pCR Rate In Patients Research Articles

Comparison of the treatment outcomes of different neoadjuvant chemoradiotherapy regimens for resectable locally advanced esophageal cancer

BackgroundNeoadjuvant chemoradiotherapy (nCRT) followed by radical esophagectomy is the standard treatment for locally advanced esophageal squamous cell cancer (LA-ESCC). However, various nCRT regimens have been used, and their comparative efficacy and safety remain unclear. MethodsPatients with histologically confirmed LA-ESCC who underwent nCRT followed by radical esophagectomy between January 2016 and February 2022 were enrolled in this study. Of note, 3 different nCRT regimens were retrospectively compared: conventional radiotherapy (RT) + cisplatin/5-fluorouracil (FP) (Conv-FP), hypofractionated RT + FP (Hypo-FP), and regimens from the ChemoRadiotherapy for Oesophageal cancer followed by Surgery Study (CROSS) trial (CROSS). The overall survival (OS), pathologic complete response (pCR), toxicity, and treatment compliance rates were analyzed. ResultsAmong the 600 patients, 225 received Conv-FP, 255 received Hypo-FP, and 120 received the CROSS regimen. The OS rates at 1 year were 78.7%, 83.9%, and 88.1% in the Conv-FP, Hypo-FP, and CROSS groups, respectively (P < .001). The pCR rates were 30.6%, 33.9%, and 35.0%, respectively (P = .653). The overall incidence of grade 3 toxicities was 10.2%. Hematologic and nonhematologic toxicities of grade ≥ 3 were observed in 8.4% and 11.4%, 0% and 7.6%, and 5.5% and 0.8% in the Conv-FP, Hypo-FP, and CROSS groups, respectively (P = .002 and P = .030). Weight loss of > 5% was observed in 44.0%, 51.4%, and 32.5% in the Conv-FP, Hypo-FP, and CROSS groups, respectively (P < .001). In the multivariate analysis, clinical T stage (P = .004), N stage (P = .012), FP chemotherapy regimen (P = .013), surgical resection (P < .001), hematologic toxicity (P = .001), and weight loss (P = .004) were significantly associated with poor OS. ConclusionThe choice of nCRT regimen did not significantly affect the pCR rates in patients with LA-ESCC. However, the CROSS regimen demonstrated better OS and lower toxicity, suggesting that it may be the optimal treatment option among the groups.

In situ HER2 RNA expression as a predictor of pathologic complete response of HER2-positive breast cancer patients receiving neoadjuvant chemotherapy and anti-HER2 targeted treatment

BackgroundImmunohistochemistry (IHC) and in situ hybridization (ISH) remain standard biomarkers for therapeutic decisions in human epidermal growth factor 2 (HER2)-positive breast cancers (BCs); however, they are insufficient to explain the heterogeneous anti-HER2 response.MethodsWe aimed to investigate the correlation of in situ HER2 RNA expression (isHRE), using RNAscope, with HER2 biomarkers and the impact of isHRE on the pathological complete response (pCR) rates of 278 patients with HER2 IHC/fluorescence ISH (FISH)-positive BC receiving neoadjuvant chemotherapy and anti-HER2 targeted treatment (NCTT).ResultsWe validated HER2 RNAscope scoring as a semiquantitative method to determine isHRE and showed a positive correlation between RNAscope scores and pCR rates, with particularly different rates between patients with a score of 5 versus 1–4 BCs (66.7% vs. 15.9%, p < 0.0001). There were higher RNAscope scores and pCR rates in patients with HER2 IHC 3 + versus IHC 2+/FISH + BCs and HER2 RNAscope scores and pCR rates showed similar non-linear positive correlations with HER2 copy numbers and HER2/centromere 17 ratios. Moreover, in each HER2-positive IHC/FISH category, higher pCR rates were observed in patients with RNAscope scores of 5 versus 1–4 BC. Patients achieving pCR had BCs with notably higher HER2 RNAscope scores. Multivariate analysis identified HER2 RNAscope 5 as a strong pCR predictor [odds ratio = 10.865, p < 0.001]. The combined impact of multivariate analysis-defined pCR predictors demonstrated that a higher pCR rate was observed in patients with a score of 5 versus a score of 1–4 BCs regardless of the status of hormone receptor and mono-or dual anti-HER2 blockade.ConcusionsOur results demonstrated that high isHRE (RNAscope score 5) is a strong pCR predictor in patients with HER2-positive BCs receiving NCTT, highlighting the complementary role of isHRE in stratifying HER2 status in tissue. Such stratification is relevant to anti-HER2 therapeutic efficacy, particularly using the cutoff of score 1–4 versus 5.

Neoadjuvant therapy using PD-1 inhibitor plus chemotherapy with different intervals between chemotherapy cycles for locally advanced gastric or gastroesophageal junction cancer: A randomized phase 2 study.

4064 Background: To explore the influence of reducing dose-intensity of chemotherapeutic agents by prolonging the interval of chemotherapeutic cycles on clinical efficacy, especially when combined with immune checkpoint inhibitors, we conducted a single-center, prospective, randomized, phase II exploratory study in patients with locally advanced gastric or gastroesophageal junction (G/GEJ) cancer. Methods: Patients were randomly assigned to receive either toripalimab plus FLOT regimen for four biweekly cycles or three triweekly cycles before the operation. The primary endpoint was pathological complete response (pCR) rate, the secondary endpoints were major pathological response (MPR) rate, event-free survival (EFS), and safety. Results: 70 patients were enrolled; of these, 69 were eligible for inclusion. The overall pCR rate was 26.1% and the MPR rate was 55.1%. There were no statistical differences in pCR rates and MPR rates between the two groups. Although no statistical differences were found among the subgroups, the pCR rate for patients with PD-L1 CPS ≥1 was 42.1% (8/19) while 6.7% (1/15) for PD-L1 CPS&lt;1 in the triweekly group ( P=0.047). Analysis of lymphocyte subsets in peripheral blood showed that CD3+CD8+PD-1+Ki-67+ T lymphocyte absolute counts were elevated in triweekly group and reduced in biweekly group before the second and third cycle of therapy. The incidence rates of pyrexia and myelosuppression in the biweekly group were higher than those in the triweekly group. Conclusions: These data support the idea that the efficacy of toripalimab plus FLOT, given triweekly for three cycles, was not inferior to its administration biweekly for four cycles in locally advanced G/GEJ cancer. The finding is particularly significant for those with PD-L1 CPS ≥1 and warrants further validation. Clinical trial information: NCT04891016 .

