bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of circulating tumor DNA to predict survival in patients with resected high-risk stage II/III melanoma.
Authors: Lee Rebecca , Gremel Gabriela , Marshall Andrea , Myers Kevin A , Fisher Nita , Corrie Philippa , Dunn Janet , Dhomen Nathalie , Middleton Mark R. , Marais Richard , Lorigan Paul
Published: September 2018

9583

Background: Patients with high-risk stage II/III resected melanoma commonly develop metastatic disease. Adjuvant high dose interferon and ipilimumab 10mg/kg are associated with survival benefit, but at the expense of toxicity. At present, we cannot differentiate between patients who will progress to stage IV disease or those cured by surgery. Circulating tumor DNA (ctDNA) is a biomarker of disease progression in many cancers including stage IV melanoma, however its utility in the adjuvant setting has not been investigated. Methods: We performed droplet digital polymerase chain reaction to detect BRAF and NRAS mutations in plasma of 161 stage IIB, IIC/III high-risk melanoma patients enrolled in AVAST-M; a randomized study of bevacizumab vs. observation. Baseline plasma samples were collected within 12 weeks of surgery for both arms. Results: Mutant BRAF or NRASctDNA was detectable ( > 1 copy of mutant ctDNA) in 12% (19/161) of patients. Patients with detectable ctDNA had a decreased disease free interval (DFI; hazard ratio [HR] 3.12; 95% confidence interval [CI] 1.79-5.47; p < 0.0001) and distant metastasis-free interval (DMFI; HR 3.22; 95% CI 1.80-5.79; p < 0.0001) vs. those with undetectable ctDNA. One year DFI rate for patients with detectable ctDNA was 26% (95% CI 10-47%) vs. 74% (95% CI 66-81%) for those with undetectable ctDNA. One year DMFI rate for patients with detectable ctDNA was 37% (95% CI 17-57%) vs. 84% (95% CI 77-89%) with undetectable ctDNA. Detectable ctDNA remained a significant predictor after adjustment for N classification and performance status (PS) (DFI HR 3.48; 95% CI 1.95-6.19, p < 0.0001; DMFI HR 3.41, 95% CI 1.88-6.20, p < 0.0001). Five year overall survival (OS) rate for patients with detectable ctDNA was 33% (95% CI 14-55%) vs. 65% (95% CI 56-72%) for those with undetectable ctDNA. OS was significantly worse for patients with detectable ctDNA (HR 2.63; 95% CI 1.4-4.96); p = 0.003) and remained significant after adjustment for PS (HR 2.5, 95% CI 1.32-4.74, p = 0.005). Conclusions: CtDNA is predictive of relapse and survival in high-risk, resected melanoma and can potentially aid stratification of patients for adjuvant therapy.
Epidemiology and clinical profile of breast cancer in central Nepal: A single institutional experience.
Authors: Shakya Sachin
Published: September 2018

e12008

Background: In this study, our objective was to determine the epidemiological and clinical profile of Breast Cancers. Different Literatures have highlighted the correlation between stage and age at diagnosis, size and age at diagnosis, correlations of different hormone receptor status with different age group etc. But precise documentation is lacking in Nepal. Methods: The study was conducted at department of Medical Oncology, Nepal Cancer Hospital and Research Centre from Dec 2014 to June 2016 and 183 patients diagnosed with breast cancer were enrolled. A retrospective cross-sectional study was conducted. Results: Prevalence of Breast Cancer was 5.59 %. Newar was the most affected ethnic group. The most frequent age group was 40 to 49. The most common symptom was mass in 80 % of patients. Stage II (49.1 %) was the most common stage at diagnosis. 83% patients had a tumour size of 2-5 cm with average size of 3.25 cm at presentation. Younger women with cancer had a strong correlation with ER-ve/PR-ve and Her-2/Neu +ve receptor status with P<.005. Triple Negative receptor status was 32.87%. Her2/neu +ve receptor status cancer was 39.72%. Conclusions: Majority of patients presented with Stage IIa and IIIa disease breast cancer. Disease is more aggressive and diagnosed at a more advanced stage in younger women. Younger women had a strong correlation with ER-ve/PR-ve and her-2/neu +ve receptor. Recommendation for the Her-2/Neu receptor test should be done in every case of breast cancer. Triple negative status was lower in comparison to the previous studies which is favourable for hormonal antibody treatment implementation.
A retrospective study of 21-gene recurrence score assay compared with clinicopathological markers in node-negative, hormone receptor-positive, HER2-negative breast cancer.
Authors: Chen Junqing , Wang Xiaojia , Chen Zhanhong
Published: September 2018

e12023

Background: The 21-gene recurrence score assay is a validated genomic predictor of cancer recurrence and the benefits of adjuvant chemotherapy in hormone receptor-positive, HER2-negative early breast cancer patients. However, the assay is rather expensive and complex, and many patients in our country can not afford it. We performed a retrospective study to evaluate the association between traditional clinicopathological features and 21-gene recurrence score in patients with node-negative, hormone receptor-positive, HER2-negative breast cancer. Methods: A total of 76 consecutive patients with node-negative, hormone receptor-positive, HER2-negative breast cancer who underwent 21-gene recurrence score testing in our hospital from 2015 to 2016 were enrolled. Data including age, tumor size, histological type, tumor grade were collected. Estrogen receptor (ER) expression, progesterone receptor (PR) expression, Ki-67 index, p53 and androgen receptor (AR) expression were detected by immunohistochemical assay. 21-gene recurrence score assay was performed by RT-PCR. The correlation between clinicopathological characteristics and 21-gene recurrence score assay was analyzed by using nonparametric tests. Results: Among the 76 patients, 43 (56.6%) had a low recurrence score of < 18, 13 (17.1%) had an intermediate recurrence score of 18-31, and 20 (26.3%) had a high recurrence score of ≥31. There was a significant difference in recurrence score in patients divided by PR expression ( P=0.027). Patients with low PR expression (<20%) had a higher recurrence score as compared to those with high PR expression. Tumor grade was observed to be significantly correlated with recurrence score ( P=0.004). No significant associations were found between recurrence score and age, tumor size, histological type, ER expression, Ki-67 index, p53 or AR expression in this study. Conclusions: Our study shows that low PR expression is associated with higher 21-gene recurrence score, and PR expression may be a promising predictor of 21-gene recurrence score assay in node-negative, hormone receptor-positive, HER2-negative breast cancer patients.
Rates of trastuzumab-associated cardiotoxicity in patients with HER2-positive breast cancer at a tertiary cancer centre.
Authors: Kumar Tyagi Nidhi , Arora Roochi , Partridge Arun , Tharmabala Mithula , Mukherjee Som , Leong Darryl , Dhesy-Thind Sukhbinder K.
Published: September 2018

