Progesterone Receptor Status Research Articles

432P Ki67 and progesterone receptor status could be predict sensitivity to cyclin-dependent kinase inhibitor

432P Ki67 and progesterone receptor status could be predict sensitivity to cyclin-dependent kinase inhibitor

Polymorphisms in genes of melatonin biosynthesis and signaling support the light-at-night hypothesis for breast cancer

Light-at-night triggers the decline of pineal gland melatonin biosynthesis and secretion and is an IARC-classified probable breast-cancer risk factor. We applied a large-scale molecular epidemiology approach to shed light on the putative role of melatonin in breast cancer. We investigated associations between breast-cancer risk and polymorphisms at genes of melatonin biosynthesis/signaling using a study population of 44,405 women from the Breast Cancer Association Consortium (22,992 cases, 21,413 population-based controls). Genotype data of 97 candidate single nucleotide polymorphisms (SNPs) at 18 defined gene regions were investigated for breast-cancer risk effects. We calculated adjusted odds ratios (ORs) and 95% confidence intervals (CI) by logistic regression for the main-effect analysis as well as stratified analyses by estrogen- and progesterone-receptor (ER, PR) status. SNP-SNP interactions were analyzed via a two-step procedure based on logic regression. The Bayesian false-discovery probability (BFDP) was used for all analyses to account for multiple testing. Noteworthy associations (BFDP < 0.8) included 10 linked SNPs in tryptophan hydroxylase 2 (TPH2) (e.g. rs1386492: OR = 1.07, 95% CI 1.02–1.12), and a SNP in the mitogen-activated protein kinase 8 (MAPK8) (rs10857561: OR = 1.11, 95% CI 1.04–1.18). The SNP-SNP interaction analysis revealed noteworthy interaction terms with TPH2- and MAPK-related SNPs (e.g. rs1386483R ∧ rs1473473D ∧ rs3729931D: OR = 1.20, 95% CI 1.09–1.32). In line with the light-at-night hypothesis that links shift work with elevated breast-cancer risks our results point to SNPs in TPH2 and MAPK-genes that may impact the intricate network of circadian regulation.

The Effect of Clinical (Anatomical) and Prognostic Stage Groups on Survival in Patients Diagnosed with Breast Cancer: MULTI-Center Study Results, TROD Breast Cancer Study Group

The American Joint Committee on Cancer (AJCC) anatomic stage groups have arguably been the most powerful method in predicting breast cancer outcomes. In the present study, we aimed to determine the differences between anatomical stage and clinical prognostic stage groups, which were obtained by adding biological markers such as histologic tumor grade, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 status to patients diagnosed with breast cancer, the rate of change in stage, and the effect of stage change on survival. The study protocol was sent to all radiation oncology centers in Türkiye. Four centers enrolled their patients to the study. A total of 1470 stage I-III breast cancer patients with complete information on biological markers (histologic tumor grade, hormone receptor, and c-erb B2 receptor status), haven't been treated with neoadjuvant therapy were included to the study and evaluated retrospectively. The 8th edition of AJCC consolidated biological markers in to clinical prognostic stage groups. Kaplan-Meier curves were used to estimate survival. The log-rank test was used to compare the difference between groups. The Cox proportional-hazards regression model was used to determine the association between anatomic-prognostic stage, disease-free survival (DFS), and overall survival (OS). The median follow-up time was 82 (6-237) months. Median age of the patients was 52 years (20-88) and 865 cases (58.8%) were in the postmenopausal period. The axillary lymph node status was negative (N0) in 765 patients (52.1%). Tumor grade was grade I in 200 patients (13.6%), grade II in 812 patients (55.2%) and grade III in 452 patients (30.7%). Estrogen receptor status was positive in 1247 patients (84.8%), PR status was positive in 1178 patients and Her2-neu status was positive in 207 patients (14.1%). A stage change has been identified in a total of 777 patients (52.9%). Compared with the anatomic stage groups, application of the clinical prognostic stage groups assigned 46.4% cases lower and 6.5% cases higher stage. Five- and ten-year OS and DFS rates of the patients are 73.7%, 44.3% and 91.9%, 86.3% respectively. Age (p<0.001), tumor grade (p<0.001), ER status (p<0.001), PR status (p<0.001), cerbB2 receptor status (p = 0.025) were found to be statistically significant variables in multivariable analysis for OS. For DFS, multivariable analysis showed that age (p = 0.027), tumor grade (p = 0.005), anatomical stage (p<0.001) and assigned to higher stage (p = .001) were statistically significant variables. Hormone receptors and c-erb B2 receptor status are independent variables which impact OS and DFS in our patient group which is mostly consisted of early-stage cases according to anatomical stage. In prognostic staging, upstaging stands out as an independent prognostic factor for DFS. The 8th edition of AJCC prognostic stage groups determines the prognosis much better in our patient cohort.

