Triple Negative Group Research Articles

Intratumoral and peritumoral radiomics for preoperative prediction of neoadjuvant chemotherapy effect in breast cancer based on 18F-FDG PET/CT

ObjectiveTo investigate the value of 18F-FDG PET/CT-based intratumoral and peritumoral radiomics in predicting the efficacy of neoadjuvant chemotherapy (NAC) for breast cancer.Methods190 patients who met the inclusion and exclusion criteria from 2017 to 2022 were studied. Features were extracted from the PET/CT intratumoral and peritumoral regions, feature selection was performed through the correlation analysis, t-tests, and least absolute shrinkage and selection operator regression (LASSO). Four classifiers, support vector machine (SVM), k-nearest neighbor (KNN), logistic regression (LR), and naive bayes (NB) were used to build the prediction models. The receiver operating characteristic (ROC) curves were plotted to measure the predictive performance of the models. Concurrent stratified analysis was conducted to establish subtype-specific features for each molecular subtype.ResultsCompared to intratumoral features alone, intratumoral + peritumoral features achieved higher AUC values in each classifier. The SVM model constructed with intratumoral + peritumoral features achieved the highest AUC values in both the train and test set (train set: 0.95 and test set: 0.83). Subtype-specific features improve performance in predicting the efficacy of NAC (luminal group: 0.90; HER2 + group: 0.86; triple negative group: 0.92).ConclusionIntratumoral and peritumoral radiomics models based on 18F-FDG PET/CT can reliably forecast the efficacy of NAC, thereby assisting clinical decision-making.

Predictors of time to brain metastasis and survival in patients diagnosed with breast cancer.

e13122 Background: Patients with breast cancer (BC) who develop brain metastases (BM) have poor survival outcomes. We aimed to identify significant predictors of time to develop BM and survival after diagnosis. Methods: Patient records were retrospectively reviewed from the Cleveland Clinic database between 2010-2020. Patients with a BC and a BM diagnosis were included for analysis. One way ANOVA was used to compare mean time to BM across subgroups (mean ± SE), and Kaplan-Meier method was used to compute median overall survival (mOS) after BM diagnosis (95% CI). Results: N=109 patients were included in the analysis with a mean age of 52 ± 13 years, mean time to developing BM of 42 ± 35 months, and mOS after BM of 12.00 months (8.99-15.01). The patients’ characteristics were as follows: female (98.2%), white (83.5%), married (56%), privately insured (43.1%), had a Karnofsky Performance Status (KPS) >80 (61.7%), and 21% had stage IV at initial diagnosis. In terms of BC characteristics, 80.4% of cases were ductal, 63.7% were Grade III, 52.3% were HR+, and 31.5% were HER2+, and 32.4% were triple negative. Most patients had extracranial metastases (ECM) at the time of BM diagnosis (67.8%), had at least 2 sites of BM (71.6%), parenchymal only BM (75%), and 10-30 mm BM (44.2%). 15.8% of patients underwent craniotomy and 86.2% received at least one form of radiotherapy (RT) for BM. The HR+/HER2- group had the longest time to BM compared to the shortest in the triple negative group (61.29 ± 6.95 vs 28.59 months ± 4.80, p<0.001). Patients receiving hormonal therapy had longer time to BM compared to those who didn’t (50.83 ± 5.04 vs 35.98 ± 4.67 months, p=0.034). Patients with Stage I disease had the longest time to develop BM (68.50 ± 13.66 months, p=0.009), while grade III status had the shortest time to BM (34.46 ± 3.46 months, p=0.002). Uninsured patients had the shortest time to BM (22.92 ± 4.09 months, p=0.003). After BM diagnosis, the HR+/HER2+ group achieved the best mOS at 35.00 months (14.20-55.80, p=0.040). Patients receiving Gamma Knife Radiosurgery (GKRS) achieved longer mOS than the other RT modalities at 30.00 months (11.46-48.51) vs 20.00 (1.26-38.74) in GKRS + Whole Brain RT (WBRT), 9.00 (3.43-14.57) in the WBRT, and 2.00 (1.12-2.88) in no RT group (p=0.022). Patients with a KPS of <80 had a shorter mOS compared to those with a KPS of >80 [5.00 (2.02-7.98) vs 17.00 (9.41-24.6), p=0.002]. Patients receiving hormonal therapy had longer mOS compared to those who did not [17.00 (6.58-27.43) vs 9.00 (3.72-14.28), p=0.016]. Patients with stage I disease had longer mOS compared to those with stage II-IV disease [41.00 (22.70-59.30) vs 10.00 (6.60-13.40), p=0.025]. Conclusions: This study identifies significant clinical predictors for BM development and survival in patients with BC including Hormone receptor status, treatment modalities, stage, and KPS. These findings emphasize the need for early BM screening in high-risk patients to improve survival.

