bluuebunny/crossref_metadata_2025 huggingface dataset:
New insights into HER2 expression in breast cancer patients analyzed by qRT-PCR.
Authors: Yu Rong , Chiu Kung Y. , Lu Sunny , Lee Zi-jia , Zhang Peter , Hsieh Wen Chuan , Wu Han-chieh , Su Ih-jen
Published: March 2020

e11068

Background: HER2 gene status is a key determinant for anti-HER2 therapy with Herceptin. The common methods used for HER2 test in breast cancer patients are IHC and FISH, which are time-consuming and often generate variable results. Quantitative real-time PCR (qRT-PCR) has emerged as a new gold standard technique for quantifying gene expression in different cells and tissues. In this study, we explored the potential of utilizing this technique to determine HER2 expression status in breast cancer patients. Methods: We collected both freshly-frozen and formalin-fixed paraffin-embedded (FFPE) breast tumor samples at three locations. The total RNA was isolated with a RNA extraction kit and was quantified by RiboGreen method. Each sample was normalized against its total RNA concentration and analyzed by a real-time PCR method with inclusion of the Standards and RNA Control. The HER2 expression level was determined by the copy number, Ct value, as well as the ΔCt against RNA control. The significance of HER2 expression and correlation among the different groups were analyzed by statistical methods. Results: A total of 80 samples have been tested. We noticed that the RT-PCR method generated very consistent results with little intra- and inter-assay variance. We also noticed that HER2 expression in the fresh tumor samples exhibited two distinct populations, although HER2 expression in the normal fresh samples showed the continuous distribution. Similar results were obtained with the FFPE samples. Study of the other breast cancer-related genes, such as EGFR, ER-a, BRCA1, and BRCA2, revealed that their expression, unlike HER2, followed a pattern of continuous distribution. In comparison with FISH test, qRT-PCR method not only produced consistent results, but also able to differentiate breast tumors into two distinct groups, HER2 positive vs. HER2 negative. Conclusions: The qRT-PCR is a more reliable method than the currently used IHC and FISH for HER2 test. Showing two distinct groups of HER2 expression by qRT-PCR further warrants its application in testing HER2 gene status for breast cancer patients.
Comparison of treatment patterns and outcomes in metastatic breast cancer (MBC) patients initiated on trastuzumab versus lapatinib: A retrospective analysis.
Authors: Gauthier Genevieve , Guerin Annie , Styles Amy , Wu Eric Q. , Brammer Melissa G. , Lalla Deepa
Published: March 2020

e11076

Background: The National Comprehensive Cancer Network (NCCN) guidelines recommend trastuzumab- or lapatinib-based therapies as the preferred agents for metastatic HER2-positive breast cancer. Few studies have compared treatment patterns and outcomes in MBC patients (pts) treated with trastuzumab vs. lapatinib. The objective of this study is to compare rates of new metastatic sites, discontinuation, healthcare resource utilization, and costs in MBC pts initiated on lapatinib vs trastuzumab. Methods: Adult women with MBC initiated on trastuzumab or lapatinib on or after 03/13/2007 (lapatinib FDA-approval date) were selected in the PharMetrics® Integrated Database (2000-2011). Pts were followed from trastuzumab or lapatinib initiation date up to the end of continuous healthcare plan enrollment/data availability, whichever occurred first. New metastatic sites and discontinuation rates (gap ≥45 consecutive days) were compared among trastuzumab and lapatinib pts using multivariate Cox proportional-hazards models. Incremental healthcare resource utilization and monthly costs (2010 USD; measured from a payer perspective) were estimated using multivariate generalized linear models. Results: Among the643 pts selected, 381 and 262 pts were initiated on trastuzumab and lapatinib, respectively. After multivariate adjustment, compared to trastuzumab pts, lapatinib pts had a higher rate of new metastases (hazard ratio [HR]=1.65; p<.001) and treatment discontinuation (HR=1.57; p<.001). There was no statistically significant difference in total healthcare cost between lapatinib and trastuzumab pts (p=.397). The incidence of medical visits associated with treatment administration was lower in lapatinib pts (Incidence rate ratio [IRR]=0.34; p<.001), however, the incidence of other outpatient visits was significantly higher in lapatinib pts (IRR=1.19; p<.001). Conclusions: Whileboth cohorts presented similar healthcare costs, pts initiated on lapatinib showed higher rates of new metastatic sites, discontinuation, more outpatient visits (non treatment-related), but fewer medical visits associated with treatment administration.
Limitations in assessment of ER, PR, and HER2 status of breast cancer patients: Yangon experience.
Authors: Mon Yin Yin
Published: March 2020

e11078

Background: Management of breast cancer become individualized nowadays especially in developed countries. Molecular profile of breast cancer is essential to have this management. However, there are still limitations to examine such molecular profile in developing countries like Myanmar. Our aim in this study is to know the number of patients who underwent ER, PR and HER 2 status assessment among breast cancer patients in Myanmar and to analyze types of limitations for the molecular assessment in management of breast cancer. Methods: Total number of 823 breast cancer patients who registered from January 2009 to December 2011 at Medical Oncology Unit of Yangon General Hospital and two private oncology clinics were studied. Results: The age range from 19-80 years and mean age of 44.36 years. Among 823 breast cancer patients, ER, PR and HER 2 status were done in 134 patients (16.28% ) whereas 689 patients( 83.71% ) were not. 604 (87.66%) out of 689 patients who did not undergo profiling were due to financial problem. 60 patients (8.70 %) were found to have lack of information about molecular profiling although they were affordable . 25 patients (3.62 %) lost their tissue due to technological limitation Conclusions: Financial problem is the major limitation to get molecular profile for breast cancer patients in Myanmar. Patients need self expense to do advanced technology examinations in different health care system of our country. In this study we also found out that there was lack of information which leads not to undergo further investigations to some well to do patients. Overall, we believe that molecular technology support with reduced expense will help more patients in future to get better management in breast cancer in Myanmar. Besides, we need to provide update information about molecular testing in breast cancer to not only patients but also health professionals in our country.
Association of higher proliferation of Ki67 with unfavorable prognostic factors and shorter survival in breast cancer.
Authors: Kilickap Saadettin , Kaya Yalcin , Yucel Birsen , Tuncer Ersin , Elagoz Sahande
Published: March 2020

