Hormone Receptor Status Research Articles

The Predictive Role of Mammography, Dynamic Contrast-Enhanced Breast Magnetic Resonance Imaging and Diffusion-Weighted Imaging in Hormone Receptor Status of Pure Ductal Carcinoma In Situ Lesions.

The aim of this retrospective study was to analyze the predictive capabilities of preoperative mammography, dynamic contrast-enhanced-magnetic resonance imaging (DCE-MRI), and diffusion-weighted imaging (DWI) in determining hormone receptor (HRc) status for pure ductal carcinoma in situ (DCIS) lesions. The study included a total of 79 patients who underwent preoperative mammography (MG) and MRI between December 2018 and December 2023 and were subsequently diagnosed with pure DCIS after surgery. The correlation between MG, DCE-MRI, and DWI features and estrogen receptor (ER) and progesterone receptor (PR) status was examined. Among the lesions, 44 were double HRc-positive (ER and PR-positive), 13 were single HRc-positive (ER-positive and PR-negative or ER-negative and PR-positive) and 22 were double HRc-negative (ER and PR-negative). The presence of symptom (p = 0.029), the presence of comedo necrosis (p = 0.005) and high histological grade (p<0.001) were found to be associated with ER and PR negativity. Amorphous microcalcifications were more commonly observed in the double HRc-negative group, while linear calcifications were more prevalent in both double and single HRc-positive groups (p = 0.020). Non-mass enhancement (NME) with a linear distribution was significantly more common in double HRc-negative lesions (38%), and NME with a segmental distribution in both double (43%) and single (50%) receptor-positive lesions (p = 0.042). Evaluation of DWI findings revealed that a higher lesion-to-normal breast parenchyma apparent diffusion coefficient (ADC) ratio statistically increased the probability of HRc positivity (p = 0.033). Certain clinicopathological, mammography, and MRI features, along with the lesion-to-normal breast parenchyma ADC ratio, can serve as predictors for HRc status in DCIS lesions.

Expression of Axl Receptor Tyrosine Kinase and Its Association With Ki-67 Proliferation Marker, BCL-2 Anti-apoptotic Protein, Hormone Receptor Status, and HER2/Neu Status in Breast Cancer Among Women From Duhok, Iraq.

Background Breast cancer (BC) is the most prevalent cancer among women worldwide, contributing to high mortality rates, especially in Iraqi women. Detecting the disease before metastasis may increase survival chances for many patients, but that is not the case for most of them. Thus the search for new prognostic biomarkers or testing the relevance of existing ones could contribute to therapeutic decisions complementing the traditional methods, including TNM (tumor, node, and metastasis) staging, tumor grade, and other clinicopathological features in addition to the use of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2/neu). The Axl receptor is frequently associated with invasion, migration, poor prognosis, and angiogenesis. Furthermore, its association with chemotherapyand targeted therapy resistance makes itan ideal biomarker for therapeutic targeting. Methodology This study involved 50 malignant cases with 25 benign fibroadenoma and non-neoplastic cases represented by inflammatory conditions, collected with their corresponding data from the central lab in Duhok Governorate, Iraq. Expression of Kiel 67 (Ki-67) proliferation marker and B-cell lymphoma 2 (BCL-2) anti-apoptotic protein was measured using immunohistochemistry (IHC) to estimate tumor growth and apoptosis. Gene expression of the Axl receptor was evaluated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Results Cases with high Ki-67 accounted for 68% and low Ki-67 cases were 32% across the graded groups and were significantly associated with tumor grade, PR, and HER2. BCL-2-negativecases accounted for 62% and BCL-2-positive cases were 38%. It was revealed that BCL-2 had a strong correlation with age, especially inthose under 50 years.As for the Axl gene expression, the average fold change in expression in the high-grade (H.) group was 1.74 times higher than in the control group, while in the low/intermediate (L.) group, it was 3.74 times higher. Additionally, when comparing these results with other variables, no significant associations were observed. Conclusion Axl receptor was not associated with all of the clinicopathological variables, the expression values were high in malignant tumors in comparison with the benign tumors, and it was found that Axl receptor expression was associated with low/intermediate grade, which is considered a favorable prognostic factor. Although Axl receptor expression was previously linked with proliferation and invasiveness in BC, its association with the Ki-67 proliferation marker and BCL-2 anti-apoptotic protein was not observed.

