bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinicopathologic factors associated with involved margins following breast conserving surgery for invasive lobular carcinoma (ILC)
Authors: Silberfein E. J. , Hunt K. K. , Broglio K. , Shen J. , Sahin A. , Le-Petross H. , Oh J. , Litton J. , Hwang R. F. , Mittendorf E. A. 
Published: August 2020

e11528 Background: ILC is characterized by a diffusely infiltrative growth pattern making it difficult to accurately assess disease extent prior to surgical resection. This has resulted in difficulty obtaining negative margins at the time of breast conserving surgery. We evaluated patients undergoing surgery for ILC to determine if there were specific clinicopathologic factors influencing the ability to obtain negative margins. Methods: We identified 211 patients with ILC treated between 1994 and 2004. Clinical data including radiographic appearance, biopsy method, initial surgical procedure (segmental vs. total mastectomy), and use of neoadjuvant chemotherapy were noted. Pathologic data included margin status (negative (>2mm), close (0–2mm), or positive), multifocality, multicentricity, ILC subtype, grade, associated LCIS or DCIS, hormone receptor status and HER2 status. Factors associated with close or positive margins were determined using univariate and multivariate analyses. Subset analysis was performed on patients whose initial surgery was segmental mastectomy. Results: 110 (52%) patients underwent total mastectomy and 101 (48%) underwent segmental mastectomy as their initial procedure. For patients undergoing segmental mastectomy, 50 (50%) had positive or close margins requiring re-excision. Patients with close or positive margins were more likely to have distortion on ultrasound (vs. mass, p=.05), to have undergone an excisional biopsy (vs. core or FNA, p=.008), and to have associated DCIS (p=.02). On multivariate analysis, only biopsy method retained significance (p = .006). Having an excisional biopsy for diagnosis was also associated with need for multiple surgeries (p < .0001). Breast conserving surgery was ultimately successful in 86 patients (85%). Conclusions: The majority of patients with ILC can undergo successful breast conserving surgery. Patients with distortion rather than a mass on imaging and those with DCIS are more likely to have close or positive margins. Diagnosis by excisional biopsy makes subsequent imaging less reliable and results in the need for multiple surgeries to ensure adequate excision. No significant financial relationships to disclose.
A phase II trial of image-guided radiofrequency ablation of small breast carcinomas: Results of a multicenter study in Japan
Authors: Kinoshita T. , Yamamoto N. , Fujisawa T. , Masuda N. , Hojo T. , Aogi K. , Seki K. , Tsuda H. 
Published: August 2020

e11535 Background: Locally ablative therapy of early breast cancer represents the next frontier in the evolution of minimally invasive breast conservative therapy. We performed this Phase II trial to determine the efficacy and safety of Radiofrequency (RF) ablation of small localized invasive breast carcinomas as a multicenter study in Japan. Methods: Thirty-nine patients with core-biopsy proven invasive breast cancer, T<2 cm in diameter on ultrasound and MRI were enrolled in this trial. Under ultrasound guidance, the tumor and at least a 5mm margin of surrounding breast tissue were ablated with saline- cooled RF electrode followed by surgical resection. Pathologic and immunohistochemical stains were preformed to assess tumor viability. Results: Thirty-seven patients completed the treatment. The mean tumor size on ultrasound was 1.50 cm. The mean ablation time was 12 minutes using mean power of 80.0 watts. During ablation, the tumor became progressively echogenic that correspond with the region of sever electrocautery injury at pathologic examination. Of the 37 treated patients, H&E and NADPH viability staining was available for 27 patients and in 25 (92.5%), there was no evidence of viable cancer cells. H&E and or ssDNA staining were available for another 10 patients. In total, complete thermal injury to the target lesions was recognized in 33 of 37 treated patients (89.2%). No sever adverse effect on the skin and chest wall were noted. Conclusions: RF ablation is a promising minimally invasive treatment of small breast carcinomas, as it can achieve effective cell killing with a low complication rate. We are planning a multicenter observation study for RF ablation of small breast carcinomas. No significant financial relationships to disclose.
Prognostic value of decrease on blood lymphocytes in breast cancer patients undergoing primary chemotherapy
Authors: Vicente A. , García-Martínez E. , Gonzalez-Billalabeitia E. , Zafra M. , Castilla-Llorente C. , García-García T. , Macías J. , García-Garre E. , Vicente V. , Ayala de la Peña F. 
Published: August 2020

