Negative HER2 Research Articles

Breast squamous cell carcinoma: Case report and review of the literature

Squamous cell carcinoma (SCC) of the breast is a rare and aggressive form of breast cancer, classified as a metaplastic carcinoma. Diagnosis of this carcinoma is challenging due to the absence of distinctive clinical or radiological features. Histopathological conformation is essential, and immunochemistry typically shows negativity for hormone receptors and HER2, with positive markers such as CK5/6 and P40. Treatment strategies are not well defined, but platinum-based chemotherapy has shown promising results in some cases. Radiotherapy can serve both curative and palliative purposes depending on disease stage. We report the case of a 57-year-old patient treated in our department with chemotherapy and radiotherapy.

Should a borderline negative HER2 result in a core biopsy of invasive carcinoma of the breast have HER2 assessment repeated in the excision specimen?

AimThe 2015 UK guidelines for HER2 assessment in breast cancer recommended repeat assessment if the core biopsy was scored as 2+ on HER2 immunohistochemistry (IHC) with borderline negative in situ...

The Great Mimicker: Goblet Cell Adenocarcinoma of the Appendix Mimicking Mammary Carcinoma in a Patient with a History of Metastatic Breast Cancer

Abstract Introduction/Objective Goblet cell adenocarcinoma of the appendix is a rare and aggressive malignancy with high- grade histological patterns that pose diagnostic challenges due to their resemblance to other tumors. Previous reports have indicated that high-grade goblet cell adenocarcinoma may exhibit similarities to well-differentiated neuroendocrine tumors, and metastatic high-grade goblet cell adenocarcinoma can manifest diverse histologic growth patterns within a single section. Methods/Case Report We present a case of an 82-year-old female with a known history of breast cancer with sacral metastasis, presenting with a left upper quadrant “pinching” sensation. Histopathological examination following colectomy showed features of metastatic mammary carcinoma with mixed lobular (pleomorphic and partial signet ring cell type) and ductal features (Figure 1); Notably, different histologic patterns were observed in two tumor deposits, highlighting the complexity of the diagnosis (Figure 2). However, further investigation of the tip of the appendix revealed goblet-like mucinous cells arranged in a tubular growth pattern (Figure 3). Immunohistochemical stains were performed with adequate controls, revealing positive staining for CK20, SATB2, and CDX2, while showing negativity for BRST2, SATB2, GATA3, CK7, PR, ER, and HER2 (Figure 4). These findings corroborate the diagnosis of goblet cell adenocarcinoma. Results (if a Case Study enter NA) NA Conclusion In our case, we observed morphological features of goblet cell adenocarcinoma that overlapped with those of established mammary carcinomas. This scenario underscores the diagnostic challenges posed by rare tumors and emphasizes the significance of identifying the low-grade component of goblet cell adenocarcinoma, particularly in patients with a history of metastatic breast cancer.

Challenges in treating coexisting scrotal apocrine carcinoma and gastric cancer: insights from an elderly patient: a case report and literature review

BackgroundApocrine carcinoma associated with Paget’s disease is a rare malignancy that typically manifests in elderly individuals, predominantly affecting the geriatric population. It commonly arises in regions rich in apocrine glands and often exhibits an insidious onset, potentially requiring several years to be diagnosed.Case presentationAn 80-year-old male was simultaneously diagnosed with scrotal apocrine carcinoma (showing Paget changes) and early-stage gastric cancer. Whole-genome exome sequencing confirmed these as independent malignancies with minimal genetic overlap, indicating that they were two primary tumors. The patient initially underwent successful surgery but experienced recurrence and metastasis. Treatment with capecitabine and paclitaxel showed promising responses, highlighting similarities between breast and apocrine carcinomas. Challenges were noted in the use of genetic testing and drug susceptibility assessments for treatment guidance. Notably, HER-2 expression in metastatic lesions, a trait of apocrine carcinoma, has remained unexplored due to negative HER-2 FISH results and a lack of available targeted therapies in China.ConclusionElderly patients often exhibit a lesser degree of aggressiveness toward treatment following a diagnosis of malignant tumors. It is imperative to carefully consider how to strike a balance between effective treatment and maintaining a satisfactory quality of life for these patients. This case underscores the complexity of treating coexisting rare cancers in older adults and emphasizes the need for personalized treatments and continued innovation in cancer therapy. The insights gained offer significant value in understanding and managing such rare cancer cases.

