Advanced Breast Cancer Patients Research Articles

Abstract B013: An mDETECT assay for monitoring treatment response in metastatic breast cancer patients

Abstract Metastatic breast cancer treatment response is currently assessed every 3-6 months and this long delay results in many patients undergoing ineffective and toxic treatments for long periods of time. We have developed the methylation DETEction of Circulating Tumour DNA (mDETECT) assay, a targeted DNA methylation-based Next Generation Sequencing liquid biopsy that detects cancer-specific patterns in all subtypes of breast cancer. The assay targets 60 differentially hypermethylated regions in breast cancer across the genome and assesses over 400 individual CpGs with an average of 8 CpGs per target amplicon. The assay has been assessed on DNA from 73 breast cancer tumour samples which on average had 40 regions hypermethylated per patient with similar rates across all subtypes. We will present results from plasma samples from locally advanced and metastatic breast cancer patients along with plasma from age-matched, healthy female controls. A prospective, multi-centre observational cohort study to monitor metastatic breast cancer patients using the mDETECT liquid biopsy as they undergo treatment is active and recruiting patients. Blood is drawn with every standard-of-care blood draw for up to 3 years. Plasma has been assessed using the mDETECT assay to determine the methylation status of the DNA at each time point. 35 patients have been enrolled to date with ongoing recruitment up to 150 patients. Patients are being monitored with the mDETECT assay for earlier detection of disease progression on a treatment. They will also be monitored through treatment changes to assess a patient’s initial response to a given treatment. Changes in mDETECT levels will be correlated with clinical response to determine if the mDETECT breast cancer assay can detect a response to treatment at an earlier timepoint. This assay could allow for improved monitoring of treatment response allowing clinicians to make informed decisions, improving outcomes and prolonging patient’s lives. Citation Format: Keira Frosst, Brooke Wilson, Katrina Cristall, Catherine Crawford-Brown, Christopher R Mueller. An mDETECT assay for monitoring treatment response in metastatic breast cancer patients [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B013.

PATH-67. THE ROLE OF STATUS OF HER-2, ESTROGEN-RECEPTOR, BRCA 1, AND BRCA 2, IN THE INCIDENCE OF BRAIN METASTASIS IN BREAST CANCER

Abstract Breast cancer (BC) is the most diagnosed tumor in women and the second-leading cause of brain metastasis (BM), with a prevalence ranging from 10-36%. According to the Epidemiological Strategy and Medical Economics research program, advanced BC patients face an estimated 25% risk of developing BM within 2-3 years after the initial diagnosis. The frequency of BM is significantly increased by the primary tumor profile, including larger tumors, higher nuclear grade, HER-2 positivity, estrogen-receptor negativity, and triple-negative status. A gap remains in the classification of the BM site relative to primary tumor biomarkers, and the absence of multimodality treatment methodologies poses challenges to survival rates and quality of life in BC patients. This retrospective cross-sectional study at Aga Khan University Hospital identified 52 cases of brain metastasis secondary to breast cancer over a 10-year period. The median age of patients was 55 years, ranging from 32 to 78 years. Primary breast tumors were predominantly high-grade ductal carcinomas (65%), followed by lobular carcinomas (25%) and other rare histological types (10%). Secondary brain metastases were primarily located in the cerebrum (60%), cerebellum (25%), and brainstem (15%). Tumor profiles indicated a significant correlation between HER-2 positivity and the development of brain metastasis, with 70% of HER-2 positive patients presenting with extensive brain metastasis. Tumor progression varied, with a median time to brain metastasis of 2.5 years from the initial breast cancer diagnosis. Despite aggressive multimodality treatments, including surgery, radiation, and chemotherapy, the overall prognosis remained poor. The study found that early detection of HER-2 positive and triple-negative tumors could potentially delay the progression of brain metastasis through targeted therapies. Mortality rates in this cohort were high, with a median survival of 8 months following the diagnosis of brain metastasis. These findings underscore the need for improved diagnostic, preventive, and therapeutic strategies to manage brain metastasis in breast cancer patients.

Treatment sequences and survival outcomes in advanced HR + HER2- breast cancer patients: a real-world cohort.

