Triple Negative Group Research Articles

Different Prognostic Values of Tumour and Nodal Response to Neoadjuvant Chemotherapy Depending on Subtypes of Inflammatory Breast Cancer, a 317 Patient-Study.

Simple SummaryInflammatory breast cancer is a rare entity associated with a poor prognosis, especially for the triple-negative subtype. This study investigates the independent prognostic value of tumour and nodal responses after neoadjuvant chemotherapy. It shows that tumour and lymph node responses did not have the same prognostic value regarding HR and HER2 statuses. We identified a subgroup of patients with triple-negative inflammatory breast cancer with residual lymph node disease for whom adjuvant treatment intensification may be worth investigating.Inflammatory breast cancer (IBC) is a rare entity with a poor prognosis. We analysed the survival outcomes of patients with nonmetastatic IBC and the prognostic value of tumour or nodal responses to assess their individual prognostic impact across IBC subtypes. This retrospective multicentre study included patients diagnosed with IBC between 2010 and 2017 to account for advances in neoadjuvant systemic therapies and modern radiotherapy at seven oncology centres in France. Three hundred and seventeen patients were included and analysed. After a median follow-up of 52 months, the 5-year DFS was lower for triple-negative (TN) (50.1% vs. 63.6%; p < 0.0001). After multivariate analyses, incomplete nodal response was the only significant prognostic factor in the triple-negative group (HR:6.06). The poor prognosis of TN-IBC was reversed in the case of nodal response after neoadjuvant chemotherapy. Breast response does not appear to be a decisive prognostic factor in patients with TN-IBC compared to lymph node response. Despite improvements in neoadjuvant treatments, IBC remains associated with a poor prognosis. In TN-IBC patients, lack of pathological complete node response was associated with poorer survival than any other group. Treatment intensification strategies are worth investigating.

PB2042: CLINICAL AND MOLECULAR CORRELATION OF PATIENTS WITH ESSENTIAL THROMBOCYTHEMIA: A RETROSPECTIVE ANALYSIS FROM A TERTIARY CARE CENTER IN INDIA.

Background: Approximately 50–70% of patients of ET harbor JAK2 mutation while about 20–30% patients carry CALR mutations. Data from developed countries has shown that CALR mutated patients have higher platelet count and lower thrombotic risk compared to JAK2 mutated patients. In India, testing for CALR and MPL mutation and next generation sequencing has become available only in last 5 years. There is lack of data regarding mutation status and its clinical correlation. We studied clinical features of ET patients presented to our hospital according to their mutation status. Aims: To study the molecular mutations and correlate them with the clinical features in ET patients Methods: We did the retrospective analysis of the patients diagnosed as ET from January 2016 to December 2021. Allele Specific PCR and fragment analysis was done to detect JAK2 (V617F), MPL (W515L/K) and CALR exon-9 mutations. Risk stratification done as per revised IPSET (International Prognostic Scoring for thrombosis in Essential Thrombocythemia) score. Therapy was started in all the patients according to their risk score with hydroxyurea or aspirin as the standard of care. Results: A total of 39 diagnosed cases of ET were identified. Median age was 55 years (30-83), 20/39 males (51.3%) and 19/39 females (48.7%). JAK2 mutation was found in 25.6% (10/39), CALR in 38.5% (15/39) and MPL in 5.1% (2/39) cases. Triple negativity was found in 30.8% (12/39) cases. Very low, low, intermediate and high-risk patients as per IPSET score were 53.9% (21/39), 10.2% (4/39), 20.5% (8/39) and 15.4% (6/39) respectively. The median age was statistically significantly lower in CALR positive cases compared to the JAK2 positive cases (45.9 vs 60.9years, p=0.011). The median Hemoglobin and platelet counts were slightly higher in CALR positive group (12.3 g/dL and 10.15x109/l) compared to JAK2 mutated and triple negative groups but the difference was not statistically significant. Three patients (7.7%) presented with thrombosis; two with cerebral venous thrombosis both CALR positive, one with arterial stroke and MPL gene mutation. Ten (25.6%) patients were lost to follow up. One (2.6%) died to pulmonary infection. Median follow up period was 24 months. None of the patient transformed to acute myeloid leukemia or myelofibrosis. None of the patient developed thrombotic event after diagnosis and appropriate treatment. Summary/Conclusion: We observed that CALR was the most common mutation in our study. The CALR mutated patients were younger in age but the median platelet counts, WBC count and Hemoglobin were not statistically different among different mutation groups. In contrast to western studies, thrombosis was observed to be higher in CALR mutated group than others in our patient population. We recommend larger multicenter study for further elucidation of these observations.

