PR-negative Status Research Articles

Identification Of Risk Factors Of Bone Metastasis Among Iraqi Breast Cancer Women

Background: The most common site of metastases in people with breast cancer is bone metastasis. Patients with advanced phases of cancer are associated with an increased prevalence of several types of metastases, one of which is bone metastasis. Object: Assessment of the risk factors for bone metastases in patients with breast cancer. Patients and Methods: This is a retrospective study of 316 patients with breast cancer who either had bone metastases at the time of diagnosis or developed it later on. The study was carried out between January 2013 and April 2018. Three hundred and sixteen patients were assigned into two groups. In the case group, 100 patients with breast cancer had been diagnosed with bone metastasis by CT, MRI, bone scan, and PET scan; in the control group, there were 216 cases in are control group with breast cancer metastasis to sites other than bone. The questionnaire was created to record all factors (with the exception of demographic information), such as age, histopathological reading for invasive lobular carcinoma, invasive ductal carcinoma, or another type of cancer, ER status, PR status, Her2neu status, lymph node status and stage, and menopausal status. Results: The majority were 45 years of age or younger, and 96.5% of them had invasive ductal carcinoma in terms of hormonal status. Positive ER and PR status is found in 67.7% and 67.1% of the cases, respectively; 40.5% of the cases had amplified Her2neu receptors, 78.5% of the cases had positive lymph nodes, and 41.9% of the cases had (N1) stage. The highest proportion of bone metastasis was associated with negative ER and PR receptors (46.2% and 49%, respectively), while no significant statistical association (P= 0.65). Conclusion: negative ER, PR status, and Her2neu receptors not amplified, lymph node involvement, age 45 and less, infiltrating lobular carcinoma (ILC) histological type, and menopausal state are significant risk factors for bone metastasis in breast cancer.

Predictors of pathological complete response to neoadjuvant treatment in invasive breast cancer with different human epidermal growth factor receptor 2 (HER2) subcategories.

Among human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients who receive anti-HER2 treatment, a noteworthy correlation between pathological complete response (pCR) and longer survival has been observed. The rate of pCR varies with the tumor's degree of HER2 protein expression. The aim of this study was to assess the correlations between clinicopathological characteristics, magnetic resonance imaging (MRI) parameters, and pCR in breast cancer with different HER2 subcategories. A total of 281 invasive breast cancer patients diagnosed with HER2-positivity were included. HER2-positive translated to immunohistochemistry (IHC) 3+ or IHC 2+/fluorescence in situ hybridization (FISH)(+). All enrolled patients underwent baseline MRI examination and received neoadjuvant chemotherapy, dual anti-HER2 therapy, and subsequent therapeutic surgery from January 2021 to May 2022. A logistic regression model was used to evaluate the effects of covariates on pCR. Compared to the IHC 2+/FISH(+) group, patients with IHC 3+ tumors had a higher pCR rate (58.1% vs. 26.7%, P<0.001), clinical stage (58.6% vs. 40%, P=0.038), apparent diffusion coefficient (ADC) value (0.96 vs. 0.88 mm2/s, P=0.004), and were more likely to be estrogen receptor (ER) negative (55.9% vs. 31.1%, P=0.002) and progesterone receptor (PR) negative (72.5% vs. 46.7%, P=0.001). In both groups, univariate analysis showed that the pCR group more often had ER-negative and PR-negative status than the non-pCR group (P<0.001). The final multivariable analysis showed that ER-negativity was associated with pCR in the IHC 2+/FISH(+) group (P=0.004). ER-negativity and the longest diameter were two independent predictors of pCR in the IHC 3+ group (P<0.001 for ER, P=0.026 for longest diameter). The IHC 3+ group had a higher pCR rate than the IHC 2+/FISH(+) group. Along with clinicopathological characteristics, MRI parameters were supplemental predictors of pCR, particularly in IHC 3+ patients.

Immunohistochemical Expression of Cyclooxygenase 2 (COX-2) as a Prognostic Marker and Its Correlation With Clinicopathological Parameters in Breast Cancer.

