Triple Negative Type Research Articles

Substitutions of the NBS1 gene and clinicopathological characteristics of young breast cancer patients

The purpose of this study was to determine characteristics potentially related to NBS1 mutations and polymorphisms in young (≤50 years of age) breast cancer patients. Blood from 80 breast cancer patients was collected. NBS1 mutations c.657_661del, p.R215W, p.I171V, and polymorphisms c.8360G>C, c.30537G>C were genotyped by the PCR-RFLP method. Two-sided Chi-square test was used for univariate analysis and logistic regression analysis was used to evaluate the odds ratio. No carriers of the c.657_661del, p.R215W and p.I171V mutations were found. NBS1 c.8360G>C logistic regression analysis showed that GC and CC genotypes compared with GG genotype had decreased risk of low grade tumour, 2.885-fold (OR = 2.885, 95% CI 0.173–0.735, P = 0.005) and 2.186-fold (OR = 2.186, 95% CI 0.188–0.888, P = 0.024), respectively. 8360 CC genotype (OR = 3.034, 95% CI 0.156–0.778, P = 0.010) significantly increased the chances of HER2 amplification compared to GG genotype. NBS1 8360 GC genotype had a higher risk for breast cancer progression (OR = 1.673, 95% CI 0.233–0.915, P = 0.027). The homozygote 8360 CC carriers had approximately a six times higher risk for the disease progress (OR = 5.946, 95% CI 0.098–0.585, P = 0.002). The prevalence of triple negative breast cancer type was significantly higher in individuals with NBS1 8360 CC genotype (OR = 2.186, 95% CI 0.188–0.888, P = 0.024). Regarding c.30537G>C polymorphism, none of the genotypes had a significant influence on pathological characteristics. NBS1 gene c.8360G>C polymorphism might be associated with breast cancer aggressiveness in young breast cancer patients.

Clinical and X-ray characteristics for expressions of different receptors in patients with breast cancer.

Clarifying the expression of breast cancer receptor is the key to clinical treatment for breast cancer. This study aims to explore the correlation between X-ray and clinical characteristics of 4 molecular subtypes and their receptor types of breast cancer. A total of 439 breast cancer patients who confirmed by pathology and performed X-ray examination were enrolled. The X-ray and clinical characteristics of 4 molecular subtypes and the expression of their receptors were analyzed. Luminal A type showed the highest proportion of spiculate masses, and the lowest calcification score, showing significant difference with other 3 subtypes (all P<0.001). The age in the human epidermal growth factor 2 (HER2) overexpression type group was older, the proportions of menopause, the calcification score, and the calcification score with 9-12 were higher, the sizes of the tumor were greater in the HER2 overexpression type group than those in the other 3 molecular subtype groups (age P<0.05, the rest P<0.01). The proportions of regular shape, edge indistinct, and high-grade invasive ductal carcinoma in the triple-negative type group were higher than those in the other 3 molecular subtype groups (all P<0.001). The proportions of non-menopausal patients and spiculate tumors in the estrogen receptor (ER) positive and/or progesterone receptor (PR) positive groups were higher than those in both ER and PR negative group (P<0.001 and P=0.001, respectively). The proportions of calcification fraction and high-grade invasive ductal carcinoma were higher, tumor sizes were greater in the HER2 positive group, Ki-67≥20% group than those in the HER2 negative group, Ki-67<20% group, respectively (P<0.001 or P<0.05, respectively). Four molecular subtypes of breast cancer and their receptor expressions are correlated with X-ray and clinical characteristics, which can provide a basis for clinical diagnosis and treatment.

Outcomes After Accelerated Partial Breast Irradiation in Women With Triple Negative Subtype and Other "High Risk" Variables Categorized as Cautionary in The ASTRO Guidelines.

