Systemic Therapy For Breast Cancer Research Articles

Abstract 7485: Microfluidic detection of dual positive cells in whole blood of metastatic breast cancer patients

Abstract Background. Dual positive cells (DPCs) that express both epithelial markers and leukocytic markers have been observed in peripheral blood of breast cancer patients. DPCs acquire functional behaviors from both cell types which may drive tumor progression. However, the lack of reliable methods to isolate and identify DPCs has hindered the investigation of their origin and clinical implications in breast cancer patients. While microfluidic devices have been widely used for the detection of circulating tumor cells (CTCs) by liquid biopsy, DPC detection is underexplored in these devices. Herein, we demonstrate rapid onchip isolation and detection of DPCs in whole blood samples from metastatic breast cancer (MBC) patients using an integrated microfluidic device. Methods. Our microfluidic device consists of a unique preconditioning component that concentrates targets in whole blood and a downstream cell immobilization component that captures target cells. We included 7 female patients with MBC, of which 29% are white (2), 57% are African American (4), and 14% are Latina (1). The median age is 50y (34y -75y). All patients were undergoing systemic breast cancer therapy at the time of blood collection. A total of 9 samples (4 mL each) were collected from either an antecubital vein (peripheral vein) or the subcutaneous port catheter (central vein) of these patients. All samples were processed within 5 hours of blood drawn in our novel microfluidic biochip. CTCs (EpCAM+/CK+, CD45-, DAPI+) and DPCs (EpCAM+/CK+, CD45+/CD66b+, DAPI+) were identified by immunofluorescence after cells were fixed. Results. Processing of each sample was completed within 40 minutes using our microfluidic device. Both DPCs and CTCs were detected in all the samples (9/9). The average DPC count was 3 DPCs per 4 mL whole blood with a standard deviation of 1.9 cells. The average CTC count was 9 with a standard deviation of 5 per 4 mL whole blood. 89% of the samples (8/9) had > 5 CTCs after the sample volume is scaled to the standard 7.5 mL. No correlation was found between DPC count and CTC count (Pearson correlation coefficient r=0.08). While the blood collection location (central vs peripheral veins) had a significant impact on the CTC count (12.6 vs 4 on average with p<0.01), there was no statistical difference in DPC counts in the samples collected from central and peripheral veins. Conclusions. Both DPCs and CTCs can be rapidly isolated and detected from MBC patient whole blood in our microfluidic device. Our preliminary results indicate no correlation between DPCs and CTCs, suggesting that DPCs might not originate in blood circulation of MBC patients. More work with a larger patient cohort will be needed to further investigate the clinical implications of DPCs on MBC patients. Citation Format: Jian Zhou, Qiyue Luan, Celine Macaraniag, Arielle B. Guzman, Maria Mantice, Oana Danciu, Kent F. Hoskins, Ian Papautsky. Microfluidic detection of dual positive cells in whole blood of metastatic breast cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7485.

Magnetically guided surgery after primary systemic therapy for breast cancer: implications for enhanced axillary mapping.

Superparamagnetic iron nanoparticles perform comparably to radioisotope ± blue dye for sentinel lymph node detection in breast cancer, even when injected up to 8 weeks before surgery. Using superparamagnetic iron nanoparticles for sentinel lymph node detection after primary systemic therapy, and the maximum time frame of superparamagnetic iron nanoparticle administration have not been investigated. This cohort study included cN0/1-to-ycN0 patients undergoing sentinel lymph node detection or targeted axillary dissection. All patients received superparamagnetic iron nanoparticles either before primary systemic therapy or before surgery, and radioisotope on the day of surgery. For 113 patients analysed, superparamagnetic iron nanoparticles were injected a median of 3 (range 0-248) days before surgery, with a 97.4% detection rate compared with 91.2% for radioisotope (P = 0.057). Concordance for radioisotope was 97.1% and this was not affected by timing of superparamagnetic iron nanoparticle injection (Kendall's tau 0.027; P = 0.746). The median sentinel lymph node yield was 3 (interquartile range (i.q.r.) 2-3) for superparamagnetic iron nanoparticles and 2 (i.q.r. 2-3) for radioisotope (P < 0.001). In targeted axillary dissection, detection was 100% for superparamagnetic iron nanoparticles and 81.8% for radioisotope (P = 0.124). The index node was magnetic in 93.9% and radioactive in 66.7% (P = 0.007), an outcome that was not affected by any factors. For patients with metastases, superparamagnetic iron nanoparticle detection was 100% and radioisotope-based detection was 84.2% (P = 0.083), with superparamagnetic iron nanoparticles detecting more metastatic sentinel lymph nodes (median of 1 (i.q.r. 1-2) for superparamagnetic iron nanoparticles compared with a median of 1 (i.q.r. 0-1) for radioisotope; P = 0.005). Injection before primary systemic therapy is feasible and does not affect concordance with radioisotope. Superparamagnetic iron nanoparticles perform comparably to radioisotope, but detect more sentinel lymph nodes and have a higher rate of detection of metastatic sentinel lymph nodes.