Spectrum of Ductal Carcinoma In Situ (DCIS) Lesions of the Breast: From Morphology to Molecular Characteristics.

Background Specific molecular characteristics of invasive breast cancer have been linked to an increased risk of early relapse. Similarly, ductal carcinoma in situ (DCIS) displays a comparable molecular profile, although their prevalence and implications are not yet fully understood. Aims and objectives The study design defined a multivariable statistical approach aimed at describing the interplay between the histopathological features of ductal carcinoma in situ (DCIS) and their molecular profile. The objective was to explore the correlations between the histopathological features of DCIS (tumor location, DCIS grade, DCIS type, and presence or absence of comedo necrosis) and various biomarkers like estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor (HER2/neu), androgen receptor (AR), and epidermal growth factor receptor (EGFR), in addition to the Ki-67 labeling index. Methods In this retrospective study, we selected and analyzed 100 diagnosed cases of ductal carcinoma in situ (DCIS) to represent various subtypes, grades, and morphological characteristics. A detailed histopathological review and immunohistopathological staining for ER, PR, HER2/neu, AR, EGFR, and Ki-67 were performed on formalin-fixed paraffin-embedded (FFPE) tumor tissue blocks. Molecular subtyping was done based on the biomarker analysis into luminal A, luminal B, luminal HER2/neu, HER2/neu enriched, and triple-negative subtypes. Statistical analysis was done to examine the correlation between tumor location, histopathological features of ductal carcinoma in situ (DCIS), and the expression of the immunohistochemical markers and the molecular subtypes. Results The majority of cases exhibited positivity for estrogen receptor (ER) and progesterone receptor (PR). A strong association was observed between histopathological features (DCIS grade, type, and comedo necrosis) of DCIS and ER/PR status. Additionally, a significant correlation was found between ductal carcinoma in situ (DCIS) grade and HER2/neu status. However, no association was identified between histopathological features and AR or EGFR status. Contrary to expectations, triple-negative DCIS did not show the most aggressive behavior, whereas HER2/neu-positive tumors, particularly high-grade ones, exhibited more aggressive features. No low-grade cases of luminal HER2/neu and HER2/neu-enriched tumors were found. A higher Ki-67 labeling index was found in cases with grade 3 and solid and comedo architectural types of DCIS, while low-grade tumors had a lower Ki-67 labeling index. Conclusion These findings suggest that hormone pathways play a crucial role in ductal carcinoma in situ (DCIS) progression, but the molecular interactions are complex and extend beyond simple binary associations. The complex relationship between the histopathological features of ductal carcinoma in situ (DCIS) and its hormone receptor status warrants further investigation with a larger sample size to fully understand the underlying mechanisms. The results challenge the expectation that triple-negative DCIS is the most aggressive subtype, highlighting the need for further research into the prognostic significance of different DCIS subtypes.

Menin in Cancer.

The protein menin is encoded by the MEN1 gene and primarily serves as a nuclear scaffold protein, regulating gene expression through its interaction with and regulation of chromatin modifiers and transcription factors. While the scope of menin's functions continues to expand, one area of growing investigation is the role of menin in cancer. Menin is increasingly recognized for its dual function as either a tumor suppressor or a tumor promoter in a highly tumor-dependent and context-specific manner. While menin serves as a suppressor of neuroendocrine tumor growth, as seen in the cancer risk syndrome multiple endocrine neoplasia type 1 (MEN1) syndrome caused by pathogenic germline variants in MEN1, recent data demonstrate that menin also suppresses cholangiocarcinoma, pancreatic ductal adenocarcinoma, gastric adenocarcinoma, lung adenocarcinoma, and melanoma. On the other hand, menin can also serve as a tumor promoter in leukemia, colorectal cancer, ovarian and endometrial cancers, Ewing sarcoma, and gliomas. Moreover, menin can either suppress or promote tumorigenesis in the breast and prostate depending on hormone receptor status and may also have mixed roles in hepatocellular carcinoma. Here, we review the rapidly expanding literature on the role and function of menin across a broad array of different cancer types, outlining tumor-specific differences in menin's function and mechanism of action, as well as identifying its therapeutic potential and highlighting areas for future investigation.