Is Oncoplastic Surgery Safe in High-Risk Breast Cancer Phenotypes?

Oncoplastic surgery (OPS) has increased in popularity over the recent years. It is a form of breast conservation surgery allowing for larger partial mastectomy (PM) resections followed by either volume displacement or volume replacement reconstruction techniques. However, there is a lack of evidence on the effectiveness and safety of OPS with radiotherapy (OPS + RT) in high-risk breast cancer phenotypes, such as triple negative breast cancer (TNBC) and HER2 positive (HER2+) patients. Our aim was to compare the breast cancer-specific survival (BCSS) and postoperative surgical complications in OPS + RT compared to PM alone with radiation (PM + RT) and total mastectomy (MTX) without radiotherapy (MTX-RT). Patient data were analyzed from the Surveillance, Epidemiology, and End Results (SEER) cancer registries from January 1, 2012 to December 31, 2020. Patients were stratified according to the type of surgery. Cox regression analysis was performed to assess prognostic factors of BCSS. A total of 24 621 patients with high-risk breast cancer phenotypes were identified, 180 underwent OPS + RT; 13 402, PM + RT; and 11 039 MTX-RT. OPS + RT was more frequently performed in younger (mean age of 65.53 years, SD: 9.29, p < 0.001), non-Hispanic White (90.5% vs. 77.7% vs. 76.3%) and single women (17.9% vs. 12.1% vs. 13.3%). MTX-RT was usually performed in patients with high histological grade, TNBC, and higher stages. Overall complication rates were higher in the MTX-RT, compared to OPS + RT and PM + RT, 2%, 1.1%, and 0.7%, respectively, p < 0.001. Rates of hematoma and surgical site infections were higher in the MTX-RT group. With a median follow-up of 46 months, OPS + RT had better BCSS rates at 5 years compared to PM + RT and MTX-RT (97.1% vs. 94.7% vs. 89.8%, p < 0.001). MTX-RT was found to be an independent prognostic factor of worse BCSS compared to OPS + RT (hazard ratio [HR] = 2.584; 95% confidence interval [CI]: 1.005-7.171), while PM + RT had no difference compared to OPS + RT (HR = 1.670, 95% CI: 0.624-4.469). OPS is a safe breast surgical option in patients with HER2+ and TNBC. Patients with high-risk phenotypes who underwent OPS + RT and have similar BCSS and complication rates compared to standard breast surgical options. As such, OPS should be considered as an option whenever breast conservation surgery is being discussed.

Prognostic significance of low HER2 expression in gastric cancer: a retrospective, single-center analysis

IntroductionMutated human epidermal growth factor receptor 2 (HER2) is an oncogene with critical pathogenic roles in breast cancer. HER2-low-positive breast cancer is a recently described subtype. We aimed to explore the clinical and molecular characteristics of gastric cancer with low HER2 expression, drawing on recent developments in breast cancer subtypes.Materials and methodsThis retrospective study involved 129 patients with HER2-non-amplified gastric cancer treated in Iwate prefectural Iwai Hospital from 2013 to 2019. Tumors were classified as HER2-null or low-positive based on immunohistochemistry score 0 or 1 + or 2 + with HER2 negativity in situ hybridization, respectively. Statistical analyses, including Kaplan–Meier analyses and Cox proportional hazards model were conducted.ResultsLow HER2 expression was present in 26% (33/129) of the patients. Clinicopathological characteristics were not significantly different between the HER2-low and null groups. Kaplan–Meier analysis of overall survival was significantly longer in the HER2-low group than in the HER2-null group (P = 0.01). In multivariate Cox regression analysis, HER2-null status was associated with worse survival (hazard ratio 3.01; 95% confidence interval 1.18–7.65; and P = 0.02).ConclusionThis study highlights the prognostic importance of low HER2 expression in gastric cancer, similar to that observed in HER2-low-positive breast cancer, and suggests reclassification of gastric cancer to improve personalized treatment. Future studies should elucidate the molecular underpinnings of low HER2 expression in gastric cancer to guide novel therapeutic strategies and improve outcomes.