Is contrast-enhanced mammography (CEM) an alternative to MRI in assessing the response to primary systemic therapy of breast cancer?

PurposeTo evaluate the accuracy of contrast-enhanced mammography (CEM) and magnetic resonance imaging (MRI) in the assessing radiological response to primary systemic therapy (PST). MethodProspective study between February 2021 and October 2022. Women with breast cancer and indication of PST were enrolled. CEM and MRI were performed before and after PST, and the findings, including size and radiological response pattern, were compared with the size of the residual lesion measured in surgical specimens and its Miller-Payne classification (considered the gold standard). Two of four independent radiologists, with 2 years of CEM experience and 10 years of MRI experience, reviewed the images while being blinded to the results of the other technique. The agreement between measurements was evaluated using the Pearson correlation coefficient (r) and Lin’s coefficient. ResultsForty-eight women with breast cancer who required PST were enrolled in the study, with a mean age of 57.21 ± 10.14 years. A total of thirty-three participants (68.75 %) completed the study. The correlation between CEM and MRI measurements was high before PST (r: 0.97), and local staging was identical for 45 out of 48 patients. MRI demonstrated better accuracy in predicting residual tumor size than CEM, with Lin’s coefficient 0.91 and 0.73, respectively. However, no significant differences were observed in predicting response to therapy. Both methods tended to overestimate the size and degree of response in our study, with mean overestimations of 2.87 mm in CEM and 0.51 mm in MRI. ConclusionCEM was found to be as accurate as MRI in predicting response to PST, indicating its potential as an alternative imaging technique, but further research is necessary.

Validation of prognostic and predictive value of total tumoral load after primary systemic therapy in breast cancer using OSNA assay

PurposeThis study aimed to validate the classification of breast cancer (BC) patients in progression risk groups based on total tumor load (TTL) value to predict lymph node (LN) affectation after neo-adjuvant systemic therapy (NAST) obtained in the NEOVATTL study.Methods/patientsThis was an observational, retrospective, international, multicenter study including patients with infiltrating BC who received NAST followed by sentinel lymph node biopsy (SLNB) analyzed with one-step nucleic acid amplification (OSNA) from nine Spanish and two Italian hospitals. Patients were classified into three groups according to the progression risk, measured as disease-free survival (DFS), based on TTL values (> 250, 250–25,000, and > 25,000 copies/μL). The previous (NEOVATTL study) Cox regression model for prognosis was validated using prognostic index (PI) and Log ratio test (LRT) analyses; the value of TTL for axillary non-SLN affectation was assessed using receiver operating characteristic (ROC) curves.ResultsWe included 263 patients with a mean age of 51.4 (± SD 10.5) years. Patients with TTL > 25,000 copies/μL had a shorter DFS (HR 3.561 [95% CI 1.693−7.489], p = 0.0008 vs. TTL ≤ 25,000). PI and LRT analyses showed no differences between the two cohorts (p = 0.2553 and p = 0.226, respectively). ROC analysis showed concordance between TTL and non-SLN involvement (area under the curve 0.828), with 95.7% sensitivity and 92.9% specificity at a TTL cut-off of > 15,000 copies/μL.ConclusionsIn BC patients who had received NAST and underwent SLNB analysis using OSNA, a TTL value of > 25,000 copies/μL was associated with a higher progression risk and > 15,000 copies/μL was predictive of non-SLN involvement.

