Non-metastatic Breast Cancer Patients Research Articles

Influence of adjuvant radiotherapy on circulating epithelial tumor cells and circulating cancer stem cells in primary non-metastatic breast cancer

Background: There is an unmet need to identify biomarkers that directly reflect response to adjuvant radiotherapy (RT). Circulating epithelial tumor cells (CETCs) represent the liquid component of solid tumors and are responsible for metastatic relapse. CETC subsets with cancer stem cell characteristics, circulating cancer stem cells (cCSCs), play a pivotal role in the metastatic cascade. Monitoring the most aggressive subpopulation of CETCs could reflect the aggressiveness of the remaining tumor burden. There is limited data on the detection and monitoring changes in CETC and cCSC numbers during RT in early breast cancer. Methods: CETC numbers were analyzed prior to, at midterm and at the end of RT in 52 primary non-metastatic breast cancer patients. Hormone receptor status was determined in CETCs prior to and at the end of RT. For the identification of cCSCs cell suspensions from the peripheral blood of patients were cultured in vitro under conditions favoring growth of tumorspheres. Results: Hormone receptor status in CETCs before RT was comparable to that in primary tumor tissue. Prior to RT numbers of CETCs correlated with aggressiveness of primary tumors. cCSCs could be successfully identified and monitored during RT. Prior to RT patients treated with neoadjuvant chemotherapy had significantly higher numbers of CETCs and tumorspheres compared to patients after adjuvant chemotherapy. During RT, the number of CETCs decreased continuously in patients after neoadjuvant chemotherapy but not after adjuvant chemotherapy. Conclusion: Monitoring the number of CETCs and the CETC subset with cancer stem cell properties during RT may provide additional clinically useful prognostic information.

An individualized food-based nutrition intervention reduces visceral and total body fat while preserving skeletal muscle mass in breast cancer patients under antineoplastic treatment

Breast cancer patients (BCP) during treatment often experience an increase in body weight and fat mass, and a decrease in muscle mass known as sarcopenic obesity, affecting their prognosis and quality of life. We aimed to evaluate the effect of a 6-month individualized food-based nutrition intervention program in nonmetastatic BCP body composition during treatment. This is a pre-post study in recently diagnosed women with invasive ductal/lobular breast carcinoma (clinical stage I-III). The individualized nutrition intervention was based on the dynamic macronutrient meal equivalent menu method (MEM). Dietary plans were developed according to WCRF/AICR guidelines, BCP total energy expenditure, 1.2-1.5g/kgBW/d of protein intake, 5-9 servings/day of fruits and vegetables, and a caloric restriction (500-1000kcal/d) when applicable (BMI≥25kg/m2). Follow-up was every 2-weeks and a different diet menu was provided in each session during 6 months. Baseline and final measurements included the assessment of anthropometry, body composition, and physical activity. Twenty-two participants completed the study and at diagnosis 68% were overweighed or obese. After the 6-month nutrition intervention program, BCP lost 3.1kg (p<0.01) of body weight, 2.7kg (p<0.01) of fat-mass, 400g (p<0.01) of abdominal fat, 118g (p<0.05) of visceral fat, 1.2kg/m2 of body mass index and 1.1kg/m2 of fat mass index (p<0.01). During the period, no changes were observed in bone mineral density (p=0.3), fat-free mass (p=0.1) and appendicular skeletal muscle mass (p=0.2). Menopausal status in BCP did not modify the effect of the nutrition intervention. The individualized food-based nutrition intervention program empowered BCP to make informed healthy food choices within their personal preferences, socioeconomic and cultural background. With this type of intervention, nonmetastatic BCP reduced body weight, fat-mass, fat mass index, visceral and abdominal fat, while preserving skeletal muscle mass, during antineoplastic treatment. ClinicalTrials.govNCT03625635.