PurposeTo report a primary objective clinical outcome of ipsilateral breast recurrence following accelerated partial breast irradiation (APBI) in women with triple negative and other high risk breast cancer (as described in 2017 ASTRO guidelines) (i.e., age 40–49, size 2.1–3.0 cm, estrogen receptor negative and invasive lobular breast cancer). Secondary objectives of axillary and regional failure as well as overall survival are also reported.Methods and MaterialPatients from two clinical trials (NCT01185145, NCT01185132) were treated with 38.5 Gy IMRT or 3D-CRT APBI w/3.85 Gy fraction/BID fractionation for 10 fractions. Triple negative and other high risk patients (n=269) were compared to a total of 478 low risk patients which ASTRO defined as “suitable” for APBI. High risk patients, for the purpose of this study, were defined as those who possess one or more high risk criteria: triple negative (n=30), tumor size >2 cm <3 cm (n=50), HER 2+ (n=54), age range 40–50 years (n=120), ER- (n=43), and ILC histology (n=52).ResultsMedian follow up was 4.0 years for all patients. No significant difference was found for this high-risk cohort at 5 years for ipsilateral breast, or regional recurrences. Axillary recurrence was significantly adversely impacted by triple negative and ER- statuses (p=0.01, p=0.04). There were significant correlations between triple negative type and axillary recurrence on multivariate analysis (p=0.03). Overall survival for all patients was unaffected by any of the high-risk categories.ConclusionThe data from this study suggests that women possessing high risk features are at no more meaningful risk for recurrence than other patients considered to be acceptable for APBI treatment. However, the finding of axillary recurrence in patients with triple negative breast cancer does warrant a degree of caution in proceeding with accelerated partial breast irradiation technique in this patient group.

Usefulness of Staging Chest CT in Breast Cancer: Evaluating Diagnostic Yield of Chest CT According to the Molecular Subtype and Clinical Stage.

The aim of this study is to investigate the clinical utility of staging chest CT in breast cancer by evaluating diagnostic yield (DY) of chest CT in detection of metastasis, according to the molecular subtype and clinical stage. This retrospective study included 840 patients with 855 breast cancers from January 2017 to December 2018. The number of patients in clinical stage 0/I, II, III and IV were 457 (53.5%), 298 (34.9%), 92 (10.8%) and 8 (0.9%), respectively. Molecular subtype was identified in 841 cancers and there were 709 (84.3%) luminal type, 55 (6.5%) human epidermal growth factor receptor 2 (HER2)-enriched type and 77 (9.2%) triple-negative (TN) type. The DYs in clinical stage 0/I, cII, cIII and cIV were 0.2% (1/457), 1.7% (5/298), 4.3% (4/92) and 100.0% (8/8), respectively. The DYs in luminal type, HER2-enriched type and TN type were 1.7% (12/709), 3.6% (2/55) and 2.6% (2/77), respectively. Clinical stage was associated with the DY (p = 0.000). However, molecular subtype was not related to the DY (p = 0.343). Molecular subtype could not provide useful information to determine whether staging chest CT should be performed in early-stage breast cancer. However, chest CT should be considered in advanced breast cancer.

Breast Cancer Type Classification Using Machine Learning.

Background: Breast cancer is a heterogeneous disease defined by molecular types and subtypes. Advances in genomic research have enabled use of precision medicine in clinical management of breast cancer. A critical unmet medical need is distinguishing triple negative breast cancer, the most aggressive and lethal form of breast cancer, from non-triple negative breast cancer. Here we propose use of a machine learning (ML) approach for classification of triple negative breast cancer and non-triple negative breast cancer patients using gene expression data. Methods: We performed analysis of RNA-Sequence data from 110 triple negative and 992 non-triple negative breast cancer tumor samples from The Cancer Genome Atlas to select the features (genes) used in the development and validation of the classification models. We evaluated four different classification models including Support Vector Machines, K-nearest neighbor, Naïve Bayes and Decision tree using features selected at different threshold levels to train the models for classifying the two types of breast cancer. For performance evaluation and validation, the proposed methods were applied to independent gene expression datasets. Results: Among the four ML algorithms evaluated, the Support Vector Machine algorithm was able to classify breast cancer more accurately into triple negative and non-triple negative breast cancer and had less misclassification errors than the other three algorithms evaluated. Conclusions: The prediction results show that ML algorithms are efficient and can be used for classification of breast cancer into triple negative and non-triple negative breast cancer types.

