Nottingham Prognostic Index Score Research Articles

The Clinicopathological and Prognostic Significance of the Expression of PD-L1 and MET Genes in Breast Cancer: Potential Therapeutic Targets.

The heterogeneity of breast cancer requires exploring novel prognostic biomarkers as well as therapeutic targets for the treatment of the disease. The METABRIC dataset was used to describe the gene expression of the programmed death-ligand 1 (PD-L1) and the hepatocyte growth factor receptor (MET) and their association with the tumor clinicopathologic characteristics and overall survival in breast cancer. The expression of the PD-L1 and MET genes correlated positively with the Nottingham Prognostic Index (NPI) (p=0.003 and p < 0.001, respectively). The expression of the two genes correlated inversely with luminal A and luminal B tumors (r= - 0.089, p= 0.021 and r= - 0.116, p= 0.013, respectively). The PD-L1 mRNA levels were significantly higher in hormone receptor-negative and HER2-positive tumors. MET mRNA expression levels were significantly higher in hormone receptor-negative, HER2-enriched, and non-luminal breast cancers. The PD-L1/MET double-high expression was associated with younger age of patients at diagnosis, higher NPI scores, larger tumors, advanced stage, high-grade, hormone receptor-negativity, HER2-positivity, and non-luminal tumors. None of the genes or their double expression status was significantly associated with overall survival in this analysis. The expression of the PD-L1 and MET genes is remarkably associated with worse tumor clinicopathologic features and poor prognosis in patients with breast cancer. Further investigations using combination drug regimens targeting PD-L1 and MET are important, particularly in breast tumors expressing high levels of both proteins.

A nomogram with Nottingham prognostic index for predicting locoregional recurrence in breast cancer patients.

The Nottingham prognostic index (NPI) has been shown to negatively impact survival in breast cancer (BC). However, its ability to predict the locoregional recurrence (LRR) of BC remains still unclear. This study aims to determine whether a higher NPI serves as a significant predictor of LRR in BC. In total, 238 patients with BC were included in this analysis, and relevant clinicopathological features were collected. Correlation analysis was performed between NPI scores and clinicopathological characteristics. The optimal nomogram model was determined by Akaike information criterion. The accuracy of the model's predictions was evaluated using receiver operating characteristic curves (ROC curves), calibration curves and goodness of fit tests. The clinical application value was assessed through decision curve analysis. Six significant variables were identified, including age, body mass index (BMI), TNM stage, NPI, vascular invasion, perineural invasion (P<0.05). Two prediction models, namely a TNM-stage-based model and an NPI-based model, were constructed. The area under the curve (AUC) for the TNM-stage- and NPI-based models were 0.843 (0.785,0.901) and 0.830 (0.766,0.893) in training set and 0.649 (0.520,0.778) and 0.728 (0.610,0.846) in validation set, respectively. Both models exhibited good calibration and goodness of fit. The F-measures were 0.761vs 0.756 and 0.556 vs 0.696, respectively. Clinical decision curve analysis showed that both models provided clinical benefits in evaluating risk judgments based on the nomogram model. a higher NPI is an independent risk factor for predicting LRR in BC. The nomogram model based on NPI demonstrates good discrimination and calibration, offering potential clinical benefits. Therefore, it merits widespread adoption and application.

Abstract PO1-14-05: A comparison of chemotherapy recommendations by NPI, Predict, and Oncotype DX testing in UK women with early node positive breast cancer

