bluuebunny/crossref_metadata_2025_split huggingface dataset:
The use of bioimpedance spectroscopy to monitor response to treatment interventions with breast cancer-related lymphedema.
Authors: Shah Chirag , Vicini Frank , Beitsch Peter D. , Anglin Beth , Laidley Alison Lisa , Ridner Sheila H. , Lyden Maureen 
Published: February 2017

138 Background: Currently, limited tools are available to assess response to therapy in patients with breast cancer related lymphedema (BCRL). The purpose of this study was to perform an exploratory analysis to determine if, in clinical settings, bioimpedance spectroscopy (BIS) can detect changes in extracellular fluid volume in response to treatment of BCRL. Methods: Three centers that had experience with BIS (L-Dex U400, ImpediMed Limited, Brisbane, Australia) provided retrospective data on 50 patients with breast cancer who were evaluated with BIS at baseline and following loco-regional procedures. Patients had a pre-surgical L-Dex measurement as well as at least 2 post-surgical measurements (before and after BCRL intervention). Decisions regarding intervention were made by physicians with no L-Dex score cut-off utilized. An analysis was performed comparing changes in L-Dex scores for those patients undergoing treatment for BCRL (n=13) versus those not undergoing intervention (n=37). A second analysis was also performed on all patients with elevated L-Dex scores compared to baseline prior to intervention (n=32). Results: The mean age was 54 years old. Fifty four percent of patients underwent SLN biopsy with a mean of 7.9 nodes removed. The mean change in L-Dex score from baseline (pre-treatment) to the first post-surgical L-Dex score measurement was 3.3 +/- 6.8. When comparing the cohort treated for BCRL to those not treated, L-Dex scores were significantly reduced (-4.3 v. 0.1, p=0.005) following intervention. For the subset of patients with elevated L-Dex scores post-surgery, the change in L-Dex score following BCRL intervention was significantly reduced (-5.8 v. 0.1, p=0.001) compared with those observed. Conclusions: These results confirm that BIS can detect increases in L-Dex scores following breast surgery and can also detect reductions in L-Dex scores following intervention for early onset lymphedema. These results demonstrate that BIS has significant clinical utility as it can be used to monitor patients with early BCRL who undergo intervention and to follow these patients (through serial measurements) to document their short and long-term response to these treatments.
Secondary cancers after breast-conserving therapy in Tokyo database.
Authors: Shiraishi Kenshiro , Nakagawa Keiichi , Kawamori Jiro , Ibukuro Kenji , Fukuuchi Atsushi , Nishi Tsunehiro , Shinozaki Tomohiro 
Published: February 2017

139 Background: The more patients overcome early breast cancer and become cancer survivors as a result of modern sophisticated approach, the more secondary cancers inevitably arise. The second malignancies after breast conserving therapy (BCT) are well-known sticky dilemma because of additional anxiety and need for medical care for longer-time. However, it is unclear whether secondary cancers negatively affect prognosis of breast cancer survivors. Methods: We performed a retrospective study of long-term cancer survivors after BCT for locoregional invasive or noninvasive breast cancer diagnosed between 1982 and mid-2012. Actuarial rates of overall (OS) and cause-specific survival (CSS) were calculated by using the Kaplan-Meier method. We compared between-group differences using the log-rank test. Results: Eight hundred sixty patients (32%) were followed-up for more than 10 years. At a median follow-up of 90 months, 146 patients had developed a second malignancy. The greatest increases in risk were for leukemia (Standardized incidence ratio (SIR): 4.24 (1.52–8.31)), ovarian cancer (SIR: 4.12 (2.40–6.31)), reno-ureteral cancer (SIR: 3.18 (1.14–6.23)), endometrial cancer (SIR: 2.48 (1.27–4.08)), and pancreatic cancer (SIR: 2.32 (1.11–3.99)). No increased risk was observed for other gastrointestinal and genitourinary cancer, malignant melanoma, lymphoma, thyroid or head and neck cancer. Overall 10-year cumulative incidence of OS without secondary cancer was 93.3%, and 10-year cumulative incidence of OS with secondary cancer was 81.5%. (p<0.001)Overall 10-year cumulative incidence of CSS without secondary cancer was 94.2%, and 10-year cumulative incidence of CSS with secondary cancer was 92.8%. (p=0.749). This likelihood of survival disadvantage is similar to that with ipsilateral breast tumor recurrecnce. Conclusions: Secondary cancers after BCT negatively impact on OS. Given the life-threatening nature to cancer survivors, lifetime caution such as smoking cessation, alcohol intake abstention, weight control, physical activity, and other healthy lifestyle must be paid.
Characterization of patients who received prior chemotherapy for advanced breast cancer (ABC) in BOLERO-2.
Authors: Yardley Denise Aysel , Campone Mario , Lebrun Fabienne , Noguchi Shinzaburo , Pritchard Kathleen I. , Burris Howard A. , Beck J. Thaddeus , Ito Yoshinori , Bachelot Thomas , Pistilli Barbara , Melichar Bohuslav , Petrakova Katarina , Arena Francis P. , Erdkamp Frans , Harb Wael A. , Litton Jennifer Keating , Brechenmacher Thomas , El-Hashimy Mona , Taran Tanya , Gnant Michael 
Published: February 2017

