Neoadjuvant Treatment Of Breast Cancer Research Articles

Efficacy comparisons of solvent-based paclitaxel, liposomal paclitaxel, nanoparticle albumin-bound paclitaxel, and docetaxel after neoadjuvant systemic treatment in breast cancer

PurposeThere are four kinds of taxanes: solvent-based paclitaxel (Sb-P), liposomal paclitaxel (Lps-P), nanoparticle albumin-bound paclitaxel (Nab-P), and docetaxel. This study aims to retrospectively evaluate the efficacy of different taxanes on neoadjuvant systemic treatment (NST) in breast cancer. MethodsPatients who were diagnosed with breast cancer and had received integral NST from August 2013 to April 2022 were enrolled. The efficacy was divided into total pathological complete response (total-pCR), breast pathological complete response (breast-pCR), and axillary pathological complete response (axillary-pCR) for in-depth analysis and discussion. ResultsThe choice of taxane was an independent risk factor for total-pCR and breast-pCR rates. The highest total-pCR and breast-pCR rates were found in the Nab-P group. The difference was not significant among all the taxanes in the axillary-pCR rate. ConclusionNab-P significantly improved the total-pCR and breast-pCR rates. It should be the first choice among taxanes in NST for breast cancer.

Can multi-modal radiomics using pretreatment ultrasound and tomosynthesis predict response to neoadjuvant systemic treatment in breast cancer?

ObjectivesResponse assessment to neoadjuvant systemic treatment (NAST) to guide individualized treatment in breast cancer is a clinical research priority. We aimed to develop an intelligent algorithm using multi-modal pretreatment ultrasound and tomosynthesis radiomics features in addition to clinical variables to predict pathologic complete response (pCR) prior to the initiation of therapy.MethodsWe used retrospective data on patients who underwent ultrasound and tomosynthesis before starting NAST. We developed a support vector machine algorithm using pretreatment ultrasound and tomosynthesis radiomics features in addition to patient and tumor variables to predict pCR status (ypT0 and ypN0). Findings were compared to the histopathologic evaluation of the surgical specimen. The main outcome measures were area under the curve (AUC) and false-negative rate (FNR).ResultsWe included 720 patients, 504 in the development set and 216 in the validation set. Median age was 51.6 years and 33.6% (242 of 720) achieved pCR. The addition of radiomics features significantly improved the performance of the algorithm (AUC 0.72 to 0.81; p = 0.007). The FNR of the multi-modal radiomics and clinical algorithm was 6.7% (10 of 150 with missed residual cancer). Surface/volume ratio at tomosynthesis and peritumoral entropy characteristics at ultrasound were the most relevant radiomics. Hormonal receptors and HER-2 status were the most important clinical predictors.ConclusionA multi-modal machine learning algorithm with pretreatment clinical, ultrasound, and tomosynthesis radiomics features may aid in predicting residual cancer after NAST. Pending prospective validation, this may facilitate individually tailored NAST regimens.Clinical relevance statementMulti-modal radiomics using pretreatment ultrasound and tomosynthesis showed significant improvement in assessing response to NAST compared to an algorithm using clinical variables only. Further prospective validation of our findings seems warranted to enable individualized predictions of NAST outcomes.Key Points• We proposed a multi-modal machine learning algorithm with pretreatment clinical, ultrasound, and tomosynthesis radiomics features to predict response to neoadjuvant breast cancer treatment.• Compared with the clinical algorithm, the AUC of this integrative algorithm is significantly higher.• Used prior to the initiative of therapy, our algorithm can identify patients who will experience pathologic complete response following neoadjuvant therapy with a high negative predictive value.

Radiomics of magnetic resonance imaging for assessment of pathological complete response to neoadjuvant therapy and long-term survival in breast cancer

Breast cancer (BC) is the most common malignant disease. The use of neoadjuvant drug therapy increases the likelihood of achieving a complete pathomorphological response (pCR), leads to an increase in resectability and ablation; helps to determine the sensitivity of tumor cells to chemopreventive agents, thereby improving the patient’s prognosis. Since pathomorphological assessment occurs aſter surgery, it is necessary to develop methods for non-invasive response assessment for timely correction of the volume of treatment. One such method is magnetic resonance imaging (MRI). Assessment of the obtained images using texture analysis allows to increase the accuracy of the method both in the control of neoadjuvant treatment and in the assessment of the response to neoadjuvant therapy during preoperative planning.This article provides an analysis of the literature data on the potential to improve the prognostic value of breast MRI in assessing the complete pathomorphological response to neoadjuvant drug treatment of breast cancer using texture analysis of data.

Neoadjuvant Doxorubicin-Paclitaxel Combined Chemotherapy in Patients with Inoperable Stage III Breast Cancer: A Retrospective Cohort Study with 10 Years of Follow-Up in Vietnam.

