Locally Advanced Breast Cancer Research Articles

Transfer learning of pre-treatment quantitative ultrasound multi-parametric images for the prediction of breast cancer response to neoadjuvant chemotherapy

Locally advanced breast cancer (LABC) is a severe type of cancer with a poor prognosis, despite advancements in therapy. As the disease is often inoperable, current guidelines suggest upfront aggressive neoadjuvant chemotherapy (NAC). Complete pathological response to chemotherapy is linked to improved survival, but conventional clinical assessments like physical exams, mammography, and imaging are limited in detecting early response. Early detection of tissue response can improve complete pathological response and patient survival while reducing exposure to ineffective and potentially harmful treatments. A rapid, cost-effective modality without the need for exogenous contrast agents would be valuable for evaluating neoadjuvant therapy response. Conventional ultrasound provides information about tissue echogenicity, but image comparisons are difficult due to instrument-dependent settings and imaging parameters. Quantitative ultrasound (QUS) overcomes this by using normalized power spectra to calculate quantitative metrics. This study used a novel transfer learning-based approach to predict LABC response to neoadjuvant chemotherapy using QUS imaging at pre-treatment. Using data from 174 patients, QUS parametric images of breast tumors with margins were generated. The ground truth response to therapy for each patient was based on standard clinical and pathological criteria. The Residual Network (ResNet) deep learning architecture was used to extract features from the parametric QUS maps. This was followed by SelectKBest and Synthetic Minority Oversampling (SMOTE) techniques for feature selection and data balancing, respectively. The Support Vector Machine (SVM) algorithm was employed to classify patients into two distinct categories: nonresponders (NR) and responders (RR). Evaluation results on an unseen test set demonstrate that the transfer learning-based approach using spectral slope parametric maps had the best performance in the identification of nonresponders with precision, recall, F1-score, and balanced accuracy of 100, 71, 83, and 86%, respectively. The transfer learning-based approach has many advantages over conventional deep learning methods since it reduces the need for large image datasets for training and shortens the training time. The results of this study demonstrate the potential of transfer learning in predicting LABC response to neoadjuvant chemotherapy before the start of treatment using quantitative ultrasound imaging. Prediction of NAC response before treatment can aid clinicians in customizing ineffectual treatment regimens for individual patients.

Inflammatory indicators as a prognostic factor of clinical response in locally advanced breast cancer (LABC) patients receiving neoadjuvant chemotherapy (NAC)

ObjectivesBreast cancer is a prevalent and fatal cancer worldwide. Neoadjuvant chemotherapy is a treatment option used to reduce tumor size in patients with locally advanced breast cancer. The neutrophil–lymphocyte ratio (NLR), lymphocyte–monocyte ratio (LMR), and platelet–lymphocyte ratio (PLR) are inflammatory markers that have been studied as prognostic factors in breast cancer. This cross-sectional study aimed to investigate the role of NLR, LMR, and PLR in the clinical response to neoadjuvant chemotherapy in women with locally advanced breast cancer. Materials and methodsWe used a cross-sectional research design for this study with the aim of observing the relation between NLR, LMR, and PLR and the clinical response of neoadjuvant chemotherapy. The study was conducted in Cipto Mangunkusumo General Hospital. We analyzed the medical records of 84 patients treated with neoadjuvant chemotherapy between 2016 and 2021. ResultsOur study found that majority of the subjects receives CAF combination of NAC with inoperable breast cancer. Most of the subjects have luminal B type of breast cancer and no clinical response to chemotherapy regimen. Surgery has significant association with clinical response in patients receiving NAC (P = <.001). There are no significant correlation between NLR, LMR, and PLR with clinical response to neoadjuvant chemotherapy. However, we did observe a significant association between NLR and 1-year mortality rate. ConclusionIn conclusion, significant association between NLR and 1-year morality rate suggest that NLR may serve as a useful prognostic factor in breast cancer patients receiving neoadjuvant chemotherapy.

Quantitative ultrasound radiomics guided adaptive neoadjuvant chemotherapy in breast cancer: early results from a randomized feasibility study.

