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Neoadjuvant therapy (NAT) is increasingly applied in patients with initially inoperable breast cancers and, frequently, in those with tumours that are initially operable, too. In most cases, the response to the applied NAT affects the scope of surgical treatment and radiotherapy, and in some situations also the complementary systemic postoperative treatment. The available studies indicate importance of response to NAT within the breast and regional lymph nodes. Assessment of response to treatment allows personalization of treatment and in some cases a change of therapy, which improves long-term outcomes. This article summarizes the current rules of conduct in patients with early breast cancer qualified for neoadjuvant thera­py, paying attention to the practical aspects and possibilities of national health insurance-covered therapies in Poland. It discusses in detail the applied regimens of systemic therapy, surgical techniques, eligibility rules and complementary radiotherapy. Systems for assessing response to neoadjuvant treatment are also presented.

Neoadjuvant therapy (NAT) is increasingly applied in patients with initially inoperable breast cancers and, frequently, in those with tumours that are initially operable, too. In most cases, the response to the applied NAT affects the scope of surgical treatment and radiotherapy, and in some situations also the complementary systemic postoperative treatment. The available studies indicate importance of response to NAT within the breast and regional lymph nodes. Assessment of response to treatment allows personalization of treatment and in some cases a change of therapy, which improves long-term outcomes. This article summarizes the current rules of conduct in patients with early breast cancer qualified for neoadjuvant thera­py, paying attention to the practical aspects and possibilities of national health insurance-covered therapies in Poland. It discusses in detail the applied regimens of systemic therapy, surgical techniques, eligibility rules and complementary radiotherapy. Systems for assessing response to neoadjuvant treatment are also presented.

Background: Determining the proper therapy is challenging in breast cancer (BC) patients with brain metastases (BM) due to the variability of an individual’s prognosis and the variety of treatment options available. Several prognostic tools for BC patients with BM have been proposed. Our review summarizes the current knowledge on this topic. Methods: We searched PubMed for prognostic tools concerning BC patients with BM, published from January 1997 (since the Radiation Therapy Oncology Group developed) to December 2021. Our criteria were limited to adults with newly diagnosed BM regardless of the presence or absence of any leptomeningeal metastases. Results: 31 prognostic tools were selected: 13 analyzed mixed cohorts with some BC cases and 18 exclusively analyzed BC prognostic tools. The majority of prognostic tools in BC patients with BM included: the performance status, the age at BM diagnosis, the number of BM (rarely the volume), the primary tumor phenotype/genotype and the extracranial metastasis status as a result of systemic therapy. The prognostic tools differed in their specific cut-off values. Conclusion: Prognostic tools have variable precision in determining the survival of BC patients with BM. Advances in local and systemic treatment significantly affect survival, therefore, it is necessary to update the survival indices used depending on the type and period of treatment.

Aim: To assess the outcomes of 737 consecutive patients with DCIS, with particular attention to the type of recurrences, other malignancies and causes of deaths. Material and Methods: A retrospective analysis of 737 consecutive DCIS patients treated in one institution in the years 1996–2011 was carried out. The cumulative recurrence risk, DFS, OS depending on the method of treatment (mastectomy, breast-conserving treatment (BCT), breast-conserving surgery (BCS)) and cause of death were assessed. Results: Sixty-six recurrences (42% DCIS, 58% invasive) were reported: 61 in the breast and 5 outside the breast. The cumulative recurrence risk after a 15-year observation after mastectomy, BCT and BCS was 3.2%, 19.5% and 31.2%, respectively (p < 0.001). The 15-year DFS after mastectomy, BCT and BCS was 72%, 65% and 48%, respectively (p < 0.001). The 15-year OS after mastectomy, BCT and BCS was 75%, 83% and 70%, respectively (p = 0.329). Deaths due to DCIS progression were reported in four (0.5%) of the overall patients and in 10.5% of patients with invasive recurrences. The majority of deaths were linked to the age of the patients or other diseases, including other neoplasms, but not DCIS. Conclusions: The highest number of recurrences was reported in patients after BCS, despite the fact that it was the lowest-risk group. In total, 79% of local recurrences were true recurrences and 58% were invasive recurrences. Local recurrences were effectively treated without an influence on the OS. The percentage of deaths due to DCIS was low and mainly concerned patients with locoregional and distant failure.

Neoadjuvant systemic therapy has now become the the standard in early breast cancer management. Chemotherapy in combination with trastuzumab +/- pertuzumab targeted therapy can improve rates of pathologic complete response (pCR) in patients with HER2-positive breast cancer. Achieving a pCR is considered a good prognostic factor, in particular in patients with more aggressive breast cancer subtypes such as TNBC or HER2 positive cancers. Furthermore, most studies demonstrate that chemotherapy in combination with trastuzumab and pertuzumab is well tolerated. The retrospective analysis presented here concentrates on neoadjuvant therapy with the TCbH-P regimen, with a particular emphasis on patients over 60 years of age. We analysed the factors affecting the achievement of pCR and presented adverse effects of the applied therapies, which opened a discussion about optimizing the therapy of older patients with HER-2 positive breast cancer.

Recently, liquid biopsy has emerged as a tool to monitor oncologic disease progression and the effects of treatment. In this study we aimed to determine the clinical utility of liquid biopsy relative to conventional oncological post-treatment surveillance. Plasma cell-free (cf) DNA was collected from six healthy women and 37 patients with breast cancer (18 and 19 with stage III and IV tumors, respectively). CfDNA was assessed using the Oncomine Pan-Cancer Cell-Free Assay. In cfDNA samples from patients with BC, 1112 variants were identified, with only a few recurrent or hotspot mutations within specific regions of cancer genes. Of 65 potentially pathogenic variants detected in tumors, only 19 were also discovered in at least one blood sample. The allele frequencies of detected variants (VAFs) were &lt, 1% in cfDNA from all controls and patients with stage III BC, and 24/85 (28.2%) variants had VAFs &gt, 1% in only 8 of 25 (32%) patients with stage IV BC. Copy number variations (CNVs) spanning CDK4, MET, FGFR1, FGFR2, ERBB2, MYC, and CCND3 were found in 1 of 12 (8%) and 8 of 25 (32%) patients with stage III and IV tumors, respectively. In healthy controls and patients without BC progression after treatment, VAFs were &lt, 1%, while in patients with metastatic disease and/or more advanced genomic alterations, VAFs &gt, 1% and/or CNV were detected in approximately 30%. Therefore, most patients with stage IV BC could not be distinguished from those with stage III disease following therapy, based on liquid biopsy results.