The combination of doxorubicin and paclitaxel (AP) is widely used in our country for the neoadjuvant treatment of breast cancer as well as metastatic breast cancer. The AP regimen has shown promise as a neoadjuvant therapy for breast cancer that improves pathological complete response (pCR), increases the rate of conservative surgery, and improves the survival of patients. However, up to now, no research has evaluated the response of this regimen for the neoadjuvant treatment of advanced breast cancer, especially with a 10-year period of follow-up. This retrospective analysis reviewed 126 patients with inoperable stage III breast cancer who received neoadjuvant chemotherapy with doxorubicin 50mg/m2 plus paclitaxel 175mg/m2 every 3weeks for a maximum of six courses followed by surgery. pCR was evaluated. Survival was analyzed for all breast cancer patients using Kaplan-Meier and log-rank models. Of 126 women treated with neoadjuvant chemotherapy (NAC), the overall pCR rate was 25.4% and was significantly higher in patients with tumor stage cT1-T2, hormone receptor-negative (HR-negative), and human epidermal growth factor receptor 2 (HER2)-positive disease. Patients achieving pCR had significantly longer disease-free survival (DFS) and overall survival (OS). Ten-year DFS rates were 43.8% vs. 25.0% (p = 0.030) and 10-year OS rates were 59.4% vs. 28.9% (p = 0.003) for patients with pCR and non-pCR, respectively. The cumulative 10-year DFS was 19.6% for patients with HR-negative disease and 37.3% for those with HR-positive disease. Achieving pCR was associated with improved 10-year OS and DFS. Several clinicopathological features were closely associated with pCR in the inoperable stage III breast cancer patients who were treated by neoadjuvant chemotherapy. Achieving pCR was associated with improved 10-year OS and DFS. Patients with advanced breast cancer with HR-negative and HER2-positive status who benefited from the AP neoadjuvant therapy regimen were significantly more likely to achieve pCR.

Taxane combined with lobaplatin or anthracycline for neoadjuvant treatment of triple-negative breast cancer: A single-center, randomized, controlled, phase-II clinical study.

593 Background: Previously, we showed that addition of lobaplatin (L) to taxane combined with anthracycline could improve the pathologic complete response (pCR) rate and lengthen survival significantly if employed as neoadjuvant therapy in patients with triple-negative breast cancer (TNBC). We evaluated the efficacy and safety of neoadjuvant chemotherapy of taxane (T) combined with lobaplatin (L) or anthracycline (E) for patients with TNBC. Methods: Ninety-five patients with TNBC (stage I–III) who had not undergone any type of treatment were divided randomly into two groups: TL (docetaxel at 75 mg/m2 and lobaplatin at 30 mg/m2, D1, one cycle = 21 days, a total of six cycles) or TE (docetaxel at 75 mg/m2 and epirubicin at 80 mg/m2, D1, one cycle = 21 days, a total of 6 weeks or epirubicin at 80 mg/m2 and cyclophosphamide at 600 mg/m2, sequential docetaxel at 75 mg/m2, D1, one cycle = 21 days, a total of eight cycles). Efficacy was evaluated every two cycles. The final surgical procedure was completed after fulfillment of neoadjuvant chemotherapy. The primary endpoint was the total pathologic complete response (tpCR) rate. The secondary endpoints were the objective response rate (ORR), safety, event-free survival (EFS), and overall survival (OS). The exploratory endpoint was biomarker analysis. Results: From June 2019 to November 2022, 97 patients were screened. Finally, 95 patients were enrolled. The median age of the study cohort was 49 years. Nine patients (9.5%) had stage-I disease, 61 patients (64.2%) had stage II, and 25 patients (26.3%) had stage III. Sixty-five patients (68.4%) had Ki67 ≥40% and 30 patients (31.6%) had Ki67 < 40%. Seventy patients (73.7%) were cytokeratin (CK)5/6+ and 25 patients (26.3%) were CK5/6−. Of 95 patients, 47 were in the TL group and 48 in the TE group. The tpCR rate in the TL group was 46.8% (22/47), which was significantly higher than that in the TE group (22.9% (11/48); odds ratio (OR) = 2.960, 95% confidence interval (CI) = 1.223–7.164, P = 0.016). The ORR in the TL group was 95.7% (45/47), which was significantly higher than that in the TE group (75.0% (36/48); OR = 27.500, 95% CI = 1.576–35.683, P = 0.011). The prevalence of grade III/IV neutropenia in the TE group was 41.0% (9/22), which was significantly higher than that in the TL group (7.7% (2/26); OR = 8.308, 95% CI = 1.557–44.320, P = 0.013). There was no significant difference in the prevalence of other adverse reactions between the two groups. Conclusions: In the neoadjuvant treatment of TNBC, the TL regimen had a higher tpCR rate and ORR than those of the TE regimen, and was safer. Clinical trial information: ChiCTR1900023776 .

Phase II trial of delta-tocotrienol in neoadjuvant breast cancer with evaluation of treatment response using ctDNA

Neoadjuvant treatment of breast cancer is applied to an increasing extent, but treatment response varies and side effects pose a challenge. The vitamin E isoform delta-tocotrienol might enhance the efficacy of chemotherapy and reduce the risk of side effects. The aim of this study was to investigate the clinical effect of delta-tocotrienol combined with standard neoadjuvant treatment and the possible association between detectable circulating tumor DNA (ctDNA) during and after neoadjuvant treatment with pathological treatment response. This open-label, randomized phase II trial included 80 women with newly diagnosed, histologically verified breast cancer randomized to standard neoadjuvant treatment alone or in combination with delta-tocotrienol. There was no difference in the response rate or frequency of serious adverse events between the two arms. We developed a multiplex digital droplet polymerase chain reaction (ddPCR) assay for the detection of ctDNA in breast cancer patients that targets a combination of two methylations specific for breast tissue (LMX1B and ZNF296) and one cancer specific methylation (HOXA9). The sensitivity of the assay increased when the cancer specific marker was combined with the ones specific to breast tissue (p < 0.001). The results did not show any association between ctDNA status and pathological treatment response, neither at midterm nor before surgery.