Evaluation of tumor-infiltrating lymphocytes and mammographic density as predictors of response to neoadjuvant systemic therapy in breast cancer

Background Response rates vary among breast cancer patients treated with neoadjuvant systemic therapy (NAST). Thus, there is a need for reliable treatment predictors. Evidence suggests tumor-infiltrating lymphocytes (TILs) predict NAST response. Still, TILs are seldom used clinically as a treatment determinant. Mammographic density (MD) is another potential marker for NAST benefit and its relationship with TILs is unknown. Our aims were to investigate TILs and MD as predictors of NAST response and to study the unexplored relationship between TILs and MD. Material and methods We studied 315 invasive breast carcinomas treated with NAST between 2013 and 2020. Clinicopathological data were retrieved from medical records. The endpoint was defined as pathological complete response (pCR) in the breast. TILs were evaluated in pre-treatment core biopsies and categorized as high (≥10%) or low (<10%). MD was scored (a–d) according to the breast imaging reporting and data system (BI-RADS) fifth edition. Binary logistic regression and Spearman’s test of correlation were performed using SPSS. Results Out of 315 carcinomas, 136 achieved pCR. 94 carcinomas had high TILs and 215 had low TILs. Six carcinomas had no available TIL data. The number of carcinomas in each BI-RADS category were 37, 122, 112, and 44 for a, b, c, and d, respectively. High TILs were independently associated with pCR (OR: 2.95; 95% CI: 1.59–5.46) compared to low TILs. In the univariable analysis, MD (BI-RADS d vs. a) showed a tendency of higher likelihood for pCR (OR: 2.43; 95% CI: 0.99–5.98). However, the association was non-significant, which is consistent with the result of the multivariable analysis (OR: 2.51; 95% CI: 0.78–8.04). We found no correlation between TILs and MD (0.02; p = .80). Conclusion TILs significantly predicted NAST response. We could not define MD as a significant predictor of NAST response. These findings should be further replicated.

Impact of Caloric Restriction in Breast Cancer Patients Treated with Neoadjuvant Chemotherapy: A Prospective Case Control Study.

Background and aims: It is well established that caloric restriction (CR) may influence metabolic and hormonal factors involved in cancer development and progression. Recently, several studies have demonstrated that CR may have a favorable impact on the response to systemic therapy in breast cancer (BC) patients. However, there is a lack of data regarding the influence of CR during neoadjuvant chemotherapy (NACT). Our study's primary aim was to evaluate CR's impact on BC patients undergoing NACT. Secondly, we investigated the nutritional efficacy and safety of this intervention. Methods: We performed a prospective, case-control study in two breast units. A diet group consisting of 39 patients undergoing NACT and CR was enrolled in our study at the same time. CR consisted of a 30% reduction in caloric intake, which increased to 50% on the days before, during, and after the administration of chemotherapy. A control group of 60 patients that underwent the same treatment approach only followed the general dietary recommendations for BC according to WCRF guidelines. The diet group was monitored during the study for both dietary adequacy and weight trends. Results: CR combined with NACT showed a statistically significant therapeutic response in tumor size (OR 2.94, IC 1.07-8.01, p = 0.009) and lymph node status (OR 3.22, IC 1.22-8.56, p = 0.001) compared to NACT alone, even after the adjustment for all biological parameters. Our data also showed the efficacy and safety of this intervention in both anthropometric and biochemical analyses. Conclusions: Patients who adhered to CR showed a better response to NACT, both in the breast and in the axillary lymph nodes, compared to the patients in the control group. Furthermore, the CR diet combined with NACT showed good tolerance and safety.

Assessment of &lt;i&gt;ERBB2&lt;/i&gt; and HER2 expression in metastatic breast cancer using the nCounter® system and a 100-gene scale

Background. Individual molecular characteristics of a tumor can serve as a basis for a tailored approach to therapy, prediction of the disease course and outcome, and timely treatment correction in cancer patients. Tumor genomic profiling allows for a more precise tumor assessment in an individual manner. Accurate identification of the HER2 status of a breast tumor is crucial for clinical decisions and appropriate treatment strategy.Aim. To increase the efficacy of systemic therapy for breast cancer, reduce inappropriate prescribing, and ensure a tailored approach to systemic breast cancer therapy using the information on individual molecular characteristics of the tumor.Materials and methods. We explored the expression of 100 genes involved in breast cancer development in 106 tumor samples from patients with metastatic breast cancer. We used the nCounter technology based on direct digital target detection using color-coded molecular barcodes. We analyzed the expression of 28 genes with a high predictive value for breast cancer.Results. The nCounter technology allowed us to perform semiquantitative assessment of the expression of 28 genes in tumor tissue samples. We compared the expression of ERBB2 and HER2. The HER2 expression between 252.32 and 6000 barcodes was equivalent to HER2 (0) status; between 6000 and 9196.25 barcodes, to HER2 (1+); between 9196.25 and 15022.46, to HER2 (2+/ISH±); and 15022.46 barcodes, to HER2 (3+). In case of HER2 (3+) and ERBB2 below 6000 barcodes, the result was considered false positive. In case of HER2 (0) or (1+) and ERBB2 above 15 000 barcodes, the result was considered false negative. In 18 tumors, the discrepancies in the results meant two principally different breast cancer subtypes requiring different treatments; in 2 cases, the discrepancies were in the level of HER2 expression.Conclusion. HER2 testing should be performed on an excision sample (ideally on the same block that was used for genomic testing). Despite the correlation between the HER2-enriched molecular class and the response to anti-HER2 therapy, the final result on HER2 status in discordant cases should be based on currently approved assays after results validation.