e11537 Background: There is evidence about chemotherapy creating a better tumor control by inmune system. Neoadjuvant treatment is an excellent situation to study tumor behaviour. The aim of this study is to determine whether decreases on blood lymphocytes (BL) absolute number have a prognostic significance on women with breast cancer receiving primary chemotherapy (PC). Methods: A retrospective analysis was performed of 105 breast cancer patients who underwent PC. Doxorubicin (60mg/m2q3w) - Cyclophosphamide (600mg/m2q3w) x4c followed docetaxel (100 mg/m2q3w) x4c was PC regimen in 73,4%. We collected data on BL before the first cycle of PC (basal BL), just before second doxorubicin- cyclophosphamide (AC) cycle (BLa), and three weeks from the end of PC (BLb). The median decrease (MD) in blood lymphocytes has been calculated: MDa = BLa - basal BL; MDb = BLb - basal BL. Results: Of 105 patients with breast cancer 16,2% were clinical stage IIA, 19% IIB, 30,5% IIIA, 14,3% IIIB, 15,2% IIIC. The mean age was 50 years. The complete pathologic response (pCR) rate was 14,9% in primary tumor, and 37,9% in axillary nodes. The median follow up is 25 months (mo). Overall survival: (OS) 25,3 mo (range 4 - 89.3). Disease-free survival: (DFS) 21,8 mo (range 5 - 80.3). The median decrease on blood lymphocytes is MDa=300 106/L(2400, -1000), MDb=700 106/L(3900, -400). A decrease on BL just before second AC cycle (> MDa=300 106/L) is correlated with worse DFS, in univariant and multivariant analysis (HR =4.022; 95% CI:1.105–14.63; p 0.035 at first; HR=5.36; 95% CI:1.1–25.82; p 0.037 at former). Patients with BL decrease three weeks after finishing PC (>MDb=700 106/L) have worse DFS in univariant as multivariant analysis (HR=5.9 95% CI:1.2–27.5; p0.022 at first; HR=9.7 95% CI:1.11- 85.07; p 0.04 at former). We have not found significant differences in OS. Conclusions: A decrease on blood lymphocyte number in women with breast cancer undergoing primary chemotherapy is correlated with worse DFS. No significant financial relationships to disclose.
Locally advanced breast cancer patients with negative pathological lymph node status after neoadjuvant chemotherapy and conservative surgery: Is lymph node irradiation necessary?
Authors: Daveau C. , Stevens D. , Berges O. , Zilberman S. , Gardner M. , Villette S. , Brain E. , Lasry S. , Labib A. , Le Scodan R. 
Published: August 2020

e11539 Background: The increased use of neoadjuvant chemotherapy (CT) in breast cancer (BC) management has raised new questions regarding the optimal locoregional treatment. The aim of this retrospective study was to compare the outcomes of BC patients (pts) with pathological N0 status (pN0) following primary CT and conservative surgery who received breast radiotherapy with or without lymph node irradiation. Methods: Between 1990 and 2004, 1054 patients received preoperative CT for locally advanced BC. Data from 248 pts (23.5%) with clinical N0 (164 pts) or N1-N2 (84 pts) lymph node status at diagnosis and pN0 status after primary CT were studied. Among them, 93 pts (37.5%) received breast irradiation alone and 155 pts (62.5%) underwent locoregional irradiation. Outcome was assessed in relation to lymph node recurrence, disease-free survival (DFS) and overall survival (OS). Results: Both groups were comparable in terms of baseline characteristics. With a median follow-up of 88 months, 3 pts experienced nodal recurrence in the breast irradiation alone group compared with 2 pts in the locoregional irradiation group (p>.05). Among the 164 N0 pN0 pts, the 5-year DFS and OS rates were respectively 84% and 89% vs 84% and 95%, according to whether they received (n=87) or not (n=77) lymph node irradiation(p>.05). Among the 84 N1-N2 pN0 pts, same outcome values did not show any significant difference according to group of treatment: 72% and 88% in 68 pts treated with locoregional irradiation vs 81% and 81% in 16 pts treated with breast irradiation alone (p>.05). Conclusions: Our results suggest that breast irradiation alone is not associated with a higher risk of regional recurrence in locally advanced BC pts with pN0 status after neoadjuvant chemotherapy. Whether this allows the omission of lymph node irradiation for such strategy should be addressed prospectively. No significant financial relationships to disclose.
Pathological characteristics, distant recurrence rates, and survival outcomes of breast cancer with triple-negative phenotype
Authors: Lee C. K. , Choo E. , Lewis C. R. 
Published: August 2020

