bluuebunny/crossref_metadata_2025 huggingface dataset:
FcGR2A genotype and change in gene expression of effecter cells in peripheral blood after administration of trastuzumab (T).
Authors: Shimizu Chikako , Mogushi Kaoru , Koizumi Fumiaki , Tamura Kenji , Yunokawa Mayu , Fujiwara Yasuhiro , Tanaka Hiroshi
Published: March 2020

e11065

Background: We have previously reported that FcGR2A polymorphisms were associated with clinical outcome of trastuzumab (T) in both neoadjuvant and metastatic settings in patients (pts) with HER2-positive breast cancer (Tamura et al, Ann Oncol 2011). We explored if antibody-dependent cell-mediated cytotoxicity (ADCC) can be observed as a change in gene expression of PBMC (effecter cells of ADCC) in patients receiving T according to FcGR2A phenotypes. Methods: FcGR2A genotypes in 34 patients with HER2-positive metastatic breast cancer were determined in the previously reported prospective study (Tamura et al, Ann Oncol 2011). All pts received single agent T (Starting dose 4mg/kg, maintenance dose 2mg/kg) as the first-line treatment for metastatic breast cancer. PBMC was purified from peripheral blood collected before T, at 1 wk and 8 wk of weekly T. Total RNA was extracted from PBMC and gene expressions were measured using Affimetrix GeneChip Human Genome U133 Plus 2.0 array. Gene set enrichment analysis (GSEA) ( www.broadinstitute.org/gsea ) using KEGG pathway DB was carried out to explore differentially expressed gene sets (GSs) after 1wk and 8 wk administration of T compared to baseline. GSs with significance level of p<0.05 and FDA<0.25 were considered statistically significant. Results: There were 15 and 19 patients with FcG2A- 131 HH and HR/RR genotypes, respectively. There were no significant GSs differentially expressed at 1 wk compared to baseline in both HH and HR/RR cohorts. 11 GSs were differentially expressed at 8 wk in HH cohort, whereas there were no significant GSs differentially expressed at 8wk in HR/RR cohort. The upregulated GSs at 8 wk in HH cohort included KEGG_NATURAL_KILLER_CELL_MEDIATED_CYTOTOXICIY and KEGG_ANTIGEN_PROCESSING_AND_PRESENTATION. Conclusions: Differential pharmacogenomic response of PBMC to T according to FcG2A genotype supports the hypothesis that ADCC is associated with the mechanism of action of T.
Clinical utility and therapeutic implications of oncotype analysis in patients with breast cancer.
Authors: Williams Stephanie A. , Tatarian Talar , Teal Christine B. , McSwain Anita P. , Siegel Robert S. , Ojong-Ntui Martin , Saini Ashima , Tabbara Imad A. , Kaltman Rebecca Davidson
Published: March 2020

e11084

Background: Oncotype DX is a 21-gene assay developed for early stage, hormone receptor positive breast cancer that generates a Recurrence Score which estimates response to chemotherapy and the likelihood of systemic recurrence at 10 years. It differentiates between patients who would benefit from chemotherapy plus hormonal therapy versus hormonal therapy alone. This study’s goal was to determine if the Recurrence Score affected clinical management at our institution and physicians’ accuracy at predicting Recurrence Scores. Methods: A retrospective review was conducted of 116 breast cancer patients treated over a 7 year period. Clinic notes, pathology reports, and additional relevant information were presented to breast surgeons, oncologists, radiation oncologists, and surgical pathologists. Individual physicians estimated recurrence risks and recommended treatment based on those estimates. The Recurrence Score was revealed and changes in therapeutic recommendations were recorded. Results: Treatment recommendations changed in 43% of patients. 29% had a change from chemotherapy followed by hormone therapy to hormone therapy alone due to a low recurrence score, while 14% initially recommended hormonal therapy were changed to chemotherapy plus hormonal therapy due to an intermediate range score. Surgical oncologists accurately predicted Recurrence Scores 52% of the time, medical oncologists 46%, radiation oncologists 45%, and surgical pathologists 15%. A nested mixed model showed that pathologists were statistically significantly worse at predicting recurrence scores than surgical oncologists, medical oncologists, and radiation oncologists. Conclusions: The Oncotype DX assay changes management of breast cancer patients at our institution, frequently downgrading the intensity of systemic therapy. Clinicians were able to accurately estimate recurrence categories about 50% of the time. We recommend the use of Oncotype DX assay along with assessment of clinicopathologic features of an individual’s disease in eligible patients to enhance the selection of appropriate adjuvant therapy.
Prognostic value of serum Cytokeratin19-2G2 in primary breast cancer patients.
Authors: Xie Xiaoming , Kong Yana , Dai Shuqin , Liu Wanli , Wei Weidong
Published: March 2020

e11091

Background: Cytokeratin19-2G2, one of cytokeratin19 fragments, has been considered as one of the most sensitive tumor markers. However, no previous studies reported of CK19-2G2 in breast cancer. The purpose of our study is to evaluate the prognostic value of CK19-2G2 in primary breast cancer patients. Methods: This study included 249 primary breast cancer patients with stage 0-III, 81 healthy controls and 21 breast benign disease patients. Serum samples were conserved before surgery. CK19-2G2, CEA and CA153 were measured by chemiluminescent assay and ER, PR, CerbB2 were assessed by Immunohistochemistry assay. Results: Serum CK19-2G2 levels in breast cancer patients were significantly higher than that in healthy and benign controls (P < 0.001). High serum CK19-2G2 levels (≥2 ng/mL) were associated with stage III (P < 0.001), tumor size (≥2cm) (P < 0.001), lymph node involvement (P < 0.001), negative estrogen receptor (P = 0.005) and progesterone receptor status (P = 0.001). Multivariate analysis revealed that high serum CK19-2G2 level was an independent factor for relapse (P = 0.029) and death (P = 0.040) in primary breast cancer patients. Conclusions: High serum CK19-2G2 levels maybe considered as an independent indicator for prognosis in primary breast cancer.
Demographic and clinicopathologic characteristics of breast cancer patients with history of oral alendronate use.
Authors: Aksoy Sercan , Sendur Mehmet Ali Nahit , Yaman Sebnem , Arik Zafer , Ozdemir Nuriye , Zengin Nurullah , Altundag Kadri
Published: March 2020