Abstract Introduction: Gene expression testing is expensive and, unless it changes the chemotherapy (CT) decision, unnecessary. Both Nottingham Prognostic Index (NPI) and Predict Breast Cancer (Predict) are free to use and based on clinico-pathological data. Each gives a guide to the prognosis. Many clinical teams in the UK have used these indices to guide treatment and more recently to help decide who should have access to gene expression testing. NPI scores of ≤2.4 have a cancer-specific ten-year survival of 96%, and &amp;gt;2.4 to ≤3.4, &amp;gt;3.4 to ≤5.4 and &amp;gt;5.4 have survivals of 93%, 78% and 44% respectively. UK oncologists use it as a guide in recommending adjuvant treatment. CT is not recommended for patients with NPI ≤3.4, is discussed as on option for NPI &amp;gt;3.4 to ≤5.4 and is recommended for NPI &amp;gt;5.4. Similarly, Predict can be used to guide CT decisions as follows: &amp;lt; 3% benefit, CT not recommended; 3-5% CT discussed as a possible option; &amp;gt;5% CT recommended. The OncotypeDX® Breast Recurrence Score® test has been assessed recently in the RxPONDER trial which concluded that postmenopausal women with a Recurrence Score (RS) result &amp;lt; 26 showed no benefit from the addition of CT. This study compares the clinical utility of three indices (NPI, Predict, and RS result) by assessing the distribution of NPI and Predict across RS result, evaluates changes in CT recommendations based on risk group, and by estimating the likelihood of CT recommendation. Methods: We recently conducted a prospective UK decision impact, decision conflict and economic analysis of Oncotype DX® test in early node positive, hormone receptor positive and HER2 negative breast cancer involving 664 women. Using these data, we calculated the NPI and the Predict score. Descriptive statistics, logistic regression and McNemar’s tests were used to assess the associations between NPI, Predict, RS result and change in CT decisions for all patients (n=664) and in the cohort of post-menopausal patients recruited after RxPONDER reported (n=176). Results: Table 1 shows similar stratification for all three indices within the low-risk groups, but not for the high-risk groups. Similar results were observed in the post-menopausal, post-RxPONDER cohort. The results of the CT decision change in the post-menopausal, post-RxPONDER patients by NPI and Predict demonstrate the utility of RS results across all NPI and Predict risk groups (Table 2). There was a stronger association between RS result (26-100 vs 0-25) and CT recommendation (OR152.8, 95% CI 53.9-433.2, p&amp;lt; 0.001) as compared to the association between either NPI or Predict (OR 8.7, 95% CI 3.8-19.8, p&amp;lt; 0.001 and OR 7.2, 95% CI 2.8-18.3, p=0.003 respectively), suggesting that UK Oncologists are predominantly using RS to guide their CT decisions. Conclusions: Either basing CT decisions or selecting which patients should undergo OncotypeDX testing by pre-screening with either NPI or Predict risks misclassifing many patients who either need potentially lifesaving CT or who can safely avoid chemotherapy altogether. Table 1. Predict and NPI risk groups by RS result for all patients and for the post-menopausal, post-RxPONDER cohort. Table 2. CT recommendation pre-and post-assay by risk group for post-menopausal, post-RxPONDER patients. Citation Format: Simon Holt, Paige Innis, Priyadharshini Sai-Giridhar, Satish Seerapu. A comparison of chemotherapy recommendations by NPI, Predict, and Oncotype DX testing in UK women with early node positive breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-14-05.

BRAF Expression and Copy Number Alterations Predict Unfavorable Tumor Features and Adverse Outcomes in Patients With Breast Cancer.

Background: The role of BRAF in breast cancer pathogenesis is still unclear. To address this knowledge gap, this study is aimed at evaluating the impact of BRAF gene expression and copy number alterations (CNAs) on clinicopathologic characteristics and survival in patients with breast cancer. Methods: The Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset was obtained from the cBioPortal public domain. Tumoral BRAF mRNA expression and CNAs along with demographic and tumor data for patients with breast cancer were retrieved. The association of BRAF expression and CNAs with breast cancer clinicopathologic characteristics was analyzed. The impact of BRAF mRNA expression on the overall survival of patients was assessed using Kaplan-Meier survival analysis. Results: BRAF gene mRNA log intensity expression was positively correlated with tumor size and the Nottingham Prognostic Index (NPI) (p < 0.001). Alternatively, BRAF gene expression was negatively correlated with the age at diagnosis (p = 0.003). The average BRAF mRNA expression was significantly higher in premenopausal patients, patients with high tumor grade, hormone receptor-negative status, and non-luminal tumors compared to postmenopausal patients, patients with low-grade, hormone receptor-positive, and luminal disease. BRAF gain and high-level amplification copy numbers were significantly associated with higher NPI scores and larger tumor sizes compared to neutral copy number status. Survival analysis revealed no discernible differences in overall survival for patients with low and high BRAF mRNA expression. Conclusion: High BRAF mRNA expression as well as the gain and high-level amplification copy numbers were associated with advanced tumor characteristics and unfavorable prognostic factors in breast cancer. BRAF could be an appealing target for the treatment of premenopausal patients with hormone receptor-negative breast cancer.

Correlation between Oncotype DX, Predict, and Nottingham Prognostic Index on HR+, HER2- early breast cancer treatment: The current value of molecular testing.

1601 Background: The Oncotype DX Breast Recurrence Score (ODX) assay is a 21-gene assay validated in hormone receptor-positive, HER2 negative invasive breast cancer (BC) to predict chemotherapy benefit and risk of distant recurrence at 10 years regardless of node status and is also a strong predictor of mortality. ODX can minimize the misuse of chemotherapy, financial burden, and improve clinical outcomes. ODX is not widely used in Ecuador due to socioeconomic and healthcare access disparities; instead, many physicians stratify patients' risk according to clinicopathological and immunohistochemical features. We aim to compare the differences between ODX and two of the most common stratification clinical tools: Predict Score (PS) and Nottingham prognostic index (NPI). Methods: Retrospective analysis of women with early BC who underwent ODX testing in Ecuador from May 2020 to January 2023. Inclusion criteria: early BC (T1-T3 / N0-N1a); estrogen receptor (ER) positive; HER2 negative by immunohistochemistry; and available data of tumor size, grade, lymph node status, and Ki67 proliferation index. Exclusion criteria: patients with recurrent BC, incomplete pathology, or immunohistochemistry data. PS and NPI were calculated using online tools. The correlation between PS, NPI, and ODX scores was analyzed using Spearman's correlation coefficient in SPSS. Results: 77 patients underwent ODX testing, of which 58 patients (mean age 55 years old) met the inclusion criteria. Invasive breast carcinoma not otherwise specified was the most common type (48 patients (82%). Risk scores generated by PS correlated strongly with NPI for all patients (r=0.47; p ≤ 0.001). A strong correlation was also found between ODX and NPI (0.79, p&lt;0.027). Risk scores were then stratified by patient risk category. For low-risk patients, 68% of correspondence between ODX and PS was found, and 98% between ODX and NPI. Intermediate-risk patients showed a correspondence between ODX and PS of 5% and 9% for ODX and NPI. High-risk patients showed a correspondence of 50% between ODX and PS and 17% between ODX and NPI. Conclusions: ODX risk recurrence for low-risk patients is highly correlated with PS and NPI. For Intermediate and high-risk patients determined by PS and NPI, ODX testing provided valuable and prognostic information and should be considered to guide adjuvant treatment. [Table: see text]