Prognostic Factors and Survival According to Tumor Subtype in Women With Breast Cancer Brain Metastases

Breast cancer (BC) is the second most cause of central nervous system (CNS) metastases. Studies report that almost one third of patients (pts) with triple-negative, one-third with human epidermal growth factor receptor 2 (HER2)-positive and 15% of those with hormone receptor-positive, HER2-negative metastatic breast cancer will develop brain metastases. It is known that the development of symptomatic brain metastases in women with advanced breast cancer is associated with poor prognosis, irrespective of local and systemic treatments. In the present study, we aim to determine the association between BC subtypes and CNS metastases occurrence and prognosis. Retrospective analysis of 309 BC patients with CNS metastases, confirmed by pathological and/or radiological methods, treated in a Cancer Center between 2003 and 2021, was obtained to identify clinicopathologic factors associated with early onset of brain metastases and survival outcomes. For analysis purposes, 3 BC subtypes were considered according to hormone receptor status and HER-2 expression: ER and/or PR positive, HER-2 positive and triple negative. The median time between diagnosis of BC and detection of CNS metastases was 43 months, and it was significantly shorter in triple negative group (8 months). Twenty-one patients (6,8%) had CNS metastases at BC diagnosis, with CNS being the first site of recurrence in 35,3%, mainly in HER2 positive. Most of the patients had parenchymal metastases (n = 245) and 37 (12%) had leptomeningeal (LM) disease, with predominance in ER and/or PR positive subtype (70,3%). In patients submitted to CNS surgery, the concordance between primary tumor and metastases subtype was higher in triple negative (76,9%) compared to 63,2% in HER-2 positive and 38,9% in ER and/or PR positive group (P < 0.05). After CNS involvement, 25,4% (n = 34) of patients with triple negative disease did not receive any systemic therapy, compared to 30,6% (n = 41) in HER-2 positive and 44% (n = 59) in ER and/or PR positive groups (P = 0.05). Median survival after CNS metastases was 9 months, but significantly longer in HER-2 positive group (16 months) and in patients submitted to surgical resection of CNS metastases, irrespectively of subtype (22 months vs 5 months in other treatment modalities). In multivariate Cox regression analysis, having HER-2 positive tumor was an independent prognostic factor for increasing survival after CNS metastases (HR 0.60, 95% CI: 0.41-0.87, P = 0.007), regardless the therapeutic strategy. Clinical behavior and prognosis of CNS metastases varies according to BC subtype. The association between LM disease and ER and/or PR positive tumors should be explored in upcoming studies. Also, these patients’ prognosis depends on the availability of specific treatment options, therefore, innovative and effective therapeutic approaches are needed, in order to improve survival and quality of life of these patients.

Deep learning algorithm to predict pathologic complete response to neoadjuvant chemotherapy for breast cancer prior to treatment.

600 Background: Pathologic complete response (PCR) to neoadjuvant chemotherapy (NAC) is associated with improved disease-free survival and overall survival in patients with breast cancer. Predicting PCR at the patient level prior to treatment initiation would allow physicians and patients to focus on therapies with the highest likelihood of success and minimize unnecessary toxicities from chemotherapy. We hypothesize that pre-treatment prediction of PCR is possible through a deep neural network algorithm trained on breast MRI imaging obtained prior to treatment. Methods: 126 tumors from patients treated with neoadjuvant chemotherapy for T3 stage breast cancer at a single institution from 2002 to 2006 were analyzed. In total, 3780 MRI slices were included. 3 MRI contrast phases (pre, immediate post, delayed post) from each slice were used as individual inputs to create separate model predictions of PCR. The 2-D CNN was trained over 50 epochs on the training set. The model was tested on the isolated test set (30% of samples). Results: Average model prediction accuracy over the total test set using a single phase of contrast (pre-, immediate post-, or delayed post-) was 90.4%. Concordance adjustment was conducted, with exclusion of slices that had produced discordant predictions across different contrast phase inputs. This resulted in an increase of overall model accuracy to 97.6%. Model accuracy was similar across subsets of age and tumor size despite differences in PCR rates. However, model accuracy was significantly lower in the triple-negative disease group. Conclusions: We demonstrate a deep neural network that accurately predicts PCR based on breast MRI imaging taken prior to NAC initiation. Our findings represent the promise of deep learning algorithms in providing personalized prognostic data for physicians and patients. [Table: see text]

NOTCH expression variability and relapse of breast cancer in high-risk groups

BackgroundIn regards to breast cancer (BC), survival or disease-free periods are still compromised mainly in Triple Negative (TN) and HER2 tumors. The participation of estrogen receptor (ER) has been reported as crucial in the signaling pathways, including the NOTCH pathway. The study was aimed to evaluate the expression of NOTCH1 and NOTCH3 in BC and its relationship with the presence of ER, as well as with relapses. MethodsNOTCH1 and NOTCH3 expression was evaluated in BC using Oncomine database, Breast Cancer Gene Expression Miner database and Kaplan Meier Plotter. Subsequently, detection of NOTCH1 and NOTCH3 in 100 paraffin-embedded BC samples from Mexican patients was achieved by immunohistochemistry (IHC) and RT-qPCR, a group of benign breast tumors were included as controls. Relapses were evaluated by BC subtypes and their relationship with NOTCH1 and NOTCH3 expression, as well as with ER expression. ResultsThe analyses from public databases of TN and HER2 groups, which are estrogen receptor-negative (ERN), revealed NOTCH1 and NOTCH3 expression variability. The overexpression was associated with lower relapse-free survival (P = 0.00019). These data were concordant with results from tumor samples of patients included in this study, which showed overexpression of NOTCH1 and NOTCH3 in ERN tumors, as well as lower relapse-free survival (P < 0.0001). ConclusionsNOTCH1 and NOTCH3 were found to be overexpressed mainly in ERN tumors. HER2 and TN groups, are related to higher relapse rates. Therefore, anti-NOTCH therapy could be justified and implemented in conventional treatments of high-risk BC groups.