151 Background: In patients with hormone receptor–positive (HR+) breast cancer, endocrine therapy is the standard of care both in the adjuvant setting and as front-line therapy for ABC. Chemotherapy (CT) is commonly used for HR+ ABC patients if disease burden is high and rapid symptom control is required (Barrios CH. GAMO. 2010). In the phase III BOLERO-2 study (NCT00863655), first-line of prior CT in the ABC setting was allowed. This subset analysis examined disease characteristics and the efficacy of everolimus (EVE) + exemestane (EXE) in patients who received CT for ABC prior to BOLERO-2 study entry. Methods: In BOLERO-2, 724 patients with HR+, human epidermal growth factor receptor 2–negative (HER2–) ABC whose disease recurred or progressed during/after a nonsteroidal aromatase inhibitor were randomized 2:1 to EVE (10 mg/d) + EXE (25 mg/d) or placebo (PBO) + EXE. The primary endpoint was progression-free survival (PFS) by local investigator review (confirmed by blinded independent central review). Results: A total of 186 patients (26%) received prior CT for ABC (125 in the EVE + EXE group and 61 in PBO + EXE). In this subset, 54% (67 of 125) of EVE+ EXE patients received prior CT in the advanced setting only while 46% (58 of 125) of EVE + EXE patients received prior CT in both the neoadjuvant/adjuvant and advanced settings. Visceral metastases (67% vs. 56%), multiple metastases (79% vs. 66%), and ≥ 4 metastatic sites (18% vs. 15%) were more frequent in ABC patients with prior CT for ABC at study entry compared with those with no prior CT for ABC. History of disease recurrence <6 months from initial diagnosis was recorded in 32% (n = 60) of prior CT patients versus 17% (n = 93) of patients with no prior CT. Median PFS (by local assessment) in patients who received prior CT for ABC was substantially longer with EVE + EXE versus PBO + EXE (6.1 vs. 2.7 mo; hazard ratio = 0.38; 95% CI, 0.27-0.53). PFS by central review showed similar results (7.1 vs. 2.8 mo, respectively; hazard ratio = 0.42; 95% CI, 0.27-0.65). Conclusions: These results demonstrate that patients with HR+, HER2 ABC who received previous CT in the advanced setting had a higher tumor burden but derived significant and clinically meaningful benefit from combination therapy with EVE + EXE. Clinical trial information: NCT00863655.
Association of bone mineral density with breast cancer and histopathologic features of the tumor.
Authors: Sharma Anurag , Youssef Elias , Roche Meaghan , Maroules Michael 
Published: February 2017