Populations of Triple Negative and Hormone Receptor Positive HER2 Negative Breast Tumors Share Immune Gene Profiles

Populations of Triple Negative and Hormone Receptor Positive HER2 Negative Breast Tumors Share Immune Gene Profiles

Multimodal analysis of methylation and fragmentomic profiles in plasma cell free DNA for differentiation of benign and malignant breast tumors.

7 Background: Breast cancer ranks as the second leading cause of cancer-related mortality among women globally. Early detection of breast cancer is crucial for improving patient outcomes and reducing mortality rates. Liquid biopsy, which relies on circulating tumor DNA (ctDNA) shed by breast tumors into the bloodstream, presents a promising non-invasive approach for early breast cancer detection. However, accurately distinguishing between benign breast abnormalities and malignant tumors remains a significant clinical challenge, as misdiagnosis can lead to unnecessary invasive procedures. Methods: Herein, we employed a multimodal analysis approach, namely SPOT-MAS (Screen for the Presence of Tumor by DNA Methylation and Size), to profile alterations in methylation and fragment length patterns of cell-free DNA (cfDNA) from 169 breast cancer-confirmed patients and 99 patients diagnosed with benign breast lumps including cysts, fibroadenomas, and fibrocystic changes. A robust machine learning model was constructed using these signatures to differentiate between breast cancer patients and individuals with benign lesions. Results: Our genome-wide analyses identified distinct profiles of methylation changes, copy number alterations, and end motifs in cfDNA, enabling discrimination between breast cancer patients and individuals with benign conditions. Notably, we observed a significant enrichment of Thymine and Adenine at cfDNA cleavage sites in breast cancer patients. Moreover, our target sequencing analyses uncovered distinct methylation patterns in the regulatory regions of multiple genes, including hypermethylation in GPR126 or hypomethylation in TOP1 or MAFB in breast cancer cfDNA. Our multi-featured model achieved an AUC of 0.92 (95% CI: 0.88–0.97), a specificity of 97.44% and sensitivities of 57.14% and 61.70% for stage I and stage II–III patients, respectively. Furthermore, our multimodal assay effectively differentiated multiple molecular subtypes of breast tumors from benign lesions, achieving the highest sensitivity of 71.43% with Luminal A, followed by Luminal B, Triple Negative Breast Cancer (TNBC), Luminal B-HER2, and HER2 with sensitivities of 66.67%, 60%, 58.33% and 55.56%, respectively. Conclusions: Our findings demonstrate the potential of cancer-specific methylation and fragmentomic patterns in plasma cfDNA as novel biomarkers for accurately discriminating between breast cancer and benign lesions. This capability reduces the false-positive rate and helps avoid unnecessary biopsies in current clinical practice.

Populations of triple negative and hormone receptor positive HER2 negative breast tumors share immune gene profiles.

In breast cancer, triple negative (TN) breast cancer has most responses to immune checkpoint inhibitor (ICI) therapy. Lymphocyte infiltrate does not impact prognosis in Hormone receptor positive HER2 negative (HR + HER2-) breast tumors and few HR + HER2- tumors respond to ICI. We contrasted immune-associated gene expression between 119 TN and 475 HR + HER2- breast tumors from The Cancer Genome Atlas (TCGA) and confirmed our findings in 299 TN and 1369 HR + HER2- breast tumors in the METABRIC database. TN and HR+ HER2- tumors grouped into immune-high or -low tumors, both subtypes were represented in the immune-high group. The largest difference between the immune-high TN and HR + HER2- tumors was TN tumors had more abundant Th1 and Th2 CD4+ T cells while HR + HER2- tumors had more abundant fibroblasts (log2FC > 0.3; p < 10×10-10). This suggests an immune-high signature is not dictated by breast cancer subtype, but fibroblast subsets associated with worse outcome were higher in the immune-high HR + HER2- tumors.

Survival Outcomes of Breast Cancer Patients in South India Over 20 Years.