In patients with locally advanced breast cancer (LABC) receiving neoadjuvant chemotherapy (NAC), quantitative ultrasound (QUS) radiomics can predict final responses early within 4 of 16-18 weeks of treatment. The current study was planned to study the feasibility of a QUS-radiomics model-guided adaptive chemotherapy. The phase 2 open-label randomized controlled trial included patients with LABC planned for NAC. Patients were randomly allocated in 1:1 ratio to a standard arm or experimental arm stratified by hormonal receptor status. All patients were planned for standard anthracycline and taxane-based NAC as decided by their medical oncologist. Patients underwent QUS imaging using a clinical ultrasound device before the initiation of NAC and after the 1st and 4th weeks of treatment. A support vector machine-based radiomics model developed from an earlier cohort of patients was used to predict treatment response at the 4th week of NAC. In the standard arm, patients continued to receive planned chemotherapy with the treating oncologists blinded to results. In the experimental arm, the QUS-based prediction was conveyed to the responsible oncologist, and any changes to the planned chemotherapy for predicted non-responders were made by the responsible oncologist. All patients underwent surgery following NAC, and the final response was evaluated based on histopathological examination. Between June 2018 and July 2021, 60 patients were accrued in the study arm, with 28 patients in each arm available for final analysis. In patients without a change in chemotherapy regimen (53 of 56 patients total), the QUS-radiomics model at week 4 of NAC that was used demonstrated an accuracy of 97%, respectively, in predicting the final treatment response. Seven patients were predicted to be non-responders (observational arm (n=2), experimental arm (n=5)). Three of 5 non-responders in the experimental arm had chemotherapy regimens adapted with an early initiation of taxane therapy or chemotherapy intensification, or early surgery and ended up as responders on final evaluation. The study demonstrates the feasibility of QUS-radiomics adapted guided NAC for patients with breast cancer. The ability of a QUS-based model in the early prediction of treatment response was prospectively validated in the current study. clinicaltrials.gov, ID NCT04050228.

Tumor Necrosis Factor-alpha Levels as a Predictor of Clinical Neoadjuvant Chemotherapy Response in a Luminal-type Locally Advance Breast Cancer in Surabaya, Indonesia

ABSTRACT Introduction: The prevalence of locally advanced breast cancer (LABC) increases annually, especially in the luminal type. Chemotherapy is one of the treatments used to manage breast cancer. Biomarkers are needed to predict the outcome of chemotherapy, one of which is tumor necrosis factor-alpha (TNF-α). The purpose of this study was to analyze TNF-α levels as a predictor factor for clinical response to anthracycline-based neoadjuvant chemotherapy. Methods: This study design used observational analysis. The study was carried out over the period from April 2021 to June 2023. The study procedure included measuring participants’ TNF-α levels the day before chemotherapy was carried out and their clinical response. Participants received anthracycline-based neoadjuvant chemotherapy (cyclophosphamide 500 mg/m2, doxorubicin 50 mg/m2, and fluorouracil/5 FU 500 mg/m2) for 3 cycles. The study analysis used the Chi-square with P &lt; 0.05. Results: The average TNF-α levels were 119.76 ± 282.18 pg/mL, ranging from 5.74 to 1.733 pg/mL. The result of the calculation of the TNF-α cutoff value in the study was 20.980 pg/mL (area under the curve = 0.882; 95% confidence interval = 0.779–0.984). Based on the cutoff, most participants with high TNF-α levels had a negative response of 83.3%, and those with low TNF-α levels had a positive response of 84.2% (P = 0.000). The statistical analysis showed a significant association between TNF-α levels and the clinical response to chemotherapy. Conclusions: TNF-α levels predict clinical response for anthracycline-based neoadjuvant chemotherapy in luminal-type LABC patients.