Palliative treatment options for HR + HER2- advanced breast cancer (ABC) patients have increased, but data is lacking about the optimal treatment sequence. We used real-world data from a comprehensive cancer center to describe applied treatment sequences and we determined treatment-related and survival outcomes. Patients aged 18 years and older with HR + HER2- ABC treated with systemic treatment were included in this historic cohort study. Sequential treatment schedules, time to treatment discontinuation, time to chemotherapy, and overall survival (OS) were determined, stratified by first-line treatment. 202 patients were included. They received a total of 650 treatment lines (median 3; range: 1-11). 91 (45%), 25 (12%), 24 (12%), 28 (14%), 22 (11%) and 12 (6%) patients started first-line treatment with non-steroidal aromatase inhibitors (NSAI), NSAI + cyclin dependent kinase 4/6-inhibitors (CDK4/6i), fulvestrant + CDK4/6i, tamoxifen, chemotherapy and other treatment, respectively. 10, 13, and 14 different treatment regimens were given in first, second and third-line, respectively. Of the patients who started first-line NSAI monotherapy (n = 91), 3 (3%) died before receiving second-line treatment. In this real-world cohort, we observed a wide variety of different treatment sequences applied in daily clinical practice, some of which were in discordance with the current guidelines. Fear that patients may never get around to treatment with CDK4/6i if a patient did not start with a CDK4/6i was not supported by our study results.

Olaparib monotherapy in advanced triple-negative breast cancer patients with homologous recombination deficiency and without germline mutations in BRCA1/2: The NOBROLA phase 2 study

PurposeTo evaluate olaparib in advanced triple negative breast cancer (TNBC) patients with homologous recombination deficiency (HRD) and no germline BRCA1/2 mutations (gBRCA1/2mut). MethodsNOBROLA (NCT03367689) is a single-arm, open-label, multicenter, phase IIa trial, enrolling adult patients with advanced TNBC without gBRCA1/2mut and with HRD, who were treated with olaparib. The primary endpoint was clinical benefit rate (CBR) per RECIST v.1.1. ResultsSix of 114 patients were eligible and received olaparib. Median follow up was 8.5 months. CBR and overall response rate (ORR) were 50 % (95 % CI, 11.8–88.2). ConclusionsThe observed results could prompt further investigation. TrialClinicalTrials.gov identifier NCT03367689.

Aneuploid Circulating Endothelial Cells with Prognostic Value in Locally Advanced Breast Cancer Patients After Neoadjuvant Chemotherapy

Aneuploid Circulating Endothelial Cells with Prognostic Value in Locally Advanced Breast Cancer Patients After Neoadjuvant Chemotherapy

Clinical outcomes after post-operative radiotherapy for breast cancer patients presenting with ipsilateral supraclavicular metastasis: considerations on the cranial border of irradiation field.

Disease recurrence at lower neck adjacent to ipsilateral supraclavicular (SCV) region represents a concern in locally advanced breast cancer patients presenting with SCV metastasis at diagnosis. This study aims to report the outcomes following post-operative radical radiation therapy and discuss the reasonable cranial border of the irradiation field for N3c patients. Between July 2016 and January 2022, a total of 268 patients were eligible for analysis. The endpoints included in-field and out-field cervical failures, local-regional recurrence-free survival (LRRFS), SCV recurrence-free survival (SRFS), distant metastasis-free survival (DMFS), relapse-free survival (RFS), and overall survival (OS). During a median follow-up of 37months (range 3-89months), 17 patients (6.3%) developed local-regional recurrence as the first recurrence event, with 13 having concomitant distant-metastasis (DM); 56 patients (20.9%) had DM alone. The 3-year rates of LRRFS, SRF, DMFS, RFS, and OS were 92.3%, 94.5%, 74.5%, 73.0%, and 90.0%, respectively. 89.2% of patients received RT with the cranial border at the top of hyoid bone, and 95.1% of patients received a boost not exceeding the level of cricoid cartilage. A total of 11 patients (4.1%) developed ipsilateral SCV failure, and 3 patients (1.1%) experienced cervical failure, including 2 in-field failures and 1 out-field failure. Neoadjuvant systemic therapy (NST) was administered to 234 patients (87.3%). In the multivariate analysis, non-ypN0, triple-negative subtype and cT4 at diagnosis were predictors of worse SRFS and RFS in NST subgroup. Our findings suggest that radical RT with cranial border of irradiation field at the hyoid bone level lead to excellent local-regional control, and out-field cervical failure was rare. The irradiation field might not extend to mastoid process.