e11083

Background: The prognostic value of Ki67 expression level is yet unclear in breast cancer (BC). The aim of this study was to investigate the association between Ki67 expression levels and other prognostic factors in BC. Methods: Demographic, clinical and pathological features of the pts were retreived from the hospital records. Results: In this study, 163 pts with BC were analyzed. The mean age of the pts was 53.4±12.2 years. Median Ki67 level was 20% in this study. Ki67-high tumors were significantly associated with high grade (p<0.001), lymphovascular invasion (p=0.001), estrogen receptor negativity (ER-) (p=0.035), Her2 (+) (p=0.001), advanced stage (p<0.001) and lymph node involvement (LNI) (p<0.003) of the tumor. There was no relationship between the age, perineural invasion, progesterone receptor and Ki67 positivity. Lower Ki67 levels were significantly associated with longer median relaps-free survival (RFS) compared to those of higher Ki67 levels (p=0.008). The overall survival (OS) was longer in pts with lower Ki67 levels than those with higher levels (p=0.017). Conclusions: High Ki67 expression was associated with ER-, Her2 (+), higher grade and LNI in BC. The level of Ki67 expression was a prognostic factor predicting the RFS and OS in BC pts. [Table: see text]
Expression of PTEN, Akt, MAPK, p53, p95 for predicting trastuzumab resistance in breast cancer.
Authors: Duman Berna Bozkurt , Sahin Berksoy , Ergin Melek , Zorludemir Suzan , Acikalin Arbil
Published: March 2020

e11088

Background: The activation of the oncogene PIK3CA and the loss of the tumor suppressor gene PTEN are mutations commonly found in breast tumors. AKT is a key activator of cell survival mechanisms. Mutant p53 proteins can actively contribute to tumorigenesis. Trastuzumab in particular are the primary treatment in the adjuvant and recurrent settings for breast cancer. Many studies reported that selected patients may present with resistance to trastuzumab due to the presence of p95 HER2 fragments. To address this challenge,we analyzied PTEN, Akt, MAPK, p53, p95expressions in breast cancer treated with trastuzumab therapy. . Methods: Ninety patients were assessed for this study and in the guidance of inclusion and exclusion criteria 25 patients were enrolled to the study. HER2 positivite, metastatic or locally advanced patients were enrolled to the study.. All of the patients that included to the study were treated with trastuzumab. Trastusumab resistance was assessed. Antracylin and taxane containing regimens were given to all patients. Gemcitabine, cisplatine capectabine, navelbine containing regimens were given on second and third line treatment choices. Tissue samples were obtained from parafine blocks and evaluated for PTEN, Akt, mapk, p53, p95 expression with immunohistochemical method. Results: The median age was 54±12. PTEN, Akt, MAPK, p53, p95 expressions were found in different levels on tumor tissue samples. Trastuzumab resistance were detected in 5 (20%) patients. Akt expression was positive in 2(8%) patients, MAPK expression was positive in 1 (4%) patient, p95 expression was positive in 1 (4%) patient, p53 expression was positive in 1 (4%) patient, PTEN expression was negative 3 (12%). Statistically significant difference was not found between trastuzumab resistance and PTEN, Akt, MAPK, p53, p95 expressions (respectively p:0,11, 0,79, 0,95, 0,88, 0,74). Conclusions: PTEN, Akt, MAPK, p53, p95expressions were assessed on HER2 positive breast cancers for predicting trastuzumab resistance. There was no statistically significant correlations between trastuzumab resistance and the expressions of these biomarkers. This study is ongoing, this is the preliminary results of this study.
Breast cancer in young women in India.
Authors: Deshmukh Sanjay P , Mane Anupama Dutt
Published: March 2020

e11506

Background: The incidence of breast cancer is rising in India. It presents at a younger age in Indian population as compared to the western countries. Methods: This is a retrospective review of all breast cancer patients less than 40 years of age treated in single tertiary care center from June 2006 to June 2011. The aim was to assess the factors that may influence clinical outcome and prognosis including demographics, clinical characteristics, surgical and pathological findings and the treatment given. Clinical data was collected from medical records and histopathology reports. Independent variables like age, stage at presentation, surgery type, chemotherapy, radiation, tumour size, grade, nodal status, no. of positive nodes, perinodal extension, lymphovascular extension, ER, PR and Her2 neu were analysed. Results: Out of a total of 613 patients, 91 were under 40 years of age, corresponding to a prevalence of 14.8%. Median age was 35 years with the youngest being 23 years old. Maximum patients were in the age group of 36-40 years. Lymphovascular emboli was positive in 42 patients (48.8%) and perinodal extension was positive in 36 patients (41.8%). 30 patients(34.8%) had ER positivity, while 39 patients (45.3%) had PR positivity. Her 2 neu receptors were positive in 20 patients (23.2%). 39 patients were triple negative (45.3%). The median follow up period for all the patients was 28 months with the DFS being 76.1% and OS being 88.3%. In univariate analysis, factors significantly associated with survival were stage at presentation (p value- 0.026), presence of lymhovascular emboli (p value- 0.019) and presence of perinodal extension (p value- 0.007 ).Grade of the tumour also correlated with survival , however it was not statistically significant (p value- 0.086). Statistical analysis was done with SPSS 17. Conclusions: The incidence of breast cancer in younger women in India is high with increased number of triple negative patients. Overall survival is quite similar to that of the western population. Longer follow up and more studies are required to confirm this finding.
Adherence to yoga practice improves symptom control and quality of life in breast cancer patients undergoing conventional treatment.
Authors: Raghavendra Rao M. , Gopinath Kodaganur Srinivasachar , Srinath B S , Patil Shekhar , Shashidhara P , Diwakar Ravi B , S Ramesh Bilimagga , Rao Nalini K , Ajaikumar Basavalinga S. , Prashanth Jayanna , Chidambaramurthy K N
Published: March 2020