Assessment of Clinico Pathological Factors as Predictive Markers in Response to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer (LABC)

Assessment of Clinico Pathological Factors as Predictive Markers in Response to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer (LABC)

Strain ultrasonic elastography imaging features of locally advanced breast cancer: association with response to neoadjuvant chemotherapy and recurrence-free survival

BackgroundDue to the highly heterogeneity of the breast cancer, it would be desirable to obtain a non-invasive method to early predict the treatment response and survival outcome of the locally advanced breast cancer (LABC) patients undergoing neoadjuvant chemotherapy (NAC). This study aimed at investigating whether strain elastography (SE) can early predict the pathologic complete response (pCR) and recurrence-free survival (RFS) in LABC patients receiving NAC.MethodsIn this single-center retrospective study, 122 consecutive women with LABC who underwent SE examination pre-NAC and after one and two cycles of NAC enrolled in the SHPD001(NCT02199418) and SHPD002 (NCT02221999) trials between January 2014 and August 2017 were included. The SE parameters (Elasticity score, ES; Strain ratio, SR; Hardness percentage, HP, and Area ratio, AR) before and during NAC were assessed. The relative changes in SE parameters after one and two cycles of NAC were describe as ΔA1 and ΔA2, respectively. Logistic regression analysis and Cox proportional hazards model were used to identify independent variables associated with pCR and RFS.ResultsForty-nine (40.2%) of the 122 patients experienced pCR. After 2 cycles of NAC, SR2 (odds ratio [OR], 1.502; P = 0.003) and ΔSR2 (OR, 0.013; P = 0.015) were independently associated with pCR, and the area under the receiver operating characteristic curve for the combination of them to predict pCR was 0.855 (95%CI: 0.779, 0.912). Eighteen (14.8%) recurrences developed at a median follow-up of 60.7 months. A higher clinical T stage (hazard ratio [HR] = 4.165; P = 0.005.), a higher SR (HR = 1.114; P = 0.002.) and AR (HR = 1.064; P < 0.001.) values at pre-NAC SE imaging were independently associated with poorer RFS.ConclusionSE imaging features have the potential to early predict pCR and RFS in LABC patients undergoing NAC, and then may offer valuable predictive information to guide personalized treatment.

Inflammatory Breast Cancer with Diffuse Breast Erythema and Swelling as Symptoms

&lt;p&gt;臨床上，乳房紅腫常會讓人聯想為乳房發炎性疾病。本案例是一位44歲女性，因右側乳房瀰漫性紅腫約四週未改善就醫，後診斷為右側乳癌第三期，並行右側乳房根除性手術，術後三週，住院計畫做化療，發現白血球升高、右胸壁及右腋下多處復發。考量疾病進展迅速，回溯過去病史、治療過程及病理報告，最後診斷為發炎性乳癌（Inflammatory Breast Cancer, IBC），予以多模式治療後，腫瘤消除。發炎性乳癌相當罕見，沒有特定組織學，易與乳房發炎性疾病及其它局部嚴重晚期乳癌（Locally Advanced Breast Cancer, LABC）混淆。建議臨床同仁，如果乳房有發炎現象，使用抗生素兩週無效時，須將發炎性乳癌列為鑑別診斷並將其特徵謹記於心，以免延誤治療和危害病人生命。&lt;/p&gt; &lt;p&gt;&amp;nbsp;&lt;/p&gt;&lt;p&gt;In clinical practice, breast erythema is often linked to breast inflammatory diseases. The case of this study is a 44-year-old female, who went to the hospital due to diffuse erythema with swelling on the right breast for four weeks. She was initially diagnosed with stage III breast cancer and received a right-side radical mastectomy. When she was admitted for chemotherapy three weeks after the sur-gery, she was found to have leukocytosis and multiple metastasis over the right chest wall and right axillary. Therefore, cancer recurrence was suspected. Considering the rapid progression of the disease and reviewing past medical history, medical treatment procedures, and pathological report, the final diagnosis of inflammatory breast cancer (IBC) was made. After multimodal treatments, the tumors were eliminated. Given that IBC is easily confused with inflammatory diseases and other locally advanced breast cancer (LABC), if the breast is inflamed and antibiotic treatments are not effective for two weeks inflammatory breast cancer (IBC) must be included in the differential diagnosis. The healthcare provider must keep IBC&amp;rsquo;s characteristics in mind to avoid delay treatment which might en-danger the patient&amp;rsquo;s life.&lt;/p&gt; &lt;p&gt;&amp;nbsp;&lt;/p&gt;

Utilizing peripheral blood inflammatory biomarker (PBIB) to predict response to systemic therapy in patients with breast cancer.