Assessment of &lt;i&gt;ERBB2&lt;/i&gt; and HER2 expression in metastatic breast cancer using the nCounter® system and a 100‑gene scale

Background. Individual molecular characteristics of a tumor can serve as a basis for a tailored approach to therapy, prediction of the disease course and outcome, and timely treatment correction in cancer patients. Tumor genomic profiling allows for a more precise tumor assessment in an individual manner. Accurate identification of the HER2 status of a breast tumor is crucial for clinical decisions and appropriate treatment strategy.Aim. To increase the efficacy of systemic therapy for breast cancer, reduce inappropriate prescribing, and ensure a tailored approach to systemic breast cancer therapy using the information on individual molecular characteristics of the tumor.Materials and methods. We explored the expression of 100 genes involved in breast cancer development in 106 tumor samples from patients with metastatic breast cancer. We used the nCounter technology based on direct digital target detection using color‑coded molecular barcodes. We analyzed the expression of 28 genes with a high predictive value for breast cancer.Results. The nCounter technology allowed us to perform semiquantitative assessment of the expression of 28 genes in tumor tissue samples. We compared the expression of ERBB2 and HER2. The HER2 expression between 252.32 and 6000 barcodes was equivalent to HER2 (0) status; between 6000 and 9196.25 barcodes, to HER2 (1+); between 9196.25 and 15022.46, to HER2 (2+ / ISH±); and ≥15022.46 barcodes, to HER2 (3+). In case of HER2 (3+) and ERBB2 below 6000 barcodes, the result was considered false positive. In case of HER2 (0) or (1+) and ERBB2 above 15000 barcodes, the result was considered false negative. In 18 tumors, the discrepancies in the results meant two principally different breast cancer subtypes requiring different treatments; in 2 cases, the discrepancies were in the level of HER2 expression.Conclusion. HER2 testing should be performed on an excision sample (ideally on the same block that was used for genomic testing). Despite the correlation between the HER2‑enriched molecular class and the response to anti‑HER2 therapy, the final result on HER2 status in discordant cases should be based on currently approved assays after results validation.

Prognostic factors and clinical outcomes of breast cancer patients with disease progression during neoadjuvant systemic therapy

Disease progression during neoadjuvant systemic therapy for breast cancer indicates poor prognosis, while predictors of the clinical outcomes of these patients remain unclear. By comparing the clinical outcomes of patients with different patterns of salvage treatment strategies, we try to evaluate the factors predicting distant failure and explore the favourable treatment for them.Patients with disease progression during neoadjuvant systemic therapy for stage I-III breast cancer diagnosed between January 1, 2008 and July 31, 2021 in Fudan University Shanghai Cancer Center were enrolled. Disease progression was defined as at least a 20% increase in the sum of diameters of target lesions or the appearance of new breast or nodal lesions. Kaplan-Meier, univariate and multivariate Cox proportional hazard regressions were utilized to compare survival outcomes between different salvage treatment strategies.Among 3775 patients treated with NST, 60 (1.6%) patients encountered disease progression. A significant difference between the outcomes of patients receiving direct surgery and other salvage modalities was found (p = 0.007). Triple-negative breast cancer (p = 0.010) and not receiving direct surgery (p = 0.016) were independently associated with distant disease-free survival on multivariate analysis.Predictors of distant failure in patients with disease progression include triple-negative breast cancer and not receiving direct surgery. Direct surgery seems to be more favourable than other treatments for patients with disease progression. For inoperable patients, neoadjuvant radiation can increase their operability but not improve their prognosis.

Recent advances in BCRP-induced breast cancer resistance treatment with marine-based natural products.