e12030

Background: Human epidermal growth factor receptor 2 ( HER2) is overexpressed in 15-25% of breast cancers and associated with decreased rates of survival. Trastuzumab (TZ) is a humanized monoclonal antibody that binds against HER-2 and improves both disease free and overall survival in the adjuvant setting. A side effect of TZ is reversible cardiotoxicity(CT), which can lead to early termination of TZ. The rates of TZ associated CT seen in trials range between 1-16%. These rates may not be representative of clinical practice. Our aim is to identify the rate of TZ-associated CT and the rate of early discontinuation of TZ associated CT at the Juravinski Cancer Centre (JCC), in Hamilton, Ontario. Methods: Patients treated with adjuvant TZ between 2006-2013 at JCC were identified using JCC pharmacy data and included in this audit. We examined patient charts for relevant clinical-pathologic variables, cardiac Results: Results are shown in the table below. Conclusions: In conclusion, we found that rates of CT were higher at JCC than in clinical trials. This is not unexpected as patients with known cardiac risk factors and history of cardiac disease were excluded from most clinical trials. Strategies to optimize cardiac risk factors and management of CT are needed. We have opened a cardio-oncology clinic at JCC and initiated a clinical trial examining the feasibility of ongoing TZ therapy in the setting of mild DLVEF. [Table: see text]
Long-term safety and survival outcomes from the Scandinavian Breast Group 2004–1 (SBG 2004-1) randomized trial of tailored dose adjuvant chemotherapy for early breast cancer.
Authors: Matikas Alexios , Margolin Sara , Hellstrom Mats , Johansson Hemming , Bengtsson Nils-Olof , Carlsson Lena , Edlund Per , Karlsson Per , Lidbrink Elisabet , Linderholm Barbro Kristina , Lindman Henrik , Malmstrom Per , Villman Kenneth Karl , Foukakis Theodoros , Bergh Jonas C. S.
Published: September 2018

e12036

Background: Although adjuvant polychemotherapy (ACT) improves outcomes for early breast cancer (BC), the significant interpatient variability in pharmacokinetics result in differences in efficacy and both short and long term toxicities. Dose tailored ACT has been shown to improve outcomes, while tailored and dose dense therapy improved 5-year event free survival in the phase 3 PANTHER trial. Methods: The SBG 2004-1 trial was a randomized feasibility/phase II study which assessed dose tailored epirubicin and cyclophosphamide (EC) followed by docetaxel (T), compared to the same fixed dose schedule and to the TAC regimen (table 1). Women aged 18-65 years old, ECOG PS 0-1 with at least one positive lymph node were randomized 1:1:1. The primary endpoint of the study was the safety and feasibility of the administered treatment. The secondary endpoint of the study was to evaluate the dose-intensity of the treatment. Toxicity was graded according to CTC-AE version 3.0. The design and short-term safety results of the trial have been previously published. Here, we report safety and efficacy data after 10 years follow-up. Results: A total of 124 patients were included and >95% of patients without relapse were followed for 10 years.Five secondary malignancies but no myelodysplastic syndrome / acute myeloid leukemias were reported. Long term disease-free and overall survival results will be presented at the meeting. Conclusions: Long term safety results from this study in combination with efficacy results from the PANTHER trial imply the feasibility of a tailor-based approach for ACT in early BC. [Table: see text]
Use of a web-based app to improve breast cancer symptom management and aromatase inhibitor adherence: A pilot randomized controlled trial.
Authors: Graetz Ilana , McKillop Caitlin N , Stepanski Edward J. , Vidal Gregory A. , Schwartzberg Lee Steven
Published: September 2018

e12044

Background: For postmenopausal women with hormone receptor-positive breast cancer, use of aromatase inhibitors (AI) significantly reduces the risk of cancer recurrence and improves survival, but many patients are nonadherent due to adverse side effects. We conducted a pilot randomized controlled trial of a web-enabled application (app) to provide real-time symptom monitoring between visits and facilitate management of treatment-related adverse symptoms among patients with hormone receptor-positive breast cancer and a new AI prescription. Methods: Patients were randomized into two groups: (1) App+Reminder: had access to the app and received weekly reminders via text or email to use it, or (2) App: had access to the app but did not receive reminders. The app asked patients about their AI use in the last 7 days and about new symptoms related to the treatment. New symptoms with severity in a clinically-relevant range or AI nonadherence triggered email alerts to the patient’s providers. The main analyses compared AI adherence and changes in quality of life. Results: We enrolled 44 patients, 21 in the App+Reminder and 23 in the App group; 83% of patients approached agreed to participate, 23% were African-American, and 32% were over the age of 65. Overall, 74% of participants in the App+Reminder group used the app at least once per week compared with 38% in the App group (p<0.01). Reported AI adherence 8 weeks after initiation was significantly higher among those in the App+Reminder group compared with the App group (100% vs. 72%, p=0.01). Using a differences-in-differences analysis, we found that the decrease in quality of life 8 weeks after AI initiation was substantially larger, but not statistically significant, in the App group compared with App+Reminder (difference=7.6, p=0.191). Conclusions: Use ofa web-enabled app to provide real-time monitoring of AI adherence and treatment-related symptoms with weekly reminders significantly improves short-term AI adherence and may limit reductions in quality of life.If short-term gains in adherence persist, this low-cost intervention could improve survival outcomes for women with hormone receptor-positive breast cancer. Clinical trial information: NCT02957526.
Treatments/clinical outcomes in ER+ HER2-negative breast cancer (BC) where treatment decisions were recurrence score (RS)-guided: Analysis by histologic subtype.
Authors: Stemmer Salomon M. , Steiner Mariana , Rizel Shulamith , Ben Baruch Noa , Geffen David B , Soussan-Gutman Lior , Bareket-Samish Avital , Nisenbaum Bella , Isaacs Kevin , Fried Georgeta , Rosengarten Ora , Uziely Beatrice , Svedman Christer , McCullough Debbie , Klang Shmuel , Evron Ella , Karminsky Natalya , Goldberg Hadassah , Shak Steven , Liebermann Nicky
Published: September 2018