Tumor suppressor genes and their interactions and neo-adjuvant therapy in paclitaxel resistance in cancer

Paclitaxel (PTX) is a drug that is often used in the treatment of solid tumours. However, PTX resistance is a significant impediment to cancer therapy. Exploration of drug resistance mechanisms reveals that tumour suppressor genes (TSGs) play a critical role in chemotherapeutic drug responsiveness. TSGs, a group of genes that are frequently inactivated in cancer, have the ability to control a variety of biological processes. A systematic study of paclitaxel and paclitaxel-containing chemotherapy regimens for advanced gastric cancer was conducted. Response rates, median progression-free survivals, and median overall survivals were studied, as well as the treatment regimens and patient numbers in each study. Taxanes, which are suggested in the adjuvant environment, are also taken into account in the neoadjuvant setting. There were twenty studies using nab-paclitaxel in the neoadjuvant context found. In the neoadjuvant treatment of breast cancer, nab-Paclitaxel displayed anticancer efficacy and a tolerable safety profile. Current and upcoming trials will assess preoperative nab-paclitaxel in breast cancer, including in conjunction with a variety of new immune targeted treatments.

Abstract 5627: Spatial protein profiling by cyclic immunofluorescence to interpret and improve bulk tumor-based predictor of response to chemotherapy with bevacizumab in neoadjuvant breast cancer treatment

Abstract Introduction: A limited number of drugs are available for use in breast cancer patients, and several are not in practical use due to the lack of adequate biomarkers. We have recently demonstrated the feasibility of using machine learning on molecular data from bulk tumor analysis to create a nine-protein signature named VEGF-inhibition Response Predictor (ViRP) for selecting BC patients for treatment with chemotherapy and bevacizumab. The ViRP score is currently being validated in the NAPEER+ clinical trial (EudraCT 2021-005850-27). Increasing evidence suggests that spatial organization of cells within the tumor microenvironment influences survival and response to therapy in numerous cancer types. In methods based on bulk tumor analysis all tumor cells are profiled simultaneously with both colocalized and distant stroma and immune cells. We are thus pursuing information on spatial organization of cellular phenotypes expressing selected cancer related proteins including our nine ViRP proteins. Methods: From the NeoAva (NCT00773695) clinical trial evaluating the effect of bevacizumab in combination with neoadjuvant chemotherapy (n=132 pts), FFPE tissue sections from patients before, during, and after treatment were made. Cyclic immunofluorescence (cyCIF) was used to profile the spatial expression of 32 cancer-signaling and 32 immune-related proteins, comprising our nine ViRP proteins, on FFPE tissue sections from selected patients (n = 20). The Galaxy-ME platform was used for image processing and downstream analysis of spatial protein profiling. Results: Use of cyCIF for spatial analysis enabled for evaluation of malignant cells in the context of surrounding microenvironmental cells, including immune cells. We found that cell type-specific protein abundance and subcellular localization formed a highly heterogenous pattern in the tissue. This was particularly evident for the nine ViRP proteins, and differences in expression between tumor cell populations will be further elucidated. Among the patients selected for cyCIF analysis, 4 were chosen based on misclassification by the ViRP signature. Ongoing studies focus on revealing spatial expression patterns to optimize the ViRP biomarker and explore why misclassification occurs. Furthermore, the observed molecular biology of the evolving tissues under treatment in responding and non-responding patients may reveal new biomarkers indicative of treatment response or resistance. Conclusion: We observe that the expression of proteins in tumor tissues is highly heterogeneous, and thus include numerous features not captured by bulk tumor analysis. Future development of new predictive tools and biomarkers that integrate molecular data which is multiparametric and spatial will set the stage for a new class of biomarkers in cancer diagnostics. Citation Format: Mads Haugland Haugen, David Kilburn, Hongli Ma, Cameron Watson, Allison Creason, Dong Zhang, Maria Aa Dahle, Ole Christian Lingjaerde, Marianne L. Smebye, Oeystein Garred, Mette S. Foersund, Mai T. Nguyen, Gunhild M. Maelandsmo, Gordon Mills, Olav Engebraaten. Spatial protein profiling by cyclic immunofluorescence to interpret and improve bulk tumor-based predictor of response to chemotherapy with bevacizumab in neoadjuvant breast cancer treatment. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5627.

Efficacy and safety of concomitant chemo-endocrine therapy in neoadjuvant treatment of hormone-positive HER2-negative breast cancer: a systemic review and meta-analysis

ABSTRACT Background The rate of pathological complete response (pCR) with both chemotherapy alone (CT) and endocrine therapy (ET) in the neoadjuvant (Na) treatment of hormone receptor (HR)-positive/HER2-negative breast cancer (BC) is unsatisfactory. Limited data on neoadjuvant concomitant chemotherapy and endocrine therapy (NaCET) are available. Research design and methods In this meta-analysis analyzed the efficacy and safety of randomized controlled trials (RCT) comparing the use of NaCET in HR-positive/HER2-negative BC. A comprehensive search was performed on PubMed, Cochrane Library and EMBASE databases, and congress paper lists for studies published/presented until 1 December 2022. Results Five RCTs involving a total of 630 patients were included. A pooled analysis of the five studies demonstrated that the pCR ratio was numerically higher in the NaCET arm than in the NaCT arm, but the difference was not statistically significant (6.5% vs. 3.8%; OR:1.72, 95% CI 0.82–3.62). Nonetheless, the NaCET arm exhibited a significantly higher objective response rate (ORR) (82% vs. 72.7%; OR:1.77, 95% CI 1.20–2.62). There was no difference between the arms in terms of grade 3–5 adverse events. Conclusions In HR-positive/HER2-negative BC, NaCET significantly increases ORR without an increase in serious adverse events. Although the pCR rate increased numerically, it was not statistically significant.

