HER2-positive Group Research Articles

Whole tumour- and subregion-based radiomics of contrast-enhanced mammography in differentiating HER2 expression status of invasive breast cancers: A double-centre pilot study.

To explore the value of whole tumour- and subregion-based radiomics of contrast-enhanced mammography (CEM) in differentiating the HER2 expression status of breast cancers. 352 patients underwent preoperative CEM from two centres were consecutively enroled and divided into the training, internal validation, and external validation cohorts. The lesions were divided into HER2-positive and HER2-negative groups. Besides the radiological features, radiomics features capturing the whole tumour-based (wITH) and subregion-based intratumoral heterogeneity (sITH) were extracted from the craniocaudal view of CEM recombined images. The XGBoost classifier was applied to develop the radiological, sITH, and wITH models. A combined model was constructed by fusing the prediction results of the three models. The mean age of the patients was 51.1 ± 10.7 years. Two radiological features, four wITH features, and three sITH features were selected to establish the models. The combined model significantly improved the AUC to 0.80 ± 0.03 (95% CI: 0.73-0.86), 0.79 ± 0.06 (95% CI: 0.67-0.90), and 0.79 ± 0.05 (95% CI: 0.69-0.89) in the training, internal validation, and external validation cohorts, respectively (All P < 0.05). The combined model showed good agreement between the predicted and observed probabilities and favourable net clinical benefit in the validation cohorts. Both whole tumour- and subregion-based ITH radiomics features of CEM exhibited potential for differentiating the HER2 expression status. Combining conventional radiological features and ITH features can improve the model's performance.

Characterization of HER2-Low Breast Tumors among a Cohort of Colombian Women.

HER2-low tumors have shown promise in response to antibody-drug conjugates (ADCs) in recent clinical trials, underscoring the need to characterize this group's clinical phenotype. In this study, we aimed to explore the clinicopathological features, survival rates, and HER2 amplicon mRNA expression of women affected with HER2-low breast cancer, compared with HER2-negative and HER2-positive groups. We included 516 breast cancer patients from Colombia, for whom we compared clinicopathological features, mRNA expression of three HER2 amplicon genes (ERBB2, GRB7 and MIEN1), survival and risk of mortality between HER2-low cases (1+ or 2+ with negative in situ hybridization (ISH) result) with HER2-positive (3+ or 2+ with positive ISH test) and HER2-negative (0+) cases. A higher proportion of patients with better-differentiated tumors and a lower proliferation index were observed for HER2-low tumors compared to the HER2-positive group. Additionally, HER2-low tumors showed higher mRNA expression of the ERBB2 gene and longer overall survival rates compared to HER2-negative cases. Nonetheless, a Cox-adjusted model by ER status and clinical stage showed no statistically significant differences between these groups. Our results show differences in important clinicopathological features between HER2-low and both HER2-positive and negative tumors. Given this unique phenotype, it is crucial to evaluate the potential advantages of ADC therapies for this emerging subtype of breast cancer.

Exploring Therapeutic Challenges in Patients with HER2-Positive Breast Cancer-A Single-Center Experience.

Breast cancer is one of the most common forms of neoplasia worldwide. The purpose of our observational study was to evaluate the status of HER2 overexpression among new cases of breast neoplasia with an impact on the natural history of breast cancer disease and therapeutic personalization according to staging. This study included 45 breast cancer patients which have an overexpression of HER2 through the mutation of the EGFR-ERBB2 receptor. Immunohistochemical staining was performed on sections of formalin-fixed paraffin-embedded breast tissue. The patients were evaluated demographically and therapeutically in all stages. The post-surgical histopathological examination revealed complete pathological responses in 19 patients and pathological responses with residual disease either at the tumor level or lymphatic or both variants in a percentage of 44% (15 cases). The disease-free interval (DFI) under anti-HER2 therapy was recorded in 41 patients, representing 91% of the study group. Anti-HER2 therapy in any therapeutic stage has shown increased efficiency in blocking these tyrosine kinase receptors, evidenced by the high percentage of complete pathological responses, as well as the considerable percentage (47%) of complete remissions and stationary disease, in relation to the HER2-positive patient group.

A plain language summary of the results from the phase 2b HERIZON-BTC-01 study of zanidatamab in participants with HER2-amplified biliary tract cancer.