The study aimed to assess factors affecting survival of breast cancer patients suffering leptomeningeal metastasis (LM) and to compare survivals in patients with LM as the first and only site of metastases at presentation to patients with LM and metastases in other organs, along with selecting a patient group which had the best survival outcomes. Subject groups consisted of 187 patients consecutively referred during 1999-2015. A Cox proportional hazards model was used to identify factors associated with prolonged survival from LM. The Cox prognostic index was created to identify the group of patients with the most favorable prognosis. Median survival for all patients and for those with LM as the first site of metastases at presentation was 17 weeks and 1 year-survival was 15 and 16%, respectively. Factors beneficially affecting survival were: KPS ≥ 70, older age, biological subtype ER/PR+HER2-, systemic treatment, intrathecal treatment and radiation therapy. Based on these factors, 4 prognostic groups were found, with the most favorable group being 24 LM patients with median survival of 9.6 months. In this group, all patients were treated systemically and all were irradiated, 88% had KPS ≥ 70, about 80% had luminal breast cancer, 75% were treated intrathecally and 58% were more than 53 years old. Out of 4 prognostic groups of patients with LM, the most favorable group was selected. The median survival of breast cancer patients with the leptomeninges as the only site of metastases was comparable to those who had metastases in the leptomeninges and in other organs.

Germline BRCA1 and BRCA2 mutations confer an increased lifetime risk for breast cancer and ovarian cancer. Several studies have investigated prognosis among BRCA1/2 mutation carriers and noncarriers, but the prognostic impact on outcomes of breast cancer patients has not been determined. The aim of this study was to determine the prognosis of TNBC patients with and without BRCA1/2 germline mutation. Among 502 patients diagnosed with TNBC between 2005 and 2008, 124 patients with a strong family history of breast cancer or ovarian cancer as well as TNBC patients diagnosed under 45 years were referred to the Genetic Counseling Unit for genetic counselling and genetic tests. In 30 (24%) of them, the BRCA1/2 mutation was detected (the most common 5382insC in 18 (60%) patients). The median follow-up of the entire group was 60 months. BRCA1/2 mutation carriers were statistically significantly younger at TNBC diagnosis compared with nonmutation patients (41 vs 47 years, respectively). Patients with the BRCA1/2 mutation had smaller tumors (stage I: 47% vs 24.5% in noncarriers), but there was no significant difference in the regional nodal status (58.5–63% with cN0). Contralateral breast cancer developed in 26.5% of BRCA1/2 mutation carriers and in 14% of noncarriers. Other primary cancers were also slightly more common in BRCA1/2 mutation carriers (16.5% vs 9.5%). The performed analysis did not show any significant differences between the groups in recurrence-free survival (p=0.312). There was no significant difference between patients with or without BRCA1/2 mutation as regards overall survival (p=0.649) and the risk of TNBC death (p=0.333). The survival from detection of metastases was similar in two groups (p=0.865). Our study demonstrated that the BRCA1 mutation does not affect TNBC patients’ outcomes.

e12592 Background: The aim of the study is to assess the results of the treatment of 737 consecutive patients with DCIS with particular attention to the character of recurrences, other neoplasms and causes of deaths. Methods: A retrospective analysis was carried out of 737 consecutive DCIS patients treated in one institution in the years 1996-2011. The percentage of failures, causes of death, cumulated recurrence risk, DFS, OS depending on the method of treatment (mastectomy, breast conserving treatment BCT, breast conserving surgery BCS), was calculated. Results: 66 recurrences (42% DCIS, 58% invasive) were reported: 61 recurrences in the breast, 5 outside the breast. The comparison of mammography images before the initial treatment and after local recurrence revealed the true recurrence in the breast in 48/61 (79%) of cases. The cumulated recurrence risk after 15-year observation, after mastectomy, BCT and BCS was 3.2%, 19.5% and 31.2 %, respectively (p < 0.001). 15-year DFS after mastectomy, BCT and BCS was 72%, 65% and 48%, respectively (p < 0.001). 15-year OS after mastectomy, BCT and BCS was 75%, 83% and 70%, respectively, p = 0.329. In the course of the whole observation period 124 other neoplastic lesions in 121 patients (16%) were reported including 58 (8%) contralateral breast cancers. Deaths due to DCIS progression were reported in 4 (0.5%) of patients. An overwhelming majority (74/86) of deaths was linked to the age of the patients or other diseases, including other neoplasms. Conclusions: The highest recurrence risk reported in patients after BCS was unacceptable and, moreover, it kept growing over the fifteen years of observation. 79% of recurrences in the treated breast were true recurrences. Local recurrences were effectively treated without influence on OS. The percentage of deaths due to DCIS was low.

