bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidence of osteonecrosis of the jaw in patients receiving denosumab or zoledronic acid for bone metastases from solid tumors or multiple myeloma: Results from three phase III trials.
Authors: Lipton Allan , Saad Fred , Van Poznak Catherine H. , Brown Janet Elizabeth , Stopeck Alison , Fizazi Karim , Henry David H. , Shore Neal D. , Diel Ingo J. , Tonkin Katia Sonia , De Boer Richard H. , Wang Huei , Braun Ada H. 
Published: March 2020

9640 Background: In patients with metastatic bone disease (MBD), the use of antiresorptive therapies such as denosumab or zoledronic acid (ZA) reduces the risk of skeletal-related events but is associated with a small risk of osteonecrosis of the jaw (ONJ). Two phase 3 clinical trials of denosumab vs ZA in patients with MBD showed overall cumulative ONJ incidences to be 3.8% to 4.7% at approximately 5 years of treatment with denosumab across blinded and open-label extension phases. ONJ associated with ZA was only assessed in the blinded treatment phases, as patients switched to denosumab once superior efficacy was demonstrated. Here we report incidence rates of ONJ by first vs subsequent years of exposure for the blinded treatment phase of all three phase III clinical trials. Methods: Patients (n = 5,677) with bone metastases from solid tumors or multiple myeloma received either SC denosumab 120 mg and IV placebo or IV ZA 4 mg (adjusted for renal function) and SC placebo Q4W in the double-blinded treatment phase of each trial. Patients who received ≥ 1 active dose during the blinded treatment phase were included in this analysis for up to 44.5 months of denosumab exposure and 41.3 months of ZA exposure. Oral assessments were conducted at baseline and every 6 months thereafter by the investigator or other qualified examiner. Potential ONJ events were independently adjudicated by a blinded committee of experts. Results: The median (Q1, Q3) time to onset of ONJ was similar in both treatment groups (15.6 [9.5, 20.0] months for denosumab, 15.8 [11.0, 23.6] months for ZA). Cumulative incidence rates of ONJ during the blinded treatment phases for all three trials by patient-years of follow-up are shown below (Table). Conclusions: The incidence of ONJ increased with longer duration of antiresorptive exposure. There were no significant differences between treatment groups in ONJ incidence at year 1 or beyond. Clinical trial information: NCT00321464; NCT00330759; NCT00321620. [Table: see text]
The efficacy of subclinical lymphedema detection in high-risk breast cancer survivors.
Authors: Soran Atilla , DeGore Lori , McGuire Kandace P. , Bonaventura Marguerite , McAuliffe Priscilla F. , Diego Emilia , Ahrendt Gretchen M. , Johnson Ronald 
Published: March 2020

9643 Background: Lymphedema (LE) is associated with profound functional, psychosocial and medical consequences. Early intervention may decrease morbidity from LE. Bioimpedance spectroscopy (BIS) allows subclinical diagnosis by detecting subtle differences in extracellular fluid volume between the limbs. In our lymphedema program, we prospectively monitor BIS in patients (pts) undergoing axillary lymph node dissection (ALND). The aim of this study is to investigate whether early diagnosis of LE after ALND using BIS can allow early intervention. Methods: BIS in the “Pre-Operative Group,” measurements using L-Dex U400 were obtained pre-operatively (n=123) and at 3-6 month intervals thereafter. In the “Follow-up Group" pts who had ALND previously (n=89) had baseline measurements and monitoring at the same intervals. Age, BMI, dominant hand use, side of ALND, type of breast surgery, receipt of radiation therapy, and number of LN removed were recorded. L-Dex values > 10 units or increase > 10 units above the initial measurement was treated with LE education, an over-the-counter compression sleeve, less intensive physical therapy sessions and daily exercise. Results: The mean age was 58 (27-90). The mean BMI was 28.5 (17.1-65.7)kg/m2. ALND was on the side of the dominant hand in 56% of pts (n=119). The mean number of LNs removed was 16 (5-49). The majority of pts underwent mastectomy (59%; n=126), 73% (n=55) received RT, and 80% (n=191) received neo- or adjuvant chemotherapy. 87 pts (41%) were followed for more than 1 year from initial measurement. Since the monitoring began, 18% (n=22) in the Preoperative Group and 23% (n=20) in the Follow-up group were diagnosed with subclinical LE and received early intervention. 41 pts (97.6%) remain stable with no worsening of LE 1 yr after diagnosis. One pt advanced to stage 2 LE but declined further monitoring at 6 mo. Conclusions: Subclinical detection of LE with BIS and timely intervention reduced the incidence of late-stage LE among women undergoing ALND to <3% compared with historical incidence of >25%. Periodic monitoring of women at high risk for LE can minimize costly and intensive LE treatment such as custom made sleeves, pump and surgery while anticipating elimination of more advanced LE.
Hepatotoxicity with chemotherapy in patients infected with hepatitis B virus.
Authors: Szpakowski Jean-Luc , Tucker Lue-Yen , Pauly Mary Pat , Nanfro John , Hwang David , Baer David M. 
Published: March 2020