Researchers wanted to study whether the research drug zanidatamab could help people with a type of cancer called biliary tract cancer. In some people, biliary tract cancer cells make extra copies of a gene called HER2 (also called ERBB2). This is known as being HER2-amplified. Zanidatamab is an antibody designed to destroy cancer cells that have higher-than-normal HER2 protein or gene levels. Zanidatamab is currently under research and is not yet approved for any diseases. Participants in this phase 2b clinical study had tumors that were HER2-amplified and at the advanced or metastatic stage. Participants also had cancer which had become worse after previous chemotherapy or had side effects that were too bad to continue chemotherapy. They also had to meet other requirements to be enrolled. Researchers measured the amount of HER2 protein in the tumor samples of the participants who were enrolled. There were 80 participants with tumors that were both HER2 amplified and had higher-than-normal HER2 protein amounts (considered to be 'HER2-positive'). There were 7 participants with tumors that were HER2-amplified, but had little-to-no levels of the HER2 protein (considered to be 'HER2-low'). All participants in the study were treated with zanidatamab and no other cancer treatments once every 2weeks. In the HER2-positive group, 33 of 80 (41%) participants had their tumors shrink by 30% or more of their original size. In half of these participants, their tumors did not grow for 13months or longer. No participant in the HER2-low group had their tumors shrink by 30% or more. In total, 63 of 87 participants (72%) had at least one side effect believed to be related to zanidatamab treatment. Most side effects were mild or moderate in severity. No participant died from complications related to zanidatamab. Diarrhea was one of the more common side effects and was experienced by 32 of 87 participants (37%). Side effects related to receiving zanidatamab through the vein, such as chills, fever, or high blood pressure, were experienced by 29 of 87 participants (33%). The results of this study support the potential for zanidatamab as a new therapy for people with HER2-positive biliary tract cancer after they had already received chemotherapy. More research is occurring to support these results.Clinical Trial Registration: NCT04466891 (HERIZON-BTC-01 study).

Integrated nomogram to predict HER2 expression in breast tumor: Clinical, Ultrasound, and Photoacoustic imaging approaches

BackgroundHER2 is a key biomarker for breast cancer treatment and prognosis. Traditional assessment methods like immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) are effective but costly and time-consuming. Our model incorporates these methods alongside photoacoustic imaging to enhance diagnostic accuracy and provide more comprehensive clinical insights. Materials and methodsA total of 301 breast tumors were included in this study, divided into HER2-positive (3+ or 2+ with gene amplification) and HER2-negative (below 3+ and 2+ without gene amplification) groups. Samples were split into training and validation sets in a 7:3 ratio. Statistical analyses involved t-tests, chi-square tests, and rank-sum tests. Predictive factors were identified using univariate and multivariate logistic regression, leading to the creation of three models: ModA (clinical factors only), ModB (clinical plus ultrasound factors), and ModC (clinical, ultrasound, and photoacoustic imaging-derived oxygen saturation (SO2)). ResultsThe area under the curve (AUC) for ModA was 0.756 (95 % CI: 0.69–0.82), ModB increased to 0.866 (95 % CI: 0.82–0.91), and ModC showed the highest performance with an AUC of 0.877 (95 % CI: 0.83–0.92). These results indicate that the comprehensive model combining clinical, ultrasound, and photoacoustic imaging data (ModC) performed best in predicting HER2 expression. ConclusionThe findings suggest that integrating clinical, ultrasound, and photoacoustic imaging data significantly enhances the accuracy of predicting HER2 expression. For personalised breast cancer treatment, the integrated model could provide a comprehensive and reproducible decision support tool.

Prognostic Significance of EGFR, HER2, and c-Met Overexpression in Surgically Treated Patients with Adenocarcinoma of the Ampulla of Vater.

Adenocarcinoma of the ampulla of Vater (AAC) is a rare malignancy with heterogeneous tumors arising from various histologic subtypes, necessitating new therapeutic strategies. This study examines epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and c-Met expression in AAC, given their potential as druggable targets. Among 87 patients who underwent curative resection, EGFR overexpression was found in 87.4%, HER2 in 11.5%, and c-Met in 50%. EGFR overexpression was more common in the pancreatobiliary subtype (p = 0.018) and associated with a higher histologic grade (p = 0.008). HER2 did not correlate with clinicopathological features, while c-Met was more common in node-negative groups (p = 0.004) and often co-expressed with EGFR (p = 0.049). EGFR-positive patients had worse disease-free (HR = 2.89; 95% CI, 1.35-6.20; p = 0.061) and overall survival (HR = 6.89; 95% CI, 2.94-16.2; p = 0.026) than EGFR-negative patients. HER2-positive AAC showed a trend towards shorter survival, although not statistically significant, and c-Met had no impact on survival outcomes. In the context of systemic disease, survival outcomes did not vary according to EGFR, HER2, and c-Met expression, but the HER2-positive group showed a trend towards inferior progression-free survival (HR = 1.90; 95% CI, 0.56-6.41; p = 0.166). This study underscores the potential of EGFR, HER2, and c-Met as targets for personalized therapy in AAC, warranting further research to evaluate targeted treatments.

The impact of human epidermal growth factor receptor-2 (low) status on the efficacy of first line cyclin-dependent kinase 4/6 inhibitors in advanced breast cancer.

