Locally Advanced Breast Cancer Research Articles

Hematologic Predictors of Chemotherapy-Induced Neutropenia in Breast Cancer Patients Receiving Anthracycline- or Taxane-Based Chemotherapy

Background: Chemotherapy-induced neutropenia (CIN) is a common and serious complication of chemotherapy in breast cancer patients, leading to increased morbidity, mortality, and treatment disruptions. This study aimed to investigate the association between hematologic profiles and the occurrence of CIN in breast cancer patients receiving anthracycline-based or taxane-based chemotherapy. Methods: A retrospective observational analytic study with a cross-sectional design was conducted using medical records of breast cancer patients treated at the Oncology Surgery Clinic between 2022 and 2023. Sixty patients were included in the study. Hematologic profiles, including hemoglobin and leukocyte counts, were analyzed to assess their association with CIN in both anthracycline- and taxane-based chemotherapy groups. Results: The majority of patients were aged 15-64 years (86.67%), normoweight (65%), had luminal B subtype (63.3%), and were in the locally advanced breast cancer (LABC) stage (45%). Most patients were non-anemic (Hb ≥12 mg/dL) and leukopenic (71.7% and 80%, respectively). No significant association was found between age, nutritional status, or breast cancer stage and CIN (p > 0.05). However, hemoglobin and leukocyte profiles were significantly associated with CIN in both chemotherapy groups (p < 0.05). No association was found between the type of chemotherapy (anthracycline- or taxane-based) and CIN occurrence. Conclusion: Anemia (Hb <12 g/dL) and leukopenia are significant predictors of CIN in breast cancer patients, regardless of the chemotherapy regimen. These findings highlight the importance of monitoring hematologic profiles in these patients to identify those at higher risk of CIN and implement appropriate preventive and management strategies.

Long-term Survival Outcomes in Locally Advanced Breast Cancer after Mastectomy with or without Breast Reconstruction.

There is ongoing debate about the safety of breast reconstruction for patients with locally advanced breast cancer (LABC) who have undergone total mastectomy (TM). More and more LABC patients are undergoing breast reconstruction after TM, but its long-term survival outcomes remain unclear. This study aims to compare the survival outcomes of LABC patients who underwent breast reconstruction after TM with those who did not, based on a large sample. We collected data for all LABC patients who underwent TM with or without breast reconstruction in the Surveillance, Epidemiology, and End Results (SEER) database. We divided patients into two groups: TM group and total mastectomy with reconstruction (TM+R) group. The primary outcomes were overall survival (OS) and breast cancer-specific survival (BCSS). Propensity score matching (PSM) analysis was used to eliminate imbalances of baseline data between the in tow groups. Data were analyzed using chi-square tests, Kaplan-Meier methods, and univariate and multivariate cox regression analyses. We identified 39,112 eligible patients (33,169 patients received TM and 5,943 received TM+R), and 8,680 patients were matched after PSM (4,340 patients received TM and 4,340 received TM+R). Patients with middle age, white, married, lived in urban, IIB-IIIA stage, invasive ductal carcinoma (IDC), pathological grade II-III, hormone receptor positive, and undergone chemotherapy were more likely to receive breast reconstruction. After PSM, Kaplan-Meier survival analysis showed better OS and BCSS in the TM+R group versus the TM group (OS:P<0.001; BCSS: P=0.008). Multivariate cox regression analysis showed that TM+R significantly improved OS and BCSS (OS: hazard ratio (HR) 0.73, 95% CI [0.68,0.79], P<0.001; BCSS: 95% CI [0.79,0.94], P=0.001). Subgroup analysis showed that patients with old age, white, and hormone receptor positive had better OS and BCSS by TM+R compared to TM. Breast reconstruction after total mastectomy is associated with better OS and BCSS in patients with LABC.

The Impact of Neoadjuvant versus Adjuvant Chemotherapy on Survival Outcomes in Locally Advanced Breast Cancer.

The utility of neoadjuvant chemotherapy is expanding in the treatment of breast cancer. Although individual trials have shown comparable survival between patients receiving neoadjuvant and adjuvant chemotherapy, large-scale data analyses for outcomes in patients with locally advanced breast cancer (LABC) are lacking. We conducted an individual-level statistical analysis using patients from six randomized controlled trials (RCTs) investigating survival outcomes with neoadjuvant versus adjuvant chemotherapy in breast cancer by abstracting and analyzing only the patients with LABC. Individual patient data for 779 patients with LABC were collected from six RCTs. Overall and disease-free survival rates were compared between patients receiving neoadjuvant vs. adjuvant chemotherapy with the Cox hazard model and log-rank statistics. Since chemotoxicity causing delays to surgical care is a potential drawback of neoadjuvant chemotherapy, local cohort data were then employed to assess the actual incidence of this, along with the causes behind any delays to surgery in patients receiving neoadjuvant chemotherapy. A time interval from neoadjuvant chemotherapy to surgery of >8 weeks was investigated in a local cohort of 563 patients, representing all locally treated patients receiving neoadjuvant chemotherapy between 2006 and 2019. The statistical analysis demonstrated no overall or disease-free survival differences in LABC patients receiving neoadjuvant vs. adjuvant chemotherapy (p = 0.96 and 0.74, respectively). Within our cohort, 31 (5.5%) patients treated with neoadjuvant chemotherapy experienced a delay of >8 weeks to surgery, with only 13 (2.3%) attributed to chemotherapy-related complications. Our study provides further support for the paradigm shift towards delivering chemotherapy for breast cancer patients in the neoadjuvant setting.