Introduction Breast cancer is considered the most common cancer among women. According to the literature, cyclooxygenase-2 (COX-2) expression in breast carcinoma is associated with aggressive tumor biology and acts as an independent prognostic marker. As COX-2 is a newly identified marker, studies are required to understand its immunoexpression and correlation with hormone receptor status and other prognostic factors, which helps in the therapeutic management of patients. Hence, this study evaluates the expression of COX-2 in breast carcinoma. Methods A hospital-based cross-sectional study was done on 55 mastectomy specimens collected at the Histopathology and Surgical Pathology Section of the Department of Pathology. The patient's age, histological type, tumor size, lymph node status, histological grade, and vascular invasion were noted. Immunohistochemical staining for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2/neu protooncogene (HER2/neu), and COX-2 markers was performed, and its results were compared with these clinicopathological and prognostic parameters. Results were subjected to statistical analysis. Results COX-2 expression was seen in 37 out of 55 cases (67.2%). Expression of COX-2 showed a statistically significant correlation with vascular invasion, ER-negative status, and PR-negative status. No statistical association was found between other parameters like age, tumor size, histological type, histological grade, lymph node status, and HER2/neu status. Conclusion The expression of COX-2 correlated strongly with well-established poor prognostic markers, such as vascular invasion, ER-negative status, and PR-negative status. Thus, expression of COX-2 suggests aggressive tumor biology, and it can be used as an independent prognostic marker.

Morphological and molecular changes of oestrogen receptor-positive breast cancer following bridging endocrine therapy: a United Kingdom multicentre study.

Standard neoadjuvant endocrine therapy (NAET) is used for 6-9 months to downstage hormone-receptor-positive breast cancer. Bridging ET was introduced during the COVID-19 pandemic to delay surgical intervention. There are no data in the literature on the effect of short course therapy on tumour response. We aimed to analyse the effect of bridging ET and validate the previously proposed neoadjuvant ET pathological reporting criteria. This was a multicentre cohort of 256 patients who received bridging ET between March and October 2020. Assessment of paired pre- and post-NAET hormone receptors and HER2 and posttherapy Ki67 expression was done. The median duration of NAET was 45 days. In all, 86% of cases achieved partial pathological response and 9% showed minimal residual disease. Histological response to ET was observed from as early as day 6 posttherapy. Central scarring was noted in 32.8% of cases and lymphocytic infiltrate was seen in 43.4% of cases. Significant changes associated with the duration of ET were observed in tumour grade (21%), with downgrading identified in 12% of tumours (P < 0.001), progesterone receptor (PR) expression with switch to PR-negative status in 26% of cases (P < 0.001), and HER2 status with a switch from HER2-low to HER2-negative status in 32% of cases (P < 0.001). The median patient survival was 475 days, with an overall survival rate of 99.6%. Changes characteristic of tumour regression and significant changes in PR and HER2 occurred following a short course of NAET. The findings support biomarker testing on pretreatment core biopsies and retesting following therapy.

Clinicopathological Significance of Cyclin-Dependent Kinase 2 (CDK2) in Ductal Carcinoma In Situ and Early-Stage Invasive Breast Cancers.

Cyclin-dependent kinase 2 (CDK2) is a key cell cycle regulator, with essential roles during G1/S transition. The clinicopathological significance of CDK2 in ductal carcinomas in situ (DCIS) and early-stage invasive breast cancers (BCs) remains largely unknown. Here, we evaluated CDK2's protein expression in 479 BC samples and 216 DCIS specimens. Analysis of CDK2 transcripts was completed in the METABRIC cohort (n = 1980) and TCGA cohort (n = 1090), respectively. A high nuclear CDK2 protein expression was significantly associated with aggressive phenotypes, including a high tumour grade, lymph vascular invasion, a poor Nottingham prognostic index (all p-values < 0.0001), and shorter survival (p = 0.006), especially in luminal BC (p = 0.009). In p53-mutant BC, high nuclear CDK2 remained linked with worse survival (p = 0.01). In DCIS, high nuclear/low cytoplasmic co-expression showed significant association with a high tumour grade (p = 0.043), triple-negative and HER2-enriched molecular subtypes (p = 0.01), Comedo necrosis (p = 0.024), negative ER status (p = 0.004), negative PR status (p < 0.0001), and a high proliferation index (p < 0.0001). Tumours with high CDK2 transcripts were more likely to have higher expressions of genes involved in the cell cycle, homologous recombination, and p53 signaling. We provide compelling evidence that high CDK2 is a feature of aggressive breast cancers. The clinical evaluation of CDK2 inhibitors in early-stage BC patients will have a clinical impact.

Global untargeted and individual targeted plasma metabolomics of breast cancer recurrence modified by hormone receptors.