e11093

Background: Bisphosphonates therapy reduces the risk of skeletally related complications in patients with bone metastases due to malignancy and bisphosphonates are the most common used agents in the treatment of osteoporosis. However, the effect on clinical and pathological properties of breast cancer with using oral alendronate has not been reported. We investigate retrospectively the demographic and clinico-pathological characteristics of patients with oral alendronate users for longer than 1 year, compared to non-users. Methods: Patients with breast cancer diagnosed from 1998 to 2010 in our clinic were retrospectively analyzed. Patient’s demographics including survival data and tumor characteristics were obtained from medical charts. Breast cancer patients who were taking oral alendronate more than 12 months at the time of breast cancer diagnosis were enrolled as an alendronate users (n=44), where the patients matched with the same age who were not taking oral alendronate were included as a control group (n=444). Results: A total of 488 patients were included in this study. Forty-four patients received an oral alendronate treatment more than one year and 444 patients were considered as nonusers. Median age of both alendronate users and nonusers was 57 (33-89). Lower incidence histological grade III, T3-T4 tumor, and node positivity was seen in alendronate users but not statistically significant. A similar trend for lower incidence of triple negative and higher incidence ER (P=0.13), PR (P=0.12) and HER2 positivity (P=0.21) was also seen in alendronate users but not statistically significant. Disease free survival rate was 150±28 months in alendronate users where as 70±24 months in nonusers (P=0.015). Median overall survival rates could not be obtained but higher in alendronate users but not statistically significant (P=0.13). Conclusions: The use of oral alendronate for longer than one year before the diagnosis of breast cancer was associated with better clinico-pathological properties and significantly improved disease free survival in breast cancer patients.
Strategies for promoting advocacy engagement in the Bay Area Physical Sciences Oncology Center (PS-OC) setting.
Authors: Samson Susan , Vincent Linda V. , Klein Connolly Hannah , Acerbi Irene , Weaver Valerie , Rugo Hope S.
Published: March 2020

e11096

Background: Bay Area physical sciences researchers, supported by funding from the National Cancer Institute (NCI), encourage broad thinking to tackle the variability of breast cancer and to address data gaps in breast cancer prevention, emergence, behavior, and treatment. Methods: In this transdisciplinary innovation focused scientific arena, the Bay Area PS-OC also established the groundwork work for engaging advocates in the research programs. Results: Emerging results of this research collaboration: (1) Promote the integration of advocates into PSOC culture:Engage the perspectives of advocates to sensitize researchers to patient needs/concerns, and to encourage disruptive change in the interests of saving lives. Encourage front end inclusion of advocates in program planning and research design. (2) Create new pathways for the translation and dissemination of information: Utilize new internet technology and transdisciplinary collaboration models to help promote science literacy and communicate the implications of a mechanics-centric view of cancer. Reconfigure consumer expectations regarding the benefits of physical sciences approaches and highlight how this cutting edge science informs translational research in both cancer prevention and therapeutics. (3) Pilot an Advocate Mentor Program: Train the next generation of professionals, and specifically engage advocates in cross sector convergence collaborations with scientists, post-doctoral fellows, students, and clinicians. Conclusions: Some of the most exciting transdisciplinary engagement lies at the intersection of disciplines when all stakeholders (scientists, clinicians, and advocates) collectively consider new approaches and strategic processes that point to synergies of interest, thorny issues, capacity building, metrics and measures, and new engagement theories. Supported by: grant U54CA143836-01 from the NCI to VMW and JL; NCI SPORE P50 CA058207 to VMW, CP, & SH; U01 ES019458-02 to ZW.
Comparison of neoadjuvant systemic treatment (chemotherapy with or without trastuzumab) responses with dynamic contrast-enhanced breast magnetic resonance imaging and histopathology in locally advanced breast cancer.
Authors: Orbay Ozge , Demirkan Hatice Mirac Binnaz , Balci Pinar , Durak Merih , Saydam Serdar
Published: March 2020

e11507

Background: It is reported that dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) may have the potential of predicting response to neoadjuvant chemotherapy (NAC) for patients with breast cancer and it is more accurate than the other radiologic methods. We aimed to compare the responses to NAC ± trastuzumab with DCE-MRI and histopathologic findings in locally advanced breast cancer. Methods: Between January 2007 and October 2011, 38 female patients patients with locally advanced breast cancer who recieved NAC ± trastuzumab and had whole breast DCE-MRI before / after treatment and who also had surgery after treatment were included in our study. Patients received 4 cycles of antracyclin based and 4 cycles of taxane based chemotherapy protocols sequentially. 9 patients with HER-2 (+) breast cancer also received trastuzumab with taxane based chemotherapy. Before and after NAC ± trastuzumab, tumor measurements were evaluated by mammography (MG), ultrasound (US), DCE-MRI and compared with postoperative histopathologic findings. Response rates were assessed with RECIST (Response Evolution Criteria in Solid Tumors) 1,1 criteria. MRI were done with 1,5 Tesla MR ( Gyroscan Achieva Intera, Philips ). SPSS 15.0 and Kappa test were used for statistical analysis. Results: After NAC ± trastuzumab, breast DCE-MRI revealed 13.2% complete response (CR), 73.7% partial response (PR), 10.5% stabile disease (SD), and 2.6% progressive disease (PD) and 15.8% CR, 73.7% PR, 7.9% SD and 2.6% PD were shown with histopathology. After neoadjuvant systemic treatment, histopathologic and DCE-MRI responses revealed high positive correlation with kappa test (kappa: 0,63), but there were low correlation between not only histopathologic and MG responses but also US responses with kappa test (kappa: 0,2). Conclusions: DCE-MRI is more effective method than other radiologic methods for the evaluation of response to NAC ± trastuzumab when compared with the histopathologic findings.
Prognosis of breast cancer in patients with peritoneal metastasis.
Authors: Petekkaya Ibrahim , Ayyildiz Veysel , Kizilarslanoglu Cemal , Sahin Ugur , Gezgen Gamze , C. Roach Emir , Karcaaltincaba Musturay , Altundag Kadri
Published: March 2020