Immunotherapy-based therapy versus chemotherapy for the neoadjuvant treatment of locally advanced dMMR/MSI-H gastric cancer.

e16121 Background: Growing evidences have suggested that immunotherapy represents a promising treatment for the neoadjuvant treatment of mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) gastric cancer. The study aimed to compare the efficacy of neoadjuvant chemotherapy and immune checkpoint inhibitor (ICI)-based therapy in locally advanced, dMMR/MSI-H gastric cancer. Methods: Patients with MSI-H/dMMR locally advanced gastric cancer who received neoadjuvant chemotherapy, or ICI-based therapy between December 2018 and June 2023 at West China Hospital, Sichuan University were included. Patient data were collected from the prospectively database program of gastric cancer at our Hospital. Demographic and clinicopathologic data of patients were collected, including age, sex, ECOG performance status, primary tumor site, tumor staging, Lauren’s classification, tumor response, tumor regression grade (TRG), R0 resection, disease-free survival (DFS) and overall survival (OS). Results: A total of 21 patients treated with ICIs-based regimens and 18 patients treated with chemotherapy were included. In the ICI-based therapy group, 10 patients (47.6%) received dual PD-1 and CTLA-4 blockade, 1 patient (4.8%) received PD-1 blockade, and 10 patients (47.6%) received PD-1 blockade combined with chemotherapy. The median age of chemotherapy group and ICI-based group were 63 years (range, 36-76 years) and 59 years (range, 34-74 years), respectively. The rates of T4b and limited metastases were significantly higher in the ICI-based therapy group compared to chemotherapy group (T4b: 11.1% vs. 23.8%; limited metastases: 0% vs. 19.0%). 17 patients (94.4%) in the chemotherapy group and 20 patients (95.2%) in the ICI-based therapy group underwent R0 radical gastrectomy. One patient in the chemotherapy group did not undergo surgery due to disease progression. One patient in the ICI-based therapy group refused radical gastrectomy. For patients undergoing surgery, TRG 0-1 rate was obviously lower in patients receiving chemotherapy compared to those treated with ICI-based regimen (0.0% vs. 78.9%). The pCR rates in the chemotherapy group and ICI-based group were 0.0% and 57.9%, respectively. The pCR rates in patients treated with dual PD-1/CTLA-4 blockade and PD-1 blockade with chemotherapy were 66.6% and 50.0% (P = 0.65). Median DFS and OS have not yet been achieved due to the short follow-up time. Conclusions: Improvements in TRG 0-1 rate and pCR rate suggested that ICI-based treatments are favorable in the neoadjuvant setting of locally advanced, dMMR/MSI-H gastric cancer compared to chemotherapy. However, within the overall favorable group, there was no differences between dual PD-1/CTLA-4 blockade and PD-1 blockade with chemotherapy in term of pCR rate. Whether high pCR rates can translate into long-term survival benefits requires longer follow-up time.

Abstract PO1-24-03: The clinicopathological and prognostic significance of HER2-low breast cancer: A comparative analysis between HER2-low and HER2-zero subtypes

Abstract Background: HER2-low breast cancer (BC) is a newly defined subset of HER2-negative BC that has a HER2 immunohistochemical (IHC)-1+ or 2+/ISH negative phenotype. Recent clinical trials have demonstrated the clinical benefits of novel HER2 directing ADCs in treating this group. It is uncertain whether HER2-low BC represents a distinct biological/clinical subgroup or if the HER2-low categorization has any prognostic significance. We retrospectively investigated the clinicopathological and prognostic significance of HER2-low BC and compared it with HER2-0 BC. Methods: Primary BC patients who underwent surgery from January 2000 to March 2023 were enrolled in this retrospective study. A total of 10,215 invasive BC cases with Stage I-III were analyzed. The HER2 status was divided into 3 groups: HER2-0, HER2-low, and HER2-positive (3+ or 2+ with positive ISH). The clinicopathological factors investigated were age, nodal status, tumor size, nuclear grade (NG), ER/PgR (cutoff points; 1% and 10%), and the Ki-67 index value (cutoff points: 15% and 30%). The pCR rate in patients who underwent neoadjuvant chemotherapy (NAC) was examined. The disease-free (DFS) and overall survival (OS) were calculated using the Kaplan-Meier method and tested with the log-rank procedure. Uni- and multivariate analyses for recurrent factors were performed using the Cox proportional hazard model. Results: 1. The HER2 status was classified as follows; HER2-0 in 1,227 cases (12.0%), HER2-low in 7,209 cases (70.6%), and HER2-positive in 1,779 cases (17.4%). In the recurrent cases, HER2-low was observed in 648 cases (66.1%), and in cases treated with NAC, HER2-low was observed in 544 cases (52.7%). 2. The HER2 status significantly correlated with age, tumor size, lymph nodal status, ER, PgR, NG, and the Ki-67 index value. A comparison between HER2-low and HER2-0 revealed that patients with HER2-low tumors were significantly more likely to be under 50 years of age and had more positive nodes. Moreover, HER2-low was significantly associated with positive ER/PgR, lower NG, and lower Ki-67 index values. 3. There was no significant difference in terms of DFS between the three HER2 groups. However, a difference was observed between the three groups in terms of OS. HER2-0 had the lowest OS rate. Moreover, there was a significant difference in OS after recurrence between HER2-0 and HER2-low. 4. When the DFS for the ER status was examined, a significant difference between the HER2 status in cases with ER &amp;lt; 1.0% and ER&amp;gt;10% was observed. Moreover, the DFS in the HER2-low cases was equivalent to the DFS in the HER2-0 cases. However, the DFS in HER2-low was lower in the ER 1-10% group. Although all the HER2 groups showed a significant difference in OS, HER2-low in the ER 1-10% group had the lowest OS, and HER2-0 in the ER&amp;gt;10% group had the lowest OS and was significantly different from HER2-low in the same group. 5. A multivariate analysis revealed that there was no significant difference between HER2-low and HER2-0 as a prognostic factor after recurrence. 6. The pCR rate for NAC was lowest in the HER2-low group, and the pCR rate in the HER2-low group was significantly lower than the HER2-0 group. 7. The DFS after NAC was significantly better in all the pCR cases, regardless of the HER2 status. However, the DFS was significantly lower in the HER2-low non-pCR cases. Conclusion: HER2-low accounted for 70% of the cases. There were more cases with positive ER/PgR, lower NG, and lower Ki-67 index values in the HER2-low group. The HER2-low group had a significantly better OS than the HER2-0 group. However, the response to NAC was low in the HER2-low group and this group had the poorest prognosis among all the non-pCR cases. These findings indicate that HER2-low has a different biology and prognosis compared to HER2-0 and it may be a new subtype. Citation Format: Reiki Nishimura, Yoshitaka Fujiki, Tetsuhiko Taira, Toshiko Miyaki, Shuichi Kanemitsu, Daisuke Yotsumoto, Megumi Teraoka, Junko Kawano, Naomi Gondo, Reiko Mitsueda, Shinichi Baba, Yasuyo Ohi, Yoshiaki Rai, Yoshiaki Sagara, Yasuaki Sagara. The clinicopathological and prognostic significance of HER2-low breast cancer: A comparative analysis between HER2-low and HER2-zero subtypes [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-24-03.