e11511

Background: Adherence plays an important role in success of mind body interventions such as yoga. In this study we evaluated the effects of adherence to yoga intervention on psychological and quality of life outcomes. Methods: Adherence to yoga program was assessed in a randomized controlled trial comparing yoga (n=45) vs. supportive therapy in breast cancer patients with stage II and III disease undergoing primary surgery followed by adjuvant radiotherapy and chemotherapy. Subjects were assessed for self reported symptoms and affective states using symptom checklist, Spielberger’s State Trait Anxiety, Becks Depression Inventory and Functional Living Index in cancer for Quality of life following surgery and during radiotherapy and chemotherapy. Adherence was categorized based on number of sessions of yoga practiced at home per week [regular (>5 sessions), not so regular (3-5 sessions), occasionally (upto 2 sessions)].Multiple hierarchical regression analysis was used to examine the variance in the above outcomes explained by independent prognostic variables (age group, clinical stage of cancer, type of surgery, respective baseline psychological outcomes and regularity of practice) in yoga group alone. Model B includes these four variables plus regularity of practice. Results: Regularity of practice emerged as a secondary predictor for symptom severity following surgery (β= 0.38, p=0.007) and primary predictor for depression (β= 0.37, p=0.05) and severity of symptoms (β= 0.42, p=0.04) during radiotherapy and depression(β= 0.35, p=0.05), severity of symptoms (β= 0.45, p=0.03), anxiety trait(β= 0.40, p=0.03) and quality of life (β= -0.61, p=0.001) during chemotherapy. Conclusions: Adherence to mind body interventions such as yoga improves psychological and quality of life outcomes in breast cancer patients undergoing conventional cancer treatment.
Metronomic chemotherapy (MC): Results of two feasibility trials in patients (pts) with HER2 positive (HER2+) and negative (HER2-) locally advanced breast cancer (LABC).
Authors: Petry Vanessa , Leal Alessandro , Arai Roberto J. , Piato Jose R. , Andrade Felipe , Paiva Marcelo , Ferraz Marcio R. , Marinho Simone , Hoff Paulo Marcelo , Mano Max S.
Published: March 2020

e11513

Background: In SWOG0012, MC improved pathologic complete response (pCR) compared to standard neoadjuvant chemotherapy (NC). We evaluated the feasibility of MC with a taxane→anthracycline schedule, which has also been shown potentially superior to the inverse sequence. We also evaluated the feasibility of MC in combination with trastuzumab. Methods: The primary objective was feasibility (defined as a febrile neutropenia (FN) rate ≤10%). Secondary objectives were cardiac safety, tolerability and efficacy as measured by objective response and pCR. The original accrual goal was 25 Her2+ pts and 40 Her2- pts. Her2- pts received paclitaxel (100mg/m2) x8 weeks followed by doxorubicin (24mg/m2) x9 weeks combined with oral cyclophosphamide (100mg/day), without G-CSF. Her2+ pts also received weekly trastuzumab (4 mg/kg followed by 2mg/kg) concurrently with the entire CT. Results: Most pts were stage III (Her+: 8/9; Her-: 4/11). The Her2+ cohort was prematurely closed after 2(22%) pts developed G3 pneumonitis (both during the MC phase). Both recovered completely. There was 1 case of asymptomatic LVEF drop to below 50% (during the taxane phase); 1 pt had G2 hand-foot skin reaction (HFS) and another had G2 mucositis. The Her2- cohort was also prematurely closed with only 11 pts due to high rates of mucocutaneous toxicity (G3 HFS in 36%, G3 rash in 9%) and also because of SWOG0221 negative results. There were 2(18%) cases of FN, but no cases of pneumonitis. 1/11(9%) Her2- and 5/9(55%) Her2 + pts had a pCR. VEGF-related biomarkers were collected and will be presented at a later date. Conclusions: The proposed MC schedules proved too toxic to be considered for further clinical development. In addition, MC resulted in unexpectedly high rates of severe pulmonary toxicity when given in combination with trastuzumab. Her2+ but not Her2- pts had an impressively high pCR rate.
Meningism as a poor risk factor in breast cancer patients with relapse in central nervous system (CNS).
Authors: Schwarz Luis Jesus , Vallejos Carlos S. , Neciosup Silvia P. , Pinto Joseph , Vidaurre Tatiana , Ferreyros Greenlandia , Gomez Henry Leonidas
Published: March 2020