The fact that the human epidermal growth factor receptor 2 (HER2)-low group, historically classified as HER2 negative in breast cancer histology, benefited from HER2-targeted treatments similarly to the HER2-positive group indicates that this group has a distinct histology from the HER2-0 group. The effectiveness of cyclin-dependent kinase 4/6 inhibitors, which are the standard first-line treatment for hormone receptor-positive, HER2-negative advanced breast cancer, in this newly defined histological subgroup remains a topic of debate. In our study, we examined the impact of HER2 status on the efficacy of CDK4/6 inhibitors. Our study is a retrospective, multicenter, real-world data analysis. One hundred sixty patients were included in the study. The relationship between HER2 status and other clinical-pathological features, as well as progression-free survival, was examined. Median follow-up was 20.33 ± 0.98 months. The mPFS could not be reached. All patients exhibited positive estrogen receptor expression. Among the patients, 111 (69.4%) were categorized as HER2-0, and 49 (30.6%) as HER2-low. The 24-month progression-free survival rates were similar between HER2-0 and HER2-low patients (60.6% vs 65.3%, hormone receptor: 1.18, CI: 0.67-2.20, P = .554). We established that the mPFS achieved with cyclin-dependent kinase 4/6 inhibitors as a first-line therapy for patients with advanced breast cancer is unaffected by HER2 status.

Multiparametric MR characterization for human epithelial growth factor receptor 2 expression in bladder cancer: an exploratory study.

To investigate the application value of multiparametric MRI in evaluating the expression status of human epithelial growth factor receptor 2 (HER2) in bladder cancer (BCa). From April 2021 toJuly 2023, preoperative imaging manifestations of 90 patients with pathologically confirmed BCa were retrospectively collected and analyzed. All patients underwent multiparametric MRI including synthetic MRI, DWI, from which the T1, T2, proton density (PD) and apparent diffusion coefficient (ADC) values were obtained. The clinical and imaging characteristics as well as quantitative parameters (T1, T2, PD and ADC values) between HER2-positive and -negative BCa were compared using student t test and chi-square test. The diagnostic efficacy of parameters in predicting HER2 expression status was evaluated by calculating the area under ROC curve (AUC). In total, 76 patients (mean age, 63.59years ± 12.84 [SD]; 55 men) were included: 51 with HER2-negative and 25 with HER2-positiveBCa. HER2-positive group demonstrated significantly higher ADC, T1, and T2 values than HER2-negative group (all P < 0.05). The combination of ADC values and tumor grade yielded the best diagnostic performance in evaluating HER2 expression level with an AUC of 0.864. The multiparametric MR characterization can accurately evaluate the HER2 expression status in BCa, which may further guide the determination of individualized anti-HER2 targeted therapy strategies.

Exploration of different immunogenomic TMEs in gastric cancer based on HER2 and PD-L1 expression.

e16073 Background: Recent results from the KEYNOTE-811 study showed that first-line pembrolizumab was superior to placebo with respect to progression-free survival (PFS) in combination with trastuzumab and chemotherapy in patients with HER2 positive metastatic gastric cancer (GC). Interestingly, In the subgroup analysis, the PFS benefit with pembrolizumab was significant in patients with tumors with PD-L1 CPS ≥1, whereas there was no benefit in the small subgroup of patients with tumors with CPS &lt; 1. Therefore, this study is to investigate immune-genomic differences in the tumor microenvironment according to the composition of surrounding cells and the expression status of HER2 and PD-L1. Methods: Utilizing single cell RNA sequencing (scRNA seq) and TCR sequencing, we examined 14 HER2 positive and 18 negative primary GC samples with CPS score based on PD-L1 IHC 22C3 pharmDx. Among the HER2-positive group, there were 4 samples in the CPS &lt; 1 (negative) and 10 samples in the CPS ≥1 (positive) group. In the HER2 negative group, there were 6 samples in the CPS &lt; 1 and 12 samples in the CPS ≥1. Results: First, when analyzing the distribution of total cells according to HER2 status, in the HER2 positive group, more endothelial cells ( p= 0.034) and fibroblasts ( p= 0.054) appeared in the PD-L1 negative group compared to the PD-L1 positive group, while there was no difference in the HER2 negative group. Furthermore, Through TCR analysis, the exhausted and cytotoxic score exhibit contrasting trends between HER2 negative and positive groups. In HER2-positive patients, the exhausted and cytotoxic score appear significantly higher in the CPS negative group. Next, we evaluated the proportion of immune cells according to HER2 status. The observed of CD4 Treg ( p= 0.084) and CD8 exhausted T (Tex), ( p= 0.036) cells was increased in the HER2 positive compared to the negative. When regrouped according to PD-L1 expression, only the HER2 positive group showed a tendency to increase the observation of CD4 Treg and CD8 Tex cells compared to positive in PD-L1 negative. In addition, we investigated whether the expression pattern of other immune checkpoint molecules differed depending on the PD-L1 expression pattern in both HER2 positive and negative patients. In the HER2 negative group, the expression of immune checkpoint proteins was similar regardless of the CPS expression group, or the expression of some proteins was higher in the CPS positive group. In other hands, in HER2 positive, CPS &lt; 1 group had higher expression of immune checkpoint proteins, such as PDCD1, LAG2, BTLA, VISTA and TIGHT. Conclusions: The high proportion of CD4 Tregs, CD8 Tex and the elevated exhausted score in the subgroup with CPS &lt; 1 in HER2 positive GCs suggesting immune exclusive environment compared to her-2 and PD-L1 coexpressing group. Considering increased expression of immune checkpoint proteins other than PD-1/PD-L1, for patients with HER2-positive and CPS &lt; 1, combination therapy with other immune checkpoint inhibitors rather than anti-PD-1/PD-L1 may be suggested.