Inflammation is a recognized factor in cancer progression and resistance to treatments. Several studies correlated inflammation-related peripheral blood inflammatory biomarkers (PBIB) to disease progression and poor survival in various cancer types and different populations. Nonetheless, inflammation is affected by the distinctive characteristics and environmental exposure of each population. There is no prior study addressing the association of pre-treatment inflammatory markers with outcomes in patients with breast cancer (BC) from Saudi Arabia. In this study, we evaluated the prognosis of locally advanced breast cancer (LABC) in relation to several PBIB. We retrospectively analyzed the data of female patients with LABC undergoing neoadjuvant chemotherapy (NACT). Demographics, body mass index (BMI), clinicopathologic characteristics and stage of the tumor, follow-up status, and response to treatment were collected. Outcomes were evaluated in relation to pre-treatment peripheral blood indices that were grouped based on the local laboratory cutoff values. Objective response rate (ORR) was predefined and assessed according to the post-NACT magnetic resonance imaging (MRI) breast and subcategorized into complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD). A total of 172 female patients with BC met the eligibility criteria from January 2014 to December 2019. The mean age at diagnosis was 53.4 ± 11, and BMI was 31.2 ± 6. Left BC accounted for 54.7%, and the majority was invasive ductal carcinoma (85.5%), moderately differentiated (51%), stage III (AJCC 8th edition) (73%), and estrogen receptor (ER)-positive tumor (79.1%). Human epidermal growth factor receptor 2 (HER2)-positive BC was reported in 32% and triple-negative breast cancer (TNBC) in 10%. Radiologic CR accounted for the majority of ORR (71.5%). Higher percentage of patients with normal red cell distribution width (RDW) of red blood cell (RBC) and low neutrophil-lymphocyte ratio (NLR) had CR with a significant P value of 0.003 and 0.014, respectively. Among several peripheral blood indices, RDW and NLR significantly influenced ORR. They can be explored further to potentially predict response after systemic therapy in patients with LABC. The great advantage of these biomarkers stems from their availability and affordability in routine clinical practice.

Effect of Neoadjuvant Concurrent Chemoradiation on Operability and Survival in Locally Advanced Inoperable Breast Cancer

PurposeInoperable locally advanced breast cancers (LABC) are treated with neoadjuvant chemotherapy (NACT). We studied the use of neoadjuvant concurrent chemoradiation (NACCRT) in patients with inoperable LABC. Patients and MethodsFrom May 2017 to Dec 2021, the study recruited patients with Stage III inoperable LABC. The treatment included 4 cycles of Adriamycin and Cyclophosphamide and 4 cycles of Paclitaxel, along with concurrent radiotherapy to a total dose of 46 Gy. Thereafter, all patients were evaluated for surgery, and additional treatments were given based on receptor status. The effects of NACCRT on the pathological complete response (pCR), operability, and survival were analyzed. ResultsThe study involved 202 female patients with a median age of 52 years. Of these, 23.7% had IIIA, 65.3% had IIIB, and 10.8% had IIIC disease. Hormone-receptor (HR) positive disease was observed in 44.6% of patients, triple-negative breast cancer (TNBC) in 24.8%, and HER2-positive disease in 30.7%. Modified radical mastectomy (MRM) was performed in 88.1% of patients, 8.5% remained inoperable, and 3.4% declined surgery. Among the patients who underwent MRM, 36.5% of patients had a pCR. Patients who were operable and underwent MRM had complete resections and had negative margins. pCR was observed in 16% with HR-positive disease, 45.6% with TNBC, and 60.7% with HER2-positive disease. Grade 3 skin reactions were observed in 19.3%. Postoperative wound morbidity requiring hospitalization was observed in 10.6% of patients.After a median follow-up of 42 months, the 4-year EFS and OS were 63.4% and 71.5%, respectively. HER2-positive patients who achieved pCR had significantly improved EFS and OS. ConclusionsOur study shows that using NACCRT can improve operability and survival outcomes in patients with inoperable LABC.