e11509

Background: Distant spread from breast cancer is commonly found in bones, lungs, liver, and central nervous system. However, peritoneal involvement is unusual and unexpected. The aim of the study was to perform a comprehensive analysis of breast cancer patients with peritoneal metastases. Methods: Twenty-one (0.9% of the cohort) breast cancer patients with peritoneal metastases were detected out of a database of 2,219 breast cancer patients treated in Hacettepe University Medical Oncology Department. Clinical characteristics, follow up times and survival rates were analyzed. Results: The mean age of the 21 patients at the time of peritoneal metastasis was 56 years (38-71). 12 (57.1%) patients were post-menopausal, 6 (28.6%) patients were pre-menopausal. Numbers of deceased patients were 7 (33.3%). Seven (33.3%) patients’ histological subtypes were invasive ductal carcinoma (IDC), five (23.8%) patients’ were invasive lobular carcinoma (ILC) and three (14.3%) patients’ were mixed (IDC and ILC). Numbers of luminal A patients were 8 (38.1%), luminal B were 5 (23.8%), triple negative were 2 (9.5%). There was no Her-2 overexpressing patient and numbers of unknown molecular subtype patients were 6 (28.6%). The median follow up times after peritoneal disease in patients deceased and living were 9.3 (range: 0.4-23.3) months and 15.6 (range: 0.3-40.4) months, respectively. Median follow up time after peritoneal metastasis of ER positive patients was 13.7 months, and it was longer than ER negative patients (4.4 months). Six months and one year survival rates after peritoneal metastasis were 83.3% and 73.3%, respectively. Disease free, progression free and overall survival data could not be obtained due to inadequate number of events. Conclusions: Peritoneal metastasis of breast cancer is very rare and median survival time is controversial in literature. Despite of a small cohort, we found the patients’ follow up times longer than reported before. Especially, ER positive patients have longer survival time than ER negative, and this result highlights the importance of hormonotherapies.
Incidence and implications of oligometastatic breast cancer.
Authors: Jain Supriya K. , Dorn Paige L. , Chmura Steven J. , Weichselbaum Ralph R. , Hasan Yasmin
Published: March 2020

e11512

Background: There is increasing evidence that prolonged disease control is possible in patients with a limited number of metastatic sites compared to those with more diffuse disease, especially when aggressive local therapy (surgery and/or stereotactic radiation) is administered. The objective of this study is to describe the frequency of oligometastatic breast cancer in patients who develop distant disease and to characterize their disease course. Methods: A retrospective review was performed of a tri-institutional database of Stage I-III breast cancer patients treated from 1978 to 2005. Patients were categorized as "oligometastatic" (OM) if ≤ 5 sites of disease were identified at time of first failure or “polymetastatic” (PM) if failure occurred at > 5 sites. Patients were followed for ≥ 3 y after first metastasis, until death, or until development of > 5 sites of metastatic disease. T and N stage, hormone receptor status, presenting symptoms of metastasis, number and site of metastases, actuarial overall survival (OS), and overall survival after first failure (OSAF) were examined. Kaplan-Meier, chi-square, and log-rank tests were used for statistical analysis. Results: Of 2,249 patients reviewed, 114 (5.1%) failed at distant sites and met inclusion criteria. The OM phenotype was observed in 21.9% (25/114). Of patients presenting with symptoms of metastasis, 18.3% were OM, whereas patients with metastases identified incidentally or by screening were OM in 42.1% of cases (p = 0.02). Median OSAF was significantly longer in OM patients (44.7 mos) than PM patients (18.1 mos) with 5 y OS of 48.5% and 10.7% respectively (p < 0.001). Outcome of OM patients compared favorably to that of patients with bone-only metastases in whom the median OSAF was 25 mos and 5 y OS was 12.5%. Baseline features of OM and PM patients did not differ according to initial tumor size (p = 0.94), nodal stage (p = 0.5), or ER+ (p = 0.28). Conclusions: A significant proportion of early stage breast cancer patients with distant failure will have OM disease, and this subset is expected to have prolonged overall survival. The relatively favorable prognosis of patients with OM disease warrants consideration of aggressive local therapy and may have implications in the design of future clinical trials.
Inflammatory breast cancer in Morocco: Experience of Hassan II University Hospital.
Authors: Daoudi Khaoula , Brahmi Sami Aziz , Boudahna Lamie , Hijri Fatima Zahra , Bouyahia Nezar , Oulla Karima , Benhammane Hafida , Chad Amine Mohammed , El mrabet Fatima Zahra , Arifi Samia , Nawfel Mellas , El Mesbahi Omar
Published: March 2020