e12620 Background: Preoperative neutrophil-lymphocyte ratio (NLR) have been suggested to be correlated with the prognosis of patients with breast cancer (BC). However, the results still remain controversial. The goal of our study was to evaluate the predictive and prognostic value of NLR in early stage triple negative and HER2-pos breast cancer patients undergoing NAC. Methods: 96 female patients (pts) with histologically proven breast cancer (51 TNBC, and 45 HER2 pos) were analysed in this retrospective analysis. The NLR before the initiation of NAC was documented. Histopathological response in surgically removed specimens was evaluated using the Residual Cancer Burden (RCB) Calculator (by MD Anderson Cancer Center). The pCR was defined as no invasive tumor in primary tumor bed and lymph nodes. The NLR variable was analyzed as both continuous and categorical. The impact on pCR and RCB was tested using Mann-Whitney, Kruskal-Willis or the Chi-2 test, respectively. Results: Only 4 categories of NAC were used: in TNBC 4 x ACdd followed by 12 x PCL (38 pts) or 4 x ACdd followed by 12 x PCL+ carboplatin AUC 1.0-2 (13 pts), in HER2-pos 39 pts received 6 x TCH (docetaxel + tratuzumab + carboplatin AUC 6) and 6 pts 4 x ACdd followed by 12 x PCL iv + 4 x trastuzumab. In 27 pts (53%) with TNBC and 24 pts (53%) with HER2-pos breast cancer pCR was obtained after NAC. RCB distribution was: 0-53.1%, 1-22%, 2-17.6%, 3-7.3%. No association with NLR and pCR could be observed (p > 0.26). No association with NLR and RCB could be observed (p > 0.18). Conclusions: In our retrospective analysis we could not demonstrate predictive or prognostic value of NLR in the cohort of early stage triple negative and HER2-positive breast cancer patients treated with NAC. Further studies are planned in a group of patients with Luminal B, HER2 – negative breast cancer, who received NAC.

e12655 Background: Pathological complete response (pCR) after neoadjuvant chemotherapy (NACT) for breast cancer predicts the risk of recurrence and increasingly may indicate the need for additional therapy postoperatively. Methods: A retrospective analysis was performed in two cohorts of patients (pts) treated with docetaxel, trastuzumab and carboplatin (TCH) or with docetaxel, carboplatin and dual blockade (TCH-P) in the neoadjuvant setting in patients with early breast cancer (tumor size < 50 mm and > 10 mm and cN0 or cN1) in our Clinic, and who had definitive surgery was conducted. Demographic data, size, grade, tumor type, receptor status prior to neoadjuvant treatment, pathological complete response (pCR) rates, and adverse effects were analyzed. The pCR was defined as ypT0 ypN0. Results: Patient in cohort A (n = 58) received TCH x 6 cycles and in cohort B (n = 25) TCH-P x 6 cycles. Median age was 51 (range 23 to 76 years) in cohort A and 46 (range: 30-68) in cohort B. In cohort A 37 (64%) of pts was HR-positive, in cohort B only 9 (36%) pts . The most common adverse events in both groups were neutropenia, diarrhea, chemotherapy induced polyneuropathy and febrile neutropenia. There are no significant differences in the frequency of adverse events in two cohorts. There was no symptomatic heart failure, but 6 pts (10%) in cohort A and 5 pts (16%) in cohort B had > 10% asymptomatic decrease in LVEF. All patients were evaluable for pCR. Higher rates of pCR were achieved in the HER2pos/HRneg pts: 66% (n = 14) in cohort A, and 87% (n = 14) in cohort B. In group HER2pos/HRpos pts, the pCR rate was 48% (n = 18) vs 55% (n = 5) respectively. Conclusions: In HER2positive early breast cancer, a dual blockade (trastuzumab and pertuzumab) together with carboplatin and docetaxel neoadjuvant chemotherapy achieved higher rates of pCR ( 76%) compared with pts treated with trastuzumab, carboplatin and docetaxel (56%). However, a much higher percentage of pCR was observed in the group of patients with non-luminal cancers, who received a double blockade (87% vs 66%).

e12603 Background: To assess the value of the Van Nuys Prognostic Index (VNPI) used in Maria Sklodowska-Curie National Research Institute of Oncology (MSCNRIO) to select the most adequate method of the treatment of DCIS patients. Methods: The database covered 737 subsequent DCIS patients treated in MSCNRIO in the years 1996 -2011. The results of the treatment with and without compliance with the VNPI index were compared. Results: In the group of 737 patients 66 (9%) failures were reported. There were 4 (0.5%) deaths due to DCIS progression. After 15 years of observation of patients treated in compliance with VNPI, the percentage of failures after local excision (4-6 VNPI points), breast conserving treatment (7-9 VNPI points) and mastectomy (10-12 VNPI points) was 29%, 21% and 9%, respectively. No differences in the overall survival was observed. In patients with 4-6 VNPI points the percentage of recurrences in the group treated in compliance with the VNPI (without radiotherapy) was 29% while in the group treated without compliance with the VNPI (with radiotherapy) - 2%. Conclusions: The Van Nuys prognostic index (VNPI) does not seem to be an ideal tool in patients with DCIS. It shows too high percentage of recurrences in the low risk group (VNPI of 4, 5 or 6 points), treated exclusively with a sparing surgery. Almost all patients after surgical excision should be irradiated.