Abstract PO5-01-05: An Open-label, Single-center Study Assessing the Efficacy of PH-based Regimen as Neoadjuvant Therapy for HER2-positive Early-stage Breast Cancer: Integrating Genomic Features and Functional Imaging

Abstract Background: Pathological complete response (pCR) has been demonstrated as a surrogate endpoint for disease-free and overall survival in HER2-positive early-stage breast cancer (EBC). Trastuzumab (H) plus pertuzumab (P) improved pCR rates in patients with HER2-positive early-stage breast cancer. Nevertheless, biomarkers to assess the effectiveness of this treatment in the neoadjuvant setting are still unclear. This study aims to evaluate the effectiveness of fluorodeoxyglucose positron emission tomography (18F-FDG-PET) and 68 Ga-Affibody HER2 Imaging PET (HER2-PET) in HER2 EBC neoadjuvant therapy, and to identify novel biomarkers for this regimen. Methods: HER2-positive EBC patients were prospectively recruited at Fudan University Shanghai Cancer Center between April 2020 and March 2022. All patients received the 1 dose of HP, followed by 6 cycles of docetaxel (T), carboplatin (Cb), and HP. We use FoundationOne to evaluate the genomic alterations before treatment. In addition, 18F-FDG-PET and HER2 PET were performed at baseline, after 1 cycle of HP, and after 6 cycles of TCbHP, to assess the effectiveness of these examinations in the prediction of pCR and correlation to disease burden. All patients were received surgery and completed 1 year of HP-based regimen in the adjuvant setting. Results: A total of 61 patients with a median age of 49 years were included. Among them, 93.5% of patients are node positive. 75.8% of the patients reported adverse events (AEs), primarily grade 1 and 2. The incidence of serious AEs was 6.6%. Patients exhibiting a greater than 40% reduction in SUVmax of 18-FDG-PET or HER2-PET scans from baseline to the fifth day after the initial HP treatment were classified as the treatment-sensitive group. The pCR rate for the 18-FDG-PET-sensitive group was 79.3%, while for the insensitive group was 48.1%. For HER2-PET scans, the pCR rate was 70.0% in the sensitive group and 59.3% in the non-sensitive group. To evaluate the potential biomarkers, 25 patients (13 pCR and 12 non-pCR) were evaluated with FoundationOne, with the identification of 1,321 somatic alterations. The most frequently altered genes were ERBB2 (100%), TP53 (96%), CDK12 (76%), MYC (56%), CCND1 (44%), PIK3CA (40%), and SRSF2 (36%). In the pCR group, we found PPM1D (38.5%) and RAD21 (38.5%) were altered more frequently than the non-pCR group. PIK3CA alterations were significantly reduced in pCR group, only 23% of cases are affected compared to 58.3% in non-pCR group. Patients were non-pCR had more MDM4 (41.7%) and ZNF217 (41.7%) alterations than pCR patients. Conclusion: The SUVmax value of 18-FDG-PET and HER2-PET scans are correlated well with the tumor burden and the residual disease in the HER2 EBCs. The reduction of SUVmax could predict pCR but need further exploration. Patients with alterations in PPM1D and RAD21 have a favorable response to the TCbHP regimen. Conversely, alterations in PIK3CA, MDM4, and ZNF217 are associated with treatment resistance. These results indicate the significance of 18-FDG-PET and HER2-PET in monitoring treatment effectiveness. The biomarker analysis in this study will help us understand the mechanism of HER2 positive breast cancer treatment resistance and assisting in tailoring personalized therapy. Clinical trial information: NCT04281641. Citation Format: Ming Chen, Benlong Yang, Sun Yuyun, Linxiaoxi Ma, Song Shaoli, Min He, Zhi-Ming Shao, Bingqiu Xiu, Jiong Wu. An Open-label, Single-center Study Assessing the Efficacy of PH-based Regimen as Neoadjuvant Therapy for HER2-positive Early-stage Breast Cancer: Integrating Genomic Features and Functional Imaging [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-01-05.

Abstract PO2-18-12: Updated Results of a Phase II Study: Neoadjuvant Inetetamab Combined with Pertuzumab, Paclitaxel and Carboplatin for Locally Advanced HER2-Positive Breast Cancer