Axillary Sampling as an Alternative Option for Complete Nodal Response in Triple Negative and HER2 Type Breast Cancer Patients after Neoadjuvant Chemotherapy

Axillary Sampling as an Alternative Option for Complete Nodal Response in Triple Negative and HER2 Type Breast Cancer Patients after Neoadjuvant Chemotherapy

Change from triple negative type to triple positive type: A case report of discordance of re-biopsy from primary breast cancer

The patient was a 60-year-old woman who had visited a clinic with the chief complaint of a mass in the right breast prior to being referred to our hospital. Breast examination revealed the presence of a 3-cm hard elastic mass in the C region of the right breast. Computed tomography (CT) further indicated metastases to the liver and lungs. Upon needle biopsy of the primary tumor, the patient was diagnosed with triple-negative (ER (-), PgR (-), HER2 (-)) invasive lobular carcinoma. Chemotherapy was successful in achieving a transient partial response (PR); however, the tumor later advanced to a progressive disease (PD) after five cycles of oral fluoropyrimidine derivative therapy (S-1). Re-biopsy of the primary tumor revealed that the tumor was triple-positive (ER (+), PgR (+), HER2 (+)). The patient was subsequently treated with anti-HER2 therapy and has since achieved complete response (CR). Although biological changes sometimes occur from the primary to the metastatic tumor, changes in the primary tumor itself during the course of treatment is a rare event. Furthermore, the transition from triple-negative to triple-positive status is very uncommon. Re-biopsy rarely changes the biological characteristics of a tumor; however, biological changes can have a significant impact on treatment if they do occur. Thus, it is important to perform a re-biopsy if the current treatment results in PD.

Relationship between degree of breast MRI background parenchymal enhancement and breast cancer subtype.

To observe the distribution of magnetic resonance imaging (MRI) breast parenchymal enhancement (BPE) among different breast cancer subtypes and to explore the relationship between the BPE and the breast cancer tumor type. A total of 150 consecutive patients with breast cancer underwent breast dynamic enhanced scanning image. According to the expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2) and Ki-67, the molecular subtypes were classified into Luminal-A, Luminal-B, HER-2 over- expression, and triple-negative breast cancer. The BPE of the whole breast was evaluated and categorized as minimal, mild, moderate, or marked according to the breast imaging reporting and data system (BI-RADS). The relationship between the distribution of BPE and the breast cancer subtypes was analyzed. In patients with mild BPE, the incidence of Luminal-B breast cancer was significantly increased, and there were statistical differences among the Luminal-B and the luminal-A, the HER-2 over-expressed type, and the triple-negative type (all P<0.01). In the marked BPE patients, the proportion of triple negative breast cancer was the highest, and there was statistical difference among the triple-negative type and the Luminal-A, the Luminal-B, and the HER-2 over-expression types (all P<0.05). The BPE can be served as an additional risk stratification index in the targeted screening of breast cancer type, which can offer reference value in the clinical diagnose and individualized treatment.

CD204-positive macrophages accumulate in breast cancer tumors with high levels of infiltrating lymphocytes and programmed death ligand-1 expression.