High Inner Centromere Protein Expression Correlates with Aggressive Features and Predicts Poor Prognosis in Patients with Invasive Breast Cancer

Introduction: Inner centromere protein (INCENP) is a member of the chromosomal passenger complex and plays a key role in mitosis and cell proliferation. This study aimed to evaluate the clinical and prognostic significance of INCENP in invasive breast cancer (BC). Methods: INCENP expression was evaluated on a tissue microarray of a large BC cohort (n = 1,295) using immunohistochemistry. At the mRNA level, INCENP expression was assessed using the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) (n = 1,980) and The Cancer Genome Atlas (TCGA) BC cohorts (n = 854). The correlations between INCENP expression, clinicopathological parameters, and patient outcome were investigated. Results: INCENP expression was detected in the nucleus and cytoplasm of the tumour cells. Its expression was significantly associated with features characteristic of aggressive BC behaviour including high tumour grade, larger tumour size, and high Nottingham prognostic index scores. High INCENP nuclear expression was a predictor of shorter BC-specific survival in the whole cohort, as well as in the luminal subtype (p < 0.001). High INCENP nuclear expression was predictive of poor prognosis in BC patients who received hormone treatment or chemotherapy. Conclusion: High INCENP expression is a poor prognostic biomarker in BC with potential therapeutic benefits.

Correlation of microvessel density with histopathological parameters of carcinoma breast.

Microvessel density (MVD) is a surrogate measure of tumour angiogenesis, and is well known for over two decades to identify individuals with a high risk of recurrence with greater prevision than traditional markers. This study aims to assess the utility of MVD and its correlation with the Nottingham Prognostic Index (NPI) and other routine histopathological parameters in carcinoma breast. This two year retrospective, cross-sectional and analytical study evaluated 143 women with breast cancer presenting to rural tertiary hospital in central India. These women were graded histopathologically, the immunophenotype was determined using ER (estrogen receptor), PR (progesterone receptor), Her2 neu (human epidermal growth factor receptor 2 neu) and Ki-67 proliferation index (Kiel-67) immunohistochemical markers and anti-CD34 antibody to stain the endothelial cell clusters displaying the microvessels. The NPI was generated for each participant based on the tumour size, histologic grade and involvement of lymph node. The parameters were compared with the CD34 scores. Differential and inferential statistics, including the independent t test, analysis of variance, Pearson's correlation coefficient, Spearman's rank correlation coefficient and point biserial correlation coefficient, were used for statistical analysis. This study showed that CD34 values ranged from 6-36 microvessels/hpf, with 24.16±6.77 microvessels/hpf as the mean. The mean microvessel counts showed a significant positive correlation with the Bloom-Richardson histological grade, vascular invasion, LN (lymph node) positivity and NPI. However, there was no significant correlation of CD34 values with the participant's age, tumour size neither any significant association of CD34 values with the individual's immunophenotype. A positive linear correlation of the microvessel counts and the NPI scores suggest that with an increase in tumour angiogenesis, there was increased proliferative potential. Based on the significant correlation between the microvessel counts and the vascular invasion of the tumour masses in this study, it can be assumed that there will be vascular invasion if the microvessel count is higher and vice-versa. Although it is established that angiogenesis and neovascularization are required for the expansion of the solid tumour tissue, the heterogeneous nature of this entity makes it difficult for obtaining a linear correlation. Hence, it is suggested that though neovascularization permits advanced tumour spread it, however, does not guarantee it.