Breast cancer is the prominent cause of cancer-related death in women globally in terms of incidence and mortality. Despite, recent advances in the management of breast cancer, there are still a lot of cases of resistance to medicines, which is currently one of the biggest problems faced by researchers across the globe. Out of several mechanisms, breast cancer resistance protein (BCRP) arbitrated drug resistance is a major concern. Hormonal, cytotoxic and immunotherapeutic drugs are used in the systemic therapy of breast cancer. It is vital to choose drugs based on the clinical and molecular attributes of the tumor to provide better treatment with greater efficacy and minimal harm. Given the aforementioned necessity, the use of marine flora in treating breast cancer cannot be neglected. The scientists also stressed the value of marine-derived goods in avoiding breast cancer resistance. Future research into the identification of anticancer drugs will heavily draw upon the marine environment's ample supply of marine-derived natural products (MNPs), which have a wide range of biological functions. Cell cycle arrest, induction of apoptosis and anti-angiogenic, anti-proliferative and anti-metastasis actions are all part of their processes. The overview of breast cancer, the mechanisms underlying its resistance, recent clinical trials based on marine-derived products in breast cancer and the use of marine products in the treatment of breast cancer are highlighted in this paper. Moreover, the authors also emphasised the importance of marine-derived products in preventing breast cancer resistance.

Patient-Friendly Summary of the ACR Appropriateness Criteria®: Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer: 2022 Update

Patient-Friendly Summary of the ACR Appropriateness Criteria®: Monitoring Response to Neoadjuvant Systemic Therapy for Breast Cancer: 2022 Update

Predictive multigenic scale. Analysis of own results in metastatic breast cancer

Background. Breast cancer is one of the most common female malignancies. Molecular diagnostic methods of tumor profiling allow us to analyze individual tumor characteristics, identify new prognostic and predictive markers. Aim. To increase the efficacy of systemic therapy for breast cancer and reduce inappropriate prescriptions using the data on individual molecular tumor characteristics; to develop a polygenic panel to ensure a tailored approach to systemic therapy for breast cancer. Materials and methods. We analyzed 84 tumor tissue samples from pre- and postmenopausal women with metastatic breast cancer who were treated and followed-up in 6 healthcare institutions. We assessed expression of genes involved in breast cancer. In a pilot study, we analyzed archived paraffin-embedded tumor specimens form 12 out of 1,216 patients with T1–2N0M0 breast cancer included into retrospective analysis. Gene expression was assessed using the nCounter technology based on direct digital detection of targets using fluorescent barcodes (nCounter Analysis System; NanoString Technologies, USA). Tumor tissue (biopsy and surgical specimens) was analyzed. The choice of genes was based on the literature data and experience in the development of other polygenic panels, as well as clinical significance of markers of prognostic scales. Gene mutations were confirmed by next generation sequencing and reverse transcription-polymerase chain reaction. Results. We analyzed the expression of 28 genes with a high predictive value that have been substantially studied (including ESR1, PGR, PIK3CA, BCAR4, BCAS2, CCND1, CCND2, CCND3, FOXA1, Erb2, EGFR, CDH3, FOXC1, KRT14, KRT5, CD274, CDK4, CDK6, P53, PTEN, BRCA1, BRCA2, CHEK2, CLDN3, CLDN7, AR, TOP2a, TUBBIII). We identified 29 cases of discrepancy (29 / 84; 34.5 %) in tumor subtype, including 11 cases of luminal A and B breast cancer, which might potentially affect the choice of the treatment regimen. In 18 cases, there were some principal discrepancies in the tumor subtype that implied totally different treatment regimens. The proposed polygenic signature allows accurate identification of the tumor subtype in patients with metastatic breast cancer and choice of an optimal treatment strategy. Conclusion. We have developed a 100-gene signature including molecular subtypes of breast cancer (luminal A, luminal B, basal, claudin-like) and treatment-oriented clusters. Molecular tumor profiling using this polygenic signature is an accurate method for determining tumor subtype in patients with breast cancer, which enables a tailored approach to therapy.

Prognostic and predictive value of a novel 100-point scale in patients with T1–2N0M0 breast cancer

