Negative Hormone Receptor Status Research Articles

Therapy Landscape in Patients with Metastatic HER2-Positive Breast Cancer: Data from the PRAEGNANT Real-World Breast Cancer Registry.

This study presents comprehensive real-world data on the use of anti-human epidermal growth factor receptor 2 (HER2) therapies in patients with HER2-positive metastatic breast cancer (MBC). Specifically, it describes therapy patterns with trastuzumab (H), pertuzumab + trastuzumab (PH), lapatinib (L), and trastuzumab emtansine (T-DM1). The PRAEGNANT study is a real-time, real-world registry for MBC patients. All therapy lines are documented. This analysis describes the utilization of anti-HER2 therapies as well as therapy sequences. Among 1936 patients in PRAEGNANT, 451 were HER2-positive (23.3%). In the analysis set (417 patients), 53% of whom were included in PRAEGNANT in the first-line setting, 241 were treated with H, 237 with PH, 85 with L, and 125 with T-DM1 during the course of their therapies. The sequence PH → T-DM1 was administered in 51 patients. Higher Eastern Cooperative Oncology Group (ECOG) scores, negative hormone receptor status, and visceral or brain metastases were associated with more frequent use of this therapy sequence. Most patients received T-DM1 after treatment with pertuzumab. Both novel therapies (PH and T-DM1) are utilized in a high proportion of HER2-positive breast cancer patients. As most patients receive T-DM1 after PH, real-world data may help to clarify whether the efficacy of this sequence is similar to that in the approval study.

Axillary Pathologic Complete Response to Neoadjuvant Chemotherapy in Clinically Node-Positive Breast Cancer Patients: A Predictive Model Integrating the Imaging Characteristics of Ultrasound Restaging with Known Clinicopathologic Characteristics

The goal of this study was to evaluate various clinicopathologic and imaging characteristics as independent predictors of axillary pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) and to determine the added value of a model that integrates imaging characteristics of ultrasound (US) restaging with known clinicopathologic characteristics. A total of 227 clinically node-positive breast cancer patients underwent axillary US after NAC (termed US restaging) before surgery. We constructed a clinicopathologic model with independent predictors of clinicopathologic characteristics in multivariate analyses. A combined model was created by integrating imaging characteristics with clinicopathologic characteristics. The predictive values of the models were compared using the area under the receiver operating characteristic curve. Of the 227 patients, 106 (46.7%) achieved axillary pCR. Multivariate analysis revealed that higher histologic grades (odds ratio [OR] = 4.21 and 10.11 for moderate and high grade, respectively), negative hormonal receptor status (OR = 2.88), smaller (≤1.5 cm) residual tumor size (OR = 2.83), absence of fatty hilum loss (OR = 14.06) and absence of eccentric cortical thickening of the axillary lymph node (OR = 4.42) were independently associated with the axillary pCR (all p values < 0.05). Integrating the imaging characteristics of the US restaging significantly increased the predictive capability of the model that applied only the clinicopathologic characteristics (c-index, 0.783 vs. 0.657; p < 0.001). Imaging characteristics of the US restaging were independently associated with axillary pCR after NAC and they significantly improved the predictive capability of the model that used only the clinicopathologic characteristics.

Concordance with NCCN treatment guidelines: Relations with health care utilization, cost, and mortality in breast cancer patients with secondary metastasis.

The impact of National Comprehensive Cancer Network (NCCN) treatment guideline concordance on costs, health care utilization, and mortality for patients with breast cancer and secondary metastases is unknown. From 2007 to 2013, women with early-stage breast cancer who received treatment for secondary metastases (n = 5651) were evaluated for first recorded systemic therapy concordance with NCCN guidelines within the Surveillance, Epidemiology, and End Results Program-Medicare linked database. Generalized linear and mixed effects models evaluated factors associated with nonconcordance and the relation between concordance status and health care utilization and costs. Mortality risk was estimated with Cox regression. Eighteen percent of the patients received nonconcordant therapy, with the most common being single-agent, human epidermal growth factor receptor 2 (HER2)-targeted therapy (36%), therapy mismatched with the estrogen receptor/HER2 status (11%), unapproved bevacizumab regimens (10%), and adjuvant regimens in a metastatic setting (6%). A younger age, a hormone receptor-negative status, and a HER2-positive status were associated with nonconcordance (P < .05). Nonconcordance was associated with 22% and 21% increased rates of emergency department visits and hospitalizations, respectively, and $1765 higher average monthly Medicare costs. Differences in adjusted mortality risk were noted by the category of nonconcordance; single-agent, HER2-targeted therapy was associated with decreased mortality risk (hazard ratio [HR], 0.66; 95% confidence limit [CL], 0.57-0.76), and increased mortality risk was observed with unapproved bevacizumab use (HR, 1.40; 95% CL, 1.13-1.74). Most patients (82%) received treatment consistent with NCCN guidelines. Nonconcordant treatment was associated with higher health care utilization and costs, with mortality differences observed by the type of guideline deviation. Consideration of both patient and financial outcomes will be important as health systems increase the emphasis on guideline-based care.