e12053

Background: The RS assay is widely used to guide treatment decisions in ER+ HER2-negative early BC regardless of tumor histology. However, the RS validation studies did not include an analysis by histologic subtype. We investigated treatments/clinical outcomes in RS-tested Clalit Health Services (CHS) patients (pts) by histologic subtype, focusing on invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC). Methods: This exploratory analysis of the CHS cohort included BC pts with N0/N1mi/N1 disease who were RS-tested from 1/2006 through 12/2010 (N0) or 12/2011 (N1mi/N1). Data from medical records were analyzed to assess risks of distant recurrence and BC death by histologic subtype. Results: The cohort included 2510 pts: 2060 (82%) IDC, 298 (12%) ILC, and 152 (6%) unknown/others. Median follow up for IDC/ILC pts was 6.0/6.1 yrs. Median age in IDC/ILC pts was 60/62 yrs; median tumor size was 1.5/1.8 cm; 71%/71% were N0, and 29%/29% were N1mi/N1. RS distribution (<18, 18-30, ≥31) was 50%, 39%, and 11%, respectively for IDC pts and 48%, 48%, and 4%, respectively, for ILC pts. Chemotherapy (CT) use for each RS group was similar between IDC and ILC pts; 5-yr Kaplan-Meier estimates for the risk of distant recurrence and BC death differed significantly across RS groups in both IDC and ILC; clinical outcomes for IDC and ILC pts were similar within risk groups see Table. Conclusions: For both IDC and ILC pts, treatment was aligned with the RS results. Within each RS group, there was no difference in clinical outcomes between these histologic subtypes, however the number of pts with ILC and RS≥31 was limited. [Table: see text]
Early-stage breast cancer patients reporting difficulty sleeping, mood issues, or pain are more likely to refuse adjuvant hormone therapy.
Authors: Thomas Christian A.
Published: September 2018

e12065

Background: Adjuvant hormone therapy is a crucial part of the treatment for patients with early stage breast cancer and an important quality measure for programs such as QOPI and the oncology care model (OCM). However, it is not known which factors influence some patients with early stage breast cancer to decline adjuvant hormone therapy. We hypothesized that specific self-reported symptoms might impact a patient’s decision to accept or decline adjuvant hormone therapy. Methods: Patients with stage 0 or I breast cancer were identified by chart review from 2011-2016 and de-identified. On the day patients received a recommendation for adjuvant treatment the following patient reported outcome measures (PROs) were analyzed: difficulty sleeping (DS), fatigue (F), mood (M such as anxiety and depression), and pain (P) on a 0-4 symptom scale based on CTCAE v. 4. PROs were then linked with a patient’s decision to accept or decline adjuvant therapy. Results: A total of 287 patients with stage 0 (n = 80) or stage I (n = 207) breast cancer were identified. 38 stage O and 103 stage I patients had evaluable PROs on the same day a recommendation for adjuvant hormone therapy was made. Overall 18/38 (47.4%) of stage 0 patients and 90 of 103 (87.4%) of stage I patients accepted adjuvant treatment. Stage 0 patients declining adjuvant therapy reported any grade of PROs: DS (40%, n = 8), F (35%, n = 7), M (35%, n = 7), P (20%, n = 4). Stage 0 patients accepting treatment reported: DS (22%, n = 4), F (44%, n = 8), M (6%, n = 1), P (20%, n = 4). Stage I patients who declined treatment reported: DS (54%, n = 7), F (46%, n = 6), M (38%, n = 5), P (62%, n = 8). Stage I patients accepting treatment reported: DS (41%, n = 37), F (49%, n = 44), M (31%, n = 28), P (36%, n = 32). Conclusions: Early stage breast cancer patients declining adjuvant hormone therapy are more likely to self report symptoms such as difficulty sleeping, mood disturbances (anxiety, depression), and pain than those accepting treatment.
Association of PD-L1/CD8+TIL and expression of PD-L1, PTEN as predictive biomarkers for long-term follow-up in early breast cancer.
Authors: Toh Uhi , Okabe Mina , Iwakuma Nobutaka , Saku Shuko , Akashi Momoko , Ogo Etsuyo , Itoh Kyogo , Akagi Yoshito
Published: September 2018