// Renata Duchnowska 1 , Piotr J. Wysocki 2 , Konstanty Korski 3 , Bogumila Czartoryska-Arlukowicz 4 , Anna Niwinska 5 , Marlena Orlikowska 6 , Barbara Radecka 7 , Maciej Studzinski 8 , Regina Demlova 9 , Barbara Ziolkowska 10 , Monika Merdalska 11 , Łukasz Hajac 12 , Paulina Myśliwiec 13 , Dorota Zuziak 14 , Sylwia Debska-Szmich 15 , Istvan Lang 16 , Malgorzata Foszczynska-Kloda 2 , Bozenna Karczmarek-Borowska 17 , Anton Żawrocki 18 , Anna Kowalczyk 18 , Wojciech Biernat 18 , Jacek Jassem 18 , for the Central and East European Oncology Group (CEEOG) 1 Military Institute of Medicine, Oncology Department, Warsaw, Poland 2 West Pomeranian Cancer Center, Szczecin, Poland 3 Greater Poland Cancer Center, Poznan, Poland 4 Bialystok Oncology Center, Bialystok, Poland 5 The Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland 6 Warmia and Masuria Oncology Center, Olsztyn, Poland 7 Opole Oncology Center, Poland 8 Oncology Center, Bydgoszcz, Poland 9 Masaryk Memorial Cancer Institute, Brno, Czech Republic 10 Chemotherapy Department, Regional Hospital, Wroclaw, Poland 11 Oncology Center, Kielce, Poland 12 Oncology Center, Wroclaw, Poland 13 Oncology Center, Zielona Gora, Poland 14 Oncology Center, Bielsko-Biala, Poland 15 Medical University of Łodź, Łodź, Poland 16 Department of Medical Oncology, National Institute of Oncology, Budapest, Hungary 17 Department of Chemotherapy, Subcarpathian Oncology Center, Rzeszow, Poland 18 Medical University of Gdansk, Gdansk, Poland Correspondence to: Renata Duchnowska, e-mail: rdtt@wp.pl Keywords: breast cancer, epidermal growth factor receptor type 2, lapatinib, mTOR, p-MAPK Received: May 19, 2015 Accepted: November 13, 2015 Published: November 24, 2015 ABSTRACT Molecular mechanisms of lapatinib resistance in breast cancer are not well understood. The aim of this study was to correlate expression of selected proteins involved in ErbB family signaling pathways with clinical efficacy of lapatinib. Study group included 270 HER2-positive advanced breast cancer patients treated with lapatinib and capecitabine. Immunohistochemical expression of phosphorylated adenosine monophosphate-activated protein (p-AMPK), mitogen-activated protein kinase (p-MAPK), phospho (p)-p70S6K, cyclin E, phosphatase and tensin homolog were analyzed in primary breast cancer samples. The best discriminative value for progression-free survival (PFS) was established for each biomarker and subjected to multivariate analysis. At least one biomarker was determined in 199 patients. Expression of p-p70S6K was independently associated with longer (HR 0.45; 95% CI: 0.25–0.81; p = 0.009), and cyclin E with shorter PFS (HR 1.83; 95% CI: 1.06–3.14; p = 0.029). Expression of p-MAPK (HR 1.61; 95% CI 1.13–2.29; p = 0.009) and cyclin E (HR 2.99; 95% CI: 1.29–6.94; p = 0.011) was correlated with shorter, and expression of estrogen receptor (HR 0.65; 95% CI 0.43–0.98; p = 0.041) with longer overall survival. Expression of p-AMPK negatively impacted response to treatment (HR 3.31; 95% CI 1.48–7.44; p = 0.004) and disease control (HR 3.07; 95% CI 1.25–7.58; p = 0.015). In conclusion: the efficacy of lapatinib seems to be associated with the activity of downstream signaling pathways – AMPK/mTOR and Ras/Raf/MAPK. Further research is warranted to assess the clinical utility of these data and to determine a potential role of combining lapatinib with MAPK pathway inhibitors.

e12062 Background: Identification of patients group with low risk DCIS that do not require radiation therapy after BCS is still a challenge. We assessed recurrence rates in patients with „good risk” DCIS with and without radiotherapy after BCS, and subsequently compared our results with the long-term data from RTOG 9804 trial [1]. Methods: Out of 737 patients with DCIS managed between 1996-2011 at the Cancer Center Warsaw, Poland, 400 were treated conservatively. Out of those 133 were classified as „good risk” patients in accordance with RTOG 9804 trial criteria (DCIS < 2.5 cm, mammographically detected, NG1/G2 with margin = > 3 mm). 79 patients received only BCS and another 54 patients were treated with BCS and radiotherapy. Competing risk of recurrence, DFS and OS were calculated for both groups. The results were compared with the long-term observation results of RTOG 9804 trial. Results: The competing risk of recurrence after 10 years in the group treated with BCS and in patients receiving BCS with radiotherapy was 26% and 6% respectively (p = 0.013). 10-year DFS was 58% and 88% (p = 0.02) and OS was 94% and 97% (p = 0.3) respectively. Based on the ASTRO Conference 2018, 10-year recurrence risk without and with radiotherapy in RTOG 9804 trial were 9.1% and 1.7% [1]. In our study in comparison to RTOG 9804 trial results, more patients had DCIS sized 1.1-2.5 cm, excision margins of 3-9 mm and no patient received adjuvant tamoxifen. Conclusions: Similarly to the results of RTOG 9804 trial [1], radiotherapy reduced recurrence rate in “good risk” DCIS, however, in our study the recurrence rate was higher - probably due to difference in risk factors and no tamoxifen use. 1.McCormick B et al. Randomized trial evaluating radiation following surgical excision for “Good Risk” DCIS: 12year report from NRG/RTOG 9804. ASTRO October 21, 2018.

Germline mutations in the BRCA1 tumor suppressor gene predispose affected individuals to breast cancer; however, incomplete cancer penetrance and the presence of phenocopies in BRCA1 families also indicate genetic and environmental modifiers of breast cancer risk. In this study, we have tested the single nucleotide polymorphism rs1655505 of the BRCA1 promoter, as candidate for the modifier of breast cancer risk. The polymorphic variants were genotyped in BRCA1-negative (729), familial breast and/or ovarian cancer cases (FBOC), including cases with a reported maternal history (154), nonfamilal (sporadic) cases (600), hereditary breast/ovarian cases with BRCA1 mutations (190) and population controls (1,590) from Central Poland. An association with the risk of FBOC was observed for the minor (T) allele and (TT) genotype (T: p = 0.006, OR = 1.40, 95% CI = 1.10-1.79; TT: p = 0.001, OR = 2.23, 95% CI = 1.37-3.62) in female cases with a reported maternal history, specifically in women with the onset of disease after 50 years of age (T: p = 0.004, OR = 1.77, 95% CI = 1.20-2.62; TT: p = 0.001, OR = 3.7, 95% CI = 1.62-8.46). The presented evidence suggests a need to conduct larger studies on the association between genetic variations at the BRCA1 promoter and the breast cancer risk, according to maternal/paternal lineage.

