Breast cancer molecular subtype and relationship with clinicopathological profiles among Vietnamese women: A retrospective study.

BACKGROUND: Molecular subtypes play an important role in predicting prognosis and guiding treatment for breast cancer. Having a better knowledge of ethnic molecular features is essential. OBJECTIVES: Determining the distribution of various breast cancer molecular subtypes and investigating the relationship between these subtypes and clinicopathological features. METHODS: Retrospective data was collected from Hanoi National Cancer Hospital and Bach Mai Hospital that included 274 women diagnosed with invasive breast cancer between January 2017 and June 2019. Patients were categorized into five subtypes according to the 2015 St. Gallen molecular classification. The variables analyzed were molecular subtypes and tumor-related characteristics. To evaluate the relationship between these subtypes and clinicopathological features, a Chi-squared test and Fisher exact test were performed. RESULTS: The most prominent subtype was Luminal A (33.2%), followed by Luminal B/Her2- (19.7%) and Luminal B/Her2 + (17.5%), then HER2 overexpression (16.4%), whereas triple negative was the least popular subtype (13.1%). Particularly, 33.9% of all patients, including the Luminal B/Her2 + and the HER2 overexpressing groups, were Her2 positive. There was a statistically significant difference between molecular subtypes and histological type (p = 0.01), tumor grade (p < 0.001), but it was independent of age, tumor size, lymph node metastasis, and lymphovascular invasion. CONCLUSIONS: In contrast to the triple negative variant, the Luminal A variant is the most common among Vietnamese women. The rate of positive tests for HER2 was rather high. These subtypes were closely related to tumor grade and histopathological type. Understanding the molecular subtypes and their relation to clinicopathological features helps clinicians with patient treatment, and prognosis. The application of the 2015 St. Gallen molecular classification should be recommended for use in clinical practice.

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

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

Rare T263P epidermal growth factor receptor extracellular domain mutation of advanced non-small cell lung cancer in a Vietnamese male patient.

T263P mutation is one of the rare EGFR mutations located on chromosome 7p11.2, which is a change in amino acid residue at position 263 of the epidermal growth factor receptor protein, where L-threonine has been replaced by L-proline. This missense mutation in the extracellular EGFR domain is not well-known in lung cancer. In this study, we first report a patient with advanced lung adenocarcinoma harbouring only a rare T263P EGFR mutation who benefited from first-line afatinib therapy in Vietnam. The patient achieved a partial response with a time-to-treatment failure of 5 months. The patient subsequently received several chemotherapy regimens as the disease progressed, with overall survival of 17 months. Non-small cell lung cancer with a rare T263P EGFR mutation responds to afatinib but has a poor prognosis. Further studies are needed to determine the efficacy of targeted therapies in this specific population.

PD-L1-negative non-small cell lung cancer harbouring a rare BRAF mutation with successful treatment of first-line pembrolizumab plus chemotherapy: A case report and review the literature.

BRAF mutations are uncommon in non-small cell lung cancer (NSCLC), accounting for less than 5% of all NSCLC cases. The utilization of targeted therapies in non-V600E BRAF mutant NSCLC is considered controversial, although non-V600E genotype is reported in ~50% of all BRAF mutant patients. We document the case of a 63-year-old patient with NSCLC harbouring a rare BRAF E501Q mutation, who had prolonged response to immunotherapy combined with chemotherapy in Vietnam. The patient was diagnosed with metastatic PD-L1-negative lung adenocarcinoma and received pembrolizumab plus chemotherapy as first-line treatment. After completing 35 cycles of pembrolizumab and pemetrexed, his disease has remained stable during the treatment-free follow-up period, and he is alive 38 months after treatment initiation at the latest follow-up. Immune-based therapy is an appropriate option for lung adenocarcinoma with rare non-V600E BRAF mutation. Further clinical studies are necessary to determine the effectiveness of using immune-based therapy in this specific population.

Combined Large-Cell Neuroendocrine and Squamous Cell Carcinoma of the Uterine Cervix with a Personal History of the Primary Breast Duct Carcinoma in situ: A Clinicopathological Characteristic and Outcome.

Squamous cell carcinoma admixed with large-cell neuroendocrine carcinoma of the uterine cervix is an extremely rare malignancy with a poor prognosis. We report a 50-year-old woman with mixed squamous cell carcinoma and large-cell neuroendocrine carcinoma of the uterine cervix with an individual history of early-stage breast cancer. She was diagnosed preoperatively with cervical cancer stage FIGO 1B2. However, during surgery, a lesion was found in Douglas's peritoneum. The histopathological result of surgical specimens was mixed squamous cell carcinoma and large-cell neuroendocrine carcinoma. Then, she received concurrent chemoradiotherapy. Currently, after 3 months of treatment, she has not developed recurrent lesions.