Although immunotherapy has been demonstrated to be promising in triple-negative (TN) breast cancer (BC), most BC cases are classified as non-TN. To enrich the responders for immunotherapy regardless of their subtypes, classification based on tumor-infiltrating lymphocyte (TIL) levels and programmed death ligand-1 (PD-L1) status may be useful. However, this classification has not been fully applied to BC. Furthermore, suppressive subsets in the local tumor microenvironment, such as tumor-associated macrophages (TAMs), which promote tumor progression, cannot be ignored to overcome immunotherapy resistance. The aims of the present study were to classify primary BC cases based on the TIL levels and PD-L1 status, and to identify suppressive immune subsets in each categorized group. A retrospective analysis of 73 patients with invasive BC was performed. The frequency of TILs was evaluated in HE-stained slides (10% cutoff), and PD-L1 levels (SP142; 1% cutoff), as well as immune subsets (CD3+, CD8+, FOXP3+, CD20+, CD68+ and CD204+ cells) were assessed using immunohistochemistry. It was revealed that 22% (16/73) of the tumors were categorized as TIL+PD-L1+, of which 69% (11/16) were TN type. By contrast, 66% (48/73) of the tumors were categorized as TIL−PD-L1−, of which 77% (37/48) were HR+ and HER2− types. The number of CD204+ M2-type macrophages was significantly associated with high histological grade (P=0.0246) and high Ki-67 (P=0.0152), whereas CD68+ macrophages were not associated with these factors. Furthermore, CD204+ macrophages and FOXP3+ Tregs accumulated in 88% (14/16) and 63% (10/16) of TIL+PD-L1+ tumors, respectively, compared with 20.8% (10/48) and 27.1% (13/48) of TIL−PD-L1− tumors. In conclusion, 22% of BC tumors were classified as TIL+PD-L1+ (69% were TN), which were enriched with suppressive immune subsets. These cell types may serve as potential novel immunotherapeutic targets.

Development of Radiotracers for Breast Cancer-The Tumor Microenvironment as an Emerging Target.

Molecular imaging plays an increasingly important role in the diagnosis and treatment of different malignancies. Radiolabeled probes enable the visualization of the primary tumor as well as the metastases and have been also employed in targeted therapy and theranostic approaches. With breast cancer being the most common malignancy in women worldwide it is of special interest to develop novel targeted treatments. However, tumor microenvironment and escape mechanisms often limit their therapeutic potential. Addressing tumor stroma associated targets provides a promising option to inhibit tumor growth and angiogenesis and to disrupt tumor tissue architecture. This review describes recent developments on radiolabeled probes used in diagnosis and treatment of breast cancer especially in triple negative type with the focus on potential targets offered by the tumor microenvironment, like tumor associated macrophages, cancer associated fibroblasts, and endothelial cells.

Clinical Analysis of 269 Ph Chromosome-Negative Myeloproliferative Neoplasms Patients Stratified by Age

To investigate the difference of clinical characteristics between young patients(age≤40 years old) and middle-older patients(age>40 years old) with the myeloproliferative neoplasms（MPN）. The clinical data (gene mutations， peripheral blood routine examinations， imaging examination and past history) of 269 MPN patients was collected and analyzed. In essential thrombocythemia (ET) group, the proportion of triple-negative type in young patients was higher than that in middle-older group, while the peripheral white blood cell（WBC） and platelets（PLT） counts in the first visit were lower. In polycythemia vera (PV) group, the total detection rate of JAK2V617F (80.65%) was lower than that of other research reports. Young patients with PV showed the lower JAK2V617F rate and lower WBC count, compared with the middle-older aged patients. Both CALR and MPL mutations were not found in PV patients. There was only 1 primary myelofibrosis (PMF) patient aged <40 years old. 91.67% of the patients merged splenomegaly and this rate was higher than that of ET or PV patients. It was found that there were a diagnosed familial MPN family and an undiagnosed family， and the youngest patient was only 8 years old. The second-generation gene sequencing detection for them was not carried out. Age is an important reference index in the assessment of risks. The MPN patients with different age and types show much difference in gene mutations, peripheral blood cell counts, thrombotic events and sizes of spleen. The onset ages of patients with familial MPN trends to be generational younger.