The study aimed to investigate the distribution and clinicopathologic features of breast cancer patients in South India, while also examining the overall survival (OS) and identifying predictive factors affecting it. Additionally, we aimed to assess the influence of risk factors on Disease Free Survival (DFS) and Distant Disease-Free Survival (DDFS). This retrospective cohort study on breast cancer trends used comprehensive follow-up including regular patient contact, medical record review and collaboration with healthcare providers. Patients without follow-up information for more than 12 months were contacted by telephone, while those with no follow-up after 2 years were labelled as lost to follow-up. A total of 3256 patients were identified from a single cancer institute in India. The median follow-up time was 8.1 years. The 5-year survival rates were 89%, 84%, 85%, 88% and 10-year were 82%, 78%, 79%, 83% for luminal cancers, Triple Negative Breast Cancers, HER2 enriched and luminal with HER2 enriched respectively. Poorer survival rates were seen among those with pT3/4 tumors, nodal involvement at diagnosis, Estrogen receptor negative status, high Ki67 proliferative index and higher TNM stage at diagnosis of the disease. Although our patients were younger and had more aggressive types of cancer, their DFS, DDFS and overall survival were comparable to other developed nations.

Impact of HER2-targeted PET/CT imaging in patients with breast cancer and therapeutic response monitoring.

Patients with breast cancer exhibit heterogeneity in the expression of the human epithelial growth factor receptor 2 (HER2). Clinically, re-biopsying recurrent or metastatic lesions presents substantial challenges. This study aimed to evaluate the efficacy of HER2-targeted PET/CT imaging in identifying HER2 expression in breast cancer lesions and monitoring therapeutic responses. This exploratory analysis used data from a prospective study that included adult patients with breast cancer who underwent both Al18F-NOTA-HER2-BCH and 18F-FDG PET/CT imaging at Beijing Cancer Hospital between June 2020 and July 2023 (NCT04547309). Fifty-nine participants, with a median age of 55 years, were analyzed. Lesions imaged with HER2-targeted PET/CT before anti-HER2 therapy exhibited higher SUVmax values than after therapy in HER2 immunohistochemistry (IHC) 3 + lesions (19.9, 95% CI: 15.7-25.3 vs 9.8, 95% CI: 5.6-14.7; P = .006). A significant positive correlation was observed between SUVmax on HER2-targeted PET/CT and IHC before therapy (P = .034), with higher SUVmax values noted in lesions with positive HER2 pathology compared to those with negative HER2 status (17.9 ± 13.2 vs 1.1 ± 0.3; P = .007). HER2 expression heterogeneity was confirmed both between primary and metastatic lesions (22.9%) and among different metastatic sites (26.7%) as assessed by HER2-targeted PET/CT. A superior therapeutic response correlated with higher pretreatment SUVmax values. The HER2-targeted PET/CT procedure was well-tolerated by all patients. HER2-targeted PET/CT imaging offers a practical, non-invasive, and quantitative approach for assessing HER2 status in breast cancer patients, facilitating the optimization and personalization of therapeutic strategies by oncologists.

Pathologic complete response to KEYNOTE522 and HER2-directed therapy for synchronous TNBC and HER2+ breast cancer

Simultaneous presentation of two separate primary breast cancers of differing histology at initial diagnosis is an uncommon phenomenon; it is even rarer to find these pathologically distinct populations within the same biopsy. Here we report the case of a patient diagnosed with clearly demarcated, pathologically heterogenous triple negative breast cancer (TNBC) and HER2+ breast cancer that was treated with a hybrid chemoimmunotherapy regimen combining elements of Keynote-522 and a standard HER2-directed neoadjuvant regimen, yielding apathologic complete response by the time of surgery with no notable adverse events. Molecular analysis of the histologically distinct tumor populations confirmed molecular evidence of differential HER2 expression but also suggested clonal relatedness of the two tumor populations based upon mutational profile, with phenotypic divergence potentially resulting from copy number alterations in NF1. Overall, this case highlights a rare histologic phenomenon that was successfully treated by combining both TNBC and HER2 directed neoadjuvant therapies.