Impact of Androgen Receptor Expression and the AR:ER Ratio on the Survival Outcomes in the Diverse Subgroups of Vietnamese Breast Cancer: A Single Institutional Retrospective Cohort Analysis.

Background: The androgen receptor (AR) has recently emerged as a useful marker for the more favorable prognosis and better outcomes among women with estrogen receptor (ER) + ve breast cancer (BC) and the further refinement of BC subtype. Furthermore, AR expression in ER - ve tumors has a particular prognostic significance. Additionally, the ratio of nuclear AR to ER may critically have an influence on tumor biology and respond to endocrine therapy. Purpose: To define the AR expression and AR:ER ratio, and explored their correlation with the clinicopathological features, prognosis, and survival outcomes in the various subclasses of invasive BC. Methods: The current study was conducted on 522 BC patients who had surgical operations, without neoadjuvant chemotherapy by applying a retrospective cohort analysis. The clinicopathological characteristics were recorded. Immunohistochemical staining was performed on AR, ER, PR, HER2, and Ki67. Expression of AR was paired into different immunophenotypes for analysis with clinicopathological features and survival. All BC patients' survival was analyzed using Kaplan-Meier and log-rank models. Results: The presence of AR was detected in 65.3%. Positive AR, the ratio of AR:ER<2, luminal androgen receptor (LAR) + and AR + HER2 + immunophenotypes were significantly associated with better prognostic features. AR:ER<2 was observed in the prolonged overall survival (OS) and disease-free survival (DFS) (87.9 and 86.2%, respectively) compared to AR:ER≥2 (25.0% in both) (P < .001). In contrast, in HR + ve BCs, the AR expression was not significantly correlated with survival. The multivariate model revealed that the ratio of nuclear AR to ER remained as an independent prognostic variable. Conclusion: The AR expression had a distinct OS and DFS. The AR:ER ratio is an independent indicator for predicting the OS and DFS of BC patients in both univariate and multivariate analyses.

Fibromatosis-Like Metaplastic Carcinoma: A Triple-Negative Breast Cancer with Clinically Indolent Behavior.

Fibromatosis-like metaplastic carcinoma is a special variant of spindle cell carcinoma, a type of metaplastic carcinomas. It has a favorable prognosis, unlike other metaplastic carcinomas, with a particular clinical behavior characterized by frequent local recurrence, the meager potential for axillary lymph nodes, and distant metastases. We presented the case of a 51-year-old female with a large mass on the left breast, which was successfully removed by surgical resection. The pathological diagnosis was fibromatosis-like metaplastic carcinoma with the help of morphology and immunohistochemistry adjustment.

Molecular classification predicts survival for breast cancer patients in Vietnam: a single institutional retrospective analysis.

BACKGROUND: The Bhagarva surrogate molecular subtype definitions classify invasive breast cancer into seven the different subgroups based on immunohistochemical (IHC) criteria according to expression levels of markers as ER, PR, HER2, EGFR and/or basal cytokeratin (CK5/6) which are different in prognosis and responsiveness to adjuvant therapy. PURPOSE: The present study aimed to classify primary breast cancers and directly compares the prognostic significance of the intrinsic subtypes. METHODS: The current study was conducted on 522 breast cancer patients who had surgery, but had not received neoadjuvant chemotherapy, from 2011 to 2014. The clinicopathologic characteristics were recorded. IHC staining was performed for ER, PR, HER2, Ki67, CK5/6, EGFR and D2-40 markers. All breast cancer patients were stratified according to Bhagarva criteria. The followed-up patients' survival was analyzed by using Kaplan-Meier and Log-Rank models. RESULTS: The luminal A (LUMA) was observed at the highest rate (32.5%). Non-basal-like triple negative phenotype (TNB-) and Luminal A HER2-Hybrid (LAHH) were the least common (3.3% in both). LUMA and luminal B (LUMB) were significantly associated with better prognostic features compared to HER2, basal-like triple negative phenotype (TNB+) and TNB-. Statistically significant differences were demonstrated between overall survival (OS), disease-free survival (DFS) and molecular subtypes (P<0.05), of which LUMB and LUMA had the highest rate of OS and DFS being 97.2 and 93.7%; and 97.2 and 90.5%, respectively. Conversely, HER2 revealed the worst prognosis with the lowest prevalence of OS and DFS (72.5 and 69.9%, respectively). CONCLUSION: The molecular subtypes had a distinct OS and DFS. The intrinsic stratification displayed inversely to clinicopathological features in breast cancer.