CTCs-oriented adjuvant personalized cytostatic therapy non-metastatic breast cancer patients: continuous non-randomized prospective study and prospective randomized controlled study

The aimTo conduct a prospective randomized controlled study of the optimization of adjuvant therapy in patients with non-metastatic breast cancer, taking into account the presence of circulating tumor cells (CTCs) with an assessment of tumor-specific OS and DFS.MaterialsStage 1 Continuous non-randomized prospective study (n = 102) to study the clinical and prognostic value of CTCs and evaluate the effectiveness of adjuvant systemic therapy in relation to CTC eradication; Stage 2 Prospective randomized controlled study (n = 128) of optimization of adjuvant therapy taking into account CTCs with an assessment of the effectiveness of the standard therapy and an optimized therapy regimen.ResultsMonitoring of CTCs during adjuvant drug treatment has established that a significant decrease in the frequency of CTC identification can be achieved only by sequential administration of anthracyclines and taxanes (paclitaxel) AC-T, which allows reducing CTCs compared to other regimens from 52.6 to 15.8% (p = 0.006).CTC-oriented personalized adjuvant therapy in the experimental group, based on the timely transition from an ineffective adjuvant chemotherapy regimen to taxanes, as well as additional monochemotherapy with gemcitabine can achieve 100% eradication CTCs. In the adjuvant therapy experimental group taking into account CTCs (n = 68), the OS 5-year tumor-specific rate was 90.3 ± 3.8%, (control group 78.7 ± 3.9%, p = 0.036). DFS tumor-specific in the experimental group was 88.0 ± 4.4%, (control group 80.6 ± 3.3%, p = 0.023).ConclusionsThe use of the method of treatment of CTC-oriented personalized adjuvant therapy for non-metastatic breast cancer makes it possible to reliably increase DFS 5-year by 7.4% and OS 5-year by 11.6%.

Obesity and high neutrophil-to-lymphocyte ratio are prognostic factors in non-metastatic breast cancer patients.

Obesity has been associated with an increased risk of breast cancer recurrence and death. Some readily available biomarkers associated with systemic inflammation have been receiving attention as potential prognostic indicators in cancer, including neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). This study aimed to explore the correlation between body mass index (BMI) and invasive breast cancer and the association of NLR, PLR, and BMI with breast cancer outcomes. We undertook a retrospective study to evaluate patients treated for breast cancer over 14 years. Clinicopathological data was obtained before receiving any treatment. Of the 1664 patients included with stage I-III, 567 (34%) were obese (BMI≥30 kg/m2). Obese patients had larger tumors compared to non-obese patients. Higher BMI was associated with recurrence and worse survival only in patients with stage I disease. NLR and PLR were classified into high and low level groups. The NLRhigh (NLR>4) was found to be an independent prognostic factor for recurrence and mortality, while the PLRhigh (PLR>150) group had no impact on survival. A subgroup of patients with NLRhigh and BMIhigh had the worst disease-free survival (P=0.046), breast cancer-specific survival (P<0.001), and overall survival (P=0.006), compared to the other groups. Patients with early-stage breast cancer bearing NLRhigh and BMIhigh had worse outcomes, and this might be explained by the dysfunctional milieu of obesity in adipose tissue and its effects on the immune system. This study highlights the importance of lifestyle measures and the immune system interference with clinical outcomes in the early breast cancer setting.

Fatty Liver in Hormone Receptor-Positive Breast Cancer and Its Impact on Patient's Survival.

PurposeLong-term estrogen inhibition may cause fatty liver disease (non-alcoholic fatty liver disease; NAFLD) among other adverse conditions such as osteoporosis, climacteric symptoms, thromboembolism, dyslipidemia, and metabolic syndrome. The prevalence of NAFLD among breast cancer patients ranges from 2.3%–45.2%. This study aimed to determine the risk factors for newly developed NAFLD among breast cancer patients after hormonal treatment and whether it influences survival outcomes.MethodsThis retrospective study investigated hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative (HR+/HER2−), nonmetastatic breast cancer patients diagnosed between January 2010 and December 2018. All patients received adjuvant hormonal treatment for at least 6 months. Clinical data on metabolic profile indicators such as body mass index (BMI), waist circumference, serum cholesterol, triglycerides, low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), diabetes, and presence of metabolic syndrome (MetS) were collected. In total, 160 eligible patients with complete covariate data and survival follow-up were included.ResultsNAFLD was diagnosed in 35% of patients. There were significant associations of being overweight (BMI ≥ 25 kg/m2), waist circumference > 80 cm, triglycerides ≥ 150 mg/dL, HDL-C ≤ 50 mg/dL, LDL-C < 150 mg/dL, and presence of MetS with the development of NAFLD. However, unlike other factors, MetS and HDL-C were not independently associated with NAFLD. Patients with breast cancer who developed NAFLD had longer disease-free survival (DFS). The median DFS was not reached in the NAFLD group, whereas it was 59.3 (45.6–73.0) months in the non-NAFLD group. No worsening of overall survival was observed in patients with breast cancer and NAFLD.ConclusionThe development of NAFLD during treatment in patients with HR+/HER2− breast cancer was associated with several independent risk factors: being overweight, waist circumference, triglycerides, and LDL-C. Interestingly, breast cancer patients with NAFLD during treatment had longer DFS than those without NAFLD.