Aim. To increase the efficacy of systemic breast cancer therapy and reduce inappropriate prescriptions using individual immunohistochemical tumor characteristics, as well as to develop prognostic scales to ensure a tailored approach to adjuvant systemic treatment in breast cancer patients. Materials and methods. We conducted a comprehensive study that included collection of literature data on clinical, pathomorphological, prognostic, and predictive factors of breast cancer, as well as a retrospective cohort study using the data from the cancer registry. We also performed histological and immunohistochemical examination of tumor tissue samples from breast cancer patients (for the retrospective cohort study) and statistical data analysis. A total of 1,216 patients with T1–2N0M0 breast cancer were included in this study. Histological and immunohistochemical examinations of tissue samples (paraffin blocks) were conducted in the laboratory of N. N. Petrov National Medical Research Center of Oncology. We stained slides for both routinely used markers (including estrogen receptors, progesterone receptors, HER2, and Ki-67) and other markers (CK14, FOXA1, FOXP3, PD-L1, P53, SMA, androgen receptors, E-cadherin, CD4, CD8, CK5 / 6, EGFR).We analyzed risk factors for lethal outcomes in patients from this group to develop prognostic scales and compared their results. Results. We evaluated the most clinically and statistically significant factors affecting mortality. Using logistic regression, we chose 10 factors that had the greatest impact on the outcomes and then produced several scales, includinga 10-point regression scale (based on 10 most significant factors identified). Survival analysis in high-risk and low-risk patients using the regression scale demonstrated significant differences between these groups (р &lt;0.00001). The assessment of adjuvant chemotherapy efficacy in the combined group of intermediate- and high-risk patients (as estimated by the regression model) showed that intermediate- and high-risk patients receiving adjuvant chemotherapy had significant differences in their survival (р = 0.0057). The regression scale for 10-year prognosis demonstrated sufficient sensitivity (58.05 %), specificity (69.47 %) and ef fectiveness (63.76 %). Conclusion. Our regression prognostic scale includes markers with a high prognostic value. The multifactorial approach used in the developed regression scale for breast cancer 10-year prognosis increases its accuracy and reliability.

Pathologic complete response after neoadjuvant systemic therapy for breast cancer in BRCA mutation carriers and noncarriers.

544 Background: Distinct pathological characteristics and mutational signatures in BRCA-associated breast cancers may result in differential response to chemotherapy but understanding of treatment response after neoadjuvant chemotherapy (NAC) is limited. We describe a single-institutional experience to compare rates of pathologic complete response (pCR) after NAC in BRCA carriers (g BRCA1/2) and noncarriers. Methods: From 11/2013 to 01/2022, 1426 consecutive women with clinical stage I-III breast cancer were treated with NAC followed by surgery. Baseline disease characteristics were compared between g BRCA1/2 and noncarriers using two-sample non-parametric tests. Conditional logistic regression was used to evaluate the association between BRCA status and pCR (i.e., ypT0/is pN0) adjusting for variables selected using backward elimination. Results: 92 (6.5%) and 73 (5.1%) had deleterious mutations in BRCA1 and BRCA2, respectively. Compared to noncarriers, g BRCA1/2 were younger (p&lt;0.001) with clinical T1 (p=0.002) and triple negative disease (TN) (57% vs 25% noncarriers, p&lt;0.001). Almost all patients received doxorubicin/cyclophosphamide/paclitaxel therapy (93%) with g BRCA1/2 more likely to receive carboplatin (p&lt;0.001). pCR rate was 42% of g BRCA1, 21% of g BRCA2, and 26% of noncarriers (p=0.001). Among clinically node positive (cN+) patients, nodal pCR was higher in g BRCA1/2 compared to noncarriers (53/96 (55%) vs 371/856 (43%), p=0.012). This difference was seen in ER+/HER2- (36% gBRCA1/2 vs 20% noncarriers; p=0.027) and TN subtypes (79% g BRCA1/2 vs 45% noncarriers; p&lt;0.001). Poorly differentiated tumors (p&lt;0.001), cN+ (p=0.010), lower cT stage (p=0.028), ductal histology (p&lt;0.001), TN and HER2+ receptor status (p&lt;0.001), absence of lymphovascular invasion (p&lt;0.001), carboplatin receipt (p=0.041), and BRCA1 status (p=0.001) were also associated with pCR on univariate analysis. After adjusting for differentiation and molecular subtype, BRCA1 status remained independently associated with pCR. Conclusions: g BRCA1 undergoing NAC have higher pCR rates relative to g BRCA2 and patients with sporadic disease. Across breast cancer subtypes, g BRCA1/2 more frequently converted to pN0. Defining biological mechanism for these findings would allow customization of treatment based on germline genetics. [Table: see text]

Evolution of HER2 scores after neoadjuvant systemic therapy in breast cancer.