e11554 Background: Breast cancer is a heterogeneous disease encompassing entities with distinct biological characteristics and clinical course. Triple-negative disease (TND) is clinically aggressive disease with limited effective therapy. We compare the clinico- pathologic characteristics, recurrence and survival rates of patients with TND and non-TND. Methods: The POWH Cancer Centre breast cancer database was retrospectively reviewed from January 1995 to December 2005. 1254 eligible women with breast cancer undergoing definitive primary breast surgery were identified. TND was defined as ER-, PR- and HER2 0 or 1+ by IHC and / or florescent in- situ hybridization (FISH) negative. Non-TND was defined as either ER+ and / or PR+ and/or HER2+. Further comparisons of survival outcomes were analyzed in a subgroup of 785 patients subdivided into three groups: ER+ and/or PR+ and HER2-, HER2+ and TND. Results: There were 135 patients (10.8%) with TND. TND tumours were characterized by larger size (p=0.02), histological grade 3 (p<0.001), presence of lymphovascular invasion (p=0.03), and less likely to be diagnosed by screening mammography (p<0.001) when compared with non-TND. Amongst those developing distant metastases, the median time to recurrence was 16 months for TND compared to 35 months in non-TND. There was a trend in visceral metastases for TND as compared to non-TND (OR=1.86, p=0.06). The adjusted rates for distant recurrence (HR=3.55, p=0.006), and death (HR=3.48, p=0.01) were significantly higher for TND when compared with non-TND only for first two years after diagnosis. Beyond the two years, there was no difference in distant recurrence and overall survival. Majority of the patients did not receive adjuvant anti-HER2 therapy during the study period. When compared to ER+ and/or PR+ and HER2- cohort, the survival rate was significantly poorer for TND (HR=2.66, p<0.001) but non-significant for HER2+ (1.61, p=0.1). Conclusions: Poorer histopathological phenotypes are observed in TND. Patients with TND have higher rates of developing distant metastases. Survival rates are also poorer in TND patients. The risks of distant recurrence and death are not proportional across time and these risks are strongly time-dependent. No significant financial relationships to disclose.
Phase I study of apoptosis gene modulation with oblimersen within preoperative chemotherapy in patients with primary breast cancer
Authors: Rom J. , von Minckwitz G. , Marme F. , Sievert M. , Kozian D. , Schuetz F. , Scharf A. , Kaufmann M. , Sohn C. , Schneeweiss A. 
Published: August 2020

e11576 Background: The expression of the Bcl-2 protein confers resistance to chemotherapy mediated apoptotic signals in patients with breast cancer. The development of chemo sensitizing drugs may result in new treatment options. We investigated the effects of Bcl-2 down-regulation by the Bcl-2 antisense oligodeoxynucleotide oblimersen in breast tumor biopsies. Oblimersen targets Bcl-2 mRNA, thereby down regulates Bcl-2 protein translation, and enhances the antitumor effects of sub therapeutic doses of docetaxel. Methods: Within a phase I trial we administered escalating doses of oblimersen (3/5/7mg/kg/day) as continuous infusion on day 1–7 in combination with standard dosed docetaxel, doxorubicin, cyclophosphamide (TAC) on day 5 as preoperative chemotherapy in 28 patients with T2–4 breast cancers. Effects of oblimersen were evaluated in tumor biopsies and peripheral blood mononuclear cells (PBMCs) 4 days after start of oblimersen continuous infusion and before TAC treatment by quantitative microfluidic real-time polymerase chain reaction (RT-PCR). Read-outs consisted in measurement of Bcl-2 mRNA modulations and of 18 other putative predictive markers. Results: Two out of 13 patients showed a diminution of Bcl-2 transcripts after 4 days of treatment with oblimersen 5 mg/kg/day. PBMCs could not be evaluated as a surrogate tissue, because no qualified RNA could be isolated. Conclusions: Nevertheless, we demonstrated the feasibility to process clinical samples and to obtain good quality RNA from tumor biopsies, and indicated the potential of oblimersen to lower Bcl-2 mRNA in breast cancer. No significant financial relationships to disclose.
Management of side effects of aromatase inhibitors (AIs) during adjuvant therapy for postmenopausal women with HR+ breast cancer: Analysis of French practices
Authors: Guastalla J. P. , Belkacemi Y. , Cutuli B. , Dalivoust P. , Dohollou N. , Hardy Bessard A. , Salmon R. , Delozier T. 
Published: August 2020