Clinicopathological Characteristics of Molecularly Classified Groups of Invasive Ductal Breast Carcinoma in Pakistani Women

Background: The incidence of breast cancer warrants special consideration and understanding of disease demography. The study aimed to determine the clinicopathological characteristics of molecularly classified groups of invasive ductal breast carcinoma in Pakistani women. Methods: Patients (n=83) undergoing modified radical mastectomy with primary microscopically proven invasive ductal carcinoma were recruited from two tertiary care hospitals, Lahore, Pakistan. Grossing, reporting and biomarker testing was performed as per the College of American Pathologists (CAP) protocols. Chi-square was applied to observe associations between variables. A p-value &lt;0.05 was considered statistically significant. Results: The mean age in years (mean ± SD) of the patients was 49.3 ±10.98, 50.9 ± 15.4, 50.6 ± 10.9 and 44.6 ± 8.2 having breast carcinoma of luminal A (37.2%), Luminal B (12%), HER2-enriched (20.5%) and triple-negative group (TN) (30.1%), respectively. Nodal involvement was 24(29%), 5(6%), 13(16%) and 17(20.5%) in all groups. Among four groups of breast carcinoma histological grade I was observed as 2.4%, 1.2%, 1.2%, 0%, grade II was recorded as 20.5%, 4.8%, 6 % and 7.2% and grade III as 14.5%, 6%, 13.3% and 22.9%, respectively. ​Luminal A patients were more in T2 stage whereas more TN patients belonged to T4 stage (p-value = 0.001). A statistically significant association was observed between T2 tumor stage with grade II (p-value = 0.003). Conclusion: Patients with Luminal A and triple-negative (TN) characteristics were the predominant molecular subtypes. TN patients presented at an earlier age and higher stage compared to other groups whereas, Luminal A profile patients were at the lower tumor stage. Keywords: Estrogen Nuclear Receptor; Mammary Ductal Carcinoma; Breast; Progesterone; Triple Negative Breast Cancer.​​​

Association of Proliferative Activity in Invasive Ductal Carcinoma Breast in Pakistani Population.

Background:Personalized medicine has played very important role in management of breast cancer. Proliferative index is one among the prognostic and predictive factor but unfortunately due to varied reports , no definite consensus and routine medical practice has been approved for it. The objective of the study is to observe the association of Ki-67 index using St. Gallen Conference criteria in invasive ductal carcinoma breast in Pakistani Population. Methods:Eighty-three patients with confirmed light microscopic diagnosis of primary invasive ductal carcinoma were recruited in this prospective study . Expression of Ki67 was determined by classifying as low (<15%) and high (>15%) Ki67 in tumour. Statistical analysis was performed to observe the association of Ki-67 with clinicopathological parameters and molecular group (i.e., Luminal A, Luminal B, Her2 enriched and triple negative). Results:Out of 83 patients, 73.5% of patients showed >15% Ki67 (p value <0.001). High expression of Ki 67 (>15%) was observed in 3.6%, 21.7% and 48.2 % of Nottingham grade I, II and III (p value=0.017) respectively. Among molecular group, high expression of Ki67 was observed 20.5% in Luminal A, 9.6% in Luminal B, 15.7% in Her2 enriched and 27.7% in triple negative groups (p= 0.017). There was no significant association observed in expression of Ki 67 among lymph node stage, tumour stage and Nottingham prognostic index. Conclusion:Higher Ki-67 reactivity is usually associated with higher-grade morphology of tumour. It can act as an independent predictor in assessment of tumour behavior. However, larger validation clinical studies are still required for confirmation of its importance and for routine practice.