Development and validation of the NCC-BC-A scale to assess patient-reported outcomes for breast cancer patients in China.

The commonly used international patient-reported outcome scales for breast cancer were developed before the advent of multiple targeted therapies and immunotherapies, rendering them potentially insufficient for current clinical practices. Therefore, it is necessary to develop a specific patient-reported outcome scale tailored for breast cancer patients in China to optimize the management model for these patients. A comprehensive literature search was performed in the PubMed, Embase, Wanfang, and CNKI databases to extract dimensions and items for a potential patient-reported outcome scale. The Delphi method was used to modify, add, subtract, and adjust the language of items until the experts reached a consensus on the first draft. This draft was further refined using a cognitive test and a presurvey. The optimized scale was used for a formal survey, and the items were further analyzed and screened using metrics such as the coefficient of variation, correlation coefficient, internal item consistency, factor analysis, reliability, and validity. A total of 10,954 articles were analyzed, and 237 were used to create a pool of 277 patient-reported outcome items. Through two rounds of Delphi expert consultation, the experts' authority coefficients were 0.739 and 0.826. After a cognitive test, several items were adjusted to enhance understanding. Further adjustments were made following a presurvey of 200 advanced breast cancer patients, resulting in a 38-item patient-reported outcomes scale, termed NCC-BC-A. In the national formal survey, 588 advanced breast cancer patients participated. Principal component analysis showed good consistency among the items and sufficient difference between the dimensions. The results were normally distributed with good variation. The Cronbach's α coefficient of the scale was 0.925 and the test-retest reliability was 0.9041. The NCC-BC-A scale has high validity and reliability. It comprehensively considered the characteristics of systemic treatment for breast cancer, and the specific context within China. Its implementation may help clinicians to pay more attention to quality of life of breast cancer patients and to optimize the system for managing this condition.

Could macrocytosis predict survival In advanced breast cancer patients that were treated with CDK 4–6 inhibitors?

IntroductionCyclin Dependent Kinase (CDK) 4–6 inhibitors are the recommended first-line treatment option for hormone-positive metastatic breast cancer (MBC). They show their effects by causing cell cycle arrest in G1-S phase. Neutropenia is the most common haematological side effect. In the literature, data on the association between CDK 4–6 inhibitors and macrocytosis are limited. We aimed to investigate the effect of macrocytosis on survival. MethodsWe retrospectively analysed 133 patients with de novo hormone positive MBC using CDK 4–6 inhibitors in first line treatment. Mean Corpuscular Volume (MCV) > 100 was considered macrocytosis and patients were divided into two groups; MCV<100 and MCV >100. The association of macrocytosis with clinicopathological features, Progression Free Survival (PFS) and Overall Survival (OS) were evaluated. Results42 patients were receiving palbociclib and 81 patients were receiving ribociclib. Median OS was determined as 33 months and median PFS was determined as 22 months. Macrocytosis ever rate was 45.8 % during follow-up. Macrocytosis was observed in 4.2 % of the patients in the first month, 16.7 % in the third month, 41.6 % in the sixth month and 42.2 % in the twelfth month. ER receptor level, ki-67, macrocytosis at 6–12 months and macrocytosis-ever which were found to affect OS as a result of univariate Cox regression analysis, were evaluated with multivariate Cox regression models and it was observed that they had significant effect on PFS and OS. ConclusionMacrocytosis may be a useful biomarker for the prediction of PFS and OS in MBC patients receiving CDK 4–6 inhibitors.