Breast cancer is a heterogeneous and complex etiological disease. Understanding perturbations of circulating metabolites could improve prognosis. We recruited breast cancer patients from Kaohsiung Medical University (KMU) to perform untargeted (case-control design) and targeted (patient cohort) metabolomics analyses in the discovery and validation phases to evaluate interaction effects between clinical factors and plasma metabolites using multivariable Cox proportional hazards model. In the discovery phase, partial least squares-discriminant analysis (PLS-DA) showed that plasma metabolites were significantly different between recurrent and non-recurrent breast cancer patients. Metabolite set enrichment analysis (MSEA) and metabolomic pathway analysis (MetPA) showed that valine, leucine, and isoleucine degradation was the significant pathway, and volcano plot showed significant ten upregulated and two downregulated metabolites between recurrent and non-recurrent cases. Combined with receiver operating characteristic (ROC) curve and biological significance, creatine, valine, methionine, and mannose were selected for the validation phase. In this patient cohort with 41 new-recurrent vs. 248 non-recurrent breast cancer cases, followed for 720.49 person-years, compared with low level of valine, high valine level was significantly negatively associated with recurrent breast cancer (aHR: 0.36, 95% CI: 0.18-0.72, P = 0.004), especially in ER-negative and PR-negative status. There were interaction effects between valine and ER (Pinteraction = 0.006) as well as PR (Pinteraction = 0.002) on recurrent breast cancer. After Bonferroni correction, stratification effects between valine and hormone receptors were still significant. Our study revealed that plasma metabolites were significantly different between recurrent and non-recurrent patients, proposing therapeutic insights for breast cancer prognosis.

Quantifying hormone receptor status in lobular breast cancer in an institutional series: the relationship between estrogen and progesterone receptor status and outcomes

PurposeRecent guidelines defined a new reporting category of ER-low-positive breast cancer based on immunohistochemistry (IHC). While low positivity of either hormone receptor is uncommon in invasive lobular carcinoma (ILC), we sought to investigate whether relatively low hormone receptor positivity was associated with tumor characteristics and patient outcomes in a single institutional cohort.MethodsWe searched an institutional database for cases of stage I-III ILC with available IHC reports. Based on prior published categories in ILC, ER was classified as low, medium, or high as defined by ER staining of 10–69%, 70–89%, and ≥ 90% respectively. PR low and high tumors were defined by < 20%, or ≥ 20% staining respectively. We used chi-squared tests, t-tests, and Cox proportional hazards models to evaluate associations between ER/PR categories and tumor characteristics or disease-free survival (DFS).ResultsThe cohort consisted of 707 ILC cases, with 11% of cases categorized as ER low, 15.1% as medium, and 73.8% as high. The majority (67.6%) were PR high. Patients with ER low/medium expression were significantly younger, and more likely to also have PR low and/or HER2 positive tumors compared to those that were ER high. In a Cox proportional hazards model adjusting for age, stage, grade, pleomorphic histology, and treatment, ER category was not prognostic for DFS, but PR negative and PR low status each had significantly worse DFS compared to PR high status (HR 3.5, 95% CI 1.8–6.7, p < 0.001; and HR 2.0, 95% CI 1.1–3.5, p = 0.015, respectively).ConclusionThese findings highlight the relevance of quantifying ER and PR within ILC.

PREDICTING RESPONSE TO NEOADJUVANT CHEMOTHERAPY IN OPERABLE BREAST CANCER: ROLE OF ER, PR, HER2 AND KI-67 INDEX

Background: Neoadjuvant (anterior or pre-operative) chemotherapy for operable breast cancer helps in down-staging of the tumor and increases the rate of breast conservation surgery. Factors that identify individuals who benet from chemotherapy have not been clearly established. This study was conducted to assess the role of estrogen receptor, progesterone receptor, HER2 and Ki-67 index in predicting response to a standard anthracycline and taxane-based chemotherapy. Methods: The study included 62 women with clinical tumor stage 1-3 and nodal stage 0 or 1. All women received preoperative anthracycline and taxane-based chemotherapy followed by surgery. Clinical and pathological response was assessed using World Health Organization (UICC) and Chevallier's criteria respectively. Results: Clinical and pathological complete response rates were 40.3% and 17.7% respectively. The pathological complete response was highest in HER2-enriched patients (45.45%) while basal-like and luminal B subtypes accounted for 27.27% each. Among those that achieved pathological complete response, 90% had Ki-67 &gt;20, 81.8% had grade 3, 72.7% had ER negative status, 81.8% had PR negative status, 63.6% had HER2 positive status. However, there was no statistically signicant association between preoperative clinical tumor size(p=0.98), ER(p=0.053), PR(p=0.17), HER2(p=0.17), Ki-67 index(p=0.26) and pathological complete response. Conclusion: Ahigh pathological complete response was observed in tumors with high grade, high proliferative activity (high Ki-67), ER/PR negative status, HER2 over-expressing tumors and aggressive molecular subtypes such as basal-like and HER2-enriched breast cancer. However, none of these pre-chemotherapy factors showed statistically signicant association with pathological complete response.

High VISTA expression is linked to a potent epithelial-mesenchymal transition and is positively correlated with PD1 in breast cancer.

