bluuebunny/crossref_metadata_2025 huggingface dataset:
Correlation between quantitative multi-detector computed tomography lung analysis and pulmonary function tests in chronic obstructive pulmonary disease patients
Authors: Abd elsalam Sahar Mahmoud , Hafez Mai , Mohmed Maha Fathy , Said Ahmed Hesham
Published: August 2020

Background

Chronic obstructive pulmonary disease [COPD] is a very common disease in developing as well as in developed countries. Using CT has a growing interest to give a phenotypic classification helping the clinical characterization of COPD patients. So, the aim of the present study was to evaluate whether there was a significant correlation between quantitative computed tomography lung analysis and pulmonary function tests in chronic obstructive pulmonary disease patients.

Results

The study included 50 male patients with a mean age of 62.82 years ± 8.65 years standard deviation [SD]. Significant correlation was found between the pulmonary function tests [FEV1 and FEV1/FVC ratio], and all parameters of quantitative assessment with – 950 HU [the percentage of low-attenuation areas (% LAA)]. Pulmonary function tests according to GOLD [Global Initiative for Chronic Obstructive Lung Disease] guidelines revealed that 4% had normal pulmonary function, 8% had mild obstructive defect, 32% had moderate obstructive defect, 26% had severe obstructive defect, and 30% had very severe obstructive defect.

Conclusion

Automated CT densitometry defining the emphysema severity was significantly correlated with the parameters of pulmonary function tests and providing an alternative, quick, simple, non-invasive study for evaluation of emphysema severity. Its main importance was the determination of the extent and distribution of affected emphysematous parts of the lungs especially for selecting the patients suitable for the lung volume reduction surgery.
Value of using adaptive statistical iterative reconstruction-V (ASIR-V) technology in pediatric head CT dose reduction
Authors: Sherif Fatma Mohamed , Said Ayman Mokhtar , Elsayed Yara Nagi , Elmogy Sabry Alameldeen
Published: August 2020

Background

With widespread use of pediatric head CT, it is critically important to protect patients from radiation hazards, using reduced dose CT techniques. In this regard, adaptive statistical iterative reconstruction-V (ASIR-V) algorithm can decrease image noise, generating CT images of reasonable diagnostic quality with less radiation. The objective of this study was radiation dose assessment, quantitative and qualitative evaluation of reduced dose pediatric head CT using ASIR-V 60% and 80% reconstruction.

Results

Retrospective analysis was performed on two groups of pediatric head CT examinations, a reduced dose CT examination group with ASIR-V reconstruction (ASIR group) (n = 27) and a standard dose CT examination group without ASIR reconstruction (non-ASIR group) (n = 14). The average effective dose (ED) of ASIR group was significantly lower than that of the non-ASIR group (1.04 ± 0.1 mS vs 3.48 ± 0.45 mS; p = 0.001). Quantitative analysis revealed comparable results of signal to noise ratio (SNR) and contrast to noise ratio (CNR) of ASIR and non-ASIR groups (p > 0.05). Qualitative evaluation of resulting images by two readers revealed comparable results of both ASIR and non-ASIR groups (p > 0.05) with excellent inter-reader agreement (κ = 0.97). Both quantitative and qualitative assessment demonstrated better ASIR-V 80% than ASIR-V 60% reconstructed images.

Conclusion

ASIR-V algorithm is a promising technology for effective dose reduction of pediatric head CT with preservation of diagnostic image quality.
Compulsory admissions of patients with mental disorders: State of the art on ethical and legislative aspects in 40 European countries
Authors: Wasserman D. , Apter G. , Baeken C. , Bailey S. , Balazs J. , Bec C. , Bienkowski P. , Bobes J. , Ortiz M. F. Bravo , Brunn H. , Bôke Ö. , Camilleri N. , Carpiniello B. , Chihai J. , Chkonia E. , Courtet P. , Cozman D. , David M. , Dom G. , Esanu A. , Falkai P. , Flannery W. , Gasparyan K. , Gerlinger G. , Gorwood P. , Gudmundsson O. , Hanon C. , Heinz A. , Dos Santos M. J. Heitor , Hedlund A. , Ismayilov F. , Ismayilov N. , Isometsä E. T. , Izakova L. , Kleinberg A. , Kurimay T. , Reitan S. Klæbo , Lecic-Tosevski D. , Lehmets A. , Lindberg N. , Lundblad K. A. , Lynch G. , Maddock C. , Malt U.F. , Martin L. , Martynikhin I. , Maruta N. O. , Matthys F. , Mazaliauskiene R. , Mihajlovic G. , Peles A. Mihaljevic , Miklavic V. , Mohr P. , Ferrandis M. Munarriz , Musalek M. , Neznanov N. , Ostorharics-Horvath G. , Pajević I. , Popova A. , Pregelj P. , Prinsen E. , Rados C. , Roig A. , Kuzman M. Rojnic , Samochowiec J. , Sartorius N. , Savenko Y. , Skugarevsky O. , Slodecki E. , Soghoyan A. , Stone D. S. , Taylor-East R. , Terauds E. , Tsopelas C. , Tudose C. , Tyano S. , Vallon P. , Van der Gaag R. J. , Varandas P. , Vavrusova L. , Voloshyn P. , Wancata J. , Wise J. , Zemishlany Z. , Öncü F. , Vahip S.
Published: August 2020

Background.

Compulsory admission procedures of patients with mental disorders vary between countries in Europe. The Ethics Committee of the European Psychiatric Association (EPA) launched a survey on involuntary admission procedures of patients with mental disorders in 40 countries to gather information from all National Psychiatric Associations that are members of the EPA to develop recommendations for improving involuntary admission processes and promote voluntary care.

Methods.

The survey focused on legislation of involuntary admissions and key actors involved in the admission procedure as well as most common reasons for involuntary admissions.