9645 Background: Patients with chronic hepatitis B virus infection (HBV) are at risk for hepatotoxicity (HT) from viral reactivation during chemotherapy courses (TC). This can be minimized with antiviral prophylaxis (AV). Screening for HBV before TC remains controversial. Methods: A retrospective observational data only study was conducted at a Northern California integrated health care delivery system examining patients undergoing TC between 2000 and 2010. Patients were categorized as HBV positive (HBV+) if they had a positive HBsAg, HBeAg, or HBV DNA any time before and 1 year post TC. Grade 3 and 4 HT was determined using the National Cancer Institute Common Toxicity Criteria, with adaptation for those who had baseline abnormal liver function tests. We excluded patients with HIV, co-infection with both HBV and hepatitis C, and HBsAb of unclear provenance. Two control groups (CTRL1 and CTRL2) were established that had tested negative for HBV and HCV 1996 through 1 year after the last TC: CTRL1 tested negative for both before TC initiation (index TC); CTRL2 tested negative for one pre and the other post index TC or both at any time after index TC. AV prophylaxis (AVP+) was defined as anti-HBV medication given before HT; the remainder were AVP-, including those given AV after HT. Electronic medical record review was conducted on all HBV+ patients. Results: We identified 9,279 patients who received 15,960 TC; 57.8% were female with a mean age of 57.8 (±14.4) at TC initiation. 464 TC were given to 289 HBV+ patients; 22.8% had HT, with 7 deaths from HT, all AVP-. The rate of HT in the controls was 9.9% in CTRL1 (34/343), 12.6% in CTRL 2 (1907/15,153). Conclusions: These findings support the recommendation that all patients planning to receive TC should be screened for HBV. Those found positive should receive AV prophylaxis during therapy. [Table: see text]
Chemotherapy-induced peripheral neuropathy in multiple myeloma patients undergoing maintenance therapy.
Authors: Shi Qiuling , Wang Xin Shelley , Reuben James M. , Cohen Evan N. , Williams Loretta A. , Mendoza Tito R. , Sailors Mary L , Ilagan Venus M , Cleeland Charles S. 
Published: March 2020

9646 Background: After 3-months autologous stem cell transplant (AuSCT), a percentage of multiple myeloma (MM) patients during maintenance therapy continue to experience a complex of symptoms related to peripheral neuropathy. This longitudinal study examined these self-reported neuropathy symptoms and identified circulating inflammatory markers associated with high neuropathy-related symptoms. Methods: MM patients (N=51) rated symptom severity on 0-10 scale via the M. D. Anderson symptom Inventory (MDASI) weekly from 3 to 9 months post AuSCT during maintenance therapy. Patient also rated pain on hand or foot in routine clinic visit. A panel of pro- and anti-inflammatory cytokines, receptors, chemokines was evaluated on serum samples by Luminex. Mixed effect analysis was used to describe the changes on cytokines and symptom outcomes across time. Trajectory analysis identified patients that persistently reported higher or lower symptom severity overtime. Results: During the study period, there was no significant reduction on pain in general or on hand/foot, or change in neuropathic symptoms such as numbness/tingling and muscle weakness. Among a third (33%) of patients who was consistently in high pain (mean 5.5), MIP-1a (p=.001) and MCP-1 (p=.032) showed significant decrease. Approximately 40 % had persistently high numbness/tingling (mean 5.2) across the observation period. Compared to low symptom group patients, this high numbness group had significantly higher IL-6 (p=.019) and TNF-alpha (p=.006). High muscle weakness (mean 3.1) was for 69% of the sample. This group had significantly higher CRP (p=.005) and TNF-alpha (p=.001). Conclusions: This is the first longitudinal study that tracked persistent neuropathy-related symptoms for MM patients post AuSCT. Approximately one third reported painful neuropathy, either from induction therapy or ongoing maintenance therapy. High levels of these neuropathy symptoms were associated with higher levels of specific pro-inflammatory markers. This study provided rationale for examining the effectiveness of anti-inflammation as mechanism driven intervention on peripheral neuropathy in this cohort of MM patients.
HER2/neu status in primary breast cancer and in metastatic site as detected using FNA.
Authors: Giotta Francesco , Asselti Maria Consilia , Petroni Stella , Popescu Onsina , Rubini Vincenza , Latorre Agnese , Lorusso Vito , Gadaleta Cosimo , Simone Giovanni 
Published: March 2020