Abstract P3-18-09: Refusal of breast surgery in breast cancer patients with clinical complete response (cCR) after neoadjuvant systemic therapy and vacuum-assisted biopsy (VAB) and sentinel lymph node biopsy (SLNB) confirmed pathological complete response (pCR). A first report of the prospective non-randomized trial results. NCT04293796

Abstract Introduction The aim of the study was to prove efficacy and safety of refusal of traditional breast surgery in BC patients who develop cCR after neoadjuvant chemotherapy. 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 20 patients with early сT1-2N0-1M0 (stage Ia-IIb) triple-negative and HER2-positive (both ER+ and ER-) unifocal tumours without in situ component 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 carboplatinum 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 under general anesthesia. 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-emtanzine up to one year. In case ER-positive, all patients received appropriate endocrine-therapy. In case of residual in-breast or nodal involvement patients with triple-negative breast cancer received 6 cycles of capecitabine. Results cCR was achieved in 8 of 10 patients in the HER2-positive group. VAB and SLNB were performed in 7 cases and confirmed pCR in 5 patients. 2 had residual in-breast disease with &amp;lt;10% cellularity. One patient with cCR requested standard surgical approach that confirmed pCR. 2 patients failed to obtain cCR. Both received standard surgery. In one of the cases no residual disease was found, in another one - a residual in-breast tumor was found at section. All HER2-positive patients were found to be sn ypN0. In the triple-negative group cCR was achieved in 6 of 10 patients. 4 patients went on to receive VAB and SLNB. After VAB and SLNB pCR was confirmed in three of them. 1 patient had residual tumor with less than 5% cellularity. Two patients with cCR after NAT opted for standard surgery. In both cases pCR was confirmed. 4 patients with clinically detectable residual in-breast tumor received standard surgery. All turned out to have pCR. All the patients in the TNBC group were also found to be sn ypN0.ConclusionVisualization modalities fail to provide reliable information on the true rate of pCR. Contemporary systemic therapy regimens provide the rate of pCR up to 60-70%. In all cases of NAT tumor bed marking at baseline is an essential procedure to guide future interventions and confirm their success. Discrepancies between radiologic assessment and true rates of pCR are a substrate for further search for the techniques that would challenge the role of surgery in exceptional responders developing cCR. The trial continues to enrol patients. Citation Format: Petr Krivorotko, Sergey Yerechshenko, Alexander Emelyanov, Ekaterina Busko, Alexander Bessonov, Viktoriya Gukova, Alexander Komyahov, Elena Zhiltsova, Kirill Nikolaev, Tengiz Tabagua, Larisa Gigolaeva, Roman Pesotsky, Sergey Novikov, Zhanna Bryantseva, Anna Artemyeva, Viktoriya Smirnova, Vladimir Kushnarev, Alexey Belyaev, Tatiana Semiglazova, Vladimir Semiglazov. Refusal of breast surgery in breast cancer patients with clinical complete response (cCR) after neoadjuvant systemic therapy and vacuum-assisted biopsy (VAB) and sentinel lymph node biopsy (SLNB) confirmed pathological complete response (pCR). A first report of the prospective non-randomized trial results. NCT04293796 [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-18-09.

CHARACTERISTICS OF RESPONSE TO NEOADJUVANT CHEMOTHERAPY IN PATIENTS WITH AGGRESSIVE BIOLOGICAL SUBTYPES OF STAGE II–III BREAST CANCER. ORIGINAL STUDY

Goal: To analyze the tumor response to NACT in patients with aggressive biological subtypes of stage II–III breast cancer based on the contemporary scoring systems for residual pathological stage evaluation and the residual cancer burden according to the RCB system. Materials and methods: A total of 172 women with stage II–III breast cancer of aggressive biological subtypes (triple negative in 34,3 %; HER2‑positive tumors in 28,5 %; luminal B Her2‑negative BC in 37,2 %) were included in this analysis. The median age of the patients was 47 years (24–81 years); сT2 was the predominant tumor size (65,1 %); 69,8 % of patients had regional lymph node involvement; 62,8 % of patients had G3 tumor; Ki67 ≥ 30 % was found in 90,7 % of cases. All patients received neoadjuvant chemotherapy (NACT) with concomitant anti-HER2 blockade in case of HER2‑positive tumors followed by surgery. Morphological assessment included evaluation of the residual pathological stage and the residual cancer burden according to the RCB system. Results: Total pathological complete response (no evidence of residual invasive tumor in the breast and lymph nodes — tpCR) was observed in 69 of 172 patients (40,1 %), which corresponded to the уpT0N0 pathological stage and RCB class 0. The highest tpCR rate was achieved in patients with HER2‑positive cancer (63 % in non-luminal HER2‑positive subtype and 59.1 % in luminal HER2 + BC) and triple negative cancer (50,8 %). Meanwhile, the tpCR rate in patients with luminal HER2‑negative BC was only 15,6 %, p &lt; 0.0001. The proportions of the RCB classes in the whole sample were 6,4 % (RCB-I), 30,2 % (RCB-II), 23,3 % (RCB-III), and differed significantly between the biological subtypes. RCB class I was nearly absent in the triple negative cancer group (1,7 % only), the residual tumor corresponded to RCB classes II and III in 25,4 % and 23,7 % of cases, respectively. In the HER2‑positive cancer group, the percentage of patients with RCB class I residual tumors was 9,1 % and 11,0 % in luminal and non-luminal cancers, respectively. One of four patients had RCB class II; RCB class III was found only in 9 % of luminal HER2‑positive cancer cases and in no patients with non-luminal HER2‑positive subtype. Most patients with luminal B HER2‑negative BC had RCB II and III: 39,1 % and 37,5 % of cases, respectively, p &lt; 0.0001. Conclusions: patients with aggressive biological BC subtypes differed significantly not only in the rates of the total pathological complete response to NACT, but also in the distribution of residual cancer burden classes, which can be translated into the disease prognosis.

