bluuebunny/crossref_metadata_2025 huggingface dataset:
Stage, biology, and age.
Authors: Kim Hee Jeong , Ko Beom Seok , Yu Jong Han , Lee jong Won , Sohn Byung Ho , Kim ku Sang , Kim Sung-Bae , Ahn Sei-Hyun
Published: March 2020

e11512

Background: Breast cancer subtypes are prognostic and predictive for patients. In this study, prognostic value of TNM stage, intrinsic subtype, and age were compared. Methods: We analyzed results from 7,626 breast cancer patients registered on the Asan medical center database between 1999 and 2009. We compared survival according to the TNM stage, intrinsic subtype using ER, PR, Her2- immunohistochemical staining, and age. Results: Luminal A subtype showed the best survival rates while triple negative subtype showed the worst survival rate amongst intrinsic subtypes. Survival analysis showed that Stage I triple negative breast cancer showed better survival compared to Stage III Luminal A subtype breast cancer (89.0% vs 76.6% P<0.001). Survival differences between intrinsic subtypes were more significant in lymph node positive breast cancer compared to lymph node negative breast cancer. Age did not affect survival between stages and intrinsic subtypes except for the young age subgroup (≤35), for whom there was no survival difference amongst intrinsic subtypes. Conclusions: Staging of breast cancer showed a more direct correlation to survival than known prognosis for intrinsic subtypes, as advanced, good prognostic intrinsic subtype breast cancer had worse survival than early, worse prognostic intrinsic subtype breast cancer. However for the young age group (≤35), the survival of all intrinsic subtypes were similar.
Targeting low-expressing ERBB-2 and acquired resistant high-expressing ERBB-2 breast carcinomas.
Authors: Karamouzis Michalis , Dalagiorgou Geena , Perez Sonia A. , Georgopoulou Urania , Papavassiliou Athanasios
Published: March 2020

e11513

Background: Human epidermal growth factor receptors and their ligands are involved in carcinogenesis. Four ERBB receptors have been identified; ERBB1 (EB1), ERBB2 (EB2), ERBB3 (EB3) and ERBB4 (EB4). EB2 is over-expressed/amplified in 20-30% of BCa. Molecularly targeting agents, such as pertuzumab (P), in combination with standard therapy have shown important clinical results in EB2 (+) BCa patients. The aim of the project is to evaluate the expression/localization and dimerization pattern of EB1, EB2, EB3, EB4 in breast cancer cell lines (BCCLs) with or without heregulin-1 (He) and various EB2, EB3 and He inhibitors. The identification of a molecular phenotype of low-expressing and acquired resistant high-expressing EB2 BCa will enhance the targeted use of EB2 inhibitors in certain BCa patients Methods: Using confocal microscopy, localization/expression patterns were studied for EB1, EB2, EB3, EB4 in various human BCCs; here presented in MCF7 and SKBR3. Additionally, the dimerization pattern of EB2, EB3 and/or EB4 was studied with and without stimulation with He plus or minus P (kindly provided by Genentech, US). The dimers formation was studied using proximity ligation assay and immunofluorescence (DUOLINK; OLINK Biosciences, Sweden). Results: In MCF7-He stimulated cells EB2/EB3, EB2/EB4 and EB1/EB3 dimmers showed a 3-fold decrease formation compared to untreated cells. The EB1/EB4 dimmers were not significantly affected. After P addition in MCF7 cells a 3-fold decrease of dimmer formation was noticed compared to untreated cells for EB2/EB3, EB2/EB4 and EB1/EB3. The EB1/EB4 formation seemed only slightly affected by P. SKBR3-He stimulated cells resulted in a similar decrease of EB2/EB3, EB2/EB4 and EB1/EB3 dimmer formation compared to untreated cells. In the same BCLL, EB1/EB4 dimmer did not show any decrease after He treatment compared to untreated control cells. Further results quantified and analyzed for statistical significance will be shown Conclusions: The addition of P seems to block ligand-dependent heterodimerization of EB2 with other ERBB family members, such as EB3 and EB4.
Mechanisms of primary AI resistance in ER-positive HER2-negative breast cancer.
Authors: Miura Daishu , Iwatani Tsuguo , Kawabata Hidetaka
Published: March 2020