Abstract PO5-24-03: Breast cancer intrinsic subtypes predict outcomes in primary and metastatic samples

Abstract Background: The prognostic and predictive value of the PAM50 intrinsic subtypes, namely Luminal A, Luminal B, Her2, and Basal-like subtypes, is well-studied in primary as well as metastatic breast cancer settings. Prosigna has emerged as a rapid PAM50 subtype predictor based on the NanoString nCounter assay. However, assay reproducibility across various RNASeq or qRT-PCR platforms can be challenging, especially when applying the predictor on metastatic breast cancer tumors. Here, we used SpinAdapt to create an intrinsic subtype predictor that works on RNA sequencing data, and validates on multiple tumor-sites. We evaluate real-world outcomes for our intrinsic subtype predictions across various immunohistochemical (IHC) labels and metastatic sites. Methods: We trained the subtype predictor on a cohort of 2,497 breast cancer patients using the PAM50 genes, profiled using Nanostring RNA nCounter assay (GSE148426). Approximately 5,423 de-identified records of breast cancer patients sequenced using whole-exome capture RNA-seq were included in our reference dataset. The reference dataset contained samples collected from various sites including breast (n=2440), liver (n=936), lymph node (n=577), lung (n=540), and bone (n=304). For subtype classification, we first batch-corrected the external dataset to Tempus RNA-seq reference dataset using SpinAdapt, then trained a Support-Vector Classifier (SVC) on the corrected data. A 10-fold CV experiment was performed on the corrected dataset to analytically validate the intrinsic subtype predictions. We retrospectively analyzed 7,021 de-identified breast cancer patients with known hormone receptor (HR) or HER2 status and a matched RNASeq sample. The concordance between HR/HER2 status and PAM50 prediction was analyzed, and these patients were excluded from training. Real-world overall survival (rwOS) was evaluated from the time of first diagnosis. The outcomes across intrinsic subtypes were further assessed according to tumor collection site and HR/HER2 IHC status. Results: The 10-fold CV experiment on the Tempus-adapted GSE148426 dataset achieved F-1 scores of 0.97, 0.86, 0.94, and 0.87 on Basal, HER2-like, Luminal A, and Luminal B PAM50 subtypes, respectively. On the Tempus evaluation dataset, 85.3% of HR+/HER2- patients (n=4,366), 65.4% of HR-/HER2+ patients (n=240), and 75.4% of HR-/HER2- patients (n=1,930) were classified as Luminal, HER2-like, and Basal, respectively. Evaluating outcomes on Tempus patients for each PAM50 group, the rwOS for the basal group was significantly shorter than patients not predicted to be basal (n=5,845, p< 2e-90). The rwOS for the predicted PAM50 basal patients remained significantly shorter than non-basal patients even when stratified by site of metastasis: breast (n=2,405; p< 1e-27), lymph node (n=577, p< 1e-7), liver (n=936; p< 1e-25), lung (n=540, p< 1e-13), and bone (n=304, p< 1e-3). Interestingly, within both HR+/HER2- (n=3,653) and HR-/HER2- (n=1,664) IHC cohorts with available outcomes data, the predicted PAM50 basal subtype could further stratify each of these populations with basal-subtype showing significantly worse prognosis than the non-basal subtype (p< 1e-27 and p< 1e-7, respectively). Conclusions: We retrospectively analyzed Tempus multimodal RWD to validate an in-house breast intrinsic subtype predictor that is agnostic to the site of metastasis. The prognostic value of the basal subtype was significant for breast cancer patients across various sites of metastasis including lymph node, liver, lung, and bones and IHC groups. For patients in each of the HR+/HER2- and triple negative IHC groups, the intrinsic molecular subtypes provided an additional level of prognostic detail with statistical significance. These data emphasize the importance of combining molecular subtypes with IHC-based diagnostics to fully characterize clinically relevant subpopulations and risk. Citation Format: Talal Ahmed, Mark Carty, Kaveri Nadhamuni, Raphael Pelossof. Breast cancer intrinsic subtypes predict outcomes in primary and metastatic samples [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 PO5-24-03.

Real-world data of HER2-negative early breast cancer patients treated with anthracycline and/or taxane regimens in Japan

BackgroundAnthracycline- and taxane-based chemotherapy regimens are established treatments for human epidermal growth factor receptor (HER)2-negative early-stage breast cancer with high risk of recurrence. This study examined the prevalence of these chemotherapy regimens as perioperative therapy, the patterns of retreatment, and factors influencing prescription choices in Japan.MethodsThis observational cohort study focused on high-risk early-stage breast cancer patients not undergoing anti-HER2 therapy, utilizing data from a hospital-based claims database in Japan spanning from April 2008 to September 2021.ResultsOf 42,636 high-risk patients who underwent breast cancer surgery, 32,133 (75.4%) were categorized as having luminal-type (received endocrine therapy) and 10,503 (24.6%) as having triple-negative cancer (not receiving any endocrine therapies). Most patients (98.7%) with luminal-type breast cancer received perioperative therapy, and 40.3% of those received anthracycline/taxane. In the triple-negative group, 57.0% of all patients received perioperative therapy and of those, 93.4% received anthracycline/taxane. Being over 40 years old, having an early stage (clinical stage ≤ II), and receiving treatment in non-specialized facilities were associated with less use of anthracycline/taxane in the luminal-type group. For the triple-negative group, associated factors with less use of anthracycline/taxane included being over 60 years old, treatment in small hospital (capacity < 200 beds), and treatment in non-specialized facilities.ConclusionsApproximately half the patients in both the luminal-type and triple-negative groups were prescribed anthracycline and/or taxane for perioperative chemotherapy. The choice was associated with patient age, cancer stage, and the scale and specialization of the treatment facilities. This study sheds light on the current state of breast cancer treatment practices in Japan.