e11593 Background: Aromatase inhibitors (AIs) are widely used as adjuvant therapy for HR+ breast cancer. Most frequently reported side effects are joint pain, osteoporosis and lipid disorders. Our aim was to describe how physicians in their clinical practice manage these side effects at initiation of treatment and during follow-up. Methods: Multicentric survey conducted in October 2008 by Internet among a sample of 293 physicians specialized in breast cancer management prescribing adjuvant AIs in post-menopausal women with HR+ breast cancer Results: At initiation of AI treatment, 97 % of the physicians interviewed declared informing their patients of the possible occurrence of joint pain; corresponding figures were 81 % for the increased risk of osteoporotic fractures, 66 % for lipid disorders, 59 % for asthenia, and only 16% for cognitive disorders. At initiation, 71% of the physicians assess fracture history, 83 % prescribe BMD, and 60 % lipid tests. Co-prescription of drugs in association with AIs from the onset of treatment is uncommon (24% of physicians interviewed), vitamin D and calcium being the most frequent prescription (19%); prescription of bisphosphonates was less frequently declared (10%). During the course of treatment, 90% of physicians assess BMD at least once, 41% repeat BMD two years after and 41% adapt monitoring of BMD according to the initial result. Lipid tests are monitored every six months by 29% of physicians, and every year by 29%. In case of joint pain, the initial therapeutic management includes: prescription of an analgesic and/or an anti-inflammatory for 66% of physicians, change of AI for 28%; the switch for tamoxifene is mentioned by only 1%. As a second step in case of failure of the initial measures, adjuvant treatment is modified by 70 % of physicians: change of AI by 50 %, switch for tamoxifene by 20 %. Conclusions: The possible side effects of aromatase inhibitors are taken into account by physicians from the initiation of treatment. They perform themselves the monitoring of the patient during follow-up, including the search for side effects. Bone-joint adverse events are managed by oncologists while the care of lipid disorders is transferred to the primary care physician. No significant financial relationships to disclose.
Benefits of preoperative chemotherapy for operable breast cancer in the community hospital setting
Authors: Komenaka I. K. , Hibbard M. L. , Bouton M. E. 
Published: August 2020

e11594 Background: The benefits of preoperative chemotherapy (PC) for operable breast cancer have been demonstrated in prospective clinical trials. For palpable breast cancers, however, operative intervention remains the most common initial treatment. The benefits of PC for operable breast cancer were examined in a community hospital. Methods: Maricopa Medical Center is the safety net hospital in Arizona. A retrospective review was performed of all breast cancer patients from 2004 to 2008. All patients who were stage IIA - IIIA breast cancer patients were included. Outcomes of breast cancer were evaluated based on whether the patient underwent PC or adjuvant chemotherapy (AC). All patients in the PC group received anthracyclines and a taxane in their treatment. The Fisher's exact test and the Chi-square test were used to determine differences between the two populations. Unpaired t-test was used to compare means of the two populations. Results: During this period, 145 patients were treated. In the PC group, the clinical response rate was 81% and the pathologic complete response rate was 26%. Patients in the PC group underwent lumpectomy more often for T2 (73% vs. 40%, P = 0.01) and for T3 tumors (73% vs. 37%, P = 0.06). The positive margin rate was lower (14% vs.37%, P = 0.02) and the lumpectomy volume was smaller in the PC group compared to the AC group (132 cm3 vs. 245 cm3, P < 0.01). Despite similar demographics, compliance with chemotherapy was improved in the PC group (100% vs. 71%, P < 0.01). In addition, compliance was also improved for adjuvant radiation (97% vs. 70%, P < 0.01) and hormone therapy (100% vs. 76%, P = 0.01) in the PC group. Conclusions: Preoperative chemotherapy improved compliance with chemotherapy. This could represent a significant benefit over AC in populations where compliance with chemotherapy recommendations is not ideal. Improvements in surgical outcomes were also seen in patients who received preoperative chemotherapy in the community hospital setting. No significant financial relationships to disclose.
Pharmacogenomics of childhood acute lymphoblastic leukemia (ALL)
Authors: Evans William E. , Relling Mary V. 
Published: August 2020