Abstract PO1-27-03: Studies on factors for pathological complete response after neoadjuvant chemotherapy in relation to HER2 status in primary breast cancer

Abstract Background: Neoadjuvant chemotherapy (NAC) has been increasingly used as the frontline therapy for the management of high-risk localized breast cancer (BC). Achieving pathological complete response (pCR) following NAC is associated with significantly better disease-free (DFS) and overall survival (OS), particularly for triple negative (TN) and HER2+ breast cancer. Among HER2 negative BC, HER2-low BC is a newly defined subset that has a HER2 immunohistochemical (IHC)-1+ or 2+/ISH negative phenotype. HER2 status is divided into 3 categories: HER2 positive, HER2-low, and HER2-zero. In this study, we investigated factors for pCR in relation to HER2 status and survival after NAC. Methods: A total of 197 cases with primary BC from January 2013 to July 2023 were enrolled in this study. There were 83 HER2 positive cases (including 7 HER2 2+/ISH+ cases) and 114 HER2 (78 HER2-low and 36 HER2-0) negative cases. HER2 3+ was dichotomized according to the staining cell rate (cut-off point; 90%) into the following two groups; HER2 3+/&amp;gt;90% (70 cases) and HER2 3+/&amp;lt; 90% (6 cases). The chemotherapy regimen was anthracycline and taxane with the addition of anti-HER2 therapy if the cases were HER2-positive. The clinicopathological factors examined were age, nodal status, tumor size, ER/PgR (cut-off points; 1% and 10%), and the Ki-67 index value (cut-off points: 20% and 40%). pCR was defined as the absence of residual invasive cancer on H&amp;E evaluation of the complete resected breast specimen (ypT0/Tis). We investigated the correlation between pCR and clinicopathological factors. The DFS and OS were calculated using the Kaplan-Meier method and analyzed using the log-rank procedure. Uni- and multivariate analyses of factors for pCR were performed using regression analysis. Results: 1. pCR was observed in 48 cases (57.8%) after NAC in the HER2 positive group and 17 cases (14.9%) in the HER2 negative group. 2. There was no significant relationship between the pCR rate and ER, PgR, Ki-67, menopausal and nodal status in the HER2 positive group. However, pCR was significantly observed more often in smaller tumors. HER2 3+( &amp;gt;90%) had a significantly higher pCR rate than HER2 3+(≤90%) and HER2 2+(ISH+). Multivariate analysis revealed that HER2 3+( &amp;gt;90%) and tumor size (≤5cm) were significant factors for pCR in HER2 positive BC cases. 3. Patients with pCR after NAC had significantly better DFS in HER2 positive BC cases. 4. There was a significant correlation between the pCR rate and ER≤10%, PgR≤10% and tumor size &amp;lt; 5cm in the HER2 negative BC cases. There was no relationship between the pCR rate and the HER2 status; 19.4% in HER2-0 and 12.8% in HER2-low. 5. Multivariate analysis revealed that the PgR status and tumor size were significant factors for pCR in the HER2 negative BC cases. 6. There was no significant difference in DFS between patients with pCR and non-pCR, especially in the luminal type BC cases. Moreover, no significant difference was observed between HER2-low and HER2-0. Conclusion: pCR rate after NAC was 57.8% in the HER2 positive cases and 14.9% in the HER2 negative cases. Moreover, the HER2 3+( &amp;gt;90%) group had a significantly higher pCR rate than the HER2 3+(≤90%) and HER2 2+(ISH+) groups. There was no correlation between the HER2 status (HER2-low and HER2-0) and pCR rate in the HER2 negative BC cases. In addition, the ER/PgR negativity (≤10%) was a significant factor for pCR in the HER2 negative cases. These findings suggest that the IHC data on the HER2 and ER/PgR status may be effective in predicting the pCR rate after NAC in BC cases. Citation Format: Nobuyuki Arima, Reiki Nishimura, Kazuhiro Muramoto, Atsushi Inayoshi, Tomio Tanigawa, Sugiko Watanabe. Studies on factors for pathological complete response after neoadjuvant chemotherapy in relation to HER2 status in primary 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 PO1-27-03.

Abstract PO5-18-09: Anthracycline-free neoadjuvant therapy with nab-paclitaxel and carboplatin in non-luminal breast cancer: a single-arm phase II trial