Abstract PO-128: Completion of nipple reconstruction in triple-negative breast cancer patients compared to triple-positive breast cancer patients: A single institutional analysis

Abstract Background: Triple-negative (TN) breast cancer is considered to be more aggressive than other subtypes of breast cancer and has a poorer prognosis. It is defined as breast cancer tumors that lack estrogen receptor (ER), progesterone receptor (PR), and HER2 expression and affects 17-20% of women with breast cancer. However, reconstructive outcomes remain to be elucidated when compared to other invasive breast cancer subtypes. The aim of this study is to determine if there is a disparity in completing nipple-areolar reconstruction in breast cancer patients with a triple-negative subtype compared to patients with a triple-positive (TP) subtype. Methods: 107 patients who underwent bilateral non-nipple sparing mastectomies from 2013 to 2017 diagnosed with a TN (n = 54) and TP (n = 53) invasive breast cancer subtype were identified. All 107 patients were seen by two attending surgeons at a single institution. Completion of nipple reconstruction and areolar tattoos, number of days from mastectomy to nipple reconstruction, and areolar tattoos were analyzed. Demographic/clinical variables, including race, age, BMI, smoking, comorbidities, neoadjuvant/adjuvant chemotherapy, hormonal therapy, radiation therapy, and choice of implants or flaps were also analyzed. Results: There was no significant difference in the proportion of patients who underwent radiation therapy in the TN group than in the TP group (55.56% vs 37.74%, p = 0.0819). Among these two groups, there was no significant difference in the percentage of patients completing nipple reconstruction (TN = 44.44%, TP = 49.06%, p = 0.7001) and acquiring an areolar tattoo (TN = 33.33%, TP = 39.62%, p = 0.5503). The differences in the average duration in days from mastectomy to nipple reconstruction (TN = 505.7, TP = 456.4, p = 0.5259) and areolar tattoos (TN = 665.6, TP = 638.5, p = 0.7653) among these two patient populations were also insignificant. Conclusion: TN subtype does not make a significant impact on completing nipple reconstruction when compared to TP patients, another extreme. These results should be considered when counseling TN patients on their reconstructive journey. Citation Format: Joshua Amaya, Kaitlin Jones, Nicholas T. Haddock, Sumeet S. Teotia. Completion of nipple reconstruction in triple-negative breast cancer patients compared to triple-positive breast cancer patients: A single institutional analysis [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-128.

Mutant Status of the P-53 Gene in Relation with microRNA, as an Unfavorable Marker in Breast Cancer, a Systematic Review

ABSTRACT Breast cancer affects more than one million patients annually in the world and is a leading cause of mortality. Histological type, grade, tumor size, lymph node involvement, and estrogen receptor and HER-2 receptor status, all influence prognosis and the probability of response to systemic therapies. Purpose: Aim of this work was to emphasize possible links between alterations of the P-53 gene, together with its protein, in the pathological features of breast cancer, resistant to a conventional therapy. Method: New genetic technologies were investigated to promote a stronger anti-oncogene response, using both RNA-based p53 vaccines and the likelihood of response to specific oncological therapies. Results: Studies have shown that mutant P-53 gene had a strongly unfavorable prognostic factor for relapse-free survival and overall survival only in a triple-negative group in patients treated with adjuvant anthracycline-containing chemotherapy. The adjuvanted vaccine induced the type T1 cells helper response in most patients. However, the response has not yet been shown to be strong enough to be beneficial as monotherapy and most patients have had T-helper cells that have failed to produce effective cytokines to kill cancer cells. The results of these studies justified attempts to discover and apply the new vaccines to cancer patients using p53-derived peptides. Conclusions: Conditions of the mutant P-53 gene or deletion of 17p chromosome were an unfavorable prognostic factor for the survival of patients, treated with adjuvant chemotherapy, in the groups with triple-negative forms of BC.

Evaluation of Thromboembolism According to Mutation Status in Patients with Essential Thrombocytosis; Single-Center Experience