Breast cancer is the most common type of tumor in women worldwide. Immune checkpoint inhibitors, particularly anti-PDL1, have shown promise as a therapeutic approach for managing this disease. However, this type of immunotherapy still fails to work for some patients, leading researchers to explore alternative immune checkpoint targets. The Ig suppressor of T cell activation domain V (VISTA) has emerged as a novel immune checkpoint that delivers inhibitory signals to T cells and has demonstrated encouraging results in various cancers. Our study investigated the association of VISTA expression with clinicopathological parameters in breast cancer patients, its involvement in the Epithelial-Mesenchymal-Transition (EMT) process, and its correlation with PD1 expression. Transcriptomic analysis revealed that VISTA was associated with lobular and metaplastic histological type, tumor size, lymph node status, ER and PR negative status, and the TNBC molecular subtype. Furthermore, VISTA expression was strongly associated with an immunosuppressive tumor microenvironment. Immunohistochemistry analysis corroborated the transcriptomic results, indicating that VISTA was expressed in most immune cells (94%) and was significantly expressed in breast cancer tumor cells compared to matched adjacent tissues. Our study also showed for the first time that VISTA overexpression in breast cancer cells could be associated with the EMT process. Additionally, we identified a positive correlation between VISTA and PD-1 expression. Together, these results highlight the immunosuppressive effect of VISTA in breast cancer patients and suggest that bi-specific targeting of VISTA and PD-1 in combination therapy could be beneficial for these patients.

Association of progesterone receptor status with 21-gene recurrence score and survival among patients with estrogen receptor-positive breast cancer

BackgroundProgesterone receptor (PR)-negative tumors have been shown to have worse prognosis and were underrepresented in recent trials on patients with estrogen receptor (ER)-positive breast cancer. The role of PR-negative status in the context of 21-gene recurrence score (RS) and nodal staging remains unclear.MethodsThe National Cancer Database (NCDB) was queried for women diagnosed between 2010 and 2017 with ER-positive, human epidermal growth factor receptor 2 (HER2)-negative, pT1-3N0-1a breast cancer. Logistic and Cox multivariable analyses (MVA) were performed to identify association of PR status with high RS (> 25) and overall survival (OS), respectively.ResultsAmong 143,828 women, 130,349 (90.6%) and 13,479 (9.4%) patients had PR-positive and PR-negative tumors, respectively. Logistic MVA showed that PR-negative status was associated with higher RS (> 25: aOR 16.15, 95% CI 15.23–17.13). Cox MVA showed that PR-negative status was associated with worse OS (adjusted hazards ratio [aHR] 1.20, 95% CI 1.10–1.31). There was an interaction with nodal staging and chemotherapy (p = 0.049). Subgroup analyses using Cox MVA showed the magnitude of the chemotherapy benefit was greater among those with pN1a, PR-negative tumors than pN1a, PR-positive tumors (PR-positive: aHR 0.57, 95% CI 0.47–0.67; PR-negative: aHR 0.31, 95% CI 0.20–0.47). It was comparable among those with pN0 tumors regardless of PR status (PR-positive: aHR 0.74, 95% CI 0.66–0.82; PR-negative: aHR 0.63, 95% CI 0.51–0.77).ConclusionPR-negative tumors were independently correlated with higher RS and were associated with greater OS benefits from chemotherapy for pN1a tumors, but not pN0 tumors.

Prognosis after Local Recurrence in Patients with Early-Stage Breast Cancer Treated without Chemotherapy

Many women with early-stage breast cancer are predicted to be at sufficiently low risk for recurrence that they may forego chemotherapy. Nevertheless, some low-risk women will experience a local recurrence, and for them the risk of death increases significantly thereafter. The utility of initiating chemotherapy at the time of local recurrence has not been adequately addressed. The purpose of this study is to identify, in a hospital-based series of patients with early-stage breast cancer who were not treated with chemotherapy, those factors which predict death post local recurrence. We identified 135 women who were diagnosed with early-stage breast cancer (node-negative, <5 cm) and who did not receive chemotherapy at diagnosis and who developed a local recurrence. They were diagnosed between 1987 and 2000 and treated at Women's College Hospital. For each patient, we abstracted information on the initial cancer (age at diagnosis, tumour size, tumour grade, ER status, PR status, HER2 status, lympho-vascular invasion, type of surgery, use of radiotherapy, tamoxifen and chemotherapy), the time from initial diagnosis to local recurrence and treatment at recurrence. The Kaplan-Meier method was used to estimate the ten-year actuarial risk of breast cancer death post recurrence. A Cox proportional hazards model was used to estimate multivariate hazard ratios for the various factors. Among the 135 women in the cohort, the mean time from initial diagnosis to local recurrence was 7.8 years (range: 0.3 to 22.6 years). A total of 38 of the 135 women (28.1%) died of breast cancer a mean of 5.3 years after experiencing the local recurrence (range: 0.3 to 17 years). The ten-year breast cancer survival post local recurrence was 71% and the 15-year survival was 65%. In a multivariate analysis, it was found that factors that were significantly associated with death after local recurrence were (1) PR-negative status, (2) young age at diagnosis (<40 years) and (3) time to local recurrence less than 2 years. Nine percent of women received chemotherapy at the time of local recurrence. For breast cancer patients with a low baseline risk of mortality, the risk of death after an isolated local recurrence is substantial. Systemic treatment at the time of local recurrence needs further study.