Abstract Background Anthracycline and taxane-based chemotherapy are the corner stone of neoadjuvant therapy in early breast cancer. Anthracycline-free regimens have been addressed widely because of cardiac toxicity especially in HER2-positive breast cancer when combining trastuzumab and pertuzumab. Aim of this trial was to assess the efficacy and safety of nab-paclitaxel combined with carboplatin in the neoadjuvant therapy of non-luminal breast cancer. Methods The Neopath trial was a prospective, single-arm phase II trial conducted in Comprehensive Breast Health Center, Ruijin Hospital between April 2019 and October 2021. Patients who had cT2-4NanyM0 or cTanyN1-3M0 triple negative breast cancer (TNBC) or HER2-positive breast cancer were enrolled. Patients were treated with neoadjuvant nab-paclitaxel (100 mg/m2) and carboplatin (area under the curve 2) on days 1, 8, and 15, for four 4-week cycles. Concurrent trastuzumab at 2 mg/kg (loading dose 4 mg/kg) and pertuzumab 420 mg (loading dose 840 mg) were given in patients with HER2-positive tumors. Surgery was performed after 4-6 cycles of neoadjuvant therapy. Trastuzumab and pertuzumab after surgery was continued every 3 weeks for a total duration of 1 year. The primary endpoint was pathological complete response (pCR) rate, defined as no invasive tumor in breast and axillary lymph nodes (ypT0/Tis N0) after neoadjuvant therapy. Secondary endpoints were pCR rate in predefined subgroups, pCR (ypT0 N0), objective response rate (ORR); event-free survival (EFS), breast conservation rate and toxicity. Results A total of 106 patients were enrolled in the study and 99 of them proceeded to surgery. The pCR (ypT0/is N0) rate was 41.41% in total, 33.78% in TNBC and 64.00% in HER2-positive breast cancer. Proportion of patients achieving pCR (ypT0 N0) was 38.38% in total, 31.08% in TNBC and 60.00% in HER2-positive tumors. In the ITT population, 93 patients were event-free at a median follow-up of 24 months, while 5 in TNBC group and 1 in HER2-positive group had relapse or distant metastasis. EFS in patients achieving pCR was higher than patients without pCR (HR=7.328, 95%CI=1.453-36.96, p=0.0158). ORR was 72.49% in total, 67.12% in TNBC and 88.00% in HER2-positive breast cancer. Total breast conservation rate was 10.1% and 12.2% in TNBC, 4.0% in HER2-positive subgroup. The most frequent grade 3 or higher adverse events were neutropenia (57%), vomiting (11%) and thrombocytopenia (8%). Conclusion Neoadjuvant anthracycline-free regimen of nab-paclitaxel combined with carboplatin in non-luminal breast cancer was an effective and well-tolerated regimen. Citation Format: Deyue Liu, Li Zhu, Jiayi Wu, Wei Wang, Shuning Ding. Anthracycline-free neoadjuvant therapy with nab-paclitaxel and carboplatin in non-luminal breast cancer: a single-arm phase II trial [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 PO5-18-09.

Abstract PO3-09-03: Dysbiosis of gut microbiota in patients with breast cancer

Abstract [Background] The effects of gut microbiome on various diseases have become widely known, and many studies reported that there was a correlation between the change of gut microbiota, that is dysbiosis, and the progression of digestive tract cancer. In addition, it is well-known that gut microbiota was correlated to the efficacy of immune checkpoint inhibitors for multiple types of cancer. However, the significance of gut microbiota in patients with breast cancer still remains unclear. The aim of this study is to analyze the gut microbiota in patients with breast cancer, compared with healthy women. [Subjects and Methods] We used the pre-treatment feces of 79 patients with primary breast cancer who received treatment at our facility and performed metagenome analysis of the V3-4 region of 16S rDNA. We also analyzed the breast cancer patients' microbiota with QIIME2 analysis method, compared to randomly selected 100 women aged 30-77 years from NIBIOHN's public data . We also assessed the characteristics of the gut microbiota of breast cancer patients by subtypes and its relationship with clinical and pathological factors. [Results] In Japanese gut microbiota, the Firmicutes and Bacteroidetes phyla make up the majority, but Firmicutes was the most common bacterial phylum in 52% of the public cohort, whereas 96.2% (76/79) of the breast cancer patients’ group (BC) showed a significantly higher proportion (p&amp;lt; 0.0001). In addition, ANCOM analysis revealed that the relative bacterial amounts of the Firmicutes, Bacteroidetes, and Proteobacteria phyla were significantly decreased in BC compared to the public cohort (PC), and at the bacterial genus level, the Feacalibacterium genus was significantly decreased in BC. Furthermore, the percentage of Fusobacteria phylum, which is a well-known oral bacteria that exacerbates digestive tract cancer, was 49.3% in BC, compared to 35% in PC (p=0.04). Among BC, the relative frequency of Fusobacteria phylum was significantly higher in the HER2-negative group than in the HER2-positive group (p&amp;lt; 0.0001). In BC, both alpha diversity (p&amp;lt; 0.0001) and beta diversity (p=0.001) were significantly lower than in PC. [Conclusion] An increase in the Firmicutes phylum is known to be associated with obesity, and also likely to affect the incidence risk of breast cancer. The results suggest that the Fusobacteria phylum and Feacalibacterium genus may be risk or preventive factors for breast cancer. Dysbiosis of gut microbiota is suggested to be associated with various diseases, and in this study the decrease in bacterial amount and diversity was observed in BC compared to PC, which may affect the onset and progression of breast cancer. Citation Format: Mai Yamada, Takafumi Morisaki, Yo Sato, Kimihisa Mizoguchi, Yuka Takao, Yurina Ochiai, Yoshiki Ootubo, Saori Hayashi, Masafumi Nakamura, Makoto Kubo. Dysbiosis of gut microbiota in patients with 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 PO3-09-03.