s3 Childhood ALL is a model for drug-responsive cancer: it is successfully cured with medications in 85%–90% of patients, but relapse remains unacceptably high for some subgroups, and therapy is complicated by the occurrence of adverse effects. Human germ-line genomic variability is common, with ∼1 in every 300 nucleotides (at least 10 million polymorphisms among humans) differing among individuals. Identifying the important genomic variants for purposes of optimizing anticancer therapy is the current challenge in cancer pharmacogenomics. Our research has been focused on elucidating the germ-line and acquired genomic variations that influence the effectiveness of and toxicity to chemotherapy regimens, with the long-term goal of individualizing therapy based on genetics to maximize cure and minimize toxicity. We and our many collaborators are pursuing candidate gene and whole genome approaches to this end, studying children enrolled on front-line ALL protocols at St. Jude and through the Children's Oncology Group. Based on these studies, candidate gene genotyping has been already incorporated into the treatment of childhood ALL and integrated with electronic medical records at St. Jude to optimize use of a few medications. This includes genetic testing for TPMT to adjust thiopurine doses and CYP2D6 to optimize use of codeine for vincristine neuropathy. Additional genotyping is conducted on a research basis and has identified SLCO1B1 as important for methotrexate disposition, IL15 as related to antileukemic drug response, ITPA as important for thiopurine toxicity, and a genomic basis to race-related differences in relapse risk. Gene expression analyses of ALL cells show expression signatures associated with resistance to chemotherapy and relapse. The principles and techniques of pharmacogenomics also have implications for adult malignancies. Because prognostic factors (including genomic variations) depend upon the details of therapy, collection of blood (for germ-line DNA) should be part of every cancer clinical trial to advance genomic research.
Reproduction Function in Male Patients With Bardet Biedl Syndrome
Authors: Koscinski Isabelle , Mark Manuel , Messaddeq Nadia , Braun Jean Jacques , Celebi Catherine , Muller Jean , Zinetti-Bertschy Anna , Goetz Nathalie , Dollfus Hélène , Rossignol Sylvie 
Published: August 2020

AbstractPurposeBardet-Biedl syndrome (BBS) is a ciliopathy with a wide spectrum of symptoms due to primary cilia dysfunction, including genitourinary developmental anomalies as well as impaired reproduction, particularly in males. Primary cilia are known to be required at the following steps of reproduction function: (i) genitourinary organogenesis, (ii) in fetal firing of hypothalamo-pituitary axe, (iii) sperm flagellum structure, and (iv) first zygotic mitosis conducted by proximal sperm centriole. BBS phenotype is not fully understood.MethodsThis study explored all steps of reproduction in 11 French male patients with identified BBS mutations.ResultsBBS patients frequently presented with genitourinary malformations, such as cryptorchidism (5/11), short scrotum (5/8), and micropenis (5/8), but unexpectedly, with normal testis size (7/8). Ultrasonography highlighted epididymal cysts or agenesis of one seminal vesicle in some cases. Sexual hormones levels were normal in all patients except one. Sperm numeration was normal in 8 out of the 10 obtained samples. Five to 45% of sperm presented a progressive motility. Electron microscopy analysis of spermatozoa did not reveal any homogeneous abnormality. Moreover, a psychological approach pointed to a decreased self-confidence linked to blindness and obesity explaining why so few BBS patients express a child wish.ConclusionsPrimary cilia dysfunction in BBS impacts the embryology of the male genital tract, especially epididymis, penis, and scrotum through an insufficient fetal androgen production. However, in adults, sperm structure does not seem to be impacted. These results should be confirmed in a greater BBS patient cohort, focusing on fertility.