A nomogram for predicting breast cancer specific survival in elderly patients with breast cancer: a SEER population-based analysis

BackgroundThe number of elderly patients diagnosed with breast cancer is increasing worldwide. However, treatment decisions for these patients are highly variable. Although researchers have identified the effects of surgery, radiotherapy, endocrine therapy, and chemotherapy in elderly patients with breast cancer, clinicians still struggle to make appropriate decisions for these patients.MethodsWe identified 75,525 female breast cancer patients aged ≥ 70 years in the Surveillance, Epidemiology, and End Results (SEER) database treated between January 1, 2010, and December 31, 2016. The patients were further divided into training and testing cohorts. The cumulative occurrence of breast cancer-specific deaths (BCSDs) and other cause-specific deaths (OCSD) was calculated using the cumulative incidence function. In the univariate analysis, risk factors were screened using the Fine-Gray model. In the multivariate analysis for competing risks, the sub-distribution hazard ratio with a 95% confidence interval for each independent predictor associated with BCSD was calculated for the construction of nomograms. Based on the above analyses, a competing risk nomogram was constructed to predict the probability of BCSD in the 1st, 3rd, and 5th years after treatment. During validation, the concordance index (C-index) was selected to quantify the predictive ability of the competing risk model.ResultsA total of 33,118 patients were included in this study, with 24,838 in the training group and 8,280 in the testing group. Age, race, marital status, cancer grade, tumor stage, node stage, estrogen receptor status, progesterone receptor status, human epidermal growth factor receptor--2 status, and treatment including surgery, radiation, and chemotherapy were used to establish a nomogram. The C-index of 0.852 (0.842-0.862) in the training cohort and 0.876 (0.868-0.892) in the testing cohort indicated satisfactory discriminative ability of the nomogram. Calibration plots showed favorable consistency between the nomogram predictions and actual observations in both the training and validation cohorts.ConclusionsOur study identified independent predictors of BCSD in elderly patients with breast cancer. A prognostic nomogram was developed and validated to aid clinical decision-making.

PR status is a more decisive factor in efficacy of adding pertuzumab into neoadjuvant therapy for HER2-positive and lymph node-positive breast cancer than ER status: a real-world retrospective study in China

BackgroundAlthough neoadjuvant trastuzumab and pertuzumab (HP)-based regimens are recommended for human epidermal receptor-positive (HER2 +)/lymph node-positive (N +) breast cancer (BC) patients according to NCCN guidelines, it is undeniable that many patients achieved pathological complete response (pCR) after trastuzumab (H)-based regimens without adding pertuzumab to treatment. Patients who specifically benefit from pertuzumab must be identified. The aim of this retrospective study was to evaluate progesterone receptor (PR) status as a predictor of response to the addition of pertuzumab in HER2 + /N + breast cancer.MethodsOne hundred forty-two patients who were diagnosed as HER2 + /N + BC without distant metastasis and followed by neoadjuvant HP-based or H-based therapy were retrospectively included. The endpoints were pCR and disease-free survival (DFS) times.ResultsIn total, the pCR occurred in 25 of 87 patients (28.74%) in group H compared with 32 of 55 (58.18%) in group HP. The results revealed that hormone receptor (HR) status was significantly different on pCR in group HP. The odds of pCR for patients who have HR-positive tumors were 0.160 times (P = 0.011) that for patients with HR-negative tumors by multivariable analysis. Moreover, a similar probability of PR-positive (PR +) patients, whatever estrogen receptor (ER) status was, achieving pCR in group HP was observed. The ROC curves showed different anti-HER2 regimens provide worst predictive value in the PR + cohort (N = AUC = 0.521, 95% CI: 0.348–0.694, P = 0.813) compared with the overall cohort (AUC = 0.644, 95% CI: 0.550–0.738, P = 0.004) and ER + cohort (AUC: 0.559, 95% CI: 0.405–0.713, P = 0.451). And PR status (AUC = 0.760, 95% CI: 0.626–0.894, P = 0.001) had a greater predictive value than ER status (AUC = 0.658, 95% CI: 0.508–0.807, P = 0.048) in group HP. DFS analyses were done on 141 patients. Although ER and PR status did not show significant difference in group HP (P = 0.789 and 0.088, respectively), HP-based therapy contributed to better DFS in the ER − and PR − cohorts (P = 0.035 and 0.015, respectively).ConclusionsCompared with ER status, PR status might be a more valuable factor predicting the efficacy of adding pertuzumab into neoadjuvant therapy for HER2 + /N + BC. PR + patients benefit little from the addition of pertuzumab.

Discrimination between human epidermal growth factor receptor 2 (HER2)-low-expressing and HER2-overexpressing breast cancers: a comparative study of four MRI diffusion models.

