bluuebunny/crossref_metadata_2025_split huggingface dataset:
The negative prognostic impact of downstaging after neoadjuvant chemotherapy in patients with hormone-receptor positive breast cancer.
Authors: Takahashi Yuko , Hayashi Naoki , Matsuda Naoko , Kajiura Yuka , Yoshida Atsushi , Yagata Hiroshi , Nakamura Seigo , Suzuki Koyu , Tsunoda Hiroko , Yamauchi Hideko 
Published: March 2020

e11524 Background: While pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) improves patients’ survival, it is not well known whether or not chemosensitivity contributes to improve survival of patients who had non-pCR. The aim of this study was to evaluate the impact of chemosensitivity presented by downstaging after NAC on prognosis in patients with primary breast cancer. Methods: We assessed retrospectively 773 patients with primary breast cancer who underwent surgical resection after NAC between 2001 and 2008 (a median age 49 years, range 26-79 years). 572 patients (74.0%) had hormone-receptor positive tumor and 131 patients (16.9%) had HER2 positive tumor. One hundred forty six patients (18.9%) underwent sentinel node biopsy before NAC. We divided patients into two groups based on chemosensitivity: the downstaging (DS) group and the non-downstaging (non-DS) group. We compared the groups with respect to both disease-free survival (DFS) and overall survival (OS).According to hormone-receptor status and HER2 positivity, pCR was defined as no residual invasive and ypN0. Results: Before NAC, 37 patients had clinical Stage I (4.8%), 613 had cStage II (79.3%), and 123 had cStage III (15.9%). After NAC, 181 had ypStage I (23.4%), 306 had ypStage II (39.6%), and 175 had ypStage III (22.6%). One hundred eleven patients (14.4%) had pCR. Two hundred ninety seven patients (38.4%) had DS and 476 patients (61.6%) had non-DS. Of all patients, patients with DS had significantly longer DFS and OS than non-DS patients (p=0.01, 0.04, respectively). However, among 252 hormone-receptor positive patients with ypStage II, patients with DS (cStage III, n=21) had significantly shorter DFS than patients with non-DS (c Stage±/II, n = 231) (p<0.001). In terms of overall survival, patients with DS had a similar trend compared to patients with non-DS in this population. Conclusions: Our results indicated that hormone-receptor positive breast cancer patients with cStage III before NAC, even after having ypStage II, have worse prognosis than patients with cStage II, therefore, these patients may need additional treatment in the adjuvant setting.
A retrospective study in the Spanish population with Oncotype dx recurrence score (RS) in breast cancer patients with positive and negative-lymph nodes.
Authors: Estevez Laura G , Calvo Isabel , Abad Maria Fernandez , Cruz Juan Jose , Perea Sofia , Suarez Ana , Lopez Rios Fernando , Hidalgo Manuel 
Published: March 2020

e11531 Background: The international guidelines include the use of Oncotype DX as a predictor of chemotherapy (CT) benefit in hormonal sensitive breast cancer patients (pts) with node negative and node positive (1-3 positive nodes) disease.The aim of this study was to assess the distribution of the RS in breast cancer pts regardless lymph nodes status, and the association with treatment recommendations. Methods: Retrospectivedata from 131 pts with invasive breast cancer for which the OncotypeDX Assay had been ordered, and pathology data were available. Estrogen (ER) and progesterone (PR) receptor was assessed by IHC (cut-off 10% nuclear staining). Ki67 by IHC [high (≥14%) and low (< 14%)]. Positive-lymph nodes pts was classified as isolated tumoral cells (ITC), micrometastasis (MIC) and macrometasis (MAC). Results: Median age: 51 (range: 35-78); premenopausal status: 74 pts (56%). Median tumor size: 1.5 cm (0.3- 6); Median Ki 67 index: 15 (3-63); Median ER: 93 (35-100) and PR: 85(0-100). 