Abstract Background: Inetetamab is a neotype HER2-targeted monoclonal antibody with amino acids modified Fc segment which optimizes the antibody-dependent cellular cytotoxicity effect. However, robust evidence evaluating the combination of inetetamab combined with pertuzumab, paclitaxel and carboplatin (TCbIP) for neoadjuvant therapy is still lacking. This study aimed to evaluate the efficacy and safety of TCbIP as a neoadjuvant therapy for patients with locally advanced HER2-positive breast cancer. We now present the updated results of this trial. Methods: This phase II trial included female patients with histologically confirmed stage IIA to IIIC HER2-positive primary invasive breast cancer. Eligible patients received TCbIP treatment every three weeks for a maximum of six cycles followed by surgery. The primary endpoint was pathologic complete response (pCR, ypT0/is ypN0) rate. Key secondary endpoints included near pCR (npCR, residual breast disease &amp;lt; 1cm) rate, objective response rate (ORR) and safety. Results: From November 2021 to July 2023, 40 patients were enrolled in the trial. One patient received one cycle of the study treatment but was lost to follow-up without surgery, and five patients received one cycle of the study treatment and were still undergoing treatment, leaving 34 patients in the intention-to-treat (ITT) population. Among these 34 patients (82.4% in stage III), 22 patients completed the study treatment and surgery (per-protocol [PP] population) and 12 patients were still undergoing neoadjuvant treatment. The ORR was 91.2% (31/34) in the ITT population and 86.4% (19/22) in the PP population. Among the 22 patients in the PP population, 12 patients (54.5%) achieved pCR, and18 patients (81.8%) achieved npCR. The pCR rates for patients with hormone receptor (HR) negative and positive tumors were 80.0% (8/10) and 33.3% (4/12), respectively. The most common grade 3 adverse event was neutropenia (17.6%). No significant reduction in the left ventricular ejection fraction was observed in any patient. Conclusions: Neoadjuvant therapy with TCbIP demonstrated promising efficacy and manageable toxicity in patients with HER2-positive locally advanced breast cancer. Registration number: NCT05749016 (www.clinicaltrials.gov). Citation Format: Yue Chai, Jiaxuan Liu, Mingxia Jiang, Maiyue He, Xin Wang, Yipeng Wang, Xue Yang, Jing Wang, Binghe Xu, Qiao Li. Updated Results of a Phase II Study: Neoadjuvant Inetetamab Combined with Pertuzumab, Paclitaxel and Carboplatin for Locally Advanced HER2-Positive Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-18-12.

Pathologic complete response among patients with esophageal cancer receiving neoadjuvant chemotherapy or chemoradiation: A meta-analysis.

305 Background: Although neoadjuvant therapy improves overall survival in esophageal cancers, the benefit is largely confined to those with the greatest pathologic response. Current estimates of pathologic complete response (pCR) rates come from individual studies and lack precision. With this study, we sought to estimate summary pCR rates in patients with non-metastatic esophageal cancer who received either neoadjuvant chemotherapy or chemoradiation by conducting a systematic review and meta-analysis of clinical trials. Methods: Studies were identified from the Medline, EMBASE, and CENTRAL database searches. Eligible studies were published in English from 1992-2022 and consisted of clinical trials that focused on incident non-metastatic esophageal cancer or cancer of the gastroesophageal junction. Trials were required to contain at least one arm of patients receiving neoadjuvant chemotherapy (including perioperative) or neoadjuvant chemoradiation (including treatment with induction chemotherapy). Eligible studies had to report pCR in at least 20 patients who underwent neoadjuvant therapy and surgery. Pooled pCR prevalence was determined using the Freeman-Tukey double arcsine transformation and a random effects model. Results: Among 6,575 records first identified, we included 75 studies with 5,988 patients in the meta-analysis. Of the included studies, 38 (51%) were single arm trials, 35 (47%) were randomized trials, and 2 (3%) were non-randomized trials of multiple treatments. Geographically, 28 (37%), 24 (32%), 21 (28%), and 2 (3%) of the included trials were performed in Asia, Europe, North America, and Australia, respectively. Across 91 trial arms that delivered either neoadjuvant chemotherapy or chemoradiation, platinum and fluorouracil-based regimens were the most common (48.4%), followed by platinum and taxane-based regimens (26.4%), regimens that contained platinum-based agents, fluorouracil, and a taxane (13.2%), and other regimens (12.1%). The pooled prevalence of pCR after neoadjuvant chemotherapy in squamous cell carcinomas was 9% (95% CI: 6% – 14%) across 16 studies, ranging from 0%-32%. The pooled prevalence of pCR after neoadjuvant chemoradiation in squamous cell carcinomas was 32% (95% CI: 26% – 39%) across 21 studies, ranging from 8% to 66%. For adenocarcinomas, the pooled prevalence of pCR was 2% (95% CI: 0% – 7%) after neoadjuvant chemotherapy, across 3 studies, and 22% (17% - 27%) after neoadjuvant chemoradiation across 11 studies. Conclusions: In this meta-analysis, we found that under one-third of patients with non-metastatic esophageal cancer who receive neoadjuvant chemo(radiation) experience pCR. As pCR represents an increasingly utilized as an endpoint in neoadjuvant trials, these estimates of pooled pCR rates may serve as an important benchmark for future trial design.

Neoadjuvant Chemotherapy and Neoadjuvant Chemotherapy with Immunotherapy Result in Defferent Tumor Shrinkage Patterns in Triple-negative Breast Cancer.

This study aims to explore whether neoadjuvant chemotherapy with immunotherapy (NACI) leads to different tumor shrinkage patterns, based on magnetic resonance imaging (MRI), compared to neoadjuvant chemotherapy (NAC) alone in patients with triple-negative breast cancer (TNBC). Additionally, the study investigates the relationship between tumor shrinkage patterns and treatment efficacy was investigated. This retrospective study included patients with TNBC patients receiving NAC or NACI from January 2019 until July 2021 at our center. Pre- and post-treatment MRI results were obtained for each patient, and tumor shrinkage patterns were classified into three categories as follows: 1) concentric shrinkage (CS); 2) diffuse decrease; and 3) no change. Tumor shrinkage patterns were compared between the NAC and NACI groups, and the relevance of the patterns to treatment efficacy was assessed. Of the 99 patients, 65 received NAC and 34 received NACI. The CS pattern was observed in 53% and 20% of patients in the NAC and NACI groups, respectively. Diffuse decrease pattern was observed in 36% and 68% of patients in the NAC and NACI groups. The association between the treatment regimens (NAC and NACI) and tumor shrinkage patterns was statistically significant (p=0.004). The postoperative pathological complete response (pCR) rate was 45% and 82% in the NAC and NACI groups (p<0.001), respectively. In the NACI group, 17% of patients with the CS pattern and 56% of those with the diffuse decrease pattern achieved pCR (p=0.903). All tumor shrinkage patterns were associated with achieved a high pCR rate in the NACI group. Our study demonstrates that the diffuse decrease pattern of tumor shrinkage is more common following NACI than that following NAC. Furthermore, our findings suggest that all tumor shrinkage patterns are associated with a high pCR rate in patients with TNBC treated with NACI.