RASEF expression correlates with hormone receptor status in breast cancer.

Breast cancer (BC) is the most frequently diagnosed malignant tumor in women worldwide, and the development of new molecules associated with BC is essential for the management of this disease. RAS and EF-hand domain-containing (RASEF) encodes the GTPase enzyme that belongs to the Rab family. Although the effects of this gene have been reported in several malignant tumor types, the role of RASEF in BC has not been completely elucidated. The aim of the present study was to investigate the importance of RASEF expression in BC. RASEF mRNA expression levels were evaluated in BC and non-cancerous mammary cell lines. The association between RASEF mRNA expression levels and clinicopathological factors in 167 patients with BC were then determined. Among the 13 examined BC cell lines, ER-negative/HER2-negative cell lines expressed lower RASEF mRNA levels, when compared with the other examined cell lines (P=0.014). Of the 167 patients examined, patients with negative hormone receptor status exhibited significantly lower RASEF mRNA expression levels (P<0.001). In addition low RASEF expression in BC tissues was associated with negative estrogen receptor status (P<0.001), negative progesterone receptor status (P<0.001), and triple-negative status (P<0.001). Additionally, although the differences were not statistically significant, patients with low RASEF expression levels exhibited poorer disease-free survival (P=0.123) and overall survival (P=0.086) than other patients. The results of the present study indicate that RASEF mRNA expression levels are associated with hormone receptor status in BC.

Incidence and predictors of 1-year mortality among 9236 breast cancer patients referred for adjuvant chemotherapy.

To evaluate the incidence and predictors of mortality in the first year following randomization among breast cancer patients recruited in five adjuvant chemotherapy clinical trials. This is a pooled analysis of 9236 patients from five clinical trials. Univariate and multivariate logistic regression analyses were conducted to evaluate the impact of relevant clinicopathological factors on early mortality. Early death rates were 0.1% (11 patients) at 6 months and 0.8% (70 patients) at 1 year. Patients with a documented relapse within 1 year have a higher risk of death within the first year (HR: 74.20, 95% CI: 42.28-130.22) in a multivariate Cox regression model. The following factors were predictive of 1-year mortality in multivariate logistic regression analysis: higher T-stage (p =0.001), higher N-stage (p=0.004) and negative hormone receptor status (p<0.0001). Six-month and 1-year mortality rates are low among breast cancer patients referred for adjuvant chemotherapy within a clinical trial.

Characteristics and follow-up of metastatic breast cancer in Ethiopia: A cohort study of 573 women

ObjectivesThere is little information on characteristics, treatment and outcome of metastatic breast cancer (mBC) patients in low-income countries. This study aims to describe mBC in the setting of Ethiopia. Materials and MethodsA retrospective cohort study was conducted among all female mBC patients from the only oncologic hospital in Addis Ababa 01/2006 to 12/2010. Time between first metastasis and known death or loss to follow-up for more than six months as surrogate for death were used for Cox proportional hazards model. ResultsA total of 573 patients were included; 188 (32.8%) women with de novo mBC (dnmBC) and 385 women with recurrent mBC (rmBC). The average age at time of first metastasis was 43.7 (standard deviation 11.9) years with an average survival probability of twelve months. Negative hormone receptor status, only present in 29% (Hazard ratio HR = 2.28 [95% confidence interval CI 1.56–3.32] p < 0.001), and grade 3 (HR = 1.72 [95% CI 1.15–2.55] p = 0.008) had significant influence on survival. Patients with initial bone metastasis (HR = 0.63 [95% CI 0.48–0.83] p = 0.001) had best chances of survival compared to more common initial visceral metastasis. About 35% of the patients received chemotherapy and 30.5% were on endocrine therapy. ConclusionThe lower survival for mBC in Addis Ababa compared to that from Western countries is presumably due to the later presentation at the hospital and lack of standard therapy. An unexpected high proportion of patients with hormone receptor positive mBC encourage consequent utilization of endocrine therapy to improve the quality of palliative care in this cohort.