Assessment of Prognostic Factors and Molecular Subtypes of Breast Cancer With a Continuous-Time Random-Walk MR Diffusion Model: Using Whole Tumor Histogram Analysis.

The continuous-time random-walk (CTRW) diffusion model to evaluate breast cancer prognosis is rarely reported. To investigate the correlations between apparent diffusion coefficient (ADC) and CTRW-specific parameters with prognostic factors and molecular subtypes of breast cancer. Retrospective. One hundred fifty-seven women (median age, 50 years; range, 26-81 years) with histopathology-confirmed breast cancer. Simultaneous multi-slice readout-segmented echo-planar imaging at 3.0T. The histogram metrics of ADC, anomalous diffusion coefficient (D), temporal diffusion heterogeneity (α), and spatial diffusion heterogeneity (β) were calculated for whole-tumor volume. Associations between histogram metrics and prognostic factors (estrogen receptor [ER], progesterone receptor [PR], human epidermal growth factor receptor 2 [HER2], and Ki-67 proliferation index), axillary lymph node metastasis (ALNM), and tumor grade were assessed. The performance of histogram metrics, both alone and in combination, for differentiating molecular subtypes (HER2-positive, Luminal or triple negative) was also assessed. Comparisons were made using Mann-Whitney test between different prognostic factor statuses and molecular subtypes. Receiver operating characteristic curve analysis was used to assess the performance of mean and median histogram metrics in differentiating the molecular subtypes. A P value <0.05 was considered statistically significant. The histogram metrics of ADC, D, and α differed significantly between ER-positive and ER-negative status, and between PR-positive and PR-negative status. The histogram metrics of ADC, D, α, and β were also significantly different between the HER2-positive and HER2-negative subgroups,and between ALNM-positive and ALNM-negative subgroups. The histogram metrics of α and β significantly differed between high and low Ki-67 proliferation subgroups, and between histological grade subgroups. The combination of αmean and βmean achieved the highest performance (AUC=0.702) to discriminate the Luminal and HER2-positive subtypes. Whole-tumor histogram analysis of the CTRW model has potential to provide additional information on the prognosis and intrinsic subtyping classification of breast cancer. 4 TECHNICAL EFFICACY: Stage 2.

Quantitative Assessment of Restriction Spectrum MR Imaging for the Diagnosis of Breast Cancer and Association With Prognostic Factors.

Restriction spectrum imaging (RSI) is an advanced quantitative diffusion-weighted magnetic resonance imaging (DWI) technique to assess breast cancer. To investigate the ability of RSI to differentiate the benign and malignant breast lesions and the association with prognostic factors of breast cancer. Retrospective. Seventy women (mean age, 49.6 ± 12.3 years) with 56 malignant and 19 benign breast lesions. 3-T; RSI-based DWI sequence with echo-planar imaging technique. The apparent diffusion coefficient (ADC) and RSI parameters (restricted diffusion f1 , hindered diffusion f2 , free diffusion f3 , and signal fractions f1 f2 ) were calculated by two readers for the whole lesion volume and compared between the benign and malignant groups and the subgroups with different statuses of prognostic factors in breast cancer. Mann-Whitney U test or Student's t-test was applied to compare the quantitative parameters between the different groups. Intraclass correlation coefficient (ICC) was used to assess readers' reproducibility. Binary logistic regression was used to combine parameters. Area under the curve (AUC) of receiver operating characteristic curve analysis was used to evaluate the diagnostic performance of parameters to distinguish benign from malignant breast lesions. A P-value <0.05 was considered statistically significant. Malignant breast lesions showed significantly lower ADC and f3 values, and significantly higher f1 and f1 f2 values than the benign lesions, with AUC of 0.951, 0.877, 0.868, and 0.860, respectively. When RSI-derived parameters and ADC were combined, the diagnostic performance was superior to either single parameter (AUC=0.973). The f3 value was significantly differed between estrogen receptor (ER)-positive and ER-negative tumors. The ADC, f1 , f3 , and f1 f2 values were significantly different progesterone receptor (PR)-positive and PR-negative status. The RSI-derived parameters (f1 , f3 , and f1 f2 ) may facilitate the differential diagnosis between benign and malignant breast lesions. 4 TECHNICAL EFFICACY: Stage 2.