To determine the value of conventional DWI, continuous-time random walk (CTRW), fractional order calculus (FROC), and stretched exponential model (SEM) in discriminating human epidermal growth factor receptor 2 (HER2) status of breast cancer (BC). This prospective study included 158 women who underwent DWI, CTRW, FROC, and SEM and were pathologically categorized into the HER2-zero-expressing group (n = 10), HER2-low-expressing group (n = 86), and HER2-overexpressing group (n = 62). Nine diffusion parameters, namely ADC, αCTRW, βCTRW, DCTRW, βFROC, DFROC, μFROC, αSEM, and DDCSEM of the primary tumor, were derived from four diffusion models. These diffusion metrics and clinicopathologic features were compared between groups. Logistic regression was used to determine the optimal diffusion metrics and clinicopathologic variables for classifying the HER2-expressing statuses. Receiver operating characteristic(ROC) curves were used to evaluate their discriminative ability. The estrogen receptor (ER) status, progesterone receptor (PR) status, and tumor size differed between HER2-low-expressing and HER2-overexpressing groups (p < 0.001 to p = 0.009). The αCTRW, DCTRW, βFROC, DFROC, μFROC, αSEM, and DDCSEM were significantly lower in HER2-low-expressing BCs than those in HER2-overexpressing BCs (p < 0.001 to p = 0.01). Further multivariable logistic regression analysis showed that the αCTRW was the single best discriminative metric, with an area under the curve (AUC) being higher than that of ADC (0.802 vs. 0.610, p < 0.05); the addition of ER status, PR status, and tumor size to the αCTRW improved the AUC to 0.877. The αCTRW could help discriminate the HER2-low-expressing and HER2-overexpressing BCs. Human epidermal growth factorreceptor 2 (HER2)-low-expressing breast cancer (BC) might also benefit from the HER2-targeted therapy. Prediction of HER2-low-expressing BC or HER2-overexpressing BC is crucial for appropriate management. Advanced continuous-time random walk diffusion MRI offers a solution to this clinical issue. • Human epidermal receptor 2 (HER2)-low-expressing BC had lower αCTRW, DCTRW, βFROC, DFROC, μFROC, αSEM, and DDCSEM values compared with HER2-overexpressing breast cancer. • The αCTRW was the single best diffusion metric (AUC = 0.802) for discrimination between the HER2-low-expressing and HER2-overexpressing breast cancers. • The addition of αCTRW to the clinicopathologic features (estrogen receptor status, progesterone receptor status, and tumor size) further improved the discriminative ability.

Neoadjuvant palbociclib plus either giredestrant or anastrozole in oestrogen receptor-positive, HER2-negative, early breast cancer (coopERA Breast Cancer): an open-label, randomised, controlled, phase 2 study

The development of more potent selective oestrogen receptor antagonists and degraders (SERDs) that can be orally administered could help to address the limitations of current endocrine therapies. We report the primary and final analyses of the coopERA Breast Cancer study, designed to test whether giredestrant, a highly potent, non-steroidal, oral SERD, would show a stronger anti-proliferative effect than anastrozole after 2 weeks for oestrogen receptor-positive, HER2-negative, untreated early breast cancer. In this open-label, randomised, controlled, phase 2 study, postmenopausal women were eligible if they were aged 18 years or older; had clinical T stage (cT)1c to cT4a-c (≥1·5 cm within cT1c) oestrogen receptor-positive, HER2-negative, untreated early breast cancer; an Eastern Cooperative Oncology Group performance status of 0-1; and baseline Ki67 score of at least 5%. The study was conducted at 59 hospital or clinic sites in 11 countries globally. Participants were randomly assigned (1:1) to giredestrant 30 mg oral daily or anastrozole 1 mg oral daily on days 1-14 (window-of-opportunity phase) via an interactive web-based system with permuted-block randomisation with block size of four. Randomisation was stratified by cT stage, baseline Ki67 score, and progesterone receptor status. A 16-week neoadjuvant phase comprised the same regimen plus palbociclib 125 mg oral daily on days 1-21 of a 28-day cycle, for four cycles. The primary endpoint was geometric mean relative Ki67 score change from baseline to week 2 in patients with complete central Ki67 scores at baseline and week 2 (window-of-opportunity phase). Safety was assessed in all patients who received at least one dose of study drug. The study is registered with ClinicalTrials.gov (NCT04436744) and is complete. Between Sept 4, 2020, and June 22, 2021, 221 patients were enrolled and randomly assigned to the giredestrant plus palbociclib group (n=112; median age 62·0 years [IQR 57·0-68·5]) or anastrozole plus palbociclib group (n=109; median age 62·0 [57·0-67·0] years). 15 (7%) of 221 patients were Asian, three (1%) were Black or African American, 194 (88%) were White, and nine (4%) were unknown races. At data cutoff for the primary analysis (July 19, 2021), the geometric mean relative reduction of Ki67 from baseline to week 2 was -75% (95% CI -80 to -70) with giredestrant and -67% (-73 to -59) with anastrozole (p=0·043), meeting the primary endpoint. At the final analysis (data cutoff Nov 24, 2021), the most common grade 3-4 adverse events were neutropenia (29 [26%] of 112 in the giredestrant plus palbociclib group vs 29 [27%] of 109 in the anastrozole plus palbociclib group) and decreased neutrophil count (17 [15%] vs 16 [15%]). Serious adverse events occurred in five (4%) patients in the giredestrant plus palbociclib group and in two (2%) patients in the anastrozole plus palbociclib group. There were no treatment-related deaths. One patient died due to an adverse event in the giredestrant plus palbociclib group (myocardial infarction). Giredestrant offers encouraging anti-proliferative and anti-tumour activity and was well tolerated, both as a single agent and in combination with palbociclib. Results justify further investigation in ongoing trials. F Hoffmann-La Roche.

