Estrogen Receptor Negative Research Articles

Abstract A012: Using clinical characteristics and molecular markers to predict the risk of subsequent ipsilateral breast events after excision of DCIS

Abstract Purpose: To examine incremental values of estrogen receptor (ER) status, body mass index (BMI), menopausal status, and a multi-gene classifier over commonly used clinical factors (i.e. age, tumor grade, comedonecrosis, surgical margins, and treatment) in predicting risk of ipsilateral recurrence (IR) within five years after DCIS diagnosis. Methods: A derivation cohort consisted of participants in the discovery cohort, a retrospective multicenter cohort study in women undergoing surgical resection for DCIS between 01/01/1998 and 02/29/2016. The validation cohort provided cases meeting the same eligibility criteria as the discovery cohort. This analysis includes 313 participants with RNA-seq data who either developed IR 1-5 years after initial DCIS diagnosis or were free from subsequent breast events at least five years. Cox proportional hazards regression was used to estimate hazard ratios (HRs) of IR in 216 TBCRC participants (76 with IR). We developed the clinical score using clinical predictors (aforementioned clinical factors and ER) and their regression coefficients from the model with the maximum predictive accuracy (e.g. c-index) and the minimum number of predictors, and the summary score integrating the clinical score and multi-gene classifier. Predictive performance of clinical and summary scores was validated in 97 RAHBT patients (20 with IR). Results: In the discovery cohort, ER negativity, but not BMI or menopausal status, was independently associated with a higher IR risk (HR=2.06, 95% CI 1.18-3.58), and adding ER to the clinical factors-based model increased predictive accuracy (c-index 0.68 to 0.70). The clinical score-adjusted HR was 14.96 (95% CI 8.64-25.91) for multi-gene classifier. Summary scores were better in predicting IR risk than clinical scores (c-index 0.82 vs. 0.70). Compared with their low-risk counterparts, the HR was 4.79 (95% CI 2.55-8.98) in the clinical score-defined high-risk group and 29.02 (95% CI 14.23-59.15) in the summary score-defined high-risk group. In the validation cohort, model performance was improved using summary scores as compared to clinical scores (c-index 0.74 vs. 0.58). Conclusion: Combination of clinical factors and multigene classifier provided more accurate risk estimates of IR within five years after excision of DCIS than clinical factors alone. Citation Format: Graham A. Colditz, Ying Liu, Siri H. Strand, Lorraine King, Jeff Marks, Carlo Maley, Robert B. West, E. Shelley Hwang. Using clinical characteristics and molecular markers to predict the risk of subsequent ipsilateral breast events after excision of DCIS [abstract]. In: Proceedings of the AACR Special Conference on Rethinking DCIS: An Opportunity for Prevention?; 2022 Sep 8-11; Philadelphia, PA. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_1): Abstract nr A012.

Survival Outcomes in Breast Cancer Patients and Associated Factors in a Border Province of Thailand: A Hospital-based Review

Objective: To evaluate the outcomes of breast cancer (BC) patients in Naradhiwas Rajanagarindra Hospital and factors associated with the outcomes. Material and Methods: A hospital-based retrospective review of patients who were diagnosed with BC in a tertiarylevel hospital in a Thailand border province was performed. Familial histories were obtained by telephone interviews. Results: There were 234 female patients diagnosed with BC during the 6-year study period. The mean age at diagnosis was 52.6 years. At presentation, 46.2% of the patients had locally advanced disease and 26.5% already had distant metastasis. Invasive ductal carcinoma (IDC) was the most common pathological subtype (84.6%) and 4.3% were ductal carcinoma in-situ. The five-year overall survival (OS) was 54% (95% confidence interval (CI) 40.25%-58.15%). On univariate analysis, factors associated with poorer survival were age >50 years, IDC pathology, T stage 3-4, N stage 2-3, distant metastasis, negative estrogen receptors, negative progesterone receptors, or both, positive human epidermal growth factor receptors 2, and Ki67 immunoreactivity >20%. Multivariate analysis showed that advanced T stage (adjusted HR1.97 95% CI 1.15-3.38), N stage (adjusted HR1.95 95% CI 1.05-3.64) and distant metastasis (HR1.86 95% CI 1.27- 2.71). Forty-nine percent of the BC women met the hereditary cancer criteria. Conclusion: The survival outcome of BC in Narathiwat province was poorer than that reported in other parts of the country. Delayed presentation might be an explanation for this disparity and a BC screening program is recommended to improve early detection.