e11502 Background: As for hormonal receptor (ER, PgR), also human epidermal growth factor receptor-2 (HER-2) expression in breast cancer primitive tumor (PT) could be different from that of metastatic site (MS). These differences arise some questions about clinically useful information given and accuracy of methods to detect biological features. Fine Needle Aspiration (FNA) of metastatic sites could be an available tool to characterize biologic pattern of lesions, using immunocytochemical and/or molecular assay. The aim of the study is to compare prognostic and predictive factors obtained from PT and corresponding MS. Methods: Thirty-eight consecutive metastatic breast cancer patients underwent FNA on metastatic sites in order to re-evaluate receptor status, proliferative activity and HER-2/Neu amplification. In MS the material was achieved using FNA with a 21-23 G needle and obtaining monolayer and the corresponding cito-inclusion. MS were localized in liver (21), lung (8) and distant lymph-nodes (9). ERs, PgRs and Ki-67 were detected in both PT and MS, in 38 cases by immunochemistry, whereas HER-2/Neu amplification was detected on citoinclusion in 35 evaluable cases by FISH. Results: ERs, PgRs and Ki-67 were detected in both PT and in MS, in 36, 34, 25 out of 38 cases respectively, showing a significant loss of hormonal receptors and a decreased proliferative activity in MS versus PT (t-test p: 0.0195, <0.0001 and 0.0120 respectively). Regarding to HER-2/Neu amplification, 28 out of 35 evaluable cases were not amplified while 6 were amplified both in PT and in MS (Pearson Test: r=0.9 p: <0.0001). Another case, HER/Neu amplified in TP, after therapy with trastuzumab resulted not amplified in MS. Conclusions: According to other authors, our data demonstrated that the lost of HER/Neu amplification in MS is a possible event and that FNA samples of MS are available for HER/Neu detection.
Breast cancer in the elderly.
Authors: Erdem Dilek , Yilmaz Bahiddin , Cilingir Fatih Mehmet , Kocasarac Selim , Teker Fatih , Gonullu Guzin , Yucel Idris 
Published: March 2020

e11506 Background: Breast cancer is one of the age-related tumors that accompany with population ageing and approximately 50 % of this disease occur in 65 years of age or older and also more than 30 % occur after age of 70. This study aims to examine characteristics of patients with breast cancer 65 years or older. Methods: The study was carried out on a series of 177 breast cancer patient followed up at our outpatient clinic who are 65 years or older chosen among 848 breast cancer patients during the period 1995-2012. Physical examination, annual chest x-ray, mammography, abdominal ultrasonography and bone scan were the tools to assess the disease status. SPSS 16 was used. Results: The mean age was 70.8 years old (range 65-85 years). There was only one patient whose age is older than 85 years. 85 % of histopathology was infiltratif ductal carcinoma. 83 % of patients underwent mastectomy while 92 % was performed axillary dissection. 56 % had node positivity and 54 % had 2 cm or bigger tumor. ER/PR status was both negative in 54 women (30 %) and both positive in 82 of them. Also cerbB2 was negative in most of the patients (70 %). At the diagnosis, 20 patients (11.3 %) had metastatic disease and 157 were without metastases. Totally 44 patients (32 %) had metastatic disease and most of them (29 patients) had bone disease. Only 52 did not have endocrine therapy with 48 % had tamoxifen as a part of hormonal therapy. Most of them received radiotherapy (54 %). DFS was within 7-182 months with a median of 54 months. PFS was between 2-60 months and patients had a median OS about 61 months. 30 patients died because several causes owing to ageing causes. Conclusions: Breast cancer is the most significant cancer of women and the screening modalities with adjuvant postoperative therapies have increased survival. Acute and chronic medical conditions, nutritional status, poly-pharmacy, level of activity, disease-spesific symptoms and patient decision all need to be taken into consideration. Both in early and advanced stages of the disease, quality of life and related aspects have critical importance in elderly women who have more limited life-expectancy. It is also essential that women with breast cancer 65 years and older be included in trials and that they be recommended the best therapies available.
Stage, biology, and age.
Authors: Kim Hee Jeong , Ko Beom Seok , Yu Jong Han , Lee jong Won , Sohn Byung Ho , Kim ku Sang , Kim Sung-Bae , Ahn Sei-Hyun 
Published: March 2020