e11516

Background: Inflammatory breast cancer (IBC) is the most virulent type of breast cancer. It represents 1 to 6% of all the breast cancer in Western countries. It is speculated that the incidence of IBC is greater in emerging countries especially in North Africa. The management of this disease requires a multidisciplinary. Methods: We recorded the cases of 80 patients with IBC admitted in the Medical Oncology Unit between January 2007 and August 2011. We included patients with IBC classified as T4d using criteria based on the tumor-node-metastasis (TNM) classification . The aims of this study is to evaluate the epidemiological, clinical, histopathological and therapeutic aspects of this disease. Results: The median age of our patients was 44.5 years ranged from 24 to 88 years. The incidence of IBC in our study was 7.8%. The lymph node involvement was noted in 60% distributed as following: N0 in 40%, N1 in 30%, N2 in 19%, N3 in 11%. For histology, ductal carcinoma represents 96% of all cases. Human epithelial receptor 2 (HER 2) was positive in 32% of the cases. Hormonal receptors were negative in 22% of the cases. The grade of the tumor according to the Scarff Bloom Richardson classification was as following: grade I ( 2.5%), grade II (52%), grade III (45.5%). All patients received neoadjuvant chemotherapy. 45% received chemotherapy with anthracyclines, 35% were treated with docetaxel and anthracycline and 10% with the association chemotherapy Trastuzumab. According to RECIST classification, a partial or total clinical response was noted in 80% of cases, 10% of patients had stability, and 10% clinical progression. According to Sattalof classification, a histological response greater than 50% in the tumor (TB) was noted in 45%. A complete pathological response (TANA or TANB) was obtained in 15% of cases. After a median follow up of 2 years 35% of the patients had a metastatic or locoregional reccurence, 45% of the cases remain in complete remission. Conclusions: The result of our study is concordant with the litterature. The incidence of IBC was greater than the incidence in western countries. The IBC was also associated with high grade and younger age. Despite a good clinical and pathological response to chemotherapy, outcomes were poor.
Clinicopathologic characteristics of triple-negative breast cancer and relationship to basal markers.
Authors: Tryfonopoulos Dimitrios , Oikonomopoulos Georgios , Demiri Stamatina , Lekakis Lazaros , Pistamaltzian Nikolaos Fragkiskos , Koumakis George , Panopoulos Chris G. , Koufopoulos Nektarios , Apostolikas Nikiforos , Misitzis Ioannis , Efremidis Anna P.
Published: March 2020

e11519

Background: Triple negative breast cancers are immunohistochemical surrogates of basal-like breast cancers. There is no complete overlap between triple negative and basal-like tumors and as gene expression studies evolve, further subclassification bearing clinical relevance is underway. Our purpose was to correlate clinicopathologic characteristics of triple negative breast cancer tumors with expression of basal markers in an effort to define immunohistochemically subgroups of this heterogenous disease Methods: Data were retrieved and analysed using our electronic databank. Patient samples were reviewed by an expert breast cancer pathologist and stained additionally for EGFR and CK 5/6 antibodies. Results: Sixty-five women with triple negative breast cancer were identified. Mean age was 58.3±12.9 years. Most tumors (86%) were of ductal histology, 53% grade 3, 48% having high Ki-67 index (>14%). 10% of patients presented with Stage IV, 25% with Stage III, 38% with stage II and 27% with stage I disease. 63% of patients were postmenopausal. EGFR staining was present in 43% of tumor samples, whereas CK 5/6 in 38.5%. Both EGFR and CK 5/6 expression was found in 18.5%, whereas 37% of tumors expressed neither EGFR or CK 5/6. No difference was observed between tumors expressing any of these 2 basal markers as compared to EGFR and CK 5/6 negative tumors in terms of Ki-67 index, grade, tumor size and nodal involvement. Lymphovascular invasion and non-ductal histology tended to occur more frequently (p=ns) in non-basal tumors. Additionally, patients with expression of any of the basal markers tended to be more obese than the non-basal triple negative breast cancer patients (p=ns). Conclusions: Further immunohistochemical markers apart from EGFR and CK 5/6 are needed in order to further define clinically meaningful subgroups of triple negative breast cancer.
Bevacizumab plus chemotherapy in the treatment of metastatic breast cancer: Hospital of Cruces experience.
Authors: Ferreiro Josefa , Ruiz de Lobera Abigail , Sancho Aintzane , Carrera Sergio , Marrodan Ines , Rubio Itziar , Iruarrizaga Eluska , Azkona Eider , Munoz Llarena Alberto , Lopez-Vivanco Guillermo
Published: March 2020

e11525

Background: Antiangiogenic therapies such as bevacizumab (BV), have proven to be effective in improving outcomes in metastatic disease from several tumor types. For metastatic breast cancer (MBC), combinations of BV and established chemotherapy regimens potentially offer new, more efficacious treatments without the significant toxicity associated with combining multiple cytotoxic agents. Methods: This is a retrospective chart review that reflects Hospital of Cruces experience with BV in combination with chemotherapy in patients with MBC. Demographic and treatment data were collected from diagnosis and follow-up period. Results: A total of 66 patients were included. Median age was 53(34-78) years. ECOG PS 0/1/2/3 was 35%/51.5%/10.5%/3%, respectively. Positive hormone receptor (66.7%) and negative hormone receptor (33.3%). Her2 negative and triple negative were 100% and 33.3% of the patients. Adjuvant treatment received was 81.8% chemotherapy and 56.1% hormone therapy. Most frequent metastasis locations: bone (68%), liver 54.5%, lymph nodes (51.5%) and lung (27.3%). Thirty-five patients reported two or 3 metastasis locations. Chemotherapy used with BV was docetaxel (68.2%) and paclitaxel (31.8%). Median of BV courses was 6 (1-20). Response rate was 57.5% (53% partial response) and 28.8% had stable disease. Median Progression Free Survival (PFS) was 11.7 months and median OS was 19.7 months. Statistical differences were observed between patients who received a maintenance therapy with BV vs patients who received no maintenance therapy (PFS: 9.34 vs 15.36 months, p<0.001; OS: 13.81 vs 25.56 months, p<0.001). Most frequent toxicities 3/4 were: neutropenia 31.8%, febrile neutropenia 21.2%, asthenia 21.2%, infection 9.1% and onycholysis 6.1%. Conclusions: BV in combination with chemotherapy improves clinical benefit in terms of increased PFS and OS in first-line treatment of metastatic breast cancer. Maintenance with BV revealed statistical differences. Toxicity profile was manageable and as expected for BV.
Phase II trial of RAD001 plus carboplatin in patients with triple-negative metastatic breast cancer.
Authors: Singh Jasmeet Chadha , Stein Stacy , Volm Matthew , Smith Julia Anne , Novik Yelena , Speyer James L. , Meyers Marlene , Adams Sylvia , Omene Coral Oghenerukevwe , Muggia Franco , Schneider Robert , Formenti Silvia , Davis Samantha , Beardslee Brian , Tiersten Amy
Published: March 2020