Primary Malignant Peripheral Nerve Sheath Tumor of the Breast: A Rare Case Report

Abstract Introduction/Objective Primary breast sarcomas are uncommon and primary mammary malignant peripheral nerve sheet tumors (MPNST) are exceptionally rare. MPNST’s are malignant variants of peripheral nerve sheath tumors. These neoplasms are often associated neurofibromatosis type I (NF-I) but can also occur sporadically. They tend to occur in the deeper soft tissues, trunk, and extremities. Methods/Case Report A 60-year-old female was referred to our University Hospital for evaluation of an abnormal mammogram. Patient noticed a mass in the left breast 3 months ago and mammogram showed a large solid mass located at the left superior breast. Subsequent biopsy of the left breast lesion showed high grade malignant neoplasm with differential diagnosis of malignant phyllodes tumor, primary sarcoma, and metaplastic carcinoma. The tumor was non-responsive to the initial neoadjuvant therapy. The patient underwent modified radical mastectomy. The excised tumor was well-circumscribed, tan-white, firm, measuring 9.6 x 6.1 x 4.3 cm. The neoplastic cells were positive for CD99, S-100, SOX-10, neuron specific enolase, p53, Vimentin, focally positive for neurofilament, D2-40, p63, and negative for epithelial, melanoma and other sarcoma markers. The tumor was triple negative ER, PR, HER-2, with Ki- 67 at 61%. A diagnosis of primary high grade malignant peripheral nerve sheath tumor of the breast was rendered. The patient does not have a history of NF-1. There was no lympho-vascular or perineural invasion. After the surgery, the patient followed up without complications. Results (if a Case Study enter NA) N/A Conclusion An accurate diagnosis of this rare entity is necessary because it plays a crucial role in the therapeutic options and prognosis. In our case the patient was treated with neo-adjuvant chemotherapy followed by modified radical mastectomy. The purpose of presenting this unique case is to provide awareness of the existence of this entity among pathologists and clinicians for better patient care.

Vitamin D Levels in Newly Diagnosed Breast Cancer Patients according to Tumor Sub-Types

Vitamin D is an important regulator of bone health. In addition, as a ligand for a nuclear receptor expressed in breast cancer cells, vitamin D exerts neoplasia modulating effects in breast cancer. However, despite extensive investigations, associations of vitamin D levels with breast cancer patient characteristics and disease sub-types are conflicting. A retrospective review of medical records of consecutive breast cancer patients treated and followed in a single cancer center was undertaken. All patients with 25-hydroxyvitamin D (25-OHD, the circulating form of vitamin D) measurements available within 3 months of their diagnosis and before the start of any systemic treatment were included. Characteristics of patients and tumors with sufficient levels of 25-OHD were compared with those of patients with 25-OHD insufficiency. Two hundred ninety-two patients were included in the study. Almost two-thirds of the patients were 25-OHD insufficient, defined as having 25-OHD levels below 75 nmol/L. Compared with the group of patients who were 25-OHD sufficient, patients with 25-OHD insufficiency were younger and more often obese. Tumors of patients with 25-OHD insufficiency were more often ductal, of higher grade, and ER negative. 25-OHD insufficiency is prevalent in breast cancer patients and even more prevalent in younger and obese patients. 25-OHD insufficiency is associated with cancers that have aggressive characteristics, including higher grade and ER negativity.

Changes in Fractionation Schedules for Breast Cancer Treatment during the COVID-19 Pandemic

Purpose/Objective(s)In 2020, 5-year results of the FAST-Forward trial and 10-year results for both the FAST trial and APBI-IMRT-Florence trials using ultrahypofractionated radiation (UHFR) were all published, each detailing equivalent outcomes for partial and whole breast UHFR schedules compared to more conventional fractionation regimes in early-stage breast cancer. Due to concerns over viral exposure, these treatment regimens were adopted in an effort to minimize patient exposure while achieving equivalent oncologic control. The purpose of this study was to compare the use of UHFR schedules for breast cancer patients before COVID-19, at the height of the pandemic and after widespread vaccination and analyze factors predictive of use.Materials/MethodsBetween October 2019 and February 2022, 733 patients with stage 0 or I breast cancer were offered radiation at our institution following breast conserving surgery. 43 patients were excluded (35 declined radiation and 8 received partial breast re-irradiation). We analyzed target volume (whole vs partial breast) and fractionation schemes (1 week vs 3 or more weeks) for 3 time periods of interest: pre-COVID-19 (October 2019-March 2020), height of COVID-19 (March 2020-March 2021) and post-COVID-19 vaccine (March 2021-February 2022). Fisher's exact test was used to compare frequencies of treatment parameters across groups and time periods. Logistic regression was used to determine factors associated with UHFR use. R (v4.1.2) was used for analysis.ResultsThe use of UHFR increased during the post-vaccine period as compared to pre-Covid-19 and the pre-vaccine time periods (p<0.001), with 4.6%, 9.2% and 23%, receiving UHFR respectively. On univariate analysis in the pre-vaccine time period, patients with grade 2 and 3 cancers were less likely to get UHFR (p = 0.003 and p = 0.005, respectively). Receiving radiation from an academic attending was associated with higher use of UHFR (p = 0.0004). On multivariate (MVA) patients with grade 2 and 3 disease remained less likely to get UHFR (p 0.001 and 0.004). Treatment by an academic attending remained a significant factor for use of UHFR (p=0.0003). In the post-vaccine time period, on univariate analysis, negative ER status and grade 3 tumors were associated with less use of UHFR (p = 0.04 and p = 0.0001, respectively). On MVA, only grade 3 was associated with less UHFR use (p = 0.0002).ConclusionDuring COVID there was a significant increase in the use of UHFR regimens for treatment of early-stage breast cancer patients at our institution that persisted and increased after the introduction of the vaccine despite return to pre-COVID patient volumes. Uptake of these new regimens was initially higher among academic radiation oncologists, however with education of community physicians and implementation of treatment planning scorecards, widespread adoption was seen.