Evaluation of Tumor Budding in Predicting Survival for Gastric Carcinoma Patients in Vietnam.

BACKGROUND: Tumor budding (Bd) has been demonstrated to be a promising prognostic factor in many carcinomas and in gastric cancer. It may represent an optimal additional parameter that is helpful for risk stratification in gastric adenocarcinoma. Hence, the present research was designed to predict the survival outcomes of gastric cancer in Vietnam, applying the tumor budding criteria of the International Tumor Budding Consensus Conference (ITBCC) 2016. METHODS: The present study was conducted on 109 gastric cancer patients who underwent surgery but did not receive neo-adjuvant chemotherapy from 2012 to 2015. The patients' clinicopathological features were recorded. Bd was evaluated according to the 2016 ITBCC criteria and classified as Bd1 (0-4 buds), Bd2 (5-9 buds), and Bd3 (≥10 buds) grades, in addition to being categorized into 2 main Bd groups: low (<10 buds) and high (≥10 buds) Bd. Kaplan-Meier and log-rank models were applied to analyze survival proportions. RESULTS: Of all the patients, 22.9% were classified as Bd1, 31.2% as Bd2, and 45.9% as Bd3 grades. Furthermore, 54.1% patients were categorized into the low and 45.9% into the high Bd groups. Patients with Bd1 and Bd2 grades (the low Bd group) exhibited the best prognosis, with 5-year overall survival (OS) rates of 85.7%, 90.8%, and90.3%, respectively. Patients with Bd3 grade (the high Bd group exhibited the worst prognosis, and none of them lived for 5 years (p < 0.001). Similar to OS rates, disease-free survival (DFS) rates markedly reduced from the Bd1 to Bd3 grade: Bd1, 95.0%; Bd2, 84.7%; and Bd3, 0% (p < 0.001). CONCLUSION: Patients with different gastric cancer Bd grades exhibited significantly different OS and DFS rates. The present study findings suggest that the ITBCC criteria can be used to stratify Bd for the treatment and prognosis of gastric cancer patients in Vietnam.

Pathological Complete Response with Neoadjuvant Trastuzumab Combined with Chemotherapy in HER2 Positive Breast Cancer: A Single Institution Retrospective Analysis from Vietnam.

PURPOSE: Neoadjuvant regimens containing trastuzumab and chemotherapy were widely used in human epidermal growth factor 2 (HER2) positive breast cancer patients. In this article, we report complete pathological response (pCR) rates from a single institution in Vietnam. PATIENTS AND METHODS: Medical records of HER2 positive breast cancer patients who received neoadjuvant treatment with trastuzumab combined with chemotherapy were reviewed. Information on patient demographics, breast cancer stage, pathology reports, surgical data, and treatment regimens were collected. Pathological response was evaluated using Chevallier's criteria, in which complete pathological response was defined as yT0yN0 or yTisN0. RESULTS: Thirty-nine eligible breast cancer patients treated with chemo-trastuzumab combined regimens in a neoadjuvant setting at Vietnam National Cancer Hospital were included in the analysis. Median age was 47 (range 32-72 years). Of these 39 patients, 5 (12.8%) were at stage II and 34 (87.2%) were at stage III. Median tumor size was 5.8 cm. There were 22 (56.4%) and 17 (43.6%) patients who had hormone receptor (HR) negative and positive diseases, respectively. Pathological complete response in the breast was demonstrated in 30 out of 39 (76.9%) patients. Of 35 patients with lymph nodal involvement, axillary pCR occurred in 25 (71.4%) patients. Total pathological complete response (tpCR) was achieved in 25 (64.1%) of the evaluated patients. There was no significant association between pathological response rates and age, tumor grade, hormone receptor status, and Ki-67 expression. CONCLUSION: Neoadjuvant treatment with trastuzumab and chemotherapy combined in patients with HER2 positive breast cancer yielded a pathological complete response rate of 64.1%.

Uterine Tumor Resembling Ovarian Sex Cord Tumor: Clinicopathological Characteristics of a Rare Case.

Uterine tumor resembling ovarian sex cord tumor (UTROSCT) is a rare indolent stromal neoplasm of unclear histogenesis with a distinct histopathological entity. Immunophenotypes of sex cord positivity are the most significant information to confirm the diagnosis. We present the case of a 61-year-old female with a polypoid mass in the uterus which was successfully removed by surgical resection as hysterectomy. The pathological diagnosis was UTROSCT, which was characterized microscopically by sex cord images and immunohistochemical features of calretinin, CD99, and WT1 positivity.