e11529

Background: Triple negative breast cancer cells are unable to repair double stranded DNA breaks and hence have sensitivity to platinum agents. Rapamycin acts synergistically with platinum agents to induce apoptosis and inhibit proliferation in breast cancer cell lines. Combination of RAD001 (oral mTOR inhibitor) and Carboplatin may have activity in triple-negative breast cancer. Methods: The primary objective of the study was to estimate the clinical benefit (complete remission (CR) + partial remission (PR) + stable disease (SD) >6 months) and the toxicity of this combination in women with triple negative metastatic breast cancer who have had 0-3 prior chemotherapy regimens for metastatic disease. 25 subjects were to be entered into a single stage open label Phase II study. Prior Carboplatin is allowed. Treated brain metastasis are eligible. The null hypothesis that the clinical benefit rate is ≤10% could be rejected if number of CR/PR/SD >6 months was ≥6. Originally, intravenous Carboplatin AUC 6 was to be administered every 3 weeks along with daily 5mg of RAD001 with a 3 patient run-in and then 10 mg daily. Due to a surprising amount of thrombocytopenia with this combination, the dose of Carboplatin was first amended to AUC 5 and most recently to AUC 4 with 5 mg of RAD001. Results: 18 patients have been recruited thus far. Median age is 59. There have been 1 CR, 4 PR’s and 2 SD's lasting > 6 months. One SD was achieved in a patient progressing on single agent Carboplatin at study entry. Median duration of CR+ SD +PR thus far is 13 weeks (range: 6-60 weeks). 5 patients had grade 3/4 thrombocytopenia and 4 patients had grade 3 neutropenia (no febrile neutropenia). However, since amendment of Carboplatin dose to AUC 4 the regimen has been well tolerated. 1 patient suffered from grade 3 dehydration. The estimated clinical benefit rate is 50% (95% C.I.: 24%, 76%). Median time to progression or death is 87.5 days from start of treatment; there is only 1 death to date on this study. Conclusions: The study has achieved it’s primary objective of demonstrating clinical benefit of RAD 001-Carboplatin combination in triple negative metastatic breast cancer. Dose limiting thrombocytopenia was an unexpected side effect requiring protocol amendment.
Clinical significance following breast conservation surgery with or without postoperative irradiation in Japanese women with breast cancer.
Authors: Tamaki Kentaro , Tamaki Nobumitsu , Kamada Yoshihiko , Uehara Kanou , Miyashita Minoru , Ishida Takanori , Sasano Hironobu
Published: March 2020

e11530

Background: Postoperative irradiation or radiotherapy following breast conservation surgery has been reported to be clinically effective in terms of prevention of local breast cancer recurrences. However, it is also true that its local recurrence rate was only 5% to 10%, suggestive of the lack of its clinical benefits in the great majority of the cases. The purpose of this study was to investigate the significance of post-operative radiotherapy in breast conservation surgery by comparing the groups with or without irradiation. Methods: We retrospectively evaluated 1197 Japanese female breast cancer patients (598 irradiation cases and 599 non-irradiation cases). Radiation was administered in a dose of 50 Gy for all conserved breast and additional 10 Gy in those with positive margins or carcinoma within 5mm from surgical margin. We examined the local recurrence rates in those with or without post-operative irradiation according to the status of surgical margin, ER and HER2 in breast cancer tissues. Results: RFS in the irradiated groups were significantly higher than non-irradiated ones in surgical margin positive (P=0.001, HR: 0.334, 95%CI: 0.14-0.79), negative (P=0.015, 0.362, 95%CI: 0.15-0.82), ER positive (P<0.001, HR: 0.249, 95%CI: 0.11-0.54), HER2 negative (P=0.002, HR: 0.316, 95%CI: 0.15-0.65) and non-triple negative patients (P=0.001, HR: 0.382, 95%CI: 0.21-0.69). However, no significant differences were detected between these two groups in ER negative (P=0.288, HR: 0.586, 95%CI: 0.22-1.57), HER2 positive (P=0.969, HR: 0.971, 95%CI: 0.22-4.24) and triple negative (P=0.336, HR: 0.282, 95%CI: 0.02-3.72) patients. Conclusions: Results of our present study could provide clinically inert information as to the selection of the breast cancer patients following conserve surgery.
Feasibility of concurrent weekly paclitaxel and radiotherapy in adjuvant treatment of breast cancer: An experience from India.
Authors: Somashekar Mohan Kumar , V Murali Subramanian , S Nirmala Srikantaiah , TR Arul Ponni , G Rajeev A , AS Kirthi Koushik , G Janaki M , R Nalini Kilara , S Ramesh Bilimagga
Published: March 2020