42 pts (32%) had positive-lymph nodes: 6 ITC (14%), 14 MIC (33%) and 22 MAC (52%). RS was low in 82 (63%) cases, intermediate 39 (30%), and high 10 (7%). RS according to nodal status was: positive nodes, 31 pts (74%) low RS, 10 pts (24%) intermediate and 1 pts (2%) high; negative nodes: 50 pts (57%) low RS, 26 (29%) intermediate and 12 pts (14%) high RS. ER and Ki67 was similar between both lymph-nodes groups whereas a higher PR expression (median 90) was seen in positive-lymph nodes vs 76 in negative nodes. First recommendation in positive-lymph nodes: hormonotherapy (HT) 33%, CT 55% and 12% no defined (ND); after RS, HT 83% and CT 17% (p=0.021). Negative nodes first recommendation: HT 68%, CT 23% and ND 14%; after RS, HT 68% and CT 32%. Conclusions: Although based on a small case series, the results show that a substantial number (73%) pts with positive-lymph nodes have low RS, indicating minimal if any benefit from adjuvant CT. The proportion of patients with low scores is higher than in the validation studies and selection bias can’t be excluded. The wide range of RS in both negative and positive-lymph nodes breast cancer confirm the important role of Oncotype DX in treatment decision- making.
Pathologic response and disease-free survival (DFS) after neoadjuvant trastuzumab (T) for HER2+ breast cancer (BC): Results from the National Cancer Institute (NCI) of Mexico.
Authors: Villarreal-Garza Cynthia Mayte , Soto-Perez-de-Celis Enrique , Sifuentes Erika , Chavarri Guerra Yanin , Ruano Santiago , Baez-Revueltas F. Berenice , Lara-Medina Fernando , Acevedo Jose Antonio 
Published: March 2020

e11533 Background: The most accurate definition of pathologic complete response (pCR) in HER2+ BC patients (pts) receiving T-based neoadjuvant chemotherapy associated with improved DFS is controversial, particularly regarding the role of residual ductal carcinoma in situ (ypTis) and focal invasive residuals (ypT1mic). The effect of pCR on DFS in various subgroups of HER2+ BC is also uncertain. Methods: Pts with localized HER2+ BC that received T-based neoadjuvant chemotherapy at NCI between January 2007 and May 2012 were identified. We conducted an exploratory analysis of DFS in pts according to their tumor response. DFS curves were derived from Kaplan-Meier estimates and compared by log-rank test. Multivariate analysis was performed using Cox’s regression model. Results: 243 pts were included for analysis. Median follow-up was 39 months (mo). 49% of pts had no invasive and no in situ residuals at surgery (ypT0), 14.4% had ypTis/ypT1mic residuals and 36.6% had gross residual BC. DFS was significantly superior in pts with both ypT0 and ypTis/ypT1mic (no gross invasive residual BC) compared with those with gross residual disease (60.6 and 62.7 mo respectively vs. 51.6 mo, p=0.011 and 0.017). There was no difference in DFS between ypT0 and ypTis/ypT1mic pts (p=0.402). The rate of no gross invasive residual BC was significantly superior in pts with ER-PR- tumors compared with patients with ER+/PR+ tumors (69.9% vs. 56.7%, p=0.034). No gross invasive residual BC was associated with improved DFS in pts with HER2+ ER-/PR- (60.3 vs. 49.0 mo; p=0.005), as opposed to HER2+ ER+/PR+ tumors (61.0 vs. 51.6 mo; p=0.100). Multivariate analysis showed that tumor size (p=0.013) and no gross invasive residual BC (p=0.13) were associated with improved DFS in all subgroups. Conclusions: The absence of gross invasive residual BC was associated with improved DFS in pts with HER2+ BC treated with T-based neoadjuvant chemotherapy, particularly in those with HER2+ ER-/PR- BC. Our data suggest a comparable DFS in HER2+ BC patients with no gross invasive residual BC regardless of the presence or absence of both ypTis and ypT1mic disease after neoadjuvant treatment.