Results.

We analyzed the survey categorical data in themes, which highlight that both medical and legal actors are involved in involuntary admission procedures.

Conclusions.

We conclude that legal reasons for compulsory admission should be reworded in order to remove stigmatization of the patient, that raising awareness about involuntary admission procedures and patient rights with both patients and family advocacy groups is paramount, that communication about procedures should be widely available in lay-language for the general population, and that training sessions and guidance should be available for legal and medical practitioners. Finally, people working in the field need to be constantly aware about the ethical challenges surrounding compulsory admissions.
Idiotype vaccine therapy (BiovaxID) in follicular lymphoma in first complete remission: Phase III clinical trial results
Authors: Schuster S. J. , Neelapu S. S. , Gause B. L. , Muggia F. M. , Gockerman J. P. , Sotomayor E. M. , Winter J. N. , Flowers C. R. , Stergiou A. M. , Kwak L. W.
Published: August 2020

2

The full, final text of this abstract will be available in Part II of the 2009 ASCO Annual Meeting Proceedings, distributed onsite at the Meeting on May 30, 2009, and as a supplement to the June 20, 2009, issue of the Journal of Clinical Oncology.

[Table: see text]
Preferential pathologic complete response (pCR) in HER-2 positive and triple-negative breast cancer to sequential FEC 100- docetaxel (T) neoadjuvant chemotherapy (NCT) in stage II-III operable breast cancer
Authors: Dubray P. , Durando X. , Abrial C. , Mouret-Reynier M. , Nayl B. , Thivat E. , Gimbergues P. , Achard J. , Chollet P. , Penault-Llorca F.
Published: August 2020

e11502

Background: NCT is increasingly used for operable breast cancer to allow breast conservation. Our objective was to evaluate clinical and pathological response after sequential NCT of FEC 100-T. This chemotherapy is currently the reference in the adjuvant setting in France.In PACS 01 trial (Roche et al. J Clin Oncol, 2006) FEC followed by T significantly improved 5 years overall survival rates (90.7%) compared to 6 FEC 100 in node-positive breast cancer. However this combination has not yet been evaluated in NCT. Methods: 101 patients (pts) from February 2005 to September 2008 with stage II-III operable breast cancer received 3 cycles (c) of FEC 100 (epirubicin 100 mg/m2 + 5-fluorouracil and cyclophosphamide 500mg/m2) followed by 3 c of T (100mg/m2) every 3 weeks. pCR was defined according to Chevallier's (Am J Clin Oncol, 1993) as level 1 and 2 and to Sataloff's classification (J Am Coll Surg, 1995) as grade A. A clinical, mammography and ultrasound breast evaluation was performed at baseline, after 3 or 4 c and before surgery. Results: Median age was 52.3 years [32–71]. Median diameter of the tumor was 42 mm [15–100]. 83 pts had a ductal, 14 a lobular, 3 ductal and lobular, 1 another carcinoma. 8.9% were grade I SBR, 58.4% grade II SBR, 28.7% grade III SBR and 4% unspecified. 74 (73.3%) tumors were HR+, 9(8.9%) Her-2 + and 18(17.8%) triple negative. Ultrasound objective response rate (ORR) was 66.3%: 6 pts had a complete response and 53 pts had a partial response. 77pts (76.2%) underwent breast-conserving surgery After the completion of NCT, complete histologic data were available for 92 pts. 10 (10.8%) achieved pCR using Chevallier's classification and 9 (9.8%) using Sataloff's classification. The pCR rate was superior in triple negative (4/12) and Her2+ (2/6) tumors than in patients with HR+/Her-2- according to Chevallier's classification (p=0.034) and to Sataloff's classification (p=0.014). Conclusions: Sequential NCT with FEC followed by T was active and significantly improved pCR in patients with triple negative and Her-2+ tumors without an anti-Her2 specific biological agent. Breast-conserving rate appeared satisfactory.

No significant financial relationships to disclose.
Who benefits from taxanes?
Authors: Piccart-Gebhart M. J. , Bedard P. L.
Published: August 2020

e11503

Over the last fifteen years, 21 clinical trials randomized nearly 36,000 women with early-stage breast cancer to taxane-based versus non-taxane-based adjuvant chemotherapy regimens to establish the role of taxanes in early breast cancer therapy. Preliminary results from the Oxford Overview –pooling individual patient data from some of these studies –suggest that the inclusion of a taxane to an anthracycline-based regimen reduces 10-year breast cancer related mortality by an absolute value of 5% over anthracycline therapy alone. In spite of this enormous global research effort, there remains considerable uncertainty regarding which patients benefit from taxane therapy. Three recent meta-analyses indicate that taxanes are beneficial irrespective of age, lymph node involvement, and hormonal receptor expression. Unfortunately, differences in trial design, pathological evaluation, and outcome reporting limit the robustness of these findings. Individual studies have suggested that patients with HER-2 positive disease derive greater benefit from taxane therapy, although the methods used to assess HER-2 status have been heterogeneous and there is no clear biological rationale to account for differential benefit in this subset. A number of promising predictive molecular markers related to taxane metabolism, microtubule dynamics, and intracellular signaling warrant further evaluation using biospecimens collected from the first-generation taxane trials. Future clinical trials should account for the molecular heterogeneity of breast cancer, by excluding the chemotherapy insensitive luminal A subset and mandating upfront central pathological assessment to further optimize the role of taxane therapy in early-stage disease.