16 Background: High bone mineral density (BMD) has been associated with increased incidence of breast cancer. We studied the differences in BMDs between females with and without breast cancer as well as the association between BMD and the histopathological features of breast cancer. Methods: Data on BMDs and Tscores of hip and spine were collected for 311 breast cancer patients from Dexa Scans available from 5 years before or within 1 year of diagnosis. The same information was collected for 1,047 females without breast cancer (age matched with study group). The following additional data was collected for breast cancer patients: TNM staging, Histology, Estrogen receptor (ER), Progesterone receptor (PR), Ki-67 and HER-2 percentages, Tumor size, and Tumor differentiation. Results: As expected, breast cancer patients were found to have higher hip/spine BMDs than women without breast cancer (p < 0.001). PR percentage was positively associated with hip BMD/Tscore and spine BMD/Tscore ([rsp=0.166/0.165, 0.145/0.164, respectively], p<0.05 for all [Spearman Correlation Analysis]). Tumor size was negatively associated with spine BMD/Tscore ([rsp=-0.134, p=0.06], [rsp=-0.136, p=0.04], respectively, [Spearman Correlation Analysis]). A negative trend was seen between Ki-67 percentages and BMD (although no significance was achieved). Patients with lymphovascular invasion had lower spine Tscores than patients without lymphovascular invasion (-1.22±1.45 vs. -0.84±1.37, p=0.04, [One-way ANOVA]). Conclusions: Amongst all women studied, women with breast cancer were likely to have a higher BMD. However, higher BMD in breast cancer patients was associated with favorable tumor characteristics. Higher BMD was also associated with higher percentage of PR while no significant association was seen with ER. Greater cumulative estrogen exposure in females with higher BMD might explain these results. Estrogens are known to affect proliferation of breast cancer cells and to alter their phenotypic and cytoarchitechtural features, including enhanced induction of PR and possible downregulation of ER. Future studies are needed to explore these underlying pathways, their effect on tumor behavior, and treatment implications.
Distant disease-free survival (DDFS) discrimination capacity of various pathologic complete response (pCR) definitions according to breast cancer subtypes.
Authors: Hattori Masaya , Matsuo Keitaro , Ichikawa Mari , Fujita Takashi , Sawaki Masataka , Kondo Naoto , Horio Akiyo , Yatabe Yasushi , Iwata Hiroji 
Published: February 2017

162 Background: pCR has been postulated to be correlated with long-term clinical benefits in some subtypes of breast cancer. Here, we analyzed the discriminatory ability and the predictive power of various pCR definitions for distant disease-free survival (DDFS) according to breast cancer subtypes. Methods: We analyzed 326 (114 Luminal A: ER+/PR+/HER2-, 44 Luminal B/HER2-: ER+/PR-/HER2-, 51 Luminal B/HER2+: ER+/PR+ and/or -/HER2+, 51 HER2: ER-/PR-/HER2+, and 66 Triple negative: ER-/PR-/HER2-) non-metastatic breast cancer patients (pts) who had received neoadjuvant chemotherapy at our institution between January 2003 and June 2012. Four pCR definitions were used: ypT0ypN0, ypT0/isypN0, ypT0/isypN0/+, ypT<1micypN0/+. DDFS was estimated by Kaplan-Meier method, and analyzed by log-rank test and Cox proportional hazard model. The receiver operating characteristic (ROC) curves analysis was used for comparing DDFS prediction models with and without various pCR definitions in addition to other covariates (tumor stage, nodal status, BMI, tumor grade, use of trastuzumab) as variables. Results: The pCR rate was comparatively low in Luminal A and high in HER2. 94.1% of HER2 and 74.5% of Luminal B/HER2+ received total 1 year of trastuzumab therapy. In multivariate analysis, no pCR definitions were associated with improved DDFS significantly in Luminal A, Luminal B/HER2-, Luminal B/HER2+ and HER2, whereas each pCR definition was associated with improved DDFS in Triple negative (ypT0ypN0: HR0.12, p=0.043, ypT0/isypN0: HR0.06, p=0.007, ypT0/isypN0/+: HR0.107, p=0.004, ypT<1micypN0/+: HR0.104, p=0.003). In the ROC curves analysis of triple-negative, a DDFS prediction model including pCR defined as ypT0/isypN0 showed the highest accuracy, but low statistical significance (AUC: 0.834 vs.0.749 p=0.076). Conclusions: pCR could discriminate good and poor prognosis groups only in Triple negative and pCR defined as ypT0/isypN0 has the potential to provide better discrimination in this subtype. The predictive power of pCR for long term clinical benefit in other subtypes may not be obvious due to the influence of effective adjuvant therapies.
Assessing breast cancer risk in primary care: What can we learn from cardiovascular disease?
Authors: Collins Ian M. , Keogh Louise A. , Steel Emma , Emery Jon , Pirotta Marie , Mann Bruce , Butow Phyllis , Trainer Alison , Moreton Jane , Antoniou Antonis C. , Cuzick Jack M. , Hopper John L. , Phillips Kelly-Anne 
Published: February 2017