Is FAST FORWARD the Way Forward in Radiotherapy for Locally Advanced Breast Cancer – Learnings From the COVID Pandemic

IntroductionLow middle-income countries (LMICs), including India, have paucity of external beam radiotherapy (RT) machines leading to prolonged wait times for RT. Delay in delivery of RT has been shown to adversely affect outcomes in locally advanced breast cancer (LABC). With the availability of results of multiple randomized controlled trials, hypofractionated RT delivered over 3 to 4 weeks became the standard of care in breast cancer RT. MethodsWe conducted a retrospective audit of 172 LABC patients treated with ultrahypofractionated adjuvant RT (radiotherapy completed in 1 week) during the COVID pandemic. Log rank and Cox-regression model used for univariate and multi-variate analyses. ResultsNo patient developed grade 3 esophagitis. Grade 2 esophagitis requiring short term narcotic analgesics was seen in 12 (6.9%) patients. Grade 2 or higher toxicity peaked between 2 and 3 weeks after RT. The estimated 2 and 3- year recurrence free survival (RFS) for the cohort is 87.1 % and 81.4 %, respectively. The estimated 2 and 3-year overall survival for the cohort is 95% and 91.3%. On multivariate analysis, presence of extra-nodal extension was found to be an independent factor associated with worse RFS (P = .028). ConclusionsFAST FORWARD protocol RT in LABC appears well tolerated.

Revolutionizing the battle against locally advanced breast cancer: A comprehensive insight into neoadjuvant radiotherapy.

Breast cancer (BC) constitutes one of the most pervasive malignancies affecting the female population. Despite progressive improvements in diagnostic and therapeutic technologies, leading to an increased detection of early stage BCs, locally advanced breast cancer (LABC) persists as a significant clinical challenge. Owing to its poor overall survival (OS) rate, elevated recurrence rate, and high potential for distant metastasis, LABC prominently impacts the comprehensive efficacy of BC treatments. Radiotherapy, encompassing preoperative, intraoperative, and postoperative modalities, is acknowledged as an effective strategy for mitigating BC metastasis and enhancing survival rates among patients. Nevertheless, the domain of preoperative neoadjuvant radiotherapy (NART) remains conspicuously underexplored in clinical studies. Available research suggests that NART can induce tumor volume reduction, provoke fibrotic changes in tumor and adjacent normal tissues, thereby mitigating intraoperative cancer propagation and enhancing the quality of life for LABC patients. This manuscript seeks to provide a review of contemporary research pertaining to LABC and its preoperative radiotherapy.

Multimodal prediction of neoadjuvant treatment outcome by serial FDG PET and MRI in women with locally advanced breast cancer

PurposeTo investigate combined MRI and 18F-FDG PET for assessing breast tumor metabolism/perfusion mismatch and predicting pathological response and recurrence-free survival (RFS) in women treated for breast cancer.MethodsPatients undergoing neoadjuvant chemotherapy (NAC) for locally-advanced breast cancer were imaged at three timepoints (pre, mid, and post-NAC), prior to surgery. Imaging included diffusion-weighted and dynamic contrast-enhanced (DCE-) MRI and quantitative 18F-FDG PET. Tumor imaging measures included apparent diffusion coefficient, peak percent enhancement (PE), peak signal enhancement ratio (SER), functional tumor volume, and washout volume on MRI and standardized uptake value (SUVmax), glucose delivery (K1) and FDG metabolic rate (MRFDG) on PET, with percentage changes from baseline calculated at mid- and post-NAC. Associations of imaging measures with pathological response (residual cancer burden [RCB] 0/I vs. II/III) and RFS were evaluated.ResultsThirty-five patients with stage II/III invasive breast cancer were enrolled in the prospective study (median age: 43, range: 31–66 years, RCB 0/I: N = 11/35, 31%). Baseline imaging metrics were not significantly associated with pathologic response or RFS (p > 0.05). Greater mid-treatment decreases in peak PE, along with greater post-treatment decreases in several DCE-MRI and 18F-FDG PET measures were associated with RCB 0/I after NAC (p < 0.05). Additionally, greater mid- and post-treatment decreases in DCE-MRI (peak SER, washout volume) and 18F-FDG PET (K1) were predictive of prolonged RFS. Mid-treatment decreases in metabolism/perfusion ratios (MRFDG/peak PE, MRFDG/peak SER) were associated with improved RFS.ConclusionMid-treatment changes in both PET and MRI measures were predictive of RCB status and RFS following NAC. Specifically, our results indicate a complementary relationship between DCE-MRI and 18F-FDG PET metrics and potential value of metabolism/perfusion mismatch as a marker of patient outcome.