ThP1.10 - Expression Pattern of Arginase In Tumour Tissue In Male Breast Cancer

Abstract Aim To study the expression pattern of arginase in tumor tissue of male breast cancer (MBC) by immunohistochemistry (IHC). Methods We retrospectively analysed the data of 21 MBC patients who were treated in our centre from January 2018 to March 2022. Immunohistochemical analysis of arginase expression was performed in tumor and lymph node tissue with primary arginase-1 antibody (1:300 dilution). Results The mean patient age was 57 years (33–81 years). 10 patients (48%) had metastatic disease at presentation, while early breast cancer (EBC) and locally advanced breast cancer (LABC) constituted 19% and 33%, respectively. Invasive ductal carcinoma was the predominant histology, with luminal being the major subtype. Modified radical mastectomy was done in 9 patients (43%), and palliative chemotherapy was given to all metastatic patients. IHC analysis revealed a lack of arginase expression in the tumor tissue even though it was expressed in the surrounding neutrophils. Conclusion Contrary to the majority of existing literature, ours was an IHC-based study, which provides a more accurate estimation of arginase expression at the cellular level. The lack of arginase expression obtained in our study may point towards the non-expression of the enzyme in MBC. This suggests that arginase is not a tissue biomarker in MBC. Taking other studies with protein expression into account, arginase should be treated, if necessary, only as a blood biomarker.

Medially Based “Abdominal Rotation Advancement Flap”: A Promising Technique for Mastectomy Defect Reconstruction in “High-Risk Patients” Awaiting Adjuvant Radiotherapy

Abstract Background Extensive postmastectomy defects and soft-tissue defects often require some additional flap cover of reconstruction after excision. The reconstruction aim in this group should be a diligent and easy closure with a quality skin cover, early recovery, and brief stay in hospital so that the patients can receive early postoperative radiotherapy/chemotherapy. Medially based abdominal transposition flap is a type C fasciocutaneous flap based on medial perforating vessels. We present our experience in significant postmastectomy defects, especially in high-risk morbid patients. Materials and Methods This is a retrospective study conducted by the department of plastic surgery, from an analysis of the breast cancer database maintained by our hospital from 2019 to 2023. A total of 826 breast cancer patients underwent surgery, of which 547 were locally advanced breast cancer (LABC) patients and 138 (32.5%) LABC patients needed flap cover for mastectomy defect. Medially based abdominal transposition flap was used in 56 of 138 (40.5%) LABC patients for defect closure, and 42 of the 56 patients were stage IIIB patients. Upfront surgery was primarily done in 20 patients and 36 patients underwent surgery after neoadjuvant chemotherapy. This analysis aimed to assess the operative duration, postoperative morbidity, hospital stay, and time taken to start adjuvant treatment by analyzing the medical records of patients who underwent this procedure. Results Fifty-six patients with breast cancer underwent surgical intervention, whereby 8 patients presented with tip and edge necrosis, and 3 patients were infected. The mean duration of operation was 58.852 minutes, and the average length of hospital stay was 5.39 days. It took 24.57 days for the patients to stabilize sufficiently for adjuvant therapy. The average age of the patients in the study was 48.73 years. Conclusion Our clinical experience has demonstrated that the medial abdominal transposition fasciocutaneous (MATF) flap represents a straightforward, reliable, and cost-effective method for managing extensive postmastectomy soft-tissue defects in a subset of patients with LABC. This group typically consists of high-risk and comorbid patients. The procedure holds considerable promise for developing countries with limited infrastructure and expertise, owing to its ease of execution and short learning curve. By its simplicity and affordability, the MATF flap offers a viable and sustainable solution for treating LABC-associated soft-tissue defects.

In Vivo Detection of Multidrug-Resistance Related Proteins in Locally Advanced Breast Cancer Using 99mTc-MIBI SPECT/CT Imaging: Correlation with Clinical Outcomes.