Possession of a BRCA1/2 mutation increases risk of contralateral breast and ovarian cancer recurrence and may have an impact on health management decisions, such as imaging screening, preventive surgical interventions and systemic therapies. A hospital-based study was conducted to assess the frequency and spectrum of pathogenic germline BRCA1 and BRCA2 mutations in Polish women with familial and nonfamilial breast cancer. Genomic DNA was extracted from 1581 women with breast cancer and from 2225 healthy individuals. For genotyping BRCA1 (5382insC, T300G, 3819del5, 185delAG, C5370T, 3875del4, 3896delT, 4153delA, 4184del4, 4160delAG, G5332A) mutations and BRCA2 (G1408T, 5467insT, 6174delT, 6192delAT, 6675delTA, 8138del5, 9152delT, C9610T, 9630delC) mutations, a Custom TaqMan (Applied Biosystems) PCR-based technology was adopted. A BRCA1 mutation was found in 26 and 12.5 % of women with familial breast cancer and in 13 and 8.3 % nonfamilial (sporadic) breast cancer, diagnosed before or after 50 years of age, respectively. A much lower frequency of BRCA2 mutation was observed. The predominance of seven BRCA1 mutations (5382insC, T300G, 3819del5, 185delAG, C5370T, 3875del4, 4153delA) studied in the Masovian voivodeship population confirmed a strong founder effect for BRCA1 mutations in the Polish population, and the results of BRCA2 testing confirmed a high diversity in the studied pathogenic mutations in BRCA2 gene. We propose offering inexpensive testing for the presence of BRCA1 founder mutations to all Polish women at the time of initial breast cancer diagnosis, regardless of the patient's family history or age of disease onset.

Purpose: The aim of the study was to present a new breast cancer recursive partitioning analysis (RPA) prognostic index for patients with newly diagnosed brain metastases as a guide in clinical decision making. Methods and Materials: A prospectively collected group of 441 consecutive patients with breast cancer and brain metastases treated between the years 2003 and 2009 was assessed. Prognostic factors significant for univariate analysis were included into RPA. Results: Three prognostic classes of a new breast cancer RPA prognostic index were selected. The median survival of patients within prognostic Classes I, II, and III was 29, 9, and 2.4 months, respectively (p < 0.0001). Class I included patients with one or two brain metastases, without extracranial disease or with controlled extracranial disease, and with Karnofsky performance status (KPS) of 100. Class III included patients with multiple brain metastases with KPS of

Aim: To perform a comprehensive analysis of patients with breast cancer and solitary or single brain metastasis and to analyze factors influencing survival from brain metastasis. Methods: One hundred consecutive patients with single or solitary brain metastasis were treated in one institution in the years 2003-2009. Brain lesions were diagnosed by magnetic resonance imaging (MRI). A total of 57% of patients underwent resection of brain metastasis, 95% of patients received whole-brain radiation therapy (WBRT) and 67% were treated systemically after WBRT. Results: Median survival from the detection of brain metastasis was 13 months and 28% of patients survived for 2 years. In 29 patients with solitary brain metastasis, median survival was 20 months (2-80 months) and in 71 patients with single brain metastasis it was 11 months (1-79 months) p = 0.01. Median survival from brain metastasis in patients with Recursive Partitioning Analysis Radiation Therapy Oncology Group (RPA RTOG) prognostic class I, II and III was 22 months (4-80 months), 13 months (2-79 months) and 6 months (0.4-28 months), respectively, p < 0.0001. Median survival from brain metastasis in triple-negative, HER2, luminal B and luminal A subtypes was 11 months, 13 months, 16 months and 15 months, respectively ( p = 0.60). Multivariate analysis revealed that RPA RTOG prognostic class I, neurosurgery and systemic therapy after WBRT were factors that correlated with survival. Conclusions: In patients with one metastatic lesion in the brain, affiliation to RPA RTOG prognostic class I and intensive local and systemic treatment had a strong correlation with survival. There was no significant correlation between biological subtype of cancer and survival. (C) 2011 Elsevier Ltd. All rights reserved.

e12561Background: Selecting patients with low risk DCIS in whom radiotherapy could be safely omitted is still debatable. The Van Nuys Prognostic Index (VNPI) which analyses 4 prognostic factors hel...

e12599Background: Trastuzumab sc with standard chemotherapy is approved for use in the neoadjuvant setting for HER2 -positive breast cancer patients. A retrospective analysis was performed in group...

The benefit of whole brain radiotherapy (WBRT) for RTOG RPA (Radiation Therapy Oncology Group Recursive Partitioning Analysis) class 3 patients with brain metastases is not well established. The aim of this study was to determine whether WBRT has any benefit in terms of symptoms palliation in such patients. Evaluation of patients' preferences for WBRT, changes in performance and neurological status were secondary aims.Ninety-one RTOG RPA class 3 patients were included. All patients received WBRT (20 Gy in 5 fractions) and were asked to complete a questionnaire about their symptoms before and one month after WBRT. The patient's symptom checklist comprised 17 items scored from 0 to 3; a higher score meant a greater symptom intensity. The mean scores at baseline and after treatment were compared. Karnofsky performance status (KPS) and neurological status before and one month after WBRT were also recorded. Patients were asked to express their preference as to the WBRT undergone.Forty-three (47%) patients completed both symptom checklists. The mean scores on the symptom checklist were 18.21 and 21.09 at baseline and one month after WBRT, respectively (p = 0.02). The KPS was estimated after WBRT in 42 patients: 57% of patients improved, 26% worsened, and 17% did not change from the baseline KPS score (p = 0.06). Neurological status did not change from baseline to one month after WBRT (p = 0.44). Only 7% of respondents would not have consented to the WBRT undergone.Our results challenge the palliative value of the WBRT in RPA class 3 patients.