Locally advanced breast cancer: breast-conserving surgery and other factors linked to overall survival after neoadjuvant treatment.

Recent data suggest that breast-conserving surgery (BCS) may positively impact overall survival (OS) in early breast cancer. However, the role of BCS in locally advanced breast cancer (LABC) following neoadjuvant therapy (NAT) remains uncertain. We conducted a retrospective cohort study involving 530 LABC patients who underwent surgery after NAT between 2010 and 2015. Outcomes examined included OS, distant recurrence rates (DRR), and loco-regional recurrence rates (LRRs). Among the 927 breast cancer patients who received NAT, 530 were eligible for our study. Of these, 24.6% underwent BCS, while 75.4% underwent mastectomy (MS). The median follow-up duration was 79 months. BCS patients exhibited a higher pathological complete response (PCR) rate compared to those who underwent MS (22.3% vs. 10%, p < 0.001). The 6-year OS rates for BCS and MS were 81.5% and 62%, respectively (p < 0.000). In multivariate OS analysis, MS was associated with worse outcomes (OR 1.678; 95% CI 1.069-2.635; p = 0.024), as was body mass index (BMI) (OR 1.031; 95% CI 1.006-1.058; p = 0.017), and stage IIIB or IIIC (OR 2.450; 95% CI 1.561-3.846; p < 0.000). Conversely, PCR (OR 0.42; 95% CI 0.220-0.801; p = 0.008) was associated with improved survival. DRR was significantly lower in BCS (15.4%) compared to MS (36.8%) (OR 0.298; 95% CI 0.177-0.504). LRRs were comparable between BCS (9.2%) and MS (9.5%) (OR 0.693; 95% CI 0.347-1.383). Our findings suggest that BCS is oncologically safe, even for patients with large lesions, and is associated with superior OS rates compared to MS. Additionally, lower BMI, lower pretreatment stage, and achieving PCR were associated with improved survival outcomes.

Check update pattern of tumorigenic vasculature signature based on MMP9 and CXCR4 expression in locally advanced breast cancer

Context: Locally advanced breast cancers (LABC) are the most common women malignant tumors. Appropriate vasculature is required for tumor growth support, formed by involving protein signaling, including matrix metalloprotein 9 (MMP9) and C-X-C chemokine receptor type 4 (CXCR4). Neoadjuvant chemotherapy (NAC) administration to inoperable LABC commonly exhibits a positive response, although recurrences may be encountered in a few cases. Aims: To evaluate the MMP9 and CXCR4 expression shifting after the NAC procedure to establish evidence of the anti-angiogenic effect of NAC, which encourages knowledge of tumor size reduction pathways in LABC. Methods: Observational designs were conducted in this study. Tissue specimens before and after NAC were collected from 45 LABC-enrolled subjects. The targeted protein expression was analyzed by immunohistochemistry, and stained sections were classified according to the percentage of nuclear-stained tumor cells. Clinicopathological features of LABC were recorded. Tumor size was measured by Vernier caliper before and after NAC. Results: The results showed the nuclear expression of MMP9 and CXCR4 protein were observed in all tissue specimens. The expression of MMP9 and CXCR4 tended to decrease after the NAC but was not statistically significant for MMP9. There was a significant correlation between expression levels of CXCR4 and tumor size reduction (p&lt;0.001) but not for MMP9. Conclusions: The results of this study demonstrate the anti-angiogenic effect of NAC by inhibiting MMP9 and CXCR4, which may be integrated with tumor size reduction in LABC. Further studies are required to highlight the possibility of recurrence following inhibition of MMP9 and CXCR4 by NAC.