e11518

Background: CNS relapse in breast cancer patients is invariably defined as a poor prognosis feature with varied and bizarre clinical presentation. We describe the commonest signs and symptoms in CNS relapse and their relation with prognosis Methods: We evaluate retrospectively 2597 women with breast cancer treated at the Instituto Nacional de Enfermedades Neoplásicas (Lima-Perú) between 2000-2005. Phenotypes were determined by IHC and categorized in [HR+, HER2-], triple-negative (TN) [HR-, HER2-] and Her-2 [HR+/-, HER2 +]. Post-CNS recurrence survival was calculated by Kaplan Meier method. We use Chi-square, or exact Fisher test when appropriate, to evaluate correlations between categorical variables. Results: 157 pts (6.04%) had CNS relapse from which 19 had only leptomeningeal carcinomatosis (LMC), 124 only brain metastases and 14 both. In regard to phenotype, 43pts were [HR+, HER2-] (5 LMC), 68 were TN (13 LMC) and 51 were [HR+/-, HER2 +] (15 LMC). 152 pts had stages I-III (96.8% of all SNC relapses). There was no association between phenotypes and age at CNS relapse, ECOG PS, extracraneal metastases, control of primary tumor, number or volume of brain metastases. Significant association was found between phenotype and time from diagnosis to CNS relapse (≤8 months: 16.3% in TN, 7.3% in Her-2 and 0% for [HR+, HER2-], [P=0.017] ) and histological grade (grade III: 74.4% in TN, 55.% in Her-2 and 30% for [HR+, HER2-], [P=0.006]). Symptoms/signs frequently described in LMC patients were cephalea (72%), meningism (24%), nausea (24%), vomiting (20%), ataxia (20%), facial palsy (16%), somnolence (16%), paraparesia (12%), hiporeflexia (12%), apraxia (12%), arreflexia (12%), poor sphincter control (12%), hemiparesia (8%), seizures (8%), bradipsiquia (8%), neuropathic pain (4%). Fifty percent of TN pts with LMC had meningism. Post recurrence survival was shorter in TN patients (3.61mo vs 4.89mo to [HR+, HER2-] vs 5.95mo to [HR+/-, HER2 +; P=0.044] and in patients with meningism (1.38mo vs 5.26mo; P=0.02). Cox regression identify meningism as a risk factor for survival in patients relapsed with LMC (HR: 4.33; P=0.066). Conclusions: Meningism seems to be the only sign related to poor prognosis in patients relapsed with LMC.
Retrospective analysis of the use of GCSF and its impact on dose-response effect for anthracycline plus taxane-based schedules in early breast cancer.
Authors: Bermejo Begona , Perez-Fidalgo Jose Alejandro , Chirivella Isabel , Catoira Isabel , Martinez Patricia , Contel Estela , Lluch Ana
Published: March 2020

e11523

Background: Previous studies have confirmed that prophylactic GCSF significantly reduced the incidence of febrile neutropenia. Less is known about its impact on the dose-density administered in taxane-based schedules. The objective of this observational, retrospective database analysis was to evaluate the relative dose-intensity (RDI) achieved in a non-selected population in whom GCSF was administered under clinician criteria according to guidelines. Methods: Early breast cancer (stage I-IIIA) patients diagnosed from January 1999 through December 2006 and considered candidates for adjuvant anthracyclines and taxanes were included. RDI administered was measured by the number of delayed cycles as well as by the number of delayed days. GCSF was considered to have been administered even if it was given in only 1 cycle, as primary or secondary prophylaxis, or to treat neutropenia. Results: 231 breast cancer patients were included. Patients had a median age of 59 years (26-80) of whom 52% had stage III cancer. Most patients had tumors positive for hormonal receptors (83%) and 7% of tumors were considered triple negative. Adjuvant schedules administered included docetaxel (68%) or paclitaxel (32%) plus anthracyclines. GCSF was given to 40% of patients, as primary (60%) or secondary prophylaxis (31%), as well as to treat neutropenia (9%). Prophylactic GCSF was mostly given in schedules with docetaxel and anthracyclines such as TAC (85% of patients). Overall, 5 patients (2%) received <85% of the RDI, 23 (10%) delayed 1 cycle and 15 (7%) delayed ≥2 cycles, and 5 (2%) showed a delay of ≥15 days. 5 and 10-year DFS rates were 0.88 (95% CI: 0.84-0.92) and 0.80 (95% CI: 0.72-0.87), respectively. No differences in terms of DFS between patients with <85% vs. ≥85% of RDI were found (p=0.695). Conclusions: With adequate use of GCSF in patients treated with taxane-based schedules, 98% of patients achieved a RDI ≥85%. Schedules with docetaxel or given concurrently with anthracyclines were more likely to receive GCSF. This study was partially funded by Amgen SA.
Local treatment of breast in de novo stage IV breast cancer patients.
Authors: Chen Peng-Yu , Cheng Skye H Hong-Chun
Published: March 2020

e11526

Background: Stage IV breast cancer is an incurable disease. Systemic therapy is usually the main treatment for these patients. Locoregional therapy, such as surgery or radiotherapy, is controversial. Recent studies suggested locoregional treatments of the primary breast cancer can provide some benefit for these patients. Methods: We conducted a chart review of de novo stage IV breast cancer patients at a cancer center hospital in TAIWAN from 1990 to 2008. A total of 276 patients were reviewed and 268 patients met the inclusion criteria. Tumor characteristics, anti-tumor treatments and survival were analyzed. Results: The median survival of 268 patients was 21.5 months. We divided these patients into two groups. There were 140 patients with less than 21.5 months of survival and 128 patients with more than 21.5 months of survival. In univariate analysis, infiltrating ductal carcinoma (p=0.002), ER-positive (p<0.0001), PR-positive (p<0.0001), and no overexpression of HER2 (p=0.0125) were associated with longer survival. The clinical primary tumor size (p=0.11) and positive axillary lymph node involvement (p=0.61) were not different significantly between two groups. About metastatic site, patients with liver mets (p<0.0001) and lung mets (p=0.025) were associated with shorter survival. Bone mets (p=0.63) was not associated with survival. Patients receiving local treatment of primary tumor, including surgery (p<0.0001) or locoregional radiation (p=0.0034), had longer survival. In multivariate analysis, patients who received surgery of primary breast cancer (HR=0.52, p=0.0006) or received systemic chemotherapy (HR=0.47, p=0.002) had better survival. In subgroup analysis, patients without liver metastasis who received surgery of primary breast cancer had longer overall survival significantly (p<0.0001). In contrast, surgery to the primary breast cancer had no benefit in survival (p=0.91) in patients with liver metastasis. Conclusions: Our institutional experience suggests locoregional treatment for primary breast cancer appear to be beneficial for de novo breast cancer patients, especially those without liver mets.
Is docetaxel (D) less efficient than anthracycline-based chemotherapy (A) in triple-negative breast cancer (TNBC) treated in neoadjuvant setting?
Authors: Simon Laurence , Belletier Christine , Rodier Jean-Francois , Weitbruch Delphine , Velten Michel , Wilt Marc , Ghnassia Jean-Pierre , Petit Thierry
Published: March 2020