No significant financial relationships to disclose.
Preliminary safety results from a multicenter phase II trial of nanoparticle albumin-bound paclitaxel/cyclophosphamide in early stage breast cancer plus trastuzumab in HER-2+ patients (pts)
Authors: Raefsky E. , Inhorn R. , Lange M. , Peacock N. , Shastry M. , Vazquez E. , Priego V. , Franco L. , Hainsworth J. D. , Yardley D. A.
Published: August 2020

e11509

Background: Docetaxel/cyclophosphamide has demonstrated superior disease free and overall survival compared to doxorubicin/cyclophosphamide in the treatment of early stage breast cancer with an acceptable safety profile, with grade (G) 3/4 neutropenia of 61% and no cardiotoxicity. Nanoparticle albumin-bound (nabtm)-paclitaxel (nab-P) is a novel formulation with demonstrated superior efficacy to conventional paclitaxel (P) in treatment of metastatic breast cancer with a comparable safety profile. We therefore conducted a multicenter phase II pilot trial of weekly nab-P/cyclophosphamide to assess the safety and tolerability of this combination in early stage breast cancer. Methods: Eligibility: T1–4pN0–3M0, ECOG PS 0–2, normal organ function, normal LVEF for pts receiving trastuzumab (T). Treatment consisted of nab-P 100 mg/m2 day (D) 1, 8, 15 with cyclophosphamide (C) 600 mg/m2 D1 q 21 days x 4 cycles. T was given in IHC 3+ or FISH HER2+ pts with an 8 mg/kg loading dose followed by 6mg/kg q21D x 52 weeks. Results: 63 pts enrolled from April 2008 through September 2008; 33 pts are evaluable for safety with a median of 2 cycles. Baseline characteristics: median age 57 years (range 33–76); ECOG PS 0–94%, T1-T2 tumors - 100%, node negative 61%, hormone receptor negative 33%, HER 2+ 15%, triple negative 27%, ductal histology 73%, premenopausal 37 %. nab-P dose modifications occurred in 10 of 33 pts with nab-P reductions in 2 pts: 1 each due to G3 neutropenia- cycle 2 and G3 neuropathy- cycle 4. All 8 nab-P treatment delays were due to G3 neutropenia at D15. G3/4 neutropenia was present in 30% with only 1 G4 episode. 1 pt utilized myeloid colony stimulating factors. There were no G3/4 non-heme toxicities present in > 5 % of pts and no LVEF declines in pts receiving T. 17 pts remain on study with 3 pts receiving T. Conclusions: The combination of weekly nab-P with cyclophosphamide is feasible and well tolerated with an acceptable safety profile as adjuvant therapy for early stage breast cancer. The addition of T to this combination did not create any safety concerns. Full safety data for the 63 pts will be updated at the time of the meeting.

[Table: see text]
Interim analysis of the multicenter phase II HEDON trial evaluating pathological response to pre-operative docetaxel and docetaxel+trastuzumab (T) in locally advanced breast cancer (BR) stratified by HER2-status
Authors: Paepke S. , Kiechle M. , Paepke D. , Klein E. , Warm M. , Augustin D. , Camara O. , Nährig J. , Kates R. , Harbeck N.
Published: August 2020

e11512

Background: Docetaxel is the most effective mono-substance in metastatic BC and highly effective in adjuvant chemotherapy. Early docetaxel-monotherapy data in primary systemic therapy (PST) showed a pCR of 18% (Amat et al; 2003), comparable with pCR-rates of standard PST combination chemotherapy. HEDON was conducted to evaluate efficacy of docetaxel ± T with regard to pCR (defined as absence of invasive and non-invasive BC in breast and lymph nodes) as primary endpoint; secondary endpoints were safety, breast conservation rate and 5-yr DFS. Additionally Trans-HEDON includes a translational research program to identify molecular RNA and methylation (DNA) based markers of response to docetaxel-monotherapy. Methods: From 2006 until 2008, the multicenter phase II HEDON trial fully recruited 93 pts, with therapy still ongoing; tumor stages: T2 (23), T3 (11), T4 (5); nodal status: N0 (16), N1–2 (23). Arm A: Docetaxel (100 mg/m2x6) in HER2-negative (n=60) and Arm B: Docetaxel (100 mg/m2x6) in combination with T (18x2mg/kg KG) preoperatively in HER2-overexpressed BC (n=33), followed by surgery and then by adjuvant epirubicin/cyclophosphamide (E90Cx4), radiotherapy if indicated, T for altogether one year, and endocrine therapy in ER+ and/or PgR+ BC. Pre-planned interim analysis (safety and efficacy) was performed after recruitment of 39 pts (Arm A 26, Arm B 13). Results: In Arm A, 7 pts. (26.9%) achieved pCR and 9 pts. (34.6%) pPR. In Arm B, 7 pts. (53.8%) achieved pCR and all 6 others (46.2%) pPR. Neutropenia occurred in 11 pts. (8 with grade 3). Moderate (25%) dose reduction was necessary in 13 pts., and 50% dose reduction in one patient. Conclusion: According to interim analysis of the HEDON trial, docetaxel-monotherapy of 6 cycles at 100mg/m2 q21 (plus T in HER2-positive BC) is an effective and safely administrable PST. There were no unexpected toxicities, and preliminary pCR rates in HER2-neg (26.9%) and HER2-pos (53.8%) pts. were comparable to those of combination chemotherapy. These interim results will be completed by final analysis on the full collective, with molecular predictors from TransHEDON hopefully identifying patients who derive extensive benefit.