e11519

Background: Current approaches of neoadjuvant endocrine therapy (NAET) are focusing on biomarker analysis of the diagnostic specimens however inadequate response occurs in 5-10% of patients treated. It has been reported hormone resistance may predict Ki67 level after treatment than ΔKi67. Much less is known about the difference between Ki67 increases and still high level of Ki67 after NAET. A pilot study was conducted to investigate the differences of biomarker changes in short-term NAET (letrozole vs. exemestane). Differences of resistant mechanisms between Ki67 increases and Ki67 still high expression and between two AIs were studied. Methods: Totally 116 samples from 58 postmenopausal women with ER positive HER2 negative stage 1-3 breast cancers comparing LET and EXE were analyzed with pre- and post-treatment mRNA expression of multiple biomarkers using QuantiGene Assay. Each of 29 patients took LET or EXE until the surgery (median 22 days). Compared with Ki67 expression of pre/post treatment, we classified resistance into 2 groups, Ki67 increase after treatment (INC) or Ki67 still high expression (equivalent over 14% in IHC) except those in INC (HIG). Results: Clinical characteristics were well balanced between the two treatment arms. Median % changes of Ki67 were -59% in both LET and EXE. Six cases (10%) were in INC (3/LET and 3/EXE). Among 10 cases of still high Ki67 expression, 6 (10%) were in HIG except 4 cases of Ki67 increases (3/LET and 3/EXE). All 6 cases in INC had increases of ERβ, MAPK, PIK3CA, ALDH1, NFkB, and RANKL and decrease of ERα. Five out of 6 in INC had an increase of HER2 and a decrease of PR. While changes in HIG were various, a nonsignificant trend to predict resistance was found. However all 3 cases whose HER2 increased in HIG had also increases of MAPK and PIK3CA. All 3 receiving EXE had increases of PR. Conclusions: Although both LET and EXE had significant decreases of Ki67, no significant difference was found between two. Both had 20% of primary resistance in terms of Ki67. Tumors which Ki67 increase seem to activate various signaling pathway, which mechanism is class effect of AI. What Ki67 is still high supposed to be nonclass effect.
PR and Ki67 in primary tumors and metastatic sites as biomarkers for benefit from endocrine therapy (ET) in metastatic breast cancer (mBC).
Authors: Ferrario Cristiano , Farolfi Alberto , Maltoni Roberta , Carretta Elisa , Melegari Elisabetta , Pietri Elisabetta , Rocca Andrea , Nanni Oriana , Amadori Dino
Published: March 2020

e11521

Background: Commonly used biomarkers (ER, PR, HER2, Ki67) are thought to identify BC subtypes with different sensitivity to ET, but data on this are scarce for the metastatic setting, where changes in receptor status between primary tumor (T) and matched metastases (M) are reported. We investigate PR and Ki67 on T and M as predictors of clinical benefit from 1st line ET in mBC. Methods: We identified mBC patients (pts) treated in our Center with 1st line ET (2002-11), excluding those receiving concomitant chemotherapy (CT) or trastuzumab or pretreated with >2 lines of CT. PR and Ki67 were scored as IHC percentage of positive cells, with a cut-off of 20% for high vs low. Clinical benefit was evaluated by time-to-progression (TTP). Results: We identified 137 pts, median age 58 (29-85), only 28% with visceral metastases. ER was >50% in 94%, HER2+ in 17.5%. With 93% receiving an aromatase inhibitor, median TTP was 14 months (median follow-up 43 months). In 34 pts with Ki67 available from T and M a strong correlation between the 2 was shown (Spearman: 0.69, p<.0001), confirming little variation. A shorter median TTP (10 vs 17 months, n=113; Wilcoxon p=0.006) was seen in pts with Ki67 >20% on T (with a similar trend on M, n=58; p=0.06). In 48 pts with PR scored on T and M only a weak trend for correlation was found, with a discordant classification (≤ or >20%) in 44%. More than the score on T (n=118), PR on M (n=64) was a strong predictor of median TTP: 12 months for PR ≤20% vs 22 months for PR >20% (p=0.02). Pts with PR≤20% + Ki67>20% on M had a median TTP of only 4 months, vs 21 months for PR>20% + Ki67≤20%, vs 14 months for either PR>20% or Ki67≤20% (p=0.006). In a multivariate Cox analysis with clinical data and biomarkers from T, visceral disease and HER2 positivity were significantly associated with the risk of progression (HR 2.22 and 2.07, respectively). With biomarkers from M, the risk of progression correlated with relapse ≤5 vs >5 years from surgery (HR 3.48) and PR ≤20% (HR 2.47, p=0.01). Conclusions: In an ER-high population, PR >20% on M identifies pts with a long TTP on ET. Ki67 on T or M can also contribute in estimating the expected benefit, but an independent prognostic role could not be fully confirmed in this small cohort.
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.
Long-term survival of women with breast cancer with ≥10 lymph nodes at diagnosis.
Authors: Cavalcante Ludimila , Zeichner Simon B. , Suciu Gabriel P , Ruiz Ana L. , Hirzel Alicia , Trif Almos , Krill-Jackson Elisa
Published: March 2020