Missing Components of Receptor Status Among Women With Invasive Breast Cancer

There are well-known differences in patient outcomes and effective therapeutic options across subtypes of breast cancer (BC), defined by the status of estrogen receptor, progesterone receptor, and erb-B2 receptor tyrosine kinase 2 (ERBB2 [formerly HER2]) expression, making testing for these receptors part of the routine workup for all patients with a diagnosis of invasive BC. Despite its importance, this information is missing in some BC cases. To identify female patients with BC without record of testing for estrogen receptor, progesterone receptor, or ERBB2 status, defined as missing components of receptor status (MCRS). This cross-sectional study used data from National Cancer Institute's Surveillance, Epidemiology and End Results Program of 18 population-based registries from women with a diagnosis of invasive BC (excluding death certificate-only and autopsy cases) from January 2012 to December 2016. The final analyses were completed in February 2022. The primary outcome was MCRS. Those with MCRS were summarized by age, race, stage at diagnosis, reporting source, primary payer, and geography. Multivariable logistic regression was used to estimate adjusted odds ratios (aORs) for MCRS. Overall, 321 913 patients with invasive BC were included (1928 [1%] American Indian or Alaska Native, 28 173 [9%] Asian or Pacific Islander, 36 357 [11%] Black, and 252 447 [78%] White individuals); of these, 15 250 (4.7%) had MCRS. The multivariable model showed that the odds of MCRS were higher in women 80 years or older compared with those younger than 49 years (aOR, 1.75; 95% CI, 1.65-1.88), Black compared with White women (aOR, 1.09; 95% CI, 1.00-1.16), and those with distant stage or unknown/unstaged cancer at diagnosis compared with a local stage at diagnosis (aOR, 3.33; 95% CI, 3.17-3.50; and aOR, 19.39; 95% CI, 18.15-20.72; respectively). With hospital inpatient/outpatient or clinic as the reference group, cases reported by laboratory only, nursing/convalescent home/hospice, and a physician's office were more likely to have MCRS (aOR, 1.42; 95% CI; 1.28-1.60; aOR, 9.37; 95% CI, 6.03-14.53; and aOR, 2.32; 95% CI, 2.06-2.62; respectively). Adjusted odds of MCRS were higher for the categories of insured/no specifics and insurance status unknown compared with those who were insured. The adjusted odds of MCRS were higher in rural compared with urban areas (aOR, 1.08; 95% CI, 1.03-1.15). The results of this cross-sectional study of women with a diagnosis of invasive BC suggest that despite a standard of care recommended by all expert guidelines, there needs to be greater focus on hormone receptor and ERBB2 testing in all women with invasive BC. The results of this study may help clinicians, public health practitioners, and policymakers target affected populations to minimize or eliminate this critical health disparity and help save more lives.

Estimation of Progression Free Survival (PFS) in Patients with Hormone Positive Metastatic Breast Cancer in Cohort of Egyptian Patients (Retrospective Cohort Study)

Background Breast cancer (BC) is the second most common cancer in the world and the most frequent cancer among women with approximately 1.7 million new cancer cases diagnosed yearly. It is the most common female malignancy accounting for 22.9% and 37.7% of all female cancers worldwide and in Egypt, respectively. BC in Egypt carries an unfavorable prognosis with 29% mortality and 3.7:1 incidence to mortality ratio. Aim of the Work to assess progression free survival (PFS) in patient with hormone positive metastatic breast cancer and prognostic factors affecting it in series of Egyptian patients treated in Ain Shams University hospitals and Maadi Medical Armed Forces Complex. Patients and Methods This retrospective cohort study was conducted in Clinical Oncology Department, Ain Shams University Hospitals and Medical Oncology Department, Maadi Medical Armed Forces Complex from January 2019 till December 2020. Progression free survival was estimated for all patients. Age of the studied patients ranged from 32 to 85 years with mean age of 58 years, 77.9% of the patients with MBC were postmenopausal, 22.9% of patients had positive family history. Most of our patients were IDC (95%) while only 5% were ILC, hormonal and molecular status among studied groups showed ER +ve in 100% of patients. Results Regarding to progesteron receptor (PR) status, 8.7% of patients were negative and 91.3% were positive. Ninety percent had HER2 overexpression. In 240 breast cancers, proliferative index Ki-67 was low in 84.6%. High levels were seen in 15.4% of cases. Progression free survival ranged from 1 to 66 months with median of 15 months. There are statistically significant relations of progression free survival with menopausal status, family history, HER2 overexpression, proliferative index Ki67, onset of metastasis evolution, site of metastasis, 1st line of treatment for metastasis, type of hormonal treatment for metastasis and ovarian ablation for premenopausal MBC patients. Conclusion There are statistically significant relations of PFS with 1st line of treatment of metastasis, as we find that Patients who received hormonal treatment only was significantly higher PFS (median PFS 17 months) compared to patients whose received both hormonal therapy and chemotherapy (median PFS 15 months) and patients whose received chemotherapy only (median PFS 5 months).