e12072

Background: The aim of this study was to investigate the correlation of immunologic factors including the expression of PD-1/PD-L1, PTEN, and the density of TILs, macrophages in the tumor area of breast cancer, using immunohistological staining and to evaluate the association between the immunologic factors and the clinical outcome for early breast cancer (EBC). Methods: A total of 97 EBC patients (pts) who underwent surgery from February 1995 to November 2005 were investigated.The postoperative adjuvant chemotherapies were routinely performed, adjuvant Tmab were not available in Japan within this period.The immunohistological staining was performed with the monoclonal antibodies for PD-1/PD-L1, PTEN, CD3, CD8, and CD163. Pathological analysis was performed to measure the expression area of each antibody, using images scanned by a CCD digital camera (Nikon), and the digitized data of the expression area (μm2) were analyzed by ‘Win ROOF’ (version 5.7) software. The association between the immunologic factors and clinical outcome was statistically analyzed for over 10-years follow-up. Results: The density of CD3+TILs, CD8+TILs, CD163+ macrophages and non-expression of PTEN was significantly higher in triple negative breast cancer (TNBC). CD8+TIL density and PD-L1+/CD8+ expression were predictive factors for DFS and OS. Her2+ pts with PTEN expression and luminal/Her2- patients without PD-L1 expression had longer OS, compared to patients without PTEN expression (p=0.049) and with PD-L1 expression (p=0.036), respectively. Furthermore, the pts with PD-L1+/CD8+ expression had worse median PFS (p = 0.022) and median OS (p = 0.037), compared with pts without PD-L1+/CD8+ expression. Conclusions: Our results demonstrated that CD3+ TILs, CD8+ TILs, and CD163+ macrophages were shown to infiltrate the tumor area of EBC. In particular, TNBC had a higher rate of TIL infiltration within the tumor environment. PTEN expression and lack of PD-L1 expression were associated with favorable survival in Her2-positive and luminal/Her2-negative EBC patients, respectively. The PD-L1 expression combined with CD8+ density was significantly associated with an aggressive clinical outcome.
Incidence of febrile neutropenia with use of docetaxel plus cyclophosphamide (TC) for breast cancer.
Authors: Patel Kiran , Diergaarde Brenda , Brufsky Adam , Jankowitz Rachel Catherine , Lembersky Barry C. , Rastogi Priya , Huggins-Puhalla Shannon Leigh
Published: September 2018

e12073

Background: Incidence of febrile neutropenia (FN) is reported as 5% in breast cancer patients receiving TC (Jones et al., JCO 2006), which would not justify the usage of prophylactic granulocyte colony stimulating factors (G-CSF). We previously showed that the incidence of FN may be as high as 23% in a small study. (N = 130, Soni et al., ASCO 2011). In the current study, we determined the incidence of FN in a larger cohort (N = 415), and evaluated the usage of G-CSF and its relation to FN, age, stage, and hormonal status. Methods: We retrospectively reviewed the electronic medical records from patients diagnosed with breast cancer who received at least one standard dose cycle of adjuvant TC between 2010-2016 at a university-based breast oncology practice. Chi-square or Fisher’s exact tests were used to assess differences between groups. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated using multiple logistic regression models. Results: We identified in total 415 patients who received adjuvant TC. Median age at diagnosis was 58 (range: 25-86), the majority had stage I or II (N = 382; 92.1%) disease, and 315 (75.9%) were ER+, 277 (66.8%) PR+, 42 (10.1%) HER2+, 22 (5.3%) triple-positive, and 81 (19.5%) triple-negative. Prophylactic G-CSF was utilized in 247 patients (59.5%), and unknown for 43 (10.4%). Overall 39 (9.4%) patients experienced febrile neutropenia. Incidence of FN among those receiving G-CSF was 4.5% versus 17.6% among those who did not (p < 0.001). Use of G-CSF significantly lowered risk of FN, OR (95%CI): 0.20 (0.10-0.43) adjusted for age at diagnosis and stage. Use of G-CSF on incidence of FN did not differ significantly by age, stage, or hormonal status. Conclusions: Our data confirms a high rate of FN in patients receiving TC without G-CSF prophylaxis. Our institutional high rate of G-CSF use ( > 50%) reduced the incidence of FN to 4.5% and the observed significant difference in FN incidence between the non G-CSF group and G-CSF group suggests that prophylaxis may be considered when administering TC. Age, stage, and hormonal status do not seem to affect the usage of G-CSF or incidence of FN in our population.
Correlation of Breast Cancer Index (BCI) prognostic and predictive results to Ki67 and tumor grade in early stage HR+ breast cancer.
Authors: Falkson Carla Isadora , Kepes Jeffrey , Poage Graham M. , Liu Junmei , Schnabel Catherine A.
Published: September 2018

e12075

Background: Markers of tumor proliferative status, e.g., Ki67 and grade (G), are prognostic for early distant recurrence (DR) in HR+ breast cancer and integrated in adjuvant chemotherapy decisions; however, their impact on late DR and extended endocrine therapy (EET) decisions is less clear. BCI is a genomic assay that provides 2 results: BCI Predictive, based on HoxB13/IL17BR (H/I ratio), reports a prediction of likelihood of benefit from EET; BCI Prognostic, based on the algorithmic combination of H/I and proliferation genes, reports risk of late DR. In this study, BCI results were examined within clinicopathologic risk categories based on Ki67 and G. Methods: The BCI Clinical Database for Correlative Studies is an IRB-approved de-identified database that contains > 50 clinicopathologic and molecular variables from cases submitted for BCI testing in clinical practice (N = 14,463). Clinicopathologic variables were abstracted from pathology reports, and were available for a subset of cases. High Ki67 was defined as ≥14%. Chi-squared tests were used to compare BCI results between Ki67 and G subgroups. Results: Analyses included 3395 LN- pts (median age 59.1y; 73% ≥ 50y). BCI Prognostic showed a wide distribution of individual risk assessments in pts with high or low Ki67. A greater proportion of pts with high Ki67 was classified by BCI as high risk of late DR compared to low Ki67 (68.2% vs 26.5%; P < 0.0001); however, substantial proportions of high Ki67 pts were classified as BCI low risk (31.8%) and pts with low Ki67 classified as BCI high risk (26.5%). Overall, there was a moderate correlation between individual BCI Scores and individual Ki67 scores (Correlation = 0.519). 45.5% of pts with high Ki67 were classified as High BCI Predictive (H/I) compared to 35.5% of pts with low Ki67 (p < 0.001). Both BCI Prognostic and BCI Predictive (H/I) classified increasing proportions of pts as high risk or high benefit with increasing G (P < 0.0001). Conclusions: These findings help characterize differential stratification based on tumor biology vs Ki67/G for pts considering EET. While moderately correlated, both BCI Prognostic and BCI Predictive (H/I) identified distinct populations compared to Ki67 and G.
Radiofrequency ablation for early-stage breast cancer: results from 5 years of follow-up in a prospective multicenter study.
Authors: Kinoshita Takayuki , Yamamoto Naohito , Fujisawa Tomomi , Takahashi Masato , Aogi Kenjiro , Hojo Takashi , Tsuda Hitoshi , Yoshida Masayuki
Published: September 2018