Analysis of the serial circulating tumor cell count during neoadjuvant chemotherapy in breast cancer patients

We evaluated the prognostic implications of the circulating tumor cell (CTC) count in non-metastatic, HER2-negative breast cancer patients who failed to achieve pathologic complete response (pCR) after neoadjuvant chemotherapy (NCT). A total of 173, non-metastatic breast cancer patients treated with NCT were prospectively enrolled. CTCs were obtained from blood drawn pre-NCT and post-NCT using a SMART BIOPSY SYSTEM isolation kit (Cytogen Inc., Seoul, Korea) with immunofluorescence staining. Excluding 26 HER2-positive patients, Relapse-free survival (RFS) and overall survival (OS) related to the CTC count and the association of the CTC count with the treatment response to given therapy were analyzed in 147 HER2-negative patients. Among 147 HER2-negative patients, 28 relapses (19.0%) and 13 deaths (8.8%, all breast cancer-specific) were observed during a median follow-up of 37.3 months. One hundred and seven patients (72.8%) were hormone receptor-positive, and 40 patients (27.2%) had triple-negative breast cancer (TNBC). One or more CTCs were identified in 88 of the 147 patients (59.9%) before NCT and 77 of the 134 patients (52.4%) after NCT. In the entire HER2-negative patient cohort, the initial nodal status was the most significant factor influencing RFS and OS. In TNBC, 11 patients (27.5%) achieved pCR and patients that failed to achieve pCR with ≥ 5 CTCs after NCT, showed worse RFS (HR, 10.66; 95% CI, 1.80–63.07; p = 0.009) and OS (HR, 14.00; 95% CI, 1.26–155.53; p = 0.032). The patients with residual tumor and a high number of the CTCs after NCT displayed the worse outcome. These findings could provide justification to launch a future, well designed trial with longer follow-up data to obtain regulatory approval for clinical use of the assay, especially for the ER-positive, HER2-negative breast cancer subset.

Circulating Tumor Cells Expressing the Prostate Specific Membrane Antigen (PSMA) Indicate Worse Outcome in Primary, Non-Metastatic Triple-Negative Breast Cancer.

Background: We analyzed mRNA profiles of prostate cancer related genes in circulating tumor cells (CTCs) of primary, non-metastatic triple-negative breast cancer (TNBC) patients (pts) before and after neoadjuvant chemotherapy to elucidate the potential of prostate cancer targets in this BC subgroup.Method: Blood from 41 TNBC pts (n = 41 before / 26 after therapy) was analyzed for CTCs applying the AdnaTest EMT-2/Stem Cell Select. Multimarker RT-qPCR allowed the detection of the prostate specific antigen PSA, the prostate specific membrane antigen PSMA, full-length androgen receptor (AR-FL), and AR splice-variant seven (AR-V7).Results: Before therapy, at least one prostate cancer related gene was detected in 15/41 pts (37%). Notably, in 73% of AR-FL positive cases, AR-V7 was co-expressed. After therapy, CTCs of only one patient harbored prostate cancer related genes. AR-V7+ and PSMA+ CTCs significantly correlated with early relapse (p = 0.041; p = 0.00039) whereas PSMA+ CTCs also associated with a reduced OS (p = 0.0059). This correlation was confirmed for PSMA+ CTCs in univariate (PFS p = 0.002; OS p = 0.015), but not multivariate analysis.Conclusion: Although CTCs that expressed prostate cancer related genes were eliminated by the given therapy, PSMA+ CTCs significantly identified pts at high risk for relapse. Furthermore, AR inhibition, often discussed for this BC subgroup, might not be successful in the primary setting of the disease since we identified AR-FL+ CTCs together with AR-V7+ CTCs, associated with therapeutic failure.