e11536

Background: Majority of the breast cancer patients require adjuvant radiotherapy and chemotherapy for better locoregional and distant control. However the sequencing of these is still debatable . Hence concurrent chemo radiation may avoid the delay in either of the adjuvant therapies. Anthracyclines are not used concurrently with radiation because of severe toxicity. Hence the current study was taken to assess the feasibility of concurrent weekly paclitaxel and radiotherapy in adjuvant treatment of ca breast. Methods: A prospective study was conducted on 22 breast cancer patients, post modified radical mastectomy or breast conservative surgery from November 2008 to April 2010. Chest wall or whole breast radiotherapy was given on Tele Cobalt or Linac for a dose of 50 – 50.4Gy in conventional fractionation. Boost of 16 Gy was given to tumor cavity with photons or electrons for those undergone breast conservative surgery. All patients received Inj.paclitaxel 60 mg/m2 once a week for 5 weeks. After completion of RT, paclitaxel dose was increased to 80mg/m2 for remaining 7 cycles. This was followed by anthracycline based treatment sequentially as per standard adjuvant guidelines. Patients assessed weekly and toxicities graded based on CTC version 03. The minimum follow up was 2 months after completion of chemoradiation. Chi-Square test and Fisher exact test were used to interpret the results with literature. Results: See table below. Skin reaction was more frequent and severe of all toxicities (p=0.003).With available literatures on adjuvant radiation alone the grade III and higher skin reactions are 3% but in our study it is 28% because of which 5/22 (22%) patients had interruption of both chemotherapy and radiation. Conclusions: Concurrent chemoradiation with weekly paclitaxel in adjuvant treatment of ca breast is associated with more skin reactions which may result in significant treatment interruptions. It should be practiced cautiously which requires further randomized control studies to assess the toxicities in detail. [Table: see text]
Demographic variation of Ki67 and its relation with prognosis in triple-negative breast cancer: A single-center pilot project.
Authors: Ahmed Mashrafi , Begum Tahmina
Published: March 2020

e11539

Background: Ki-67 is a proliferation marker expressed during cell cycle. ASCO does not recommend this biomarker to be done routinely in breast cancer. As triple negative breast cancer lacks all the ASCO recommended biomarkers (estrogen, progesterone and HER-2 gene), non-recommended markers may carry significant prognostic value in different demographic population. Methods: A retrospective chart review was conducted on patients who were diagnosed with triple negative breast cancer at Saint Joseph Hospital, Chicago from 2005 to 2010. We analyzed the data for Ki67 value among age group, race, menstrual status, tumor histology, stage, treatment given and outcome of the treatment. The data was obtained from medical record, cancer registry and department of pathology. Results: Only 35 cases were found retrospectively. The mean age was 55.6 year. Nearly 47% were African American, 38% White and rest was other races. Most of the cases (71%) were post-menopausal. The average follow-up was 214 days with nearly 62% patients remained disease free, 21% suffered from relapse but alive and 18% died from relapse. The analysis of data is presented here in tabulated form. Conclusions: In our study, we could not reach to statistical significance mostly due to small size of the population. Being a rare subtype of breast cancer, a single center data analysis is not sufficient. This pilot study will encourage us to go for a large scale study involving multi-center or cancer registry data of the state of Illinois. [Table: see text]

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Efficacy and safety of weekly oral vinorelbine (NVBO) as single agent in first- or second-line metastatic breast cancer (MBC).
Authors: Morales Serafin , Blancas Isabel , Gonzalvez Maria Luisa , Barnadas Agust , Diaz Nieves , Servitja Sonia , del Barco Sonia , Margeli Mireia , Garcia Carbonero Iciar , Alvarez Ruth , Lopez de Ceballos Maria Helena , Perez Francisco Javier , Llombart Cussac Antonio
Published: March 2020

e11545

Background: NVBO has shown high activity and good safety profile when given as single agent chemotherapy (CT) for MBC. Oral CT formulations allow maintenance of quality of live and minimal interference with a normal lifestyle. Methods: Main inclusion criteria for this retrospective study were: Histologically or citologically confirmed MBC, no more than 1 prior CT line for MBC; prior (neo)adjuvant CT, hormonetherapy or radiotherapy allowed; adequate bone marrow, kidney and liver function. The study protocol was approved by an ethics committee. Data was collected from patients (p) treated between Apr/2006 and Dec/2010 with NVBO 60 mg/m2 weekly until progression or unacceptable toxicity. 70 patients fulfilled the inclusion criteria. Patient’s characteristics were: Median age, 65 years (range 38-82); >75 years old, 20%; ECOG PS 0-1 in 91% p and PS 2 in 9%; ER+ &/or PR+, 41 p (59%); >2 metastatic sites in 61%; prior (neo)adjuvant CT in 48 p (69%); prior hormonotherapy, 44 p (63%). Measurable disease in 68 p (97%). 1 p received trastuzumab concomitantly. Results: Median number of administrations (a) 11 (range 2-36). 1st/2nd line: 41%/59%. We analyzed 923 a. Dose delayed or reduced due to hematological toxicity in 2.7% a, related non-hematological toxicity in 0.3% a. Dose was reduced in 1% a. Hematological toxicities (%a): neutropenia grade (g) 3, 0.8%; febrile neutropenia 1 p who died due to septic shock after 9 a. Non-hematological toxicities (%a): pain g 3-4, 0.5%; constipation g 3-4, 0.3%; ileus paraliticus g 3, 0.1%; infection g 3, 0.1%; nausea/vomiting g4, 0.1% . 68 p were evaluable for response. 1 CR (1.5%), 19 PR (27.9%) and 16 SD (23.5%) were reported. Objective response (OR) rate 29.4% [CI 95%: 19%-41.7%]. Median progression free survival 4 m [CI 95%, 2.3-5.8]. Median survival has not been reached at the time of analysis. Conclusions: Our findings confirm the consistently produced clinically meaningful efficacy of single agent NVBO for MBC. We observed a favorable safety profile with a particular low incidence of myelosupression and alopecia. We consider that oral vinorelbine is a suitable 1st or 2nd-line treatment for convenient administration in an outpatient environment in selected p with MBC.
Clinicopathologic features of breast cancer in the Texas-Mexico border city of El Paso.
Authors: Nahleh Zeina A. , Zhou Jenny , Ulloa Adolph
Published: March 2020