Neoadjuvant radiotherapy in ER+, HER2+, and triple-negative -specific breast cancer based humanized tumor mice enhances anti-PD-L1 treatment efficacy.

Pre-operative radiation therapy is not currently integrated into the treatment protocols for breast cancer. However, transforming immunological "cold" breast cancers by neoadjuvant irradiation into their "hot" variants is supposed to elicit an endogenous tumor immune defense and, thus, enhance immunotherapy efficiency. We investigated cellular and immunological effects of sub-lethal, neoadjuvant irradiation of ER pos., HER2 pos., and triple-negative breast cancer subtypes in-vitro and in-vivo in humanized tumor mice (HTM). This mouse model is characterized by a human-like immune system and therefore facilitates detailed analysis of the mechanisms and efficiency of neoadjuvant, irradiation-induced "in-situ vaccination", especially in the context of concurrently applied checkpoint therapy. Similar to clinical appearances, we observed a gradually increased immunogenicity from the luminal over the HER2-pos. to the triple negative subtype in HTM indicated by an increasing immune cell infiltration into the tumor tissue. Anti-PD-L1 therapy divided the HER2-pos. and triple negative HTM groups into responder and non-responder, while the luminal HTMs were basically irresponsive. Irradiation alone was effective in the HER2-pos. and luminal subtype-specific HTM and was supportive for overcoming irresponsiveness to single anti-PD-L1 treatment. The treatment success correlated with a significantly increased T cell proportion and PD-1 expression in the spleen. In all subtype-specific HTM combination therapy proved most effective in diminishing tumor growth, enhancing the immune response, and converted non-responder into responder during anti-PD-L1 therapy. In HTM, neoadjuvant irradiation reinforced anti-PD-L1 checkpoint treatment of breast cancer in a subtype -specific manner. According to the "bench to bedside" principle, this study offers a vital foundation for clinical translating the use of neoadjuvant irradiation in the context of checkpoint therapy.

Significance of Serum Lactate Dehydrogenase as a Prognostic Marker and Outcome Predictor in Patients With Breast Cancer.

Background Breast carcinoma has been the most prevalent cancer in women, with research-based evidence showing a significant rise in the incidence of cancer and related morbidity and mortality in the Indian subcontinent. The predictive value of plasmatic lactate dehydrogenase (LDH) levels has been studied in breast cancer. Numerous studies have connected high LDH values to a poor prognosis, increased risk of incidence, recurrence, and associated mortality in patients with breast carcinoma. This study aimed to assess the clinical profile of breast carcinoma and determine the correlation of serum lactate dehydrogenase levels with the stage of the disease and assessment of high-risk features using histopathology and immunohistochemistry. Methods A total of 75 patients with carcinoma breast were enrolled for this study and classified into two groups: upfront surgery and post-adjuvant therapy. Serum LDH levels were estimated a day before the surgery (baseline) and on postoperative days 1, 7, 14, and 30. The clinical tumor, node, metastasis (cTNM) staging was correlated with pathological tumor, node, metastasis TNM (pTNM) staging and immunohistochemistry findings. Results The clinical characteristics of breast cancer, serum LDH levels, and stage of the disease were collected and analyzed. A significant decreasing trend was noted in LDH values post-op days, and statistically significant higher LDH values were noted in the triple-negative group, positive lymph nodes, and positive lymphovascular invasion patients. Conclusion Regularly elevated levels or an unanticipated rise in serum LDH might indicate poor outcomes. Hence, this non-specific enzyme marker can be suggested to be used routinely to assess disease outcomes.

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.

Diagnosis and treatment outcomes of urethritis-like symptoms in young males: a retrospective cohort study

The study evaluated the prevalence of gonorrhoea and chlamydia infections and find out other non-infectious diseases in sexually active young males with urethritis-like symptoms and their treatment outcomes. We retrospectively reviewed the young adult males (aged 20–50 years) who visited our clinic with urethritis symptoms from March 2019 to April 2022. All patients underwent urinalysis, urine culture, and urinary polymerase chain reaction (PCR) testing for gonorrhoea and chlamydia. Student’s t-test and Pearson’s chi-square test were used to compare the differences between the triple-negative group (i.e., negative results in urinalysis, urine culture, and urinary PCR) and the any-positive group. Logistic regression analyses were used to evaluate the predictive factors for positive PCR results for gonorrhoea or chlamydia in patients with negative urinalysis and urine culture. Of the 365 participants with urethritis-like symptoms, 139 patients were diagnosed of gonococcal or chlamydia urethritis. Among the 202 patients with negative urinalysis and urine culture, 60 patients were diagnosed with gonorrhoea or chlamydia using PCR. Urethral discharge was an independent predictor. 142 patients with triple negative results were attributed to other non-infectious diseases. Empirical antibiotic treatment is recommended for patients with urethritis symptoms showing positive or negative urinalysis results but with urethral discharge.