P120 Cardiac safety of pertuzumab, trastuzumab and standard chemotherapy as neoadjuvant treatment for HER2 positive breast cancer: real world data from NeoPowER trial

P120 Cardiac safety of pertuzumab, trastuzumab and standard chemotherapy as neoadjuvant treatment for HER2 positive breast cancer: real world data from NeoPowER trial

A different yet traditional approach to neoadjuvant treatment of breast cancer: The combination of epirubicin and docetaxel

A different yet traditional approach to neoadjuvant treatment of breast cancer: The combination of epirubicin and docetaxel

Abstract P2-01-08: The Efficacy of Anlotinib Combined with TEC in Neo-adjuvant Treatment for Triple-Negative Breast Cancer and The Value of Multi-point Core Needle Biopsy in Prediction of Pathologic Complete Remission: A Retrospective analysis

Abstract background While neo-adjuvant anthracycline and taxane-based chemotherapy remains the standard of care for locally advanced TNBC, the optimal chemotherapy regimen is debatable. Anlotinib, a novel multi-target tyrosine kinase inhibitor that effectively inhibits VEGFR, FGFR, c-KIT, c-MET, and RET, monotherapy has been proven effective in HER-2 negative metastatic breast cancer. This study aims to evaluate the efficacy and safety of anlotinib combined with TEC in neo-adjuvant treatment for locally advanced TNBC, and to evaluate the value of predicting pathological response by multi-point core needle biopsy during neo-adjuvant therapy. method This study retrospectively analyzed 18 patients (Pts) with locally advanced triple-negative breast cancer who received anlotinib combined with TEC neo-adjuvant therapy and surgical treatment from August 2020 to January 2022 in the Breast Diagnosis and Treatment Center of Anhui Cancer Hospital. Pts with clinical stage IIb/III TNBC were to be treated with 6 cycles of anlotinib (12mg, d1-14, q3w) plus 6 cycles of docetaxel (75 mg/m2, d1, q3w), Epirubicin (90 mg/m2, d1, q3w) and cyclophosphamide (600 mg/m2, d1, q3w) followed by surgery. Before the fifth cycle of treatment, ultrasound-guided multi-point Core needle biopsy was performed to evaluate the efficacy of neo-adjuvant therapy and predict the pathological complete response, as well as to guide the selection of surgical methods. The primary endpoint was pathological complete response (pCR, ypT0/is). Result Eighteen pts, the median age was 48 years (range, 23-60), were included in the statistical analysis. All patients completed 6 cycles of anlotinib combined with TEC neo-adjuvant therapy followed by radical mastectomy for breast cancer. Regarding pathological response, there were 4 (22.2%), 2 (11.1%), and 12 (66.7%) patients realizing Miller-Payne grade G3, G4, and G5, respectively. Besides, 12 (66.7%) patients achieved pCR. Additionally, the accuracy of multi-point core needle biopsy in predicting pCR was 94.4% in the interval between neo-adjuvant therapy. The grade 3 or 4 AEs were neutropenia and thrombocytopenia in 3 cases each, anemia, arrhythmia, and ALT increased in cases 1 case each. One patient dropped out of the group due to tumor rupture and bleeding. conclusion Anlotinib combined with TEC as neo-adjuvant therapy showed manageable toxicity and promising antitumor activity for locally advanced TNBC. It is safe, reliable, feasible and accurate to evaluate the efficacy of neo-adjuvant therapy and to predict pathological complete response by multi-point core needle biopsy. It means that the clinical evaluation of neo-adjuvant therapy can transition from imaging evaluation to pathological evaluation, which is helpful for the choice of surgical methods. Citation Format: Kuojun Ren, Shikai Hong, Zhengzhi Zhu, Shengying Wang, Jianjun Liu, Hong Gao, Shuhan Wang. The Efficacy of Anlotinib Combined with TEC in Neo-adjuvant Treatment for Triple-Negative Breast Cancer and The Value of Multi-point Core Needle Biopsy in Prediction of Pathologic Complete Remission: A Retrospective analysis [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-01-08.

Abstract P5-10-01: Phase 2 study of anlotinib combined with taxanes and lobaplatin in the neoadjuvant treatment of triple-negative breast cancer: efficacy, safety and biomarker analysis from the SWH-B006 (neoALTALL) trial