e11542

Background: BRCA1 mutation is associated with the TNBC phenotype. Loss of BRCA1, due to genetic mutation or post-genomic inactivation, should confer susceptibility to DNA-damaging agents, such as anthracyclines, but resistance to mitotic-spindle poisons such as taxanes. However, optimal adjuvant systemic therapy for TNBC is difficult to define because of a lack of prospective data in TNBC restricted populations. As our neo-adjuvant regimen changed in 2008 (A followed by D before 2008 then D followed by A from 2008); we were able to compare retrospectively A and D efficacy in matched cohorts of TNBC treated in neo-adjuvant setting. Methods: Group 1 includes 24 patients with TNBC treated between 2005 and 2008 with A followed by D (3x 5FU 500 mg/m², epirubicine 100 mg/m², cyclophosphamide 500 mg/m² followed by 3x docetaxel 100 mg/m²). Group 2 includes 24 patients with TNBC treated in NAS between 2008 and 2011 with D followed by A. Characteristics of group 1 and 2 (median age at diagnosis, tumor grade, Ki67, TNM) were similar. All patients had a core-biopsy before chemotherapy. Chemotherapy response was evaluated by CT scan before 1st cycle, between 3rd and 4th cycle then after the 6th cycle. Surgery was performed 4 weeks after the 6th cycle. Results: In group 1, objective response rate after 3 cycles was 58% (14/24) (RECIST criteria). There was no progression. Complete pathological response rate (no residual invasive and in-situ tumor in breast, no tumor in axillary nodes) was 25%. In group 2, objective response rate after 3 cycles was 25% (6/24). Progression rate was 13% (3/24). Complete pathological response rate was 29%. The objective response rate after the first three cycles was significantly different between group 1 and group 2 (two-sided p-value = 0,039, Fisher exact test). Conclusions: Our retrospective analysis showed that docetaxel was significantly less efficient than anthracycline-based chemotherapy in chemo-naïve TNBC patients. These data should be taken in consideration for clinical practice and further phase III trials design in TNBC.
Prolonged clinical benefit with metronomic capecitabine plus oral vinorelbine as treatment of metastatic breast cancer: Results from a phase II study.
Authors: Orlando Laura , Fedele Palma , Schiavone Paola , Nacci Angelo , Calvani Nicola , Mazzoni Enrica , Quaranta Annamaria , Cinefra Margherita , Cinieri Saverio
Published: March 2020

e11547

Background: Metronomic chemotherapy regimens have shown efficacy in patients with metastatic breast cancer through antiangiogenic mechanisms. We present preliminary data of a phase II trial of metronomic capecitabine (CAP) in combination with oral vinorelbine (VIN) as treatment of metastatic breast cancer (MBC). Methods: Patients with advanced breast cancer, pretreated or not for metastatic disease, were treated with VIN (60 mg/m2, on days 1 and day 8 of a 21-day cycle) combined with metronomic CAP (1500 mg daily). Primary end-point was overall response rate (ORR), secondary end-point time to progression (TTP), clinical benefit rate (CBR; PR+ CR + prolonged SD for ≥ 24 weeks) and tolerability. Results: A total of 31 patients with histologically confirmed, Her2 negative MBC, have been enrolled, 22 actually valuable for response and toxicity. Median age was 62 years (range 34-75), visceral metastases were present in 18 patients (58%), 11 patients (35%) were pretreated with chemotherapy, most of them with anthracycline and taxanes. Triple negative tumors were 5 (16%). Median number of cycles was 12 (range 4-34). The ORR was 54.5 % (95% CI, 44-63%), with two CR (9 %) and 10 PR (45%). Seven patients had SD, 5 prolonged (23%). The CBR was 77% (95% CI , 71%-84%). Three progressions of disease were observed (14%). Median TTP was 8 months (range 3- 24 +). Median overall survival was 32 months (range, 6-39 + ). The most frequent toxicities were WHO diarrhea grade 1 and neutropenia grade 2. Grade 3 skin toxicity was observed in two patients subsequently found to have DPD enzyme deficiency. No grade 2 alopecia was reported. Conclusions: In this phase II study, the all oral combination of low dose metronomic CAP combined with VIN seems to be very active, confirming data with standard doses, and allows a very long duration of response and treatment. The observed toxicity was mild and manageable. Thus, patients accrual is ongoing to the pre-set target of 66 patients.
Continuous low-irradiance photodynamic therapy (CLIPT) as a novel treatment for cutaneous recurrences of breast cancer.
Authors: Persico Justin , Wazer David E. , Melanson Anne Marie , Rogers Gary S , Graham Roger
Published: March 2020