Impact of postmastectomy radiotherapy on the outcomes of breast cancer patients with T1-2 N1 disease : An individual patient data analysis of three clinical trials.

To assess the impact of postmastectomy radiotherapy (PMRT) on overall survival and relapse-free survival among breast cancer patients with T1-T2 N1 disease who received standard adjuvant systemic therapy. This is an individual patient data pooled analysis of 1053 breast cancer patients referred for adjuvant therapy in three clinical trials (BIG02/98, BCIRG001, and BCIRG005). Overall survival was assessed according to whether or not patients received adjuvant radiotherapy through Kaplan-Meier analysis. Univariate and multivariate analyses of predictors of overall and relapse-free survival were conducted through Cox regression analysis. Locoregional relapse rates (after amedian follow up of 116months) were 5.6% among patients who received adjuvant radiotherapy vs. 6.6% among patients who did not receive adjuvant radiotherapy. Actuarial 5‑ and 10-year locoregional relapse-free survival rates were 94 and 93%, respectively, among patients who did not receive adjuvant radiotherapy versus 95 and 92% among patients who received adjuvant radiotherapy. The following factors were associated with worse overall survival in multivariate Cox regression analysis: age < 40years (P < 0.0001), T2 stage (P = 0.004), higher lymph node ratio (P < 0.0001), and negative hormone receptor status (P < 0.0001). Likewise, the following factors were predictive of shorter locoregional relapse-free survival: age ≤ 40 (P < 0.0001), no PMRT (P = 0.034), fluorouracil/adriamycin/cyclophosphamide (FAC) chemotherapy (P = 0.001), and higher Tstage (P = 0.002). The current analysis does not show abeneficial impact of PMRT on overall or relapse-free survival among patients with T1-T2 N1 disease who received standard adjuvant systemic therapy. There is, however, evidence of improvement in locoregional relapse-free survival with PMRT. These findings need to be prospectively validated.

Impact of Regional Nodal Irradiation on the Outcomes of N1 Breast Cancer Patients Referred for Adjuvant Treatment: A Patient-Level Pooled Analysis of 2 Clinical Trials

PurposeTo evaluate the impact of regional nodal irradiation (RNI) among N1 operable breast cancer patients who underwent adequate axillary dissection and received adjuvant chemotherapy. Patients and MethodsThis is a pooled analysis of 812 breast cancer patients referred for adjuvant systemic therapy in 2 prospective randomized studies: NCT00174655 (BIG 02/98) and NCT00312208 (BCIRG005). Overall survival was assessed according to whether patients received supraclavicular and/or internal mammary radiotherapy through Kaplan-Meier estimates. Univariate and multivariate analyses of variables affecting overall and relapse-free survival were performed through Cox regression analysis. Additionally, recurrence rates were analyzed according to regional irradiation patterns. ResultsRegional relapse rates (after a median follow-up of 76 months) were 1.5% in both groups of patients who received or did not receive supraclavicular radiotherapy. The risk of regional recurrence was 0.7% in patients who received internal mammary node radiotherapy versus 1.6% in patients who did not receive internal mammary node radiotherapy. The following factors were associated with worse overall survival in multivariate Cox regression analysis: age < 40 years (P < .0001), > T1 stage (P = .003), and negative hormone receptor status (P = .002). Neither supraclavicular nor internal mammary radiotherapy was associated with improvement in overall or relapse-free survival in Cox regression analysis. ConclusionThe current analysis does not endorse the routine use of supraclavicular or internal mammary radiotherapy among N1 operable breast cancer patients who have undergone adequate dissection of axillary lymph nodes and who have received standard adjuvant systemic therapy. Given the limited power and potential selection bias of the current analysis, further prospective studies are needed to tackle this research question.

Outcomes of early-stage breast cancer patients treated with sequential anthracyclines–taxanes in relationship to relative dosing intensity: a secondary analysis of a randomized controlled trial