Abstract PO4-05-11: Effects of body mass index on the treatment outcome of patients with metastatic breast cancer in the real world

Abstract Purpose: Metastatic/recurrent breast cancer has a relatively long survival compared to other cancers and depending on the biologic subtype, the treatment outcome is different. In general, obesity or overweight is associated with poor prognosis of breast cancer, but the relationship between body mass index (BMI) and prognosis in metastatic cases is not clear. The aim of this study is investigating the effect of BMI on survival outcome through long-term follow-up in single institution, retrospectively. Method: This study included the patients with metastatic/recurrent breast cancer who has been diagnosed from January 2000 to December 2022 in an institution. BMI was calculated based on weight at diagnosis of metastatic disease, divided into 4 groups according to Asian-Pacific classification, and clinical characteristics including biologic subtype and overall survival (OS) were retrospectively reviewed. The statistical analysis was performed using Kaplan-Meier survival analysis and Cox proportional hazard model. Result: A total of 679 patients were enrolled. Median age was 51 years-old (25~89), 672 patients (99.0%) were female and 425 patients (62.6%) showed pre-menopausal status. The frequencies of HR+, HER2, and TNBC subtype were 335 (50.7%), 191 (28.9%), and 135 (20.4%), respectively and the BMI classification was 33 (5.5%), 251 (41.6%), 124 (20.5%), 196 (32.4%) for underweight, normal, overweight, and obesity, respectively. During a median follow-up of 33.8 months, the median OS in each of the HR+, HER2+, and TNBC subgroups was 54.9 (95% CI 38.7-71.1), 62.8 (95% CI 47.8-77.8), and 20.8 months (95% CI 12.0-29.7). In univariate analysis, there was no statistically significant difference in OS according to BMI in whole patients, however, in the HER2-positive group, the underweight BMI group showed poor OS (p=0.045). In multivariate analysis, the factors affecting OS were age (HR 0.59, 95% CI 0.41-0.87, p=0.008), poor ECOG PS (HR 8.35, 95% CI 2.54-27.49, p&amp;lt; 0.001), TNBC subtype (HR 2.14, 95% CI 1.56-2.94, p&amp;lt; 0.001), visceral metastasis (HR 2.13, 95% CI 1.63-2.79, p&amp;lt; 0.001), 5% or more weight loss during treatment (HR 1.46, 95% CI 1.09-1.97, p=0.012) and obesity BMI group (HR 0.69, 95% CI 0.51-0.94, p=0.019). Conclusion: In the case of patients with metastatic/recurrent breast cancer, there is concern about an increase in body weight, a known risk factor for breast cancer, while receiving palliative aim treatment. For the past 20 years, the mainstay of treatment for metastatic/recurrent breast cancer has been cytotoxic chemotherapy or anti-HER2 agents, and in this case, the higher BMI group patients showed better treatment outcomes compared with normal BMI patients. Citation Format: Kyoung Eun Lee, Ahrong Ham, Sewon Lee, Jungmin Jo, Soo Ji Hong, Ji Eun Lee, Haena Lee, Sungchan Gwark, Jeongshin An, Hyun-Goo Kim, Jun Woo Lee, Joohyun Woo, Woosung Lim, Byung-In Moon, Sei Hyun Ahn, Hye Ah Lee. Effects of body mass index on the treatment outcome of patients with metastatic breast cancer in the real world [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 PO4-05-11.

Clinicopathologic features and prognosis of HER2- positive gastric cancer

Abstract Background The role of human epidermal growth factor receptor 2 (HER2) overexpression has been well established in breast cancer, with corresponding targeted therapies. In contrast, the clinicopathological features and prognosis of HER2 overexpression in gastric cancer remain inconclusive. Methods In this study, 334 patients with gastric cancer who received surgical resection between May 2017 and June 2021 were enrolled at a single medical center in Taiwan. HER2 status was determined by immunohistochemistry (IHC) staining or fluorescence in situ hybridization (FISH). The clinicopathological features and survival curves of the HER2-positive and HER2-negative gastric cancer patients were analyzed. Results The HER2-positive ratio was 7.2%. HER2-positive gastric cancer was associated with more differentiated tumors (P=0.016), more Lauren’s intestinal type (P=0.010) and a higher portion of Ming’s expanding type (P=0.033) in the univariate analysis, but only Lauren’s intestinal type was an independent factor in the logistic regression model (P=0.015). The overall survival and disease-free survival between the HER2-positive and HER2-negative groups were not significantly different. Patients with HER2-positive gastric cancer were more likely to have distant lymphatic recurrence than those with HER2-negative gastric cancer (P=0.026). Conclusions HER2-positive gastric cancer is associated with intestinal histological type and distant lymphatic recurrence, but HER2 is not an independent prognostic factor.