e11512 Background: Breast cancer subtypes are prognostic and predictive for patients. In this study, prognostic value of TNM stage, intrinsic subtype, and age were compared. Methods: We analyzed results from 7,626 breast cancer patients registered on the Asan medical center database between 1999 and 2009. We compared survival according to the TNM stage, intrinsic subtype using ER, PR, Her2- immunohistochemical staining, and age. Results: Luminal A subtype showed the best survival rates while triple negative subtype showed the worst survival rate amongst intrinsic subtypes. Survival analysis showed that Stage I triple negative breast cancer showed better survival compared to Stage III Luminal A subtype breast cancer (89.0% vs 76.6% P<0.001). Survival differences between intrinsic subtypes were more significant in lymph node positive breast cancer compared to lymph node negative breast cancer. Age did not affect survival between stages and intrinsic subtypes except for the young age subgroup (≤35), for whom there was no survival difference amongst intrinsic subtypes. Conclusions: Staging of breast cancer showed a more direct correlation to survival than known prognosis for intrinsic subtypes, as advanced, good prognostic intrinsic subtype breast cancer had worse survival than early, worse prognostic intrinsic subtype breast cancer. However for the young age group (≤35), the survival of all intrinsic subtypes were similar.
Targeting low-expressing ERBB-2 and acquired resistant high-expressing ERBB-2 breast carcinomas.
Authors: Karamouzis Michalis , Dalagiorgou Geena , Perez Sonia A. , Georgopoulou Urania , Papavassiliou Athanasios 
Published: March 2020

e11513 Background: Human epidermal growth factor receptors and their ligands are involved in carcinogenesis. Four ERBB receptors have been identified; ERBB1 (EB1), ERBB2 (EB2), ERBB3 (EB3) and ERBB4 (EB4). EB2 is over-expressed/amplified in 20-30% of BCa. Molecularly targeting agents, such as pertuzumab (P), in combination with standard therapy have shown important clinical results in EB2 (+) BCa patients. The aim of the project is to evaluate the expression/localization and dimerization pattern of EB1, EB2, EB3, EB4 in breast cancer cell lines (BCCLs) with or without heregulin-1 (He) and various EB2, EB3 and He inhibitors. The identification of a molecular phenotype of low-expressing and acquired resistant high-expressing EB2 BCa will enhance the targeted use of EB2 inhibitors in certain BCa patients Methods: Using confocal microscopy, localization/expression patterns were studied for EB1, EB2, EB3, EB4 in various human BCCs; here presented in MCF7 and SKBR3. Additionally, the dimerization pattern of EB2, EB3 and/or EB4 was studied with and without stimulation with He plus or minus P (kindly provided by Genentech, US). The dimers formation was studied using proximity ligation assay and immunofluorescence (DUOLINK; OLINK Biosciences, Sweden). Results: In MCF7-He stimulated cells EB2/EB3, EB2/EB4 and EB1/EB3 dimmers showed a 3-fold decrease formation compared to untreated cells. The EB1/EB4 dimmers were not significantly affected. After P addition in MCF7 cells a 3-fold decrease of dimmer formation was noticed compared to untreated cells for EB2/EB3, EB2/EB4 and EB1/EB3. The EB1/EB4 formation seemed only slightly affected by P. SKBR3-He stimulated cells resulted in a similar decrease of EB2/EB3, EB2/EB4 and EB1/EB3 dimmer formation compared to untreated cells. In the same BCLL, EB1/EB4 dimmer did not show any decrease after He treatment compared to untreated control cells. Further results quantified and analyzed for statistical significance will be shown Conclusions: The addition of P seems to block ligand-dependent heterodimerization of EB2 with other ERBB family members, such as EB3 and EB4.
Mechanisms of primary AI resistance in ER-positive HER2-negative breast cancer.
Authors: Miura Daishu , Iwatani Tsuguo , Kawabata Hidetaka 
Published: March 2020