Abstract Background: Anlotinib, a novel multi-target tyrosine kinase inhibitor that effectively inhibits VEGFR, PDGFR, FGFR, c-KIT, c-MET, and RET, monotherapy has been proven effective in HER-2 negative metastatic breast cancer, but its efficacy in early-stage triple-negative breast cancer (TNBC) is unknown. This phase 2 study aims to evaluate the efficacy and safety of adding anlotinib to neoadjuvant chemotherapy in patients (pts) with primary TNBC. Methods: Pts with clinical stage II/III TNBC were to be treated with 5 cycles of anlotinib (12mg, d1-14, q3w) plus 6 cycles of taxanes (docetaxel 75 mg/m2 or nab-paclitaxel 125 mg/m2, d1 and d8, q3w) and lobaplatin (30 mg/m2, d1, q3w), followed by surgery. The primary endpoint was pathological complete response (pCR) in the breast and axilla (tpCR; ypT0/is ypN0) and the secondary endpoints include pCR in the breast (bpCR; ypT0/is), event-free survival (EFS), invasive disease-free survival (iDFS), overall survival (OS), and safety. Exploratory study included biomarker analysis and efficacy comparation based on FUSCC classification (IHC-based). Results: From Jan 2021 to Feb 2022, a total of 24 pts were enrolled. The median age was 50 years (range, 26-64), 54% were postmenopausal, 75% were nodal involved, 29% had stage III, and 79% were Ki-67 high (≥30%). At the data cut off time of 30th Jun 2022, all 24 pts received at least one dose of study treatment and underwent surgery. Overall, 21 pts received five courses of anlotinib. Two pts discontinued anlotinb for safety reason, and one pt discontinued anlotinb due to missed dose in cycle 4. After surgery, 14 out of 24 pts achieved a tpCR (58.3%; 95% CI, 36.6%–77.9%), and the bpCR rate was also 58.3% (14/24). Of the 18 pts with the node-positive disease at diagnosis, 15/18 (83.3%) became ypN0. Based on the FUSCC IHC-based subtypes, the tpCR rates were 66.7% (6/9) for BLIS subtype, 80% (4/5) for IM subtype and 0% (0/4) for LAR subtype, respectively. Next-generation sequencing revealed that the most commonly mutated genes in these pts were TP53 (19/21, 90.5%), MYC (7/21, 33.3%), BRCA1 (5/21, 23.8%), PIK3CA (4/21, 19.0%), BCL2L11 (4/21, 19.0%), and RB1 (3/21, 14.3%). Subgroup analysis showed that the tpCR were 71.4% (5/7) and 42.9% (6/14) in MYC-amplified and wild-type pts, respectively, and 80% (4/5) and 43.8% (7/16) in BRCA1-mutated and wild-type pts, respectively. All of 24 pts in the safety population showed at least one treatment emergent adverse events (TEAEs). Grade 3 or 4 TEAEs occurred in 14 pts (58.3%), and the most common events were leucopenia (29.2%; n=7), neutropenia (29.2%; n=7), thrombocytopenia (20.8%; n=5), anemia (16.7%; n=4), hypertension (12.5%; n=3), and oral mucositis (8.3%; n=2), respectively. No treatment-related deaths occurred. Conclusions: The addition of anlotinib to neoadjuvant chemotherapy showed manageable toxicity and promising antitumor activity for pts with early-stage TNBC. The study is still ongoing, and the enrollment has been completed. Clinical trial information: ChiCTR2100043027. Funding: Chia Tai Tianqing Pharmaceutical Group Co., Ltd. L. Corresponding author: Dr. Xiaowei Qi, qxw9908@foxmail.com. Department of Breast and Thyroid Surgery, Southwest Hospital, Army Medical University, Chongqing. Citation Format: Yan Liang, Jing Liu, Tao Luo, Jia Ge, Hao Tian, Guozhi Zhang, Linjun Fan, Lin Ren, Li Chen, Peng Tang, Kai Zhu, Xiuwu Bian, Jun Jiang, Yi Zhang, Xiaowei Qi, Peng Tang, Kai Zhu, Xiuwu Bian, Jun Jiang, Yi Zhang, Xiaowei Qi. Phase 2 study of anlotinib combined with taxanes and lobaplatin in the neoadjuvant treatment of triple-negative breast cancer: efficacy, safety and biomarker analysis from the SWH-B006 (neoALTALL) trial [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-10-01.

Abstract P1-11-18: The efficacy and safety of trastuzumab and pertuzumab in combination with different chemotherapy regimens for neoadjuvant treatment of HER2-posotive breast cancer: a multi-center real-world study in China

Abstract Background: Dual HER2 targeted therapy with trastuzumab (H) and pertuzumab (P) has been approved as neoadjuvant therapy for patients with HER2-positive breast cancer in China in 2019 based on the results from NeoSphere and PEONY study. However, the real-world efficacy and safety data are currently lack of evidence in China. Therefore, this multi-center real-world study aims to retrospectively analyze the efficacy and safety of neoadjuvant trastuzumab and pertuzumab combined with different chemotherapy regimens of HER2-positive early breast cancer. Methods: Patients received trastuzumab and pertuzumab in combination with different chemotherapy regimens, including taxanes (T), cyclophosphamide (C), anthracyclines (A) were collected retrospectively from 12 centers. The primary endpoint was total pathological complete response (tpCR, ypT0/is ypN0) rate. Results: A total of 357 patients were enrolled, among which 204 (57.5%) recieved TCbHP, 92 (25.9%) recieved EC-THP, and 51 (14.4%) received THP as chemotherapy regimens. The median age was 48 years old (range, 22-76), 142 (39.8%) of patients were classified as hormone receptor (HR)-positive, and 215 (60.2%) were HR-negative. The overall tpCR rate was 58.5% (95%CI, 53.2%-63.7%). tpCR rate for HR-negative patients was significantly higher than HR-positive patients (65.6% vs. 47.9%, p=0.001) and there was not any statistical difference according to chemotherapy regimens (56.9% for TCbHP, 56.5% for EC-THP, and 66.7% for THP, p=0.445). The most common adverse events included anemia (40.1%), white blood cell count decreased (34.3%), ejection fraction decreased (19.5%), Alanine aminotransferase increased (18.9%), platelet count decreased (12.8%) and neutrophil count decreased (12.0%). There was not any toxicity leading to death. Conclusions: Multi-center real-world data show satisfactory tpCR rate and tolerable adverse events of trastuzumab and pertuzumab in combination with different chemotherapy regimens in China. Citation Format: Xiaowei Qi, Hong Hu, chen wenlin, xu yan, liu shu, fang yanman, Taolang Li, ming jia, zhou sihai, chai fan, liang yueyang, fan yuanming, Yi Zhang, Peng Tang, jiang jun, nie jianyun, Li Chen, Shushu Wang. The efficacy and safety of trastuzumab and pertuzumab in combination with different chemotherapy regimens for neoadjuvant treatment of HER2-posotive breast cancer: a multi-center real-world study in China [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-11-18.