ABSTRACT&#x0D; Aim: The presence of Janus kinase 2 (Jak2) mutation in essential thrombocytosis (ET) patients is associated with an increased risk of thrombosis, while the presence of calreticulin (Calr) mutation is associated with a decrease in thrombosis risk. The aim of this study is to compare patients with mutation (Jak2, Calr, myeloproliferative leukemia virus oncogene [Mpl]) and non-mutation (triple-negative) patients in terms of the development of thromboembolism.&#x0D; Methods: 95 patients who were followed up with the diagnosis of ET between 2009 and 2020 were included in this study. The clinical characteristics, laboratory results, and mutation status of the patients were analyzed retrospectively, based on the patients’ files. The patients in mutation positive (Jak2, Calr, Mpl) group a, only jak2 mutation-positive group b, and triple-negative (Jak2, Calr, Mpl negative) group c were compared.&#x0D; Results: The median age of ET patients was 53 years (18-91). The Jak2 mutation was found positive in 42% (n:40) of the patients with ET. 4 patients (4%) were calr mutation-positive, but mpl mutation was not detected. 51 patients (54%) were triple-negative. A total of 22 (23%) patients had a thrombotic event at diagnosis and follow-up. Thrombotic events were detected in 27.5% (11/44) of the patients with positive Jak2 mutation and in 21.5% (11/51) of the patients with triple-negative. No thrombotic event was detected in 4 patients with a positive calr mutation. No statistically significant difference was found for thrombotic events in mutation-positive patients compared with triple-negative patients (p = 0.7). No statistically significant difference was found in terms of white blood cell count, thrombocyte count and spleen size examined at the time of diagnosis. When compared in terms of hemoglobin, age and gender distribution (male / female), the difference was found statistically significant in those with positive mutation (p = 0.001 *, p = 0.001 *, p = 0.03*).&#x0D; Discussion and Conclusion: The results of this study showed that Jak2V617F gene mutation is an important finding for diagnosis and complications in patients with ET, and its presence increases the risk of thrombosis development. The presence of calr mutation reduces the risk of thrombosis and appears at an earlier age than Jak2V617F mutation. Thrombosis risk in triple-negative ET patients is similar to the one in patients with Jak2V617F mutation.

Breast Imaging Findings of Microcalcifications in Ductal Carcinoma in Situ and Their Correlations with Pathological and Biological Features

Background: Mammography (MMG) is the primary screening tool for breast cancer, as microcalcifications are the most common MMG finding in ductal carcinoma in situ (DCIS). The use of high-frequency transducers facilitates the visualization of calcifications on ultrasonography (USG), especially in patients with dense breasts and cancer symptoms. Although a correlation has been reported between the imaging features of DCIS and pathological features, few studies have focused on multiple imaging modalities. Objectives: To evaluate the correlation of DCIS microcalcifications in breast imaging with pathological and biological features. Patients and Methods: The MMG and USG findings of 125 lesions detected in 123 patients, diagnosed with pure DCIS, were retrospectively reviewed according to the breast imaging-reporting and data system (BI-RADS). The USG and comparable MMG findings of microcalcifications were divided into three groups: group 1 (MMG negative, USG negative), group 2 (MMG positive, USG negative), and group 3 (MMG positive, USG positive). The pathological findings (nuclear grade and comedo necrosis) and biological features [estrogen (ER) positive group, human epidermal growth factor receptor 2 (HER2) positive group, triple negative group, and Ki-67 index] were compared with the MMG and USG features using Chi-square test. Results: Microcalcifications were observed on MMG in 83 (66.4%) DCIS lesions. Positive microcalcifications on MMG were significantly associated with a high nuclear grade (P = 0.001) and comedo necrosis (P = 0.001). Positive microcalcifications on MMG were significantly associated with ER negativity (P = 0.023), HER2 positivity (P = 0.002), and increased Ki-67 index (P = 0.001). There were 62 lesions (49.6%) without microcalcifications on USG (group 1 and group 2), while there were 63 (50.4%) lesions with microcalcifications on USG (group 3). Positive microcalcifications on MMG were significantly associated with ER-negative group (P = 0.023), HER2-positive group (P = 0.002), and increased Ki 67 index (P = 0.001). Conclusion: Based on the present results, DCIS microcalcifications detected via imaging were significantly associated with poor prognostic pathological factors, such as a high nuclear grade and comedo necrosis, as well as poor prognostic biological factors, including ER negativity, HER2 positive group, and a high Ki-67 index.

The choice of a neoadjuvant chemotherapy cycle for breast cancer has significance in clinical practice: results from a population-based, real world study.

Objective:Neoadjuvant chemotherapy (NAC) is currently used in both early stage and locally advanced breast cancers. The survival benefits of standard vs. non-standard NAC cycles are still unclear. This study aimed to investigate the relationship between NAC cycles and survival based on real world data.Methods:We identified patients diagnosed with invasive primary breast cancers who underwent NAC followed by surgery. Patients who received at least 4 NAC cycles were defined as having received standard cycles, while patients who received less than 4 NAC cycles were defined as having received non-standard cycles. Kaplan-Meier curves and Cox proportional hazard models were used to estimate the disease-free survival (DFS) and overall survival (OS).Results:Of the 1,024 included patients, 700 patients received standard NAC cycles and 324 patients received non-standard NAC cycles. The DFS estimates were 87.1% and 81.0% (P = 0.007) and the OS estimates were 90.0% and 82.6% (P = 0.001) in the standard and non-standard groups, respectively. Using multivariate analyses, patients treated with standard NAC cycles showed significant survival benefits in both DFS [hazard ratio (HR): 0.62, 95% confidence interval (CI): 0.44–0.88] and OS (HR: 0.54, 95% CI: 0.37–0.79). Using stratified analyses, standard NAC cycles were associated with improved DFS (HR: 0.59, 95% CI: 0.36–0.96) and OS (HR: 0.49, 95% CI: 0.28–0.86) in the HER2 positive group. Similar DFS (HR: 0.50, 95% CI: 0.25–0.98) and OS (HR: 0.45, 95% CI: 0.22–0.91) benefits were shown for the triple negative group.Conclusions:Standard NAC cycles were associated with a significant survival benefit, especially in patients with HER2 positive or triple negative breast cancer.