e11549

Background: Breast cancer is the leading cause of cancer death in Hispanic women in Texas. El Paso, TX is a large border city of 900,000, 85% Hispanic. Very limited research has been published on this population. Methods: After IRB approval, we analyzed the variables at initial diagnosis of 111 consecutive patients with breast cancer treated at a single academic institution in El Paso, in 2011. Descriptive statistics were utilized. Results: Mean age was 54 years; 101 were Hispanics (91%), 4 White non-Hispanic, 4 African-Americans and 2 Middle Eastern. Six patients (5%) had stage 0, 61 (55%) localized (stages I and II), 32 (29%) loco-regional (stage III), and 12 (11%) stage IV disease. Histology was: 104 ductal (94%), 6 lobular (5%) and 1 neuroendocrine. Sixty two patients (59%) had Estrogen Receptor (ER) positive tumors versus 32 (31%) ER negative. 79 patients (75%) had HER2 negative and 25 (24%) HER2 positive tumors, 1 had unknown HER2. Sixty two (59%) invasive tumors were ER / PR positive/HER2 negative; 11 (10%) were ER/ PR positive/HER2 positive; 14 (13%) ER/PR negative/ HER2 positive; and 17 (16%) Triple negative. 36 patients (32%) were diagnosed at younger than 50 years; 13 (12%) between ages 30 and 40. 16 (45%) of these patients present at advanced or metastatic stages. The Median BMI was 35.5 (range 18-50.4). Treatment was as follows: Mastectomy 44 patients (42%) versus lumpectomy 56 (54%); 84 patients (76%) received chemotherapy and 71 patients (64%) received hormonal therapy. 14 patients (13 %) had cancer recurrences at median of 5.5 years. Conclusions: Consistent with other studies, Hispanic breast cancer patients in El Paso are diagnosed at a younger age , more advanced stages and have a higher prevalence of ER negative and HER2 positive tumors, compared to non-Hispanic historical controls. In addition, our patients had a higher prevalence of metastatic stage IV at diagnosis 11% compared to 6% statewide. Breast cancers among Hispanic women may comprise a distinct biologic spectrum of tumors. Also, more focused research looking at the geographical and socioeconomic differences should be conducted. Dietary and lifestyle habits should also be investigated. Increasing awareness particularly among young Hispanic women is needed.
Results of the East Carolina Breast Center phase II trial of neoadjuvant metronomic chemotherapy in triple-negative breast cancer (NCT00542191).
Authors: Tiley Stephen , Raab Rachel Elizabeth , Bellin Lisa Sheri , Wong Jan H. , Unger Jackie , Walker Paul R.
Published: March 2020

e11550

Background: Triple negative (ER negative, PR negative and HER 2 negative) breast cancers (TNBC) lack effective targeted therapy. We sought to determine the benefit of metronomic neoadjuvant chemotherapy utilizing doxorubicin with cyclophosphamide followed by paclitaxel with carboplatin in women with TNBC. Methods: Patients (pts) with TNBC>2cm were eligible (including locally advanced or inflammatory breast cancer). Pretreatment sentinel node biopsy (SLNB) was performed in patients with clinically N0 disease. Treatment consisted of weekly doxorubicin 24 mg/m2 + daily oral cyclophosphamide 60 mg/m2 x 12 weeks followed by weekly paclitaxel 80 mg/m2 + weekly carboplatin AUC 2 x 12 weeks. Granulocyte colony stimulating factor was added for ANC<= 1000. Pts received standard surgery and radiation therapy as indicated. The primary endpoint was pathologic response. Results: Between 2006 and 2011, 17 pts with infiltrating ductal TNBC were enrolled and 15 were analyzed. Age ranged from 25 to 83 (mean age 45yrs), primary tumor size ranged from 2cm to 7cm (mean 3.5cm). Three pts presented with inflammatory breast cancer, 4 had clinical N1 disease and 2 had clinical N0 disease that did not receive SLNB. Six pts underwent SLNB; 3 were pN0 and 3 were pN positive. Two pts came off study due to prolonged neutopenia. Three pts died during therapy-one of MI, one of PE and one had progressive pulmonary disease. No deaths were therapy related. Ten pts completed therapy. One experienced grade 3 (G3) thrombocytopenia, five patients had G4 neutropenia and one developed G3 neuropathy. Ten pts had a clinical complete response (cCR), four had a clinical partial response (cPR) and one progressed on therapy. The rate of pathologic complete response (pCR) was 46.6% (40% pCR, 6.6% CR with foci of DCIS). One patient had a 0.7cm focus of residual invasive carcinoma. Positive nodes were identified in 13.3%-one patient who progressed on therapy and one who experienced a cPR. Conclusions: Neoadjuvant metronomic chemotherapy with weekly doxorubicin plus daily oral cyclophosamide followed by weekly paclitaxel plus carboplatin revealed high rates of pCR with toxicities limited to marrow suppression.
Predictive factors for achieving a pathologic complete remission (pCR) rate after neoadjuvant radiochemotherapy in locally advanced noninflammatory breast cancer: Results of a multivariant analysis.
Authors: Boelke Edwin , Matuschek Christiane , Roth Stephan L. , Bojar Hans , Janni Johann Wolfgang , Audretsch Werner , Gerber Peter Arne , Speer Vanessa , Baldus Stephan , Nestle-Kraemling Carolin , Peiper Matthias , Budach Wilfried
Published: March 2020