e12098

Background: Given the increasing number of early-stage breast cancers detected by screening mammography, we aim to establish RFA as a minimally invasive, cost-efficient, and cosmetically acceptable local treatment. In our Phase 1 study, localized tumors with a maximum diameter of 2 cm, preoperatively diagnosed by imaging and histopathology, were treated with RFA. A 90% complete ablation rate was confirmed histopathologically. Building on these results, we designed a Phase 2 clinical trial to investigate the efficacy of a non-surgical RFA procedure. Methods: From Nov. 2009 to Nov. 2012, 58 patients with early-stage breast cancer received non-surgical RFA therapy. Patients had localized solitary N0 tumors with a maximum diameter of 1 cm. They underwent RFA and sentinel lymph node biopsy under general anesthesia and adjuvant therapy and breast irradiation. Follow-up evaluation for residual tumor at 3, 6, and 12 months after RFA included clinical breast examination, diagnostic imagings (ultrasound, magnetic resonance, and mammography), and vacuum-assisted biopsy. Surgical resection was recommended for patients with suspected residual disease or incomplete ablation. The primary endpoint was the frequency of adverse events. Secondary endpoints included the complete ablation rate and ipsilateral breast relapse-free rate. The diagnostic performance of the follow-up examinations and cosmetic outcomes were evaluated for exploratory purposes. Results: The follow-up period ranged from 450 to 2552 days (median, 1832 days). The 57 patients completed the non-surgical RFA procedure and underwent diagnostic imaging and needle biopsy after 3 months. Seven patients with suspected incomplete ablation underwent surgical resection; incomplete ablation was confirmed in 5 (8.6%, 2 with invasive and 3 with non-invasive ductal carcinoma). During subsequent follow-up, 1 patient each was diagnosed with contralateral breast cancer and brain tumor. No ipsilateral breast tumor relapse or distant recurrence was documented. Cosmetic results were excellent in 94% of patients. Conclusions: RFA is a promising alternative to surgery for treating localized, early-stage breast cancers. Clinical trial information: UMIN000008675.
Features of p53 expression in residual tumors in Russian women after neoadjuvant chemotherapy of breast cancer stage T1-3N0-1.
Authors: Kolyadina Irina Vladimirovna , Poddubnaya Irina , Pavlikova Olga , Komov Dmitrii , Andreeva Yulia , Frank Georgii , Vishnevskaya Yana V
Published: September 2018

e12121

Background: Residual tumor is an important prognostic factor after neoadjuvant therapy, however, p53 expression in the residual breast tumors poorly understood. Methods: In our study included 164 Russian women (24-76, median age - 47) with breast cancer stage T1-3N0-1 treated in RCRC from 2004 to 2016. Biological subtype of primary tumor was luminal A (8,1%), luminal B HER2-negative (43,6%), luminal HER2+ (15,4%), triple negative (22,8%) and non-luminal HER2+ (10,1%). After neoadjuvant chemotherapy by anthracycline ± taxanes (in HER2+ cancer ± trastuzumab) patients had radical surgery. We analyzed pathological response after neoadjuvant therapy and features of p53 expression in residual tumors. Results: The rate of pCR was 23% for all women, and was a very various for biological type (luminal A – 0%, HER2- luminal B - 11%, HER2+ luminal - 38%, triple negative – 35% and HER2+ non-luminal - 50%), p=0,003. In 15% cases pathological response was a very similar to pCR, in 62% - was low. In analyze of 38 residual tumors we found p53 low expression (<10% stained cells) in 66% cases and high (>10% stained cells) - in 34%. We did not find any correlation between p53 rate in residual tumors and stage, Ki67 and PR-status (p>0,05). But p53 expression strongly correlated with age, tumor grade and biological type (p<0,05). So, high rate of p53 was found more often in women <45 years (50%) vs women 45-59 years (15,4%) and patients 60 years older (20%), p=0,04. All G1-tumors was p53-negative, p53 high expression was seen in 29% of G2 tumors and 80% - G3, p=0,04. The high rate of p53 residual tumor was seen in luminal A subtype in 0%, HER2- luminal B – 30%, HER2+ luminal – 75%, triple negative -50%, HER2+ non-luminal - 100%, p=0,01. Conclusions: High expression of p53 in the residual tumors after neoadjuvant chemotherapy is associated with younger age and unfavorable biological characteristics that may be a very important for the further prognosis in breast cancer.
Neutropenic complications with neo/adjuvant adriamycin and cyclophosphamide in early stage breast cancer patients: A prospective study at the McGill University health center.
Authors: Saleh Ramy , Elkrief Arielle , Afshar Elmira , Azoulay Laurent , Meterissian Sarkis H. , Bouganim Nathaniel
Published: September 2018