Inflammatory markers in early-stage breast cancer.
Authors: Petekkaya Hilbrahim , Aksoy Sercan , Gecmez Gizem , Kulahcioglu Emre , Okoh Alexis K. , Isler Deniz Cagın , Demirci Abdullah Fatih , Sahin Ugur , Dogan Erkan , Altundag Kadri 
Published: March 2020

e11537 Background: In a few number of studies a possible relationship between inflammatory markers and the prognosis, chemotherapy response and survival in breast cancer has been reported. The aim of this study is to point out the place of serum markers as a prognostic factor in early stage breast cancer. Methods: This study was conducted in Hacettepe University Cancer Institute. Patients operated and stage IA to III C for breast cancer between December 2009 and June 2012 were included the study. Before the any adjuvant therapy inflammation markers were studied. Results: A total of 704 patients were included in the study. The median age of the patients was 50 (25-92). 42,8% of the patients were premenopausal and 48,2% postmenopausal. The median follow up period for the whole study group was 22 months (3-287). We studied the CRP, erythrocyte sedimentation rate, B2 microglobulin, LDH, albumin, and ferritin studied and values for each marker were grouped as high and normal. There was no statistically significant difference in disease free survival and overall survival for each marker who had high and normal levels. Conclusions: We did not found any inflammatory markers as a prognostic value. However our follow up time is short and we should be wait for more mature data.
Efficacy of exemestane and everolimus in HR positive (including HER2-neu positive) heavily pretreated cases of metastatic breast cancer in north India.
Authors: Aggarwal Shyam , Yadav Prashant , Rawat Krishna , Bhalla Sunita 
Published: March 2020

e11546 Background: M-Tor pathway is deregulated in significant percentage of patients with breast cancer. This pathway is responsible for tumor growth and metastasis especially in hormone receptor (HR) positive cases. Thus dual blockade of estrogen and M-Tor pathway has shown efficacy in this setting. Methods: Twenty patients with hormone receptor positive metatstatic breast cancer were treated with combination of everolimus 5 mg and exemestane 25 mg daily since November 2011. The median age was 53 years (age range- 32 to 75 years). All patients had two more sites of metastasis. 14 cases had 3 or more sites of metastasis. Liver- 10, lungs – 15, bones – 12, skin -3, lymph nodes – 10, and CNS – 5. Six of twenty cases were Her2 neu positive and were pretreated with Herceptin and lapatinib. All except 2 patients were treated with chemotherapy, 13 with minimum three lines of chemotherapy. All patients were ER and or PR positive and preteated with tamoxifen (5) and or aromatase inhibitors (anastrozole 9 and letrozole 11). The time gap between starting exemestane and everolimus and onset of metastatic disease was 2.5 years. Results: 7 out of 20 patients achieved disease control (either partial response-6 or stable disease -1). Out of 6 cases who were her2 neu positive, two achieved partial response. 5 out of 20 cases survive beyond nine months. Only two patients could go on to 10 mg daily everolimus. The dose limiting toxicity was development of oral ulcers. One patient had fever. No case of pneumonitis was noted with this dose. Conclusions: Combination of everolimus and exemestane is effective in HR positive cases and also in Her2 neu positive cases. 5 mg everolimus is well tolerated by most women. There is a need to further study the efficacy of this combinantion in Her2 neu positive cases.
Association of CYP1A1 A4889G and T6235C polymorphisms with the risk of breast cancer in Brazilian women.