e11548

Background: Photodynamic therapy (PDT) has been used for the treatment of many malignancies. This binary therapy involves the administration of a photosensitizer followed by exposure to light. Treatment toxicity has historically limited the use of PDT. Our study aimed to assess whether a novel approach, termed continuous low irradiance photodynamic therapy (CLIPT), would result in enhanced efficacy with reduced toxicity. Preclinical data suggest decreased toxicity and increased cell death by apoptosis with CLIPT. Methods: Breast cancer patients with chest wall progression were eligible for our study. No systemic anti-cancer therapy within 30 days and no radiation to the target site within 60 days of enrollment was allowed. All patients received porfirmer sodium intravenous 0.8mg/kg at time 0 and returned at time 48 hours for light exposure. A wavelength of 630nm was delivered continuously over 24 hours by a Diomed laser via a flexible light patch. An area of uninvolved normal skin was used as a control. Post-treatment biopsy was performed to assess for apoptosis by TUNEL assay. Results: Eight breast cancer patients were enrolled in our study. The initial dose of light was 100J/cm2 and was given to subjects 1 and 2 but resulted in partial-thickness ulceration of the epidermis. Subjects 3-8 received light at 50J/cm2 and experienced erythema at the intervention site, with no ulceration observed. All patients reported mild pain at the treatment site and 6 required short-term narcotic analgesia. Five of the 8 patients showed evidence of response, and no patients had progression of treated lesions. Four of 7 biopsy specimens showed evidence of apoptosis on TUNEL assay. Conclusions: CLIPT may prove to be a valuable option for treatment of breast cancer chest wall recurrence. The dose-limiting toxicity was skin ulceration and the maximum tolerated dose (MTD) was determined to be 50J/cm2/24h. A 50% response rate was seen in patients treated at the MTD, with apoptosis seen on post-treatment biopsy specimens. Further investigation of CLIPT as a therapeutic modality is warranted.
Which is your choice? Neoadjuvant doxorubicin hydrochloride and doxetaxel (AD) versus doxorubicin hydrochloride, cyclophosphamide, and paclitaxel (AC-T) in locally advanced breast cancer.
Authors: Kang Seok Yun , Choi Jin-Hyuk , Kim Ku Sang
Published: March 2020

e11559

Background: It is well known that neoadjuvnat chemotherapy is acceptable for women with locally advanced breast cancer. However, it is not achieving consensus that what kind of regimen is most effective and tolerable, although lots of regimens and dosages were clinically used. Methods: We compared the patients who were received adriamycine and doxetaxel (AD) and adriamycin, cyclophosphamide followed by paclitaxel (AC-T) as neoadjuvant chemotherapy and then received operation from 1 January 2006 to 30 September 2011. The group of AD regimen was scheduled for 3 cycles of AD (50mg/m2 and 75mg/m2, respectively) with 3 weeks interval and then completes resection. The group of AC-T was scheduled for 4 cycles of AC regimen (50mg/m2 and 500mg/m2, respectively) and then 4 cycles of paclitaxel(175mg/m2) with 3 weeks interval and then completes resection. Results: The patients who were enrolled in this study were totally 78(AD and AC-T were equally 38.) The significant differences of patients’ characteristics between two groups were not observed. However, the significant differences were identified in hematologic toxicity including neutropenia more than grade 3 p<0.001), neutropenic fever p<0.001), dose reduction rate due to hematologic toxicity (p=0.012) and chemotherapy induced anemia (p=0.012)), although chemotherapy induced thrombocytopenia (p=1.0) was not different between two groups. No differences were identified in non-hematologic toxicity including hepatic toxicity, gastrointestinal toxicity and peripheral neuropathy. The response of chemotherapy was no difference between two groups, which was estimated by conversion rate of breast conserving surgery, clinical response of chemotherapy (p=0.148), clinically downstaging rate (p=0.464) and pathologic complete response rate (p=1.0). There is no factor to predicting pathologic complete response or conversion to breast conservation in this study. Conclusions: The neoadjuvant AC-T regimen is more tolerable with similar clinical outcome compared to AD regimen.
Significance of chromosome 17 polysomy in breast cancer.
Authors: Galamaga Robert W. , Mariani Rachel , Almanaseer Imad , Bitran Jacob D.
Published: March 2020

e12002

Background: Human epidermal growth factor receptor 2 (HER-2) overexpression occurs in up to 30% of breast cancers and has been associated with poor clinical outcomes that have improved with advances in HER-2 directed therapy. The HER-2 gene resides on the long arm of chromosome 17 and amplification is typically assessed via immunohistochemistry or fluorescence in situ hybridization (FISH); HER-2 is interpreted as amplified, non-amplified, or equivocal. The effect and clinical impact of chromosome 17 polysomy in specimens interpreted as HER-2 non-amplified has not been well-established in breast cancer patients. This subgroup may represent a unique set of patients who may benefit from HER-2 directed therapy given the increase in HER-2 gene copy number. If tumors with polysomy 17 share biologic similarities with those positive for HER-2 amplification this may significantly influence the approach to treating these patients. In a single institution study we reviewed all breast cancer cases diagnosed in 2008 which were reported as HER-2 equivocal or non-amplified via FISH and with chromosome 17 polysomy in order to extrapolate disease-free and overall survival data within this subset. Methods: HER-2 expression via FISH from patients diagnosed with breast cancer in 2008 was reviewed. In those patients with equivocal or non-amplified HER-2 expression we selected those with chromosome 17 polysomy defined as a chromosome 17 centromere copy number of > 3 per tumor cell. A total of 9 patients were identified. Results: The median age was 74 (36-88). Median tumor size was 1.6 cm (0.7-4.9) and 8 patients (88%) had both estrogen and progesterone positive tumors. Stage distribution was as follows: stage IA: 4 (44%); stage IIA: 2 (22%); stage IIB: 2 (22%) and stage IIIA: 1 (11%). The actuarial 3 year disease free survival was 67%. Conclusions: Breast cancers with equivocal or non-amplified HER-2 expression with chromosome 17 polysomy represent a unique subset of tumors with a biology that is not well-understood. Previously published studies have yielded conflicting results regarding the prognostic significance of this genotype. Our study reflects a three year survival of 67% which suggests that these patients represent an aggressive subset.
Comparison of real prognosis and estimated prognosis by Adjuvant! Online in breast cancer in sites of Itajaí, Brazil.
Authors: Santos Borges Giuliano , De Azambuja Evandro , Rovere Rodrigo , Colchon Paulo Henrique , Staak Junior Marcos Cesar
Published: March 2020