265P Circulating PIK3CA mutation detection at diagnosis in non-metastatic inflammatory breast cancer patients

265P Circulating PIK3CA mutation detection at diagnosis in non-metastatic inflammatory breast cancer patients

Clinicopathologic Features and Survival Analysis of Non-metastatic Breast Cancer Patients in Guatemala

Background: Breast cancer (BC) is a leading cause of cancer related death worldwide. Unfortunately, data concerning clinicopathologic features of this malignancy in non-developed countries is scarce. This study aims to characterize a cohort of Guatemalan female patients with non-metastatic BC and to determine risk factors for overall survival (OS).Methods: We retrieved data on consecutive patients from the Instituto Guatemalteco de Seguridad Social that were treated from 2008 to 2014. Clinical features and long-term outcomes were retrieved from medical records. Univariate and multivariate Cox regression analyses were conducted to identify variables associated with OS. Results: 954 BC patients were identified during the time frame. A total of 436 women (46%) were younger than 50 years old. BC molecular subtypes categorized 537 patients (56.3%) with luminal A disease, 186 (19.5%) patients with triple negative tumors, 153 cases (16.1%) with HER-2 enriched tumors, and 78 patients (8.2%) with luminal B tumors. Clinical stage at presentation was stage I: 4.7% (n=45); stage II: 48.1% (n=459), and stage III: 47.2% (n=450). The overall 5-year survival rate was 75.2% (95% Confidence Interval: 72.0–78.3). In the multivariate analysis clinical stage, triple negative tumors and HER2 enriched tumors were independently associated with poor survival.Conclusion: The majority of patients with non-metastatic BC are diagnosed with advanced disease and many of them are younger than 50 years old. OS in this cohort of Guatemalan patients is lower than that reported in developed countries.

From Multiple Quality Indicators of Breast Cancer Care Toward Hospital Variation of a Summary Measure

To improve quality in breast cancer care, large numbers of quality indicators are collected per hospital, but benchmarking remains complex. We aimed to assess the validity of indicators, develop a textbook outcome summary measure, and compare case-mix adjusted hospital performance. From a nationwide population-based registry, all 79 690 nonmetastatic breast cancer patients surgically treated between 2011 and 2016 in 91 hospitals in The Netherlands were included. Twenty-one indicators were calculated and their construct validity tested by Spearman's rho. Between-hospital variation was expressed by interquartile range (IQR), and all valid indicators were included in the summary measure. Standardized scores (observed/expected based on case mix) were calculated as above (>100) or below (<100) expected. The textbook outcome was presented as a continuous and all-or-none score. The size of between-hospital variation varied between indicators. Sixteen (76%) of 21 quality indicators showed construct validity, and 13 were included in the summary measure after excluding redundant indicators that showed collinearity with others owing to strong construct validity. The median all-or-none textbook outcome score was 49% (IQR 42%-54%) before and 49% (IQR 48%-51%) after case-mix adjustment. From the total of 91 hospitals, 3 hospitals were positive (3%) and 9 (10%) were negative outliers. The textbook outcome summary measure showed discriminative ability when hospital performance was presented as an all-or-none score. Although indicator scores and outlier hospitals should always be interpreted cautiously, the summary measure presented here has the potential to improve Dutch breast cancer quality indicator efforts and could be implemented to further test its validity, feasibility, and usefulness.