Neoadjuvant chemotherapy (NACT) is widely used for treating locally advanced Breast cancer (LABC). However, development of multidrug resistance (MDR) is the main underlying factor for chemoresistance. Technetium-99m methoxyisobutylisonitrile (99mTc-MIBI) is a substrate for MDR. This study aimed to analyze the relationship between expression of MDR-related proteins (P-gp and Bcl-2) and 99mTc-MIBI uptake and retention in BC tumor cells, pathologic response to NACT, disease free survival (DFS) and overall survival (OS). prospective analysis recruited 31 patients with LABC who received NACT between January 2019 and March 2020. 99mTc-MIBI planar and SPECT/CT imaging was conducted before and after NACT. Qualitative and quantitative analyses were performed, pre and post-NACT early and delayed lesion to non-lesion (LNL) ratios, and retention index (RI) of 99mTc-MIBI were calculated. Expression of P-gp and Bcl-2 in tumor cells was determined by immunohistochemistry. Quantitively, inter-reader ICC for SPECT/CT based quantification was consistently higher than that of planar images. Post-NACT LNL ratios were significantly higher in patients with pathologic persistent disease (PPD). A change in RI between pre- and post-NACT scans demonstrated a significant association with DFS with a hazard ratio of 0.7 (95%CI: 06-1.0). Qualitatively, SPECT/CT was significantly more accurate compared to planar imaging in identifying residual viable tumor (81% compared to 57%). Her2neu positivity and high post-operative Bcl-2 and P-gp were associated with worse DFS. A significant association was found between increased expression of post-NACT Bcl-2 and PPD, advanced tumor stage and poor OS. 99mTc-MIBI SPECT/CT based qualitative evaluation of BC response to NACT is more accurate than planar imaging. Post-NACT MIBI retention is positively correlated with P-gp and Bcl-2 expression. 99mTc-MIBI SPECT/CT may predict MDR development. High post-NACT Bcl-2 expression is significantly associated with advanced tumor stage and OS. High post-NACT P-gp expression has a worse impact on pathologic response and DFS.

Optimizing treatment sequence for inoperable locally advanced breast cancer: Long-term outcomes of surgery first versus neoadjuvant chemotherapy in a real-world setting.

Locally advanced breast cancer (LABC) is challenging with limited treatment options. This study investigates the feasibility and long-term outcomes of upfront surgery compared to neoadjuvant chemotherapy (NAC) in a real-world cohort. This retrospective study analyzed 243 inoperable LABC patients (excluding T3N1M0) that underwent upfront surgery (n = 187) or NAC (n = 56) in matched groups. Disease-free survival (DFS) and overall survival (OS) are primary outcomes. Secondary outcomes included NAC response rate and subgroup analyses based on age, tumor stage, and treatment response. Survival was estimated using Kaplan-Meier methods with log-rank tests for comparisons. Cox proportional hazards models were used for subgroup analyses. With a median follow-up of 60.9 months, no significant difference emerged in 5-year OS (upfront surgery: 89.6%, NAC: 81.9%, p = .12) or 5-year DFS rates (73.0% vs. 67.1%, p = .24). Subgroup analyses revealed upfront surgery offered significantly better OS for patients under 60 (HR = 0.32; 95% CI: 0.10-0.96; p = .0429) and stage IIIA disease (HR = 0.22; CI: 0.06-0.86; p = .03). Upfront surgery showed a trend towards improved OS for tumors under 5 cm (HR = 0.37; 95% CI: 0.13-1.03; p = .056). Patients with progressive disease (PD) or stable disease (SD) after NAC had significantly worse DFS (HR = 0.27; 95% CI: 0.09-0.79; p = .017) and OS (HR = 0.09; 95% CI: 0.02-0.48; p = .004) compared to responders. Upfront surgery may be viable for LABC patients, particularly younger patients, those with stage IIIA disease, or smaller tumors. NAC response can inform treatment decisions. These findings highlight the need for personalized LABC treatment considering patient characteristics and NAC response.

Effect of neoadjuvant chemotherapy on the expression of hormone receptors and Ki-67 in patients with locally advanced breast cancer