Abstract P6-04-08: Machine learning-based characterization of the breast cancer tumor microenvironment for assessment of neoadjuvant-treatment response

Abstract Background: Neoadjuvant treatment of breast cancer has been shown to potentially reduce the extent and morbidity of subsequent surgery. Response to neoadjuvant therapy may also be prognostic; complete pathologic response (pCR) following neoadjuvant treatment is associated with improved long-term outcomes. pCR, defined as the absence of residual invasive cancer, is determined by evaluation of H&amp;E-stained breast resections and regional lymph nodes following neoadjuvant treatment; however, pathologist assessment is subject to intra- and inter-reader variability. Here we report machine learning (ML)-based models to identify tissue regions and cell types in the tumor microenvironment (TME) of H&amp;E-stained breast cancer specimens. Model predictions were used to derive tumor bed area, a key component of the residual cancer burden score (RCB) used to assess neoadjuvant-treatment pathological response. Methods: Convolutional neural network (CNN) models were trained using digitized H&amp;E-stained whole slide images (WSIs) of 2700 neoadjuvant-treated breast cancer specimens (resections and biopsies) from 4 sources, and an additional 1100 breast cancer primary resections from TCGA. 229,901 pathologist annotations were used to train CNN models to segment tissue regions (cancer epithelium, stroma, diffuse inflammatory infiltrate, ductal carcinoma in situ, lymph nodes and necrosis) and cell types (cancer epithelial cells, fibroblasts, lymphocytes, macrophages, foamy macrophages and plasma cells) at single-pixel resolution. These tissue region segmentations were then used to derive tumor bed area using a convex hull algorithm. Each model was evaluated by board certified pathologists for performance. Model predictions of tumor bed area were evaluated in comparison to mean measurements from 3 pathologists for each of 22 held-out test slides. To further assess cell model performance, 5 pathologists exhaustively annotated 120 frames (300 x 300 pixels) on test samples from a dataset not used in model development (N=536; resections and biopsies) to produce consensus ground truth cell labels. Model predictions were compared with pathologist annotations in these frames using Pearson correlation, precision, recall, and F1 metrics. Only those classes with greater than 50 consensus cells identified were evaluated. Results: CNN predictions of tissue and cell classes within H&amp;E breast cancer WSIs showed concordance with manual pathologist consensus labels. The weighted average Pearson correlation (across the relevant cell types) between the model and consensus was 0.75, comparable to the correlation of 0.81 between pathologists and consensus. Classification metrics for each cell class are reported in Table 1. Reduced performance of the model relative to the average pathologist performance may be due to heterogeneous slide characteristics and infrequency of some cell types in the data. For prediction of tumor bed area, CNN model predictions showed moderate correlation with pathologist consensus (Pearson r=0.65, 95% CI: 0.38-0.81). Conclusions: CNN model classification of cell types and tissue regions across entire H&amp;E breast cancer WSIs shows concordance with pathologist consensus. Model predictions of tumor bed area also show concordance with pathologist assessment and can be used to derive the RCB score. These models can be reproducibly applied to quantify diverse histological features in large datasets, potentially enabling improved standardization and efficiency of pathologist evaluation of the breast cancer TME and neoadjuvant response. Classification Metrics for Individual Cell Classes Citation Format: Christian Kirkup, Sanjana Vasudevan, Filip Kos, Benjamin Trotter, Murray Resnick, Andrew H. Beck, Michael Montalto, Ilan Wapinski, Ben Glass, Mary Lin, Stephanie Hennek, Archit Khosla, Michael G. Drage, Laura Chambre. Machine learning-based characterization of the breast cancer tumor microenvironment for assessment of neoadjuvant-treatment response [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-04-08.