Survival Outcomes and Prognostic Staging in Locally Advanced Breast Cancer Patients Receiving Radiotherapy: A Single Center Experience

The American Joint Committee on Cancer (AJCC) 8th edition prognostic staging was introduced to improve breast cancer staging by incorporating factors like hormone receptor status and human epidermal growth factor receptor-2 (HER2) expression. This study assesses its effectiveness in locally advanced breast cancer (LABC). A total of 557 patients with locally advanced breast cancer (Stage III) were re-evaluated using prognostic staging. Overall survival (OS), disease-free survival (DFS), and distant metastasis free survival (DMFS) rates were evaluated using the Kaplan-Meier method, and the log-rank test was employed to compare outcomes between anatomic and prognostic staging. According to restaging 34.5% of patients remained in the same stage, while 55.8% were downstaged, and 9.7% were upstaged. When patients reassigned using prognostic staging patients classified as stage IIA showed improved OS rates compared to those in stages IIIA, IIIB, and IIIC (p&lt; 0.001 for each). Patients with prognostic stage IIA had better DFS compared to IIIA, IIIB (p= 0.003, and p&lt; 0.001, respectively). Both anatomic and prognostic staging were found to significantly impact OS in patients with Luminal-A tumors (p= 0.008 and p= 0.001, respectively), whereas neither anatomic nor prognostic stage had any impact on triple negative subgroup. When stage IIIA patients restaged, downstaged individuals showed better OS than those who stayed at the same stage or were upstaged (p= 0.01 and p= 0.02, respectively). This study highlights the prognostic staging system’s superiority over anatomic staging in predicting survival outcomes for LABC, and the use of the prognostic staging system for more personalized treatment strategies. Keywords: Breast cancer, Radiotherapy, Anatomic staging, Prognostic staging

Descriptive Analysis of CT Scan Findings in Breast Cancer Patients with Bone Metastases in Universitas Andalas Hospital Radiotherapy Installation

Background: Breast cancer is experiencing the most significant increase in cases among all cancers worldwide. Approximately 65% to 75 % of advanced breast cancer patients will experience bone metastases. CT scan is the most affordable and accessible method for evaluating bone metastases. This study aims to describe the characteristics of CT scan examination of bone metastases in breast cancer patients in the radiotherapy installation at Universitas Andalas Hospital from 2019 until 2021. Methods: A total of 51 patients with breast cancer who had bone metastases were included in this quantitative descriptive study, using a total sampling approach. The clinical data was taken from the medical records at the radiotherapy installation at Andalas University Hospital. The collected data was processed and analyzed using SPSS statistical software. Results: Based on the results, the mean age of patients was 49 years. The most histopathological type was invasive carcinoma mammae of no special type (57%). The most common site for bone metastases is osteo vertebrae (35%). Mixed lesions were the most frequent bone metastatic finding (51%), with fractures occurring in 27% of cases. Conclusions: The results of this study are breast cancer with bone metastases occurring on average at the age of 49 years, histopathological type the most is invasive carcinoma mammae of no special type. Breast cancer with bone metastases is most common in Osteo Vertebrae with mixed lesions as well as pathological fracture with a low percentage.

Breast cancer and cardiovascular health.

Modern cancer therapies greatly improve clinical outcomes for both early and advanced breast cancer patients. However, these advances have raised concerns about potential short- and long-term toxicities, including cardiovascular toxicities. Therefore, understanding the common risk factors and underlying pathophysiological mechanisms contributing to cardiovascular toxicity is essential to ensure best breast cancer outcomes. While cardio-oncology has emerged as a sub-speciality to address these challenges, it is essential that all cardiologists recognize and understand the cardiovascular consequences of cancer therapy. This review aims to provide a comprehensive overview of the potential adverse cardiovascular effects associated with modern breast cancer therapies. A preventive, diagnostic, and therapeutic workflow to minimize the impact of cardiovascular toxicity on patient outcomes is presented. Key aspects of this workflow include regular monitoring of cardiovascular function, early detection and management of cancer therapy-related cardiovascular toxicities, and optimization of cardiovascular risk factor control. By highlighting the gaps in knowledge in some areas, this review aims to emphasize the critical role of cardio-oncology research in ensuring the holistic well-being of patients with breast cancer.

PI3K/PTEN/mTOR pathway dynamic tracking and prognostic value in HR+/HER2− BC patients with residual disease after neoadjuvant chemotherapy: a cohort study

AimsHormone receptor-positive (HR)+/HER2− breast cancer (BC) is highly heterogeneous, with PI3K/PTEN/mTOR pathway alterations emerging as possible players within this complexity. We longitudinally tracked PI3K/PTEN/mTOR pathway dynamics from baseline biopsy to...

Clinical benefit and safety profile of cross-line therapy with CDK4/6 inhibitors: a retrospective study of HR+/HER2- advanced breast cancer.