3139 Background: Breast cancer (BC) is a malignancy with a wide array of histopathological characteristics and tumor heterogeneity leading to major clinical implications for management. With the recent approval of antibody-drug conjugates (ADCs) for human epidermal growth factor receptor 2 (HER2)-low advanced BC, there is increased significance for characterizing the spectrum of HER2 expression in the curative setting. Methods: We conducted a single institution retrospective review of patients with BC who received neoadjuvant systemic therapy (NAST) followed by definitive surgical resection from 2008 to 2022. The initial tumor biopsies were tested for estrogen receptor (ER), progesterone receptor (PR), and HER2 status per ASCO/CAP guidelines and repeated on the residual tumor tissue after NAST. HER2 status was categorized into HER2-negative (IHC 0), HER2-low (IHC 1 or IHC 2/ Fluorescence in situ hybridization [FISH] negative), and HER2-positive (IHC 2/ FISH positive or IHC 3). Concordance and discordance with HER2 status in the pre and post NAST tumor samples were analyzed using descriptive statistics. Results: Of 340 patients with BC who received NAST, 55 patients with residual disease had pre and post treatment biomarker data available for analysis. Prevalence of HER2-low was 70.9 % (39/55) in the pretreatment tumors while it was 58.2% (32/55) in the post treatment tumors. 40% of tumors (22/55) had HER2 discordance while 60% (33/55) demonstrated concordance with HER2 expression after NAST. Among the changes in HER2 status, a shift from HER2-low to HER2-negative status occurred most frequently in 18.2% of tumors (10/55). In tumors with HER2 discordance, 36.4% (8/22) were also noted to have changes in ER or PR status while this was seen in 48.5% (16/33) of tumors with HER2 concordance. For rates of recurrence, 22.7% (5/22) of patients in the HER2 discordant group had relapsed compared to 18.2% (6/33) patients in the HER2 concordant group. Conclusions: Dynamics of HER2 expression is increasingly important in the rapidly changing therapeutic landscape of BC. Our study shows high prevalence of HER2-low expression in tumors with residual disease after NAST and frequent conversion of HER2-low to HER2-negative status with NAST. Further studies are warranted to determine the clinical and therapeutic relevance of biomarker evolution and tumor heterogeneity in the curative setting. [Table: see text]

A whole-food, plant-based dietary intervention and cognitive function in women with metastatic breast cancer.

e24160 Background: Disease-specific quality of life (QOL) is consistently regarded as one of the most important outcomes by women with metastatic breast cancer (mBC), and it predicts survival. Treatment-related symptoms such as cognitive impairment greatly impact QOL in women with mBC. Patients undergoing treatment for breast cancer are highly interested in diet and nutrition, but despite this high level of interest, very few trials have tested dietary interventions in women receiving systemic breast cancer therapy and; the majority of research has been conducted in survivors who have completed primary treatment. Given the limited treatment options for cognitive impairment we evaluated whether our results show a whole food plant based (WFPB) dietary intervention might improve perceived cognitive function (CF) in women undergoing treatment for metastatic breast cancer. Methods: Patients with stage 4 breast cancer receiving treatment were randomized 2:1 into 2 arms: 1) WFPB diet (n = 20) or 2) usual care (n = 10) for 8 weeks with assessments at baseline, and 8 weeks. Our WFPB diet consisted of an ad libitum whole-food, plant-based diet; 3 meals/day were provided, which included fruits, vegetables, whole grains, nuts/seeds and excluded meat, dairy, eggs, added oils, solid fats and most sugars. Patient reported outcomes for perceived CF were collected using FACT- COG and EORTC-QLQ-C30. Paired t-tests were used to assess within group changes from baseline to week 8. The between group difference (WFPB diet vs control) was assessed by ANCOVA model. Results: Patients on the WFPB diet began with a mean baseline score of 140.8 on the FACT-COG which significantly improved to 156.6 (p = 0.005) at 8-weeks post intervention. The reported minimally important difference (MID) between groups is (9.6) and we observed a clinically significant difference of 17.1 (p = 0.03). Similar results in CF were observed for EORTC-QLQ-C30. The baseline mean score of 73.3 was improved to 84.7 (p = 0.004) at 8-weeks post intervention. The reported MID between groups is (4) and we observed a clinically significant difference of 12.6 (p = 0.07), with no significant changes in perceived CF for the control group. Conclusions: Our 8-week WFPB diet resulted in clinically meaningful and statistically significant improvements in perceived cognitive function in women with metastatic breast cancer. A phase 3 clinical trial is needed to confirm the results of this novel intervention. Funding: 3UG1CA189961. Clinical trial information: NCT03045289 .[Table: see text]

Control of resection margins after neoadjuvant systemic therapy in breast-conserving surgery in breast cancer patients