Additional confirmation of successful cell suspension fractionation of metastatic axillary node tissue

We present herein an extension to our recently developed and published method termed "Fractionation of Nodal Cell Suspension" (FNCS). The method enables efficient subcellular fractionation into nuclear (N) and cytosolic (C) compartments of extremely fibrous and problematic metastatic axillary lymph node (mALN) tissue, using the entire nodule. For the purpose of the present study, a case of invasive lobular breast cancer (BC) patient with pT2N3aMx status and defined primary tumor markers (ERα 8, PR-B 8, and HER2 score 0) was available. Initially, the mALN tissue of this patient was analyzed by immunohistochemistry (IHC), and a positive correlation of nodal ERα, PR-B and HER2 biomarkers to those of the primary tumor was obtained. Subsequently, the mALN was FNCS fractionated into N and C, and Western blot (WB) analysis demonstrated a single band for ERα, PR-B and nuclear loading control (HDAC1) in nuclear, but not in the cytosolic compartments, confirming the efficiency of our fractionation protocol. At the same time, HER2 bands were not observed in either compartment, in accordance with HER2 negativity determined by IHC in both primary tumor and mALN tissue. In conclusion, by confirming the nuclear expression of ERα and PR-B biomarkers in metastatic loci, we demonstrate the purity of the FNCS-generated compartments - the protocol that offers a reliable tool for further analysis of nuclear versus cytosolic content in downstream analysis of novel biomarkers in the whole mALN of BC patients.

Serum lipid ratios as novel prognostic biomarkers for patients with locally advanced breast cancer treated with neoadjuvant therapy

ABSTRACT Objectives To investigate the association between lipid ratios and survival outcomes in patients with locally advanced breast cancer (LABC) undergoing neoadjuvant chemotherapy. Method This retrospective study included patients with LABC receiving neoadjuvant chemotherapy. Serum lipid levels were prospectively measured at baseline. Associations of triglyceride to total cholesterol (TG/TC), triglyceride to high-density lipoprotein (TG/HDL) and triglyceride to low-density lipoprotein (TG/LDL) ratios with prognosis were evaluated. Results Patients with high TG/TC (adjusted hazard ratio [aHR] = 2.47, 95% CI: 1.10, 5.56, p = 0.029), TG/HDL (aHR = 2.73, 95% CI: 1.16, 6.41, p = 0.021) and TG/LDL (aHR = 2.50, 95% CI: 1.11, 5.65, p = 0.027) ratios were more likely to experience disease-free survival (DFS) events. Subgroup analysis suggested that the prognostic impact of lipid ratios was more pronounced in patients with negative HER2 status or those at a high risk of recurrence (e.g. clinical stage III, Ki67 > 30%). Additionally, higher lipid ratios tended to indicate early DFS events (0 ~ 2 years) (TG/TC p = 0.021, TG/HDL p = 0.046, TG/LDL p < 0.001), and the TG/LDL ratio demonstrated the best predictive efficacy (TG/TC vs. TG/HDL vs. TG/LDL, 1-year AUC: 0.724 vs. 0.676 vs. 0.846, 2-year AUC: 0.653 vs. 0.638 vs. 0.708). Conclusion Baseline serum TG/TC, TG/HDL and TG/LDL ratios were independent prognostic factors in patients with LABC undergoing neoadjuvant therapy. However, their utility in predicting the early DFS events warrants further investigation. Clinical trial registration NCT05621564.

The survival benefit of adjuvant trastuzumab with or without chemotherapy in the management of small (T1mic, T1a, T1b, T1c), node negative HER2+ breast cancer

There is limited data regarding the added benefit of adjuvant systemic therapy in the management of small, node-negative, HER2+ breast cancer. In a multi-institutional retrospective analysis using the American Society of Clinical Oncology CancerLinQ database, we compared survival outcomes among T1a-c N0 HER2+ patients diagnosed between 2010 to 2021 who received locoregional therapy alone or in combination with adjuvant trastuzumab (+/− chemotherapy). Primary outcomes were invasive disease-free survival (iDFS) and overall survival (OS). Of the 1,184 patients, 436 received locoregional therapy alone. We found a statistically significant improvement in iDFS (HR 0.73, P = 0.003) and OS (HR 0.63, P = 0.023) on univariate analysis with adjuvant trastuzumab with or without chemotherapy which remained statistically significant on multivariate analysis. Three-arm univariate analysis found that iDFS was significantly improved with trastuzumab monotherapy (P = 0.003) and combination therapy (P = 0.027) compared to observation. Subgroup data suggests that T1b/c tumors derive the greatest benefit.