Recombinant SLAMblind Measles Virus Is a Promising Candidate for Nectin-4-Positive Triple Negative Breast Cancer Therapy

One of the most refractory breast cancer types is triple negative (TN) breast cancer, in which cells are resistant to both hormone and Herceptin treatments and, thus, often cause recurrence and metastasis. Effective treatments are needed to treat TN breast cancer. We previously demonstrated that rMV-SLAMblind, a recombinant measles virus, showed anti-tumor activity against breast cancer cells. Here, we examined whether rMV-SLAMblind is effective for treating TN breast cancer. Nectin-4, a receptor for rMV-SLAMblind, was expressed on the surface of 75% of the analyzed TN breast cancer cell lines. rMV-SLAMblind infected the nectin-4-expressing TN breast cancer cell lines, and significantly decreased the viability in half of the analyzed cell lines in vitro. Additionally, intratumoral injection of rMV-SLAMblind suppressed tumor growth in xenografts of MDA-MB-468 and HCC70 cells. To assess treatment for metastatic breast cancer, we performed intravenous administration of the luciferase-expressing-rMV-SLAMblind to MDA xenografted mice. Virus replicated in the tumor and resulted in significant suppression of the tumor growth. The safety of the virus was tested by its intravenous injection into healthy cynomolgus monkeys, which did not cause any measles-like symptoms. These results suggest that rMV-SLAMblind is a promising candidate as a therapeutic agent for treating metastatic and/or TN type breast cancer.

Membrane mesothelin expression positivity is associated with poor clinical outcome of luminal-type breast cancer.

Mesothelin is expressed in various types of malignant tumors. The present study immunohistochemically investigated mesothelin expression and its clinicopathological significance in each subtype of breast cancer, with special reference to its cellular localization, in particular, membrane mesothelin expression. Using tissue specimens from 482 patients with breast cancer, immunohistochemistry was used to study mesothelin expression and help classify its localization as membrane or cytoplasmic expression. Mesothelin expression was detected in 77 (16.0%) cases and was the highest in triple-negative breast cancer (31/75; 41.3%), followed by human epithelial growth factor receptor type 2 type (6/33, 18.2%) and luminal type (36/374; 9.6%). Among the 482 cases, membrane mesothelin expression was detected in 73 cases and was significantly associated with a negative hormone receptor status, higher Ki-67 labeling index, nuclear grade 3 and a lower relapse-free survival rate. Cytoplasmic mesothelin expression was not significantly associated with a lower relapse-free survival rate (P=0.058). In the 343 cases of luminal type, the membrane mesothelin expression-positive group had significantly worse prognosis than the membrane mesothelin-expression-negative group (P=0.042). There was no significant difference in the relapse-free survival rate according to the membrane mesothelin expression status in the triple-negative type and other types. It was suggested that membrane mesothelin expression in luminal type breast cancer is associated with a lower rate of relapse-free survival.

Early Death Incidence and Prediction in Stage IV Breast Cancer.

BackgroundThe early death of patients is a global cancer issue. We aimed to identify the risk factors for early death in stage IV breast cancer. Predictive nomograms for early death evaluation were generated based on the risk factors.Material/MethodsBased on the Surveillance, Epidemiology, and End Results (SEER) database, patients diagnosed with IV breast cancer were selected. The risk factors for early death (survival time ≤1 year) were identified using logistic regression model analysis. Predictive nomograms were constructed and internal validation was performed.ResultsA total of 5998 (32.6%) breast cancer patients were diagnosed as early death in the construction cohort. Age older than 50 years, unmarried status, black race, uninsured status, triple-negative type, grade (II and III), tumor size >5 cm, and metastasis to lung, liver, and brain were risk factors for total early death, while Luminal B subtype, N1 stage, and surgical interventions were associated with lower risk of early death. As for cancer-specific and non-cancer-specific early death, several factors were not consistent between the 2 groups. Nomograms for all-cause, cancer-specific, and non-cancer-specific early death were constructed. The calibration curve showed satisfactory agreement. The areas under the ROC curve (AUC) were 78.3% (95% CI: 77.7–78.9%), 75.8% (75.1–76.4%), and 72.3% (71.6–72.9%), respectively. In the validation cohort, a total of 689 (19.3%) patients were diagnosed as early death and the calibration curve showed satisfactory agreement. The AUCs of the all-cause, cancer-specific, and non-cancer-specific early death prediction were 74.0% (95% CI: 72.5–75.4%), 73.5% (72.0–74.9%), and 68.6% (67.0–70.1%), respectively.ConclusionsNomograms were generated to predict early death, with good calibration and discrimination. The predictive model can provide a reference for identifying cases with high risk of early death among stage IV breast cancer patients and play an auxiliary role in guiding individual treatment.