Datopotamab-deruxtecan plus durvalumab in early-stage breast cancer: the sequential multiple assignment randomized I-SPY2.2 phase 2 trial.

Sequential adaptive trial designs can help accomplish the goals of personalized medicine, optimizing outcomes and avoiding unnecessary toxicity. Here we describe the results of incorporating a promising antibody-drug conjugate, datopotamab-deruxtecan (Dato-DXd) in combination with programmed cell death-ligand 1 inhibitor, durvalumab, as the first sequence of therapy in the I-SPY2.2 phase 2 neoadjuvant sequential multiple assignment randomization trial for high-risk stage 2/3 breast cancer. The trial includes three blocks of treatment, with initial randomization to different experimental agent(s) (block A), followed by a taxane-based regimen tailored to tumor subtype (block B), followed by doxorubicin-cyclophosphamide (block C). Subtype-specific algorithms based on magnetic resonance imaging volume change and core biopsy guide treatment redirection after each block, including the option of early surgical resection in patients predicted to have a high likelihood of pathologic complete response, which is the primary endpoint assessed when resection occurs. There are two primary efficacy analyses: after block A and across all blocks for six prespecified HER2-negative subtypes (defined by hormone receptor status and/or response-predictive subtypes). In total, 106 patients were treated with Dato-DXd/durvalumab in block A. In the immune-positive subtype, Dato-DXd/durvalumab exceeded the prespecified threshold for success (graduated) after block A; and across all blocks, pathologic complete response rates were equivalent to the rate expected for the standard of care (79%), but 54% achieved that result after Dato-DXd/durvalumab alone (block A) and 92% without doxorubicin-cyclophosphamide (after blocks A + B). The treatment strategy across all blocks graduated in the hormone-negative/immune-negative subtype. No new toxicities were observed. Stomatitis was the most common side effect in block A. No patients receiving block A treatment alone had adrenal insufficiency. Dato-DXd/durvalumab is a promising therapy combination that can eliminate standard chemotherapy in many patients, particularly the immune-positive subtype.ClinicalTrials.gov registration: NCT01042379 .

PAM50 breast cancer subtypes and survival of patients in rural Ethiopia without adjuvant treatment: a prospective observational study

PurposeSurvival rates of breast cancer (BC) patients are particularly low in rural regions in sub-Saharan Africa (SSA) which is due to limited access to therapy. In recent years, gene expression profiling (GEP) of BC showed a strong prognostic value in patients with local tumour surgery and (neo)adjuvant treatment. The aim of this study was to evaluate the impact of intrinsic subtypes on survival of patients in rural Ethiopia without any (neo)adjuvant therapy.MethodsIn total, 113 female patients from Aira Hospital with histologically proven BC and treated only with surgery were included in this study. All samples were analysed by immunohistochemistry (IHC) for estrogen receptor, progesterone receptor, HER2 and Ki67, as well as RNA-expression analysis for PAM50 subtyping.ResultsA positive hormone receptor status was found in 69.0% of the tumours and intrinsic subtyping demonstrated Luminal B to be the most common subtype (34.5%). Follow-up data was available for 79 of 113 patients. Two-year overall survival (OS) was 57.3% and a considerably worse OS was observed in patients with Basal-like BC compared to Luminal A BC. Moreover, advanced tumours showed an increased risk of mortality.ConclusionThe OS was very low in the patient cohort that received no (neo)adjuvant treatment. Immunohistochemistry and GEP confirmed endocrine-sensitive tumours in more than half of the patients, with a large proportion of Luminal B, HER2-enriched and Basal-like tumours so that adjuvant chemotherapy should be recommended.