Authors: Oliveira Camila Borges Martins , Cardoso-Filho Cassio , Bossi Leonardo Da Silveira , Costa-Gurgel Maria Salete , Lourenco Gustavo Jacob , Lima Carmen Silvia Passos 
Published: March 2020

e11551 Background: Estrogen, activated by cytochrome P450 enzymes (CYP1A1), participates in the breast cancer (BC) development. G and C variant alleles of CYP1A1 A4889G and T6235C polymorphisms encode enzymes with increased activity in activation of this compound when compared with the respective wild alleles. This study aimed to clarify the roles of the polymorphisms in the risk of BC. Methods: CYP1A1 A4889G and T6235C genotypes of 742 sporadic breast cancer (SBC) patients (median age: 52 years, 638 Caucasians, 104 non-Caucasians) and 742 healthy women (median age: 40 years, 638 Caucasians, 104 non-Caucasians) were obtained in genomic DNA by PCR and enzymatic digestion. Results: Patient’s and control’s samples were in HW equilibrium at CYP1A1 A4889G (χ2= 0.15, P= 0.70; χ2= 1.15, P= 0.28) and T6235C (χ2= 2.65, P= 0.10; χ2= 1.93, P= 0.16) loci. The frequency of CYP1A1 4889AG+GG genotypes was higher in patients than in controls (29.0% versus 23.2%, P= 0.004). Carriers of the G allele were under a 1.50 (95% CI: 1.14-1.97)-fold increased risk for SBC than those with the wild AA genotype. The frequencies of 4889AG+GG genotypes in Caucasian SBC patients were higher than those found in Non-Caucasian (30.4% vs 20.2%, P= 0.03), and also in controls (30.4% vs 23.2%, P= 0.002). Carriers of G allele were under a 1.61 (95% CI: 1.20-2.15)-fold increased risk for SBC than others. A higher frequency of the CYP1A1 4889AG+GG genotypes was also seen in patients with an earlier median age at first full-term pregnancy (FFTP), compared to those who had the first pregnancy with a later medium age (33.8% vs 26.1%, P=0.03), and also when compared to controls (33.8% vs 23.2%, P= 0.001). Women with the CYP1A1 4889AG+GG genotypes and with earlier FFTP were under a 1.87 (95% CI: 1.32-2.67)-fold increased risk for SBC than others. The CYP1A1 6235CC genotype was more common in pre-obese or obese SBC patients than in underweight or normal SBC patients (6.8% vs 4.0%, P= 0.04). Conclusions: Our data suggest that CYP1A1 A4889G and T6235C polymorphisms alter BC risk in Brazilian women. We believe that women with variant alleles of the referred polymorphisms should receive additional medical attention for disease prevention and early diagnosis.
Outcomes of patients with HER2-negative breast cancer with central nervous system metastasis treated with capecitabine.
Authors: Altundag Kadri , Aksoy Sercan , Sendur Mehmet Ali Nahit , Guler Emine Nilufer , Gullu Ibrahim Halil , Ozisik Yavuz Yasin 
Published: March 2020

e11553 Background: Systemic chemotherapy is often ineffective due to the impermeability of the blood-brain barrier (BBB) and inherent chemoresistance of CNS metastases. There are limited data supporting the use of capecitabine in this setting. The aim of this study was to evaluate the effectiveness and toxicity of capecitabine in breast cancer patients with CNS metastasis. Methods: The records of all patients with HER-2 Negative breast cancer with CNS metastasis that treated with capecitabine monotherapy were evaluated. All patients recieved capecitabine at a dose of 2,500mg/m2/day for 14 days at 3 weeks intervals. Results: Fifty-eight female patients with a median age of 42 years (min-max; 20-68) were included in this retrospective analysis. The median time to brain metastasis was 3.1 years (min-max; 0.5-15.5). Thirty (51%) patients were hormone positive, and twenty-nine (49%) were triple-negative. Forty-seven (78%) patients recieved capecitabine as first line treatment after the CNS metastasis. Only 4 patients had undergone surgery for CNS metastasis, and all patients had recieved whole brain radiotherapy before the capecitabine treatment. Five (8.5%) patents were treated with cyberknife radiosurgery. There were 6 (10%) complete (2 patient had metastasectomy for brain metastasis), and 21 (36%) partial responses with 9 (15%) patients having stable disease. Progressive disease was observed in 16 (28%) patients. 6 patients were not evaluabled for radiological evaluation. Median progression free survival time was 5 months, and median overall survival was 8.6 months. Dose reduction was required due to adverse effects in 20 patients (24%). The most frequent side effect was the hand-food syndrome (HFS), which developed in 29 patients (50%). Forty-percent of them developed grade 3 HFS disease. Diarrhea occurred in 21% of the patients, nausea in 19% of the patients. Grade 3-4 myelosupression were developed in 15% of the patients. There was no treatment-related death. Conclusions: Capecitabine is effective and well tolerated in the treatment of breast cancer patients with CNS metastases. It is feasible options HER2 negative breast cancer patients especially with neurological deficits.