Cost-effectiveness of talazoparib for patients with germline BRCA1/2 mutated HER2-negative advanced breast cancer in China and the US

Breast cancer is one of the tumors with the highest prevalence rate among women in the world, and its BRCA1/2 gene is a common mutation site. Talazoparib, as a targeted PARP inhibitor, can effectively control the occurrence and development of breast cancer with BRCA1/2 gene mutation, and play a therapeutic role. Based on the findings from the Phase III EMBRACE trial (NCT01945775 clinical trial), our analysis reveals that the talazoparib group demonstrated a significant extension in progression-free survival, along with improved response markers and patient-reported outcomes when compared to conventional therapies. This study aims to assess the cost-effectiveness of talazoparib for treating advanced breast cancer with germline BRCA1/2 mutations and HER2 negativity, considering the perspectives of health services in China and the United States. The results obtained will serve as a valuable reference for promoting rational drug utilization and enhancing medical resource efficiency. To evaluate the cost-effectiveness of Talazoparib more scientifically and provide clinicians with chemotherapy options, this paper developed a Markov model based on the EMBRACA clinical trial (clinical Trails.gov No., NCT01945775) to simulate the survival events of breast cancer patients in the Talazoparib group and the standard treatment group. The state transition probability and clinical data of breast cancer patients during treatment were extracted from the phase III EMBRACA clinical trial. The cost data generated during the treatment process comes from local hospital pricing, other references, and expert consultation. This article uses US dollars to calculate the treatment cost and incremental cost-effectiveness ratio. Health outcomes are expressed in Quality Adjusted Life Years (QALYs). In addition, Outcomes were measured in quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio, which robustness was evaluated by deterministic and probabilistic sensitivity analyses. This article establishes a Markov model for single-item sensitivity analysis. The results show that the economic benefits of using Talazoparib as a new treatment strategy in both China and the United States are higher than other drugs, and it is cost-effective. Compared to the control group, the incremental cost incurred by the Talazoparib treatment group in China was $2484.48/QALY, with an incremental QALY of 1.5. However, Talazoparib in the United States holds a dominant position, saving costs of $10,223.43 and increasing QALYs by 1.5. The clinical treatment effect of Talazoparib group in BRCA1/2 mutant advanced breast cancer patients is better than that of the standard treatment group, and the progression free survival period is significantly prolonged. From the perspective of medical and health services in China and the United States, the Talazoparib group is more economical than the standard treatment group in treating patients with BRCA1/2 mutant advanced breast cancer.

Immunohistochemical Expression of Human Epidermal Growth Factor Receptor 2 and Ki67 in Apocrine Gland Anal Sac Adenocarcinoma.

Apocrine gland anal sac adenocarcinoma is an aggressive neoplasm, and surgery remains the treatment of choice, although it is controversial in advanced cases. The prognostic factors are not well established. Human Epidermal Growth Factor Receptor 2 (HER2) is a membrane protein related to tumorigenesis, whereas Ki67 is a nuclear protein related to cell proliferation. Both are potential prognostic markers and therapeutic targets. This study aimed to evaluate the expression of HER2 and Ki67 markers in canine apocrine gland anal sac adenocarcinoma. The tumor samples were divided into four groups: largest tumor diameter less than 2.5 cm, largest tumor diameter greater than 2.5 cm, metastatic lymph nodes, and control group of non-neoplastic anal sacs. Each contained 10 samples. Immunohistochemistry was performed to verify the expression of HER2 and Ki67 markers. Positive HER2 staining was observed in 45% of the neoplastic cases and negative HER2 staining in 100% of the control group. The Ki67 expression had a median of 25% in all groups, except for the control group, which had a median of 8%. The HER2 and Ki67 expression was present in apocrine gland anal sac adenocarcinoma, making them potential therapeutic targets. However, it was not possible to determine the clinical value of either marker.