[Table: see text]
HER-2 central confirmatory testing using ASCO/CAP guidelines for trastuzumab/lapatinib trial MCCR RC0639
Authors: McCullough A. , Dueck A. , Chen B. , Reinholz M. , Wiktor A. , Lingle W. , Jenkins R. , Perez E.
Published: August 2020

e11527

Background: 118 Her2 positive invasive carcinomas were retested centrally at the Mayo Clinic for Her2 status confirmation prior to inclusion in Mayo Clinic Cancer Research Consortium study RC0639 phase II study of cardiac safety and tolerability of adjuvant chemotherapy plus trastuzumab with lapatinib for resected Her2+ breast cancer (MCCRC RC0639). Methods: Central confirmatory methods were immunohistochemical (IHC) Dako HercepTest on a Dako Autostainer using the manufacturer's recommendations and HercepTest kit epitrope retrieval kit and fluorescent in situ hybridization (FISH) using Vysis PathVysion probe kit. Test results are interpreted using ASCO/CAP guidelines (IHC >30%, Her2:CEP 17 ratio >2.2). Results: There is local and central test 3+ IHC concordance in 48 of 53 tumors (agreement 90.6%) and FISH amplification in 29 of 33 tumors (agreement 87.9%), improved or similar results using identical methods to results in NCCTG N9831 adjuvant trial (n=1063, 81.6% IHC; n=813, 88.1% FISH). Of 92 centrally tested 3+ IHC positive tumors, 88 (95.7%) were FISH amplified. 5 centrally tested patients interpreted as Her2 positive by pre-ASCO/CAP guidelines (IHC >10%; HER2:CEP17 ratio >2) are Her2 ineligible using ASCO/CAP guidelines. IHC not confirmed centrally was reviewed by a second pathologist in 16 of 118 specimens. IHC concordance between two central pathologists was 10/16 (62.5%) in negative or equivocal (≤30% IHC staining) specimens; 7/10 (70%) with two reader agreement were FISH amplified and 4/6 (66%) with disagreement were FISH amplified. Conclusions: Concordance in IHC and FISH results between local and central labs is similar or improved since N9831. New ASCO/CAP Her2 testing guidelines change eligibility based on Her2 status in 4.2 % of patients. Equivocal IHC results falling between pre- and post- ASCO/CAP IHC positive thresholds (>10% and <30% IHC strong staining) are only partially resolved by repeat IHC review and/or FISH testing.

No significant financial relationships to disclose.
Current status of treatment of local recurrence and distant metastasis of triple negative breast cancer in Japanese population
Authors: Osako T. , Nishimura R. , Okumura Y. , Hayashi M.
Published: August 2020

e11548

Background: Triple-negative breast cancers have an aggressive clinical history such as high incidence of visceral metastases, high rate of cerebral metastases, high rate of local recurrence, and early age of onset. However, there are limited long-term clinical data evaluating outcomes of locoregional and systemic therapy. The purpose of this study was to evaluate the clinical outcome of current therapy with TNBC retrospectively. Methods: From the medical records of our hospital, we retrospectively reviewed breast cancer patients whose three markers were available and describe the relationship between current therapy and clinical outcome. Results: Between 1998 and 2007, 1967 breast cancer patients were treated in Kumamoto City Hospital. Of 1967 patients, 264 (13.4%) were classified as TNBC by immunohistochemical technique. As of December 2008, with a median follow-up time of 31months, 53 patients (20.0%) with TNBC had locoregional recurrences or distant metastases (17 local recurrences, 15 nodal recurrences, 44 distant metastases). Forty out of 53 patients with recurrent TNBCs had adjuvant or neoadjuvant chemotherapy around surgery. Of 53 patients with recurrences, 31 had initial locoregional recurrence and 19 had initial distant metastases. Forty two patients had already been dead and common causes of death were lung metastases (19 patients), liver metastases (11 patients), and brain metastases (8 patients). Patients with TNBCs had a poorer 5 year-survival compared with those with non-TNBCs. Furthermore, patients with initial distant metastases had significantly poorer survival than those with initial locoregional recurrence (p=0.015). Focusing on chemotherapy, no specific cytotoxic agent had high effectiveness for recurrent TNBCs. However, patients who had responded to first regimens had a tendency to respond to the next regimens. Conclusions: TNBC had an aggressive behavior and poorer prognosis. However, TNBC with locoregional recurrence and benefits from the first regimen had favorable prognosis. Therefore, to distinguish the subgroup that respond to chemotherapy might contribute to the prolongation of survival of in TNBC.

No significant financial relationships to disclose.
A retrospective review of demographics and stage of triple-negative breast cancer
Authors: Rana F. N.
Published: August 2020

e11553

Background: Triple negative breast cancer (TNBC) is a recently recognized subtype of breast cancer, notable to metastasize early. It accounts for 15–20% of all breast cancers, and is more prevalent in African-American and Hispanic women, and women younger than 40 years of age. Continual decline in breast cancer deaths since 1990 has been attributed to earlier detection, better treatment including hormonal blockade in estrogen- and progesterone-receptor positive cancers, as well as the addition of Trastuzumab, a monoclonal antibody directed against the Her2/neu receptors. These hormone receptors are not found in TNBC, and therefore the traditional targets for endocrine manipulation cannot be therapeutically exploited. While lower socioeconomic status and racial predisposition to this disease have been observed, there exists a paucity of research into other demographic risk factors. We reviewed data between January 2000 to December 2005 from our tumor registry with particular attention to age, race, family history, tobacco use, and stage of presentation, comparing this subset of patients (n=39) to other records (n=303). We included only those patients in whom the status of all three receptors were recorded. Results: Comparisons were made for TNBC vs non-TNBC patients respectively as follows: mean age (59.87± yrs vs 60.09±yrs). Analysis using χ2 test (χ2=0.855) and CMH test for Linear Trend analysis (p=0.47) showed no difference in percentages in association with the 5 stages or TNBC status and no linear trend respectively. Conclusions: This data suggests that at our institution, TNBC is less prevalent (12.87%) than estimates of 15- 20% published in other studies. There was no difference in age at diagnosis (p=0.92), with black patients more likely to have TNBC (p=0.004, OR=2.75). There was no significant association between smoking status and TNBC (p=0.43). There was no significant association between a family history of cancer and TNBC (p=0.8384). When accounting for samples size, TNBC was as prevalent as non TNBC at all stages of diagnosis. These results differ from other published data and may reflect differences in statistical analysis.