To assess the impact of relative dosing intensity (RDI) on the outcomes of breast cancer patients referred for adjuvant anthracycline-taxane chemotherapy. This is a secondary analysis of the outcomes of patients in the comparator arm of the BCIRG005 study who received adjuvant adriamycin/cyclophosphamide (AC)-docetaxel regimen. Overall survival was assessed according to RDI through Kaplan-Meier analysis. Univariate and multivariate analyses of parameters affecting overall survival were then conducted through Cox regression analysis. Kaplan-Meier analysis of overall survival according to RDI for the AC-docetaxel regimen (< 90 vs. ≥ 90%) was conducted and it showed that RDI < 90% is associated with worse overall survival (P = 0.006). In univariate Cox regression analysis, the following parameters significantly affected overall survival (P < 0.05): age, T stage, lymph node ratio, hormone receptor status, and grade of the disease and RDI for AC-docetaxel regimen. When these factors were included in multivariate analysis, the following factors were associated with worse overall survival: age less than 40years (P < 0.0001), greater T stage (P < 0.0001), greater lymph node ratio (P < 0.0001), negative hormone receptor status (P = 0.001), high grade (P < 0.0001) and RDI ≤ 90% (P = 0.015). Formal interaction testing between RDI and hormone receptor status has a non-significant P value (P = 0.794). Lower RDI for the whole anthracycline-taxane protocol is associated with worse patient survival. Every effort should be exercised to avoid unnecessary dose reductions and/or interruptions among early breast cancer patients receiving adjuvant anthracycline-taxane chemotherapy.

Contralateral prophylactic mastectomy rate and predictive factors among patients with breast cancer who underwent multigene panel testing for hereditary cancer.

Although multigene panel testing is increasingly common in patients with cancer, the relationship between its use among breast cancer patients with non‐BRCA mutations or variants of uncertain significance (VUS) and disease management decisions has not been well described. This study evaluated the rate and predictive factors of CPM patients who underwent multigene panel testing. Three hundred and fourteen patients with breast cancer who underwent multigene panel testing between 2014 and 2017 were included in the analysis. Of the 314 patients, 70 elected CPM. Election of CPM by gene status was as follows: BRCA carriers (42.3%), non‐BRCA carriers (30.1%), and VUS (10.6%). CPM election rates did not differ between non‐BRCA carriers and BRCA carriers (P = 0.6205). Among non‐BRCA carriers, negative hormone receptor status was associated with CPM (P = 0.0115). For those with a VUS, hormone receptor status was not associated with CPM (P = 0.1879). Although the rate of CPM between BRCA carriers and non‐BRCA carriers was not significantly different, the predictors of CPM were different in each group. Our analyses shed the light on the increasing use of CPM among patients who are non‐BRCA carriers as well those with a VUS. Our study elucidates the differing predictive factors of CPM election among BRCA carriers, non‐BRCA carries, and those with a VUS. Our findings reveal the need for providers to be cognizant that non‐BRCA genes and VUS drive women to elect CPM despite the lack of data for contralateral breast cancer risk associated with these genes.

Abstract P2-11-24: Disparities in the application of post-mastectomy radiotherapy in Switzerland: A pooled analysis of 7 cancer registries over the 2003-2005 period

Abstract Background: The aim of this study was to identify factors that influence the delivery of post-mastectomy radiotherapy (PMRT) in Switzerland, and to analyze the adherence to consensus guidelines. Methods: Based on 7 regional cancer registries covering 45% of the Swiss population, we identified 1408 women which underwent mastectomy for stage I-III breast cancer between January 1, 2003 and December 31, 2005. We categorized patients according to ASCO grouping in similar fashion to other comparable studies: low-risk group (T1/T2 N0): PMRT not routinely recommended; intermediate-risk group (T1/T2 N1): PMRT controversial; high risk group (T3-T4 and/or N2-N3): PMRT recommended. We further investigated factors leading to potential overtreatment (PMRT in low-risk group) or undertreatment (absence of PMRT in high-risk group). Data analysis was performed for the entire cohort, and separately for patients &amp;lt;70 years and ≥ 70 years of age. Probability of receiving PMRT was assessed using multivariable logistic regression. Results: A total of 421 patients (29.9%) received adjuvant RT after mastectomy. The rate of PMRT delivery was 67% in the high-risk group, compared to 6% and 18% in the low-risk and intermediate-risk groups, respectively. For patients at high-risk of chest wall recurrence after mastectomy (T3-T4 or N2-N3 disease), the risk of PMRT omission wassignificantly associated to older age (OR 4.25 [95% CI: 2.27-7.95] for patients ≥ 70 years) and to the absence of chemotherapy (OR 4.30 [95% CI: 1.97-9.36]). In patients with T3-T4 disease, PMRT was delivered in 77% of patients &amp;lt; 70 years and in 42% of patients ≥ 70 years (p&amp;lt;0.001). In patients with N2-N3 disease, PMRT was delivered in 82% of patients &amp;lt; 70 years and in 51% of patients ≥70 years (p&amp;lt;0.001). PMRT was delivered to 28 patients (7%) at low-risk of recurrence after mastectomy (T1-T2 N0, negative margins). It was more frequently offered to patients &amp;lt;40 years of age (OR 3.86 [95% CI: 1.01-14.76]), with T2 tumors (OR 3.43 [95% CI: 1.45-8.11]) and negative hormone receptor status (OR 2.60 [95% CI: 1.04-6.50]). Positive or close surgical margins (&amp;lt; 1mm) were a strong indicator for PMRT (p=0.001) and chest wall boost (p&amp;lt;0.03). Conclusions: After mastectomy, one third of patients (33.26%) with high-risk disease did not receive PMRT. Even if we consider only patients &amp;lt; 70 years, a non-trivial proportion of patients with clear indication for treatment delivery did not receive PMRT (T3-T4 disease: 23%; N2-N3 disease: 18%). Further analyses are planned to explain the apparent failure of evidence-based guidelines to impact the adoption of PMRT in women with high-risk breast cancer. Citation Format: Zwahlen DR, Ess S, Zimmermann M, Bordoni A, Bouchardy C, Frick H, Konzelmann I, Mousavi M, Rohrmann S, Oehler C. Disparities in the application of post-mastectomy radiotherapy in Switzerland: A pooled analysis of 7 cancer registries over the 2003-2005 period [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-11-24.