Abstract P1-11-20: Trastuzumab (HLX02) plus Pertuzumab as Dual-target Neoadjuvant Therapy for HER2-positive Breast Cancer: A Real-World Study

Abstract Background: The effect of neoadjuvant therapy on tumor downstaging and breast-conserving during surgery is well documented. Pathologic complete response (pCR) after neoadjuvant treatment was associated with long-term survival. HLX02 (Zercepac®), a biosimilar of trastuzumab, showed the same efficacy, safety, and immunogenicity as the reference drug in human epidermal growth factor receptor-2 (HER2)-positive patients. Despite this, real-world evidence of its effectiveness when combined with pertuzumab in neoadjuvant treatment of HER-2 positive breast cancer still lacks. Methods: In this retrospective real-world study, women with confirmed invasive HER2-positive breast cancer who have received chemotherapy plus HLX02 and pertuzumab (Perjeta®) as neoadjuvant therapy were enrolled. Patients must be over 18 years old, have an Eastern Cooperative Oncology Group performance status score of 0 or 1, and have a baseline left ventricular ejection fraction of ≥ 55%. Patients without pathological assessment after neoadjuvant therapy were excluded. Pathologic complete response (pCR) was defined as no residual invasive tumors in mammary glands and axillary lymph nodes. Clinical response was assessed using RECIST1.1. To investigate the factors associated with pCR, univariate and multivariate logistic regression (forward stepwise) analyses were conducted. Results: A total of 85 patients were enrolled in this study, and 55 patients (64.71%) achieved pCR after neoadjuvant therapy. There were 84 (98.82%) patients with partial response (PR), one (1.18%) patient with stable disease (SD). According to the univariable analysis, when compared to those with a tumor diameter ≤ 5 cm, patients with a tumor diameter &amp;gt; 5 cm at baseline showed a lower pCR rate (odds ratio [OR] = 0.286; 95% confidence interval [CI]: 0.108-0.758, P = 0.01). Patients with preoperative PR positivity &amp;gt; 10% showed lower pCR rate than those with preoperative PR positivity &amp;lt; 1% (OR = 0.115, 95% CI 0.036-0.372, P = 0.02). Besides, pCR was more common in patients with preoperative hormone receptor (HR)-negative than in those with preoperative HR-positive (ER or PR positivity &amp;gt; 10%) (OR = 4.452, 95% CI 1.679-11.804, P &amp;lt; 0.01). Multivariable analyses showed that patients with tumor diameter &amp;gt; 5 cm had a lower pCR rate than those with tumor diameter ≤ 5cm (OR = 0.213; 95% CI 0.070-0.644, P = 0.01). Patients with preoperative HR-negative tumors were more likely to achieve pCR than those with preoperative HR-positive tumors (OR =5.649, 95% CI 1.927-16.556, P &amp;lt; 0.01) (Table 1). The treatment were well tolerated by patients, and no additional adverse events were reported. Conclusion: According to this real-world study, HLX02 in combination with pertuzumab as neoadjuvant therapy for HER2-positive breast cancer patients showed a similar pCR rate to that of dual-target neoadjuvant therapy reported in previous clinical trials. The treatment showed an encouraging effectiveness, and may become a novel neoadjuvant option for patients with HER2-positive breast cancer. The study was supported by the Natural Science Foundation of Shanghai (21ZR1414700). Table 1. Logistic regression for pCR. Citation Format: Yin Liu, Wen-Jia Zuo, Ruo-Xi Wang, Zhong-Hua Wang, Zhi-Ming Shao. Trastuzumab (HLX02) plus Pertuzumab as Dual-target Neoadjuvant Therapy for HER2-positive Breast Cancer: A Real-World Study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-11-20.

Abstract P3-07-25: Efficacy and safety of neoadjuvant pertuzumab biosimilar TQB2440, trastuzumab and docetaxel in HR negative, HER2 positive breast cancer: a single-arm trial

Abstract Background: Despite that dual anti-HER2 therapy (Trastuzumab and Pertuzumab, TP) is one of the commonly used regimens for neoadjuvant treatment of HER2-positive breast cancer, previous studies showed that its pCR rate rarely exceeds 63%. Additionally, it is associated with higher risk of cardiac adverse events. TQB2440, a biosimilar of pertuzumab, with strong affinity and specificity, can effectively bind with HER2 epitope. In the PDX mouse model, TQB2440 showed promising biological activity and minimal cardiotoxicity. In this study, we designed a single-arm trial of dual anti-HER2 therapy (TQB2440 and trastuzumab, TT) plus docetaxel in neoadjuvant therapy of HER2 positive breast cancer. We aimed to examine the efficacy and safety of TQB2440 and study whether new dual anti-HER2 therapy (TT) can boost pCR rate in the neoadjuvant treatment. The cardiotoxicity and other adverse reactions were closely monitored. Methods: Upon approval by the Medical Ethics Committee of Xijing Hospital, patients with HR negative HER2-positive breast cancer (cT2-3/N0-1/M0) receiving neoadjuvant therapy were enrolled. The patients were treated with docetaxel 75 mg/m2, trastuzumab 8 mg/kg loading, then 6 mg/kg, TQB2440 840 mg loading, then 420 mg, iv, q3w for 4 cycles, with strict monitoring of cardiotoxicity. The primary endpoint was pCR rate, and secondary endpoint was cardiotoxicity. Results: From April 2021 to February 2022, a total of 28 patients were recruited. Among the 28 patients with a median age of 52 (28-74), 12 patients had positive lymph node status. Overall, the pCR rate was 67.9% (19/28). The pCR rate was higher than that in the NeoSphere trial (pCR 63.2%) and the PEONY study (pCR 52.5%). The lymph-positive tumor achieved a higher pCR rate than lymph-negative tumor (70.8% vs 52.3%, p = .019). Multivariate regression analysis showed that for participants aged 50 or above, HER2 3+ (IHC) showed a statistically significant positive influence on pCR rate. The common adverse reactions of grade ≥3 were leukopenia (46.4%), neutropenia (35.7%), asthenia (3.6%), and peripheral sensory neuropathy (2.3%). Left ventricular insufficiency was detected in 1 patient, and no cardiotoxic events higher than grade 2 occurred during the neoadjuvant therapy. There was no treatment-related death. Conclusion: TQB2440 and trastuzumab plus docetaxel is a feasible and effective neoadjuvant therapy for early-stage HR negative HER2-positive breast cancer, showing high pCR rate and acceptable cardiotoxicity. These results support a further random controlled trial testing for dual anti-HER2 therapy using TQB2440 in neoadjuvant or adjuvant therapy of HER2 positive breast cancer. Citation Format: Jiang Wu, Jing Yu, Yuqing Yang, Xinxin Wen, Jixin Yang, Hongliang Wei, Xiaolong Xu, Yike Li, Liu Yang, Dongdong Xu, Lei Wang, Yijia Wang, Wen Ma, Nanlin Li. Efficacy and safety of neoadjuvant pertuzumab biosimilar TQB2440, trastuzumab and docetaxel in HR negative, HER2 positive breast cancer: a single-arm trial [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-07-25.