Neoadjuvant Chemotherapy and Pathologic Complete Response in HR+/HER2− Breast Cancer: Impact of Tumor Ki67 and ER Status

Introduction: Neoadjuvant chemotherapy (NAC) is extensively employed in breast cancer (BC), primarily for aggressive subtypes like triple-negative and human epidermal growth factor receptor 2 (HER2)-positive BC and in estrogen receptor-positive (ER+)/HER2− BC with high-risk features. In ER+/HER2− BC, pathological complete rates are much lower (Methods: Retrospective data analysis from Kartal Dr. Lütfi Kırdar City Hospital included HR+/HER2− BC patients who received NAC. Clinicopathological factors, NAC response, and surgical outcomes were assessed. Statistical analyses evaluated the association between Ki67, ER status, and pCR. Results: Of 203 patients, 11.8% achieved pCR. Ki67 (p p p = 0.003, HR: 1.02) and ER percentage (p = 0.019, HR: 0.97) as independent predictors of pCR probability. Conclusion: Consideration of Ki67 and ER percentage aids in NAC decisions for HR+/HER2− BC, identifying patients with high NAC response rates, facilitating axillary preservation, and potentially avoiding axillary dissection. The pCR rates in patients with Ki67 ≤24 are particularly low, especially in patients with a high ER percentage. In these cases, upfront surgery and adjuvant treatment should be considered instead of NAC.

Neoadjuvant Chemotherapy and Neoadjuvant Chemotherapy With Immunotherapy Result in Different Tumor Shrinkage Patterns in Triple-Negative Breast Cancer.

This study aims to explore whether neoadjuvant chemotherapy with immunotherapy (NACI) leads to different tumor shrinkage patterns, based on magnetic resonance imaging (MRI), compared to neoadjuvant chemotherapy (NAC) alone in patients with triple-negative breast cancer (TNBC). Additionally, the study investigates the relationship between tumor shrinkage patterns and treatment efficacy was investigated. This retrospective study included patients with TNBC patients receiving NAC or NACI from January 2019 until July 2021 at our center. Pre- and post-treatment MRI results were obtained for each patient, and tumor shrinkage patterns were classified into three categories as follows: 1) concentric shrinkage (CS); 2) diffuse decrease; and 3) no change. Tumor shrinkage patterns were compared between the NAC and NACI groups, and the relevance of the patterns to treatment efficacy was assessed. Of the 99 patients, 65 received NAC and 34 received NACI. The CS pattern was observed in 53% and 20% of patients in the NAC and NACI groups, respectively. Diffuse decrease pattern was observed in 36% and 68% of patients in the NAC and NACI groups. The association between the treatment regimens (NAC and NACI) and tumor shrinkage patterns was statistically significant (p = 0.004). The postoperative pathological complete response (pCR) rate was 45% and 82% in the NAC and NACI groups (p < 0.001), respectively. In the NACI group, 17% of patients with the CS pattern and 56% of those with the diffuse decrease pattern achieved pCR (p = 0.903). All tumor shrinkage patterns were associated with achieved a high pCR rate in the NACI group. Our study demonstrates that the diffuse decrease pattern of tumor shrinkage is more common following NACI than that following NAC. Furthermore, our findings suggest that all tumor shrinkage patterns are associated with a high pCR rate in patients with TNBC treated with NACI. ClinicalTrials.gov Identifier: NCT04909554.

Impact of relative dose intensity on pathologic complete response in human epidermal growth factor receptor 2 positive breast cancer patients receiving neoadjuvant TCHP.

The standard of care for locally advanced, human epidermal growth factor receptor 2 positive (HER2+) breast cancer includes neoadjuvant chemotherapy with docetaxel, carboplatin, trastuzumab, and pertuzumab (TCHP). Many patients do not receive the full course of therapy due to various complications, possibly affecting the potential to achieve a pathologic complete response (pCR). The amount of therapy received is typically measured by relative dose intensity (RDI). This study aimed to evaluate pCR rates in patients receiving optimal and suboptimal RDI TCHP. This study was a retrospective chart review of patients treated between 2014 and 2021 at UK HealthCare. Patients included were 18 years of age or older with HER2+ breast cancer and received at least one cycle of neoadjuvant TCHP. The primary objective compared pCR rates in patients receiving ≥ 85% RDI or <85% RDI. Secondary objectives included pCR rates based on clinical stage, age, body mass index, or hormone receptor status; factors leading to discontinuation or delay in treatment; and impact of dose reductions and delays on pCR. A total of 101 patients were included and divided into two cohorts: 54 patients received ≥ 85% RDI and 47 patients received <85% RDI. Patients who received ≥ 85% total RDI had an approximate increase of 17% in pCR rates (59.3% vs 42.6%, p = 0.11). Additionally, 82% of patients experienced a dose delay or adjustment. Patients who received ≥ 85% RDI had increased pCR rates compared to patients receiving <85% RDI. A larger patient population is needed to formulate definitive conclusions on the impact of RDI and pCR rates.

Real-world evidence of neoadjuvant chemotherapy for breast cancer treatment in a Brazilian multicenter cohort: Correlation of pathological complete response with overall survival

ObjectivesWe aimed to evaluate the pCR rate in patients receiving NAC for the treatment of breast cancer (BC) in a multicenter cohort in Brazil. Additionally, we aimed to use RWD to assess the impact of pCR on OS and DFS. MethodsThis was a retrospective, multicenter cohort study that included female patients over 18 years of age who were diagnosed with nonmetastatic breast cancer and received NAC. OS and DFS at five years were estimated by the Kaplan‒Meier method. Additionally, we conducted a multivariate analysis to identify factors that were significantly associated with pCR and OS. ResultsFrom 2011 to 2020, 1891 patients were included in the study, and 421 (22,3%) achieved pCR (ypT0 ypN0). Considering the presence of residual DCIS, pCR was achieved in 467 patients (23,5%). The pCR rate varied between the subtypes: HER-2+ (p = 0,016) and clinical stage IIIA and IIIB (p < 0,001). Among HER-2+ patients, those who received trastuzumab had a significantly higher pCR rate than those who did not receive trastuzumab (p < 0.0001). Similarly, patients with TNBC who received treatment with platinum-based regimens also showed higher pCR rates (p < 0.0001). OS was grouped according to pCR status, and the OS rate was 88,3% in the pCR group and 58.1% in the non-pCR group (p < 0.0001). The five-year DFS was 92.2% in the pCR group and 64.3% in the non-pCR group (p < 0.0001). ConclusionThe pCR rate and its prognostic value varied across BC subtypes. In our study, pCR could be used as a surrogate of favorable clinical outcome, as it was associated with higher OS and DFS rates.