Clinicopathological Factors Predicting Pathological Complete Response to Neoadjuvant Anti-HER2 Therapy in HER2-Positive Breast Cancer

Plain Language SummaryNeoadjuvant treatment is the standard approach for human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Especially, pathologic response is an important prognostic factor and the adjuvant treatment is dependent on the response. Therefore, predicting the response is important for modulating the treatment sequence, especially in the initial stage of treatment decision. Therefore, we aimed to identify factors that can predict the effectiveness of neoadjuvant chemotherapy, and our results suggest that factors such as tumor size, grade, hormone receptor, and HER2 status should be considered in the treatment of breast cancer.

Nomograms for predicting recurrence of HER2-positive breast cancer with different HR status based on ultrasound and clinicopathological characteristics.

This study aimed to identify ultrasound and clinicopathological characteristics related to recurrence in HER2-positive (HER2+) breast cancer, and to develop nomograms for predicting recurrence. In this dual-center study, we retrospectively enrolled 570 patients with HER2+ breast cancer. The ultrasound and clinicopathological characteristics of hormone receptor (HR)-/HER2+ patients and HR+/HER2+ patients were analyzed separately according to HR status. Eighty percent of the original samples from HR-/HER2+ and HR+/HER2+ patients were extracted by bootstrap sampling as the training cohorts, while the remaining 20% were used as the external validation cohorts. Informative characteristics were screened through univariate and multivariable Cox regression in the training cohorts and used to develop nomograms for predicting recurrence. The predictive accuracy was calculated using Harrell's C-index and calibration curves. Three informative characteristics (axillary nodal status, calcification, and Adler degree) were identified in HR-/HER2+ patients, and another three (histological grade, axillary nodal status, and echogenic halo) in HR+/HER2+ patients. Based on these, two separate nomograms were constructed to assess recurrence risk. In the training cohorts, the C-index was 0.740 (95% CI: 0.667-0.811) for HR-/HER2+ nomogram, and 0.749 (95% CI: 0.679-0.820) for HR+/HER2+ nomogram. In the validation cohorts, the C-index was 0.708 (95% CI: 0.540-0.877) for HR-/HER2+ group, and 0.705 (95% CI: 0.557-0.853) for HR+/HER2+ group. The calibration curves also indicated the excellent accuracy of the nomograms. Ultrasound performance of HER2+ breast cancers with different HR status was significantly different. Nomograms integrating ultrasound and clinicopathological characteristics exhibited favorable performance and have the potential to serve as a reliable method for predicting recurrence in heterogeneous breast cancer.

A Retrospective Study of Fertility Counseling and Preservation Rates for Women of Reproductive Age With Breast Care After Integrating a Fertility Specialist Into a Multidisciplinary Tumor Board

IntroductionMany breast centers have adopted multidisciplinary tumor boards to discuss and develop treatment plans for patients diagnosed with breast cancer. This study aims to determine whether adding a fertility specialist to tumor board will improve fertility counseling and utilization in breast cancer patients MethodsA retrospective study of reproductive age patients diagnosed with breast cancer between January 1, 2012, and January 31, 2020, before and after integrating a designated fertility specialist into a comprehensive multidisciplinary care (cMDC) tumor board. Rates of fertility counseling and preservation were assessed for patients treated before (pre-cMDC) and after (post-cMDC) tumor board enhancement. Associations of race/ethnicity, age, chemotherapy, hormone receptor status, insurance type, parity, stage, site of treatment, and home county with fertility care rates were assessed in the post-cMDC group. ResultsOf 306 patients diagnosed with breast cancer, 117 (38%) were in the pre-cMDC and 189 (62%) were in the post-cMDC tumor board group. Significantly more patients in the post-cMDC tumor board group were offered fertility counseling than patients in the pre-cMDC tumor board group (23.3% (44) vs. 0.9% (1); P < .001). However, rate of fertility preservation did not differ significantly between groups. ConclusionIntegrating a fertility specialist within a cMDC tumor board may help improve rates of fertility counseling among breast cancer patients but may not improve preservation rates.