Comparison of the efficacy of adjuvant letrozole and anastrozole in hormone-receptor positive postmenopausal breast cancer patients.
Authors: Sendur Mehmet Ali Nahit , Aksoy Sercan , Altundag Kadri 
Published: March 2020

e11554 Background: In the adjuvant hormonal treatment of postmenopausal breast cancer patients, most of the trials have showed the superiority of aromatase inhibitors over tamoxifen. However, there are limited data in the literature comparing the efficacy of aromatase inhibitors in postmenopausal women. Thus, the aim of this study is to compare the efficacy of letrozole and anastrozole in hormone-receptor positive postmenopausal breast cancer patients. Methods: Newly diagnosed breast cancer patients from 2001 to 2012 in our clinic were retrospectively analyzed. A total 566 hormone receptor-positive postmenopausal breast cancer patients were analyzed. The patients were divided into two group; anastrozole group (n=235) and letrozole patients (n=331). Kaplan–Meier survival analysis was carried out for disease free survival (DFS) and overall survival (OS). The log-rank test was used to examine the statistical significance of the differences observed between the groups. Results: The mean age was 59.2±8.5 in anastrozole group, and 60.1±8.4 in letrozole arm (P = 0.19). The mean BMI was 29.4±5.1 kg/m2 and 29.3±5.3 kg/m2 of anastrozole and letrozole arm, respectively (P =0.84). The median follow-up time for this analysis was 25.1 months. The histology of the primary tumor and type of surgery was similar and not statistically significant in both groups. Also in both arms the incidence of lymphovascular invasion, perineural invasion, HER2 positivity and histological grade were similar and not statistically significant. There were no apparent differences in baseline nodal status (P = 0.43), tumor size (P = 0.58) and tumor stage (P = 0.15) between two treatment arms. In anastrozole arm DFS rate was 93.7%, 81.3% and 66.0% whereas in letrozole arm DFS rate was 90.6%, 78.7% and 68.5% in the first, third and fifth years respectively. Median OS could not be obtained due to low events in both groups. Three year survival rate in anastrozole group was 98.8%, whereas in letrozole arm was 96.7% (P=0.84). Conclusions: In this retrospective study, the efficacy of letrozole and anastrozole was similar in hormone-receptor positive postmenopausal breast cancer patients.
Phase II chemoprevention trial: Anastrozole in DCIS and early invasive hormone-receptor (HR) positive breast cancer in postmenopausal women.
Authors: Huynh Richard , Mehta Rita S. 