17 Background: Routine assessment of breast cancer (BC) risk by primary care clinicians (PCCs) might improve uptake of (BC) prevention and screening interventions and thus reduce morbidity and mortality. Methods: Australian PCCs were recruited through local professional networks. Facilitated focus group discussions about current practice of assessing and managing BC risk were audiotaped, transcribed verbatim and managed using QSR NVivo qualitative data management software. A coding framework was developed based on the transcripts, data was coded and each code further analyzed to identify key themes. Results: 17 PCCs (12 doctors, 5 practice nurses) participated in 2 focus groups. 41% were male, median age 49 years, median number of years as a PCC was 15. Approaches to assessment and management of BC risk differed markedly from that of cardiovascular (CV) risk. PCCs see assessment and management of CV risk as an intrinsic, expected part of their role. Sidebar prompts on practice software trigger CV risk assessment and PCCs often use an online tool (www.knowyournumbers.co.nz) to provide personalized risk estimates and to discuss management options for CV risk. Conversely, assessment of BC risk is haphazard, generally patient (not clinician) initiated, and management, beyond routine BC screening (e.g. chemoprevention), is considered outside the domain of the PCC. BC risk assessment is not prompted by practice software. Most PCCs are not familiar with, or using, BC risk assessment tools. PCCs suggested they could potentially routinely assess and manage BC risk, but such an approach would need to be widely endorsed as within the remit of primary care and would be enhanced by an online tool that is accessible, quick, visual (graphs and pictograms), evidence-based and regularly updated. Ideally, its use would be prompted by their practice software. Conclusions: There is a clear opportunity in primary care to enhance the capacity and motivation of clinicians to assess and manage BC risk. A risk assessment and decision aid tool, integrated into primary care software, might facilitate routine appropriate management of BC risk in the Australian primary care setting, modelling what has already been achieved for CV disease.
Detection of new or additional significant breast disease by MRI compared to standard imaging in “high-risk” and “non-high–risk” patients.
Authors: Banks Amy Lynn , Titus Rachel , Melnik Marianne 
Published: February 2017

22 Background: Mammography is the standard of care for the early detection of breast cancer. Recently, studies have shown that Magnetic Resonance Imaging (MRI) has greater sensitivity in cancer detection. However, there have been reports identifying a high false positive rate. The aim of our study was to determine if breast MRI aids in the detection of new clinically significant disease, even in “low risk” patients, when compared to ultrasound (US) or mammography alone. Methods: A review of all patients who underwent breast MRI under the care of a single surgeon between 1/1/07 through 6/1/11 was conducted. Patients were categorized as high or non-high risk based on a history of breast cancer, genetic mutation, significant family history or >20% lifetime Gail model risk. For this study a clinically significant disease is defined as a new cancer or high-risk lesion that requires close follow-up and monitoring. Results: A total of 163 patients had a breast MRI and all had concerning findings. Compared to US or mammogram, MRI identified new or additional disease that changed plans in 150/159 (94.3%) patients. Of these, MRI added clinically relevant findings in 85 patients (56.7%, p<0.001). In those considered “high risk” MRI detected clinically significant disease in 37/76 (48.7%) and in 46/76 (60.5%) of the non-high risk group. 16 patients were <40 and MRI found new disease in 2/7 (28.6%) high risk patients compared to 3/9 (33.3%) non-high risk patients. 48 patients were 41-50 years old and MRI detected new disease in 12/24 (50%) high risk patients compared to 13/24 (54.2%) non-high risk. Of the 37 patients aged 51-60, MRI found new disease in 11/19 high risk patients (57.9%) compared to 14/18 (77.8%) non-high risk. 50 patients >60 years of age, MRI found new disease in 12/25 (48%) high risk patients compared to 16/25 (64%) who were non-high risk. Conclusions: We confirm that MRI provides extremely relevant data in identifying new or additional disease when compared to US or mammogram. MRI not only aided in finding additional disease in patients that were high risk but more importantly, MRI found pathology-proven new disease in non-high risk patients across all age groups. These results hold a substantial clinical implication in the ability to find new cancers or high-risk lesions early on, especially in non-high risk patients.
Induction of breast cancer progression and metastasis by HOXB9 gene’s activation by sequence specific binding factors.
Authors: Zhussupova Aisulu , Hayashida Tetsu , Takahashi Maiko , Jinno Hiromitsu , Kitagawa Yuko 
Published: February 2017