Contribution of constitutional BRCA1 promoter methylation to early-onset and familial breast cancer patients from Pakistan.

Constitutional BRCA1 promoter methylation has been identified as a potential risk factor for breast cancer (BC) in the Caucasian population. However, this data is lacking for BC patients of Asian origin. Therefore, we assessed the contribution of constitutional BRCA1 promoter methylation in Pakistani BC patients. A total of 385 BRCA1/2-negative index BC patients (197 early-onset BC (≤ 30years), 152 familial BC, 17 familial BC and ovarian cancer, 19 male BC) and 107 healthy controls were screened for the constitutional BRCA1 promoter methylation by methylation-sensitive high-resolution melting assay. Overall, 131 patients displayed triple-negative BC (TNBC) and 254 non-TNBC phenotypes. The prevalence of BRCA1 promoter methylation was calculated based on clinicopathological characteristics using univariable and multivariable logistic regression models. Constitutional BRCA1 promoter methylation was identified in 19.5% (75/385) of BC patients and 13.1% (14/107) of controls. The frequency of methylation was higher in early-onset BC (23.4% vs. 13.1%, P = 0.035) and TNBC patients (29.0% vs. 13.1%, P = 0.004) compared to controls. Methylation was also more prevalent in patients with high-grade than low-grade tumors (21.7% vs. 12.2%, P = 0.034) and progesterone receptor (PR)-negative than PR-positive tumors (26.0% vs. 13.9%, P = 0.004). Constitutional BRCA1 promoter methylation remained independently associated with TNBC phenotype (odds ratio 1.99; 95% CI 1.12-3.54; P = 0.02) after adjusting for BC diagnosis age, tumor grade, ER, and PR status. Constitutional BRCA1 promoter methylation is associated with TNBC and can serve as a non-invasive blood-based biomarker for Pakistani TNBC patients.

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.

Clinical importance and PI3K/Akt pathway-dependent anti-proliferative role of PALMD and DPT in breast cancer

This study aimed to identify novel differentially expressed genes in breast cancer and to explore the clinical value and the anti-tumor or oncogenic effects of the identified genes using bioinformatics analysis and in vitro experiments. The differentially expressed genes in breast cancer patients were identified using Gene Expression Omnibus (GEO) database with the cut-off criteria p < 0.05 and |logFC| > 1. The expression levels of palmdelphin (PALMD) and dermatopontin (DPT) in normal tissues and breast cancer tissues were evaluated based on GEPIA and UALCAN databases. PALMD and DPT expression levels in clinical subgroups of patients with breast cancer were analyzed to assess the association of PALMD and DPT expression with clinical characteristics. The prognostic and diagnostic values of PALMD and DPT in breast cancer were evaluated from Kaplan-Meier (K-M) survival curves and receiver operating characteristic (ROC) curves. Pearson’s correlation coefficient was performed using LinkedOmics. KEGG pathway enrichment analysis was performed using DAVID. The protein levels were evaluated using western blot analysis. Cell proliferation was assessed using MTT and EdU assays. Two important genes, PALMD and DPT, were identified in breast cancer. The expression levels of PALMD and DPT were significantly lower in breast cancer tissues. The expression levels of PALMD were closely related to age, histological type, and T stage of breast cancer patients. The expression levels of DPT were closely related to age, histological type, T stage, N stage, estrogen receptor status, and progesterone receptor status of breast cancer patients. The K-M survival curves showed that PALMD or DPT was not an independent prognostic factor for breast cancer. The ROC curves showed that both PALMD and DPT had good diagnostic potential for breast cancer. KEGG pathway enrichment results showed that PI3K/Akt pathway was an important overlapping signaling for PALMD and DPT. Further studies proved that overexpression of PALMD and DPT inhibited proliferation in MCF-7 and MDA-MB-231 cells by suppressing the PI3K/Akt pathway. PALMD and DPT knockdown promoted proliferation in MCF-7 and MDA-MB-231 cells by activating the PI3K/Akt pathway. These results collectively suggested that PALMD and DPT might serve as potential diagnostic biomarkers and therapeutic targets for breast cancer.