Assessment of Apparent Diffusion Coefficient Parameters and Coefficient of Variance in Discrimination of Receptor Status and Molecular Subtypes of Breast Cancer.

The objective of this study was to investigate the diagnostic power of apparent diffusion coefficient/coefficient of variance (ADCcV) as well as ADC parameters formed based on magnetic resonance images (MRI) in the distinction of molecular breast cancer subtypes. The study involved 205 patients who had breast cancer at stages 1-3. Estrogen receptor (EsR), progesterone receptor (PrR), human epidermal growth factor receptor 2 (Her2), and proliferation index (Ki-67) were histologically analyzed in the tumor. The correlations between the immunohistochemistry and intrinsic subtypes were analyzed using ADC and ADCcV. The maximum whole tumor (WTu) ADC (p=0.004), minimum WTu ADC (p<0.001), and mean WTu ADC (p<0.001) values were significantly smaller in the EsR-positive tumors than those in the EsR-negative tumors. Compared to the PrR-negative tumors, the PrR-positive tumors showed significantly smaller maximum, minimum, and mean WTu ADC values (p=0.005, p=0.001, and p<0.001, respectively). In the comparisons of the molecular subtypes in terms of ADCcV, the p-values indicated statistically significant differences between the luminal A (lumA) group and the triple negative (TN) group, between the luminal B (lumB) group and the TN group, and between the Her2-enriched and TN groups (p<0.001, p=0.011, and p=0.004, respectively). Considering the luminal and non-luminal groups, while a significant difference was observed between the groups considering their minimum, maximum, and mean WTu ADC values, their ADCcV values were similar (p<0.001, p=0.004, and p<0.001, respectively). Using ADCcV in addition to ADC parameters increased the diagnostic power of diffusion weighted-MRI (DW-MRI) in the distinction of molecular subtypes of breast cancer.

The relationship between 18F-FDG PET/CT parameters and histopathological-immunohistochemical properties in breast cancer

In this study, it is aimed to determine the correlation between histopathologic-immunohistochemical factors, tumor subtypes and fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) parameters such standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG) in breast cancer (BC). Initial PET/CT examination of 110 histopathologically proven BC patients (age ranging 27-92, mean age 56.18 ± 14.59) were included in this retrospective study. The relationship between histopathological-immunohistochemical factors, tumor subtypes and PET/CT parameters were analyzed by regression analysis. The mean SUV max value of 110 breast tumors was 7.73 ± 5.62 (range 1.4 - 34.15). Histological subtypes were; invasive ductal carcinoma (n:94, 85.5%), invasive lobular carcinoma (n=6, 5.5%) and other types (n=10, 9.1%). The distribution of BC subtypes was as follows; Luminal A (Lum A) (n=38; 34.5%), Luminal B (Lum B) (n=56; 50.9%), HER2-positive (n=3; 2.7%) and Triple Negative (TN) (n=13; 11.8%). Univariate regression analysis revealed significantly higher SUV max values in ductal carcinomas than lobular carcinomas (p=0.03). SUVmax values of the Lum B, HER2 positive and TN groups were higher than Lum A group (p=0.03, p&lt;0.001, p&lt;0.001 respectively). Univariate regression analyses also showed that the MTV and TLG values of TN group were significantly higher than Lum A group (p=0.011, p=0.007, respectively). In multivariate regression analyses, no significant difference was observed in above mentioned groups. MTV, TLG and SUVmax values significantly correlated with histopathological-immunohistochemical factors and tumor subtypes in BC. So that, these parameters can be used to predict the tumors’ behavior.

EMT Features in Claudin-Low versus Claudin-Non-Suppressed Breast Cancers and the Role of Epigenetic Modifications.

Breast cancers are heterogeneous and are classified according to the expression of ER, PR and HER2 receptors to distinct groups with prognostic and therapeutic implications. Within the triple-negative group, with no expression of these three receptors, molecular heterogeneity exists but is currently not exploited in the clinic. The claudin-low phenotype is present in a subset of triple-negative breast cancers and constitutes together with basal-like cancers the most extensive groups within triple-negative breast cancers. Suppression of epithelial cell adhesion molecules in claudin-low cancers is also a hallmark of Epithelial Mesenchymal Transition (EMT). The groups of claudin-low and claudin-non-suppressed breast cancers from the extensive publicly available genomic cohorts of the METABRIC study were examined to delineate and compare their molecular landscape. Genetic and epigenetic alterations of key factors involved in EMT and potentially associated with the pathogenesis of the claudin-low phenotype were analyzed in the two groups. Claudin-low cancers displayed up-regulation of several core transcription factors of EMT at the mRNA level, compared with claudin-non-suppressed breast cancers. Global promoter DNA methylation was increased in both groups of triple-negative cancers and in claudin-low ER-positive cancers compared with the rest of ER-positive cancers. Histone modifier enzymes, including methyltransferases, demethylases, acetyltransferases and deacetylases displayed amplifications more frequently in claudin-non-suppressed triple-negative cancers than in claudin-low counterparts and the expression of some of these enzymes differed significantly between the two groups. Claudin-low and claudin-non-suppressed triple-negative breast cancers differ in their landscape of EMT core regulators and epigenetic regulators. These differences may be explored as targets for therapeutic interventions specific to the two groups of triple-negative breast cancers.