Relationship of Nottingham Prognostic Index with prognostic parameters of breast carcinoma

Background: Breast cancer (BC) is the commonest malignancy in the female and it is gaining its significance due to worldwide rising incidence. It is also important due to 2.5% higher incidence in Pakistan as compared to neighbouring countries. Nottingham prognostic index (NPI) is an important prognostic factor of BC. It provides information about survival and morbidity. There are significant variations in different studies. Aim: To carry out current study relating NPI with various histopathological parameters of BC. Methods: This was a descriptive cross-sectional study. The study was done at the Department of Pathology, King Edward Medical University Lahore with the collaboration of four surgical units of Mayo Hospital Lahore from 2010 to 2019. Total 137 cases of breast carcinoma were included. Information about age, grade, primary tumor size, axillary lymph node status and stage was entered in the pre designed proforma. NPI was calculated as 0.2xtumor size(cm)+lymph node grade. NPI was scored as excellent, good, moderate and poor and its correlation was calculated against primary tumor size, lymph node grade, tumor grade and stage. Results: We studied 137 cases of breast carcinoma with mean age 49.32±11.64 years. Mean NPI was 5.4±1.4 with range of 2.4 to 9.4. NPI scores in poor 65(47.4%) and moderate 61(44.5%) groups were significantly high as compared to good 10(7.3%) and excellent scores 1(0.7%). Most of the cases of poor NPI were in p T3 and p T4 whereas this was p T2 with moderate score. Poor score of NPI was significant in grade 3 which is in contrast to moderate score where grade 2 dominated the picture. Correlation of NPI with LNG was in favor of LNG 1 with good and moderate scores while LNG3 dominated in the poor group. In stage III, 49 cases (35.8%) were seen with poor score of NPI. Conclusion: NPI is an important prognostic parameter and it can be studied with different histopathological parameters to see correlation between them. In the current study majority of the cases of NPI scored at poor and moderate levels. Correlation coefficient was linear, strong and positive especially with LNG. Mean NPI has ascending correlation with these parameters. Thus NPI can be used as a prognostic indicator when comparing with histopathological parameters of BC. Keywords: Breast cancer, NPI, tumor grade, tumor stage, LNG

Abstract 5405: Expression of cathepsin D in early-stage breast cancer and its prognostic and predictive value

Abstract Purpose: Cathepsin D is a proteolytic enzyme that is normally localized in the lysosomes and is involved in the malignant progression of breast cancer. The expression of Cathepsin D is regulated by steroid hormones including oestrogen and growth factors. There are conflicting results between different studies regarding Cathepsin D significance as prognostic and predictor marker in breast cancer. Furthermore, Cathepsin D has not been recommended for clinical use by the American Society of Clinical Oncology because of insufficient evidence. This study was aimed to fill the gap in the lack of recent and large studies on prognostic significance of Cathepsin D expression by studying a large well-characterized series of primary breast cancer for cathepsin D expression using immunohistochemistry. Methods: Expression of Cathepsin D was assessed by immunohistochemical staining of tissue microarrays, in a large well-characterized series of early-stage operable breast cancer (n=954) from Nottingham Primary Breast Carcinoma Series between the period of 1988 and 1998 who underwent primary surgery. Correlation of cathepsin D expression with clinicopathological parameters and prognosis was evaluated. Results: Cathepsin D expression was positive in 28.8% (275/954) of breast cancer tumors. Positive expression of cathepsin D was significantly associated with high histological grade (p=0.007), pleomorphism (p=0.002), poor Nottingham Prognostic Index score (NPI) (p&amp;lt;0.002), recurrence (p=0.005) and distant metastasis (p&amp;lt;0.0001). Kaplan-Meier analysis showed that Cathepsin D expression was significantly associated with shorter breast cancer specific survival (BCSS) (p=0.001), higher risk of recurrence (p=0.001) and distant metastasis (p&amp;lt;0.0001). Cathepsin D positive tumors with ER positive staining who were treated with tamoxifen were associated with lower BCSS and higher risk of developing distant metastasis (p=0.001). Conclusion: This study shows Cathepsin D expression as a promising prognostic biomarker for early operable invasive breast cancer. Our results indicate that Cathepsin D expressing tumors are associated with shorter breast cancer specific survival and higher risk of recurrence and metastasis. Cathepsin D could be clinically useful to predict response to tamoxifen treatment. Targeting Cathepsin D either through inhibition of action or interference with the proteolytic pathway could be used to treat metastatic breast cancers expressing Cathepsin D. Citation Format: Inas M. Alhudiri, Christopher C. Nolan, Ian O. Ellis, Emad A. Rakha, Adam Elzagheid, Andrew R. Green, Caroline J. Chapman. Expression of cathepsin D in early-stage breast cancer and its prognostic and predictive value [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5405.

Male Breast Cancer: Clinical, Demographical, and Pathological Features in a Cohort of 41 Patients.