FHER2, PR, ER, Ki-67 and Cytokeratin 5/6 Expression in Benign Feline Mammary Lesions.

Simple SummaryFeline mammary neoplasias are highly prevalent in domestic cats and present many similarities to their human counterparts. Since information about benign feline mammary lesions is still scarce and often controversial, studies using a wider panel of oncological biomarkers are necessary to understand their potential contribution to malignant lesions. This study analyzed 47 benign lesions from 27 queens, regarding the expression of estrogen and progesterone receptors (ER and PR, respectively), fHER2 protein and two malignancy indicators (Ki-67 and CK 5/6). Our results showed that most of the lesions were ER positive (91.5%), PR negative (63.8%), fHER2 negative (64.4%), Ck 5/6 negative (76.6%) and with a low Ki-67 index (78.7%). Additionally, significant correlations were found between younger ages and ER positivity and between larger lesions and negative PR status. Our results highlight the importance of estrogen receptors in the development of benign feline mammary lesions, further contributing to the development of preventive and monitoring strategies in feline mammary oncology.Biomarkers are essential in the characterization of neoplastic lesions and aid not only in the classification of the nature of the lesions, but also in the understanding of their ontogeny, development and prognosis. In cats, while mammary carcinomas are increasingly being characterized, information on their benign lesions is still scarce. Indeed, a better characterization of benign lesions could have an important role in unravelling mammary oncogenesis, similar to that in human breast cancer. Thus, in this study, the expression of five markers was analyzed in 47 benign mammary lesions (hyperplasia, dysplasia and benign tumors) collected from 27 queens. Dysplastic and hyperplastic lesions were the most common (41/47, 81.7%). Most of the lesions were classified as ER positive (43/47, 91.5%), PR negative (30/47, 63.8%), fHER2 negative (29/47, 64.4%), CK 5/6 negative (36/47, 76.6%) and with a low Ki-67 index (37/47, 78.7%). Statistical analysis revealed a correlation between younger ages and ER positivity (p = 0.013) and between larger lesions and negative PR status (p = 0.038). These results reinforce the importance of evaluating the expression of the ER status, prevalent in benign lesions, as a putative precursor in cancer progression.

Association of progesterone receptor status with 21-gene recurrence score and survival among patients with estrogen receptor-positive breast cancer.

529 Background: Among patients with estrogen receptor (ER)-positive breast cancer, progesterone receptor (PR)-negative tumors were shown to have worse prognosis than PR-positive tumors. However, PR-negative tumors were underrepresented in trials such as TAILORx and RxPONDER, and the role of PR status in the setting of 21-gene recurrence score (RS) remains unclear. We performed an observational cohort study to evaluate the association of PR status with RS and the magnitude of chemotherapy benefits on survival. Methods: The National Cancer Database (NCDB) was queried for women diagnosed between 2010 and 2017 with ER-positive, human epidermal growth factor receptor 2 (HER2)-negative, pT1-3N0-1a breast cancer who underwent surgery and endocrine therapy. Logistic and Cox multivariable analyses (MVA) were used to identify variables associated with high RS (&gt; 25) and overall survival (OS), respectively. Interaction test was performed among PR status, chemotherapy, and nodal staging. Propensity score matching was performed to reduce selection bias. Sensitivity analysis was performed after excluding those with postdiagnosis survival of less than 6 months to reduce immortal time bias. Results: A total of 143,828 patients met our criteria (n = 110,421 for PR-positive/pN0, n = 11,897 for PR-negative/pN0, n = 19,928 for PR-positive/pN1a, n = 1,582 for PR-negative/pN1a). Median follow up was 51.5 months (interquartile range 34.8-71.9). On logistic MVA, PR-negative tumors were more likely to have high RS (adjusted odds ratio [aOR] 6.68, 95% confidence interval [CI] 6.40-6.97, p &lt; 0.001). On Cox MVA, PR-negative tumors were associated with worse OS (adjusted hazards ratio [aHR] 1.20, 95% CI 1.10-1.31, p &lt; 0.001). Interaction among PR status, chemotherapy, and nodal staging was statistically significant (interaction p = 0.049). On subgroup analyses, the magnitude of chemotherapy benefit for OS was comparable among pN0 tumors (PR-positive: aHR 0.74, 95% CI 0.66-0.82; PR-negative: aHR 0.63, 95% CI 0.51-0.77) and was greater for PR-negative status among pN1a tumors (PR-positive: aHR 0.57, 95% CI 0.47-0.67; PR-negative: aHR 0.31, 95% CI 0.20-0.47). Similar findings were noted in 9,979, 1,822, 4,196, and 354 matched pairs for PR-positive/pN0 (HR 0.43, 95% CI 0.37-0.50), PR-negative/pN0 (HR 0.53, 95% CI 0.41-0.69), PR-positive/pN1a (HR 0.55, 95% CI 0.45-0.67), and PR-negative/pN1a (HR 0.25, 95% CI 0.14-0.45) tumors, respectively. On sensitivity analysis, our findings were consistent in Cox MVA using interaction and subgroup analyses. Conclusions: To our knowledge, this is the largest study using a nationwide oncology database suggesting that PR-negative status is an independent, adverse prognostic factor for survival associated with high RS, with greater chemotherapy benefits compared to PR-positive status among pN1a tumors even after adjusting for RS.