Epidemiology, Pattern of Recurrence and Survival in Triple-negative Breast Cancer

Background: Breast cancer is the most common cancer in the world. Triple-negative breast cancer (TNBC) characterized by the absence of estrogen receptor (ER), progesterone receptor (PR), and Her2neu receptor. This study investigated the epidemiological characteristics and survival in non-metastatic TNBC. Materials and methods: Data from medical records of patients with breast cancer between 20014 and 2018 were retrieved, and patients with TNBC were identified and analyzed for demographic and clinicopathological features. Survival analyses were performed using the Kaplan–Meier method for disease-free survival (DFS) and overall survival (OS). Results: A total of 457 nonmetastatic breast cancer patients were registered at our institute from January 2014 to August 2018, of which 137 were triple-negative breast cancer (TNBC). This accounted for 29.9% of nonmetastatic breast cancer during this period. With the median age of 45 years at diagnosis, the most common presenting complaint was breast lump. The median duration of symptoms was 30 months. The most commonly affected age group was 41-50 years. The majority of the patients were in a locally advanced stage (69.3%) while 30.7% were in the early stage. 29.2% recurrence at 38 months of median follow up. Recurrence was statistically significantly correlating with age ≤ 35 (p= &lt; 0.001), pathological stage (p= &lt; 0.001), nodal status at diagnosis (p= &lt; 0.001), perineural invasion (PNI) (p= &lt; 0.001), number of positive lymph nodes (p= &lt; 0.001). The mean DFS and OS were 43.6 and 46 months respectively. 3-year DFS and OS were 65.5% and 66.2 % respectively. Conclusion: TNBCs are high-grade tumors mostly presented in locally advanced stages and most of the patients are young. TNBCs are clinically aggressive with high risk of metastasis to visceral organs. The survival of TNBCs in the Indian scenario is poor in comparison to Western populations, probably due to racial factors, socioeconomic factors and health care access facility. &#x0D;

Relative dose intensity and pathologic response rates in HIV-infected and HIV-uninfected breast cancer patients who received neoadjuvant chemotherapy.

e19140 Background: HIV-infected (HIV+) breast cancer patients may have significantly worse survival compared to HIV-uninfected (HIV-). If so, identifying the underlying mechanism might lead to effective interventions to reduce the disparity. Relative dose intensity (RDI) &lt; 0.85 has been associated with worse survival outcomes in non-metastatic breast cancer patients. We aimed to determine if RDI of chemotherapy and pathologic complete response (pCR) rates were lower for HIV+ patients who received neoadjuvant chemotherapy (NAC) compared with HIV-. Methods: We conducted a prospective cohort study in newly diagnosed breast cancer patients with locally advanced disease who initiated NAC at Princess Marina Hospital in Botswana between 2/2017 and 9/2019. Clinical and treatment data were collected at baseline and at every treatment visit. Surgical pathology post-NAC was graded as pCR if there was no invasive disease in the breast or lymph nodes. RDI was calculated for each patient, with optimal RDI ≥ 0.85. Dichotomous variables were compared using Fisher’s exact and chi-squared tests; and continuous variables using rank sum tests. Results: 111 patients were enrolled, of whom 84 (75.7%) were HIV-, 26 (23.4%) HIV+ and 1 (0.9%) with unknown status who was excluded from final analysis. HIV+ patients were less likely to receive optimal RDI (0.74 vs. 0.88; p = 0.03). Of the 110 patients 15 (13.6%) were still receiving chemotherapy; 22 (20%) prematurely discontinued chemotherapy of whom 11 (10%) received surgery; 7 (6.4%) completed chemotherapy but had no surgery. 77 (70%) completed surgery which included 11 (10%) with no pathology reports available, 3 (2.7%) inadequate surgical specimens and 63 (57.3%) complete pathology results included in pCR analysis: 1/13 (7.7%) HIV+ patients had a pCR compared to 12/50 (24%) in HIV-(p = 0.27). Conclusions: HIV+ patients were significantly more likely to receive inadequate neoadjuvant chemotherapy dose intensity, and trended towards a lower pCR in this small cohort, which may contribute to adverse treatment outcomes. Further study needed to validate high rate of treatment discontinuation and specific risk factors to inform targeted interventions to improve therapy delivery.