Association of FTH1-Expressing Circulating Tumor Cells With Efficacy of Neoadjuvant Chemotherapy for Patients With Breast Cancer: A Prospective Cohort Study.

The association between different phenotypes and genotypes of circulating tumor cells (CTCs) and efficacy of neoadjuvant chemotherapy (NAC) remains uncertain. This study was conducted to evaluate the relationship of FTH1 gene-associated CTCs (F-CTC) with/without epithelial-mesenchymal transition (EMT) markers, or their dynamic changes with the efficacy of NAC in patients with non-metastatic breast cancer. This study enrolled 120 patients with non-metastatic breast cancer who planned to undergo NAC. The FTH1 gene and EMT markers in CTCs were detected before NAC (T0), after 2 cycles of chemotherapy (T1), and before surgery (T2). The associations of these different types of CTCs with rates of pathological complete response (pCR) and breast-conserving surgery (BCS) were evaluated using the binary logistic regression analysis. F-CTC in peripheral blood ≥1 at T0 was an independent factor for pCR rate in patients with HER2-positive (odds ratio [OR]=0.08, 95% confidence interval [CI], 0.01-0.98, P = .048). The reduction in the number of F-CTC at T2 was an independent factor for BCS rate (OR = 4.54, 95% CI, 1.14-18.08, P = .03). The number of F-CTC prior to NAC was related to poor response to NAC. Monitoring of F-CTC may help clinicians formulate personalized NAC regimens and implement BCS for patients with non-metastatic breast cancer.

Gene expression signatures, stromal tumor infiltrating lymphocytes (sTILs), and change in tumor cellularity to predict pathological complete response (pCR) after 12 week de-escalated neoadjuvant endocrine therapy (ET) vs paclitaxel + dual HER2 blockade in the WSG-TP-II trial.

519 Background: There are limited data on predictive biomarkers for de-escalated ET or chemotherapy with dual anti-HER2 blockade in HR+/HER2+ early breast cancer (BC). In this translational pre-planned project of the WSG-TP-II phase II-trial (NCT03272477), we aimed to identify associations of gene expression signatures and sTILs with pCR. Methods: Patients with cT1c-cT4c, cN0-3 centrally confirmed HR+/HER2+ BC were randomized to 12 weeks of standard ET (n = 100) or paclitaxel (Pac; n = 107). All patients received trastuzumab + pertuzumab (T+P) q3w as neoadjuvant and adjuvant treatment. Gene expression signatures were analyzed using NanoString BC360 panel in baseline biopsies (T+P+ET: n = 72; T+P+Pac: n = 78). sTILs were analyzed in 93 (T+P+ET) and 97 patients (T+P+Pac) at baseline and in 65 (T+P+ET) and 57 patients (T+P+Pac) at week 3. Impacts of standardized BC360 gene expression signatures and sTILs on pCR (ypT0/is ypN0; primary endpoint) expressed in odds ratios (OR) were estimated by logistic regression analysis. Results: pCR rate in patients with BC360 analysis was 39.3% (T+P+ET: 23.6%; T+P+Pac: 53.9%). Overall, ERBB2 (OR 2.37; 95%CI 1.55, 3.62) and cytotoxic cells signature (OR 1.42; 95%CI 1.02, 1.99) were favorable for pCR, while apoptosis (OR 0.64; 95%CI 0.44, 0.92), estrogen receptor 1 (OR 0.60; 95%CI 0.42, 0.85), estrogen receptor signaling (OR 0.64; 95%CI 0.45, 0.91), and progesterone receptor (OR 0.67; 95%CI 0.47, 0.94) signatures were unfavorable. Analyzing by treatment arm, a similar pattern was observed in the T+P+Pac arm (ERBB2: OR 2.01; apoptosis: OR 0.59; estrogen- and progesterone-related signatures: OR 0.41-0.58), but not in the T+P+ET arm where only ERBB2 was prognostic for pCR (OR 7.24; 95%CI 2.12, 24.05). Baseline ≥30% sTIL levels (vs &lt; 30% sTILs; n = 16 vs n = 174) were associated with pCR (OR 5.16; 95%CI 1.60, 16.66); significance was not achieved in either trial arm. Compared to &lt; 30% sTILs (n = 90), low tumor cellularity at week 3 precluding sTILs analysis ( &lt; 500 invasive tumor cells, n = 22), but not ≥30% sTILs (n = 10), was prognostic for pCR in all patients (OR 9.47; 95%CI 2.94, 30.50) and in individual trial arms (OR 6.00-11.79). Conclusions: This hypothesis-generating translational results suggest that gene expression signatures (particularly ERBB2), baseline sTILs, and low tumor cellularity at week 3 predict pCR after ET + double HER2 blockade. Future neoadjuvant trials are needed to prospectively test the use of baseline gene expression and sTILs analysis, and early on-treatment cellularity measurement to select patients with HR+/HER2+ tumors for de-escalated endocrine-therapy-based approaches. Clinical trial information: NCT03272477 .

Abstract PD18-04: Prognostic implications of PIK3CA mutation by hormone receptor status and intrinsic subtype in early stage HER2-positive breast cancer: a correlative analysis from CALGB 40601