BACKGROUND: Surgical treatment of breast cancer plays a major role in the combined and complex treatment of patients. The purity of the examined edges of the resected breast tissue is the main indicator of the reliability of the breast-conserving surgery and one of the main factors in the development of local recurrence. Neoadjuvant (preoperative) systemic therapy allows evaluating the effectiveness of therapy in vivo and reducing the size of the initial formation, both in locally advanced and resectable forms of breast cancer. The main advantage of this treatment is the ability for surgeons to perform breast-conserving surgery to improve patients quality of life and aesthetic outcomes without compromising disease-free and overall survival.&#x0D; AIM: To study the clinical and pathological characteristics and analyze of the breast-conserving surgery in patients with breast cancer after neoadjuvant chemotherapy.&#x0D; MATERIALS AND METHODS: 156 performed breast-conserving surgery after neoadjuvant chemotherapy were analyzed. Breast-conserving resection implied radical removal of the residual tumor node within healthy breast tissues with the achievement of negative resection margins. If pathologists detected stained invasive cells/cancer in situ in a formalin-fixed preparation, a second surgical intervention was performed.&#x0D; RESULTS: Of the 156 studied anatomical preparations after breast-conserving surgery, a positive margin was found in 4 (2.56%) cases. In 4 patients, positive margin was represented by ductal carcinoma in situ. According to the results of trephine biopsy, no intraductal component was found before neoadjuvant chemotherapy. The greatest length of the ductal carcinoma in situ section is 2.2 mm. In 3 cases, the distance to the stained resection margin of the micropreparation was 1 mm. As a result of repeated pathomorphological examination of pre-cut margins after surgical intervention, cancer in situ was not found.&#x0D; CONCLUSIONS: The ongoing neoadjuvant systemic therapy for breast cancer with a partial or complete response of the tumor increases the percentage of breast-conserving surgery performed in patients who initially belong to the group of radical mastectomy, but who want to save breast tissue.

147P Germline BRCA mutation status and response to neoadjuvant systemic therapy in breast cancer

It remains inconclusive whether germline BRCA mutation affects the response of neoadjuvant systemic therapy in breast cancer. Here, we present a retrospective analysis which estimated the pathologic complete response (pCR) rate in breast cancer patients according to gBRCA1/2 mutation status. We reviewed a total of 442 breast cancer patients who underwent gBRCA1/2 tests and received neoadjuvant chemotherapy in 2 institutions between 2001 and 2022. Chemotherapy response was compared between patients with or without deleterious BRCA1/2 mutation and we assessed the association of the pCR rate and clinical characteristics of the patients. For pCR rates, the ypT0/is ypN0 definition was used as a primary end point. We detected pathogenic BRCA1/2 mutations in 145 (32.8%) of the 442 patients, 83 (18.8%) in BRCA1 and 62 (14.0%) in BRCA2. Overall pCR rate was 34.6% (153/442). The pCR rate was 37.9% (55/145) and 33.0% (98/297) for gBRCA1/2 carriers and non-carriers, respectively. Germline BRCA1/2 mutation status, mutation type and locus were not significantly different from a pCR rate (OR:0.806, 95% CI=0.533-1.219, P =0.306). With respect to the demographic and clinicopathological characteristics, higher pCR rate observed in breast cancer with hormone-receptor negative (OR:2.845, 95%CI 1.791-4.520, p<0.001) and HER2 negative (OR:2.823, 95%CI=1.6-4.984, p<0.001) tumor and high ki-67 level (OR:2.165, 95%CI 1.347-3.480, p=0.001), irrespective of gBRCA1/2 mutation. In this analysis, patients with gBRCA1/2 mutations showed no significantly different response in neoadjuvant systemic therapy. Further large-scale analysis with survival data may provide robust evidence on the impact of the gBRCA1/2 mutation status for breast cancer patients.

Neoadjuvant systemic therapy for breast cancer.

The role of neoadjuvant therapy in the management of breast cancer has evolved dramatically over the past few decades. Preoperative treatment has the potential to downstage tumours and improve breast conservation rates as well as reduce the morbidity of axillary surgery. Furthermore, the in vivo sensitivity of the primary tumour to systemic therapy may be assessed at the time of final pathology when treatment is administered before operation. Monitoring of treatment response provides important prognostic and predictive information, with a pathological complete response (pCR) being associated with improved oncological outcomes1. Adjuvant therapy may also be affected in patients with residual disease who do not attain a pCR2–4. Neoadjuvant therapy for breast cancer may involve chemotherapy or endocrine therapy. The focus of this review is neoadjuvant therapy for the primary tumour in the breast. Axillary management after neoadjuvant therapy has been discussed previously5–8 and is beyond the scope of this review.

Axillary Pathologic Complete Response after Neoadjuvant Systemic Therapy of Breast Cancer in Patients with Initially Clinically Node-Positive Disease

Journal of the American College of Surgeons 236(5):p S8, May 2023. | DOI: 10.1097/01.XCS.0000932296.31500.6a