To study the expression of estrogen, progesterone receptor and p53 immunohistochemistry markers in subtyping endometrial carcinoma.

Endometrial cancer is one of the most commonly diagnosed cancers in women worldwide. To study the expression of estrogen receptor (ER), progesterone receptor (PR) and p53 immunohistochemistry (IHC) markers in subtyping endometrial carcinoma. Materials and Methods: A total of 100 cases of carcinoma endometrium submitted during January 2016 to October 2018 were included in our study. The ER, PR and p53 expressions were scored as per the adopted scoring system. Agreement between ER, PR and p53 IHC expression and the consensus HE diagnosis, FIGO grading and tumour staging were assessed using Chi square tests. There was a statistical association between ER, PR and p53 status and tumour histologic type with a P value < 0.01. There was no statistical significance observed between ER and PR expressions and different FIGO grades. Statistical significance (P = 0.036) between p53 and different FIGO grades seen. No statistical significance was observed between ER, PR and p53 expressions and different tumour stages and tumour invasiveness. There was a statistical association between ER and PR status and lymph node metastasis. p53 did not show a statistical significance. Combination of ER, PR and p53 IHC markers can be used to distinguish type 1 and type 2 endometrial cancers. PR expression is more specific than ER in endometrioid carcinomas. p53 expression is more specific in serous carcinoma, however, p53 IHC alone cannot be used to distinguish different grades of endometrioid carcinomas as there is variability of staining in endometrioid carcinomas.

Assessment of HER2NEU Gene Amplication by Flourescence in Situ Hybridization in Breast Carcinoma with Equivocal Findings on Immunostaining

Objective: To determine the frequency of HER2/neu gene amplification by fluorescence in situ hybridization in Breast carcinoma patients with equivocal findings and to see its association with different clinicopathological features. Study Design: Cross-sectional study. Place and Duration of study: Medical Oncology Department, Jinnah Postgraduate Medical Center, Karachi, from Jan 2019 to Jan 2020. Methodology: Total 166 females of age 22-72 years with diagnosis of invasive breast carcinoma which scored 2+ for HER2/neu by immunostaining were included in the study. Data regarding socio-demographics and clinicopathological features were noted for all the cases. Each patient was evaluated for estrogen and progesterone receptor status by immunostaining and score of 0 to 2 was deemed as negative while score 3 to 8 was deemed as positive. Patients having equivocal HER2/neu on immunostaining was further tested for gene amplification by fluorescence in situ hybridization. Results: The mean age of study participants was 46.98±11.22 years (Range: 22-72 years). Out of 166(56.5%) showed gene amplification by fluorescence in situ hybridization. Statistically significant association was found between stage of tumor and HER2/neu (p=0.036). Conclusion: HER2/neu gene amplification by fluorescence in situ hybridization is detected in more than half of patients with equivocal findings on IHC and HER2/neu is strongly correlated with stage of tumor.

Association Between Level of Expression of Human Epidermal Growth Factor Receptor 2 (Her-2 Neu) And Age Among Breast Cancer Patients

Objective: To determine the association between human epidermal growth factor receptor 2 with age among patients presenting with breast cancer. Study Design: Comparative cross-sectional study. Place and Duration of Study: Medical Oncology Department, Jinnah Postgraduate Medical Centre, Karachi Pakistan, from Aug 2019-Jan 2020. Methodology: Total 194 females of age 20-85 years with confirmed diagnosis of breast cancer were included in the study. The immunohistochemistry was done for the status of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 and the validation of human epidermal growth factor receptor 2 was done by Fluorescent In situ Hybridization technique in each female. Results: The patient’s age was from 24-82 years old with mean age of 46.57±11.45 year. Out of 194, 108 cases had positive progesterone receptor expression (55.7%), 114 had positive estrogen receptor expression (58.8%) and 67 had positive human epidermal growth factor receptor 2 expression (34.5%). The females of age greater 46 years were more likely to be human epidermal growth factor receptor 2 positive as compared to females of age less and equal to 46 years. Conclusion: The results showed that females with age more than 40 years have significant association with human epidermal growth factor receptor 2, whereas age is an independent variable with regards to estrogen receptor and progesterone receptor status.