e11575

Background: Axillary lymph node status is one of the most important prognostic factors in patients with breast cancer, and those with more than ten metastatic lymph nodes at diagnosis have a decreased overall survival. The purpose of this study is to better characterize the clinical course of this high-risk, poorly described patient population and determine the factors associated with long-term survival. Methods: A retrospective cohort analysis of all breast cancer patients with greater than ten metastatic lymph nodes diagnosed at Mt. Sinai Medical Center from January 1990 to December 2007 (n= 175). Descriptive frequencies, overall median survival (OMS), 5- and 10-year survival were calculated for standard prognostic factors and treatment variables. Univariate statistical analysis was performed, followed by a multivariate prognostic analysis for time-to-event data, using the Cox and extended Cox regression model. Results: The majority of patients were non-Hispanic white females between the ages of 56-70, diagnosed between 1990-1999, with tumors between 2-5 cm and 10-15 metastatic lymph nodes. Most were ER/PR positive, HER2 negative, and treated with surgery, chemotherapy, radiation and hormonal therapy. The OMS was 94 months (CI = 69-114) with 5- and 10-year survival rates of 64.3 and 41.6%, respectively. Ages between 21-45 years (OMS of 187 months, p = 0.03), tumors less than 2 cm (146 months (95% CI = 85-198), p = 0.02), ER positivity (131 months (95% CI = 94-157) vs. 39 months (95% CI = 27-59), p = 0.0003) and treatment received between 2000-2003 (98 months (95% CI = 55-133), p = 0.02) were all associated with significantly improved survival. Conclusions: Over the past decade there were significant gains in the long-term survival of breast cancer patients with greater than ten positive nodes at diagnosis, possibly due to improvements in multimodality therapy, such as the introduction of taxanes, although stage migration may be another contributing factor. Our study further showed an encouraging survival for ER positive patients and a dismal one for ER negative patients, highlighting the need for new targeted therapies directed towards ER negative tumors.
The impact of estrogen depletion by aromatase inhibitors on adiponectin serum levels in postmenopausal patients with breast cancer.
Authors: Pfeiler Georg , Konigsberg Robert , Hadji Peyman , Fitzal Florian , Tea Muy-Kheng Maria , Vogl Sonja , Berger Andreas , Exner Ruth , Seifert Michael , Singer Christian F. , Gnant Michael , Dubsky Peter Christian
Published: March 2020

e11601

Background: Adiponectin impacts on breast cancer risk and prognosis. Obesity and insulin resistance are correlated with low adiponectin serum levels, which increase breast cancer risk and lead to a worse outcome regarding breast cancer. Additionally a cross talk between the adiponectin and estrogen signaling system has been suggested. Here we prospectively investigated the impact of estrogen depletion via aromatase inhibitors (AI) on adiponectin serum levels in postmenopausal patients with breast cancer. Methods: 68 postmenopausal ER positive patients with breast cancer, scheduled to receive anastrozole or letrozole as adjuvant endocrine treatment were prospectively included in this study. Serum was taken before (T1) and 3 months after start with aromatase inhibitors (T2). Non-fasting serum levels of adiponectin, FSH, LH, E2, glucose and insulin were analyzed immediately in the clinical routine lab and in a dedicated central lab able to measure E2 in serum at low concentrations with high sensitivity. Results: At baseline, a strong significant negative correlation between adiponectin and body mass index (BMI) as well as a positive correlation between adiponectin and FSH serum levels could be observed (r=-0.43, p=0.01 and r=0.38, p=0.03, respectively). Taking the previously proposed cut off of 15.5μg/ml, patients with low adiponectin serum levels had a significantly higher BMI and significant lower FSH serum levels. No interaction between adiponectin and estradiol serum levels could be detected. As previously shown, AI treatment significantly decreased estradiol serum levels and consequently increased FSH serum levels. However, 3 months of AI treatment did not alter adiponectin, insulin and c-peptide serum levels, respectively. Conclusions: Short term estrogen depletion via aromatase inhibitors does not impact on non-fasting adiponectin, insulin and c-peptide serum levels in postmenopausal patients with breast cancer.
Do oncology patients in an outpatient hospital receive the same care as patients in an office/clinic setting? A case study evaluating patients with non-metastatic HER2+ breast cancer (BC) receiving adjuvant trastuzumab.
Authors: Lalla Deepa , Brammer Melissa , Guérin Annie , Gauthier Geneviève , Giguere-Duval Philippe , Wu Eric Q. , Santos Eduardo
Published: March 2020