Long-term results of combined treatment of triple-negative breast cancer

The most dangerous immunohistochemical type of breast cancer is the triple-negative type. This subtype is detected in 10-20 % of breast cancer cases and is characterized by an aggressive clinical course with high proliferative activity and growth rate, which leads to more active surgical tactics and systemic treatment.The aim of the study was to study the long-term results of the combined treatment of triple-negative type of breast cancer in comparison with other immunohistochemical types.Materials and methods. The treatment results of 140 women with breast cancer who underwent radical surgery and were available for contact after 6 months and more after the operation were analyzed depending on the initial clinical and pathological parameters and treatment features using the methods of descriptive statistics, χ2 criterion and correlation analysis, survival tables and the Kaplan-Meier method.Results. During the analyzed period, distant metastases were detected in 5 (3.6 %), locoregional recurrence in 15 (10.7 %), 12 (8.6 %) patients died. Long-term results with triple-negative type of breast cancer are worse than with luminal forms. A significant dependence of survival on neoadjuvant chemotherapy was revealed. Radiation therapy, the volume of surgery (radical resection or radical mastectomy), breast reconstruction did not significantly affect the long-term result of treatment.Conclusion. Triple-negative type of breast cancer has the worst long-term results with an increase in the frequency of distant and locoregional metastases and a decrease in overall and relapse-free survival compared with luminal types. After neoadjuvant chemotherapy, the frequency of locoregional relapses decreases and the life expectancy of patients increases

Ultrafast dynamic contrast-enhanced breast MRI may generate prognostic imaging markers of breast cancer

BackgroundUltrafast dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI)-derived kinetic parameters have demonstrated at least equivalent accuracy to standard DCE-MRI in differentiating malignant from benign breast lesions. However, it is unclear if they have any efficacy as prognostic imaging markers. The aim of this study was to investigate the relationship between ultrafast DCE-MRI-derived kinetic parameters and breast cancer characteristics.MethodsConsecutive breast MRI examinations between February 2017 and January 2018 were retrospectively reviewed to determine those examinations that meet the following inclusion criteria: (1) BI-RADS 4–6 MRI performed on a 3T scanner with a 16-channel breast coil and (2) a hybrid clinical protocol with 15 phases of ultrafast DCE-MRI (temporal resolution of 2.7–4.6 s) followed by early and delayed phases of standard DCE-MRI. The study included 125 examinations with 142 biopsy-proven breast cancer lesions. Ultrafast DCE-MRI-derived kinetic parameters (maximum slope [MS] and bolus arrival time [BAT]) were calculated for the entire volume of each lesion. Comparisons of these parameters between different cancer characteristics were made using generalized estimating equations, accounting for the presence of multiple lesions per patient. All comparisons were exploratory and adjustment for multiple comparisons was not performed; P values < 0.05 were considered statistically significant.ResultsSignificantly larger MS and shorter BAT were observed for invasive carcinoma than ductal carcinoma in situ (DCIS) (P < 0.001 and P = 0.008, respectively). Significantly shorter BAT was observed for invasive carcinomas with more aggressive characteristics than those with less aggressive characteristics: grade 3 vs. grades 1–2 (P = 0.025), invasive ductal carcinoma vs. invasive lobular carcinoma (P = 0.002), and triple negative or HER2 type vs. luminal type (P < 0.001).ConclusionsUltrafast DCE-MRI-derived parameters showed a strong relationship with some breast cancer characteristics, especially histopathology and molecular subtype.