Background: Neoadjuvant chemotherapy (NACT) affects the tumor protein marker’s expression and status. Changes in the expression of biomarkers during NACT may influence the clinical decision of adjuvant molecular and hormonal therapy. Hence, re-evaluation of receptor status has to be done after NACT to give a specific adjuvant therapy for patient benefit. Aims and Objectives: The aim of this study was to study the status of hormone receptors (HRs) – estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor (Her-2/Neu), and Ki-67 in patients with locally advanced breast cancer (LABC) in both core needle biopsies and post-mastectomy specimens after administering neoadjuvant chemotherapy. Materials and Methods: The present study was conducted in the Department of Pathology in collaboration with the Department of Surgery, Pt B D Sharma PGIMS, Rohtak, for a period of 1 year. The study comprised 52 patients with LABC who received neoadjuvant chemotherapy and 20 control cases who did not receive neoadjuvant chemotherapy. Each case comprised two specimens: Trucut biopsy and a mastectomy specimen. Results: ER changed from positive to negative in 15.4% of the cases and from negative to positive in 1.9% of the cases. The overall change in ER was statistically significant (P=0.020). For PR, 9.6% of the cases changed from positive to negative while none of the cases showed change from negative to positive. The overall change in PR was statistically significant (P=0.025). For HER2/Neu, 19.2% of the cases changed from positive to negative, and 11.5% of the cases changed from negative to positive. The overall change in HER2/Neu was not statistically significant (P=0.317). For Ki-67, 30% of patients changed from positive to negative while 11.5% of patients changed from negative to positive. The overall change in Ki-67 was statistically significant (P=0.024). Conclusion: There was discordance in the HR status and proliferation marker after NACT in patients with breast cancer. The administration of NACT might be the main reason for the change in receptor status thus understanding the chemotherapy-induced biological conversion in the tumor cell behavior is strategically important in planning adjuvant endocrine therapy and for disease follow-up.

A prospective single arm cohort study: An analysis of the effectiveness of surgical treatment of locally advanced breast cancer

BackgroundBreast cancer stands as a globally significant contributor to both incidence rates and mortality among women. Approximately 10–15 % of women will face a diagnosis of an advanced yet potentially treatable stage of the disease. When individuals diagnosed with locally advanced breast cancer (LABC) exhibit resistance to preoperative chemotherapy and experience tumor progression, they unfortunately forfeit the opportunity for surgical intervention, thereby diminishing the prospects for a radical cure. MethodWe conducted a prospective, single-arm cohort study aimed at evaluating the feasibility of locally modified radical resection for LABC with skin invasion. The primary endpoints encompassed overall survival (OS) and disease-free survival (DFS), whereas the secondary endpoint focused on the quality of life (QoL) among breast cancer patients. ResultsBetween March 2018 and December 2022, a total of 38 eligible patients were enrolled in this study. The Kaplan-Meier estimates for 1-year, 3-year, and 5-year DFS among all patients were 69.8 %, 53.3 %, and 37.5 %, respectively. Correspondingly, the OS rates were 100.0 %, 85.6 %, and 68.0 %. Both univariate and multivariate analyses revealed that patients with a history of neoadjuvant chemotherapy who exhibited stable or progressive disease had inferior DFS outcomes. Notably, patients demonstrated clinically meaningful and statistically significant enhancements in functional status and overall QoL. However, no notable improvement was observed in specific symptom domains. ConclusionPatients with locally advanced breast cancer, specifically those presenting with T4 tumors, who undergo surgical intervention followed by postoperative adjuvant therapy, can attain favorable prognostic outcomes and experience an enhanced quality of life.

Effect of Interval Between Neoadjuvant Chemotherapy and Surgery on Oncological Outcomes in Poor Responders With Locally Advanced Breast Cancer.

The interval between neoadjuvant chemotherapy (NAC) and surgery for locally advanced breast cancer (LABC) remains controversial. At the same time, the prognostic effect of delayed surgery in patients with poor responses is currently unclear. Data was collected from patients who had poor responses to NAC and underwent modified radical surgery from January 2013 to December 2018. The interval from completion of NAC to surgery was divided into two groups: a longer (greater than four weeks) or shorter (four weeks or less) interval. The associations of these interval groups with overall survival (OS) and recurrence-free survival (RFS) were evaluated by multivariable Cox models adjusting for the existing prognostic factors. Propensity score matching (PSM) was used to minimize election bias. A total of 1,229 patients (mean age, 47.2 ± 8.9 years; median follow-up duration, 32.67 [6.57-52.63] months) were included. The 5-year OS rates were 73.2% and 60.8% in the shorter (n = 171) and longer interval group (n = 1,058), respectively, while the 3-year RFS rates were 80.8% and 71.7%, respectively. In multivariate Cox analysis, the longer interval was associated with an increased risk of mortality (hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.01-2.02; p = 0.046) and recurrence (HR, 1.50; 95% CI, 1.12-1.99; p = 0.006). There was an interaction between the molecular subtype and the surgery interval for OS (pinteraction = 0.014) and RFS (pinteraction = 0.027). After PSM, no significant difference in OS (p = 0.180) and RFS (p = 0.069) was observed between the two groups. Among LABC patients with a poor response, those with a longer interval between NAC and surgery had worse OS and RFS. The results indicate that these patients should receive modified radical surgery timely, which may in turn improve their prognosis.