e12035

Background: Internet-available programme Adjuvant! Online is widely regarded as one of the best tools to estimate prognosis as well as benefit of adjuvant therapy in breast cancer. Methods: It is a retrospective cohort study, with a post hoc analysis with 214 patients of three different Brazilian services in which were measured the year overall and disease free survivals in a follow up of three years, and the same endpoints were estimated on a 10 year basis by the Adjuvant! Online programme. Results: See table. Conclusions: Our study shows interesting trends in breast cancer survival, even though the number of patients accrued may not be enough to have full external validity. We conclude that the OS and DFS rates in our sample compared to the one calculated by the Adjuvant! Online programme display agreement, following the same pattern, considering different periods of follow up (much longer in the internet tool). The only group which had poor concordance was the group of younger patients (i.e., under 40), even though it was the least represented group in our sample. Nevertheless, it can be suggested that the programme underestimates the usually bad prognosis in these cases, as broadly documented in medical literature. Our study shows interesting trends in breast cancer survival, even though the number of patients accrued may not be enough to have full external validity. [Table: see text]
Ten-year trends in colorectal cancer (CRC) control in Texas.
Authors: Vugrin Davor
Published: March 2020

e12044

Background: The 2015 colorectal cancer control goals are to reduce age-adjusted incidence to 34.8/100,000 and mortality to 12.0/100,000 and to increase the number of 50 year and older undergoing screening per national guidelines up to 75%. Methods: In order to determine progress and trends toward meeting the 2015 objectives we have reviewed Texas Cancer Registry 2000 – 2009 data for incidence, 1999 – 2008 data for mortality, and BRFSS 2002 0 2010 data for screening rates. Results: 91,260 Texans were diagnosed with CRC and 32,840 died from it. Non-Hispanics represent 50.1% of population they account for 66.4% of cases diagnosed with it. Hispanics account for 34.7% of population and contribute to 18.7% of diagnoses. Blacks, 12.1% of population contribute 12.6% of cases. Male and female contribution to diagnosed CRC was 53.5 % and 46.% of cases. Black male incidence rates were highest 74.7 and Hispanic females lowest 32.7/100,000. While NH White and Blacks reduced incidence rates by about 1% per year, Hispanics rate of decrease was 0.5/yr. Gender and race played role in this decrease. Mortality rates declined most in Blacks and NH Whites, while no appreciable improvement was observed in Hispanics. Race and gender mortality rates varied. Black male mortality rates were highest, 36.0 and Hispanic females lowest, 10.5. Frequency of sigmoidoscopy-colonoscopy increased in all 3 racial/ethnic groups, but was lowest among Hispanics. Lack of insurance is big obstacle to progress. Conclusions: Major coordinated screening push will be needed to reach 2015 goals.
Small business technology transfer (STTR) phase I study (1 R41 MD006148-01) of an automated voice response (AVR) system to improve symptom management in neuro-oncology patients.
Authors: Chowdhary Sajeel A. , Given Barbara Ann , Given Charles W , Majeske Cindy , Decker Paul D , Decker Brian
Published: March 2020

e12500

Background: This STTR Phase 1 study focused on enhancing and improving the technology of a prior AVR system (Grant #R01 CA30724) to manage symptoms in cancer patients. Neuro-Oncology patients were enrolled to test our proof of concept (POC). Methods: Previous AVR function was replicated using Asterisk software enhancing the branching logic, configurability and operational capacity on multiple operating systems; limitations of the previous AVR. Eligibility criteria: access to a telephone; actively on chemotherapy. Nurse recruiters provided detailed information about the study and answered questions. Following signed consent patients provided a preferred phone number and chose a day and time of the week to receive AVR calls. Patients received a Symptom Management Guide (SMG) at time of consent. Patients were contacted a total of 4 times over a 4 week period by the AVR. At each contact patients were asked to rate 17 symptoms on a scale of 1-9 for severity and interference with 4 domains of quality of life on a 1-5 scale. Patient’s reporting a 4 or higher severity level were directed by the AVR to reference their SMG for self-care strategies to manage their symptoms. At the end of the study patients completed a satisfaction survey. Results: Ten patients were enrolled. The AVR placed 38 of 40 scheduled calls. No errors in survey branching were evident with confirmation. Patient satisfaction surveys were completed with 70% of patients. One patient did not complete any scheduled calls and was not contacted, two patients were unreachable. All patients reported satisfaction. 86% reported they would recommend this system to their oncology provider. 71% felt it was helpful in individualized monitoring of symptoms between visits. 57% liked knowing their symptom(s) were being checked regularly. One indicated the system was too overwhelming. Complaints included: not being able to change responses (1) and not allowing them to answer questions as fast as they wanted (2). Conclusions: Patient satisfaction results and system performance confirmed that the POC was feasible and that this system should be studied in larger groups of oncology patients.
Analysis of two consecutive series of unresectable high-grade glioma (HGG) patients (pts) treated with or without neoadjuvant chemotherapy before estandar radiochemotherapy (CRT) and adjuvant temozolamide (TMZ).
Authors: Capdevila Laia , Cros Sara , Pardo Nuria , Cuadra Jose Luis , Etxaniz Olatz , Villà Salvador , Balana Carmen
Published: March 2020