e11519 Background: Current approaches of neoadjuvant endocrine therapy (NAET) are focusing on biomarker analysis of the diagnostic specimens however inadequate response occurs in 5-10% of patients treated. It has been reported hormone resistance may predict Ki67 level after treatment than ΔKi67. Much less is known about the difference between Ki67 increases and still high level of Ki67 after NAET. A pilot study was conducted to investigate the differences of biomarker changes in short-term NAET (letrozole vs. exemestane). Differences of resistant mechanisms between Ki67 increases and Ki67 still high expression and between two AIs were studied. Methods: Totally 116 samples from 58 postmenopausal women with ER positive HER2 negative stage 1-3 breast cancers comparing LET and EXE were analyzed with pre- and post-treatment mRNA expression of multiple biomarkers using QuantiGene Assay. Each of 29 patients took LET or EXE until the surgery (median 22 days). Compared with Ki67 expression of pre/post treatment, we classified resistance into 2 groups, Ki67 increase after treatment (INC) or Ki67 still high expression (equivalent over 14% in IHC) except those in INC (HIG). Results: Clinical characteristics were well balanced between the two treatment arms. Median % changes of Ki67 were -59% in both LET and EXE. Six cases (10%) were in INC (3/LET and 3/EXE). Among 10 cases of still high Ki67 expression, 6 (10%) were in HIG except 4 cases of Ki67 increases (3/LET and 3/EXE). All 6 cases in INC had increases of ERβ, MAPK, PIK3CA, ALDH1, NFkB, and RANKL and decrease of ERα. Five out of 6 in INC had an increase of HER2 and a decrease of PR. While changes in HIG were various, a nonsignificant trend to predict resistance was found. However all 3 cases whose HER2 increased in HIG had also increases of MAPK and PIK3CA. All 3 receiving EXE had increases of PR. Conclusions: Although both LET and EXE had significant decreases of Ki67, no significant difference was found between two. Both had 20% of primary resistance in terms of Ki67. Tumors which Ki67 increase seem to activate various signaling pathway, which mechanism is class effect of AI. What Ki67 is still high supposed to be nonclass effect.
PR and Ki67 in primary tumors and metastatic sites as biomarkers for benefit from endocrine therapy (ET) in metastatic breast cancer (mBC).
Authors: Ferrario Cristiano , Farolfi Alberto , Maltoni Roberta , Carretta Elisa , Melegari Elisabetta , Pietri Elisabetta , Rocca Andrea , Nanni Oriana , Amadori Dino 
Published: March 2020

e11521 Background: Commonly used biomarkers (ER, PR, HER2, Ki67) are thought to identify BC subtypes with different sensitivity to ET, but data on this are scarce for the metastatic setting, where changes in receptor status between primary tumor (T) and matched metastases (M) are reported. We investigate PR and Ki67 on T and M as predictors of clinical benefit from 1st line ET in mBC. Methods: We identified mBC patients (pts) treated in our Center with 1st line ET (2002-11), excluding those receiving concomitant chemotherapy (CT) or trastuzumab or pretreated with >2 lines of CT. PR and Ki67 were scored as IHC percentage of positive cells, with a cut-off of 20% for high vs low. Clinical benefit was evaluated by time-to-progression (TTP). Results: We identified 137 pts, median age 58 (29-85), only 28% with visceral metastases. ER was >50% in 94%, HER2+ in 17.5%. With 93% receiving an aromatase inhibitor, median TTP was 14 months (median follow-up 43 months). In 34 pts with Ki67 available from T and M a strong correlation between the 2 was shown (Spearman: 0.69, p<.0001), confirming little variation. A shorter median TTP (10 vs 17 months, n=113; Wilcoxon p=0.006) was seen in pts with Ki67 >20% on T (with a similar trend on M, n=58; p=0.06). In 48 pts with PR scored on T and M only a weak trend for correlation was found, with a discordant classification (≤ or >20%) in 44%. More than the score on T (n=118), PR on M (n=64) was a strong predictor of median TTP: 12 months for PR ≤20% vs 22 months for PR >20% (p=0.02). Pts with PR≤20% + Ki67>20% on M had a median TTP of only 4 months, vs 21 months for PR>20% + Ki67≤20%, vs 14 months for either PR>20% or Ki67≤20% (p=0.006). In a multivariate Cox analysis with clinical data and biomarkers from T, visceral disease and HER2 positivity were significantly associated with the risk of progression (HR 2.22 and 2.07, respectively). With biomarkers from M, the risk of progression correlated with relapse ≤5 vs >5 years from surgery (HR 3.48) and PR ≤20% (HR 2.47, p=0.01). Conclusions: In an ER-high population, PR >20% on M identifies pts with a long TTP on ET. Ki67 on T or M can also contribute in estimating the expected benefit, but an independent prognostic role could not be fully confirmed in this small cohort.