Abstract 3748: Evaluation of immune cells from patient-derived tumor tissue and peritoneal washing cytology in correlation with immunohistochemical markers in endometrial cancer

Abstract Background This study aims to evaluate the characteristics and clinical correlations of tumor-infiltrating lymphocytes (TILs) in endometrial cancer, derived from fresh tumor tissue and peritoneal washing cytology. Furthermore, it seeks to explore the correlation between TILs and immunohistochemical markers in endometrial cancer. Methods In this study, we investigated the nature of TILs extracted from endometrial tissue and peritoneal washing cytology, along with their correlation with immunohistochemical markers. Samples collected from endometrial cancer patients during surgery, with informed consent, were analyzed for immune cell composition using flow cytometry. We examined the association between pathological findings, a range of immunohistochemical markers (including LVSI, PD-L1, ER, P53, HER2, MLH1, MSH2, MSH6, PMS2, MSI), and the status of tumor-infiltrating immune cells (such as CD3-CD19+ B Cells, CD3-CD16+CD56+ NK Cells, CD4+CD25+ regulatory T cells (Treg), and CD3+CD8+ cytotoxic T cells). Results Our analysis encompassed 25 endometrial cancer-derived samples. Notable observations include an increase in CD3-CD19+ B cells in the LVSI-positive group and a decrease in the ER-positive group (p&amp;lt;0.05, respectively). CD3-CD16+CD56+ NK Cells decreased in the ER-positive group, while CD3+CD8+ cytotoxic T cells were decreased in the HER2-positive group (p&amp;lt;0.001, p&amp;lt;0.05, respectively). Other immunohistochemical markers showed no significant differences. Conclusion The study suggests that tumor-infiltrating immune cells from patient-derived tissue and peritoneal washing cytology may reflect the molecular and clinical characteristics of endometrial cancer. However, further research with an expanded sample size and correlation with oncologic outcomes is warranted to validate these findings. Citation Format: Changmin Shin, Seungmee Lee, Hyewon Chung, Jin Young Kim, Eunyoung Ha, Ji Hae Seo, Sojin Shin. Evaluation of immune cells from patient-derived tumor tissue and peritoneal washing cytology in correlation with immunohistochemical markers in endometrial cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3748.

Pathological complete response and associated factors in breast cancer after neoadjuvant chemotherapy: A retrospective study.

This study aimed to determine clinical and pathological factors that identify a pathological complete response (pCR) in breast cancer patients undergoing neoadjuvant chemotherapy (NAC). A retrospective, single-center study was conducted in women over the age of 18 who had been diagnosed with pathologically confirmed invasive breast cancer and who had received NAC between July 2016 and October 2021. Patient demographics, clinical, radiological, treatment, and pathological data were reviewed from the electronic hospital records. The primary outcome of interest was pCR, defined as the absence of residual invasive breast cancer in both the breast and axillary lymph nodes. Multivariable logistic regression analysis was used to identify factors associated with pCR. A total of 119 patients were included in the analysis. The distribution of age was 54.5 ± 11.5 years. pCR was observed in 33 (27.7%) patients. pCR for breast tissue was observed in 43 (36.1%) patients. There was no statistically significant relation between the clinical stage and pCR. Age, age at first labor, extent of disease in the breast, NAC completeness, clinical tumor size (cT) stage, clinical lymph node (cN) stage, and molecular subtype were analyzed in a multivariable model. Analysis showed that molecular subtype was the only independent factor related to pCR. pCR rates across molecular subtypes were: 8.7% in luminal-A, 10.8% in luminal-B, 54.5% in human epidermal growth factor receptor 2 (HER-2)-positive, 42.4% in luminal-B (HER-2 positive) and 46.7% in triple-negative. There was no statistically significant difference between luminal-A and luminal-B subgroups (odds ratio 1.15, 95% confidence interval, 0.19-9.35, p= 0.881). Despite the limited number of patients in HER2-positive and triple-negative groups, both demonstrated statistically significant higher odds compared to reference group. The presented study underscores the relevance of molecular subtypes in determining the response to neoadjuvant chemotherapy in breast cancer patients. Particularly HER2-positive and triple-negative subtypes may demonstrate more favorable response rates.

Trastuzumab and first-line taxane chemotherapy in metastatic breast cancer patients with a HER2-negative tumor and HER2-positive circulating tumor cells: a phase II trial

PurposeHER2 overexpressing circulating tumor cells (CTCs) are observed in up to 25% of HER2-negative metastatic breast cancer patients. Since targeted anti-HER2 therapy has drastically improved clinical outcomes of patients with HER2-positive breast cancer, we hypothesized that patients with HER2 overexpressing CTCs might benefit from the addition of trastuzumab to chemotherapy.MethodsIn this single-arm, phase II trial, patients with HER2-positive CTCs received trastuzumab as addition to first-line treatment with taxane chemotherapy. Patients with detectable CTCs but without HER2 overexpression that received taxane chemotherapy only, were used as control group. The primary outcome measure was progression-free rate at 6 months (PFR6), with a target of 80%. In November 2022, the study was terminated early due to slow patient accrual.Results63 patients were screened, of which eight patients had HER2-positive CTCs and were treated with trastuzumab. The median number of CTCs was 15 per 7.5 ml of blood (range 1–131) in patients with HER2-positive CTCs, compared to median 5 (range 1–1047) in the control group. PFR6 was 50% in the trastuzumab group and 54% in the taxane monotherapy group, with no significant difference in median PFS (8 versus 9 months, p = 0.51).ConclusionNo clinical benefit of trastuzumab was observed, although this study was performed in a limited number of patients. Additionally, we observed a strong correlation between the number of evaluable CTCs and the presence of HER2-positive CTCs. We argue that randomized studies investigating agents that are proven to be solely effective in the HER2-positive patient group in patients with HER2-positive CTCs and HER2-negative tissue are currently infeasible. Several factors contribute to this impracticality, including the need for more stringent thresholds, and the rapidly evolving landscape of cancer treatments.