Background and objectiveMale breast cancer (MBC) is a rare malignancy, and it accounts for less than 1% of all cancers in men. The pathogenesis of MBC remains unclear, with most available data obtained from single-center studies and retrospective series. The aim of this study was to share our experiences of MBC cases and to describe the characteristics of MBC patients.Materials and methodsWe retrospectively reviewed the records of 41 MBC cases and recorded the pathological, clinical, and demographic features of the patients. Data on progression-free survival (PFS) and overall survival (OS) were also recorded.ResultsThe mean age of the patients was 64.1 ± 10.0 years. The most common histopathological subtype was invasive ductal carcinoma. Hormone receptor positivity was detected in 39 (95.1%) patients. Human epidermal growth factor receptor 2 (HER2) positivity was present in five (12.2%) patients. Most of the patients had early-stage disease. Surgery was the treatment of choice for most primary tumors. Thirty-nine (95.1%) patients received hormonotherapy, and 21 (51.2%) received systemic chemotherapy. OS was found to be 126.4 months and PFS was 83.2 months. The OS and PFS time in patients with a Nottingham Prognostic Index (NPI) score of <5.4 were longer than those with an NPI score of >5.4.ConclusionThe hormone receptor status of most of the MBC patients was positive, and their HER2 status was negative. A multimodality approach was associated with longer survival, which has been reported in female patients with breast cancer as well. The NPI score is a useful tool for predicting survival time in MBC patients.

A study on Nottingham prognostic index and its correlation with ER, PR, HER-2/NEU AND KI-67 in breast carcinomas

Aim: Carcinoma of the breast is one of the most common malignancy in women. Considering the tumour size, histological grade and number of lymph nodes involved, Nottingham Prognostic index (NPI) is calculated. This study has been designed to acquire information about various parameters in breast carcinomas and to calculate NPI score in each case and determine the relationship of NPI with various prognostic markers in breast carcinomas. Materials and Methods: The present study was undertaken in the Department of Pathology, Father Muller Medical College, Mangalore for a period of two years. Breast cancers, diagnosed as Invasive carcinoma breast of no special type on lumpectomy and mastectomy was studied and cases were assessed with regard to age, laterality, quadrant involved, size of the tumour, lymph node status, modified SBR grade, hormonal receptor status (ER, PR), HER-2/Neu, Ki-67 and NPI status of the tumour. Statistics: Cross tabulation was done to check for correlation and Kappa statistics was done to check the level of agreement between NPI and modified SBR grade, ER, PR, HER-2/Neu and Ki-67. Results and Conclusion: This study included a total of 100 infiltrating ductal carcinomas of the breast. The mean age of presentation was 52.05 years. On cross tabulation of NPI with pathological parameters only modified SBR grade showed statistically significant association with NPI at 5% level of significance(‘p’ Keywords: Breast neoplasms, Carcinoma, Ductal, NPI.

NCAPG upregulation mediated by four microRNAs combined with activation of the p53 signaling pathway is a predictor of poor prognosis in patients with breast cancer.

The role of non-SMC condensin I complex subunit G (NCAPG) in breast cancer remains unclear. The present study used online databases, reverse transcription-quantitative PCR, flow cytometry and western blotting to determine the expression levels, prognosis and potential molecular mechanisms underlying the role of NCAPG in breast cancer. The association between NCAPG expression and several different clinicopathological parameters in patients with breast cancer was determined, and the results revealed that NCAPG expression was negatively associated with estrogen receptor and progesterone receptor positive status, but was positively associated with HER2 positive status, Nottingham Prognostic Index score and Scarff-Bloom-Richardson grade status. Furthermore, upregulated expression levels of NCAPG resulted in a poor prognosis in patients with breast cancer. A total of 27 microRNAs (miRNAs/miRs) were predicted to target NCAPG, among which four miRNAs (miR-101-3p, miR-195-5p, miR-214-3p and miR-944) were predicted to most likely regulate NCAPG expression in breast cancer. A total of 261 co-expressed genes of NCAPG were identified, including cell division cyclin 25 homolog C (CDC25C), and pathway enrichment analysis indicated that these co-expressed genes were significantly enriched in the p53 signaling pathway. CDC25C expression was downregulated in breast cancer and was associated with a poor prognosis. These findings suggested that upregulated NCAPG expression may be a prognostic biomarker of breast cancer.

Relationship of Oncotype Dx score with tumor grade, size, nodal status, proliferative marker Ki67 and Nottingham Prognostic Index in early breast cancer tumors in Saudi Population