Incidence and Prognostic Values in Human Epidermal Growth Factor Receptor 2-Low Expression Metastatic Breast Cancer in Southeast Asian Population: A 10-Year Retrospective Study.

Breast cancer progression varies across molecular subtypes, and treatment options for human epidermal growth factor receptor 2 (HER2)-low expression tumors are limited compared with those of HER2 overexpression tumors. Comprehensive information regarding the epidemiology and clinical outcomes of metastatic HER2-low expression breast cancer in a Southeast Asian population is lacking. This retrospective cohort study was performed to analyze data from patients with de novo advanced breast cancer, including HER2 expression, tumor stage, and metastatic pattern. Statistical analyses, including chi-square tests and survival analyses, were used to compare HER2-low expression and HER2-negative groups. Of the 491 patients, 21.2% had HER2-low expression, 30% had HER2 overexpression, and 50% had HER2-negative expression. Among the hormone receptor (HR)-positive patients, 34% had HER2-low expression; in the triple-negative patients, the HER2-low incidence was 20.6%. No significant differences in clinical characteristics between HER2-low and HER2-negative groups were observed, except for more HR-positive patients in the HER2-low group. HER2-low patients had a longer overall survival (OS) than HER2-negative patients (43 v 23 months; hazard ratio, 0.7; P < .001), especially in HR-positive patients. After adjusting for HR status, HER2-low patients maintained improved outcomes. HR-positive HER2-low patients showed nonsignificant OS gains compared with HR-positive HER2-negative patients, regardless of first-line chemotherapy or endocrine therapy. This study revealed the incidence and clinical outcomes of HER2-low expression in de novo advanced breast cancer, suggesting favorable outcomes, particularly in HR-positive breast cancer. These findings may inform personalized treatment strategies. Further research into the mechanisms and implications of HER2-low expression in breast cancer is required.

Retrieval of the Clipped Axillary Lymph Node and Its Impact on Treatment Decisions.

We examined clinically node-positive (cN+) breast cancer patients undergoing neoadjuvant chemotherapy and clipped lymph node (CLN) localization to determine the rate of CLN = non-sentinel lymph node (SLN), the factors associated with cN+ to pN0 conversion, and the treatment impact. We conducted a single institution review of cN+ patients receiving NAC from 2016 to 2022 with preoperative CLN localization (N = 81). Demographics, hormone receptor (HR) and HER2 status, time to surgery, staging, chemotherapy regimen, localization method, pathology, and adjuvant therapy were analyzed. Pathologic complete response (pCR) of the CLN was observed in 41 patients (50.6%): 18.8% HR+/HER2-, 75% HR+/HER2+, 75% HR-/HER2+, and 62.5% triple-negative breast cancer (p-value = 0.006). CLN = SLN in 68 (84%) patients, while CLN = non-SLN in 13 (16%). In 14 (17.3%) patients, the final treatment was altered based on +CLN status: 11 patients underwent axillary lymph node dissection (ALND), and 3 had systemic treatment changes. pCR rates varied, with the highest conversion rates observed in HER2+ disease and the lowest in HR+/HER2- disease. In 2 (2.5%) patients, adjuvant therapy changes were made based on a non-sentinel CLN, while in 97.5% of patients, a SLN biopsy alone represented the status of the axilla. This demonstrates that a +CLN often alters final plans and that, despite also being a SLN in most cases, a subset of patients will be undertreated by SLN biopsy alone.