High rate of epidermal growth factor receptor-mutated primary lung cancer in patients with primary breast cancer.

BackgroundWith increased survival in breast cancer, resulting from advances in treatment, patients incur the possibility of subsequent primary malignancies, especially lung cancer. The aim of this study was to assess the frequency of CT-detected pulmonary ground-glass nodules and lung cancer following breast cancer diagnosis, the associations between breast cancer and lung cancer, the pathological features of double primary cancer, and the status of epidermal growth factor receptor (EGFR) mutations in second primary lung cancer.MethodsClinical data from more than 9000 individuals who were diagnosed with primary breast cancer at Jiangsu Province Hospital (Jiangsu, China) between January 2008 and December 2021 were retrospectively analyzed.ResultsOf the 9179 patients, 6512 underwent diagnostic CT, 55 (0.8%) were diagnosed with a second primary lung cancer, which accounted for approximately 18.4% of the pulmonary ground-glass nodules (GGNs) detected. The incidence was higher than in the general female population (standardized incidence ratio 1.4 [95% confidence interval (CI): 1.25-1.55]). Patients who experienced a second primary lung cancer exhibited a significantly higher rate of EGFR mutation (78.5%) than those with lung adenocarcinoma alone, with most exhibiting low-grade malignancy, older age, estrogen receptor negativity, low Ki67, and no lymph node metastasis.ConclusionsBreast cancer patients, especially those with low-grade malignancy, were at high risk for developing primary lung cancer. For isolated GGN in patients with high-risk factors, clinicians should insist on close follow-up. Furthermore, EGFR may play an important role in primary lung adenocarcinomas and breast cancer.

The value of potential immunohistochemical biomarkers and clinicopathological findings in predicting response to neoadjuvant chemotherapy in breast cancer.

Following neoadjuvant chemotherapy (NAC) in breast cancer (BC), complete treatment response is achieved in some patients, while treatment response is limited in others. Predicting non-responder patients can prevent exposure to adverse effects associated with chemotherapeutic agents and delays in selecting other treatment modalities. In this study, we aimed at identifying predictive factors related to tumor regression in patients with BC who received NAC. This single-center cohort included 91 patients with BC who underwent surgery following NAC based on pretreatment tumor biopsy. According to BC molecular subtype, tumor regression grade (TRG) was determined using the Miller-Payne scoring system in patients who received standard NAC. Immunohistochemical stainings for VEGFR3 and CD44 were applied to needle core biopsies obtained prior to NAC in these patients. Pathological complete response (pCR) was achieved in 20 patients (22%). In univariate analysis, high Ki-67 expression, ER negativity, and HER2 positivity were determined to be predictive factors of TRG (p < 0.05). In multivariate analysis, Ki-67 was the single independent predictor of TRG, with a 1.05-fold effect size. CD44 and VEGFR3 levels did not affect TRG or survival (p > 0.05). There was a significant difference in TRG according to molecular subtype of BC (p < 0.001). The treatment response was 5.5-fold higher in HER2-positive patients compared with HER2-negative patients. pCR rates were significantly higher in TNBC, HER2, and luminal HER2+ subtypes when compared with luminal HER2- subtype. Ki-67 >25% and ER negativity had a favorable effect on TRG after NAC. CD44 and VEGFR3 were not effective in predicting treatment response.