BackgroundOncotype Dx is a 21-gene recurrence score, which is used as a diagnostic tool for the recurrence of breast cancer. It is also used to determine the benefit of chemotherapy for breast cancer in early stages. This study investigates the relationship of Oncotype Dx with pathological prognostic markers of protein Ki 67, Nottingham Prognostic Index (NPI) and tumor grade. MethodsData for early breast cancer patients treated at our tertiary care center was collected for statistical analysis. Data for patients from 2014 to 2018 was recorded for patient's age, ER/PR status, Ki 67, nodal status, tumor grade, NPI along with Oncotype Dx score. Metric measurements were described as mean ± SD and the non-metric data was represented by frequency (%). Chi-square or Fisher's exact tests as well as logistic regression was applied to assess the associations at 95% CI. ResultsAmong 156 breast cancer patients, the mean age was 55.7 ± 9.4 years. The tumors were classified into Grade-I (12.8%), Grade-II (67.3%) and Grade-III (19.9%). Ki67 score was 12.8 ± 12.0 and NPI score was 3.7 ± 0.8. The mean Oncotype Dx score was 17.0 ± 9.1; it was 14.1 ± 6.8 for Grade-I tumors; 15.7 ± 7.5 for grade -II tumors; and 23.2 ± 12.3 for grade-III tumors [Mean Oncotype Dx score across Tumor grades was compared by ANOVA (η = 0.121), p < 0.001]. While logistic regression analyses for the dichotomized Oncotype Dx higher score (≥25) was significantly associated with grade-III tumors odds ratio (OR) = 13.72 (95% CI: 1.62–115.89), higher Ki67 (>20) OR = 14.40, (95% CI: 1.44–143.71), average NPI score (2.41–3.40), OR = 13.60, (95% CI: 1.57–117.94) to poor NPI (>5.4). The association of Oncotype Dx with age, tumor size and nodal status was statistically not significant. ConclusionsThis study revealed that age, Ki67, tumor size and nodal status did not have a statistically significant impact on Oncotypye Dx recurrence score in the targeted patient population. There was a significant correlation of low grade node negative patients with Oncotype Dx while high grade node negative patients had poor correlations with Oncotype Dx. The use of Oncotype Dx has shown to be less cost-effective and has no noticeable association with improved life expectancy in the targeted patient population (i.e., hormone positive, node negative cases) in comparison with current clinical practices in Saudi Arabia and it is less likely to be cost-effective in this group of patients.

Patient satisfaction with nurse-led end of treatment telephone consultation for breast cancer during COVID-19 pandemic.

Patient satisfaction with nurse-led end of treatment telephone consultation for breast cancer during COVID-19 pandemic.

Insulin resistance contributes to racial disparities in breast cancer prognosis in US women

BackgroundRacial disparities in breast cancer survival between Black and White women persist across all stages of breast cancer. The metabolic syndrome (MetS) of insulin resistance disproportionately affects more Black than White women. It has not been discerned if insulin resistance mediates the link between race and poor prognosis in breast cancer. We aimed to determine whether insulin resistance mediates in part the association between race and breast cancer prognosis, and if insulin receptor (IR) and insulin-like growth factor receptor (IGF-1R) expression differs between tumors from Black and White women.MethodsWe conducted a cross-sectional, multi-center study across ten hospitals. Self-identified Black women and White women with newly diagnosed invasive breast cancer were recruited. The primary outcome was to determine if insulin resistance, which was calculated using the homeostatic model assessment of insulin resistance (HOMA-IR), mediated the effect of race on prognosis using the multivariate linear mediation model. Demographic data, anthropometric measurements, and fasting blood were collected. Poor prognosis was defined as a Nottingham Prognostic Index (NPI) > 4.4. Breast cancer pathology specimens were evaluated for IR and IGF-1R expression by immunohistochemistry (IHC).ResultsFive hundred fifteen women were recruited (83% White, 17% Black). The MetS was more prevalent in Black women than in White women (40% vs 20%, p < 0.0001). HOMA-IR was higher in Black women than in White women (1.9 ± 1.2 vs 1.3 ± 1.4, p = 0.0005). Poor breast cancer prognosis was more prevalent in Black women than in White women (28% vs 15%. p = 0.004). HOMA-IR was positively associated with NPI score (r = 0.1, p = 0.02). The mediation model, adjusted for age, revealed that HOMA-IR significantly mediated the association between Black race and poor prognosis (β = 0.04, 95% CI 0.005–0.009, p = 0.002). IR expression was higher in tumors from Black women than in those from White women (79% vs 52%, p = 0.004), and greater IR/IGF-1R ratio was also associated with higher NPI score (IR/IGF-1R > 1: 4.2 ± 0.8 vs IR/IGF-1R = 1: 3.9 ± 0.8 vs IR/IGF-1R < 1: 3.5 ± 1.0, p < 0.0001).ConclusionsIn this multi-center, cross-sectional study of US women with newly diagnosed invasive breast cancer, insulin resistance is one factor mediating part of the association between race and poor prognosis in breast cancer.

Myxovirus resistance 1 (MX1) is an independent predictor of poor outcome in invasive breast cancer

BackgroundBreast cancer (BC) is a disease with variable morphology, clinical behaviour and response to therapy. Identifying factors associated with the progression of early-stage BC can help understand the risk of metastasis and guide treatment decisions. Myxovirus resistance 1 (MX1), which is involved in the cellular antiviral mechanism, plays a role in some solid tumours; however, its role in invasive BC remains unknown. In this study, we aimed to explore the clinicopathological and prognostic significance of MX1 in BC.MethodsMX1 was assessed at the protein level using tissue microarrays from a large well-annotated BC cohort (n = 845). The expression of MX1 mRNA was assessed at the transcriptomic level using the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC; n = 1980) and validated using three publicly available cohorts on Breast Cancer Gene-Expression Miner (bc-GenExMiner version 4.4). The associations between MX1 expression and clinicopathological factors, and outcome were evaluated.ResultsHigh MX1 protein expression was associated with features of aggressiveness, including large tumour size, high tumour grade, high Nottingham prognostic index scores, hormone receptor negativity and high Ki67 expression. High MX1 expression showed an association with poor patient outcome and it was an independent predictor of short BC-specific survival (p = 0.028; HR = 1.5; 95% CI = 1.0–2.2). Consistent with the protein results, high MX1 mRNA levels showed an association with features of aggressive behaviour and with shorter survival.ConclusionThis study identified MX1 as an independent predictor of poor outcome in patients with BC. Further functional studies are needed to investigate the biological role of MX1 in BC and its potential value as a therapeutic target.