Ovarian stimulation response and fertility outcomes in patients with breast cancer across different stages, grades, and hormone receptor status for fertility preservation

BackgroundThis study aimed to explore the potential impact of stage, grade, and hormone receptor profile on ovarian stimulation response and fertility preservation outcomes. MethodsThis retrospective cohort study evaluated data from breast cancer patients who underwent fertility preservation at a tertiary medical center between 2014 and 2022. The outcomes of women with low-stage cancer (stages I and II) were compared with those of women with high-stage disease (stages III and IV or lymph node metastasis). Similarly, we compared those with low-grade (grades 1 and 2) and high-grade (grade 3) malignancies. In addition, we compared different hormone statuses of breast cancer (1) estrogen receptor (ER) positive vs. ER-negative and (2) triple-negative breast cancer (TNBC) vs. non-TNBC. The primary outcome measured was the number of mature oocytes, while the secondary outcomes included the numbers of total oocytes retrieved, peak estradiol levels, and subsequent fertility preservation outcomes. ResultsA total of 47 patients were included. Patients with high-grade tumors had a comparable number of mature oocytes (8 vs. 10, p = 0.08) compared to patients with low grade cancers. The stage-based analysis revealed a similar number of mature oocytes (8 vs. 10, p = 0.33) between high/low stage patients. In the hormone receptor-based analysis, no differences were seen in mature oocytes collected between the ER-positive/ER-negative group (9 vs. 9, p = 0.87) and the TNBC/non-TNBC group (11 vs. 9, p = 0.13). The utilization rate was 27.6% (13/47). ConclusionOur study showed similar ovarian stimulation response and fertility preservation outcomes among breast cancer patients with different prognostic factors.

Systematic assessment of HER2 status in ductal carcinoma in situ of the breast: a perspective on the potential clinical relevance

In many countries, hormone receptor status assessment of ductal carcinoma in situ (DCIS) is routinely performed, as hormone receptor-positive DCIS patients are eligible for adjuvant anti-hormonal treatment, aiming to reduce the ipsilateral and contralateral breast cancer risk. Although HER2 gene amplification and its associated HER2 protein overexpression constitute a major prognostic and predictive marker in invasive breast carcinoma, its use in the diagnosis and treatment of DCIS is less straightforward. HER2 immunohistochemistry is not routinely performed yet, as the role of HER2-positivity in DCIS biology is unclear. Nonetheless, recent data challenge this practice. Here, we discuss the value of routine HER2 assessment for DCIS. HER2-positivity correlates strongly with DCIS grade: around four in five HER2-positive DCIS show high grade atypia. As morphological DCIS grading is prone to interobserver variability, HER2 immunohistochemistry could render grading more robust. Several studies showed an association between HER2-positive DCIS and ipsilateral recurrence risk, albeit currently unclear whether this is for overall, in situ or invasive recurrence. HER2-positive DCIS tends to be larger, with a higher risk of involved surgical margins. HER2-positive DCIS patients benefit more from adjuvant radiotherapy: it substantially decreases the local recurrence risk after lumpectomy, without impact on overall survival. HER2-positivity in pure biopsy-diagnosed DCIS is associated with increased upstaging to invasive carcinoma after surgery. HER2 immunohistochemistry on preoperative biopsies might therefore provide useful information to surgeons, favoring wider excisions. The time seems right to consider DCIS subtype-dependent treatment, comprising appropriate local treatment for HER2-positive DCIS patients and de-escalation for hormone receptor-positive, HER2-negative DCIS patients.

Long-term exposure to air pollution at residential and workplace addresses and breast cancer risk: A case-control study nested in the French E3N-Générations cohort from 1990 to 2011