Meme kanseri hastaları için izotonik orantılı tehlike modeli

Aim: There are many survival analysis methods in oncological studies. Each model is used in different data structures. The isotonic proportional hazard model is a survival model among these methods. The use of isotonic models is proposed to evaluate the relationship between time to event outcome and monotonically increasing covariate in survival analysis. The aim of this study is to explain the theoretical properties and usage of isotonic models and demonstrate their application on an appropriate dataset.Methods: Data on breast cancer patients treated at Seoul National University Hospital was used to make the application of isotonic models. In the modeling of recurrence risk, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and proliferation marker (Ki-67) variables were considered as independent risk factors. The tumor size was included in the model as covariate. The isotonic proportional hazard model was used in modeling. Estimation of model coefficients was made by partial likelihood method. Results: The tumor size had monotone increasing effect on recurrence events. It was determined that the risk of recurrence increased 1.008 times as the value of Ki-67 increased. It has been observed that ER and PR negativity increase the risk, while HER2 positivity increases the risk.Conclusion: As a result, in cases where the covariate variable has a monotone increasing effect on the disease process, the isotonic regression model can be used by considering the relationships between the covariate and the event. Thus, the function that takes into account the monotone relationship between the covariate and the event will be included in the survival analysis.

Radiomics Nomogram: Prediction of 2-Year Disease-Free Survival in Young Age Breast Cancer.

Simple SummaryBreast cancer in young women under 40 years of age shows a poor prognosis, and its treatment is difficult due to premenopausal status and fertility preservation. The early prediction of prognosis of young age breast cancer would be helpful for planning treatment and postoperative surveillance. In this study, the radiomics-based nomogram for the prediction of recurrence shows good predictive ability, especially 2-year disease-free survival after surgery. Several radiomics features presumed to be unique imaging features of young age breast cancer were also observed: tumor homogeneity and tumor sphericity. As these radiomics features are quantitative parameters extracted through the texture analysis of breast MRI, they may reflect the information of tumors more objectively, such as the tumor microenvironment. Furthermore, these results will be the basis for identifying the unique biology of young age breast cancer through multi-omics studies such as radio-genomics.This study aimed to predict early breast cancer recurrence in women under 40 years of age using radiomics signature and clinicopathological information. We retrospectively investigated 155 patients under 40 years of age with invasive breast cancer who underwent MRI and surgery. Through stratified random sampling, 111 patients were assigned as the training set, and 44 were assigned as the validation set. Recurrence-associated factors were investigated based on recurrence within 5 years during the total follow-up period. A Rad-score was generated through texture analysis (3D slicer, ver. 4.8.0) of breast MRI using the least absolute shrinkage and selection operator Cox regression model. The Rad-score showed a significant association with disease-free survival (DFS) in the training set (p = 0.003) and validation set (p = 0.020) in the Kaplan–Meier analysis. The nomogram was generated through Cox proportional hazards models, and its predictive ability was validated. The nomogram included the Rad-score and estrogen receptor negativity as predictive factors and showed fair DFS predictive ability in both the training and validation sets (C-index 0.63, 95% CI 0.45–0.79). In conclusion, the Rad-score can predict the disease recurrence of invasive breast cancer in women under 40 years of age, and the Rad-score-based nomogram showed reasonably high DFS predictive ability, especially within 2 years of surgery.

COX-2 expression in mammary invasive micropapillary carcinoma is associated with prognostic factors and acts as a potential therapeutic target in comparative oncology.

Pure human and canine mammary invasive micropapillary carcinoma is a rare malignant epithelial tumor accounting for 0.9 to 2% of all invasive mammary carcinomas and present a high rate of lymphatic invasion and metastasis, with unfavorable prognosis. Surgery and chemotherapy are standard treatments for almost all mammary cancer in both species, as well as hormonal and target therapies available for human patients. However, depending on the patient's clinical staging, satisfactory therapeutic results for invasive micropapillary carcinoma are a challenge due to its high capacity of invasion and metastasis. Cyclooxygenase-2 (COX-2) isoform is an important enzyme stimulated by cytokines, growth factors and oncogenes activation to synthetizes prostaglandins in inflammatory process. COX-2 overexpression is associated with angiogenesis and invasion and contributes to cancer development, disease progression, tumor recurrence and regional lymph node metastasis in human and canine mammary carcinomas. This enzyme can be targeted by non-steroidal anti-inflammatory drugs and its inhibition can reduce tumor growth and metastasis in several cancer types. Given the similarity between both species, the present study aims to elucidate the involvement of COX-2 mRNA and protein expression in canine (cIMPC) and human (hIMPC) pure invasive mammary micropapillary carcinoma, with clinicopathological and survival data. Twenty-nine cases of cIMPC and 17 cases of hIMPC were analyzed regarding histologic type, grade, age, tumor size, lymph node condition, extracapsular extension, inflammatory infiltrate and immunophenotype. When available, information on adjuvant treatment, recurrence, metastasis and overall survival were collected. The present study demonstrated COX-2 protein expression in 65.5% of cIMPC and 92.3% of hIMPC, and an association with more advanced histological grades in bitches and higher Ki67 in women. COX-2 mRNA expression was significantly higher in cIMPC than in hIMPC, and its expression was not associated with COX-2 protein expression in both species. COX-2 mRNA expression was associated with negative-ER hIMPC as well as higher Ki67. cIMPC demonstrated proportional early development, more regional metastasis, and a prevalence of negative estrogen receptor, than hIMPC. This is the first time COX-2 expression is associated with negative prognostic factors in both cIMPC and hIMPC, besides the overexpression of COX-2 protein in such unfavorable histological type, which suggests that COX-2 can act as a potential target in IMPC.