Ultra-Deep Massive Parallel Sequencing of Plasma Cell-Free DNA Enables Large-Scale Profiling of Driver Mutations in Vietnamese Patients With Advanced Non-Small Cell Lung Cancer.

Population-specific profiling of mutations in cancer genes is of critical importance for the understanding of cancer biology in general as well as the establishment of optimal diagnostics and treatment guidelines for that particular population. Although genetic analysis of tumor tissue is often used to detect mutations in cancer genes, the invasiveness and limited accessibility hinders its application in large-scale population studies. Here, we used ultra-deep massive parallel sequencing of plasma cell free DNA (cfDNA) to identify the mutation profiles of 265 Vietnamese patients with advanced non-small cell lung cancer (NSCLC). Compared to a cohort of advanced NSCLC patients characterized by sequencing of tissue samples, cfDNA genomic testing, despite lower mutation detection rates, was able to detect major mutations in tested driver genes that reflected similar mutation composition and distribution pattern, as well as major associations between mutation prevalence and clinical features. In conclusion, ultra-deep sequencing of plasma cfDNA represents an alternative approach for population-wide genetic profiling of cancer genes where recruitment of patients is limited to the accessibility of tumor tissue site.

Aggressive lactating adenoma mimicking breast carcinoma: A case report.

INTRODUCTION: Lactating adenoma is a rare breast tumor which is commonly found in late pregnancy or lactation period. Despite its benign nature, lactating adenoma might develop aggressively and can be misdiagnosed as breast cancer. CASE PRESENTATION: We report a case of a 25-year-old female presenting with two large, ulcerative and bleeding breast masses. An open biopsy demonstrating lactating adenoma was considered discordant and surgery was performed to confirm the diagnosis. CONCLUSION: Careful clinical and histological evaluations are necessary to diagnose and manage lactating adenoma.

Actionable Mutation Profiles of Non-Small Cell Lung Cancer patients from Vietnamese population.

Comprehensive profiling of actionable mutations in non-small cell lung cancer (NSCLC) is vital to guide targeted therapy, thereby improving the survival rate of patients. Despite the high incidence and mortality rate of NSCLC in Vietnam, the actionable mutation profiles of Vietnamese patients have not been thoroughly examined. Here, we employed massively parallel sequencing to identify alterations in major driver genes (EGFR, KRAS, NRAS, BRAF, ALK and ROS1) in 350 Vietnamese NSCLC patients. We showed that the Vietnamese NSCLC patients exhibited mutations most frequently in EGFR (35.4%) and KRAS (22.6%), followed by ALK (6.6%), ROS1 (3.1%), BRAF (2.3%) and NRAS (0.6%). Interestingly, the cohort of Vietnamese patients with advanced adenocarcinoma had higher prevalence of EGFR mutations than the Caucasian MSK-IMPACT cohort. Compared to the East Asian cohort, it had lower EGFR but higher KRAS mutation prevalence. We found that KRAS mutations were more commonly detected in male patients while EGFR mutations was more frequently found in female. Moreover, younger patients (<61 years) had higher genetic rearrangements in ALK or ROS1. In conclusions, our study revealed mutation profiles of 6 driver genes in the largest cohort of NSCLC patients in Vietnam to date, highlighting significant differences in mutation prevalence to other cohorts.

Ultra-deep massively parallel sequencing with unique molecular identifier tagging achieves comparable performance to droplet digital PCR for detection and quantification of circulating tumor DNA from lung cancer patients.

The identification and quantification of actionable mutations are of critical importance for effective genotype-directed therapies, prognosis and drug response monitoring in patients with non-small-cell lung cancer (NSCLC). Although tumor tissue biopsy remains the gold standard for diagnosis of NSCLC, the analysis of circulating tumor DNA (ctDNA) in plasma, known as liquid biopsy, has recently emerged as an alternative and noninvasive approach for exploring tumor genetic constitution. In this study, we developed a protocol for liquid biopsy using ultra-deep massively parallel sequencing (MPS) with unique molecular identifier tagging and evaluated its performance for the identification and quantification of tumor-derived mutations from plasma of patients with advanced NSCLC. Paired plasma and tumor tissue samples were used to evaluate mutation profiles detected by ultra-deep MPS, which showed 87.5% concordance. Cross-platform comparison with droplet digital PCR demonstrated comparable detection performance (91.4% concordance, Cohen's kappa coefficient of 0.85 with 95% CI = 0.72-0.97) and great reliability in quantification of mutation allele frequency (Intraclass correlation coefficient of 0.96 with 95% CI = 0.90-0.98). Our results highlight the potential application of liquid biopsy using ultra-deep MPS as a routine assay in clinical practice for both detection and quantification of actionable mutation landscape in NSCLC patients.