Abstract P5-07-10: Circulating microRNAs as early predictors of relapse in operable breast cancer

Abstract Background: Metastasis remains a major threat for patients (pts) with operable breast cancer (BC). Recurrence could arise from a state of tumour dormancy during which there is growth restriction of undetectable micrometastases. The expression of dormancy and metastasis related miRNAs was evaluated in the plasma of pts with operable BC obtained before adjuvant therapy in order to discover novel biomarkers for the prediction of relapse. Methods: Plasma miR-21, miR-23b, miR-190, miR-200b and miR-200c expression was assessed by qRT-PCR in 133 pts with early BC (non-relapsed, n=84; relapsed, n=49). Expression was classified as high or low according to the median values and was associated with pts' clinicopathological characteristics and clinical outcome. Results: No correlation was observed between the expression of miRNAs and the clinicopathological characteristics of pts. After a median f-up of 90.5 mo, median Disease Free Interval (DFI) was significantly lower in pts with high compared to low miR-21 [105 mo vs not reached (NR); p=0.001], miR-200c (105.2 mo vs NR; p=0.007), or both miR-21 and miR-200c expression (81.37 mo vs NR; p=0.001). miR-21-high was also associated with decreased median Overall Survival (OS; p=0.041). In multivariate analysis the number of infiltrated axillary lymph nodes (N3 vs N0-N2, HR: 2.86; p= 0.004) and miR-21 expression (high vs low, HR: 2.824; p=0.001) were independent negative prognostic factors for DFI, whereas negative hormone receptor status (HR: 3.062; p=0.024) and miR-21 high (HR: 3.545; p=0.029) independently predicted for worse OS. Moreover, miR-21 expression was higher in pts presenting early relapse (defined as relapse at ≤ 3 yrs) compared to those without relapse at 5 yrs (p=0.032). Furthermore, higher miR-21 (p=0.038), miR-23b (p=0.039), miR-200b (p=0.027) and miR-200c (p&amp;lt;0.001) levels were observed in pts with late relapse (at ≥ 5 yrs) compared to those without relapse. Conclusions: Differential expression levels of metastasis and/or dormancy related circulating miRNAs are encountered before adjuvant therapy in pts with operable BC presenting subsequent relapse compared to non-relapsed pts. In addition, circulating miRNAs could predict for early or late recurrence years before clinical detection of metastases. These results merit prospective validation in an independent pt cohort. Citation Format: Agelaki S, Papadaki C, Stratigos M, Spiliotaki M, Markakis G, Mastrostamatis G, Mavroudis D, Ioannis S. Circulating microRNAs as early predictors of relapse in operable breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-07-10.