MPL gene mutation is a possible risk factor for thrombosis in patients with essential thrombocythemia in Japan

ABSTRACTObjectivesSince MPL mutation is a rare driver gene mutation found in a small number of essential thrombocythemia (ET) patients, the clinical characteristics of patients with MPL mutations and their association with thrombotic events have not yet been elucidated in Japan.MethodsWe enrolled 579 Japanese ET patients based on the diagnostic criteria of the WHO classification 2017 and compared clinical characteristics of MPL-mutated patients (n = 22; 3.8%) to JAK2V617F-mutated (n = 299; 51.6%), CALR-mutated (n = 144; 24.9%), and triple-negative (TN) (n = 114; 19.7%) patients.ResultsThrombosis during follow up was observed in 4 out of 22 (18.2%) in the MPL-mutated group, which was the highest among all driver gene mutation groups (JAK2V617F-mutated, 8.7%; CALR-mutated, 3.5%; TN,1.8%). The MPL- and JAK2V617F-mutated groups had worse thrombosis-free survival (TFS) than the CALR-mutated (p = 0.043) and TN groups (p = 0.006). Univariable analysis revealed that a history of thrombosis was a possible risk factor for thrombosis among MPL-mutated patients (hazard ratio: 9.572, p = 0.032).ConclusionsMPL-mutated ET patients should require more intensive management to prevent recurrence of thrombosis.

Androgen receptor expression in female patients with triple-negative breast cancer: Relation to clinical, pathological, and ethnical data and comparison with non–triple-negative breast cancer.

e13022 Background: Breast cancer is the most common tumor among women. It constitutes 33% of all tumors in women in Israel. In addition to stage of the disease, other detective factors such as estrogen and progesterone receptors (ER) (PR), Human epidermal growth factor receptor 2 (HER2) and proliferation index (KI67) are examined to determine the treatment for metastatic disease and for the adjuvant therapy. Despite a good prognosis of breast cancer about 10-15% of breast tumors do not contain ER, PR, HER2. This group of is more, aggressive, called Triple negative (TN) tumor. In TN tumors the treatment is mainly chemical therapy, and the survival is lower than other types (Non triple negative: NTN) of breast cancers. Androgen receptor (AR) receptor is very important in prostate cancer and forms the basis of hormonal treatments for prostate cancer. AR can also be present in some breast cancer patients. This study examined AR levels in patients with TN breast cancer in order to evaluate whether AR could be used as a prognostic or therapeutic factor in patients with TN breast cancer. Methods: Demographic, clinical and pathological data were collected from the files of breast cancer patients treated at the Oncology Institute at Ziv Medical Center, Israel, between 2013 and 2020. Tissue samples were taken from the tumors at the Ziv Pathological Institute which were stored in paraffin. The evaluation of AR in breast cancer tissues was done by immunohistochemistry test. 55 TN cases were examined along in addition 90 cases with NTN were examined for comparison. Results: The mean age of the patients in the TN group was 56.9 ± 16.2 compared with 59.8 ± 13.5 years in the NTN group. 83.6% were Jewish and 16.4% Arab. 36.4% of TN patients were of childbearing age. 61.8% of the tumors in TN were Grade 3 compared to 32.2% in the NTN group (P = 0.001). Ki67) was 57.4 ± 27.8 in TN tumors and 24.9 ± 25.4 in NTN (0.001 &lt;P =). In 69.1% of TN patients AR was found to be negative compared to 26.7% in NTN (P = &lt;0.001). AR was found to be high in 9% of TN patients and in 72.8% in NTN who survived 5 years without disease (P = &lt;0.001). Negative AR was found in 75% of the patients who died from the disease in both groups. Positive AR was found in 30.9% of TN tumors compared to 73.3% in NTN (P = &lt;0.001). Conclusions: The AR receptor has a prognostic importance in breast cancer. We found that positive AR is more common in NTN patients than in TN. Survival of patients with low expression of AR is lower. The test is also relatively inexpensive, and it could be possible to be checked in all patients with TN breast cancer all over the hospitals. On the basis of the recent results, we suggest performing a new multicenter study for the treatment of AR-positive TN patients who failed conventional therapies with AR based hormone therapy.

Simultaneous expression of androgen receptor and tumor-associated neutrophil in breast cancer subtypes.

e12539 Background: Considering the heterogeneity of breast cancer phenotypes and different response rates to treatment, it is essential to determine prognostic markers that could confer therapeutic role as well. In this study, androgen receptor (AR) and tumor-associated neutrophil (TAN) in female breast cancer were investigated and their coherency with different subtypes of breastcancer and pathology findings were assessed. Methods: This cross-sectional study was conducted on patients with Stage I-IV breast cancer who were referred to Borna Pathology Center in Zanjan, Iran during 2018-2021. The tumoral paraffine blocks were evaluated for AR (by the IHC method) and TAN (by morphology and the IHC staining for myeloperoxidase). Relationships in different subtypes and stages were assessed.Using univariate logistic regression between 5 subtypes (defended by ER, PR, HER2, and Ki67), stage, age, metastasis (M), and grade with AR and TAN were studied separately and simultaneously. Results: We collected data from 83 women with Stage I-IV breast cancer with mean ± SD age of diagnosis 49.3±11.2 years. Percentage of AR+, TAN+, and AR+&amp;TAN+ were 71.1, 43.4, and26.5, respectively. The frequency of AR+ and AR-&amp;TAN- was high in hormone-positive subtypes, while TAN+ was frequent in the triple-negative group and AR+&amp;TAN+ in Luminal A and B groups. The relation between age, M, and Stage with AR, TAN, and AR &amp; TAN was not significant. AR was significantly related to subtype and grade. Conclusions: AR+ probability was significantly lower in Triple Negative subtype and poorly differentiated grade. Based on the heterogeneity of the presentation of these markers, survival evaluation can be important in risk assessment of them. Relationship between AR, TAN, and AR&amp;TAN with study variables. [Table: see text]