e11556

Background: In contrast to neoadjuvant chemotherapy they are no predictive factors to estimate the pathologic complete remission (pCR) rate after preoperative chemotherapy (NRT-CHX) in locally advanced breast cancer (LABC). Methods: 315 LABC patients were included in this trial. They were treated during 1991-1998. The last follow up was in November 2011. Radiotherapy was applied with 50 Gy (5x2 Gy / week) to the breast and the supra-/infraclavicular lymph nodes. 101 patients received a 10 Gy interstitial boost (breast conservation). Chemotherapy (CMF, EC or Mitoxantron was applied in 192 patients prior to radiotherapy and in 113 patients simultaneously. Ten patients had no chemotherapy. Age, tumor grade, nodal status, hormone receptor status, simultaneous vs. sequential CHX and the time period up to surgery were examined in multivariate terms for pCR and overall survival. Results: The pCR rate for NRT-CHX after surgery was 29.2%. In multivariante analysis a longer time interval to surgery increased the probability of a pCR (HR 1,17 [95% CI 1,05-1,31], p<0,01). In term of overall survival, the achievement of a pCR is the strongest predictor for long term survival (HR 0,28 [95% CI 0,19-0,56], p<0,001). Conclusions: A long time interval to surgery (> 2 months) increases the probability of a pCR after NRT-CHX. Like in neoadjuvant CHX the achievement of a pCR is an important prognostic factor for long term survival.
Long-term results of capicitabine application in metastatic breast cancer patients.
Authors: Vladimirova Liubov Yu , Kit Oleg I
Published: March 2020

e11558

Background: Options available after the failure of anthracyclines and taxanes are very limited in BC patients. The long-term experience of Cap application brought us to analyse long-term results of the treatment in this patients. Methods: pts progressed after anthracyclines and taxanes were recruited in 2000-2010. Key elegibility criteria included measurable or nonmeasurable triple-negative MBC or locally recurrent disease, ECOG ≤2, no brain metastases. Cap was administered 1250 mg/ m² BID 1-14 days q3w. Treatment was continued until progression or unacceptable toxicity. A total of 266 courses were estimated. Endpoints include response rate, OS, PFS and safety. Results: 63 patients aged 30-80 years were recruited. 92% had infiltrative ductal carcinoma, triple negative. Time to disease progression was 2.5 mon.- 16 years(mean- 2.6 years). 22% (14) had one disease site: liver 5, lung 5, bones 3, lymphonodes 1. The rest 78% (49)had ≥2 disease sites: lung 32(50.8%), bones 30(47.6%), liver 33(52.3%), soft tissues 21(33.3%). Mean # of disease sites = 2.06. Overal RR was 63.5%(40) including 4 CR(6.3%), 6PR(9.5%) and 30SD(47.6%). Med OS= 9mo, Med PFS= 5 mo. For detailed survival analysis patients were devided into two groups: 1) with RR (40 pts); 2) without RR (23 pts). Med OS was 13 v 4 months (p=0.00004), Med PFS was 6 v 3months respectively(p=0.00016). 8 pts(12.7%) are alive till the abstract submission. Main hematological toxicity was leucopenia1/2 Gd-28.6%, neutropenia 1/2Gd.-26.3%, anemia 1/2 Gd.-19.9%, thrombocytopenia 1/2Gd.- 3.1% courses. Nonhematological toxicity included nausea 1/2 Gd.- 28.5%, vomiting 1/2Gd.- 12.5% and diarrhea 1/2 -16%, hand-foot syndrome 1/2 Gd.-16.9%, thrombophlebitis-3.8%, myalgia and ossalgia -15%, headache 3 Gd. prevented to continue Cap intake in 1 case(1.57%). No significant long-term toxicity was recorded. Conclusions: Cap has a satisfactory effect as well as controlled toxicity. The favorable long-term PFS and OS allow to use Cap in this heavily pretreated pts.
The new primary chemotherapy with S-1 and docetaxel for advanced breast cancer: A first report of N-1 trial.
Authors: Nakagawa Misako , Morimoto Masami , Takechi Hirokazu , Kawakami Yukikiyo , Tangoku Akira
Published: March 2020

e11560

Background: We reported the result of the efficacy and toxicity of S-1 combined with docetaxel (S-1+DOC) in ASCO 2011 (abstract No.1075). It showed good objective response rate (ORR) and some cases showed of complete response (CR) before middle of 8 cycles regimen. But this regimen was difficult to keep compliance of per oral S-1 intake. To improve pathological CR (pCR) rate, we planned a new protocol of primary chemotherapy with S-1+DOC (N-1 trial). Methods: Patients with advanced breast cancer (stage II-IV) were treated with i.v. docetaxel (40mg/m2) on day1 and oral S-1 (80mg as FT/m2/day) on day1 to 14 every 3 weeks for 4 cycles. According to the RECIST criteria, patients with CR were underwent operation, partial response were continued more 4cycles of S-1+DOC. Stable disease or progressive disease cases were changed regimen for EC or Trastuzumab and Paclitaxel (HT) according to their HER2 status. Adequate supportive therapy was provided for typical adverse events. Primary endpoint is a pCR rate. Secondary endpoints are ORR, breast conservation rate and safety. Results: Between 2009 and 2011, Forty-two patients were originally entered. After 4 cycles of S-1+DOC, CR was noted in 6 cases, and PR in 20 cases. 8 cases of SD and 1 case of PD were underwent EC, 4 cases of SD were underwent HT. Among 36 patients who had completed the whole regimen, 30.7% achieved pCR. ORR was 79.4% and breast conservation rate was 97.4%. Patients could keep an intake more than 80% dose of S-1 was 87%. Adverse events over grade3 were peripheral sensory neuropathy, nausea, nail change and neutropenia. Grade 3, 4 of neutropenia was noted in 62%. Conclusions: The new primary chemotherapy with S-1 and Docetaxel is expected to exhibit satisfactory efficacy and showed the possibility of shortened the term of primary chemotherapy. In order to establish this treatment, it is important to proper response assessment.