Neoadjuvant inetetamab and pertuzumab with taxanes and carboplatin (TCbIP) In locally advanced HER2-positive breast cancer: a prospective cohort study with propensity-matched analysis

BackgroundInetetamab is the first domestically developed innovative anti-HER2 monoclonal antibody in China, proven effective and safe in HER2-positive advanced breast cancer. However, its efficacy and safety in neoadjuvant treatment of HER2-positive locally advanced breast cancer (LABC) remain to be validated.MethodsThis prospective cohort study aimed to evaluate the efficacy and safety of inetetamab combined with pertuzumab, taxanes, and carboplatin (TCbIP) in neoadjuvant therapy for HER2-positive LABC, comparing it to data from patients treated with the TCbHP regimen (trastuzumab combined with pertuzumab, taxanes, and carboplatin) using propensity score matching (PSM). The primary endpoint was total pathological complete response (tpCR). Adverse events (AEs), objective response rate (ORR), and near-pCR were key secondary endpoints.ResultsForty-four patients with clinical stage IIA-IIIC HER2-positive LABC were prospectively enrolled and treated with the TCbIP regimen. The tpCR rate among 28 patients who completed surgery was 60.7%, comparable to and slightly higher than the TCbHP group in PSM (60.7% vs. 53.6%, P = 0.510). The ORR was 96.4%, and the DCR reached 100.0%. The most common ≥ grade 3 AE was neutropenia (21.4% vs. 11.9%, P = 0.350). No significant reduction in left ventricular ejection fraction was observed, and no patient withdrew from treatment due to AEs.ConclusionNeoadjuvant therapy with TCbIP showed good efficacy and safety in patients with HER2-positive LABC and might be another promising option for neoadjuvant treatment.Trial registrationNCT05749016 (registration date: Nov 01, 2021).

Prognostic significance of the neutrophil to lymphocyte ratio in locally advanced breast cancer.

The present study aimed to clarify the prognostic role of the pre-treatment neutrophil-to-lymphocyte ratio (NLR) for the response to neoadjuvant chemotherapy (NAC) in locally advanced breast cancer (LABC). Due to conflicting results in currently available data, the specific focus of the present study was on evaluating the associations between the pre-treatment NLR and the rate of achieving a pathological complete response (pCR) and survival outcomes. For the present study, data from a cohort of 465 consecutive patients with LABC who underwent NAC at King Feisal Specialist Hospital and Research Center (Riyadh, Saudi Arabia) between 2005 and 2014 were obtained from a prospective BC database and analyzed. Patients were stratified into two groups based on an optimal NLR cut-off determined using the receiver operating characteristic curve. Logistic regression analyses were conducted to assess variables associated with pCR, and Cox regression analyses were used to assess variables associated with survival outcomes. The low pre-treatment NLR group (≤2.2) was found to exhibit a higher likelihood of achieving a pCR (odds ratio, 2.59; 95% CI, 1.52-4.38; P<0.001), along with higher 5-year disease-free survival (DFS) [75.8 vs. 64.9%; hazard ratio (HR), 0.69; 95% CI, 0.50-0.94; P=0.02] and 5-year overall survival (OS; 90.3 vs. 81.9; HR, 0.62; 95% CI, 0.39-0.98; P=0.04) rates compared with those in the high NLR group (>2.2). Sub-group analysis revealed that the observed significance in survival outcomes was driven by the triple-negative BC (TNBC) subgroup. Patients with residual TNBC disease and a high pre-treatment NLR were observed to have lower 5-year DFS (44.4 vs. 75.0%; P=0.02) and 5-year OS (55.9 vs. 84.5%; P=0.055) rates compared with those with residual TNBC disease and a low NLR. To conclude, data from the present study suggest that the pre-treatment NLR can serve as a viable independent prognostic factor for pCR following NAC in patients with LABC and for survival outcomes, particularly for patients with TNBC.

A Single-Arm Phase II Clinical Trial of Fulvestrant Combined with Neoadjuvant Chemotherapy of ER+/HER2- Locally Advanced Breast Cancer: Integrated Analysis of 18F-FES PET-CT and Metabolites with Treatment Response.

This Phase II trial was objected to evaluate the efficacy and safety of adding fulvestrant to NCT in patients with ER+/HER2- locally advanced breast cancer (LABC). Additionally, the study aimed to investigate the association of 18F-FES PET-CT and metabolites with efficacy. Fulvestrant and EC-T regimen were given to ER+/HER2- LABC patients before surgery. At baseline, patients received 18F-FES PET-CT scan, and plasma samples were taken for LC-MS analysis. The primary endpoint was ORR. Secondary endpoints included tpCR and safety. Among the 36 patients enrolled, the ORR was 86.1%, the tpCR rate was 8.3%. The incidence of grade ≥3 TEAEs was 22%. The decrease in ER value in sensitive patients was larger than that in non-sensitive patients, as was Ki-67 (p<0.05). The SUVmax, SUVmean, TL-ER of 18F-FES PET-CT in sensitive patients were significantly higher than those in non-sensitive patients (p<0.05). Moreover, these parameters were significantly correlated with MP grade and the change in ER expression before and after treatment (p<0.05). Thirteen differential expressed metabolites were identified, which were markedly enriched in 19 metabolic pathways. This regimen demonstrated acceptable toxicity and encouraging antitumor efficacy. 18F-FES PET-CT might serve as a tool to predict the effectiveness of this therapy. Altered metabolites or metabolic pathways might be associated with treatment response.