Efficacy, Safety and Cost Effectiveness of Metronomic Low Dose Versus Intermittent High Dose Capecitabine in Metastatic Breast Cancer

AIM: The aim of the study is to compare the toxicity and cost-effectiveness between metronomic and intermittent capecitabine as maintenance therapy in female patients with metastatic breast cancer. PATIENTS AND METHODS: All metastatic breast cancer patients with HER2 negative were included. The whole study population received six cycles of Docetaxel/Capecitabine then patients were randomized to either continuous (650 mg/m2 twice daily continuous) or intermittent Capecitabine (1000 mg/m2 twice daily every 21 days) as maintenance. RESULTS: The study included 51 patients, 26 in the metronomic arm and 25 in the continuous. The median number of maintenance cycles, as well as the partial response, was higher in the continuous (18 vs. 13 cycles, p: 0.031; p: 0.038). The continuous arm was tolerable with significant less Grade 3 and 4 toxicity regarding nausea, vomiting, hand and foot syndrome, neutropenia, and elevated liver enzymes. (p: 0.03, 0.045, 0.051, 0.048, 0.06, respectively). On multivariate analysis, only patients receiving treatment as first-line had a better clinical response (p: 0.03) especially in the triple-negative group (p: 0.07). The metronomic therapy was more cost-effective with a 35.9% reduction of cost. ($ 746 vs. $1164). The progression-free survival and overall survival were not significant between the two groups. CONCLUSION: Metronomic continuous capecitabine proved to be less toxic and more cost-effective.

Multi Institutional Retrospective Study about Median Survival Outcome for Women with Metastatic Triple Negative and HER2 Positive Breast Cancer in Egypt

Abstract Background Breast cancer is the most common malignant tumor among females around the world. It represents 1.7 million new cases per year and 25% of all types of cancers. Objectives Assessment of median overall survival in most aggressive subtypes of metastatic breast cancer (Triple –Ve and HER2+Ve) &amp; to compare survival of metastatic HER2+Ve breast cancer in group received targeted versus that did not receive. Patient and Methods Multi institutional retrospective study for assessment of median OS in metastatic breast cancer for themost aggressive subtypes (HER2+Ve &amp;Triple-Ve) at Ain Shams University Hospitals and El-Matarya teaching Hospital. Results Seventy-three metastatic breast cancer patients were included (31 Triple-Ve &amp; 42 HER2+Ve) in the period between January 2014 and December 2016 At Ain Shams University Hospitals and El-Matarya teaching Hospital, we found that median OS for Triple negative group is 16 months with (95% CI 8.8- 23.6) , that for HER2+Ve group is 17 months with (95% CI 13.9 – 20.6) &amp; for patients did not receive targeted therapy, median OS is 10 months (95% CI. 4-19.4,P.000). Conclusion From our study,we highlight that metastatic breast cancer patients (HER2+Ve subtype) &amp;received targeted therapy, had the most superior survival outcome. so,targeted therapy must be included in first line treatment.

PROFILE OF SURROGATE MARKERS OF MOLECULAR SUBTYPES USING THE EXPRESSION PATTERN OF ER, PR, AND HER2/NEU RECEPTORS IN OPERABLE BREAST CANCER

Objective: The present study was planned with an aim to study the profile of surrogate markers of molecular subtypes using the expression pattern of ER, PR, and HER2/NEU receptors in operable breast cancer so that most effective and advantageous treatment can be offered for better surgical outcomes. Methods: A cross-sectional observational study was carried out in one of the tertiary care centers in Central UP. All patients presenting to the center with early and locally advanced breast cancer with age bracket between 18 and 75 years during 2-year period and willing to participate in the study were included in the sample size. Clinical staging was done using the standard TNM criteria and all the specimens were subjected to immunohistochemical evaluation for surrogate molecular subtyping Results: Out of 94 cases enrolled in the study, a total of 32 (34.4%) were identified as luminal A, 3 (3.2%) were identified as luminal B, 35 (37.6%) were identified as HER2 positive, and remaining 23 (24.7%) were identified as triple negative. Statistically, there was no significant difference among groups with respect to age (p=0.958) and BMI (p=0.332). However, there was a significant difference among groups with respect to clinical stage (p=0.031), clinical nodal involvement (p=0.014), pathological staging (p=0.006), and pathological nodal involvement (p=0.023). Among those with nodal involvement, all the cases had involvement of one node except for one patient in Group I who had involvement of thrMost of the luminal A cases (81.3%) were clinically Stage 1 or 2. All the luminal B cases were clinically Stage 2 or 3 (100%). Almost half (48.8%) of Her2-negative cases were Stage 3 or 4. Majority of triple-negative cases were Stage 3 or 4 (65.2%). Clinically, nodal involvement was seen to be maximum in Her2-negative and triple-negative groups (54.3% and 52.2% of cases, respectively). Pathologically, most of the luminal A (83.9%), Her2 negative (81.8%), and all the luminal B cases were Stage 2. Pathologically, nodal involvement was seen in 16.1% of luminal A, 42.4% of Her2-negative, and 50% of triple-negative cases. Conclusion: The findings of the present study provided a glimpse of expression pattern of ER, PR, and HER2/NEU receptors in operable breast cancer based on which most effective and advantageous treatment can be offered for better surgical outcomes.