The relationship between the difference neutrophil to lymphocyte ratio before and after anthracycline-based neoadjuvant chemotherapy with clinical response in locally advanced breast cancer

Link of Video Abstract: https://youtu.be/Jb1SATaI8oQ Introduction: The difference in the Neutrophil-to-Lymphocyte Ratio (NLR) before and after chemotherapy, which is commonly called the delta NLR, is thought to be a better predictive factor than pre-chemotherapy NLR or post-chemotherapy NLR in breast cancer patients. Methods: We analyzed 130 locally advanced breast cancer (LABC) patients who received anthracycline-based neoadjuvant chemotherapy (NACT) at Dr. Soetomo General Hospital Surabaya from January 2017 – December 2021. Results: Out of 130 patients, 91 (70.0%) responded to chemotherapy. Bivariate analysis showed a significant relationship between delta NLR and chemotherapy response (p = 0.002). Patients with delta NLR &lt; 0 achieved a significantly higher rate of clinical response to NACT compared to those with delta NLR ≥ 0 (OR: 4.67, 95% CI: 1.69 – 12.85, p: 0.003) Conclusion: LABC patients with delta NLR &lt; 0 have better clinical response to anthracycline-based NACT than those with delta NLR ≥ 0.

357P Prediction of pathologic response to neoadjuvant chemotherapy (NAC) using diffuse optical breast scanner (DOB-Scan) in patients with locally advanced breast cancer (LABC)

357P Prediction of pathologic response to neoadjuvant chemotherapy (NAC) using diffuse optical breast scanner (DOB-Scan) in patients with locally advanced breast cancer (LABC)

Role of 99mTc-sestamibi Scintimammography in Predicting Response to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer: A Prospective Study.

Neoadjuvant chemotherapy (NACT) is the first line of management for locally advanced breast cancer (LABC). However, chemoresistance is prevalent in 18%-50% of the cases. One of the important and most studied causes of chemoresistance is P-glycoprotein (Pgp) expression. 99mTc-sestamibi scintimammography may serve as a useful imaging tool to predict Pgp expression, thereby response to NACT. The aim was to study the role of 99mTc-sestamibi scintimammography in predicting response to NACT in treatment-naive, biopsy-proven LABC patients. 99mTc-sestamibi scintimammography (early and delayed images) was performed on a total of 34 patients. Eight patients were lost to follow-up, and only 26 (25 females and 1 male) patients were available for final analysis, with a mean age of 49.7 ± 10.7 years. 99mTc-sestamibi washout rate (WOR) (%) and T/B buildup were calculated. Pre-NACT and Post-NACT tumor sizes were measured clinically, and a % decrease in tumor size was calculated. The WOR and T/B buildup values were correlated with the % decrease in tumor size. We found a statistically significant negative correlation between WOR (%) and % decrease in tumor size and a statistically significant positive correlation between T/B buildup and % decrease in tumor size. Furthermore, we found a positive correlation between the early T/B ratio and the Ki-67 index (P = 0.22). Early categorization of responders and nonresponders can help in optimal therapy planning. 99mTc-sestamibi scintimammography can serve as an imaging marker for Pgp expression, thereby predicting clinical response to NACT in LABC patients. Further studies with larger sample sizes are warranted to consolidate the above findings.

367P Sentinel lymph node biopsy (SLNB) in patients with locally advanced breast cancer (LABC): Descriptive, inferential and survival analysis

367P Sentinel lymph node biopsy (SLNB) in patients with locally advanced breast cancer (LABC): Descriptive, inferential and survival analysis

Is Ki-67 Really Useful as a Predictor for Response to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer?