The expanded indications of HER2-targeted therapies by monitoring of circulating tumor cells.

385 Background: Despite success in the HER2 targeted therapies for metastatic gastric cancer patients, the conventional assessment of HER2 status in tumor tissue specimens is still under debate. Methods: Twenty-seven patients with metastatic gastric cancer were treated according to histological HER2 status. On-chip sorting system was used for the isolation of circulating tumor cells (CTCs) before treatments. Epithelial mesenchymal transition (EMT) was assessed by the vimentin and cytokeratin. DNA was extracted from CTCs and applied to the gene panel with 409 cancer related genes. The fluorescence signal intensity &gt; 50 is set to be a threshold value for distinguishing between positive and negative HER2 on CTCs. Results: Thirteen patients (48%) with HER2 positive in tumor tissues (Group A) were treated with cytotoxic agents and trastuzumab (anti HER2 antibody) while 14 patients (52%) were negative and treated with cytotoxic agents. In these 14 patients, 8 patients (30%) showed HER2 positive (Group B) and 6 patients (22%) displayed HER2 negative (Group C) on CTCs. Increased expression of EMT was seen in Group A and B, indicating they are likely to have metastasis. Group B showed worse PFS than others (13.8 M in A, 7.0 M in B and not reached in C, p=0.012), suggesting Group B could be a candidate for expand indication of Trastuzumab. Genomic analysis showed some mutated genes involved in the PI3K signaling pathway which associated with drug resistance. Conclusions: Monitoring of circulating tumor cells leads to the expand indication of the HER2 targeted therapies in patients with metastatic gastric cancer.

Multi-directional Changes in 8-OHdG Concentration in Saliva during HER2 Expression in Breast Cancer

The purpose of this work was to evaluate changes in the structure of 8-OHdG in saliva in patients with breast cancer depending on molecular biological subtypes. The findings show that decreased salivary 8-OHdG concentrations in the HER2-positive group rapidly correlated with decreased cell differentiation and high Ki-67 levels, reflecting the aggressive nature of the tumor disease and poor survival prognosis. Thus, the presence of high levels of 8-OHdG in the oral cavity may lead to the development of the role of a biological marker of the HER2-positive group with a poor prognosis of breast cancer and can be used as an additional method of diagnosis, patient condition and response to therapy.

HER2 becomes a novel survival biomarker for gastric cancer patients: a pooled analysis.

Although anti-HER2 therapies have been widely used against gastric carcinoma, the prognostic significance of HER2 overexpression remains unclear. Previous studies failed to provide convincible evidence due to inconsistent HER2 evaluation criteria and heterogeneous clinical characteristics. To figure out the prognostic significance of HER2 expression in gastric cancer, we rigorously designed and conducted this study. Meta-analysis. Record retrieval was performed by searching PubMed, Web of Science, Cochrane Library, Embase, ASCO, and ESMO meeting libraries from inception to November 2022. Cohort studies investigating overall survival comparison between HER2-positive and HER2-negative gastric cancer patients were included. Both resectable and advanced cases were separately collected while HER2 evaluation standards should be consistent across eligible studies. Newcastle-Ottawa Scale was used for quality assessment. Overall survival was the only endpoint and effect size was presented by hazard ratio (HR) with its 95% confidence interval. The pooled calculation was conducted on Review Manager 5.4. Thirty studies were eligible, including 9945 patients. Eligible studies were mostly high quality (n = 31). Regarding resectable cases (n = 22), HER2-positive groups had significantly worse prognosis than HER2-negative counterparts (HR 1.56, 95%CI 1.32-1.85, p < 0.00001). For HER2-positive patients with advanced gastric cancer (n = 10), HER2 overexpression was also an unfavorable survival indicator (HR 1.70, 95%CI 1.23-2.35, p = 0.001). Potential heterogeneous studies had been eliminated while outcomes remained stable by sensitivity analysis. Subgroup analysis suggested HER2-positive patients had a poorer prognosis in both East Asian (resectable: HR 1.56; advanced: HR 1.32) and non-East Asian countries (HR 1.58; HR 3.27). As a novel survival biomarker in gastric cancer, HER2 overexpression indicates unfavorable prognosis among both resectable and advanced patients, irrespective of East Asian or non-East Asian populations. PROSPERO (CRD42020168051).