Correlation of hormonal receptor level and survival outcome in HER2-positive nonmetastatic breast cancer.

e12568 Background: In human epidermal growth factor 2 (HER2)-positive breast cancer, emerging evidences imply that clinical behavior and prognosis differ according to hormone receptor (HR) status. However, there is no conclusion about the relevance between estrogen receptor (ER) or progesterone receptor (PR) expression and clinical outcome of HER2-positive breast cancer. Our study is designed to determine the effect of different ER/PR levels on survival benefit of HER2-positive early breast cancer. Methods: 984 non-metastatic HER2-positive breast cancer patients between January 2009 and December 2016 were retrospectively reviewed and HR+/HER2+ patients were further classified into several subgroups based on ER expression level (Low/L: 1-9%; Median/M: 10-74%; High/H: 75-100%) and PR expression level (Low/L: 0-19%; High/H: 20%-100%). Clinical features and survival outcomes were evaluated. Results: A total of 461 HR+/HER2+ and 523 HR-/HER2+ breast cancer patients were included in our study and 69.8% of them received target therapy (HR+ 67.5%, HR- 71.9%). While HR+/HER2+ breast cancer showed better survival than HR-/HER2+ subtype in 5-year disease free survival (DFS, 92.6% vs 87.6%, p = 0.002), no significant difference was observed between 5-year DFS rates in ER+/PR+ and ER+/PR- subgroup (94.3% vs 89.7%, p = 0.150). However, a possible correlation was found between ER/PR levels and DFS both in HR+/HER2+ (p = 0.057) and all HER2+ (p &lt; 0.001) breast cancer. In HR+/HER2+ breast cancer, all subgroups showed DFS improvement trend versus M-ER/L-PR patients and hazard ratio of H-ER/H-PR subtype had a statistical difference (0.36, 95%CI 0.13-0.99, p = 0.047). In all HER2+ patients, hazard ratio of H-ER/H-PR compared with HR- subtype was 0.32 (95% CI, 0.13-0.80, p = 0.015). M-ER/L-PR presented similar DFS outcome with HR- subtype in our study. Conclusions: ER/PR expression may become a predictor of survival benefit in HER2-positive non-metastatic breast cancer and a higher ER/PR expression level might be associated with better DFS.

Association between obesity and the clinical stage of newly diagnosed breast cancer: Experience with 2212 patients.

e12602 Background: Excess weight is currently recognized as a risk factor for several cancer types, including breast cancer. The primary goal of this study was to evaluate the impact of overweight and obesity in newly diagnosed breast cancer patients at the time of presentation. Methods: A retrospective analysis of breast cancer from a prospective database of all newly diagnosed non-metastatic breast cancer patients seen at King Faisal Specialist Hospital and Research Center between 2002 and 2014 was performed. The clinical stages were divided into early stage breast cancer and locally advanced breast cancer. The body mass index (BMI) groups were underweight, normal, overweight, and obese based on the World Health Organization classifications of BMI. The patient characteristics are presented as medians with interquartile ranges (IQRs) and frequencies for continuous and categorical variables, respectively. The association between BMI groups and clinical stage at presentation was evaluated using the logistic regression model. Survival probabilities were calculated using the Kaplan-Meier estimator. Results: In total, 2212 patients were eligible for the study. The median age at diagnosis was 45 (IQR = 39-52) years; 62% patients were pre-menopausal, and 31% were post-menopausal. The median BMI was 30 (IQR = 26-34) kg/m2. In this population, 53% patients were obese; 31%, overweight; and 14.7%, in the normal range at diagnosis. Regression analysis revealed a significant association between clinical stage and BMI at the time of presentation (p = 0.006). Obese patients showed a 40% higher chance of having locally advanced presentation than the normal BMI group (OR = 1.41, 95% confidence interval = 1.06-1.86, p = 0.02). However, overweight had no significant association with clinical stage (OR = 1.03, 95% confidence interval = 0.76-1.8). The median follow-up duration was 39 (IQR = 22-66.6) months. Overall survival showed no significant association with different BMI groups and breast cancer subtypes. Conclusions: The prevalence of overweight and obesity was found to be high (85%) in newly diagnosed breast cancer patients in Saudi Arabia. Obesity is associated with a more advanced clinical stage at the time of diagnosis of breast cancer and may be a contributing factor for more locally advanced presentations in the region.