BackgroundAn increasing evidence links air pollution to breast cancer (BC) risk. Yet, pollutant exposure estimates at the workplace location in pollution exposure assessment have not been considered. ObjectivesThis study investigates the association between particulate matters (PM2·5, PM10) and nitrogen dioxide (NO2) atmospheric concentrations (1990–2011), at the women’s residential and workplace locations, and BC risk. MethodsThis case-control study of 2419 BC cases and 2984 controls, was nested in the French prospective E3N cohort. The annual mean PM2·5, PM10 and NO2 concentrations were estimated using a Land Use Regression model (50 m x 50 m resolution) and assigned to the women’s geocoded residential and workplace locations, from cohort recruitment to their index date (date of case diagnosis). Odds ratios (OR) and 95 % confidence intervals (CI) were estimated using multivariate logistic regression models. ResultsAn increased BC risk was observed for a 10 µg/m3 increase of the 1990–2011 average PM2·5 concentration estimates (OR=1·28; CI 1·00, 1·63). An increased risk was suggested for a 10 µg/m3 increase for PM10 (OR=1·09; CI 0·92, 1·30) and NO2 (OR=1·05; CI 0·97, 1·13). No effect modification by menopausal status, nor difference by hormone receptor status were observed. DiscussionThis study is the first to estimate BC risk and long-term air pollutant exposure from both, residential and workplace location histories. Results suggest that residential PM2·5, PM10 and NO2 concentrations are strongly correlated with workplace ones, indicating that residential data may serve as proxy for overall exposure. Future studies should consider exposure during commuting.

Association between tumor-infiltrating lymphocytes and survival in patients with metastatic breast cancer receiving first-line chemotherapy: analysis of CALGB 40502

Association of stromal tumor-infiltrating lymphocytes (sTILs) with survival outcomes among patients with metastatic breast cancer (MBC) remains unclear. The primary objective was to evaluate the association of sTILs with progression-free survival in randomized phase III trial CALGB 40502. sTILs were associated with progression-free and overall survival in chemotherapy-treated MBC when controlling for treatment arm; however, this effect did not remain significant after additional adjustment for hormone receptor status. CALGB is now part of the Alliance for Clinical Trials in Oncology. Trial Registration: ClinicalTrials.gov: NCT00785291.

Prognostic and predictive impact of NOTCH1 in early breast cancer.

Systemic therapy plays a major part in the cure of patients with early breast cancer (eBC). However, personalized treatment concepts are required to avoid potentially harmful overtreatment. Biomarkers are pivotal for individualized therapy. The Notch signalling pathway is widely considered as a suitable prognostic or predictive marker in eBC. This study aimed primarily at assessing the relationship between NOTCH1 mRNA expression levels and histopathological features of breast cancer tumors, as well as clinical characteristics of the correspondent eBC patients. As a secondary aim, we investigated the prognostic and predictive value of NOTCH1 by assessing possible associations between NOTCH1 mRNA expression and recurrence-free interval (RFI) and overall survival after five years of observation. The relative NOTCH1 mRNA expression was determined in 414 tumour samples, using quantitative PCR in a prospective, multicenter cohort (Prognostic Assessment in Routine Application (PiA), 2009-2011, NCT01592825) of 1,270 female eBC patients. High NOTCH1 mRNA expression was detected in one-third of the tumours and was associated with negative hormone receptor status and high uPA/PAI-1 status. In addition, high NOTCH1 mRNA expression was found to be associated with more RFI related events (adjusted hazard ratio 2.1, 95% CI 1.077-4.118). Patients who received adjuvant chemotherapy and had high NOTCH1 mRNA expression in the tumour (n = 86) were three times more likely to have an RFI event (adjusted hazard ratio 3.1,95% CI 1.321-7.245, p = 0.009). In this cohort, NOTCH1 mRNA expression had a prognostic and predictive impact. Tumours with high NOTCH1 mRNA expression may be less sensitive to cytotoxic treatment and downregulation of the Notch signalling pathway (e.g. by γ-secretase inhibitors) may be valuable for eBC therapy as an individualised treatment option.