Abstract OT2-18-03: Neoadjuvant anlotinib plus nab-paclitaxel based chemotherapy in patients with HER2-negative breast cancer: A prospective, single-arm, single-center, phase II clinical study

Abstract BACKGROUND: Antiangiogenic agent plus neoadjuvant chemotherapy confers an improvement in pathological complete response (pCR) rate among patients with HER2-negative breast cancer. Anlotinib is a novel multi-target tyrosine kinase inhibitor that effectively inhibit VEGFR, FGFR, c-KIT, c-MET, and RET. This phase II study aims to evaluate the efficacy and safety of anlotinib combined with chemotherapy as neoadjuvant treatment in HER2-negative breast cancer. PATIENTS AND METHODS: Eligible patients (pts) were women, aged 18-70 years, ECOG status 0-2, previously untreated HER2-negative breast cancer. The HER2-negative, defined as immunohistochemistry of 0, 1+, and 2+/ISH-. Pts were required to have a palpable primary tumor at least 200mm in diameter in the breast, as assessed by physical examination, and to be classified as having tumor stage T1c to T3, nodal stage N0 to N2a, and metastasis stage M0. Thirty pts will be enrolled and received 5 cycles of anlotinib (12 mg qd, d1-14; 21 days per cycle) plus 6 cycles of nab-paclitaxel (200 mg/m2, once every 3 weeks), anthracycline (pirarubicin 50 mg/m2) and cyclophosphamide at 500 mg/m2, followed by surgery. The primary endpoint is pCR rate (ypT0/Tis ypN0) and the secondary endpoints include disease-free survival (DFS), overall survival (OS), and safety. The study was initiated in August 2021.This study is currently open and 10 patients had been enrolled. The estimated primary completion date is October 1, 2023. Results: The trail is in progress. Conclusion: The trail is in progress. Citation Format: Jing Fan, Ting Wang, Huimin Meng, Songpeng Li, Jing Kong, Yidi Wang. Neoadjuvant anlotinib plus nab-paclitaxel based chemotherapy in patients with HER2-negative breast cancer: A prospective, single-arm, single-center, phase II clinical study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT2-18-03.

Surgical Planning after Neoadjuvant Treatment in Breast Cancer: A Multimodality Imaging-Based Approach Focused on MRI

Neoadjuvant chemotherapy (NACT) today represents a cornerstone in the treatment of locally advanced breast cancer and highly chemo-sensitive tumors at early stages, increasing the possibilities of performing more conservative treatments and improving long term outcomes. Imaging has a fundamental role in the staging and prediction of the response to NACT, thus aiding surgical planning and avoiding overtreatment. In this review, we first examine and compare the role of conventional and advanced imaging techniques in preoperative T Staging after NACT and in the evaluation of lymph node involvement. In the second part, we analyze the different surgical approaches, discussing the role of axillary surgery, as well as the possibility of non-operative management after-NACT, which has been the subject of recent trials. Finally, we focus on emerging techniques that will change the diagnostic assessment of breast cancer in the near future.

Is the Level of Contrast Enhancement on Contrast-Enhanced Mammography (CEM) Associated with the Presence and Biological Aggressiveness of Breast Cancer?

There is limited information about whether the level of enhancement on contrast-enhanced mammography (CEM) can be used to predict malignancy. The purpose of this study was to correlate the level of enhancement with the presence of malignancy and breast cancer (BC) aggressiveness on CEM. This IRB-approved, cross-sectional, retrospective study included consecutive patients examined with CEM for unclear or suspicious findings on mammography or ultrasound. Excluded were examinations performed after biopsy or during neoadjuvant treatment for BC. Three breast radiologists who were blinded to patient data evaluated the images. The enhancement intensity was rated from 0 (no enhancement) to 3 (distinct enhancement). ROC analysis was performed. Sensitivity and negative likelihood ratio (LR-) were calculated after dichotomizing enhancement intensity as negative (0) versus positive (1-3). A total of 156 lesions (93 malignant, 63 benign) in 145 patients (mean age 59 ± 11.6 years) were included. The mean ROC curve was 0.827. Mean sensitivity was 95.4%. Mean LR- was 0.12%. Invasive cancer presented predominantly (61.8%) with distinct enhancement. A lack of enhancement was mainly observed for ductal carcinoma in situ. Stronger enhancement intensity was positively correlated with cancer aggressiveness, but the absence of enhancement should not be used to downgrade suspicious calcifications.