N-terminal pro-brain natriuretic peptide levels after receipt of anthracycline for breast cancer.

e24103 Background: Many of the 200,000 patients diagnosed with breast cancer (BC) annually in the United States receive anthracycline-based therapy, increasing their risk of future congestive heart failure. N-terminal brain natriuretic peptide (NT-proBNP) has been used as a biomarker of asymptomatic cardiac dysfunction in the general population and is of interest to identify patients who might benefit from echocardiography during survivorship. This study aimed to assess how age, baseline comorbidities, and time since BC diagnosis impact NT-proBNP levels after anthracycline-based chemotherapy. Methods: This retrospective study, using samples collected in our ongoing prospective Mayo Clinic Breast Disease Registry, included 20 survivors of non-metastatic BC patients per year for each of the first 5 years after anthracycline-based chemotherapy (n=100 total). NT-pro-BNP levels were assessed using a Roche immunoassay. Cardiac risk factors were obtained by chart review. Multivariable linear regression models assessed associations between NT-proBNP values and these independent variables: baseline cardiac risk factors (including hypertension, hyperlipidemia, obesity, diabetes mellitus, and smoking), tumor ER status (surrogate for possible endocrine therapy), time between diagnosis and serum collection, T and N status, use of trastuzumab, and age. Results: The mean age at the time of BC diagnosis was 52.2 (SD 9.8). 13% of tumors were human epidermal growth factor receptor (HER2)-positive and 71% were estrogen receptor (ER) positive. NT-proBNP was elevated in 34%. Mean NT-BNP level was higher (p=0.047) for those in years 4-5 (158 pg/mL) compared to those in years 1-3 (106 pg/mL) (See Table.) Models revealed years from diagnosis to serum draw (p=0.026), older age (p=0.006), more cardiac risk factors (p=0.064), and N2-3 (p=0.001) were associated with elevated NT-pro-BNP level. Use of trastuzumab, ER status, and tumor size were not associated with NT-proBNP. Conclusions: NT-proBNP is elevated in 1/3 of survivors who received anthracycline therapy for BC. As expected, cardiac risk factors and advancing age are associated with higher NT-proBNP. NT-proBNP values &gt;300 were only found in patients who were 4-5 years after diagnosis. Additional research will be needed to further define the diagnostic and prognostic merit of NT-proBNP in survivors after receipt of anthracycline therapy. [Table: see text]

76P Retrospective study about the prevalence of (TILs) tumour infiltrating lymphocytes in non-metastatic triple negative breast cancer patients and its prognostic value

Among breast carcinomas, TNBC comprises a distinct disease entity with a unique microenvironment of TILs ,To clarify the biological and prognostic function of TILs, which is a host factor in tumor microenvironment, we focused on effector CD8+ T cells in our study as marker for TILs , CD8+ TILs represent a vital component of the local anti-cancer immune response.

A multi-institutional real world data study from India of 3453 non-metastatic breast cancer patients undergoing upfront surgery

The present analysis reports the clinical, pathological, treatment profile and overall survival (OS) and disease-free survival (DFS) outcomes of consecutive breast cancer patients from three Indian centres, who underwent curative surgery as their first treatment. Among the 3453 patients, stage I, II, and III cases were 11.75%, 66.79%, and 21.64%, respectively while hormone receptor positive/HER2 negative, triple negative (TNBC) and hormone receptor any/HER2 positive cases were 55.2%, 24.2% and 20.6%, respectively. The five-year OS in the entire cohort, node-negative and node-positive patients were 94.1% (93.25–94.98), 96.17% (95.2–97.15) and 91.83% (90.36–93.31), respectively, and the corresponding DFS were 88.1% (86.96–89.31), 92.0% (90.64–93.39) and 83.93% (82.03–85.89), respectively. The five-year OS in hormone receptor positive/HER2 negative, TNBC and HER2 subgroups were 96.11% (95.12–97.1), 92.74% (90.73–94.8) and 90.62% (88.17–93.15), respectively, and the corresponding DFS were 91.59% (90.19–93.02), 85.46% (82.79–88.22) and 81.29% (78.11–84.61), respectively. This is the largest dataset of early breast cancer patients from India with survival outcome analysis and can therefore serve as a benchmark for future studies.