No significant financial relationships to disclose.
Comparison of the sensitivity to endocrine therapy of PR+/ER- patients and ER+/PR- patients with HER2+ breast cancer
Authors: Hao X. , Liu Y. , Hui R. , Zhang J.
Published: August 2020

e11558

Background: Her2 and PR expression are important indicators for prognosis of breast cancer. Aslo, it's proved that their expression could guide chemotherapy, endocrine therapy and targeted therapy in many studies. Methods: Collected 3,677 primary breast cancer cases from 2002 to 2004 in Tianjin University Cancer Hospital. All of the cases were confirmed by pathohistological method. All patients are female, aged from 15 to 92 years old, with median age 50 years old. Median follow-up time is 40 months. Her-2, PR and ER expression were detected by immunohistochemical methods. Results: 1. With Her2+ breast cancer, 168 patients are PR+/ER- and 211 patients are ER+/PR-. 2. All patients treated with anthracycline-based adjuvant chemotherapy with 6 cycles and then given endocrine therapy: Pre-menopausal patients were given TAM (10mg P.O Bid); Post-menopausal patients were given AI (letrozole 2.5m po. bid or anastrozole 1 mg P.O Qd). Median follow-up time is 45 months. With Her2+ BC, 3-year DFS(disease-free survival rate) of PR+/ER- patients is 94.53%, higher than that of PR-/ER+ ones (91.81%).With Her2- BC, 3-year DFS of PR+/ER- patients is lower than that of PR-/ER+ (p<0.05). 3. Total of 1853 cases with 5-year followed up, and 1297 cases have been given endocrine therapy. 5-year overall survival rate was 83.41%. With Her2+ BC, it's significant difference that 5-year OS of PR+/ER- patients is higher than that of PR-/ER+ ones. However, there's no difference of 5- year OS between them with Her2- BC. Conclusions: With Her2+ breast cancer, 3-year DFS of PR+/ER- patients is higher than ER+/PR- and also PR+/ER- patients may more sensitive to endocrine therapy than ER+/PR- patients.

No significant financial relationships to disclose.
Postlumpectomy loco-regional breast cancer therapy with liposomal therapeutic agents: Retention and distribution in nude rats
Authors: Li S. , Goins B. , Phillips W. T. , Saenz M. , Otto P. , Bao A.
Published: August 2020

e11562

Background: Post-lumpectomy loco-regional radiation therapy, such as brachytherapy, has been shown to decrease breast cancer recurrence and increase patient survival. Limitations of current brachytherapy are the relatively high radiation absorbed dose delivered to normal breast and the inability to treat potentially involved lymph nodes. Locally administered liposomes are being investigated for delivery of drugs and therapeutic radionuclides. We propose a new post-lumpectomy loco-regional therapy with liposome-carried therapeutic agents. To investigate, radiolabeled liposomes were injected into the surgical cavity of a nude rat model one day following surgical removal of the breast tumor, and in vivo retention and distribution were monitored with nuclear imaging and post- mortem dissection. Methods: Six liposome formulations containing 0.2% molar ratio Rhodamine B-lipid and cationic, neutral, or anionic surface charges were manufactured at diameters of 400 or 100 nm and characterized. Breast cancer xenograft model in female nude rats was set up by inoculating MDA-MB-231 cells into the fat pad of the left breast of each rat. When tumor volumes reached 1.9 cm3 on average, the majority of each tumor was surgically removed, leaving ∼0.05 cm3 tumor tissue in the cavity. Then, each rat (3–4 rats/group) was intracavitarily injected with 0.5 ml of 99mTc-liposomes (4 mCi., 30 mg total lipids/kg body weight). In vivo distribution of 99mTc-activity was measured with planar gamma camera and SPECT imaging at various times. Post-mortem stereo fluorescent images of surgical cavity and the surrounding lymph nodes at 44 h were acquired. Results: All 99mTc-liposome formulations had approximately ≥ 50% retention in the surgical cavity at 44 h after injection. 99mTc-anionic liposomes of 100 nm diameter had an optimal lymph node targeting with ∼6%/g tissue in the surrounding lymph nodes at 44 h. Fluorescence imaging of the liposomes clearly showed their clearance through surrounding lymphatics and retention in lymph nodes. Conclusions: Anionic liposomes of 100 nm diameter are promising carriers for the simultaneous treatment of the surgical cavity and its draining lymph nodes.

No significant financial relationships to disclose.
Frequency of zoledronic acid (ZOL) administration to prevent aromatase inhibitor-associated bone loss (AIBL)
Authors: Lipton A. , Campbell-Baird C. , Chen Y. , Dias R. , Kelly B.
Published: August 2020