e12127

Background: We prospectively investigated the incidence of neutropenic complications (NC) with neo/adjuvant AC (doxorubicin and cyclophosphamide) chemotherapy (CTX) among early-stage breast cancer (ESBC) patients. NC was defined as febrile neutropenia (FN), dose delay/reduction or need of granulocyte colony-stimulating factors (G-CSF) to proceed with CTX. Methods: This was a single-center, observational, prospective cohort study conducted at the McGill University Health Center. All ESBC patients who received AC regimen as neo/adjuvant CTX between February 2016 and February 2017 were included. Hazard ratios (HRs) with 95% confidence intervals (CIs) of predictors of NC were estimated using Cox-proportional hazards models. Results: A total of 118 patients, corresponding to 409 cycles of AC were analyzed. Most patients underwent Q3week cycles (83.1%). Median age was 52 years old (IQR 43-61). Prophylactic G-CSF was given to 20 dose-dense patients and 10 Q3weeks patients. In patients not receiving prophylactic G-CSF, 57 (65.5%) manifested at least one episode of NC (corresponding to an incidence rate of 26.4%/cycle of CTX [95% CI: 20.0%-34.2%]), of which 9 developed FN requiring hospital admission. In the final prediction model, body mass index < 25 kg/m2(HR: 2.36, 95% CI: 1.16-4.78) and increasing glucose levels (HR: 1.56, 95% CI: 1.14-2.14) were significantly associated with NC. Baseline absolute neutrophil count (ANC) was protective. Conclusions: The incidence of NC in our prospective study is significantly higher than previously reported in retrospective studies (26.4% vs. 12%). Normal BMI and high glucose were associated with the highest risk of NC. More importantly, 65% of ESBC on AC will require G-CSF during their treatment due to a NC episode. [Table: see text]
Duration of neoadjuvant endocrine therapy and breast cancer outcomes.
Authors: Mougalian Sarah Schellhorn , Soulos Pamela R. , Lannin Donald R. , Pusztai Lajos , Gross Cary Philip , Killelea Brigid K.
Published: September 2018

e12129

Background: Interest in the use of neoadjuvant endocrine therapy (NET) has increased over the past decade, and recent studies have demonstrated similar response rates compared to neoadjuvant chemotherapy. We examined the associations between duration of NET and type of surgery and change from clinical stage to pathologic stage. Methods: We used the National Cancer Data Base to identify women diagnosed with stage II-III, ER and/or PR positive breast cancer who received endocrine therapy from 2004-2014 and underwent surgery. We classified patients according to timing and duration of NET. We performed logistic regression to examine the impact of NET duration on likelihood of 1) receiving breast conserving surgery (BCS) versus mastectomy and 2) being downstaged. Downstaging was defined as pathologic stage lower than clinical stage and upstaging as pathologic stage higher than clinical stage. Results: In our sample of 159,676 patients, 6584 received NET (4.1%). NET was more frequently used in older women with multiple comorbid conditions, larger tumors, and higher nodal stage. The highest rates of NET were in academic/research or integrated network cancer programs. Of patients who underwent NET, 26.5% received it for ≤3 months, 41.0% for 3-6 months, 27.7% for 6-12 months, and 4.9% for 12-24 months. Patients who received NET for 3-6, 6-12, and 12-24 months were all significantly more likely to receive BCS versus mastectomy than patients who did not receive NET (Table). Patients who underwent NET compared to adjuvant endocrine therapy were more likely to be downstaged (Table). Conclusions: The most common duration of NET was 3-6 months, but >26% of patients received NET for less than 3 months. Longer durations of NET were strongly associated with BCS and downstaging. Further research is needed to determine the population of patients mostly likely to benefit from NET and the optimal length of treatment. [Table: see text]
Discrepancy of pathologic complete response and outcome between breast tumor and axillary node in HER2 positive breast cancer after neoadjuvant chemotherapy.
Authors: Chen Shin-Cheh , Chang Hsien-Kun , Lin Yung-Chang , Shen Shih Che , Kuo Wen-Lin , Yu Chi-Chang , Chou Hsu-Huan , Huang Yi-Ting , Ueng Shir-Hwa
Published: September 2018

e12503

Background: The pathologic complete response (pCR) rate in primary tumor and axillary node after different chemotherapy regimens of neoadjuvant chemotherapy (NAC) in HER2 positive breast cancer (BC) is unknown, the impact of pCR on disease free survival (DFS) and overall survival (OS) is still controversial. Methods: A cohort of 350 HER2 positive BC (296 cytologically proved axillary node metastasis) received NAC with different regimens, antracyclin with taxotere (AT), docetaxel with transtuzumab (DT) and docetaxel with transtuzumab and pertuzumab( DTP) between 2005 and 2016 in a large medical center were analyzed retrospectively. The impact of pCR rates of breast and axillary node on DFS and OS were analyzed. Results: Of 350 women with HER2 positive BC received NAC, median age was 50 years(18~93), median tumor size was 4.3 cm, the pCR rates of breast and axillary node were 16.2% and 28.7% ( P= 0.018) in patients received AT( n= 130) , 47.6% and 66.9% ( P= 0.00028 ) in patients received DT( n= 191) ,65.5% and 77.8% ( P= 0.372 ) in patients received DTP( n= 29), respectively. The 5-year DFS were 79.3% and 66.0% ( p= 0.0023), 5-year OS were 89.5% and 76.6% ( P= 0.0201) in patients with breast pCR and non-pCR, respectively. The 5-year DFS were 75.7% and 58.4% ( P= 0.00037), 5-year OS were 85.7% and 72.6% ( P= 0.0024) in axillary pCR and non-pCR patients, respectively. The 5-year DFS were 79.3% and 75.7% ( P= 0.430), and 5-year OS were 89.5% and 85.7% ( P= 0.695) in breast and axillary pCR, respectively . The 5-year DFS in breast pCR whom received targeted therapy (DT and DTP groups) was significantly better than whom not received targeted therapy (AT groups), 85.3% and 65.0% ( P= 0.039), respectively Conclusions: Higher pCR rate in axillary node than breast was found in this cohort. Either pCR in axillary node or breast was associated with improved DFS and OS, but no difference of DFS and OS between breast and axillary pCR . The 5-year DFS in breast pCR received targeted therapy were significantly better than breast pCR patients received chemotherapy alone.
Effects of erybuline/capecitabine (EC) treatment in very elderly women (VEW) with MBC.
Authors: Russo Antonio , Bazan Viviana , Carreca Ignazio Ugo , Cicero Giuseppe , Carreca Anna Paola
Published: September 2018