EARLY SURGICAL OUTCOMES OF OPERABLE BREAST CANCER PATIENTS BASED ON MOLECULAR SUBTYPING – A SINGLE-CENTRE STUDY

Objectives: The aim of the study was to assess patients belonging to four main molecular subtypes (Luminal A, Luminal B, HER2 neu positive and Triple negative) and their treatment plans with a view to compare their early surgical complications and the final outcomes specific to the surgical procedure adopted and molecular subtype. Methods: A Cross-sectional observational study at a Tertiary care center in central UP in a two-year period with Inclusion Criteria and Exclusion Criteria. Data Collection was carried out from the patients, diagnostic confirmation to rule out any exclusion criteria was performed. Clinical staging was done using the standard TNM criteria. All the specimens were subjected to immune-histochemical evaluation for surrogate molecular subtyping to see later the early surgical outcomes. Results: Mean age ranged from 47.57±9.57 (Group III) to 50.67±8.08 (Group II) years and BMI ranged from 23.71 (Group IV) to 26.38 kg/m2 (Group II). Neoadjuvant chemotherapy use was reported in 15.6% of Luminal A group, 33.3% of Luminal B group, 40% of Her2 negative and 52.2% of Triple negative group cases. Statistically, there was a significant difference among groups with respect to use of neoadjuvant chemotherapy. Breast conservation therapy was the preferred surgical intervention in majority of cases with Luminal A (60%) and Luminal B subtype (66.7%) whereas MRM was preferred in 54.3% of Her2 negative and 65.2% of Triple negative cases. MRM was performed in 36% of Luminal A cases. Primary surgical intervention failure (BCS) was seen in 1 (4%) case with Luminal A subtype. In this patient, mastectomy was performed as the corrective measure. Surgical site infection was noted in 1 (4%) case in Luminal A group only. Seroma formation was noted in 4 (16%) of Luminal A, 8 (22.9%) of Her2 negative and 2 (8.7%) of Triple negative patients. No case of flap necrosis was noted. Follow-up duration ranged from 15 days to 36 months. Median duration of follow-up was 6 months. No mortality was noticed in any group. Conclusion: Different surgical management strategies suggested that breast conservative surgery was more feasible in Luminal A cases whereas MRM was the preferred mode of surgery in other molecular subtypes. Within the limitations of short duration of follow-up, there was no significant difference among different molecular subtypes with respect to late complications and survival. Further studies with longer duration of follow-up and larger sample size are recommended.

Abstract OT3-20-03: Refusal of Breast Surgery in Breast Cancer Patients With cCR After Neoadjuvant Systemic Therapy and Vacuum-assisted Biopsy (VAB) and SLNB Confirmed pCR. An interim report of the prospective non-randomized trial. NCT04293796