e11567

Background: Cancer patients (pts) are at increased risk of osteoporosis because of cancer treatment-induced bone loss. A hypogonadal state can increase bone resorption and turnover. Estrogen depletion with aromatase inhibitors (AIs), the preferred adjuvant treatment in postmenopausal women with early breast cancer (EBC), is associated with accelerated bone resorption and increased fracture risk. Several studies have demonstrated that IV ZOL can prevent AIBL in pts with EBC. ZOL to prevent AIBL was shown to be effective when administered every 6 mo in 4 large, randomized phase III trials. It is unknown if this is the optimal regimen. Methods: Pts who were receiving adjuvant breast cancer therapy with an AI and had a urinary N-telopeptide (uNTX) level > 50 nmol/mmol creatinine (Cr) and a bone density T-score < 1.5 at screening were treated with a single dose of ZOL 4 mg IV. Serum C-telopeptide (sCTX) and uNTX were obtained at baseline and then every 2 mo. Data are presently available from 10 pts who were followed for at least 6 mo and 1 pt followed for 2 mo after receiving ZOL. Wilcoxon signed-rank tests were performed for % change from baseline values. Results: Median baseline uNTX in these patients was 57.5 nmol/mmol Cr (range, 42.7 to 104.5). Median suppression of uNTX from baseline was 76.7% (range, 55.0% to 81.4%; P = .008) at 1 mo after therapy. At 6 mo, suppression of uNTX from baseline was 56.5% (range, 3.5% to 72.6%; P = .03). Similar significant suppression of sCTX up to 6 mo was observed. Continued suppression of uNTX and sCTX (approximately 50% decrease in median from baseline) was observed out to mo 12, although the number of pts studied is too small (n = 5 for uNTX and 4 for sCTX) to draw significant conclusions at this time. Pt accrual continues. Conclusions: A single dose of ZOL significantly suppressed bone resorption markers for at least 6 mo in pts receiving an adjuvant AI. It is not necessary to administer ZOL more frequently to prevent AIBL. These data suggest that ZOL administered every 6 mo is sufficient to prevent AIBL in this population. Further study will define whether this suppression of bone resorption markers continues for longer periods of time.

[Table: see text]
Lymphorrea incidences after modified radical mastectomy with auto cut versus spray mode electro coagulation
Authors: Stäcker S. , Thill M. , Röder K. , Diedrich K. , Fischer D.
Published: August 2020

e11571

Background: Lymphorrea is one of the most common side effects subsequent to mastectomy. It is a predicting factor for seroma, which are usually painless; however, lymphorrea is also linked to wound infection, wound healing complications and lymphedema. Electrocautery is a significant risk factor for lymphorrea and seroma. Two electrocautery methods—auto cut and spray mode electro coagulation—were compared in this prospective randomized study. Methods: 68 patients with operable breast cancer intended for modified radical mastectomy with axillary lymph node dissection or sentinel node biopsy were randomized into two groups by their date of birth. The patients in the first group were operated by using high frequency coagulation with auto cut, the members of the second group in spray mode. All wounds were drained by two self-regulating suction drainages. The drainages were removed as soon as the drain volume decreased to less than 30 ml/24 hours. Results: The mean drain volume amounted to 276 ml (range 20- 1,200 ml) in the auto cut group and 546 ml (range 100 -1,600ml) in the spray mode group. This difference is highly significant (significance level <0.01, t= -2.9987; p=0.003896). The incidence of seroma formation was 5% in the auto cut group and 23.5% in the spray mode group. Patients who were treated with spray mode electrocautery in average had to be hospitalized two days longer. Conclusions: The lower need for instrument changes makes the spray mode electro coagulation more comfortable for the surgeon. Nonetheless the conventional electrocautery should be preferred to operate radical mastectomy in order to decrease the morbidity risk for patients.

No significant financial relationships to disclose.
Radiotherapy for breast cancer: Can the heart be protected with respiratory gating in patients with left-sided breast cancer?
Authors: Von Briel C.
Published: August 2020

e11572

Background: Because there are hints for an increased risk of cardiovascular diseases after radiotherapy of the left chest wall the dose to the heart should be reduced as far as possible. With respiratory gating technique irradiation can be restricted only in the inspiratory plateau phase and so the distance between heart and chest wall will be increased. As a result the dose to the heart, in particular to the anterior wall, can be reduced. We investigated in all patients with left sided breast cancer dose reduction to the heart when treated only in the inspiration phase compared with not gated treatments. Methods: Between September 2004 and March 2008 97 pat. with left sided breast cancer were treated with respiratory gating technique. We irradiate only in maximum inspiration with a range between 10% - 20%. For the investigation of real dose reduction to the heart we performed for all of these patients a normal and a respiratory gated planning CT. DVH for the entire heart and the anterior wall of the left ventricle wall were calculated. 96/97 of these pat. were treated with 2 Gy single dose to a total dose of 50 Gy to the entire left breast, 1 pat with 1.8 Gy single dose to 50.4 Gy. 72 pat. had an additional boost of 10 Gy. The PTV was in 75 pat. after breast conserving surgery the left breast, in 22 pat. after mastectomy the left chest wall. Results: To median dose to the anterior ventricle wall was 2.3 Gy (0.5 Gy - 7.9 Gy) without and 1.3 Gy (0.1 Gy - 5.6 Gy) with respiratory gating (p = 0.001). The median maximal dose to the anterior wall was 45.2 Gy (5.5 Gy - 52.3 Gy) without and 4.5 Gy (0.9Gy - 50.6 Gy) with respiratory gating (p = 0.000). In 72 pat. the maximal dose reduction to the anterior wall was > 20 Gy. In this pat. the mean movement of the diaphragma was 26mm against 16 mm for pat. with dose reduction <20 Gy (p = 0.000). The mean up and down movements ot the chest wall were 7.9mm (>20 Gy) and 5.2 mm (>20Gy) (p = 0.05). Conclusions: Respiratory gating and irradiation only in the inspiratory phase reduce radiation dose to the heart and especially to the anterior wall of the heart significantly. Pat breathing with diaphragm seems to profite mostly from treating only in inspiratory phase.