e11603

Background: It is unknown if quality of care received by patients (pts) with BC is impacted by the location at which care is received. Using a sample of pts with HER2+ BC receiving adjuvant trastuzumab (T), we compared T treatment patterns between pts treated in office/clinic (MD) or outpatient hospital (HOSP) settings. Methods: Non-metastaticBCadult women who received ≥2 T infusions in an MD or HOSP setting from 2008-2012 were selected from the US-based Humana database. Based on the site of care where T was received, pts were classified into MD or HOSP cohorts. Pts were followed from first T infusion date to treatment discontinuation, first metastasis, or end of continuous eligibility, for a maximum of 12 months (mos). T treatment duration, discontinuation (treatment gap of ≥45 consecutive days), and the proportion of pts completing the recommended 12 mos treatment indication were compared between cohorts. Results: 730 pts were included; 67% received T in an MD setting vs. 33% in a HOSP setting. Differences between cohorts were observed in terms of healthcare insurance plan: more pts in the HOSP setting had Medicare coverage (55.5% vs. 67.1%; p=.003). Average T duration was shorter in the HOSP setting (MD cohort: 241.9 days ; HOSP cohort: 191.3 days). Among pts observed for 12 mos, a higher proportion in the MD cohort completed the 12-mo treatment (84.3% in MD vs. 75.6% in HOSP [p=.034]). After adjusting for confounding factors, the HOSP cohort was 2.4 times more likely to discontinue treatment compared to the MD cohort ( p<.001). Conclusions: Duration of adjuvant T treatment for pts with non-metastatic HER2+ BC differed based on the site at which treatment was received. This suggests that oncology pts treated in an HOSP setting, vs. MD, may be at higher risk for treatment discontinuation or to receive a shorter course of treatment than recommended. Further research should explore the impact of these differing treatment patterns on outcomes.
Fulvestrant for advanced breast cancer: A meta-analysis.
Authors: Al Mubarak Mustafa Mohammed
Published: March 2020

e11613

Background: Fulvestrant is an endocrine agent which degrades the estrogen receptor, thereby downregulating its signaling. While fulvestrant has been consistently tested in postmenopausal women with inoperable locally advanced or metastatic breast cancer, there has been substantial heterogeneity in study populations and drug dosing. The optimal use of fulvestrant in advanced breast cancer is therefore unclear. Methods: A systematic review of electronic databases was conducted to identify randomized trials of fulvestrant versus other endocrine therapy. The hazard ratios (HR) for time to progression (TTP) and the odds ratios (OR) for serious adverse events (SAEs), discontinuation of treatment due to toxicity and commonly reported toxicities (hot flashes, venous thrombosis, gastrointestinal disturbance, arthralgia, and asthenia) were pooled in a meta-analysis. Meta-regression explored heterogeneity in study population and fulvestrant dosing. Results: Eight studies were included in the analysis. Overall, there was no difference in TTP between fulvestrant and control groups (HR:0.94, 95% CI 0.85-1.03, p=0.18). On meta-regression, fulvestrant showed reduced hazards for TTP compared to aromatase inhibitors (AI) if used in first line (p for trend <0.001), in studies where fewer patients received adjuvant endocrine therapy (p for trend <0.001) and at higher doses (p for trend <0.001). Rates of SAEs and treatment discontinuation were similar for fulvestrant and control groups, but fulvestrant monotherapy was associated with significantly less arthralgia (OR:0.73,95% CI 0.57-0.95, p=0.02). The addition of fulvestrant to AI compared with AI alone was not associated with improved TTP (HR:0.88, 0.72-1.09,P=0.25), but led to increased hot flashes (OR: 1.68,95% CI 1.30-2.16, P<0.001) and gastrointestinal disturbances (OR:1.28, , 95% CI 1.01-1.63, p=0.04). Conclusions: In unselected patients, fulvestrant monotherapy is associated with similar efficacy, but reduced arthralgia. Use of high dose fulvestrant monotherapy in first line or in patients with limited prior exposure to adjuvant endocrine therapy may delay progression compared with AI. Fulvestrant combined with AI was not associated with improved efficacy but led to increased toxicity.
Cardiotoxicity and related risk factors in long-term trastuzumab (T) administration for metastatic breast cancer (MBC): A retrospective analysis.
Authors: Pistilli Barbara , Marcellusi Andrea , Valeri Michele , Torresi Umberto , Nacciarriti Dania , Saladino Tiziana , Mariani Cinzia , Santinelli Alfredo , Ferretti Benedetta , Latini Luciano , Benedetti Giovanni
Published: March 2020