e12508

Background: Eribuline mesylate, is widely prescribed for MBC pts alone or in combination with Capecitabine in patients pretreated with at least 1-2 lines of chemotherapy, including anthracyclines and taxanes (A&T). Elderly Patients (EP) develop rapid and sometimes fatal toxicity during treatments due to pharmacokinetic features of these drugs.A combination schedule (E+C) to evaluate its suitability for VEW with MBC patients ,was used in this study. Methods: Treatment plan: E 0.96 mg/sqm IV on d1 every 21d - C 900 mg/sqm bid d1-14 every 28d (Dose-adjustement if necessary was according to Kintzel-Dorr’s formula for elderly), schedule administration continued until progression or intolerable toxicity . Eligibility criteria: histologically confirmed diagnosis of BC, 1 or more measurable lesion,(bone or visceral ) not brain mts, age > 75 years, failure of previous treatment with A or T , Comprehensive Geriatric Assessment evaluation (CGA) permissive for chemotherapy, adequate renal (CCl evaluation), bone marrow and liver function. Charlson's Score Comorbidity Scale was also considered. Evaluations tools: Clinical Benefit (CB) as Stable Disease + Objective Response Rates according to ESMO CB scale v.2a, Toxicity Profile using CTCAE v3.0 Criteria and Quality of Life (QoL) score through EORTC QLQ-C30 questionnaires V.3. Results: From 2014 jan to 2016 dec ,39 metastatic VEW, mean age 83.5 were treated and 37 are still under maintenance therapy (2 pts discontinued treatment for personal reasons). A total of 659 cycles were delivered to the 37 pts without any G4 toxicity. No delay in therapy delivery was needed. QoL score shows no worsening with improvement in about 79% after treatment in comparison with baseline. Clinical Benefit was evaluated about 80%. Conclusions: A further period of monitoring allowed to confirm our previous report in this setting with this combination schedule. It appears more fit with comorbidity or frailty than other chemotherapy regimens for MBC. The analysis of preliminary data shows a non-inferiority vs other usual treatments ,more suitability for very elderly women. An enlarged polycentric study is ongoing in order to confirm these outcomes.
Cerebellar metastases as the only brain metastatic site and correlation with molecular characteristics of primary breast cancer.
Authors: Tomasevic Zorica , Tomasevic Zoran , Grujicic Danica , Kovac Zeljko , Milovanovic Zorka , Minic Ivana , Kolarevic Daniela
Published: September 2018

e12509

Background: Contrary to well recognized higher incidence of brain metastases (BM) in HER2 3+ and triple negative (TN) BC, correlation with BC molecular subtypes and cerebellar metastases is not well explored. Methods: From January 2007 to Jun 2016, 269 patients with BCBM have been prospectively registered at the Institute for Oncology and Radiology of Serbia. We analyzed metastases localization within brain, and identified 28 patients with cerebellar metastases. Correlation with molecular subtype of primary BC, median time to cerebellar metastases development, treatment and survival were also analyzed Results: 28 patients (10.4%) of median 47 years (29-63) had cerebellar metastases as the only brain metastatic site confirmed by CT/MRI. Median time to cerebellar BM was 21 months (range 0-141). Cerebellum was the first distant metastatic site in 20/28 patients (71.4%), and 8 (28. 5%) patients had inoperable BC and/or distant metastases before cerebellar metastases development. Molecular subtype of primary BC was known for 27/28 pts (96.4%): 21 pts (77.7%) had HER2 3+BC; 14 (52%) had ER/PR negative BC and there were no TNBC. Fifteen patients (53.5%) were treated with brain surgery + postoperative WBRT, 4 (14%) with gamma knife, while remaining 9 pts (32%) underwent WBRT only. Patients with good performance (PS 0-2) also received various systemic treatments +/- trastuzumab/ lapatinib. Mean survival upon cerebellar metastases was 19.2 months (median 9, range 2-123+ months); 39% patients were alive after 12 months; 21% after 24 months; 14% after 36 months. One patient (3.6%) is alive without relapse/progression 123 months+ after cerebellar metastases extirpation; trastuzumab is ongoing through all that period. Conclusions: Majority of analyzed patients with cerebellar metastases had HER2 3+ BC (77.7%). It is also interesting that none of patients within this group had TNBC Therefore, it seems reasonable to speculate that some still unrecognized BC and/or cerebellar soil characteristic, contribute to HER2 3+ BC predilection to cerebellum in this rare patient subgroup.
Development of a breast and lung cancer research panel to target therapeutically relevant copy number and gene fusion variants from blood.
Authors: Bagai Varun , Schageman Jeoffrey , Brinza Dumitru , Li Yanchun , Gu Jian , Bramlett Kelli
Published: September 2018