Correlation Between Oncotype DX, PREDICT and the Nottingham Prognostic Index: Implications for the Management of Early Breast Cancer.

IntroductionBreast cancer remains the most common cancer diagnosis in the UK. The current clinical practice utilises two different types of modalities to estimate the prognosis, risk of recurrence and benefit from adjuvant chemotherapy treatment in patients with early breast cancer. The first set of modalities includes risk calculators based on clinicopathological features, e.g. PREDICT or the Nottingham Prognostic Index (NPI); the second includes genetic profiling of tumour tissue using Oncotype DX (ODX; Genomic Health, Redwood City, CA) testing. PREDICT, NPI and ODX stratify breast cancers into high-, intermediate- and low-risk categories to help guide adjuvant chemotherapy treatment decisions. This study compares PREDICT, NPI and ODX Recurrence Scores (RS), with the aim of assessing 1) the correlation between the RS for PREDICT, NPI and ODX and 2) whether early breast cancer patients are stratified into similar risk categories by all three modalities.MethodsThis retrospective study included early breast cancer patients treated at a National Health Service (NHS) hospital over a 12-month period (October 1, 2017 to September 30, 2018). Inclusion criteria: consecutive patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative and lymph node-negative breast cancer. All patients were discussed at the local multidisciplinary team (MDT) meeting and underwent ODX testing. Exclusion criteria: patients without ODX test scores; patients with an in-breast recurrence; patients who did not undergo a sentinel lymph node biopsy (SLNB); and patients with ductal carcinoma in situ (DCIS) only. NPI and PREDICT scores were calculated for each patient using online tools, and ODX data was obtained through Genomic Health and MDT records. Patients were risk-stratified into high, intermediate and low risk of recurrence groups based on their PREDICT, NPI and ODX scores. The thresholds for risk stratification were based on current practice, which is evidence-based. Correlations between PREDICT, NPI and ODX scores were analysed using Spearman's correlation coefficient.ResultsForty-six patients (mean age: 56 years), with a total of 57 early breast cancers, underwent ODX testing. Risk categories generated by PREDICT very strongly correlated with NPI for all patients (r=0.92; P<0.0001). However, the RS generated by ODX testing only strongly correlated for patients with low-risk PREDICT scores (r=0.51; P=0.0134), while no correlation between RS and PREDICT was observed for patients with intermediate- or high-risk PREDICT scores (r=-0.0064; P=0.9767). Similar results were seen between NPI and RS. Overall, only 19/46 (41.3%) patients had an RS which corresponded to PREDICT risk category, while 18/46 (39.1%) patients had an RS that indicated a higher risk of recurrence than PREDICT, and 9/46 (19.6%) patients had an RS indicating a lower risk of recurrence than PREDICT. Similar results were found when comparing RS and NPI.ConclusionThe risk of recurrence estimated by ODX in patients deemed low risk by PREDICT or NPI highly correlated, while no such correlation existed in patients with an estimated intermediate- or high-risk breast cancer. In PREDICT- or NPI-estimated intermediate- and high-risk patients, ODX provided valuable additional prognostic information to guide adjuvant treatment, while the potential avoidance of ODX testing in low-risk patients presents significant cost-savings.

Histomorphological study of invasive breast carcinoma and its prognostic scoring using Nottingham prognostic index

Introduction: Breast carcinoma is the common malignant tumor in women accounting for 15% of cancer related deaths. Clinical history, examination and use of mammography has improved the diagnostic approach to breast cancer. Nottingham prognostication index is considered to be a useful marker that takes into consideration some of the important factors like tumor size, histologic grade and lymphnode stage. Aims and Objectives: 1. To study histomorphological distribution pattern of various invasive breast carcinoma. 2. To estimate prognosis by using Nottingham prognostic index score. Materials and Methods: One year six months descriptive study was performed which included all the invasive breast carcinoma cases comprising of mastectomy specimen with lymphnode sampling. Based on tumor size, histologic grade and lymphnode stage; Nottingham prognostic index score was calculated and cases were categorised into different prognostic group. Results: 68 cases were included in the study with 67 female patients and one male patient. Histopathologically, 80.88% were Infiltrating ductal carcinoma – not otherwise specified. Tumor size belonging to T2 in 66.17%. 45.58% showed no lymphnode involvement and 33.82% belonged to lymphnode stage N1. Majority (50%) belonged to histologic grade II. Nottingham Prognostic Index (NPI) score in 42.64% showed moderate prognosis. Conclusion: Histomorphological study showed commonest lesion to be Infiltrating Ductal carcinomanot otherwise specified and majority belonged to moderate prognosis category according to Nottingham Prognostic Index score. Keywords: Histomorphology, Infiltrating ductal carcinoma, Tumor size, Nottingham Prognostic index.