Neoadjuvant chemotherapy (NACT) is routinely offered to operable locally advanced breast cancer (LABC) patients desirous of breast conservation surgery and inoperable LABC patients. Pathological complete response (pCR) following chemotherapy is recognized as a surrogate for survival outcomes in high grade tumour subtypes. Many biological and tumor characters have been shown to predict pCR. The current study was performed with the aim of investigating the ability of Ki-67 in predicting pCR with NACT in breast cancer patients. A total of 105 patients with locally advanced breast cancer who completed NACT followed by surgery were included in this study from January 2020 till December 2022. Patients with advanced metastatic breast carcinoma, who did not give consent for NACT, who did not complete NACT and who did not undergo surgery were excluded. All patients were assessed for Ki-67 score on core-needle biopsy samples and response rate was assessed clinically and by histopathological examination of resected specimen. Quantitative variables were compared using unpaired t-test or Mann-Whitney 'U' test and for categorical variables Chi-square or Fisher's exact test were used. Receiver operating characteristic (ROC) curve analysis was performed to assess the predictive potential of Ki-67 expression levels in predicting pCR. To identify the predictive factors associated with pCR, univariate analysis was performed. The P value < 0.05 was considered as statistically significant. Mean age was 51.57 ± 10.8years. 51 patients achieved clinical complete response (cCR) and 33 achieved pCR after NACT. Mean Ki-67 index in overall study population, in pCR group and no pCR group was 46.44 ± 22.92%, 51.60 ± 22.3% and 44.06 ± 22.7%, respectively. On univariate analysis, ER negativity, PR negativity and Her 2neu positivity were found predictive of pCR. On subgroup analysis, TNBC and Her 2neu positive sub groups were associated with higher cCR and pCR rate. We found no significant association between Ki-67 and pCR. This result may be confounded by the fact that a significant duration of the study was in the COVID-19 pandemic. Validation of this data is required in a large prospective study.

Impact of Neoadjuvant Concurrent Chemoradiation (NACCRT) on Operability and Survival in Locally Advanced Inoperable Breast Cancer

Inoperable locally advanced breast cancers (LABC) are treated with neoadjuvant chemotherapy (NACT). However, many patients remain inoperable after NACT due to an inadequate response. We, therefore, investigated the role of neoadjuvant concurrent chemoradiation (NACCRT) in this setting. Patients with inoperable Stage III LABC were prospectively recruited in the study between May 2017 and December 2021. NACT consisted of 4 cycles of q3weekly Adriamycin (60 mg/m2) and Cyclophosphamide (600mg/m2), and 4 cycles of q3weekly Paclitaxel (175 mg/m2). Concurrent radiotherapy with 6 MV X-rays was given using a 3D conformal technique to a total dose of 46 Gy (2 Gy/fraction, 5 days/week) to the involved breast, axilla, supraclavicular fossa, and internal mammary chain (upper 3 intercostal spaces) along with the first two cycles of paclitaxel. A 0.5 cm bolus was used to boost the skin till the appearance of hyperpigmentation. All patients were assessed for surgery after the completion of the planned neoadjuvant treatment. Adjuvant treatments were given based on the receptor status. The impact of neoadjuvant CTRT on the pathological complete response (pCR), operability, and survival was analyzed. Event-free survival (EFS) and Overall Survival (OS) were analyzed using the Kaplan-Meier method. The study enrolled 202 female patients with a median age of 52 years, with 23.7% having IIIA, 65.3% IIIB, and 10.8% having IIIC disease. Hormone-receptor (HR) positive disease was observed in 90/202 (44.6%) patients, triple-negative (TNBC) in 50/202 (24.8%) and Her2/neu positive in 62/202 (30.7%) patients. Modified radical mastectomy was performed in 88.1% of patients, with 8.5% remaining inoperable and 3.4% declining surgery due to clinical complete response (cCR). Among the patients who underwent MRM, 65/178 (32.2%) patients had a pCR. pCR was observed in 13/81 (16%) with HR-positive disease, 21/46 (45.6%) with TNBC, and 31/51 (60.7%) patients with Her2/neu-positive disease. Grade 3 skin reactions were observed in 39/202 (19.3%). Postoperative wound morbidity requiring hospitalization was observed in 19/178 (10.6%) patients. The median follow-up was 42 months, with 4-year EFS and OS of 63.8% and 71.5%, respectively. Six out of 7 patients who were in cCR and declined surgery are alive and remain in cCR. On subgroup analysis of Her 2 positive patients, pCR was significantly associated with improved EFS and OS (89.8% vs 33.3%, p = 0.001 and 89.1% vs 44.4%, p = 0.001 respectively). Our study demonstrates the feasibility and efficacy of NACCRT in improving operability, pCR rates and survival outcomes in patients with inoperable LABC. The results suggest that NACCRT can be considered for use in clinical practice with careful patient selection. These findings contribute to the ongoing efforts to optimize treatment for this patient population and warrant further investigation in larger, randomized trials.