e11616

Background: Continuing T beyond progression has become a common strategy in the treatment of human epidermal growth receptor 2- overexpressing (HER2) MBC. However, T administered for several years with concomitant chemotherapy elicits concern about cardiac safety especially in patients (pts) with risk factors. Methods: Cardiac events (CEs) and survival of HER2 MBC pts treated with T +/- chemotherapy at our institution from Dec 2003 to Jun 2012 were evaluated. CEs were graded by NCI-CTCAE v 3.0. Risk factors assessed for cardiotoxicity were: age, body mass index, antihypertensive therapy, history of cardiac disease, diabetes, hypothyroidism, smoking, prior radiotherapy on the chest wall, prior cumulative dose of anthracycline(A), interval between last A dose and first T dose, baseline LVEF, continued/interrupted T exposure, concomitant chemotherapy. Chi-square test was used to compare distribution of CEs over different times of T exposure (p≤ 0.05). Univariate and multivariate Cox regression analysis were used to assess the effect of risk predictors. Results: Sixty-two pts assessable. Median age 52 years (range, 29 to 76), median cumulative time receiving T 29.5 months (range, 3 to 99 months); 40 pts (64.5%) received T without interruption and 19 pts (30.6%) were treated for more than 36 months. CEs occurred in 11 out of all pts (17.7%): grade 1 in 3 pts (4.8%), grade 2 in 5 (8.1%) and grade 3 in 3 (4.8%). The rate of CEs showed no statistically significant difference in pts receiving T for up to 36 months and over: 7/43 (16.3%) and 4/19 (21%), respectively, (p =0.724). In univariate Cox regression analysis significant risk factors were: history of cardiac disease (HR 6,814, 95% CI: 1,384-33,542) and smoking (HR 5,228, 95% CI: 1,403-19,491). In multivariate analysis smoking was the only independent predictor (HR 5,886, 95% CI: 1,479-23,247). Median survival from MBC diagnosis was 50 months (range, 6 to 101 months). Conclusions: Despite the limited sample size, our analysis suggests that cardiotoxicity does not hamper a long-term use of T, since the rate of CEs did not increase in pts treated over 36 months. Moreover, smoking appears to be a predictive factor of T cardiotoxicity.
Phase II study of vinorelbine and capecitabine as first-line treatment for metastatic breast cancer.
Authors: El-Sadda Wael , Abdel Halim Inas Ibraheim , Abdel Aziz Mohamed
Published: March 2020

e12004

Background: Vinorelbine (V) and capecitabine (C) are likely to have a synergisitic interaction. Vinorelbine upregulates thymidine phosphorylase; a key enzyme in the conversion of capecitabine to active 5-FU in tumor tissue. Available phase II clinical data reports response rates ranging from 48-70% in first line metastatic breast cancer (MBC) for this combination. We evaluated the efficacy and safety of vinorelbine plus capecitabine in patients with MBC relapsing after adjuvant anthracycline based treatment. Methods: Sixty patients were enrolled between Oct 2008 through Dec 2010. All patients had measurable MBC relapse after adjuvant anthracycline and/or taxanes, WHO PS < 2, adequate bone marrow, renal and hepatic functions. Patients received intravenous vinorelbine 25 mg/m2 on day 1 and 8 and oral capecitabine 1000 mg/m2 bid on days 1 to 14, cycles to be repeated every 3 weeks. Patients with PD went off the study while those with CR, PR or SD continued treatment for a maximum of 8 cycles. Results: Median age 54 years (range 35-67 years), Median WHO PS 0 (range 0-1). Previous adjuvant therapy anthracycline (100%) and hormone therapy (60%). Median disease free interval was 6 months. Main metastatic sites were lung (40%), liver (25%), bone (40%) skin (35%), and lymph nodes (35%). Twenty five percent of patients had one metastatic site, 60% had two sites, 10% had three sites and 5% had more than three sites. The total number of cycles delivered was 441 with a median number of cycles/patients of 7 (range 3-8). An objective tumor response was achieved in 36 pts (60%), complete response (CR) in 6 pts (10%), 12 pts (20%) had stable disease (SD). After a follow up period of 6-36 months, the median time to progression and median survival were 14 and 23 months, respectively. No WHO G4 toxicities were noted, 3 pts (5%) developed G3 neutropenia and one patient (1.7%) developed G3 hand and foot syndrome. G2 anemia, neutropenia and diarrhea were reported in 2 pts (3.3%), 3 pts (5%) and 6 pts (10%), respectively. Conclusions: The combination of vinorelbine and capecitabine showed significant efficacy and mild toxicity as a first-line treatment for patients with metastatic breast cancer after failure of adjuvant anthracycline based therapy.