Breast Cancer in Chinese Females Aged 25 Years and Younger.

Background Breast cancer has both aggressive clinicopathological characteristics and a poor prognosis in young females. However, limited information is available for breast cancer in Chinese females aged ≤25 years. Therefore, we aimed to explore prognostic factors for invasive disease-free (iDFS) and overall survival (OS) among breast cancer patients aged ≤25 years. Methods We retrospectively analyzed data from 174 Chinese females aged ≤25 years with invasive breast cancer treated in the Cancer Hospital of the Chinese Academy of Medical Sciences from January 1, 1999, to December 31, 2018. Univariate and multivariate Cox regression analyses were performed to identify independent prognostic factors. Results The median follow-up time was 75 months (ranging from 1 to 236 months). Breast cancer patients aged ≤25 years exhibited aggressive clinicopathological characteristics, including advanced tumor stage (21.8%), lymph node metastasis (47.1%), lymphovascular invasion (24.1%), estrogen receptor negativity (44.3%), progesterone receptor (PR) negativity (42.5%), and triple-negative breast cancer (25.3%). Among them, 50 cases had locoregional recurrence and metastasis, 20 had bilateral invasiveness, and 33 had breast cancer-specific deaths. Cox multivariate analysis identified that diagnosis delay, PR status, and radiotherapy were significant prognostic factors for both iDFS and OS (P < 0.05). The risk of recurrence and metastasis was five times higher in N3 than in N0 (HR: 6.778, 95% CI: 2.268–17.141, P < 0.001). Patients with lymphovascular invasion had a threefold increase in the risk of breast cancer-specific death (HR: 4.217, 95% CI: 1.956–9.090, P < 0.001). No differences were observed between mastectomy and breast-conserving surgery (BCS) plus radiotherapy for iDFS or OS (iDFS: χ2 = 0.678, P=0.410; OS: χ2 = 0.165, P=0.685). Conclusions Breast cancer in females ≤25 years old was associated with aggressive clinical features and a worse prognosis. Young females with breast lumps should receive timely diagnosis and treatment. Young breast cancer patients with lymphovascular invasion, PR-negative status, and lymph node metastasis have an increased risk of experiencing recurrence and metastasis and should hence be closely monitored. Age at diagnosis should not be the sole deciding factor for surgical treatment methods.

Significant difference between coagulation parameters and clinicopathological characteristics in breast cancer.

The purpose of this research is to investigate the correlation between coagulation parameters and survival on patients with breast cancer. A total of 244 patients with breast cancer and 84 patients with metastatic advanced breast cancer admitted to the Second Affiliated Hospital of Chongqing Medical University from January 2017 to February 2019 were selected as the research objects. Their age, tumor size, status of estrogen receptor and progesterone receptor status, status of Her-2 receptor and lymph node were evaluated. Additional 99 cases of benign breast tumors were selected as the control group. All patients were newly diagnosed. PTA, PT ratio, PT, APTT, APTT ratio, TT, TT ratio, PT-INR, FIB, and FDP were detected on all patients. There were significant differences in APTT, APTT ratio, FIB, TT, TT ratio, and FDP between breast cancer and benign tumor control group (P < 0.05). The changes of FIB were correlated with age (P = 0.007), PR status (P = 0.017), and Her-2 status (P = 0.008). The older the age, the higher the FIB level. The FIB level of Er negative state is higher than that of positive state, and the FIB level of PR negative state is also higher than that of positive state. Survival analysis showed that PR negative status, the elevated level of APTT, APTT ratio, TT increased, and TT ratio were the indicators affecting 3-year DFS of patients (P < 0.05). Multivariate COX regression analysis showed that APTT and TT were independent prognostic factors affecting 3 years DFS (P < 0.05). Blood hypercoagulable state in patients with breast cancer, abnormal coagulation system plays an important role in the progress of breast cancer.

A clinical calculator to predict disease outcomes in women with hormone receptor-positive advanced breast cancer treated with first-line endocrine therapy.