1721P Hereditary component of HER2-positive breast cancer

In recent years, a greater number of germinal mutations that predispose to the development of tumors have been found. Understanding the interactions between mutations and breast cancer’s subtype is essential for opening new therapeutic and preventive strategies. It is well known what type of breast cancer develops in a hereditary syndrome context; however, the prevalence of HER2 positive tumors with some deleted mutation in genes predisposing to breast cancer, is still not entirely clear. This study aims to know the prevalence of HER2-positive tumors, either with positive or negative estrogen and/or progesterone receptors, associated with some germline mutation in a hereditary syndrome context. It is a descriptive and longitudinal study, with retrospective collection of data from patients diagnosed of HER2-positive breast cancer and positive or negative hormone receptors in the intercenter Clinical Management Unit of Medical Oncology. A total of 1,070 patients diagnosed with HER2-positive breast carcinoma were obtained. Of it, 189 (17.66%) patients underwent a genetic study, finding a germline mutation in 33 patients (3.08% of the global population and 17.46% of the population studied). The most frequent genes were BRCA 1 and 2, MUTYH and ATM. Breast cancer with overexpression of the HER2 protein and a germline mutation is rare, with an unknown true prevalence. It is associated with mutations in prevalent genes such as BRCA 1 and 2, but also with less frequent ones such as TP53. Prospectives studies are needed to elucidates which patients with HER2 positive breast cancer are better candidates for a germinal test.

Correlation of TBK1, AR, and other serum cancer-related biomarkers in breast cancer patients: An observational study.

Breast cancer (BC) ranks first for incidence and mortality in gynecological malignant tumors. This study aims to investigate the diagnostic value of Tank-binding kinase 1 (TBK1) and its correlation with androgen receptor (AR) and other serum cancer-related biomarkers in BC patient. The present observational study included 451 female BC patients and 451 healthy controls. Serum levels of TBK1, AR and other cancer-related biomarkers were detected in all the patients and healthy controls. Patients’ demographic data and clinical data including age, body mass index (BMI), tumor node Metastasis (TNM), pathological type, tumor size and lymph node metastasis were collected. The follow-up lasted for 5 years.The deceased group had higher rate of patients with TNM III~IV, lymph node metastasis or tumor diameter >2. Deceased group had much higher rate of patients with negative ER and positive Ki67. Besides, increased TBK1 was found in BC patients with positive correlation with AR, CA15-3, CA125, CEA, and CA19-9. Serum TBK1 was associated with the clinic outcomes of BC patients and those with high TBK1 had lower 5-year survival rate. Moreover, cutoff value of 13.95 ng/mL TBK1 showed AUC of 0.981 (93.6% for sensitivity and 86.3% for specificity) for diagnosing BC, and cutoff value of 22.65 ng/mL TBK1 had AUC of 0.996 (97.7% for sensitivity and 96.3% for specificity) for diagnosing the death of BC patients. Serum TBK1 was positively correlated with AR and other serum cancer-related biomarkers. In addition, high TBK1 predicted the poor prognosis and might be used for the diagnosis of BC.

Clinicopathological characteristics related to Miller/Payne grading system of breast carcinoma after neoadjuvant therapy and establishment of novel prediction models

Objective: To investigate the correlation between clinicopathological features and Miller/Payne (MP) grading system of breast carcinoma after neoadjuvant treatment and to establish novel prediction models. Methods: A total of 1 053 cases of invasive breast carcinoma NOS that undertaken neoadjuvant treatment according to Guidelines of CSCO for Breast Cancer were selected at the Key Laboratory of Carcinogenesis and Translational Research, Peking University Cancer Hospital & Institute from September 2016 to September 2019, and the clinical, pathologic data, MP grading and immunohistochemical staining were evaluated. Statistical analysis was conducted using R software. Several novel computer models on prediction of MP grading were established and validated. Results: Among 1 053 patients who accepted neoadjuvant treatment, 316 patients (316/1 053, 30%) were evaluated as MP5 postoperatively, and 737 patients (737/1 053, 70%) did not meet MP5 level. MP5 had significant association with histological grade, ER and PR expression, HER2 status, Ki-67 index and molecular classification (P<0.05). Univariate/multivariate logistic regression analyses further showed that the above clinicopathological features were also independent influencing factors of MP5 grade; five-fold cross-validation was used to evaluate the performance of the models, and the sensitivity and specificity of different models were obtained. Conclusions: MP grading of invasive breast carcinoma NOS after neoadjuvant treatment is associated with high histological grade, negative ER and PR expression, HER2 positivity, high Ki-67 index and molecular classification, which are independent influence factors. GBM model recommended through comparison can provide some help for clinical diagnosis and treatment.