Published: March 2020

e11562 Background: Anastrozole, an aromatase inhibitor, decreases estrogen synthesis and is therefore, an effective treatment of (HR) positive breast cancer. We hypothesized that a short course of anastrozole can decrease levels of Ki-67, a surrogate measure of chemoprevention (the primary endpoint), and there may be correlation in Ki-67 reduction and decreased size of tumor on MRI (the secondary endpoint). Methods: In a single group phase II trial, 42 postmenopausal women with HR positive DCIS or early invasive breast cancer following diagnostic biopsy were enrolled. Patients were given 1 mg anastrozole for 2-4 weeks. Patients had an MRI before and after anastrozole, and then underwent surgery for measurement of change in Ki-67. The specimens were histologically graded on Ki-67, estrogen receptor (ER), progesterone receptor (PR), and Nottingham grade to compare pre and post-therapeutic effects of anastrozole. The two-sided Wilcoxon signed-rank test and Fisher’s exact test were utilized to analyze the data. Spearman correlation coefficients were obtained to assess the correlation between Ki-67 and MRI. Results: 34 patients were eligible. 15 out of 23 patients (65.2%) had decreased Ki-67, 5 (21.7%) had no change and 3 (13.0%) had increased Ki-67 levels. On average, there was a significant decrease in Ki-67 level of 4.9 from baseline (95% CI 1.8, 8.0; p-value=0.004). There was a significant decrease in grade of 0.3 (0.10, 0.49; p-value=0.016). Out of 34 patients, 5 patients (14.7%) showed a pathological complete response. In terms of HR, on average, there was a significant decrease in PR of 34.5 (8.98, 60.2; p-value=0.021). However, there was no significant change in ER (p-value=0.96). Among the 12 patients who had both Ki-67 and tumor size data available, there was low correlation between the change of Ki-67 level from baseline and the change of tumor size determined by MRI (R=0. 34). Conclusions: Anastrozole, as preoperative therapy for 2-4 weeks was effective in reducing Ki-67 in early invasive HR positive breast cancer. Thus the study met its primary endpoint, and therefore supports chemo preventive effects of aromatase inhibitors as shown in large chemoprevention trials. Clinical trial information: NCT00256217.
ER, PR, and HER2 assessment in Hispanic women with breast cancer: A comparison between IHC and AQUA technology.
Authors: Di Marco Anna Maria , Ruiz Jose Alberto , Moreno Maryangely , El Hader Carlos , Baez Luis 
Published: March 2020

e11568 Background: Estrogen (ER), progesterone (PR) receptors and HER2 are important markers for breast cancer (BC) treatment planning. These markers are often measured by immunochemistry (IHC) but IHC is subject to limitations of operator subjectivity and equivocal results making selection of appropriate therapy difficult and ultimately affecting patient outcome. Methods: 135 females with BC were recruited in Puerto Rico between Sept and Dec 2012. Median patient age was 57 and 95 % had invasive ductal carcinoma. Our aim was to compare discordance rates of ER, PR and HER2 between IHC and AQUA, an automated fluorescent technology that quantifies antigen expression, in a population of Hispanic women and to investigate whether specimen type or tumor grade influence discordance rate between the two technologies. Results: 103 of 135 patient samples were found to be ER+ by both technologies and 28 samples were ER- by both IHC and AQUA. 4 samples (3%) were discordant; 2 each were AQUA+/IHC- and AQUA-/IHC+. 73 of 135 samples expressed PR by both technologies and 55 samples were PR- by both IHC and AQUA. 14 samples (10%) were discordant; 7 each were AQUA+/IHC- and AQUA-/IHC+. 87 of 135 samples were HER2- and 13 patients were found to be HER2+ by both technologies. However 35 samples (26%) were discordant for HER2 status; 31 were AQUA+/IHC- while 4 AQUA-/IHC+. 100 of the HER2 results were scored 0-1 (negative) by IHC and 25 % of these cases were overturned by AQUA to HER2 +. 19 of the HER2 results were scored 2 (borderline) by IHC. 32 % of these cases were positive by AQUA. Conclusions: Discordance rate were 3% for ER, 10 % for PR but 26% for HER2 between IHC and AQUA. The Cohen’s Kappa coefficient for ER and PR were 0.914 and 0.785 respectively but only 0.299 for HER2 (p values < 0.00001 for all 3 values). Needle/core biopsy yielded more HER2 discordance than lumpectomy/mastectomy (31% vs. 16%). HER2 discordance between IHC and AQUA was more common in higher grade tumors. The large number of HER2 negative IHC cases scored positive by AQUA, and considering the data demonstrating that HER2 by AQUA better predicts benefit from trastuzumab (Slamon D, SABCS 2012) suggests that a significant additional number of patients could benefit from such targeted therapy.