ER-Targeted PET for Initial Staging and Suspected Recurrence in ER-Positive Breast Cancer

There are insufficient data comparing 16α-18F-fluoro-17β-estradiol (FES) positron emission tomography (PET) computed tomography (CT) with standard-of-care imaging (SOC) for staging locally advanced breast cancer (LABC) or evaluating suspected recurrence. To determine the detection rate of FES PET/CT and SOC for distant metastases in patients with estrogen receptor (ER)-positive LABC and recurrences in patients with ER-positive BC and suspected recurrence. This diagnostic study was conducted as a single-center phase 2 trial, from January 2021 to September 2023. The study design provided 80% power to find a 20% detection rate difference. Participants included patients with ER-positive LABC (cohort 1) or suspected recurrence (cohort 2). Data were analyzed from September 2023 to February 2024. Participants underwent both SOC imaging and experimental FES PET/CT. When there were suspicious lesions on imaging, 1 was biopsied for histopathological reference standard to confirm presence (true positive) or absence (false positive) of malignant neoplasm. The outcome of interest was the detection rate of FES PET CT vs SOC for distant metastases and recurrences. A total of 124 patients were accrued, with 62 in cohort 1 (median [IQR] age, 52 [32-84] years) and 62 in cohort 2 (median [IQR] age, 66 [30-93] years). In cohort 1, of 14 true-positive findings, SOC imaging detected 12 and FES detected 11 (P > .99). In cohort 2, of 23 true-positive findings, SOC detected 16 and FES detected 18 (P = .77). In 30 patients with lobular histology, of 11 true-positive findings, SOC detected 5 and FES detected 9 (P = .29). There were 6 false-positive findings on SOC and 1 false-positive finding on FES PET/CT (P = .13). In this diagnostic study with pathological findings as the reference standard, no difference was found between FES PET/CT and current SOC imaging for detecting distant metastases in patients with ER-positive LABC or recurrences in patients with ER-positive tumors and suspected recurrence. FES PET/CT could be considered for both clinical indications, which are not part of current Appropriate Use Criteria for FES PET. The findings regarding FES PET/CT in patients with lobular tumors, and for lower false positives than current SOC imaging, warrant further investigation.

Clinicopathological Profiles of and Patterns of Recurrence in Triple-Negative Breast Cancer Patients at a Cancer Care Center in Southern India.

Triple-negative breast cancer (TNBC) is characterized by the absence of expression of the estrogen receptor and the progesterone receptor by immunohistochemistry and human epidermal growth factor receptor overexpression absence either by immunohistochemistry or absence of amplification by fluorescence in-situ hybridization. TNBCs tend to have rapid growth when compared to other subtypes of breast cancer. TNBC is associated with higher histologic grade and more advanced disease at presentation. TNBC shows aggressive behavior and a high chance of recurrence. The aim was to analyze the clinicopathological profiles of and recurrence patterns in TNBC patients at our institute where most patients are from rural areas. This retrospective study was done at a tertiary cancer care center in Southern India where most patients come from rural backgrounds. Institutional Ethics Committee approval was obtained before the study. Case files of all breast cancer patients registered and treated at our center from 2014 to 2019 were retrieved from the medical record department and reviewed. Data from patients diagnosed with triple-negative breast cancer were identified and analyzed. Among the 841 breast cancer patients registered in our study, 150 (17.8%) were diagnosed with TNBC. The median age of diagnosis was 47 years. The majority of the patients, 89 (59.3%) presented with T2 tumors, and lymph node involvement was observed in 88 (58.6%) cases. Patient distribution based on cancer stage revealed that 77 (51.3%) had early-stage breast cancer (EBC), 70 (46.6%) had locally advanced breast cancer (LABC), and only three patients were categorized as having metastatic breast cancer (MBC). Modified radical mastectomy (MRM) was the preferred surgical approach in 144 (96%) cases, while only four patients underwent breast-conserving surgery (BCS). Adjuvant chemotherapy was administered to 119 (79.3%) patients, with 30 (20%) receiving both neoadjuvant and adjuvant chemotherapy (NACT/ACT). Among those who underwent NACT/ACT, a pathological complete response was observed in five (16.6%) patients out of 30 patients. The median duration of follow-up was 32.8 months. Among all patients, 36 (24%) experienced recurrence, with seven (19.4%) having local recurrence, 24 (66.6%) developing distant metastases, two patients experiencing both local and distant recurrence, and three patients developing contralateral breast cancer. Additionally, three patients experienced a second primary cancer. The most common sites of metastases were the lungs (14), followed by the bone (seven), the liver (four), and the brain (four). Recurrence rates were notably high within the first one to three years post-diagnosis. The median disease-free survival (DFS) of TNBC patients was estimated to be 65.6 months with no statistically significant difference (p=0.174) between EBC and LABC patients. TNBC is known for its heterogeneity. While it is often regarded as being more responsive to chemotherapy compared to other subtypes of breast cancer, TNBCs tend to behave aggressively, basically due to the underlying aggressive tumor biology. Though there are many treatment options for different subtypes of breast cancer, therapeutic modalities are limited for TNBCs. Aggressive tumor biology with limited treatment options denotes a gap in the development of novel strategies to improve outcomes in this subset of breast cancer patients.

