent hurdles of clinical trials, we set out to replicate the NeoSphere Trial in silico. We posit that never-before-possible in silico clinical trials can accurately forecast regimen efficacy/pathological complete response (pCR) rates and expand insights well in advance of human clinical trials. Analysis of tumor microenvironment and chemical interactions therein can enable drug developers to garnish more comprehensive insights than ex vivo or in vitro techniques. We aim to comprehensively understand cancer by leveraging our commercially available biophysical modeling platform and using all major hallmarks of cancer variation as input. Methods Selecting from the SimBioSys Virtual TumorBank of 3000+ past patient breast tumors and accompanying standard of care (SoC) clinical data, we matched NeoSphere sample composition based on age, tumor/node stage, cancer subtype, and HER2 receptor status. This generated a sample of n=144 patients, which were included across all four study arms (TH, THP, HP, and TP). Drug models used in our simulations were derived from publicly available data. Our main outcomes of interest (in operable breast cancer) included pCR rate by treatment arm, and pCR by treatment arm stratified by hormone receptor (HR) status (+/-). pCR was assessed per patient based on final simulation volume threshold of 0.1cc. Parameters from the NeoSphere study were mirrored in our SimBioSys Virtual Trial where possible, including treatment time, and time to surgery. We did not simulate post-surgery treatment. pCR rates were compared between virtual and clinical trials using two-tailed Fisher’s Exact tests. Results In non-stratified analyses, we observed pCR rates of 20.1% (TH), 42.4% (THP), 2.8% (HP), and 20.8% (TP) per arm, compared to 23.4% (TH), 47.7% (THP), 16.9% (HP), and 26.7% (TP) in the NeoSphere trial. Our non-stratified results were not significantly different from NeoSphere in the TH (p=0.72, OR=0.86), THP (p=0.69, OR=0.89) or TP (p=0.48, OR=0.78) arms. In our HP arm, we observed lower pCR rates (p=0.002, OR=0.17) than NeoSphere. Importantly, we predicted disease progression in 8.3% of HP patients, closely mirroring NeoSphere HP disease progression (7.4%). In our HR+ analyses, none of our results from the TH, THP, HP, or TP arms were significantly different than NeoSphere (prange = 0.34 to 0.69, ORrange = 0.61 to 1.36). In our HR- analyses, our results were not significantly different from NeoSphere in the TH (p=1.00, OR=1.03), THP (p=0.87, OR=0.92) or TP (p=0.55, OR=1.33) trial arms. However, as in our non-stratified analysis, in our HR-negative sample we observed a significantly lower proportion of pCR in patients treated with HP than in NeoSphere (p=0.0003, OR=0.00). Conclusion Using bleeding-edge biophysical simulations, our never-before-possible in silico clinical trial retrospectively predicted regimen efficacy, pCR rate, and disease progression of the NeoSphere clinical trial. Currently, we are investigating the impact of drug delivery, drug sensitivity, metabolism, and spatial heterogeneity on tumor responses within our trial. In the near future, our virtual clinical trials will curtail the negative aspects of real-world clinical trials, while enabling drug developers to garnish more comprehensive insights than ex vivo or in vitro techniques. Citation Format: John Ryan Pfeiffer, Tim Foley, Eduardo Braun, Anu Antony. Virtual replication of the NeoSphere trial using SimBioSys TumorScope: Associating standard of care data with clinical outcomes in HER2 positive breast cancer patients to garnish novel insights in silico [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-08-02.