Phase II randomized study of maintenance therapy with regorafenib (REGO) versus placebo after first-line platinum and fluoropyrimidines-based chemotherapy in HER2 negative locally advanced/metastatic gastric (GC) or gastroesophageal junction (GEJ) cancer: Results of a-MANTRA study (GOIRC-05-2016).

4056 Background: REGO is an oral multi-targeted TKI that showed promising activity in advanced HER2-neg gastric cancer pts. The a-MANTRA study aimed to evaluate the efficacy and safety of REGO as maintenance after first-line (1L) therapy in advanced GC/GEJ tumors. Methods: This is a randomized, double-blind, placebo-controlled, multicenter Phase-II study in which HER2 neg advanced GC/GEJ pts with disease control after 1L platinum and fluoropyrimidines-based therapy, were randomized (1:1 ratio) to receive maintenance placebo (ARM A) or REGO (ARM B) starting at 80 mg with an escalation up to 160 mg (once daily on d1-21 q28 days), until intolerance or PD. The primary endpoint was Progression Free Survival 1 (PFS1). Two-sided 80% CIs were calculated to detect HR of 0.57, using a one-sided α=0.10 to have 90% power, translating to 3 months of improvement in mPFS. 118 subjects were required to observe 88 events. The interim analysis (IA) was planned after 44 events. Results: 67 pts were randomized in 18 Italian Cancer Centers; 64 pts (33 in ARM A and 31 in ARM B) received treatment. Most of the pts were male (64.1%), Caucasian (96.8%), ECOG PS 0 (81.2%), and median age 66 (40-80) yrs; the main primary tumor side was proximal (64.1%) with intestinal subtype (54.7%). Peritoneum metastases were present in 42.2%. IA showed a 98% probability of achieving a positive and statistically significant result for mPFS1. The study was stopped early due to the introduction of ICIs as 1L in PD-L1-positive pts. The objective responses to 1L chemotherapy were RP (50.0%), SD (42.2%), and CR (7.8%). At a median follow-up of 31 months (IQR 19.1-33-8), 28 (84.8%) and 26 (83.8%) events for each arm were reported. The main reason for discontinuation was PD (66.7% and 35.5%). The mPFS was 3.91 (80% CI, 2.27-5.98) and 5.19 months (80% CI, 4.0-7.26) with HR= 0.736 (80%CI, 0.51-1.04; p=0.1318). The mOS was 11.25 and 16.97 months (80%CI, HR=0.596 [0.318-1.103], p=0.1003). The most common G3-4 toxicities in ARM A and B were fatigue (3.0 vs 6.4%), thrombocytopenia (3.0 vs 3.2%), hand-foot syndrome (0 vs 12.9%), diarrhea and skin rash (0 vs 3,2%, respectively). Conclusions: Despite the promising trend, considering the sample was not sized for the statistical study hypothesis, REGO maintenance therapy after 1L chemotherapy did not reach statistically significant results in mPFS1. No significant safety concerns were raised. New study designs following the REGO with ICIs are currently underway. Clinical trial information: NCT03627728 .

Clinicopathological characteristics and outcomes of patients with HER2-low breast cancer: 6-year ambispective cohort study from India.