Establishment of a logistic regression model nomogram for clinicopathological characteristics and risk factors with axillary lymph node metastasis in T1 locally advanced breast cancer: a retrospective study.

Although the research reports on locally advanced breast cancer (LABC) are increasing year by year, there are few reports on T1 LABC axillary lymph node metastasis (ALNM). By establishing a prediction model for T1 LABC ALNM, this study provides a reference value for the probability of ALNM of related patients, which helps clinicians to develop a more effective and individualized treatment plan for LABC. Cases with pathologically confirmed T1 breast cancer (BC) between 2010 and 2015 in the Surveillance, Epidemiology, and End Results (SEER) database were identified. Logistic regression was used to analyze the correlation between LABC lymph node metastasis and every factor, and the odds ratio (OR) and 95% confidence interval (CI) were used to identify any influencing factors. A nomogram was drawn after incorporating meaningful factors identified in multivariate logistic regression into the model. The receiver operating characteristic (ROC) curve of the model was drawn, and the area under the curve (AUC) and its 95% CI were calculated. Hosmer-Lemeshow goodness-of-fit test and clinical decision curve analysis (DCA) were performed. The results were validated in the validation group. A total of 200,933 female T1 BC patients were included in this study. Univariate and multivariate logistic regression analysis of T1 BC showed that progesterone receptor (PR)-negative, race, age, lobular carcinoma, micropapillary ductal carcinoma, axillary tail tumor, poor differentiation, and larger tumor diameter increased the probability of ALNM in T1 LABC. A predictive nomogram was established using the above predictors, the AUC of the modeling group was 0.739 (95% CI: 0.732-0.747), and when the AUC cut-off value was 0.026, the specificity and sensitivity of the model were 65.78% and 69.99%, respectively. Validation of the model showed that the AUC of the validation group (n=60,280) was 0.741. When all the risk factors were met, the predicted probability of N2-N3 was 50.40%. In this study, it was found that PR-negative, Black race, age, lobular carcinoma, micropapillary ductal carcinoma, axillary tail tumor, poor differentiation, and tumor diameter increased the probability of large lymph node metastasis in T1 LABC small tumors.

Serum lipid ratios as novel prognostic biomarkers for patients with locally advanced breast cancer treated with neoadjuvant therapy

ABSTRACT Objectives To investigate the association between lipid ratios and survival outcomes in patients with locally advanced breast cancer (LABC) undergoing neoadjuvant chemotherapy. Method This retrospective study included patients with LABC receiving neoadjuvant chemotherapy. Serum lipid levels were prospectively measured at baseline. Associations of triglyceride to total cholesterol (TG/TC), triglyceride to high-density lipoprotein (TG/HDL) and triglyceride to low-density lipoprotein (TG/LDL) ratios with prognosis were evaluated. Results Patients with high TG/TC (adjusted hazard ratio [aHR] = 2.47, 95% CI: 1.10, 5.56, p = 0.029), TG/HDL (aHR = 2.73, 95% CI: 1.16, 6.41, p = 0.021) and TG/LDL (aHR = 2.50, 95% CI: 1.11, 5.65, p = 0.027) ratios were more likely to experience disease-free survival (DFS) events. Subgroup analysis suggested that the prognostic impact of lipid ratios was more pronounced in patients with negative HER2 status or those at a high risk of recurrence (e.g. clinical stage III, Ki67 > 30%). Additionally, higher lipid ratios tended to indicate early DFS events (0 ~ 2 years) (TG/TC p = 0.021, TG/HDL p = 0.046, TG/LDL p < 0.001), and the TG/LDL ratio demonstrated the best predictive efficacy (TG/TC vs. TG/HDL vs. TG/LDL, 1-year AUC: 0.724 vs. 0.676 vs. 0.846, 2-year AUC: 0.653 vs. 0.638 vs. 0.708). Conclusion Baseline serum TG/TC, TG/HDL and TG/LDL ratios were independent prognostic factors in patients with LABC undergoing neoadjuvant therapy. However, their utility in predicting the early DFS events warrants further investigation. Clinical trial registration NCT05621564.