Abstract Background PIK3CA mutations have been described in 20-25% of early-stage HER2-positive breast tumors [1], and are associated with reduced pathologic complete response (pCR) rate after chemotherapy and anti-HER2 agents [2]. However, the independence of this finding and association with long-term outcomes within HER2+ patients is still largely unknown. Here, we studied the prognostic implications of PIK3CA mutations by hormone receptor (HR) status and intrinsic subtype in patients with early stage HER2+ breast cancer enrolled in CALGB 40601. Method In CALGB 40601, gene expression profiling by RNA sequencing (RNAseq) with PAM50-determined intrinsic subtype and PIK3CA mutations from whole exome sequencing (WES) were obtained from 184/305 (60%) pretreatment core biopsies. We examined the association of PIK3CA mutations with pCR and event free survival (EFS) by HR status and intrinsic subtype using logistic and Cox regression analyses. Results PIK3CA mutations were found in 32 patients (32/184, 17%). The most frequent mutation was H1047R (12/32,38%), followed by E545K (7/32,22%) and E542K (5/32,16%). PIK3CA mutations were present in 20% and 15% of HR-positive and HR-negative BC subpopulations, respectively. Within Luminal-B, Luminal-A and HER2-Enriched breast tumors, PIK3CA mutations occurred in 36%, 10% and 19% respectively. In the overall population there was lower rate of pCR in mutated-PIK3CA patients than wild-type (34% vs 49%). Using only the subset of patients treated with neoadjuvant trastuzumab-based therapy as standard of care (excluding the lapatinib plus paclitaxel arm), we found a statistically significant lower pCR rate among PIK3CA-mutated tumors using logistic regression model (30% vs 54%, OR=0.30, p=0.045). At a median follow-up of 9.1 years, the presence of PIK3CA mutation was significantly associated with worse EFS in the overall study population (HR 2.58, 95% CI 1.24- 5.35, p=0.011). In a multivariable model including pCR status, HR status and intrinsic subtype (HER2-E vs. not), PIK3CA mutation was independently and significantly associated with worse EFS (HR 2.18, 95% CI 1.04- 4.56, p=0.039). The negative impact of PIK3CA mutation on EFS was statistically significant only in patients with HR-positive (HR 3.6, 95% CI 1.45-8.96, p=0.06) and luminal breast tumors (HR 4.84, 95% CI 1.08-21.7, p=0.039), but not in HR-negative and non-luminal subtypes. Conclusion In our study, the presence of PIK3CA mutation was significantly associated with lower pCR rates in patients treated with chemotherapy plus trastuzumab. Moreover, in uni- and multivariable Cox models, PIK3CA mutations were associated with worse long-term survival, which appeared to be driven by HR-positive and luminal HER2-positive breast tumors.

Abstract P1-04-10: Association of stromal tumor infiltrating lymphocytes (sTILs) in pretreatment biopsies in different molecular subtypes of HER2+/ER+ breast cancer: Assessment of NRG Oncology/NSABP B-52

Abstract Background: The primary aim of the NRG Oncology/NSABP B-52 clinical trial was to test if estrogen deprivation (ED) administered concomitantly with neoadjuvant docetaxel, carboplatin, trastuzumab, and pertuzumab (TCHP), would improve the pCR rate in patients with HER2+/ER+ early breast cancer. A numerical increase in the pCR rate was observed with ED (46.1% v 40.9%), but the difference was not statistically significant. The purposes of this study were to assess the association of sTILs in pretreatment biopsies with pCR in the total population and within the molecular subtypes of breast cancer and to assess changes in sTILs between pre- and on-treatment biopsies. The secondary endpoints of recurrence-free interval (RFI) and overall survival (OS) are currently being analyzed and will be presented along with association of these endpoints with sTILs in pretreatment biopsies in the total cohort and within molecular subtypes. Methods: Scoring of sTILs on routine H&amp;E slides from pre-treatment biopsies with sufficient tumor from 249 of the 315 patients (79%) entered in B-52 were performed by one of two pathologists (SKM, RSM). Both pathologists scored sTILs on a subset of 64 patients to document concordance. Wilcoxon two-sided test, box and whisker plots, and forest plots were used to assess associations with pCR. Molecular subtypes were determined utilizing RNA-seq data and AIMS subtyping method. On-treatment biopsies were available in 46 patients and were scored and compared to paired baseline samples. Results: Good concordance between pathologists was established with an inter-pathologist difference of ˂20% difference between scores in 92% of cases. sTILs in pre-treatment samples were associated with pCR across both arms of the trial (p=0.0074) and in the TCHP+ED arm (p=0.033), but not in the TCHP arm (p=0.093). The distribution of intrinsic subtypes was 34% luminal B, 29% luminal A, 28% HER2E, 5.8% normal, and 2.7% basal, with no significant differences between the arms. Presence of sTILs showed a trend for association with pCR in HER2E pre-treatment samples (p=0.054) but not in non-HER2E (p=0.75). Similarly, sTILs were associated with pCR in non-luminal tumors (p=0.055) but not in luminal tumors (p=0.44). Stratification by treatment arm and menopausal status suggested sTILs are associated with pCR in premenopausal women treated with TCHP (OR: 1.04, 95% CI=1.00-1.09). Interestingly, decreases in the sTIL scores with treatment were associated with pCR in the TCHP+ED arm (p=0.01) but not in the TCHP arm. Analysis of RFI and OS on B-52 is ongoing and will be presented along with associations of sTILs with intrinsic subtypes for RFI and OS. Conclusions: Although a positive correlation between sTILs and pCR was observed, the clinical utility appears limited because of the extensive overlap in the TIL scores between pCR and non-pCR tumors. Significance for a positive association of sTILs with pCR was detected in HER2E but not in luminal tumors. This may be due to the molecular differences of the subtypes, or the make-up of the TILs, or both. The association of a decrease in sTILs with TCHP+ED treatment needs further investigation. The small number of samples is a limitation of the study; however, the B-52 protocol specified that the collection of the B-52 samples was for the purpose of exploratory analysis. Our results highlight the molecular heterogeneity of the HER+/ER+ patient population and suggests that different treatment strategies may be required in future treatment regimens for this patient population. Support: NSABP Foundation; BCRF; 3U10CA180868-03S2, -180822; UG1CA189867; Genentech. Citation Format: Katherine L. Pogue-Geile, Sai K. Maley, Rim S. Kim, Ying Wang, Roberto Salgado, Corey Lipchik, Huichen Feng, Reena S. Cecchini, Samuel A. Jacobs, Ashok Srinivasan, Eleftherios (Terry) Mamounas, Charles E. Geyer Jr, Priya Rastogi, C. Kent Osborne, Soonmyung Paik, Norman Wolmark, Peter C. Lucas, Mothaffar Rimawi. Association of stromal tumor infiltrating lymphocytes (sTILs) in pretreatment biopsies in different molecular subtypes of HER2+/ER+ breast cancer: Assessment of NRG Oncology/NSABP B-52 [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 P1-04-10.

Assessment of immunoscore and MRI tumor regression grade to predict complete pathologic response in patients with locally advanced rectal cancer: Data from phase II Averectal study.