8. American Joint Commision on Cancer score and hormone receptor status predicts 1-, 2-, and 5-year mortality rates in patients that undergo spine surgery for metastatic breast cancer to the spine

8. American Joint Commision on Cancer score and hormone receptor status predicts 1-, 2-, and 5-year mortality rates in patients that undergo spine surgery for metastatic breast cancer to the spine

Somatic mutational landscape across Indian breast cancer cases by whole exome sequencing

Breast cancer (BC) has emerged as the most common malignancy among females. The genomic profile of BC is diverse in nature and complex due to heterogeneity among various geographically different ethnic groups. The primary objective of this study was to carry out a comprehensive mutational analysis of Indian BC cases by performing whole exome sequencing. The cohort included patients with a median age of 48 years. TTN, TP53, MUC16, SYNE1, and OBSCN were the frequently altered genes found in our cohort. The PIK3CA and KLC3 genes are driver genes implicated in various cellular functions and cargo transportation through microtubules, respectively. Except for CCDC168 and PIK3CA, several gene pairings were found to be significantly linked with co-occurrence. Irrespective of their hormonal receptor status, RTK/RAS was observed with frequently altered signaling pathways. Further analysis of the mutational signature revealed that SBS13, SBS6, and SBS29 were mainly observed in our cohort. This study supplements the discovery of diagnostic biomarkers and provides new therapeutic options for the improved management of BC.

Role of textural and radiomic analysis parameters in predicting histopathological parameters of the tumor in breast cancer patients.

Texture and radiomic analysis characterizes the tumor's phenotype and evaluates its microenvironment in quantitative terms. This study aims to investigate the role of textural and radiomic analysis parameters in predicting histopathological factors in breast cancer patients. Two hundred and twelve primary breast cancer patients underwent 18F-FDG PET/computed tomography for staging. The images were processed in a commercially available textural analysis software. ROI was drawn over the primary tumor with a 40% threshold and was processed further to derive textural and radiomic parameters. These parameters were then compared with histopathological factors of tumor. Receiver-operating characteristic analysis was performed with a P-value <0.05 for statistical significance. The significant parameters were subsequently utilized in various machine learning models to assess their predictive accuracy. A retrospective study of 212 primary breast cancer patients was done. Among all the significant parameters, SUVmin, SUVmean, SUVstd, SUVmax, discretized HISTO_Entropy, and gray level co-occurrence matrix_Contrast were found to be significantly associated with ductal carcinoma type. Four parameters (SUVmin, SUVmean, SUVstd, and SUVmax) were significant in differentiating the luminal subtypes of the tumor. Five parameters (SUVmin, SUVmean, SUVstd, SUVmax, and SUV kurtosis) were significant in predicting the grade of the tumor. These parameters showcased robust capabilities in predicting multiple histopathological parameters when tested using machine learning algorithms. Though textural analysis could not predict hormonal receptor status, lymphovascular invasion status, perineural invasion status, microcalcification status of tumor, and all the molecular subtypes of the tumor, it could predict the tumor's histologic type, triple-negative subtype, and score of the tumor noninvasively.

A histomorphological and immunohistochemical analysis of invasive lobular carcinoma of breast: A case series

Invasive lobular carcinoma (ILC) is the second most common special subtype of invasive breast carcinoma comprising 5–15%. ILC defines as invasive carcinoma comprising non-cohesive single-file linear pattern in fibrous stroma. The aim of the study was to evaluate the histomorphological features and immunohistochemical analysis of ILC. A total of 19 cases were encountered from March 2020 to February 2024 out of 129 breast cancers. The sociodemographic profiles and clinicopathological parameters of the patients were studied with special emphasis on their morphology and hormone receptor status. The mean age of patients is 42.8 years. Out of 19 cases, 84.2% showed feature of classic type, 5.2% of tubule-lobular, and 10.5% of pleomorphic lobular carcinoma. The majority of cases (63.2%) showed histologic Grade 2, and 10.5% showed Grade 3. On immunohistochemistry examination, 79% were estrogen receptor (ER) and progesterone receptor (PR) positive with 10.5% of cases was human epidermal growth factor receptor 2/neu (HER2/neu) positive. Our study showed higher cases of classic type ILC, mostly of histologic Grade 2; higher ER-PR receptor positivity and HER2/neu negativity.