No significant financial relationships to disclose.
Survival in patients with locally advanced breast cancer after neoadjuvant docetaxel (T), carboplatin (C), and trastuzumab (H)
Authors: Chang H. R. , Prati R. , Gornbein J. A. , Chung D. , Glaspy J. A.
Published: August 2020

e11573

Background: Neoadjuvant chemotherapy (NAC) has been widely used in patients with LABC. Although survival rates after neoadjuvant and adjuvant therapy are similar, NAC was shown to increase lumpectomy surgery and allow in vivo evaluation of treatment response. It is thought that pathologic complete response (pCR) after NAC by itself or together with other factors could predict overall survival (OS) and/or relapse free survival (RFS). Methods: Seventy-one of the 74 enrolled patients (mean tumor size=7.7cm) were analyzed. All patients received 4 cycles of T (75mg/m2) and C (AUC=6) before and after surgery. HER2+ patients were randomized to receive either TCH or TC preoperatively; both received 1 year of H. Tumor size and nodal status were estimated clinically at baseline and pathologically after surgery. Bi & multivariate analyses were performed on pCR, clinical and pathologic characteristics to predict OS and RFS. Hazard ratios (HR) are reported. Results: The median follow up was 2.0 years with 8 deaths and 9 recurrences. Nineteen (26.8%) had pCR. Kaplan-Meier RFS was 82.0% & 54.2% and OS was 88.9% vs 70.6% at 3 years follow up for pCR & non-pCR respectively. In the bivariate analysis, pCR (HR=0.32, p=0.114), lower tumor stage (p=0.097) and negative LN (p=0.0695) trended a favorable RFS. Lower tumor stage (p=0.032), negative LN (p=0.029) and lumpectomy surgery (p=0.023) were associated with better OS. In multivariate analysis, inflammatory breast cancer (p=0.041) and triple negative breast cancer-TNBC (p=0.044) predicted poor OS. Conclusions: With few deaths/recurrences we were unable to conclusively identify predictors for OS or RFS. Inflammatory and TNBC remain poor prognosticators for OS and RFS. pCR was a suggestive predictor (HR<1) but not statistically significant probably due to low sample size and high number of pCR cases that were TNBC.

[Table: see text]
Comparison of serum HER-2/neu between trastuzumab-based regimen and anthyracycline-based regimen during neoadjuvant chemotherapy in advanced primary breast cancer
Authors: Lee J. , Min W. , Kim S. , Son B.
Published: August 2020

e11582

Background: Serum Her-2/neu has been known as molecular surrogating marker of predicting treatment response in Her-2 positive breast cancer. We compare the change of serum Her-2/neu during neoadjuvant chemotherapy between trastuzumab(H) and anthyracyline(A) based treatment. Methods: All breast cancers were tested by immunohistochemical stain and FISH for Her-2/neu before treatment. Serum Her-2/neu was twice measured by Chemiluminescence immunoassay(ADVIA centaurTMsystem) before neoadjuvant chemotherapy and before operation. The cutoff value was 10.2 mg/ml according to previous study. Pathologic complete response (pCR) was considered as no residual tumor or remnant ductal carcinoma in situ, partial response (PR) was less than 50% decrease in maximal diameter in pathologic tumor size. Results: Serum Her-2/neu of trastuzumab group was more decreased than of anthyracyline group (H; 12.9 ± 14.5 ng/mL vs. A; 2.2 ± 1.2 ng/mL, p=0.024). In trastuzumab group, pCR was relatively correlated with decrease of serum Her-2/neu (PR: 0.8 ± 0.84 ng/ml vs. pCR: 21.1 ± 13.2 ng/ml, p=0.08). Conclusions: A decrease in serum Her-2/neu levels during treatment was associated with pathologic response in patients receiving neoadjuvant chemotherapy, particularly, trastuzumab-based regimen. Serum Her-2/neu levels may serve to monitoring neoadjuvant therapy in Her-2/neu positive breast cancer.

No significant financial relationships to disclose.
Effect of neoadjuvant chemotherapy on oestrogen, progesterone, and HER-2 receptor expression in breast cancer
Authors: Sircar T. , Chaudhri S. , Francis A.
Published: August 2020

e11588

Background: Neoadjuvant chemotherapy(NC) is used in treating locally advanced operable breast cancer. After surgery, further adjuvant treatment is offered based on the estrogen receptor (ER), progesterone receptor (PR) and HER2 status. Treatment post operatively can be based on the ER/PR/HER2 status of the core biopsy taken preoperatively. It is not a usual practice in the United Kingdom to repeat these markers on the surgical specimen. However a change in ER/PR or HER2 status following NC could have a profound effect on adjuvant treatment with the real possibility of appropriate therapy being unknowingly withheld. The aim of our study was to determine the percentage of patients whose ER/PR, HER2 receptor expression change with NC and if these changes lead to change in their adjuvant treatment. Methods: This is a retrospective study of 32 patients with locally advanced breast cancer who had NC followed by breast conservation surgery or mastectomy. Quick score (Q score) for ER/PR and the HER2 expression was measured both from the preoperative core biopsy and from the excision specimen following NC. Results: After NC, 5 patients had complete pathological response and 2 patients had residual ductal carcinoma in situ. 25(78%) patients had residual invasive malignancy. Quantitative change in Q scores for ER and PR was seen in 6 patients(24%) and 10 patients (40%) respectively. ER status changed from positive to negative in 1 patient(4%). PR status changed from positive to negative in 4 patients(16%) and from negative to positive in one patient (4%). One patient(4%) changed from HER2 negative to HER2 positive after NC. Conclusions: Change in 1 patient(4%) from HER2 negative to HER2 positive lead to change in adjuvant treatment who would have otherwise not received transzutumab.Q scores changed in 24% and 40% for ER and PR respectively, however, no change was observed with regards to hormonal adjuvant treatment. A study with a bigger cohort might address this issue. We suggest that ER/PR/HER2 status should routinely be checked in both core biopsy sample and also resection specimen.