Assessing Metabolic Risk Factors for LVSI in Endometrial Cancer: A Cross-Sectional Study.

ObjectiveThis study analyzed metabolic factors associated with lymphovascular space invasion (LVSI) and compared the difference between type 1 and type 2 endometrial cancer (EC).MethodsFour hundred patients primarily diagnosed with EC who underwent hysterectomy with pathological results at Fujian Medical University Cancer Hospital from January 2019 to January 2021 were included. Demographic variable data were collected as well as pathological results. Laboratory evaluations included fasting blood glucose (FBG), serum cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), apolipoprotein A (Apo A) and apolipoprotein B (Apo B). Characterization of binary logistic regression models was used to test the odds ratios (ORs) between LVSI and its metabolic parameters with different subtypes of EC.ResultsThe results indicated that CA125, ROMA, Ki67 score, FBG and TC were higher in EC patients with LVSI (all p<0.05). Negative ER and PR expression was positively associated with LVSI (P<0.05). CA125, ROMA, FBG, TC and ER were found to be independent risk factors for LVSI. CA125, ROMA and FBG were significantly elevated in type 1 EC patients with LVSI compared with those without LVSI (all p<0.05). TC and Ki67 scores were much higher in type 2 EC patients with vs without LVSI (all p<0.05). Negative PR expression was positively related to both type 1 and type 2 EC patients with LVSI. Consequently, CA125, ROMA, FBG and Apo B were found to be independent risk factors for LVSI in type 1 EC, and TC was found to be an independent risk factor for LVSI in type 2 EC.ConclusionFBG and TC were both independent risk factors for LVSI in EC. FBG and Apo B were independent risk factors for LVSI in type 1 EC. TC was an independent risk factor for LVSI in type 2 EC.

Factors associated with prolonged uterine ischemia time and impact on biomarker expression for patients undergoing surgical management of endometrial cancer (537)

<b>Objectives:</b> The College of American Pathologists recommends < 60 min of ischemia time (IT) for breast cancer specimens to preserve biomarker expression. Our institution implemented a quality improvement initiative in 2019 to limit IT for the uterus to < 60 min for patients undergoing surgery for endometrial cancer (EC) in order to optimize immunohistochemistry (IHC) detection of HER2, ER, PR, and Mismatch Repair (MMR) proteins. We sought to determine patient and surgical factors that influence IT and analyze the association between prolonged IT (≥ 60 min) and biomarker expression in EC specimens. <b>Methods:</b> This is a retrospective review of patients who had a hysterectomy for EC in a comprehensive cancer center from June 2019 to February 2021. Clinical, surgical, and pathologic data were abstracted from medical records. IT was defined as the time between uterine vessel ligation to tissue fixation in formalin. We compared demographic and clinical-pathologic features for patients whose uterine specimens had IT of < 60 min to those with prolonged IT (≥ 60 min). IHC results for HER2, ER, PR, and MMR proteins were also compared between the two groups. Categorical data were compared using Chisquare or Fisher's exact test. Table 1 <b>Results:</b> Two hundred ninety-nine patients underwent hysterectomy for EC with documented IT during the study period. Most patients had endometrioid histology preoperatively (68%), had FIGO stage IA (64%), and underwent minimally invasive surgery (97%). The average length of surgery was 144 min and the average IT was 41 min. Prolonged IT occurred in 37 (12.4%) cases. Demographic factors associated with prolonged IT included age < 50 (p=0.047) and African American race (p<0.001). Uterine weight (p<0.001), need for minilaparotomy (p<0.001), additional procedures performed (p=0.006), and length of surgery (p<0.001) were associated with prolonged IT (Table 1). Day of the week, time of day, trainee involvement, and surgeon were not associated with ischemia time. IHC for HER2, ER, and PR was performed on 10%, 11%, and 10% of specimens, respectively, whereas IHC for MMR proteins was performed in 98% of cases. Though not statistically significant, there was a trend noted toward negative ER expression on IHC in specimens with prolonged IT (p=0.056). There was no association between IT and expression of HER2 (p=0.508), PR (p=0.25), and MMR proteins (p=0.143-1). <b>Conclusions:</b> Approximately 12% of EC specimens had ischemia time > 60 min. Patient factors (age < 50, race) and surgical factors (need for mini-laparotomy, additional procedures, and length of surgery) were associated with prolonged ischemia time. We suspect this is primarily due to uterine size and surgical complexity, which are not modifiable. The potential impact of IT on IHC detection of HER2, ER, PR, and MMR merits further investigation.