Evaluation of breast cancer malignancy, prognostic factors and molecular subtypes using a continuous-time random-walk MR diffusion model

PurposeTo assess the continuous-time random-walk (CTRW) model’s diagnostic value in breast lesions and to explore the associations between the CTRW parameters and breast cancer pathologic factors. MethodThis retrospective study included 85 patients (70 malignant and 18 benign lesions) who underwent 3.0T MRI examinations. Diffusion-weighted images (DWI) were acquired with 16b-values to fit the CTRW model. Three parameters (Dm, α, and β) derived from CTRW and apparent diffusion coefficient (ADC) from DWI were compared among the benign/malignant lesions, molecular prognostic factors, and molecular subtypes by Mann-Whitney U test. Spearman correlation was used to evaluate the associations between the parameters and prognostic factors. The diagnostic performance was assessed by the area under the receiver operating characteristic curve (AUC) based on the diffusion parameters. ResultsAll parameters, ADC, Dm, α, and β were significantly lower in the malignant than benign lesions (P < 0.05). The combination of all the CTRW parameters (Dm, α, and β) provided the highest AUC (0.833) and the best sensitivity (94.3%) in differentiating malignant status. And the positive status of estrogen receptor (ER) and progesterone receptor (PR) showed significantly lower β compared with the negative counterparts (P < 0.05). The high Ki-67 expression produced significantly lower Dm and ADC values (P < 0.05). Additionally, combining multiple CTRW parameters improved the performance of diagnosing molecular subtypes of breast cancer. Moreover, Spearman correlations analysis showed that β produced significant correlations with ER, PR and Ki-67 expression (P < 0.05). ConclusionsThe CTRW parameters could be used as non-invasive quantitative imaging markers to evaluate breast lesions.

Absence of lobular carcinoma in situ is a poor prognostic marker in invasive lobular carcinoma

AimTo determine if the outcomes of patients with ILC co-occurring with LCIS are similar to pure ILC and if the presence of LCIS is a prognostic factor for ILC. MethodsIn an observational, population-based investigation using data from the MD Anderson breast cancer prospectively collected electronic database, we analysed patients with a diagnosis of stage I-III ILC. Patients were divided into two groups: those with ILC with co-occurring ipsilateral LCIS (ILC + LCIS) and those with pure ILC without a histologically detected co-occurring ipsilateral LCIS (ILC alone). We obtained data on demographics, pathologic tumour size (pT), pathologic lymph node (pN) involvement, estrogen (ER), progesterone (PR) receptor status, HER2 status, Ki67, treatment received, distant recurrence-free and overall survival (DRFS, OS). ResultsWe identified 4217 patients with stage I-III ILC treated at MD Anderson between 1966 and 2021. 45% of cases (n = 1881) had co-existing LCIS. Statistically and numerically, ILC alone tended to associate with pT4 and pN3 stage (P < 0.001), ER/PR negativity (P = 0.0002), HER2 positivity (P = 0.010), higher Ki67 (P = 0.005), non-classical ILC subtype (P = 0.04) and more exposure to neoadjuvant chemotherapy (P = 0.0002) compared to the ILC + LCIS group. The median follow-up time was 6.5 years. Patients with ILC + LCIS had better median DRFS (16.8 versus 10.1 years, Hazard ratio [HR] 0.55, 95% confidence interval [CI] 0.50–0.60, P < 0.0001) and better median OS (18.9 versus 13.7 years, HR 0.62, 95% CI 0.56–0.69; P < 0.0001). Multivariate analysis showed the absence of LCIS to be an independent poor prognostic factor along with a higher pT stage and higher pN stage for DRFS and OS. ConclusionThe findings of this study suggests that the absence of ipsilateral LCIS with ILC is an independent poor prognostic factor and that further studies are warranted to understand this phenomenon.

Clinical Behavior, Management, and Treatment Response of Estrogen Receptor Low (1-10%) Breast Cancer.

Estrogen receptor (ER) and progesterone receptor (PR) guide management and impact outcomes of breast cancer (BC). This study compares ER-low (1-10%) with ER-negative (< 1%) and ER-positive (>10%) BCand investigates the significance of PR expression within ER-low disease. All patients with HER2-negative invasive BC were identified from the National Cancer Database 2018-2019. Treatment and outcomes were compared using chi-squared tests and multivariable logistic regression. Of 232,762 patients, ER expression was: negative (13.8%), low (2.0%), and > 10% (84.2%). Chemotherapy was given in 83.9% of ER- disease, 82.4% of ER-low/PR- disease, 58.9% of ER-low/PR+ disease, and only in 22.9% of ER+ disease. Within the ER-low subgroup, adjuvant endocrine therapy, recurrence score, and Ki67 varied by PR status (all < 0.01). Patients with ER-low disease selected for neoadjuvant chemotherapy (NAC) were younger and had higher T and N category, tumor grade, and Ki67. With NAC, pathological complete response (pCR) rates were similar between ER-low/PR- and ER-low/PR+ (39.5% and 38.1%, respectively, p = 0.67), and were closer to the ER- group (39.7%) than the ER+ group (8.4%). On multivariable analysis, the adjusted effect of ER status (1-10% versus > 10%) on chemotherapy administration was odds ratio (OR) 8.2 (95% CI 7.3-9.2, p < 0.001) for PR-negative, and OR 3.3 (95% CI 7.3-9.2, p < 0.001) for PR-positive. This study suggests that the tumor features and clinical management of ER-low tumors vary significantly by PR expression. Within ER-low tumors, PR- tumors more closely resemble ER- BC, while PR+ tumors exhibit less aggressive characteristics. In ER-low disease selected for treatment with NAC, response is similar to ER- regardless of PR status.