Abstract P5-23-05: Prognostic value of PD-L1 expression in male breast cancer

Abstract Background Growing evidence have shown promise for targeting programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) signaling in several tumors. In female breast cancer, PD-L1 expression has been correlated with poor clinical outcome. However, whether PD-L1 has any indication for prognosis in male breast cancer (MBC) patients remains unknown. The purpose of this study was to examine the expression levels of PD-L1 in MBC and to identify the relationship between PD-L1 expression and patient survival. Methods We retrospectively identified 110 male breast cancer patients diagnosed between 2000 and 2013 at Salah Azaïz Cancer Institute. PD-L1 expression was evaluated by immunohistochemistry (IHC) using CD274 antibody. Specimens were scored as IHC low or high, when &amp;lt; 5% or ≥ 5% of cells were PD-L1 positive, respectively. The association between expression of PD-L1 and survival was investigated using Kaplan-Meier survival and COX proportional hazard regression analyses. Results Median follow up was 12.5 months [range 1-132 months]. High expression of PD-L1 was observed in 64.5% of MBC samples (71/110). PD-L1 expression was significantly associated with advanced clinical stage (p=0.012), higher histological grade (p=0.014), higher Ki67 expression (p=0.023) and hormone-receptor negative status (p=0.024). Patients with high PD-L1 expression had significantly shorter overall survival (OS) than patients with low expression (p=0.002, hazard ratio (HR) =5 [2.624–10.642]). Multivariate analysis identified PD-L1 as an independent prognostic factor for OS (p&amp;lt;0.001, HR = 0.775 [0.680–0.870]). Conclusion Our results indicate that high PD-L1 expression may be a prognostic indicator for reduced OS. Thus, PD-L1 expression is a promising novel biomarker with prognostic significance in MBC and may suggest a potential therapeutic target of anti-PD-L1 antibody therapy in MBC patients. Citation Format: Abdeljaoued S, Bettaieb I, Adouni O, Goucha A, Chiba D, Bouzaiene H, Ben Hassouna J, Boussen H, Rahal K, Gamoudi A. Prognostic value of PD-L1 expression in male breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-23-05.

Role of postoperative radiotherapy in reducing ipsilateral recurrence in DCIS: an observational study of 1048 cases

BackgroundThe objective of the present study was to evaluate the effectiveness of postoperative radiotherapy after breast conserving surgery (BCS) in DCIS in a large patient population treated in clinical practice.MethodsData were provided by the population-based Munich Cancer Registry. Between 1998 and 2014, 1048 female patients with diagnosis of DCIS and treated at two Breast Care Centres were included in this observational study. The effectiveness of postoperative radiotherapy and variables predicting the use of radiotherapy were retrospectively analysed.ResultsAfter adjusting for age, tumour characteristics and therapies, Cox regression analysis for local recurrence-free survival identified RT as an independent predictor for improved local control (HR: 0.579; 95%CI: 0.384–0.872, p = 0.008). Ten-year cumulative incidence of in-breast recurrences was 20.0% following BCS, compared to 13.6% in patients receiving postoperative radiotherapy (p = 0.012). As an estimate for disease-specific survival, 10-year relative survival was 105.4% for patients receiving postoperative radiotherapy and 101.6% without radiotherapy. On multivariate analysis, postoperative radiotherapy was not associated with improved overall survival (HR 0.526; 95%CI: 0.263–1.052, p = 0.069). Over time, a significant increase of RT was registered: while 1998 only 42.9% of patients received postoperative radiotherapy, the proportion rose to 91.2% in 2014. Women aged < 50 years (OR: 2.559, 95%CI: 1.416–4.625, p < 0.001) or with negative hormone receptor status (OR: 2.625, 95%CI: 1.458–4.728, p = 0.001) or receiving endocrine therapy (OR: 1.762, 95%CI: 1.060–2.927, p = 0.029) were more likely to receive postoperative radiotherapy after BCS.ConclusionsIn conclusion, this study provides insights regarding the adoption and treatment pattern of postoperative RT following BCS for DCIS in a large cohort reflecting “real-life” clinical practice in this setting. Postoperative RT was found to be associated with a reduced risk of ipsilateral recurrence and no survival benefit compared to observation alone.

Predictors of Pathological Complete Response to Neoadjuvant Chemotherapy in Iranian Breast Cancer Patients

Background:Achievement of pathologic complete response (pCR) in breast cancer patients receiving neoadjuvant chemotherapy (NAC) is associated with both overall survival and disease-free survival. The aim of present study was to identify clinical and pathological factors associated with achieving pCR in Iranian breast cancer patients receiving NAC.Methods:A retrospective review of all breast cancer patients treated with neoadjuvant chemotherapy between April 2012 and September 2016 at our institution was performed; 207 cases were evaluable for analysis. pCR was defined as having no residual invasive tumor in the breast surgical specimen removed following neoadjuvant therapy.Results:In univariate analysis, factors associated with pCR were age less than 35 years (p = 0.03), absence of Lymphovascular invasion (LVI) (p = 0.002) and negative hormone receptor status (p = 0.003). Hormone receptor status (P = 0.01; OR, 2.45; CI, 1.20 - 4.99) and LVI (P = 0.001; OR, 0.22; CI, 0.10 - 0.46) remained predictive variables in multivariate analysis after correction for the other variables.Conclusions:In conclusion, the results of this study suggests that presence of Lymphovascular invasion and positive hormone receptor status are associated with poorer response to neoadjuvant chemotherapy in breast cancer patients.