212 Background: In patients with locally advanced rectal cancer (LARC), magnetic resonance imaging is the most accurate non-invasive staging tool, enabling response assessment to total neoadjuvant therapy. Wang et al had reported that 46.6% of patients with Magnetic Resonance Tumor Regression Grade 1 (mrTRG=1; complete radiologic response) achieved pathologic complete response (pCR; no residual tumor cells). We reported previously in a Phase II Averectal study the correlation between pre-treatment biopsy Immunoscore (IS) and pCR probability (68% ± 22 SD in patients with a high IS as opposed to 52% ± 22 SD in patients with a low IS; P=0.036). This study explores the value of combining IS and mrTRG to predict pCR among LARC patients. Methods: This is an open-label, single-arm multicenter stage-2 phase II study investigating the efficacy and safety of 5 fractions of short course radiotherapy, followed by 6 cycles of mFOLFOX-6 plus avelumab, followed by Total Mesorectal Excision (TME), in patients with LARC. Mean density percentiles of CD3 and CD8 positive T cells infiltrating the tumor and the invasive margin in baseline tissue samples were used to calculate IS (62% is considered the cutoff between high and low IS). Baseline and post treatment MRI were reviewed by two independent radiologists to measure mrTRG and other variables. Results: Between July 2018 and October 2020, 44 patients were accrued, out of which 40 (90%) completed at least 1 cycle of mFOLFOX/Avelumab and underwent TME. Of the 40, 36 (90%) had baseline IS, mrTRG (pre-post treatment) and pTRG (pathologic Tumor Regression Grade) assessed. Out of 36, 15 (41.6%) achieved pCR, 24 (66.7%) had mrTRG=1 and 22 (61%) had high IS. Of the high IS (n=22) patients, 10 (45.45%) achieved pCR. Also, out of 24 patients with mrTRG=1, 11 (45.8%) attained pCR. Most importantly, of the patients with combined high IS and mrTRG=1 (n=14), 11 (78.6%) achieved pCR. In patients with both mrTRG=1 and high IS, pCR rate was 78.6% (11/14). This result is significantly different from pCR rate for patients with either high IS (10/22, 45.45%) or mrTRG=1 (11/24, 45.8%) with P=0.0247 and P=0.0243 respectively. Conclusions: Combining both IS and mrTRG achieved a promising predictive value for pCR in LARC and therefore upon further validation may be potentially used for patient selection in non-operative management strategies. Clinical trial information: NCT03503630 .

Efficacy analysis of neoadjuvant chemotherapy with or without anthracyclines in female patients with HER2-positive breast cancer in China: a nationwide, multicenter, 10-year retrospective study (CSBrS-012).

In the era of targeted therapy, whether patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer are exempted from anthracycline usage in the neoadjuvant setting is controversial. Our objective was to retrospectively analyze the differences in pathological complete remission (pCR) rates between the anthracycline group and the nonanthracycline group. The CSBrS-012 study (2010-2020) included female primary breast cancer patients with neoadjuvant chemotherapy (NAC) who underwent standard breast and axillary surgery post-NAC. A logistic proportional hazard model was applied to estimate the association of covariates with pCR. Propensity score matching (PSM) was performed to balance the differences in baseline characteristics, and subgroup analyses were performed using the Cochran-Mantel-Haenszel test. A total of 2507 patients were enrolled: the anthracycline group (n = 1581, 63%) and the nonanthracycline group (n = 926, 37%). A pCR was recorded in 17.1% (271/1581) of patients in the anthracycline group and in 29.3% (271/926) in the nonanthracycline group, and the difference in the pCR rate between the two groups was statistically significant [odds ratio (OR) = 2.00, 95% confidence interval (CI) (1.65-2.43); p < 0.001). In the subsequent subgroup analysis, substantial differences in pCR rates between the anthracycline and nonanthracycline groups were detected in the nontargeted [OR = 1.91, 95% CI (1.13-3.23); p = 0.015] and dual-HER2-targeted populations [OR = 0.55, 95% CI (0.33-0.92); p = 0.021) before PSM, whereas differences vanished after PSM. The pCR rates between the anthracycline and nonanthracycline groups did not differ for the single target population, either before or after PSM. In the presence of trastuzumab and/or pertuzumab, the pCR rate of patients with HER2-positive breast cancer receiving anthracycline was not superior to that of patients receiving nonanthracycline. Thus, our study further provides clinical evidence for exempting anthracycline treatment in HER2-positive breast cancer in the era of targeted therapy.

A multicenter study on efficacy of dual-target neoadjuvant therapy for HER2-positive breast cancer and a consistent analysis of efficacy evaluation of neoadjuvant therapy by Miller-Payne and RCB pathological evaluation systems (CSBrS-026).

The aim of this study was to investigate the factors influencing pathological complete response (pCR) rate in early breast cancer patients receiving neoadjuvant dual-target [trastuzumab (H) + pertuzumab (P)] therapy combined with chemotherapy. Additionally, the consistency of the Miller-Payne and residual cancer burden (RCB) systems in evaluating the efficacy of neoadjuvant therapy for early human epidermal growth factor receptor-2 (HER2)+ breast cancer was analyzed. The clinicopathological data of female patients with early-stage HER2+ breast cancer who received dual-target neoadjuvant therapy at 26 hospitals of the Chinese Society of Breast Surgery (CSBrS) from March 2019 to December 2021 were collected. Patients were allocated to four groups: the HER2 immunohistochemistry (IHC) 3+/hormone receptor (HR)-, IHC3+/HR+, IHC2+ in situ hybridization (ISH)+/HR- and IHC2+ ISH+/HR+ groups. The overall pCR rate for patients, the pCR rate in each group and the factors affecting the pCR rate were analyzed. The consistency between the Miller-Payne and RCB systems in assessing the efficacy of neoadjuvant therapy was analyzed. From March 1, 2019, to December 31, 2021, 77,376 female patients with early-stage breast cancer were treated at 26 hospitals; 18,853 (24.4%) of these patients were HER2+. After exclusion of unqualified patients, 2,395 patients who received neoadjuvant dual-target (H+P) therapy combined with chemotherapy were included in this study. The overall pCR rate was 53.0%, and the patients' HR statuses and different HER2+ statuses were significantly correlated with the pCR rate (P<0.05). The consistency of the pathological efficacy assessed by the Miller-Payne and RCB systems was 88.0% (κ=0.717, P<0.001). Different HER2 expression statuses and HR expression statuses are correlated with the pCR rate after dual-target neoadjuvant therapy in HER2+ breast cancer patients. There is a relatively good consistency between Miller-Payne and RCB systems in evaluating the pathologic efficacy of neoadjuvant therapy for HER2+ breast cancer.