26 Background: HOXB9 is a member of class I HOX genes and is known to be overexpressed in human breast cancer and related to EMT, tumor angiogenesis, and radio-resistance (PNAS 2010), being significant prognostic factor in breast cancer patients. (Ann Surg Oncol 2012). Methods: We analyzed the upstream promoter region to determine the critical sequence for HOXB9 transcription. The multiple lengths of HOXB9 promoter region were cloned into pGL3 luciferase vector and each of them were checked by luciferase assay. Then made E2F1 overexpressed cell-lines: MCF7, MCF10A and MDA-MB231 to check HOXB9 gene expression. ChIP assay performed using E2F1 induced MCF7 cell-line model and EMSA made with T47D cells and E2F1 antibody. Results: We demonstrated luciferase activity of MDA-MB231 cells and overexpressed HOXB9 was determined at the region from -404 to -392 bps, showing that the mentioned region plays the critical role for the transcription of HOXB9. Computer prediction system for the binding ability to critical sequence raised several candidate: E2F1, PAX-5, P53, ETS-1, NFY-A, Sp-1, which are known to be related with cancer progression and we confirmed these genes could induce HOXB9. E2F1 overexpressed breast cancer cell-lines indicate high expression of HOXB9 show the correlation between E2F1 and HOXB9 expression. Luciferase assay method done by constructing pGL3 with HOXB9 critical sequence and analyzed using wild-type MCF7 and E2F1 induced MCF7 cells showed high luciferase activity of HOXB9 critical sequence plasmid in E2F1 induced MCF7 cell-line by compare to WT. ChIP assay and EMSA assay methods performed using E2F1 overexpressed MCF7 and T47D cell-lines model revealed high precipitation rate with E2F1 antibody and HOXB9 expression than negative control. Conclusions: HOXB9 is plays the role as the accelerator of breast cancer progression and discovering the properties of the gene and related factors will help to understand new signaling pathways of breast cancer development. E2F1 is a strong candidate direct binds to HOXB9 critical sequence and correlates with HOXB9 expression. Manipulating of E2F1 expression may regulate HOXB9 and reduce cancer progression and metastasis.
Is MRI suitable for conclusive work-up of suspicious findings in mammography and ultrasound?
Authors: Strobel Kevin , Schrading Simone , Kuhl Christiane K. 
Published: February 2017

3 Background: The current ACR practice guidelines discourage use of MRI for work-up of suspicious findings in mammography (Mx) and ultrasound (US). We investigated whether additional breast MRI assessment of suspicious Mx and U.S. findings could improve PPV and thus possibly help reduce the number of biopsies for false positive findings in Mx or U.S. Methods: Between 06/2010 and 04/2012, a total 2,754 patients underwent DCE breast MRI. Of these, 277 underwent MRI for further work-up of suspicious findings made in Mx (n=173, 57 patients with mass lesions, 33 with asymmetries, 12 with architectural distortions, and 71 with suspicious calcifications) or U.S. (n=104, 74 with masses, 30 with miscellaneous U.S. findings such as suspected intraductal pathology, focal acoustic shadowing or architectural distortions) . All lesions categorized as MR-BIRADS 4 and 5 underwent biopsy, lesions categorized as MR-BIRADS 1 or 2 did not proceed to biopsy, except for selected women with mammographic calcifications suggestive of DCIS. Lesions categorized as MR-BIRADS 3 underwent additional short term follow-up by MRI, US and/or Mx. All women who did not undergo biopsy (MR-BIRADS 1-3) underwent long term follow-up for so far 12-24 months. Results: For suspicious lesions in mammography, MRI increased PPV from 19.3% (11/57) to 92.3% (12/13) for masses, from 3% (1/33) to 33.3% (1/3) for asymmetries, from 8.3% (1/12) to 25% (1/4) for architectural distortions and from 21.1% (15/71) to 62.5% (15/24) for calcifications. For suspicious lesions in ultrasound, MRI increased PPV from 13.5% (10/74) to 71.4% (10/14) for masses and from 3.3% (1/30) to 50% (1/2) for non-mass U.S. findings. In 4/277 patients, MRI showed additional suspicious findings, requiring MR-guided biopsy, one of which was histologically proven malignant. So far, none of the patients who, because of an MR-BIRADS 1-3, did not undergo biopsy has been diagnosed with invasive cancer or DCIS or with progressive conventional imaging findings necessitating secondary biopsy. Conclusions: MRI improves PPV for both suspicious Mx and U.S. findings, especially mass lesions. In experienced hands, careful use of MRI can help avoid biopsies for false positive diagnoses made in Mx and U.S.