Vaginal Estrogen Therapy for Vulvovaginal Atrophy in Women with a Personal History of Breast Cancer – A Claims Database Analysis

ABSTRACT Introduction Systemic therapies for breast cancer – selective estrogen receptor modulators (SERM), aromatase inhibitors (AI), oophorectomy, and chemotherapies – often result in vulvovaginal atrophy (VVA or atrophic vaginitis), in up to 70% of postmenopausal breast cancer survivors. While systemic estrogen therapy is often avoided in these patients, vaginal estrogen therapy is a safe treatment option that can be used to treat VVA symptoms in breast cancer survivors. Objective Our objective is to assess the use of vaginal estrogen for women with a diagnosis of VVA and a personal history of breast cancer using a large US claims database. Methods The TriNetX Diamond network database was queried: a US health research network of 190 million patients, encompassing healthcare encounters and prescriptions between 2009-2021. Females with a diagnosis of postmenopausal atrophic vaginitis or atrophy of the vulva (ICD-10 N95.2, N90.5) were included. Of these, women with breast cancer (C50 or Z86.000) were included if the diagnosis was at least 1 month prior to VVA diagnosis. Estrogen receptor status was collected when available (ICD-10 Z17.0, Z17.1). Prescriptions for treatment of VVA were included if prescribed within 1 year of VVA diagnosis. Incidence of vaginal estrogen use in patients with a history of breast cancer was determined for 2013-2015, 2016-2018, and 2019 to present. Results A total of 2,159,766 women with VVA were identified; of whom, 4.8% (n=104,327) had a personal history of breast cancer.Vaginal estrogen prescriptions were less frequent prescribed to women with history of breast cancer compared to women without (11% vs 22%, p&amp;lt;0.01, Table 1). Incidence rate of vaginal estrogen prescriptions for women with VVA and history of breast cancer remained stable around 10-11% from 2013 to present. 25,410 women with VVA and history of breast cancer had positive estrogen receptor status (ER+) and 4,893 had negative estrogen receptor status (ER-). There was no difference in vaginal estrogen prescribing between ER+ and ER- patients (7.4% vs 8.4%). Conclusions While vaginal estrogen can be safely used in women with VVA and personal history of breast cancer, it is prescribed for few eligible patients. Barriers to prescribing and using vaginal estrogen in this population should be explored, in order to significantly improve quality of life for those living with vulvovaginal atrophy. Disclosure No

Correlation of magnetic resonance imaging quantitative parameters and apparent diffusion coefficient value with pathological breast cancer.

BACKGROUNDChina ranks 120th worldwide for the incidence of breast cancer and 163rd for mortality. Early screening, diagnosis, and timely determination of the optimal treatment plan can help ensure clinical efficacy and prognosis.AIMTo investigate the relationship between quantitative magnetic resonance imaging parameters, apparent diffusion coefficient value, pathological immunohistochemical status, and patient prognosis.METHODSA total of 108 patients with breast cancer (breast cancer group) and 110 patients with benign breast tumors (benign group) confirmed by pathological examination at our Hospital from September 2013 to August 2016 were selected. All patients had undergone preoperative magnetic resonance imaging (MRI) examinations, and the quantitative parameters of MRI and apparent diffusion coefficient (ADC) values for the two groups were compared. The MRI quantitative parameters and ADC values of patients with different estrogen receptor (ER), progesterone receptor, and human epidermal growth factor receptor-2 expression were statistically analyzed. The relationship between the quantitative parameters of MRI and ADC values and patient recurrence was analyzed using receiver operating curves.RESULTSThe measured values of the quantitative parameters of MRI- Ktrans, Kep, and Ve in the breast cancer group were higher than those in the benign group; the ADC value in the breast cancer group was lower than that in the benign group, and the difference was statistically significant (P < 0.05). The Ktrans, Ve, and ADC values in patients with ER-positive breast cancer were significantly lower than those in patients with negative ER expression (P < 0.05). After 5 years of follow-up, 22 patients with breast cancer experienced postoperative recurrence. The Kep, Ve, and ADC values of the recurrence group were significantly lower than those of the non-recurrence group, and the difference was statistically significant (P < 0.05). CONCLUSIONMRI quantitative parameters and ADC are related to the expression of breast cancer-related immunological receptor factors and have certain clinical value in assessing postoperative recurrence in patients.