Clinicopathologic Parameters and Survival Data in Non-Metastatic Breast Cancer Patients in Correlation with Tumour Infiltrating Lymphocytes, Androgen Receptor and Insulin-Like Growth Factor Receptor 1 Expression

Introduction: The constantly evolving nature of breast cancer (BC) makes it paramount to identify and evaluate more biomarkers that may have a predictive and prognostic value. We explored the relationship between the androgen receptor (AR), insulin-like growth factor 1 receptor (IGF-1R) and tumour infiltrating lymphocytes (TILs), and clinicopathologic variables and survival in BC. Materials and Methods: In this retrospective study, we collected clinical and pathological data of 105 BC patients who had been treated at Alexandria Main University Hospitals from January 2010 to December 2016. These patients’ formalin fixed paraffin-embedded blocks were retrieved and analyzed for AR and IGF-1R expression immunohistochemically; TILs were assessed by hematoxylin and eosin staining. Chi square and Kaplan Meier curves were used to study the correlation between the three biomarkers and clinicopathologic parameters and survival respectively. Results: 59% and 51.4% of patients were AR and IGF-1R positive respectively. AR immunoreactivity correlated with a tumour size less than 5 centimeters (p=0.001), presence of carcinoma in situ (p=0.008), negative Her 2 status (p=0.007) and negative lymphovascular invasion (p&lt;0.001). Negative AR expression predicted a longer disease free survival (p=0.017). A positive IGF-1R was associated with carcinoma in situ (p&lt;0.001) and negative extra-nodal extension (p=0.042) but no impact on the disease free survival (p=0.227). A high TIL expression was associated with a tumour size less than 5 centimeters (p=0.005), invasive lobular carcinoma (p=0.006), carcinoma in situ (p=0.047), negative LVI (p&lt;0.001) and longer survival. A positive AR expression was associated with a positive IGF-1R expression (p&lt;0.001). Conclusions: AR, IGF-1R and TILs correlate differently with various clinicopathologic variables used in BC; in addition they all have a prognostic value. The two receptors are a promising target in BC. More clinical studies are required to further confirm the utility of these three biomarkers.

Cicaderma Efficacy vs Standard Care of Sites in Preventing Radiodermatitis in Non-metastatic Breast Cancer Patients

Cicaderma Efficacy vs Standard Care of Sites in Preventing Radiodermatitis in Non-metastatic Breast Cancer Patients

Metabolic Pathway Analysis and Effectiveness of Tamoxifen in Danish Breast Cancer Patients.

Tamoxifen and its metabolites compete with estrogen to occupy the estrogen receptor. The conventional dose of adjuvant tamoxifen overwhelms estrogen in this competition, reducing breast cancer recurrence risk by nearly half. Phase I metabolism generates active tamoxifen metabolites, and phase II metabolism deactivates them. No earlier pharmacogenetic study has comprehensively evaluated the metabolism and transport pathways, and no earlier study has included a large population of premenopausal women. We completed a cohort study of 5,959 Danish nonmetastatic premenopausal breast cancer patients, in whom 938 recurrences occurred, and a case-control study of 541 recurrent cases in a cohort of Danish predominantly postmenopausal breast cancer patients, all followed for 10 years. We collected formalin-fixed paraffin-embedded tumor blocks and genotyped 32 variants in 15 genes involved in tamoxifen metabolism or transport. We estimated conventional associations for each variant and used prior information about the tamoxifen metabolic path to evaluate the importance of metabolic and transporter pathways. No individual variant was notably associated with risk of recurrence in either study population. Both studies showed weak evidence of the importance of phase I metabolism in the clinical response to adjuvant tamoxifen therapy. Consistent with prior knowledge, our results support the role of phase I metabolic capacity in clinical response to tamoxifen. Nonetheless, no individual variant substantially explained the modest phase I effect on tamoxifen response. These results are consistent with guidelines recommending against genotype-guided prescribing of tamoxifen, and for the first time provide evidence supporting these guidelines in premenopausal women.