Endocrine therapy (ET) is an effective strategy to treat hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (ABC) but nearly all patients eventually progress. Our goal was to develop and validate a web-based clinical calculator for predicting disease outcomes in women with HR+ABC who are candidates for receiving first-line single-agent ET. The meta-database comprises 891 patient-level data from the control arms of five contemporary clinical trials where patients received first-line single-agent ET (either aromatase inhibitor or fulvestrant) for ABC. Risk models were constructed for predicting 24-months progression-free survival (PFS-24) and 24-months overall survival (OS-24). Final models were internally validated for calibration and discrimination using ten-fold cross-validation. Higher number of sites of metastases, measurable disease, younger age, lower body mass index, negative PR status, and prior endocrine therapy were associated with worse PFS. Final PFS and OS models were well-calibrated and associated with cross-validated time-dependent area under the curve (AUC) of 0.61 and 0.62, respectively. The proposed ABC calculator is internally valid and can accurately predict disease outcomes. It may be used to predict patient prognosis, aid planning of first-line treatment strategies, and facilitate risk stratification for future clinical trials in patients with HR+ABC. Future validation of the proposed models in independent patient cohorts is warranted.

Abstract 3190: PD-L1 protein expression in Middle Eastern breast cancer predicts favorable outcome in triple negative breast cancer

Abstract Programmed cell death ligand 1 (PD-L1) has been shown to induce potent T-cell mediated anti-tumoral immunity. The significance of PD-L1 expression on prognosis of breast cancer remains controversial and its prevalence and prognostic value in breast cancer from Middle Eastern ethnicity is lacking. A total of 1003 unselected Middle Eastern breast cancers were analyzed for PD-L1 expression using immunohistochemistry. The association with clinico-pathological markers and impact on overall survival as well as recurrence free survival was determined. PD-L1 expression was seen in 32.8% (329/1003) cases. PD-L1 positivity was significantly associated with poor prognostic indicators such as younger patients (p = 0.0499), high grade tumors (p = 0025), ER negative (p &amp;lt; 0.0001) and PR negative (p = 0.0001) status as well as high Ki-67 index (p &amp;lt; 0.0001). We also found a significant association between PD-L1 expression and deficient mismatch repair protein expression (p = 0.0009). No association was found between PD-L1 expression and clinical outcome. However, on further subgroup analysis, PD-L1 expression was found to be an independent marker for favorable prognosis in triple negative breast cancer (TNBC) (Hazard ratio = 0.27; 95% confidence interval = 0.10 - 0.63; p = 0.0018). In conclusion, we demonstrated strong association between PD-L1 and MSI in Middle Eastern BC patients and showed that PD-L1 overexpression on tumor cells was an independent favorable prognostic factor in TNBCs from this ethnicity. Overall, these findings might help in the development of more appropriate treatment strategies for BC in Middle Eastern population. Citation Format: Khawla S. Al-Kuraya, Abdul K. Siraj, Sandeep K. Parvathareddy, Saeeda Ahmed, Allianah Benito, Kaleem Iqbal. PD-L1 protein expression in Middle Eastern breast cancer predicts favorable outcome in triple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 3190.

Morphological and molecular changes following neoadjuvant endocrine therapy of oestrogen receptor‐positive breast cancer: implications for clinical practice

Neoadjuvant endocrine therapy (NAET) is used in the management of oestrogen receptor (ER)-positive breast cancer. The optimal method for histological assessment of response and the effect of NAET on the tumour morphology, grade and molecular profile remain unclear. The aim of this study is to investigate the NAET effect on tumour type, grade and molecular profile by analysing a well-characterised cohort of breast cancer samples in a single large UK tertiary referral centre, and to provide guidance on the pathological assessment of those lesions to inform adjuvant management and prognosis. A single large-institution cohort of 132 patients who received NAET over a 13-year period was identified. Comprehensive clinical, histopathological and follow-up data were collected. A detailed histological review of a subset with residual post-treatment carcinoma was undertaken. Two carcinomas (both of the lobular type) achieved complete pathological response. Central scarring was seen in 49.3% of tumours post-treatment. Significant changes in tumour type (41.6%), tumour grade (downgrading in one-third of tumours), and progesterone receptor (PR) expression (22.3%), with a switch to PR-negative status in 17.6% of cases, were observed. The last of these was associated with an absence of tumour-infiltrating lymphocytes (P=0.005). Ten percent of cases showed a change in HER2 expression (P=0.002). The median patient survival was 60months, and downgrading of tumours was associated with better overall survival (P=0.05). We propose a histological method for assessment of residual carcinoma following NAET, and recommend repeat ER/PR/HER2 testing to inform management and prognosis.