Sub-Classification of Triple-Negative Breast Cancer using Androgen Receptor and Cytokeratin 5/6

Background: Triple negative breast cancer (TNBC) is a unique heterogenous subtypes of breast cancer which is characterized by negative estrogen, progesterone, and human epidermal growth factor receptor (HER-2) status. TNBC displays different molecular phenotype with which basal-like tumour can be identified using high molecular weight basal cytokeratin 5/6 (CK5/6).&#x0D; Methods: Ninety-five (95) formalin fixed cases from Korle Bu Teaching Hospital in Ghana’s (KBTH) archives were sampled in a retrospective study from 2012-2016. Blocks of these triple-negative breast cancer was subclassified using CK5/6 and Androgen Receptor (AR) antibodies. Subclasses were also identified.&#x0D; Results and Conclusion: In all ninety-five (95) TNBC cases, hormonal subtyping was sub-classified using CK 5/6 and AR. The mean ±SD of these cases was recorded as 53.96 (±13.56) years and the age range of these cases was 22-104 years. The average size (±SD) of the tumour was recorded to be 14.43(±7.62) and it had a range of 2.4-45cm. lymph nodes retrieved also had a mean ± SD of 10.35(±6.05) with an average tumour lymph nodes involvement of 2.6(± 3.697).&#x0D; Invasive Ductal carcinoma was identified as the commonest histologic type of TNBC with approximately 95% of the cases. This was followed by invasive lobular (2.1%), medullary carcinoma (2.1%) and metaplastic carcinoma (1.1%).&#x0D; Approximately 30% of TNBC stained positive for CK5/6.&#x0D; It can however be concluded that, most TNBC are not basal-like when the basal marker CK5/6 is used.

Microinvasive breast cancer and the role of sentinel lymph node biopsy

Whether sentinel lymph node biopsy (SLNB) should be performed in patients with microinvasive breast cancer (MIBC) has been a matter of debate over the last decade. MIBC has a favorable prognosis and while metastasis to the axilla is rare, it can impact treatment recommendations. In this study we evaluated clinical and histological features in both MIBC and background DCIS including ER, PR, and HER-2, number of foci of MIBC, the extent of the DCIS, nuclear grade, presence of comedo necrosis, as well as surgical procedures, adjuvant treatment and follow up to identify variables which predict disease free survival (DFS), as well as the factors which influence clinical decision making. Our study included 72 MIBC patients with a mean patient follow-up time of 55 months. Three patients with MIBC had recurrence, and two deceased, leaving five patients in total with poor long-term outcomes and a DFS rate of 93.1%. Performing mastectomy, high nuclear grade, and negativity for ER and HER-2 were found to be associated with the use of SLNB, although none of these variables were found to be associated with DFS. One positive lymph node case was discovered following SLNB in our study. This suggests the use of SLNB may provide diagnostic information to some patients, although these are the anomalies. When comparing patients who had undergone SLNB to those which had not there was no difference in DFS. Certainly, the use of SLNB in MIBC is quite the conundrum. It is important to acknowledge that surgical complications have been reported, and traditional metrics used for risk assessment in invasive breast cancer may not hold true in the setting of microinvasion.

Menopoz Durumunun Moleküler Meme Kanseri Alt Tipleri İle İlişkisi.

Objective&#x0D; Breast cancer is a heterogeneous disease group that exhibits quite different biological behaviors and bear many genomic traces. Its dependence on sex hormones also determines its relationship with menopausal status. It is divided into five molecular subtypes according to receptor analysis and Ki67 level with immunohistochemical (IHC) markers. This study aimed to examine the relationship between the menopausal status and these molecular subtypes to help determine our treatment strategies.&#x0D; Material and Method&#x0D; The database of 250 patients who were operated on for breast cancer in our Oncology Clinic between 2012 and 2020 was retrospectively analyzed. The patients were grouped by their menopausal status and clinicopathological characteristics. Statistical analysis was made at a 95% confidence interval, and a p-value lower than 0.05 was considered statistically significant.&#x0D; Results &#x0D; The patients were divided into 2 groups by their menopausal status as 44.8% (n = 112) as premenopausal and 65.2% (n=138) as postmenopausal. In the statistical analysis performed, the level of Ki67 was high in premenopausal women (p=0.015). Also, tumors seen in premenopausal women were associated with ER negativity (p=0.024) and high histological grade (grade3) (p=0.015). It was found that luminal subtype (luminal A, luminal B) breast cancers were observed more frequently in postmenopausal women and non-luminal subtypes (HER2+, TNBC) were observed more frequently in premenopausal women.&#x0D; Conclusion&#x0D; The genomic complexity that will determine personalized treatment strategies soon remains to be clarified. There is still a need for randomized, prospective, multidisciplinary, and population-based studies to help us understand this unknown nature.