Background: Our research focused on the relations between the age at onset of bilateral breast cancer and the prevalence of selected hereditary BRCA1, BRCA2 and &

The role of systemic treatment was assessed after local therapy for breast cancer patients who developed central nervous system (CNS) metastases as a first and isolated recurrence. Subjects were 128 breast cancer patients with brain metastases as the first and isolated site of recurrence that were selected from 673 consecutive breast cancer patients with brain metastases treated at the same institution. Median survival from brain metastases in patients with and without systemic treatment after local therapy was respectively 15 and 4 months (p

Recent studies have demonstrated that heterozygous carriers of the NBS1 657del5 mutation have an increased risk for familial and bilateral breast cancer, but similar studies in consecutive breast cancer patients were inconclusive. Here, in a study of 562 nonselected breast cancer patients from Central Poland, we found 11 (1.96%) 657del5 mutation carriers vs. 3.47 expected (OR 3.21, 95%CI: 1.36-7.61, p = 0.0107) and only 9 (1.6%) carriers of the 5382insC mutation of the BRCA1 gene, most frequently found among breast cancer patients in Poland. No carriers of R215W, another pathogenic mutation of the NBS1 gene, were found in the present study. All carriers of the 657del5 mutation had sporadic breast tumors while 5 of 9 5382insC carriers had a family history of breast/ovarian cancer or bilateral breast carcinoma. In the pooled group of patients from the present and our previous study, carried out also in patients from Central Poland, we obtained the following risk estimates (OR) for 657del5 carriers, as related to the age at breast cancer diagnosis:40 years: 8.36; (95%CI: 2.57-27.27) p = 0.0003;50 years: 4.27 (95%CI: 1.67-10.89) p = 0.003;or = 50 years: 2.40 (95%CI: 0.91-6.35) p = 0.1250; all ages: 3.13 (95% CI: 1.40-7.00) p = 0.0066. These findings demonstrate conclusively that NBS1 657del5 mutation carriers have a significantly, though moderately increased, age-related risk of breast cancer, and imply that in populations with a high 657del5 carrier frequency this mutation may contribute substantially to the overall incidence of breast cancer, particularly in younger age groups.

This was a prospective observational study to assess the results of the treatment of patients with breast cancer leptomeningeal metastasis (LM) and to compare the efficacy of methotrexate and liposomal cytarabine in patients treated intrathecally by lumbar puncture.In this prospective observational study, 149 consecutive patients with breast cancer and LM treated between the years 1999 and 2011 were assessed. Multimodality treatment methods were used: systemic therapy in 77 patients, radiotherapy in 92 patients, intrathecal methotrexate in 81 patients, and intrathecal liposomal cytarabine in 15 patients.The median survival of all patients was 4.2 months. The median survival of patients in whom systemic intravenous/oral treatment was used was 6 months, in those who did not have systemic treatment, the median survival was 2 months (P .001). The median survival of patients treated with intrathecal methotrexate was 4.2 months; in patients treated with intrathecal liposomal cytarabine, the median survival was 4.6 months, and in patients who did not receive intrathecal treatment, the median survival was 3.7 months (P = .717). Median survival after whole-brain radiotherapy was 4.6 months and with no radiotherapy, it was 3.2 months (P = .028). Multivariate analysis revealed a Karnofsky performance status (KPS) of 70. Systemic intravenous/oral treatment and bone as a site of metastasis were factors prolonging survival from LM.Among treatment methods, only systemic therapy prolonged survival in patients with LM. Neither radiotherapy nor lumbar intrathecal therapy influenced survival in those patients; however, both methods alleviated signs and symptoms of LM. No difference in survival was observed in patients treated intrathecally with methotrexate and those treated with liposomal cytarabine. Treatment with both drugs was comparable.

Background Breast cancer is the most common type of cancer and the second leading cause of cancer-death among women in Poland. The known high-risk mutations account for 25% of familial aggregation cases and 5% of total breast cancer predisposition. Genome-wide association studies have identified a number of common low-penetrance genetic variants, but their contribution to disease risk differs between populations. Methods To verify selected associations with breast cancer susceptibility among Polish women, the replication study was performed, included 1424 women with breast cancer and 1788 healthy persons. Sixteen single-nucleotide polymorphisms (SNPs) were analyzed using TaqMan SNP Genotyping Assays. Allele frequency differences were tested using chi2-test implemented in PLINK v1.07 and Cochran-Armitage trend test was performed using R software. Results Significant differences (Bonferroni corrected p-valuecor ≤ 0.0197) in the frequency of alleles distribution between all cancer and control subjects were observed for four (rs2736098, rs13281615, rs1219648, rs2981582) out of 16 SNPs. The same result was obtained for group of patients without high-risk BRCA1/2 mutations. The rs1219648 (p-valuecor ≤ 6.73E-03) and rs2981582 (p-valuecor ≤ 6.48E-03) SNPs showed significant association with both familial and sporadic cancers. Additionally, rs2736098 (p-valuecor ≤ 0.0234) was associated with only sporadic cancers; also in group without carriers of high-risk mutation. All these associations revealed their significance also in Cochran-Armitage trend test. Opposite to other SNPs, rs2736098 was associated with a decreased risk of breast cancer. Conclusion The association of four known susceptibility SNPs, representing three individual loci, with breast cancer risk in Polish women was confirmed. One of them (rs2736098) seems to be specific for the Polish population. Due to the population differences in allele frequencies, identification of general genetic risk factors requires sets of association studies conducted on different populations.