CDK4/6 inhibitors (CDK4/6is) in combination with endocrine therapy have secured a central role in the treatment of hormone receptor (HR)-positive advanced breast cancer (ABC) and have transformed the therapeutic landscape. Cross-line CDK4/6i therapy in which another CDK4/6i is continued after progression on a prior CDK4/6i may still offer advantageous therapeutic effects. Cross-line CDK4/6i therapy is an area of active investigation in the ongoing pursuit to improve outcomes for patients with HR+/human epidermal growth factor receptor 2 (HER2)- ABC. This retrospective study enrolled 82 patients with HR+/HER2- ABC who were treated with cross-line CDK4/6is (abemaciclib, palbociclib, ribociclib, and dalpiciclib) after progression with another CDK4/6i. The primary endpoint was progression-free survival (PFS) according to version 1.1 of the Response Evaluation Criteria in Solid Tumors. Secondary endpoints included toxicity, objective response rate, disease control rate, and overall survival. Adverse events (AEs) were graded according to version 5.0 of the Common Terminology Criteria for Adverse Events, as promulgated by the U.S. Department of Health and Human Services. Eighty-two HR+/HER2- ABC patients who received cross-line CDK4/6i therapy from January 2022 to February 2024 were enrolled. The median age of the patients was 60 years. The median PFS of all patients was 7.6 months (95% CI, 5.9-9.2). Cox regression analysis identified lung metastasis and a switch to endocrine therapy following prior CDK4/6i therapy as independent predictive factors for PFS. Notably, patients who previously received abemaciclib and switched to palbociclib upon disease progression had a median PFS of 10.7 months. The strategy of transitioning to chemotherapy after progression on a prior CDK4/6i, then to a subsequent CDK4/6i merits further investigation. Hematologic toxicity was the most common grade ≥ 3 AEs. No instances of fatal safety events were observed. Cross-line CDK4/6i therapy is associated with significant clinical benefits and manageable safety profiles in patients with HR+/HER2- ABC, which underscores cross-line CDK4/6i therapy potential as an effective treatment strategy.

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.

Curcumin's effect in advanced and metastatic breast cancer patients treated with first or second-line docetaxel: A randomized trial.

In this study, we investigated whether the association of curcumin and docetaxel among advanced and metastatic breast cancer patients in first or second-line treatment potentiated the objective response rate. A multicentre, randomized, open label, phase-II study was conducted and included 42 patients from July 2009 to January 2017. The primary endpoint was the objective response rate of the docetaxel-curcumin combination in comparison with docetaxel alone. The secondary endpoints were the assessment of clinical benefit, overall survival, time-to-progression, progression-free survival, compliance, and safety. An interim analysis was planned to evaluate safety and efficacy. In this interim analysis conducted on 37 patients (19 in the control group vs. 18 in the experimental group), no difference was observed for the objective response rate (p = 0.25, control 73.7% vs. experimental 55.6%). Concerning clinical benefit, overall survival and time-to-progression, we also failed to show any difference between the two arms. A slight tendency towards longer progression-free survival at 12 months after randomization was observed in the curcumin group (65.5% vs. 41.4%) but this difference did not reach significance (p = 0.14). In this study, we showed for the first time that adding oral curcumin for advanced and metastatic breast cancer patients treated with first or second-line docetaxel was not efficacious, although safe. Consequently, this study was stopped for reasons of futility. Further studies with a larger number of patients, a different curcumin preparation, a longer treatment period and a pharmacokinetic evaluation of curcumin are needed to explore the real efficacy of this compound.

405P HRD biomarkers in blood samples from BRCA1/BRCA2-associated advanced breast cancer (BC) patients (pts)

405P HRD biomarkers in blood samples from BRCA1/BRCA2-associated advanced breast cancer (BC) patients (pts)

427P The role of patient navigation (PN) in delivering goal-concordant care to advanced breast cancer (ABC) patients

427P The role of patient navigation (PN) in delivering goal-concordant care to advanced breast cancer (ABC) patients

Study the effect of FGFR2 and FGFR4 gene variants on the response to cyclophosphamide doxorubicin-docetaxel based chemotherapy in locally advanced breast cancer patients

Study the effect of FGFR2 and FGFR4 gene variants on the response to cyclophosphamide doxorubicin-docetaxel based chemotherapy in locally advanced breast cancer patients

Siglec-7 and Siglec-9 expression in primary triple negative and oestrogen receptor positive breast cancer and in vitro signalling.