e23260 Background: Patients with low HER2-positive breast cancers are treated like those who are entirely HER2-negative. The DESTINY-Breast trials have proven Trastuzumab deruxtecan's benefit in the low HER2 subset. In Literature, limited data is available regarding the characteristics and outcomes of patients with low HER2 positivity from India. This study is done to address this research gap. Methods: This was an ambispective cohort study where we analysed the patients with carcinoma breast who were treated at our institute in the last 6 years. Out of 1845 patients, 243 were identified to have low HER2 expression. Patients were classified as Low HER2 positive if they had HER2 1+ or 2+ by IHC and negative by FISH. The clinical and pathological characteristics, progression-free survival (PFS) and overall survival (OS) of HER2 low subset, Estrogen Receptor (ER) positive and negative HER2 low cohorts and Metastatic (MBC) HER2 low patients were analysed separately. Results: A total of 243 patients were analysed. Of which 157 had HER2 2+ and 86 had 1+ expression. 240 were females. 79.8% were ER+ and 20.2% were ER negative among the total patients. 76.7% and 81.5% were ER+ in HER2 1+ and 2+ cohorts respectively. 78.2% were non-metastatic and 21.8% had MBC. 34.6% were treated with Neoadjuvant chemotherapy (NACT) and 42.4% with adjuvant chemotherapy (CT). 4.5% of patients treated with NACT attained PCR. 53.1% had T2, 16.8% had T4 disease. Most of the patients had N0 (35.4%) and N1(37%) disease. The OS of all low HER2+ patients were 4.97 years 95%CI(4.72-5.22). The OS in HER1+ and 2+ cohorts were 4.08 years and 5.04 years respectively. The PFS in low HER2+ patients was 5.01 years 95%CI(4.74-5.27) and 4.29 years and 4.89 years in HER2 1+ and 2+ cohorts. In the ER+ and negative cohorts, 31.4% of ER+ were treated with NACT and 45.4% of ER+ patients were treated with adjuvant CT. Most of ER+ low HER2 patients were of T2 stage (53.6%, p = 0.037). 36.6% were N0 and 34% were N1. 14.4% of ER+ low HER2 were MBC and 16.3% ER negative low HER2 were MBC. The OS of ER+ lowHER2+ cohort was 4.44 years and ER- HER2+ cohort was 4.43 years. Patients with MBC had a larger tumour size and nodal positivity (T4 43.4%, N1 37.8%,p = 0.001). The PFS and OS in MBC were 3.42 and 3.07 years compared to 5.29 years and 5.37 years in non-metastatic patients. Patients who were treated with NACT had an OS and PFS of 4.24 and 4.20 years and those who were treated with adjuvant CT had an OS of 5.39 years. Conclusions: The data on low HER2-positive patients is scarce in the Indian population. The low HER2+ patients had a PFS of 4.97 years and an OS of 5.01 years. Most of the patients had a T2 and N1 disease. The research gap low HER2+ subset is significant, especially considering the recent approval of trastuzumab deruxtican in India. With ongoing trials in MBC and non-metastatic settings, the benefit from this newer option may become clearer, particularly in ER+ low HER2 subset.

Analysis of risk factors for recurrence within 12 months after surgery in patients with breast cancer receiving neoadjuvant therapy at a Brazilian cancer center.

e13039 Background: Early recurrence following treatment for localized breast cancer typically occurs within 5 years, and is commonly linked to high-risk clinicopathologic factors. However, literature focusing on risk factors for earlier recurrence timeframes is scarce, particularly within the neoadjuvant treatment population. Therefore, this study aims to investigate potential predictors for recurrence within 12 months post-surgery in breast cancer patients submitted to neoadjuvant therapy. Methods: This is an observational, descriptive, retrospective study involving 310 patients with recurrent breast cancer who received neoadjuvant therapy between January 2007 and March 2022, at AC Camargo Cancer Center in São Paulo, Brazil. Patients were compared based on relapse time after surgery (&lt;12 months or ≥12 months), and risk factors were analyzed using the Chi-Square test or Fisher’s Exact test. Results: From 310 patients analyzed, 108 relapsed within 12 months and 202 after this period. Factors predicting recurrence in less than 12 months included: Histologic grade (HG) III ( p &lt; 0.01); nuclear grade (NG) III ( p &lt; 0.001); mitotic counts &gt;20/mm2 ( p = 0.02); Ki67 &gt; 20% ( p = 0.010); triple negative breast cancer (TNBC) and HER2+/HR- subtypes ( p &lt; 0.001); interruption of neoadjuvant therapy due to disease progression or toxicity ( p &lt; 0.001); chemotherapy dose reduction or delay ( p = 0.001); omission of adjuvant radiotherapy ( p &lt; 0.001) and interruption of adjuvant HER2 targeted therapy ( p &lt; 0.001). Menopausal status, Residual Cancer Burden (RCB) index, type of surgery and clinical stage showed no significant correlation with the outcome. Conclusions: Recurrence in less than 12 months was associated with intrinsic factors, such as HG III, NG III, high mitotic counts, Ki67 &gt; 20%, TNBC, as well as interruption or delay of neoadjuvant therapy, omission of adjuvant radiotherapy and interruption or delay of HER2 targeted therapy, pointing out potential risk factors in this population.