e11553 Background: The aim of the study was to assess the rate, pattern and time of recurrence in patients with triple-negative breast cancer (TNBC) treated in one institution. The second goal was to evaluate factors influencing recurrence and overall survival in this group of patients. Methods: 2534 consecutive breast cancer patients were diagnosed at the Cancer Center and Institute of Oncology in Warsaw, Poland, between January 2005 and December 2006. Out of 2534 patients, 228 (9%) were TNBC (ER/PR/HER2-negative). The clinicopathological characteristics were determined using descriptive statistics. The overall survival (OS) and disease-free survival (DFS) were calculated using the Kaplan-Meier method. The univariate and multivariate analyses were developed to identify factors influencing recurrence and survival in TNBC patients. Results: Most of the patients were diagnosed with stage II or III breast cancer (47% and 34%, respectively), the median age at diagnosis was 54.5 years. The most common histological type was ductal cancer (81%). 31% of patients were treated with neoadjuvant chemotherapy and 49% with adjuvant chemotherapy – almost all consisted of anthracyclines. 6 years of observation revealed that the metastatic disease occurred in 35% of all TNBC patients: 15% in the brain, 14% in the lungs, 11% in the bones, 8% in the liver and 14% had locoregional relapse. The highest risk of recurrence was during the first 3 years after primary treatment and then during the next two years of observation it did not change. Median DFS and OS were not reached at the time of analysis, 6-year DFS and OS were 68% and 62%, respectively.Factors influencing recurrence were: tumor size and systemic adjuvant chemotherapy while factors influencing overall survival were: tumor size, nodal status, adjuvant/neoadjuvant treatment and metastases in the brain, liver and bones. Conclusions: Characteristic pattern of recurrence in time was revealed. The tumor size was responsible for recurrence despite lack of involvement of lymph nodes. Aggressive adjuvant/neoadjuvant treatment ordered in all clinical stages of TNBC (including N0) was factor responsible for avoiding local and distant relapse and prolonging overall survival.

The aim of the study was to define biological subtypes of breast cancer that have the propensity to metastasize to the leptomeninges and to assess factors influencing survival from detection of leptomeningeal metastatis (LM). One hundred and eighteen consecutive breast cancer patients with LM were treated in one institution, between the years 1999 and 2009; 40.5 % of patients had triple-negative subtype, 37.5 % had luminal A subtype and 22 % had HER2-positive subtypes (luminal B and HER2). Of patients with LM, 35 % had lobular cancer. Median survival from the detection of LM was 18 weeks, and 1-year survival was 16 %. Cox multivariate analysis revealed that performance status and systemic treatment statistically significantly influenced survival of patients with LM. Triple-negative biological subtype and lobular histological type of breast cancer had the propensity to metastasize to the leptomeninges. Performance status and systemic treatment ordered after detection of LM statistically significantly influenced survival.

e13527Background: The role of systemic treatment was assessed after local therapy for breast cancer patients who developed central nervous system (CNS) metastasesas a first and isolated recurrence....

The aim of this study was to divide the group of triple-negative breast cancer patients with brain metastases into basal-like and non-basal-like biological subtypes in order to compare clinical features and survival rates in those two groups. A comprehensive analysis of 111 consecutive triple-negative breast cancer patients with brain metastases treated in the years 2003–2009 was performed. In 75 patients, immunohistochemistry was used as a surrogate of microarray in order to evaluate the expression of three basal markers: cytokeratin 5/6 (CK 5/6), EGFR/HER1 and c-KIT. The basal-like (ER/PgR/HER2-negative, CK5/6positive and/or HER1-positive) and non-basal-like (ER/PgR/HER2-negative, CK5/6-negative, HER1-negative) subsets were selected. Clinical features and survivals were compared in both groups. In the group of 111 triple-negative breast cancer patients, median DFS, OS and survival from brain metastases were 20, 29 and 4 months, respectively. In 75 patients who were evaluable for basal markers, median DFS, OS and survival from brain metastases were 18, 26 and 3.2 months, respectively. In the basal-like subtype, the survival rates were 15, 26 and 3 months, respectively, and in the non-basal-like subtypes, they were 20, 30 and 2.8 months, respectively. No statistically significant differences in survivals were detected between the basal-like and non-basal-like biological subtypes. Factors influencing survival from brain metastases were: Karnofsky performance status (KPS), the status of extracranial disease and age. Biological markers differentiating triple-negative group into basal-like and non-basal-like subtype (CK 5/6, HER1, c-KIT) had no influence on survival. In patients with triple-negative breast cancer and brain metastases, well-known clinical, but not molecular, features correlated with survival.

BACKGROUND: The aim of this study was to assess the role of systemic treatment after whole-brain radiotherapy (WBRT) in immunohistochemically defined biological subsets of breast cancer patients with brain metastases. METHODS: The group of 420 consecutive breast cancer patients with brain metastases treated at the same institution between the years of 2003 to 2009 was analyzed. Patients were divided into 4 immunohistochemically biological subsets, based on the levels of estrogen, progesterone, and human epidermal growth factor receptor 2 (HER2) receptors, and labeled as luminal A, luminal B, HER2, and triple-negative. Survival from brain metastases with and without systemic treatment after WBRT was calculated in 4 subsets. RESULTS: In the entire group, the median survival from brain metastases in patients without and with systemic treatment after WBRT was 3 and 10 months, respectively (P < .0001). In the triple-negative subset, the median survival from brain metastases with and without systemic treatment was 4 and 3 months (P ¼ .16), and in the luminal A subset, it was 12 and 3 months, respectively (P ¼ .003). In the luminal B subset, the median survival without further treatment, after chemotherapy and/or hormonal therapy, and after chemotherapy and/or hormonal therapy with targeted therapy was 2 months, 9 months, and 15 months, respectively (P < .0001). In the HER2 subset, the median survival was 4 months, 6 months, and 13 months, respectively (P < .0001). No significant response to systemic treatment was noted in the triple-negative breast cancer population. CONCLUSIONS: Systemic therapy, ordered after WBRT, appears to improve survival in patients with the luminal A, luminal B, and HER2 breast cancer subtypes. Targeted therapy was found to have an additional positive impact on survival. In patients with triple-negative breast cancer, the role of systemic treatment after WBRT appears to be less clear, and therefore this issue requires further investigation. Cancer 2010;116:4238–47. V C 2010 American Cancer Society.