In silico studies of some 2-anilinopyrimidine derivatives as anti-triple-negative breast cancer agents

BackgroundBreast cancer is a major form of health problem on the globe and the second cause of death related to cancer amidst women. A prediction of about 1 to 1.3 million cases on cancer of the breast are detected yearly globally. Triple-negative type of breast cancers (TNBCs) are described by the lack of human epidermal growth factor receptor 2 (HER2), estrogen receptor (ER), and progesterone receptor (PR). TNBCs metastasize to the central nervous system and lungs regularly. Such metastatic actions reduce the life expectancy of patients with TNBC than patients with non-TNBC due to non-enhanced inhibitor compounds. The purpose of this research was to explore the anti-proliferative activities of 2-anilinopyrimidine derivatives against triple-negative cancer cell line MDA-MB-468 via in silico studies like QSAR and molecular docking studies to further design and develop new anti-breast cancer drug with high potency and low toxicity.ResultsThe quantitative structure–activity relationship QSAR model predicts the bioactivities of the compounds, and molecular docking studies comprehend the interaction between the derivatives (ligand) and thyroid hormone (TRβ1) (receptor). Model 4 was chosen as the best model from the statistical assessment; R2 = 0.8760, R2adj = 0.8451, Q2 = 0.6141, and R2pred of 0.5390. From the external validation of the QSAR model, the coefficient of the mean effect on the model parameters indicates that decreasing (VR1_Dzv and MOMI-R) and increasing (SpMin1_Bh and C3SP3) would increase the anti-proliferative activities (pIC50) of the compounds. The molecular docking studies revealed that ligands 15 and 18 had the highest docking scores of − 7.3 and − 7.4 kcal/mol with thyroid hormone receptor (TRβ1). The ligands had docking scores better than the standard anti-breast cancer drug gefitinib (− 5.3 kcal/mol).ConclusionsThe results indicate that model 4 can be used in developing new 2-anilinopyrimidine derivatives, with better anti-breast cancer prediction activity and performance. It was proved that some series of 2-anilinopyrimidine derivative compounds bind tightly to the receptor, stabilizing the receptor (TRβ1) which is evident from the receptor–ligand interactions, and these compounds would serve as the most promising inhibitors against TRβ1. This shows a breakthrough for pharmaceutical researchers in designing and developing new anti-triple-negative breast cancer drugs.

Risk factors of ipsilateral breast tumor recurrence in triple-negative or HER2-positive breast cancer patients who achieved pathological complete response after neoadjuvant chemotherapy.

e12599 Background: To date, patients undergo breast surgery after neoadjvant chemotherapy (NAC) even though they achieve clinical complete response (cCR). The safety of omitting breast surgery for the patients who are predicted to be pCR has recently investigated in some research, however we still have not reached to a definite consensus yet. We may consider the breast surgery omission on the assumption that the rate of ipsilateral breast tumor recurrence (IBTR)after achieving pCR is acceptably low. The purpose of this study is to examine the rate of and evaluate the clinical features of IBTR in patients achieving pCR after NAC. Methods: In this study, a total of 278 patients with HER2-positive or Triple negative type primary breast cancer were enrolled from4 institutions. They were all diagnosed as ypT0 after breast conserving surgery and received postoperative radiotherapy. Occurrence of IBTR and other clinicopathological factors were collected by retrospective chart review. Results: Of the 278 patients, 49 patients (18%) were ER+/HER2+, 106 patients (38%) were ER-/HER2+ and 123 patients (44%) were ER-/HER2-. We found breast recurrence in 11 patients (4%) as a first recurrence. The 5-year breast recurrence rate was 4.5% in total, 2.2% in ER+/HER2+, 4.0% in ER-/HER2+ and 4.6% in ER-/HER2-, respectively. There was no significantly difference among subtypes. Interestingly, the 5-year breast recurrence rate of patients under 40-year-old was 12.3% which was significantly higher than patients with and above 40-year-old (3.1%, p=0.002). Conclusions: We should be extremely careful when consider omitting breast surgery for patients younger than 40 even if they achieved pCR after NAC.