The Utility of Oncotype DX for Adjuvant Chemotherapy Treatment Decisions in Estrogen Receptor-positive, Human Epidermal Growth Factor Receptor 2-negative, Node-negative Breast Cancer.

IntroductionBreast cancer is the most common cancer diagnosis in the UK. Recently, there has been a reduction in breast cancer-specific mortality and recurrence attributed, in part, to the delivery of adjuvant chemotherapy. The National Institute for Health and Care Excellence (NICE) recommends the use of genetic profiling with Oncotype DX (ODX) to guide decisions to offer adjuvant chemotherapy after surgery in intermediate-risk early breast cancer patients. This study aimed to evaluate the utility of ODX testing in routine clinical practice in a National Health Service (NHS) hospital. MethodsConsecutive early breast cancer patients, identified through the multidisciplinary team (MDT) records, treated in our institution over 12 months (October 2017-September 2018) were included. PREDICT and Nottingham prognostic index (NPI) scores (from online clinicopathological recurrence risk tools) were calculated for each patient, and ODX data obtained through Genomic Health, Inc. (Redwood City, California). Patients were divided into two groups, those that underwent ODX testing (ODX group) and those that did not (non-ODX group). Descriptive statistics were used to analyse patient and tumour characteristics. The Gaussian distribution of each data set was assessed using the Anderson-Darling test. For comparisons between patient groups, the non-parametric equivalent of the two-tailed t-test (Mann-Whitney) was used. Dichotomous variables (e.g. chemotherapy decisions) were compared using chi-squared tests.ResultsOne-hundred thirty-three patients (mean age 62 years) treated for 152 early breast cancers, were included in the final analysis. Breast cancers in the ODX group were of greater median tumour size (24 vs 16 mm; P<0.0001) and higher median tumour grade (3 vs 2; P<0.0001). PREDICT scores (3 vs 1, P<0.0001) and NPI scores (3.40 vs 2.30, P<0.0001) for the ODX group were also significantly higher than the non-ODX group. A greater proportion of patients were offered chemotherapy in the ODX group (39.9% vs 6.9%, P<0.001). However, for the PREDICT-calculated intermediate-risk patients, ODX testing resulted in a lower proportion of patients being offered chemotherapy compared to the intermediate-risk patients who were not genetically profiled (54.5% vs 83.3%, P=0.3547), although this result was not statistically significant.ConclusionsPatients selected for ODX testing were younger, with significantly higher-grade and larger-sized tumours compared to patients not selected for genetic profiling. ODX testing significantly impacted the delivery of chemotherapy, as the recurrence score generated through ODX testing guided the final decision.

The Correlation of Nottingham Prognostic Index with Immunoexpression of ER, PR, HER2, and Ki67 in Breast Cancer Tissue

Abstract Background In the underdeveloped and developing countries, the application of immunohistochemistry (IHC) to assess the status of oestrogen receptor (ER), progesterone receptor (PR), HER2 receptor, and Ki67 proteins in formalin-fixed, paraffin-embedded tissue sections of primary invasive breast carcinoma is utterly hindered by high cost, long procedure, and need for both skilled operator and pathologist. The objective of this study was to evaluate the correlation of Nottingham prognostic index (NPI) with immunoexpression of ER, PR, HER2, and Ki67 proteins in the formalin-fixed, paraffin-embedded tissue sections of primary invasive breast carcinoma. The ethical approval reference number is IRBRTA 306/2560. Methods Two hundred and forty primary invasive breast carcinoma cases were determined their NPI which was calculated as [0.2 × maximum tumour diameter in cm] + tumour grade + axillary lymph node score. Tumour grade was given a score 1 to 3 based on the Nottingham Combined Histologic Grade system (Elston-Ellis modification of Scarff-Bloom-Richardson grading system) of primary invasive breast carcinoma. Axillary lymph node metastasis (ALNM) was given a score 1 if no ALNM, a score 2 if 1 to 3 metastatic nodes, and a score 3 if at least 4 nodal involvement. The correlation between NPI and the IHC status of ER, PR, HER2, and Ki67 was analysed at the 95% confidence interval. Results The NPI had a significant association with the immunoexpression of ER, PR, and Ki67 proteins. There was no correlation with HER2 immunohistochemical reactivity. The proposed NPI score less than 4.5 will significantly correlate with positive immunoexpression of ER and PR. The NPI score greater than or equal to 4.5 will correlate with high Ki67. Conclusion The NPI might have a role in predicting the results of ER, PR and Ki67 expression in the formalin-fixed, paraffin-embedded tissue sections of primary invasive breast carcinoma, if immunohistochemical method is unavailable.