Diversity index as a novel prognostic factor in breast cancer.

Intratumoral genetic heterogeneity leads to tumor progression and therapeutic resistance. However, due to the difficulty associated with its assessment, the use of this heterogeneity as a prognostic or predictive marker remains limited. To investigate the significance of the Shannon diversity index of gene copy number variation as a tool for measuring genetic heterogeneity in breast cancer, we performed fluorescence in situ hybridization of c-MYC in two sets of invasive breast cancer samples and correlated the Shannon index of c-MYC copy number variation with clinicopathologic features and patient survival. The Shannon index was correlated with average c-MYC copy number and was higher in tumors in which c-MYC was amplified and in those with c-MYC genetic or regional heterogeneity. A high Shannon index was associated with adverse pathologic features including high histologic grade, lymphovascular invasion, p53 overexpression, high Ki-67 proliferation index and negative hormone receptor status. It was also associated with poor disease-free survival in the whole group, in a subgroup excluding c-MYC-amplified cases, and in the hormone receptor-positive subgroup of both a test and a validation set. A high Shannon index for FGFR1 gene copy number variation was also an independent adverse prognostic factor. Our findings suggest that the Shannon diversity index is a measure of intratumoral heterogeneity and can be used as a prognostic factor in breast cancer.

Variation in use of neoadjuvant chemotherapy in patients with stage III breast cancer: Results of the Dutch national breast cancer audit

ObjectivesNeoadjuvant chemotherapy (NAC) is important in the optimal treatment of patients with locally advanced (stage III) breast cancer (BC). The objective of this study was to examine the clinical practice of NAC for stage III BC patients in all Dutch hospitals participating in BC care. Materials and methodsAll patients aged 18–70 years who received surgery for stage III BC from January 2011 to September 2015 were selected from the national multidisciplinary NABON Breast Cancer Audit. Multivariable logistic regression was used to assess independent predictors of NAC use, focussing on hospital factors. ResultsA total of 1230 out of 1556 patients with stage III BC (79%) received NAC prior to surgery. The use of NAC did not change over time. We observed a large variation of NAC use between hospitals (0–100%). Age <50 years, breast MRI, large tumour size, advanced nodal disease, negative hormone receptor status and hospital participation in neoadjuvant clinical studies were significant independent predictors of NAC use (all P < 0.001). NAC use in stage III BC was not influenced by hospital type and hospital surgical volume. After adjustment for all independent predictors, variation in NAC use between hospitals remained (0% to 97%). ConclusionNAC was used in 79% of patients with stage III BC, which represent a high quality of care in the NL. Patient, tumour, clinical management and hospital factors could not explain considerable variation in its use between hospitals. Hospital participation in neoadjuvant studies did show to improve the use of NAC in daily practice.

Different outcome in node-positive breast cancer patients found by axillary ultrasound or sentinel node procedure

BackgroundThe Z0011 trial initiated a paradigm shift in the axillary treatment of breast cancer patients with a positive sentinel lymph node biopsy (SLNB), disregarding patients with a positive ultrasound-guided lymph node biopsy (UGLNB). We examined whether relevant differences exist between these patients to determine if the conclusions of the ACOSOG Z0011 trial are applicable to UGLNB-positive patients.MethodsPatients diagnosed with invasive breast cancer in the Netherlands between January 2008 and December 2014 were selected from the Netherlands Cancer Registry.ResultsA total of 11,820 cases were included: 9149 cases in the SLNB group and 2671 in the UGLNB group. Multivariate analyses showed that UGLNB-positive patients were older (p < 0.001), more likely to have a poorly differentiated tumor (p < 0.001), had a negative hormone receptor status (p < 0.001), and more often had extensive nodal involvement (p < 0.001). However, they were less likely to undergo adjuvant radiation (p = 0.004) or systemic therapy (p < 0.001). Even after adjusting for these factors, UGLNB-positive patients had a worse overall survival (HR = 1.38; 95% CI 1.23–1.56) than SLNB-positive patients.ConclusionThis nationwide retrospective study shows that young patients found positive by UGLNB have less favorable disease characteristics and a worse prognosis compared to patients with a positive SLNB. Selection by ultrasound plays an important role when axillary treatment strategies are considered. Hence, the conclusions of the Z0011 trial cannot unconditionally be applied to patients with a positive UGLNB.