Assessment of androgen receptor expression in breast cancer patients using 18 F-FDG PET/CT radiomics and clinicopathological characteristics

ObjectiveIn the present study, we mainly aimed to predict the expression of androgen receptor (AR) in breast cancer (BC) patients by combing radiomic features and clinicopathological factors in a non-invasive machine learning way.Materials and methodsA total of 48 BC patients, who were initially diagnosed by 18F-FDG PET/CT, were retrospectively enrolled in this study. LIFEx software was used to extract radiomic features based on PET and CT data. The most useful predictive features were selected by the LASSO (least absolute shrinkage and selection operator) regression and t-test. Radiomic signatures and clinicopathologic characteristics were incorporated to develop a prediction model using multivariable logistic regression analysis. The receiver operating characteristic (ROC) curve, Hosmer-Lemeshow (H-L) test, and decision curve analysis (DCA) were conducted to assess the predictive efficiency of the model.ResultsIn the univariate analysis, the metabolic tumor volume (MTV) was significantly correlated with the expression of AR in BC patients (p < 0.05). However, there only existed feeble correlations between estrogen receptor (ER), progesterone receptor (PR), and AR status (p = 0.127, p = 0.061, respectively). Based on the binary logistic regression method, MTV, SHAPE_SphericityCT (CT Sphericity from SHAPE), and GLCM_ContrastCT (CT Contrast from grey-level co-occurrence matrix) were included in the prediction model for AR expression. Among them, GLCM_ContrastCT was an independent predictor of AR status (OR = 9.00, p = 0.018). The area under the curve (AUC) of ROC in this model was 0.832. The p-value of the H-L test was beyond 0.05.ConclusionsA prediction model combining radiomic features and clinicopathological characteristics could be a promising approach to predict the expression of AR and noninvasively screen the BC patients who could benefit from anti-AR regimens.

Relative Burden of Cancer and Noncancer Mortality Among Long-Term Survivors of Breast, Prostate, and Colorectal Cancer in the US

Improvements in cancer outcomes have led to a need to better understand long-term oncologic and nononcologic outcomes and quantify cancer-specific vs noncancer-specific mortality risks among long-term survivors. To assess absolute and relative cancer-specific vs noncancer-specific mortality rates among long-term survivors of cancer, as well as associated risk factors. This cohort study included 627 702 patients in the Surveillance, Epidemiology, and End Results cancer registry with breast, prostate, or colorectal cancer who received a diagnosis between January 1, 2003, and December 31, 2014, who received definitive treatment for localized disease and who were alive 5 years after their initial diagnosis (ie, long-term survivors of cancer). Statistical analysis was conducted from November 2022 to January 2023. Survival time ratios (TRs) were calculated using accelerated failure time models, and the primary outcome of interest examined was death from index cancer vs alternative (nonindex cancer) mortality across breast, prostate, colon, and rectal cancer cohorts. Secondary outcomes included subgroup mortality in cancer-specific risk groups, categorized based on prognostic factors, and proportion of deaths due to cancer-specific vs noncancer-specific causes. Independent variables included age, sex, race and ethnicity, income, residence, stage, grade, estrogen receptor status, progesterone receptor status, prostate-specific antigen level, and Gleason score. Follow-up ended in 2019. The study included 627 702 patients (mean [SD] age, 61.1 [12.3] years; 434 848 women [69.3%]): 364 230 with breast cancer, 118 839 with prostate cancer, and 144 633 with colorectal cancer who survived 5 years or more from an initial diagnosis of early-stage cancer. Factors associated with shorter median cancer-specific survival included stage III disease for breast cancer (TR, 0.54; 95% CI, 0.53-0.55) and colorectal cancer (colon: TR, 0.60; 95% CI, 0.58-0.62; rectal: TR, 0.71; 95% CI, 0.69-0.74), as well as a Gleason score of 8 or higher for prostate cancer (TR, 0.61; 95% CI, 0.58-0.63). For all cancer cohorts, patients at low risk had at least a 3-fold higher noncancer-specific mortality compared with cancer-specific mortality at 10 years of diagnosis. Patients at high risk had a higher cumulative incidence of cancer-specific mortality than noncancer-specific mortality in all cancer cohorts except prostate. This study is the first to date to examine competing oncologic and nononcologic risks focusing on long-term adult survivors of cancer. Knowledge of the relative risks facing long-term survivors may help provide pragmatic guidance to patients and clinicians regarding the importance of ongoing primary and oncologic-focused care.