No significant financial relationships to disclose.
Nanoparticle-targeted delivery of nonanticoagulant heparin and doxorubicin in doxorubicin-resistant breast cancer
Authors: Bharali D. J. , Yalcin M. , Dier U. , Mousa S. , Mousa S. , Hanko C. , Phillips P. , Mousa S. A.
Published: August 2020

e11599

Background: In comparison to low molecular weight heparin (LMWH), non-anticoagulant heparin (NACH), originally developed in our laboratory, has minimal effects on hemostasis. Encapsulation of chemotherapeutic agents and NACH in biodegradable nanoparticles has tremendous potential in improving survival among the breast cancer patients. Furthermore, custom-made nanoparticles with a targeted moiety on the surface would enable us to increase the efficacy and decrease the adverse effects of doxorubicin. Methods: PLGA-PEG nanoparticles co-encapsulating NACH and doxorubicin were synthesized by double emulsion solvent evaporation method. The in vitro efficacy of these nanoparticles was examined in MCF-7 doxorubicin resistant (MCF-7R) cells using MTT cell viability assay. Confocal microscopy was used to examine the uptake of αvβ3 antibody conjugated nanoparticles in human dermal microvascular endothelial cells (HDMEC), which are known to over express αvβ3 integrins. Results: Size measurement by DLS revealed that these nanoparticles co-encapsulating doxorubicin and heparins to be 200–300 nm in size. Data from the MTT assays in MCF-7R cells showed synergy between NACH and doxorubicin when encapsulated in PLGA-PEG nanoparticles. Confocal imaging in HDMEC cells indicates that these nanoparticles have the potential to be used for site specific delivery to the tumor neovascularization. In vivo data in nude mice xenograft (MCF-7R) are shown in the table below (doses of doxorubicin and NACH injected subcutaneously were 0.625 mg/kg and 2.5 mg/kg body weight, respectively). Significant decrease in tumor weight was observed in the mice xenograft, when treated with αvβ3 conjugated nanoparticles co-encapsulating doxorubcin or to greater extent doxorubicin and NACH compares to its non encapsulated counterparts. Conclusions: These data indicated distinct improvement in the anti-tumor efficacy using αvβ3site directed delivery doxorubicin and NACH encapsulted in PLGA-PEG nanoparticles.

[Table: see text]

No significant financial relationships to disclose.
A family-based approach to primary prevention of breast cancer
Authors: Olopade Olufunmilayo
Published: August 2020

s2

We are currently focusing on the interplay of genes and environment in the development of estrogen receptor (ER)-negative breast cancer, which is aggressive, less responsive to treatment, and more likely to strike young women and those of African ancestry. Unfortunately, there are no strategies to prevent ER-negative breast cancer and research is urgently needed. Nevertheless, we have made progress in understanding genetic risk factors for some familial forms of breast cancer, which is reason enough to adopt family-based interventions for breast cancer prevention, especially among families with identifiable highly penetrant mutations in breast cancer susceptibility genes. In 1997, I chaired the ASCO Task Force on Cancer Genetics Education, charged to educate oncologists about the importance of genetics in clinical oncology practice. Since then, a growing body of evidence documents the benefits of preventive measures with minimal risk to women with identifiable highly penetrant mutations in BRCA1 and BRCA2 genes. Whereas other genes, such as TP53 in Li-Fraumeni Syndrome and PTEN in Cowden syndrome, contribute to a small fraction of hereditary breast cancer, mutations in these genes are rare. Germ-line mutations in BRCA1 or BRCA2 are strong predictors of breast and/or ovarian cancer development, and the contribution of these mutations to breast cancer risk within any specific population is a function of both their prevalence and penetrance. Mutation prevalence varies among ethnic groups and may be influenced by founder mutations as observed in Ashkenazi Jews and Icelanders. Although estimates of mutation prevalence and penetrance rates are inconsistent and occasionally controversial, understanding them is critical for providing individualized risk assessment. Although the contribution of other genes to early onset and familial breast cancer needs clarification, genetic testing for BRCA1 and BRCA2 has become standard of care and an important component of personalized breast cancer risk assessment and prevention.
Physical Activity, Genetic Susceptibility, and the Risk of Latent Autoimmune Diabetes in Adults and Type 2 Diabetes
Authors: Hjort Rebecka , Ahlqvist Emma , Andersson Tomas , Alfredsson Lars , Carlsson Per-Ola , Grill Valdemar , Groop Leif , Martinell Mats , Sørgjerd Elin Pettersen , Tuomi Tiinamaija , Åsvold Bjørn Olav , Carlsson Sofia
Published: August 2020

Purpose

Physical activity (PA) has been linked to a reduced risk of type 2 diabetes by reducing weight and improving insulin sensitivity. We investigated whether PA is associated with a lower incidence of latent autoimmune diabetes in adults (LADA) and whether the association is modified by genotypes of human leukocyte antigen (HLA), transcription factor 7-like 2 (TCF7L2)-rs7903146, or the fat mass and obesity-associated gene, FTO-rs9939609.

Methods

We combined data from a Swedish case-control study and a Norwegian prospective study including 621 incident cases of LADA and 3596 cases of type 2 diabetes. We estimated adjusted pooled relative risks (RRs) and 95% CI of diabetes in relation to high (≥ 30 minutes of moderate activity 3 times/week) self-reported leisure time PA, compared to sedentariness.

Results

High PA was associated with a reduced risk of LADA (RR 0.61; CI, 0.43-0.86), which was attenuated after adjustment for body mass index (BMI) (RR 0.90; CI, 0.63-1.29). The reduced risk applied only to noncarriers of HLA-DQB1 and -DRB1 (RR 0.49; CI, 0.33-0.72), TCF7L2 (RR 0.62; CI, 0.45-0.87), and FTO (RR 0.51; CI, 0.32-0.79) risk genotypes. Adjustment for BMI attenuated but did not eliminate these associations. For type 2 diabetes, there was an inverse association with PA (RR 0.49; CI, 0.42-0.56), irrespective of genotype.

Main Conclusions

Our findings indicate that high PA is associated with a reduced risk of LADA in individuals without genetic susceptibility.