PD-1/PD-L1 immune checkpoint blockade can be an effective treatment for advanced breast cancer patients. However, patients with oestrogen receptor positive (ER+) tumors often display only low lymphocyte infiltration, while a large part of triple negative (TN) breast tumors does not generate an effective immunotherapy response. Therefore, new treatment strategies have to be developed. Here, we investigate Siglec-7 and Siglec-9 as novel ITIM-bearing inhibitory immune checkpoint receptors similar to PD-1, but expressed on a broader range of immune cells. We assessed Siglec-7 and Siglec-9 (ligand) expression in TN and ER+ breast cancer tumors and their breast cancer cell line-induced signalling. We report that Siglec-7 and Siglec-9 are highly expressed in TN tumors, and to a low extent in ER+ tumors. Siglec-7 was observed on myeloid cells, Tcells, and NKcells and Siglec-9 preferentially on myeloid cells. Expression of sialoglycans, including Siglec-7 and Siglec-9 ligands, was observed in both TN and ER+ breast cancer tissue sections. Expression levels of Siglec-7 and Siglec-9 ligands were higher on in vitro cultured TN cell lines than ER+ cell lines. Importantly, by applying chimeric Siglec-7 reporter cells, we showed the induction of Siglec-7 signalling by multiple TN cell lines, but only by one ER+ cell line. Moreover, Siglec-7 signalling is directly related to Siglec-7 ligand expression levels of breast cancer cell lines. These data imply that immunotherapy targeting Siglec receptors may be particularly interesting for TN breast cancer patients not responding to current treatment strategies with tumors displaying high immune cell infiltration.

Fluctuations in serum lipid levels during neoadjuvant treatment as novel predictive and prognostic biomarkers for locally advanced breast cancer: a retrospective analysis based on a prospective cohort

BackgroundWith increasing attention given to host-specific lipid metabolism status, it is of urgent need to identify lipid metabolism indices with predictive or prognostic value in locally advanced breast cancer patients treated with neoadjuvant chemotherapy (NAC), and to evaluate the performance improvement by incorporating them into the existing Neo-Bioscore staging system.MethodsPatients from a prospectively maintained database of locally advanced breast cancer patients who received radical surgery after NAC between January 2014 to December 2020 were enrolled in this study. The enrolled patients were randomly divided into a training set and a test set at a ratio of 6:4. The random forest algorithm was applied to rank the importance of prognostic factors, top-ranked lipid metabolism indices of which were then incorporated into Neo-Bioscore to construct an updated prognostic model. The performances of these two models were compared in both training set and test set from multiple perspectives. Study outcomes included disease-free survival (DFS), relapse-free survival (RFS), distance-recurrence-free survival (DRFS), locoregional-recurrence-free survival (LRFS) and overall survival (OS).ResultsA total of 200 eligible patients were included in this study. After a median follow-up of 4.73 years, it was demonstrated that the relative increase in total cholesterol (TC; DFS: HR = 4.782, 95%CI 1.410 ~ 16.217, P = 0.012) and low-density lipoprotein (LDL; DFS: HR = 4.622, 95%CI 1.517 ~ 14.088, P = 0.007) during NAC led to poorer survival outcomes. Patients with either a higher body mass index (BMI) or elevated LDL during NAC had a worse prognosis (DFS: HR = 6.351, 95%CI 1.938 ~ 20.809, P = 0.002; OS, HR = 6.919, 95%CI 1.296 ~ 36.932, P = 0.024). Incorporating BMI and LDL fluctuations during NAC into Neo-Bioscore improved the prognostic stratification, especially in terms of LRFS (P = 0.046 vs. P = 0.65) and OS (P = 0.013 vs. P = 0.61). Multidimensional evaluation confirmed the improvement in model fit and clinical use for the updated model in both training set and test set.ConclusionsThis is the first study to illustrate the relative elevation of LDL and TC levels during NAC as independent prognosticators for locally advanced breast cancer. This is also the first attempt to incorporate lipid metabolism indices into the original Neo-Bioscore staging system, which further improves the prognostic stratification of patients receiving NAC.