Optimal neoadjuvant treatment and prognostic factors in patients with HR-positive/HER2-positive early or locally advanced breast cancer: A national real-world study in China.

e12514 Background: Few data have been reported regarding breast cancer (BC) population characterized by HR+/HER2+ especially in a real-world setting in China. This analysis aimed at identifying differences in short-term treatment outcomes of different neoadjuvant therapy (NAT) regimens, effects of the demographics and clinical features on short-term outcomes of NAT, and further understanding the prognostic factors related to those outcomes in HR+/HER2+ early (EBC) or locally advanced BC (LABC) pts by using dataset from National Cancer Information Database (NCID) in China. Methods: This retrospective, multicenter, real-world study used electronic medical record data from NCID. We analyzed HR+/HER2+ EBC or LABC Chinese pts who were initially diagnosed between Jan 1, 2019 and May 31, 2022 and received NAT followed by surgery during study period. Primary endpoints included total pathological complete response (tpCR) and breast pCR (bpCR). Secondary endpoints included disease-free survival (DFS) and event-free survival (EFS). Results: 3792 pts from NCID covering 51 hospitals, 26 provinces met inclusion criteria and were included. After controlling for age and post-surgery N staging, 1-, 2- and 3-yr DFS was similar between trastuzumab (T) and T+pertuzumab (P) NAT subgroup (92.79%, 87.20% and 83.32% vs 94.83%, 88.82% and 87.88%; p=0.1120). 1-, 2- and 3-yr EFS was higher in T+P subgroup (T vs T+P: 85.24%, 82.35%, 77.01% vs 90.86%, 89.65%, 82.78%; p = 0.0003). Logistic regression multivariate analysis showed improved tpCR and bpCR was independently positively associated with receiving T+P NAT (vs T: both p &lt; 0.0001), platinum NAT (vs anthracycline: p = 0.0071 and 0.0122, resp.), while negatively associated with receiving no targeted therapy (vs T: p = 0.0002 and &lt; 0.0001, resp.), ≥ 65 yrs (vs &gt; 40 yrs, &lt; 64 yrs: p = 0.0116 and 0.0290, resp.), or post-surgery ER positive (vs negative: both p &lt; 0.0001). Conclusions: HR+/HER2+ EBC or LABC gained short- and long-term benefit from HER2 dual-blockade therapy in clinical practice. Prognostic factors for improved tpCR and bpCR included T+P and platinum NAT, whereas ≥ 65 yrs and post-surgery ER+ were predictive of decreased tpCR and bpCR. [Table: see text]

A propensity-matched analysis of the efficacy and safety of neoadjuvant inetetamab and pertuzumab with paclitaxel and carboplatin (TCbIP) on locally advanced HER2-positive breast cancer.

e12609 Background: Inetetamab is an Fc segment-modified innovative anti-HER2 monoclonal antibody. It has been proven to be effective and safe in HER2-positive advanced breast cancer. However, its efficacy and safety in the neoadjuvant treatment of HER2-positive locally advanced breast cancer (LABC) remains to be validated. This study aimed to evaluate the efficacy and safety of Inetetamab-based neoadjuvant therapy (TCbIP). Methods: In this prospective cohort study, we investigated the efficacy and safety of TCbIP in neoadjuvant therapy for HER2-positive LABC, and compared with TCbHP regimen (trastuzumab combined with pertuzumab, paclitaxel, and carboplatin) with propensity score matching (PSM). Thirty-four patients (clinical stage IIA-IIIC, HER2-positive LABC) were prospectively enrolled in this study and treated with the TCbIP regimen. The primary endpoint was total pathological complete response (tpCR). Adverse events (AEs), objective response rate (ORR), and near-pCR were key secondary endpoints. Results: The pCR rate of 28 patients who finished surgery was 60.7%, and was comparable and slightly higher (60.7% vs. 53.6%, P = 0.510) than the TCbHP group in PSM. The ORR was 96.4% and DCR reached 100.0%. The most common ≥grade 3 AE was neutropenia (21.4% vs. 11.9%, P = 0.350). No significant reduction in left ventricular ejection fraction was observed, and no patient withdrew from treatment due to AEs. Conclusions: Neoadjuvant therapy with TCbIP resulted in good efficacy and safety in patients with HER2-positive LABC, and might be another promising option for neoadjuvant treatment. Clinical trial information: NCT05749016 .

Clinical and Pathologic Tumor Response Following Response-guided Neoadjuvant Chemotherapy for Locally-advanced Breast Cancer in a Tertiary Hospital Breast Center in the Philippines

Clinical and Pathologic Tumor Response Following Response-guided Neoadjuvant Chemotherapy for Locally-advanced Breast Cancer in a Tertiary Hospital Breast Center in the Philippines