Significant Diagnostic and Prognostic Value of FLAD1 and Related MicroRNAs in Breast Cancer after a Pan-Cancer Analysis.

The identification of biomarkers plays an important role in the diagnosis and prognosis of cancers. In this study, we explored the diagnostic and prognostic value of the FLAD1 expression across pan-cancer analysis from online databases (Oncomine, cBioPortal, Breast Cancer Gene-Expression Miner, UALCAN, GEO, BCIP, TNMplot, ENCORI, Kaplan-Meier Plotter, and LinkedOmics). We found that FLAD1 was overexpressed in a number of different kinds of cancers, especially in breast cancer, and higher FLAD1 expression level was associated with the HER+, p53 mutant, node-involved, NPI stage 3, basal-like, and triple-negative groups compared with the other subgroups of breast cancer. The FLAD1 expression levels were higher in patients that were 21–40 years old than those in patients of other ages and were higher in the African-American group than in the Caucasian group. We also analyzed the FLAD1-related microRNAs and their prognostic values in breast cancer. This study highlights the significance of FLAD1 in cancers and provides evidence for its potential as a biomarker for the diagnosis and prognosis of cancers.

Ki-67 proliferative index correlation to the immunohistochemistry profile in early female breast cancer: a review of 515 cases

Introduction: Many biological markers are used as prognostic and predictive indicators in invasive breast cancers management. Among them, tumour size, grade, patho-morphological subtype, hormone receptors status and HER2 receptor expression in addition to Ki-67 proliferative index. Also, they play a key role in adjuvant treatment decision making. Our aim was to evaluate the association between Ki-67 proliferative index and breast cancer immunological subtype. Material and methods: A total of 515 early invasive patients were enrolled, tumour biological characteristics as histopathological subtype, immune-histo-chemistry (ER,PR,HER2) status and Ki-67 proliferation index values have been collected. The Ki-67 index level of 20%, was used as the cut-off point to differentiate between low and high Ki-67 expression levels. Statistical analysis has been performed using the Chi square test online tool. Results: In this cohort, about 42%, 33%, 7%, and 18% of the cases were grouped as luminal A-like, luminal B-like, HER2 enriched subtype, and triple-negative, respectively. All luminal A-like patients had Ki-67 level less than 20%. About 3% of the cohort, are luminal B-like tumours with Ki-67 level less than 20%, where 30.3% of the patients were luminal B-like tumours with Ki-67 level ≥ 20%. In HER2 enriched subtype, Ki- 67 of < 20% level seen in 1.9% of cases, and Ki-67 levels ≥ 20% was observed in 5.2% of the cases. In the triple-negative group, Ki-67 was 20% or higher in 16% of cases, and only 1.7% of patients had Ki-67 level less than 20%. Conclusion: Luminal A-like tumours were the most frequently encountered subtype, they have low Ki-67 levels and are known to be of a low histological grade tumour, and usually associated with a good prognosis. Also, data indicates that high Ki-67 levels are seen more often in Luminal B-Like breast cancers as well as in triple-negative breast cancers and HER2 enriched tumours.

The importance of androgen receptors in breast cancer.

Breast cancer (BC) is the most common malignancy among women worldwide, and one of the leading causes of cancer-related deaths in females. For the breast malignant tumors there are numerous targeted therapies, depending on the receptors expressed. Regulating the process of epithelial-mesenchyme transcription, the steroid nuclear receptors are important in invasion and progression of BC cells. Till now, it is known that androgen receptor (AR) is present in about 60-80% of BC cells but, unfortunately, there is no targeted therapy available yet. We revised the recent literature that included the AR mechanism of action in patients diagnosed with breast cancer, the preclinical, retrospective and clinical studies and the aspects related to the prognosis of these patients, depending on the molecular subtype. A total of 12 articles were eligible for this review. AR positivity was assessed using immunohistochemistry. Herein, neither 1 nor 10% cut-points were robustly prognostic. AR was an independent prognostic marker of BC outcome, especially in triple negative BC group. AR is a potential targeted pathway which can improve the prognostic of AR positive patients with BC. Further preclinical and clinical studies are necessary to clarify the mechanism of action and to establish the drugs which can be used, either alone or in combination.