Abstract Introduction The aim of the study was to prove efficacy and safety of de-escalation of traditional breast surgery in BC patients who develop cCR after neoadjuvant systemic therapy. Refusal of surgery was offered to exceptional responders after vacuum-assisted tumor bed biopsy and sentinel lymph node biopsy confirmed absence of residual disease (pCR). Materials and methods A single-center prospective study was run in the NMRC n.a. N.N. Petrov. Starting from August of 2020, 35 patients with early сT1-2N0-1M0 (stage Ia-IIb) triple-negative and HER2-positive (both ER+ and ER-) unifocal tumours without DCIS in core-biopsy specimen enrolled in the study. Primary lesions were marked with a single clip in the centre. In cases with nodal involvement (cN1) the affected lymph nodes were also clipped. Patients with triple-negative breast cancer received 4 cycles of AC q21d followed by 12 cycles of weekly paclitaxel and carboplatin AUC 2.0. HER2-positive patients received 4 cycles of AC followed by 4 cycles of docetaxel combined with trastuzumab and pertuzumab q21d. Breast US, mammography and SPECT were used at baseline and at response evaluation. Vacuum-assisted biopsy was performed with 7G needle and US-guidance in the OR simultaneously with the SLNB. VAB protocol included retrieval of the tumor clip as first stage. Subsequently surrounding tissues were sampled, and markers were placed to guide radiotherapy. In case residual tumor was found patients received standard breast-conserving surgery. In case the sentinel lymph nodes were found to be positive, standard level II axillary clearance was performed. HER2-positive patients with pCR confirmed by VAB and SLNB received adjuvant trastuzumab up to one year. HER2-positive patients with residual breast or nodal involvement received trastuzumab emtansine up to one year. In case ER+, all patients received appropriate endocrine-therapy. In case of residual in-breast or nodal involvement patients with triple-negative breast cancer received standart capecitabine. Results The interim analysis included 25 patients in both groups. The median follow-up of disease-free survival for patients is 12 months. In the triple-negative group 12 patients achieved cCR. All patients went on to receive VAB and SLNB. After VAB and SLNB pCR was confirmed 11 patients (91.7%). 1 patient had invasive residual tumor with less than 5% cellularity. FNR in this group was 8.3% (1/12). Patient with invasive residual tumor received standard breast-conserving surgery. All the patients in the TNBC group were also found to be (sn)ypN0. In the HER2-positive group cCR was achieved 13 patients. All patients went on to receive VAB and SLNB. After VAB and SLNB pCR was confirmed 10 patients (77%). 3 patients had invasive residual tumor with less than 5% cellularity. FNR in this group was 23% (3/13). Patients with invasive residual tumor received standard breast-conserving surgery. All HER2-positive patients were found to be (sn)ypN0. One patient with HER2-positive subtype experienced a local reccurence in the postoperative zone 16 months after surgery. Initially, this patient achieved cCR and undergone VAB with SLNB. On final pathomorphologic examination isolated focuses of DCIS were found (ypTisN0). Standard breast-conserving surgery was performed and histologically only DCIS was found. This patient recieved 1-year of Trastuzumab and standard radiotherapy with boost. After the histologic confirmation of local reccurence patient underwent nipple-sparring mastectomy with reconstruction and nowadays she is recieveing therapy with trastuzumab emtansine (T-DM1). Conclusion All visualization modalities fail to provide reliable information on the true rate of pCR. Contemporary systemic therapy regimens after accurate selection of patients, following the inclusion criteria, allows to achieve pCR in 75-90%, thereby reducing the risk of FNR after VAB. The trial continues to enroll patients and further follow-up is needed. Citation Format: Petr Krivorotko, Sergey Yerechshenko, Alexander Emelyanov, Ekaterina Busko, Tengiz Tabagua, Viktoria Mortada, Konstantin Zernov, Alexander Komyakhov, Kirill Nikolaev, Elena Zhiltsova, Larisa Gigolaeva, Roman Pesotsky, Diana Enaldieva, Yana Bondarchuk, Nikolay Amirov, Valentin Channov, Sergey Novikov, Zhanna Bryantseva, Anna Artemyeva, Viktoriya Smirnova, Tatiana Semiglazova, Alexey Belyaev, Vladimir Semiglazov. Refusal of Breast Surgery in Breast Cancer Patients With cCR After Neoadjuvant Systemic Therapy and Vacuum-assisted Biopsy (VAB) and SLNB Confirmed pCR. An interim report of the prospective non-randomized trial. NCT04293796. [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT3-20-03.

Evaluation of breast cancer metastasis and mortality rates based on molecular subtype: Adescription study.

Breast cancer in Indonesia has continued to increase. One diagnostic modality is immunohistochemical examination to determine breast cancer subtypes. To determine breast cancer metastasis and mortality rates based on molecular subtypes. A descriptive study was conducted based on retrospective data from hospital medical records from January 2016 to December 2019. The data comprised age, clinical stage, histopathological grade, molecular subtype, location, metastasis, and breast cancer mortality. The data were processed and analyzed. This study involved 172 patients. The most prevalent breast cancer subtypes were luminal A (60, 34.8%), followed by HER2 (47, 27.4%), triple-negative (38, 22.4%), and luminal B (27, 15.4%). The metastasis rate was 37.21% (64/172), with bone the tissue most affected (32 cases, 50%), followed by lung (24 cases, 37.5%) and liver (8 cases, 12.5%). The highest rates of bone, lung, and liver metastases were subtypes luminal A (31%), HER2 (29%), and triple-negative (38%), respectively. The mortality rate was 21% (36/172), with most in the triple-negative group (28.9%), followed by luminal B (25.9%), HER2 (21.2%), and luminal A (13.3%). Determination of breast cancer molecular subtypes through immunohistochemistry can determine the level of metastasis and mortality in breast cancer.

Molecular Profiles and Clinical Features of Myeloproliferative Neoplasms Unclassifiable (MPN-U) with and without JAK2/CALR/MPL Mutations