e12518

Background: With recent advances in next-generation sequencing (NGS) technologies, it is now possible to detect somatic mutations with allele frequencies in blood samples as low as 0.1% from circulating tumor DNA. A natural extension to this achievement is adding the ability to simultaneously detect copy number variants and gene fusions. A panel such as this addresses a full repertoire of variant classes found to be linked with certain tumors and would enable researchers additional tools to profile cancer samples more dynamically thus enriching current diagnostic tool sets. Here, we present progress on such an approach and apply current NGS technology to achieve our goals. Methods: Samples were sequecned using the Ion S5™ system. Results: Using control samples, we can reproducibly demonstrate detection of ERBB2 (HER2/neu) gene amplifications with high statistical significance and as low as a 2 fold difference versus non-amplified loci in titration experiments. In addition, this ERBB2 gene amplification was detected in the context of a validated breast cancer somatic mutation panel in which no negative impact was exhibited and mutation detection specificity and sensitivity were both greater than 90%. Lastly, we developed an additional panel to detect gene fusions relevant to lung cancer. Using the titration approach above, the EML4-ALK fusion variant was shown to have a limit of detection near 1% with no negative impact on detection sensitivity and specificity when combined with the validated lung cfDNA somatic mutation panel. Conclusions: From the outcomes of these experiments, we have shown the ability to reproducibly and simultaneously detect copy number and gene fusion variants as well as somatic mutations at very low limits of detection in a cell free DNA background derived from blood samples.
Pre-clinical analysis of the CDK4/6 inhibitor palbociclib in HER2-positive breast cancer.
Authors: ElChaarani Bilal , Stires Hillary , Pohlmann Paula Raffin , Riggins Rebecca
Published: September 2018

e12520

Background: There has been substantial progress in treatment of metastatic HER2+ breast cancer, unfortunately, treatment progression of the disease is universal. Palbociclib is an oral cyclin-dependent kinase (CDK) 4/6 inhibitor that is FDA approved in combination with endocrine therapy for treatment of patients with ER+ metastatic breast cancer. Here we present pre-clinical studies in HER2+ breast cancer cell lines investigating whether addition of palbociclib to the combination of trastuzumab and pertuzumab (TP) is an effective therapy, and whether we could identify predictive biomarkers for palbociclib in this setting. Methods: Crystal violet assays to measure growth of BT-474 (HER2+, ER+), SKBr3 (HER2+, ER-) and MDA-MB-361 (HER2+, ER+ but resistant to TP) were performed in the presence and absence of TP (5 µg/ml each) with increasing concentrations of palbociclib (25-500 µg/ml). Western blots were performed in the presence and absence of TP with and without palbociclib to demonstrate efficacy of TP (blocking phosphorylation of HER2), palbociclib (blocking phosphorylation of Rb), and expression of NIMA-related kinase 2 (NEK2), an established downstream target of CDK4 in HER2+ breast cancer cells. Results: We found growth inhibition in response to palbociclib as single agent in a dose-dependent manner in BT-474, SKBr3, and MDA-MB-361 cells (P < 0.05). Treatment with TP prevented growth in BT-474 and SKBr3 cells to such a great extent that an additive effect between TP and palbociclib was not detectable. However, treatment with palbociclib maintained a dose-dependent decrease in growth in the presence of TP in MDA-MB-361 cells (P < 0.05). Western blots showed decreased expression of pHER2 in response to TP in BT-474 and SKBr3, but not in MDA-MB-361. Treatment with palbociclib decreased pRB in BT474, SKBr3, and MDA-MB-361 with or without TP. NEK2 expression, however, was not affected in any of these cell lines. Conclusions: Palbociclib has an inhibitory effect in resistant and non-resistant HER2-positive cell lines suggesting palbociclib represents an alternate targeting pathway for growth inhibition. Our initial work did not show reliable biomarkers to predict palbociclib effects.
Safety of trastuzumab in women with HER2+ breast cancer.
Authors: Nowsheen Somaira , Aziz Khaled , Park Jae Yoon , Villarraga Hector R. , Herrmann Joerg , Ruddy Kathryn Jean
Published: September 2018

e12522

Background: Trastuzumab is widely used in management of HER2+ breast cancer patients. A known adverse effect of trastuzumab use is cardiac dysfunction, which can often be reversed with cessation of therapy. Our objectives were to 1) assess if trastuzumab can be safely administered to breast cancer patients with reduced cardiac function and 2) identify patient characteristics that predict susceptibility to trastuzumab-induced cardiac dysfunction. Methods: A retrospective analysis was performed on female patients seen at Mayo Clinic for HER2+ breast cancer and treated with trastuzumab for localized or metastatic disease between January 1, 2000 and August 31, 2015. Eligibility criteria included documentation of and results from at least one echocardiogram prior to and at least one after trastuzumab initiation. Left ventricular (LV) ejection fraction (EF) of 53% or more was considered normal. Any LVEF reduction of 10% or more was considered significant. Among patients with normal EF, age strata of < 45, 45-60, and > 60 at time of trastuzumab initiation were used to assess risk factors for clinically diagnosed cardiac dysfunction (defined as EF < 53 or abnormal strain and physical symptoms of heart failure (HF)). Results: We identified 335 women (mean age 53.3, with 25.3% age < 45, 44.5% age 45-60, and 30.1% age > 60) who had normal LVEF (median EF 64, range: 53-75) and 23 women (mean age 53.4, with 30.4% age < 45, 43.5% age 45-60, and 26.1% age > 60) who had low LVEF at baseline (median EF 52, range: 25-52). Approximately a third (34.3%) of women with normal LVEF prior to initiation of therapy had at least one subsequent echocardiogram showing a drop of 10% or a low LVEF ( < 53). Approximately a quarter (26%) of women with low LVEF at baseline had a 10% drop in LVEF. HF incidence increased with age. Predictive factors for trastuzumab-induced cardiac dysfunction were obesity and history of coronary artery disease (CAD) across all age strata, and chest irradiation (IR) for those aged 45-60 only. Conclusions: Our results suggest that trastuzumab can be administered in women with reduced cardiac function at no greater risk than in those with preserved cardiac function. Some women with no obesity, history of CAD, or history of chest IR may not need echocardiograms during trastuzumab therapy.