e12504

Background: Standard treatment of HGG is based in CRT with TMZ. Neoadjuvant treatment before radiotherapy has been studied in small series. Methods: We retrospectively analyzed 2 consecutive series of non-resectable HGG pts treated with neoadjuvant chemotherapy (TMZ & cisplatin) before the 2005 with those treated with TMZ and concurrent and adjuvant TMZ & radiotherapy (after 2005). Results: 46pts diagnosed between August 2003 and October 2010 were selected. 23 received neoadjuvant therapy with TMZ (200mg/m2/d x 5d) and cisplatin (75mg/m2) followed by radiotherapy -60Gy 6w- (NA group), and the remaining 23pts received standard treatment with concomitant TMZ and radiotherapy -60Gy 6w- and adjuvant TMZ (CRT group). In the NA group, 87% of pts were ≥50 years, 43.5% were men, 65.2% had performance status (PS) <2, 38.4% Barthel index <70. Histology: 78.3% were glioblastoma (GB). 30.4% of pts had multifocal lesions and 43.5% had seizures at the diagnosis. 95.7% of pts required dexamethasone. In the CRT group, 91.3% of pts were ≥50 years, 78.3% were men, PS was <2 in 60.9% and Barthel index <70 in 21.7% of cases. Histology: 69.6% were GB, 26.1% pts had multifocal lesions and 26.1% had seizures at diagnosis. 87% of pts required dexamethasone. All factors were uniformly distributed in the two groups. 82.6% of pts completed scheduled radiotherapy in NA group in front 91.3% in the CRT group (P= 0.66). PFS was 2.9 months (m) (CI 95%: 0.5 – 5.5) in NA group versus 5.1m (CI 95%: 3.1 – 7.1) in the CRT group (p=0.62), OS was 8.5m (CI 95%: 4.0 – 12.9) vs 8.2m (CI 95%: 1.2 – 15.2) respectively (p=0.45). Conclusions: No differences were found in either PFS or OS between the two treatment groups. The administration of neoadjuvant therapy does no have a negative impact on the ability to receive radiotherapy. These results provide a basis to justify clinical trials in this setting with promising drugs before radiotherapy treatment.
Correlation of pharmacokinetics of CPT-11 in FOLFIRI with phenotyping of CYP3A4 and UGT1A1 activity.
Authors: Chan Daniel Boon Yeow , Lee Lawrence Soon-U , Wang Ling-Zhi , Yong Wei-Peng , Fan Lu , Chuah Benjamin , Hee Kim-Hor , Ling Winnie Hui Yee , Soh I Peng Thomas , Babu Thambidurai Ganesh , Cheong Pei Fen , Voon Pei Jye , Soo Ross A. , Lee How-Sung , Lee Soo-Chin , Goh Boon C.
Published: March 2020

e13002

Background: CPT-11 has complex PK and PD; genotyping of UGT1A1 is recommended for higher doses in *28 carriers (Caucasian) and *6 carriers (Asian) because of a higher risk of toxicity. Raltegravir is mainly metabolized to raltegravir glucuronide by UGT1A1. CPT-11 is mainly eliminated by cytochrome P450 isoform 3A (CYP3A)-mediated oxidation and by esterase cleavage to form SN-38, which is further conjugated by uridine-diphosphate glucuronosyltransferase (UGT) isozymes to the inactive SN-38 glucuronide. We prospectively explored the correlation of midazolam and raltegravir PK with CPT-11 clearance (CL) and SN-38 levels respectively and toxicity in patients undergoing chemotherapy with CPT-11. Methods: Twenty-five Asian patients with advanced cancer received CPT-11 as a 2-weekly 90-minute infusion (180 mg/m2) as part of the FOLFIRI regimen. Subjects were administered raltegravir 400 mg orally (as a UGT1A1 probe) and intravenous midazolam 1 mg (as a CYP3A4 probe) one day before the first dose of their chemotherapy. Blood sampling for drug concentrations was performed for 2 days after probe drug administration. Non-compartmental PK analyses were performed using WinNonLin. Genomic DNA was isolated and screened for the known genetic variants in UGT1A1*6. Results: One patient developed grade 3 diarrhea and 16 developed grade 3-4 neutropenia. The mean CPT-11 CL was 21.9 + 7.8L/h. SN-38G/SN-38 AUC ratio was highly correlated with Raltegravir glucuronide/ Raltegravir AUC ratio (r=0.784 p<0.01). Midazolam CL was highly correlated with CPT-11 CL (r=0.563 p<0.01). SN38 AUC correlated well with neutropenia (Log10Nadir Absolute Neutrophil Count (ANC) (r=-0.397 p<0.05). Neither CPT-11 nor midazolam CL correlated with Log10 Nadir ANC. Of the 24 patients with genotyping of UGT1A1*6 done, 17 were wild type (GG), 7 heterozygotes (AG) and 0 were mutant (AA). No differences in toxicity or SN38 pharmacokinetics were observed in the UGT1A1*6 variants. Conclusions: Raltegravir glucuronide ratio is a good predictor of SN-38 glucuronidation, and has potential to predict neutropenia from FOLFIRI treatment. Prospective studies with dose adjustments should be done to develop raltegravir as a probe to optimize CPT-11 therapy.