The association between MRI findings and breast cancer subtypes: focused on the combination patterns on diffusion-weighted and T2-weighted images.

To assess morphology on diffusion-weighted imaging (DWI) and intratumoral signal intensity (SI) on T2-weighted images (T2WI) of breast carcinomas, and to evaluate the association between the combined DWI and T2WI findings and breast cancer subtypes. Two hundred and eighty breast cancer patients who underwent breast MRI prior to therapy were included in this retrospective study. All had invasive carcinomas, which were classified into five subtypes: Luminal A-like (n = 149), Luminal B-like (n = 63), Hormone receptor-positive HER2 (n = 31), Hormone receptor-negative HER2 (n = 13), or Triple-negative (TN) (n = 24). Based on the morphology on DWI, the tumors were classified into two patterns: DWI-homogeneous or DWI-heterogeneous. If DWI-heterogeneous, an assessment of intratumoral SI on T2WI was performed: tumors with intratumoral high/low SI on T2WI were classified as Hete-H/Hete-L, respectively. The associations between (1) the morphological patterns on DWI and the five subtypes, and (2) the intratumoral SI patterns on T2WI and the five subtypes in DWI-heterogeneous were evaluated. There was a significant association between (1) the morphological patterns on DWI and the five subtypes (p < 0.0001), and (2) the intratumoral SI patterns on T2WI and the five subtypes in DWI-heterogeneous (p < 0.0001). DWI-homogeneous was dominant in Luminal A-like (67.1%), and Hete-H was dominant in TN type (75%). Hete-H, suggesting the presence of intratumoral necrosis, included high proliferative and/or aggressive subtypes more frequently (80%) than Hete-L, suggesting the presence of fibrotic focus. Fibrotic focus was seen more commonly in the luminal subtypes. The combined findings on DWI and T2WI revealed breast carcinomas that were associated with particular subtypes.

Clinico-pathological co-relation using various immuno-histochemistry markers likeER, PR, HER-2 NEU, CK5/6, EGFR, KI-67 in carcinoma breast

In India, for the year 2012, 144,937 women were newly detected with breast cancer and 70,218 women died of it. For every 2 women newly diagnosed with breast cancer, one lady is dying of it. The aim of this study is to evaluate clinical parameters and pathological findings including various Immuno-histochemistry (IHC) markers like ER, PR, HER-2 NEU, CK5/6, EGFR, Ki-67 in cases of carcinoma breast and classify them into molecular classification based on IHC markers and try to correlate them clinically. This prospective, observational study was carried out in 56 patients with early carcinoma breast (stage-I and stage-II) and IHC evaluation for various markers was done. Data was analysed by using Molecular Classification, divide them into estrogen positive (luminal HER-2, luminal A and luminal B) and estrogen negative (Triple negative or basal cell type, HER-2Neu type and normal breast like phenotype) subtypes. We had correlated this data with parameters like age of the patient, clinical and pathological staging of the breast carcinoma, presence or absence of nodes and presence or absence of other IHC parameters. We used ANOVA-F test to catagories variables and measure the test of significance. On IHC in Her-2 neu equivocal cases (patients who had two “++” positive points), we performed FISH test. Out of these 17 equivocal cases, only 3 were positive, 10 were negative and 4 patients did not underwent this test due to several reasons. Finally, Ki-67 value is significantly high in triple negative and Luminal-B patients. NPI is also having low ‘P’value, although not reaching the level of significance. Types of breast carcinoma, which look histologically similar behaves differently in their clinical presentation and in prognosis.In our study only Ki-67 was correlated with poor prognostic subtype of molecular classification but no any poor risk of clinical or histological parameter was correlated significantly with bad prognostic subtype of molecular classification as Luminal-B or triple negative type. We can say that this molecular classification is different in terms of prognosis in patients with similar looking clinical and histological parameters.