Circulating microRNAs (miRNAs) as predictors of relapse in early breast cancer (BC).

e23030 Background: Disease relapse is usually a lethal development following treatment of early BC. Recurrence could arise from a state of tumour dormancy during which there is growth restriction of undetectable micrometastases. The expression of dormancy and metastasis related miRNAs was evaluated in the plasma of patients (pts) with early BC obtained before adjuvant therapy in order to discover novel biomarkers for the prediction of relapse. Methods: PlasmamiR-21, miR-23b, miR-190, miR-200b and miR-200c expression was assessed by qRT-PCR in 133 pts with early BC (non-relapsed, n = 84; relapsed, n = 49). Expression was classified as high or low according to the median values. Results: No correlation was observed between the expression of miRNAs and the clinicopathological characteristics of pts. After a median follow-up of 94 mo, median Disease Free Interval (DFI) was significantly lower in pts with high compared to low miR-21 [105.03 mo vs not reached (NR); p= 0.001], miR-200c (105.2 mo vs NR; p= 0.007), or both miR-21 and miR-200c expression (81.37 mo vs NR; p= 0.001). miR-21-high was also associated with decreased median Overall Survival (OS; p= 0.041). In multivariate analysis the number of infiltrated axillary lymph nodes (N3 vs N0-N2, HR: 2.86; p= 0.004) and miR-21 expression (high vs low, HR: 2.824; p= 0.001) were independent negative prognostic factors for DFI, whereas negative hormone receptor status (HR: 3.062; p= 0.024) and miR-21 high (HR: 3.545; p= 0.029) independently predicted for worse OS. Moreover, miR-21 expression was higher in pts with early relapse (defined as relapse at ≤ 3 yrs) compared to non-relapsed at 5 yrs ( p= 0.032). In addition, higher miR-21 ( p= 0.038), miR-23b ( p= 0.039), miR-200b ( p= 0.027) and miR-200c ( p&lt; 0.001) levels were observed in pts with late relapse (at ≥ 5 yrs) compared to those without relapse. Conclusions: Differential expression levels of metastasis and/or dormancy related circulating miRNAs are detectable before adjuvant therapy in pts with early BC presenting subsequent relapse compared to non-relapsed pts. Circulating miRNAs can predict for early or late recurrence years before clinical detection of metastases. These results merit prospective validation in an independent patient cohort.

Use of regional nodal irradiation and its association with survival for women with high-risk, early stage breast cancer: A National Cancer Database analysis

PurposeThe role of regional nodal irradiation (RNI) for patients with breast cancer remains controversial, particularly on the basis of nodal involvement. Using the National Cancer Database, we aimed to validate published data on whether expanding treatment fields from whole-breast irradiation (WBI) to encompass the regional nodes (WBI+RNI) affected overall survival (OS) for patients with node-positive (pN1-3) or high-risk node-negative (pN0) breast cancer treated with breast-conserving surgery and adjuvant chemotherapy. Methods and materialsWomen diagnosed with invasive breast cancer between 2004 and 2012 who met the selection criteria for the National Cancer Institute of Canada MA.20 trial were identified and stratified by receipt of RNI. Propensity score matching was used to compare 1:1 matched pairs of patients. Five-year OS was estimated using the Kaplan-Meier method. We used multivariate logistic regression to predict receipt of WBI+RNI and a multivariable Cox model to examine associations between patients' demographic, tumor, and treatment characteristics and OS using double robust estimation. ResultsOf 23,567 patients, 6,920 (29%) received WBI+RNI and 16,647 (71%) WBI. Median follow-up was 56 months. Use of WBI+RNI increased from 25.2% in 2004 to 32.2% in 2012 (P < .001). Patients receiving WBI+RNI more often had negative hormone-receptor status, ≥5 cm tumors and >1 involved node, and were not privately insured. For all patients, the 5-year OS rates were 90.8% with WBI+RNI versus 92.6% with WBI (P < .001). In the matched cohort (n = 10,922), the corresponding 5-year OS rates were 92% and 91.9% (P = .45), respectively. On multivariate analysis, WBI+RNI did not affect OS in the matched cohort (hazard ratio, 1.02; 95% confidence interval, 0.89-1.17, P = .76), regardless of pathologic nodal status. ConclusionsIn this large retrospective analysis, use of WBI+RNI did not affect 5-year OS rates for women with high-risk, early stage breast cancer undergoing breast-conserving surgery and adjuvant chemotherapy, regardless of nodal status, which confirms the findings of the MA.20 trial.