Identification of mutations in the BRCA2 gene and estimation of their clinical consequences for women and men treated in the Maria Sklodowska-Curie Memorial Cancer Center Warsaw, Poland in the years 1998-2008. The probands (97 women and 8 men) had a family history of breast and ovarian cancer (median age 46). The presence of molecular changes was examined in DNA isolated from peripheral blood lymphocytes. Germline mutations in 27 exons of the BRCA2 gene were screened by 'touchdown' PCR amplification, DHPLC and sequencing. Missense mutations were classified by multiple-sequences alignments of orthologous BRCA2 protein sequences with T-Coffee software. 39 molecular changes (8 novel) were identified in the BRCA2 gene in 105 investigated patients. In 12 patients the following pathogenic mutations were identified: 5467insT, 6174delT, 6192delAT, 6675delTA, 8141del5, 9152delT, 9326insA, 9631delC, IVS23-2A > G and E394X. The presence of 10 missense type mutations was detected including the following: D1420O, T1915 M, N3124I. The determination of pathogenic status of molecular variants detected in BRCA2 gene, described in the BIC mutation database as 'UV' depends on many parameters. Important is the assessment of the evolutionary conservation of their protein sequences and studying of the frequency of molecular variants detected in breast cancer patients and in population. A high diversity was found of the pathogenic mutations detected in BRCA2 gene in the Polish population.

Our research focused on the relations between the age at onset of bilateral breast cancer and the prevalence of selected hereditary BRCA1, BRCA2 and CHEK2 gene mutations with reference to their positive family history of cancer.The DNA of peripheral blood lymphocytes of patients was examined for the presence of selected hereditary mutations in the BRCA1, BRCA2 and CHEK2 genes, using molecular biology techniques. The family history of neoplasms was also analyzed.The following mutations in the BRCA1 gene were identified: 185delAG, C61G, 5382insC, 3875 del11ins7, and R1751X. In the BRCA2 gene, the 9631delC and A9599T mutations were found. In the CHEK2 gene, the 1100delC and I157T mutations were identified. BRCA1/2 gene mutations were identified in 19.4% of patients and CHEK2 gene mutations in 7%.It was shown that the presence of the mutations in the BRCA1/2 genes among patients with bilateral breast cancer is associated with an earlier occurrence of the first and the second breast cancer than in patients without hereditary mutations in these genes (a difference of 7.2-8.4 years). In patients with CHEK2 gene mutations, breast cancer occurred 2.1-3.8 years earlier than in patients without mutations in the CHEK2 gene.

Purpose The aim of the study is to evaluate disease-free survival, survival from the detection of brain metastases, overall survival, and cause of death in patients with occult brain metastases (Group I) vs. patients with symptomatic brain metastases (Group II). Methods and Materials In 80 HER2-positive breast cancer patients, treated with trastuzumab and cytostatic agents for metastatic disease, magnetic resonance imaging screening of the brain was performed, and in 29 patients (36%) occult brain metastasis was detected (Group I). Whole-brain radiotherapy was delivered to Group I. This first group was compared with 52 patients who had symptomatic brain metastases (Group II) and was treated the same way, at the same clinic, during the same time period. Results Median disease-free survival was 17 months in Group I and 19.9 months in Group II ( p = 0.58). The median time interval between the dissemination of the disease and the detection of occult or symptomatic brain metastases was 9 and 15 months, respectively ( p = 0.11). When the brain metastases were detected, the median survival was 9 and 8.78 months, respectively ( p = 0.80). The median overall survival was 53 and 51 months, respectively ( p = 0.94). In the group with occult brain metastases (Group I) 16% of patients died because of progression within the brain. In the group with symptomatic brain metastases (Group II) the rate of cerebral death was 48% ( p = 0.009). Conclusions Whole-brain radiotherapy of occult brain metastases in HER2-positive breast cancer patients with visceral dissemination produces a three-fold decrease in cerebral deaths but does not prolong survival.

The aim of the study was to assess the efficacy of multimodality treatment of patients with Leptomeningeal metastasis (LM) and to establish which method of treatment has the greatest positive impact on survival.Clinical material included 67 consecutive breast cancer patients with LM treated at the Cancer Center in Warsaw between the years 2000 and 2005. Intrathecal chemotherapy was given to 57 pts (85%), intravenous chemotherapy to 41 pts (61%), whole brain radiotherapy to 33 pts (49%) and radiotherapy to the spinal leptomeninges to 10 (15%). For 27 pts (40%) three methods of treatment were used. Univariate and multivariate analyses were used to evaluate the impact of the particular method of treatment on survival and to assess the efficacy of combined modalities.Clinical response was achieved in 49 pts (76%). Median survival calculated from the diagnosis of LM was 16 weeks (range 1-402 weeks). Univariate analysis showed positive impact of systemic intravenous chemotherapy (P = 0.0009), intrathecal chemotherapy (P = 0.008) and whole brain radiotherapy (P = 0.004) on survival. The results of Cox multivariate analysis have shown systemic chemotherapy (P0.001) and intrathecal chemotherapy (P = 0.001) to be significant.Intravenous chemotherapy and, independently, intrathecal chemotherapy improve survival in breast cancer patients with LM. Radiotherapy has a positive impact on the quality of life due to the alleviation of neurological symptoms. The role of radiotherapy in prolonging survival is questionable.