Introduction: Myeloproliferative neoplasms (MPNs) are clonal hematopoietic neoplasms and include polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), etc., each with specific diagnostic criteria. Patients who display features compatible with MPN but do not meet the diagnostic criteria for a specific entity are commonly assigned a diagnosis of MPN, unclassifiable (MPN-U). JAK2, CALR, and MPL are well-known driver mutations in PV, ET, and PMF. With the advancement and application of next-generation sequencing (NGS), the molecular profiles of the above 3 well-defined MPNs have been extensively studied. However, the molecular profile of MPN-U remains ill-defined. In this study, we aimed to describe the clinical and molecular features of MPN-U in our institution and then compare these features between patients with and without JAK2, CALR, or MPL mutations to better understand the clinicopathologic characteristics and prognosis of MPN-U. Method: The patients with a diagnosis of MPN-U and available NGS test results at our cancer center were identified and divided into two groups: cohort A) MPN-U with mutations in JAK2, CALR, or MPL, and cohort B) triple-negative. The patients' survival data, clinical parameters, bone marrow findings, and cytogenetics were collected for comparison. Baseline characteristics and somatic mutation distributions were compared using the chi-square test (categorical variables) and Wilcoxon rank sum test (continuous variables). Overall survival (OS) was calculated using the Kaplan-Meier method and compared using the log-rank test. A Cox proportional-hazards model was used to evaluate the association between OS and clinical factors. Results: Out of 8285 patients in our institutional clinical molecular database which houses NGS, we identified and confirmed MPN-U diagnosis in 53 patients. Among this group, 39 patients harbored JAK2 (n=36), CALR (n=1), MPL (n=1), or JAK2 and CALR co-mutations (n=1) and were assigned to cohort A. The remaining 14 patients were triple-negative and assigned to cohort B. The triple-negative patients in cohort B had higher median WBC count (18.5 x 10 9/L vs 9.98 x 10 9/L, p=0.04) and bone marrow cellularity (81% vs 64%, p=0.02) (Table 1). The mutational profile of cohort B was enriched for CUX1, ETV6, NRAS, SETBP1, and SRSF2 mutations. ASXL1 and SETBP1 were the most frequently mutated genes in the triple-negative group, and were often co-mutated with ETV6, NRAS, and/or SRSF2 (Figure 1). TET2 mutations appeared more common in cohort A, but this finding was not statistically significant. There were no significant differences in the other parameters, including gender, bone marrow blast percentage, karyotype, hemoglobin concentration, platelet count, and bone marrow fibrosis. Kaplan-Meier analysis demonstrated that the median OS time in cohorts A and B was not reached, and survival differences were not statistically significant (p-value 0.23). We used a Cox proportional-hazards model to evaluate the association between OS and clinical factors. Via backward elimination, we uncovered that high WBC count and low hemoglobin concentration were significantly associated with worse outcome (hazard ratios of 1.04 and 1.33, respectively, and p-values of 0.007 and 0.01). Conclusion: In our small cohort, the patients with MPN-U who were triple-negative for JAK2,CALR, and MPL mutations had more frequent CUX1, ETV6, NRAS, SETBP1, and SRSF2 mutations. ASXL1 and SETBP1 were the most frequently mutated genes in the triple-negative group, and were often co-mutated with ETV6, NRAS, and/or SRSF2. In addition, triple-negative patients had higher WBC counts and higher bone marrow cellularity. A Cox proportional-hazards model identified high WBC count and low hemoglobin concentration as being significantly associated with a worse outcome. Kaplan-Meier analysis did not reveal a difference in OS between triple-negative and JAK2, CALR, or MPL mutated MPN-U. A larger cohort is needed to evaluate the survival outcome of these two distinct groups. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Triple-Negativity Identifies a Subgroup of Patients with Better Overall Survival in Essential Thrombocythemia.

Essential thrombocythemia, as defined by the WHO in 2016, is a Philadelphia-negative chronic myeloproliferative neoplasm showing a better prognosis than polycythemia vera and myelofibrosis. In a variable percentage, patients with essential thrombocythemia show none of the known driver-gene mutations that may occur on JAK2, CALR, and MPL genes. Such patients are classified as triple-negative and their clinical features and prognosis have not been described with precision yet. In this study, we evaluated some of the characteristics of this population by comparing them with those of patients with driver-gene mutated ET. Data from 266 consecutive essential thrombocythemia patients were analysed. Triple-negative patients had a significantly lower symptom load and a lower frequency of splenomegaly at diagnosis. The results show that the rate of thrombosis was equal in the two subgroups. Overall survival was slightly better in the triple-negative group of patients.

Breast Cancer Patients with Brain Metastases: A Cross-Sectional Study

The prognosis of breast cancer patients with brain metastasis is poor. It was aimed to define the clinicopathological features of breast cancer patients with brain metastases and to determine the risk factors and survival outcomes associated with brain metastasis. This is a single-center, retrospective, cross-sectional study. A total number of 127 patients diagnosed with breast cancer and who developed brain metastasis between January 2011 and March 2021 were retrospectively analyzed. The survival and clinicopathological data of these patients according to 4 biological subtypes were evaluated (luminal A, luminal B, HER-2 overexpressing, and triple-negative). The median overall survival for all patients was 45.6 months. The median time from the diagnosis of breast cancer to the occurrence of brain metastasis was 29.7 months, and the median survival time after brain metastasis was 7.2 months. The time from the diagnosis of breast cancer to brain metastasis development was significantly shorter in HER-2 overexpressing and triple-negative subtypes than in luminal A and B subtypes. The median time from breast cancer diagnosis to brain metastasis was 33.5 months in luminal A, 40.6 months in luminal B, 16.8 months in HER-2 overexpressing, and 22.8 months in the triple-negative groups (p=0.003). We found the worst median survival after brain metastasis in the triple-negative group with 3.5 months. Early and close surveillance of high-risk patients may help early diagnosis of brain metastasis and may provide to perform effective treatments leading to longer overall survival times for this patient population.