bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulating tumor cells in metastatic breast cancer: Are they a strong and independent predictor of poor progression-free and overall survival?
Authors: Wallwiener Markus , Schneeweiss Andreas , Baccelli Irene , Riethdorf Sabine , Pantel Klaus , Marme Frederik , Schott Sarah , Trumpp Andreas , Taran Florin-Andrei , Hahn Markus , Schuetz Florian , Mueller Volkmar , Rack Brigitte Kathrin , Sohn Christof , Solomayer Erich-Franz , Janni Wolfgang , Hartkopf Andreas D. , Fehm Tanja N. ,   DETECT Study Group
Published: March 2020

1090 Background: Circulating tumor cells (CTCs) are detected in 30–60% of patients with metastatic breast cancer (MBC). The aim of this prospective multi-center study was to evaluate the impact of CTCs on progression free survival (PFS) and overall survival (OS) in a large cohort of 486 patients with progressive metastatic disease. Methods: CTC levels were determined for 486 patients at nine German University Breast Cancer Centers between 12/2007 and 06/2011. Samples of 7.5 ml blood were taken before initiation of a new line of therapy and CTCs were enumerated using the CellSearch System (Veridex LLC, Raritan, NJ, USA). CTC status (≥ 5 CTCs vs. < 5 CTCs per 7.5 ml blood) was assessed as a prognostic factor for PFS and OS using univariate (log-rank test) and multivariate (Cox regression model) statistical methods. Results: CTCs were detected in 205/486 (42%) patients. The median CTC count was 2 (range 0–6380) per 7.5 ml blood. The presence of ≥ 5 CTCs/7.5 ml blood did not correlate with any of the established clinicopathological factors except estrogen receptor status (p = 0.038). PFS and OS were both significantly shorter in patients with ≥ 5 CTCs/7.5 ml than in those with < 5 CTCs/7.5 ml blood. PFS was 5.0 [95% CI 4.1–5.8] months vs.7.6 [95% CI 5.9–9.3] months, p < 0.001; and OS was 15.0 [95% CI 13.5–16.5] months vs. 18.3 [95% CI 17.4–19.2] months, p < 0.001. In the multivariate analysis considering all clinicopathological factors and the CTC status, independent predictors of reduced OS and PFS were site of metastasis (visceral vs. bone), number of metastatic sites (multiple sites vs. one site), and CTC status. Conclusions: The presence of ≥ 5 CTCs/7.5 ml blood is a strong and independent predictor of poor PFS and OS in patients with MBC.
The relative value of anti-Müllerian hormone to predict premature menopause in patients receiving adjuvant chemotherapy for breast cancer: Results from the OPTION trial.
Authors: Leonard Robert C. F. , Adamson Douglas , Bertelli Gianfilippo , McLinden Michelle , Haiying Nan , Dunlop Joanna , Mansi Janine , Coleman Robert Edward , Thomas Gerry , Anderson Richard 
Published: March 2020

1094 Background: The OPTION trial in premenopausal women tested the ovarian protection effect of goserelin (G) given randomly before and during adjuvant chemotherapy for breast cancer. Methods: Using standard chemotherapy, women were randomised in 2 strata, under 40 yrs and over 40 yrs at diagnosis. 227 patients were recruited by end December 2009. 173 met the criteria for 1 year follow-up for this analysis; 140 patients of these had provided adequate data on menstrual bleeding; 87 patients were aged under 40 and 53 patients were aged over 40 at the time of chemotherapy. Cessation of menstruation during chemotherapy was defined as at least two consecutive cycles with no menstrual bleeding since the previous cycle and no return of menstrual bleeding prior to the final cycle of chemotherapy. Of those patients who had ceased periods during chemotherapy, those with no further menstrual bleeding at 12 months follow up were deemed to be menopausal. Patients were randomised to receive G or no G at start of chemotherapy. Primary endpoint was recovery of menses at 12 months from start of chemotherapy. AMH was measured in 117 women pre-treatment, and at 1 year after starting chemotherapy. Results: There were no differences in pretreatment AMH between control and goserelin-treated groups, thus further analyses were performed on all women grouped together. AMH was lower following chemotherapy (0.40±0.65 vs 1.38±1.82ng/ml; mean±SD; P<0.001)). Pre-treatment AMH was a significant predictor of post-treatment amenorrhoea (P=0.001). By multivariate logistic regression analysis with age and AMH, age remained significant (P=0.003) whereas AMH did not (P=0.07). Grouping pre-treatment and post-chemo AMH into quartiles showed that AMH became undetectable in 94% of women with lowest pre-treatment AMH vs 46.2% of women with the highest pretreatment AMH. We have previously demonstrated in a small cohort that pretreatment AMH can predict long-term (5 year) ovarian activity in women with breast cancer. Conclusions: The present data confirm the value of pretreatment AMH in assessing the likelihood of ongoing ovarian activity after chemotherapy for early breast cancer.
Neoadjuvant epirubicin, gemcitabine, and docetaxel for primary breast cancer: Survival and prognostic factors in two consecutive neoadjuvant phase I/II trials.
Authors: Marme Frederik , Bermejo Justo Lorenzo , Sinn Hans-Peter , Lichter Peter , Schuetz Florian , Rom Joachim , Aigner Julia , Sohn Christof , Schneeweiss Andreas 
Published: March 2020

1096 Background: We previously reported primary end points of two consecutive phase I/II trials which evaluated two different schedules of neoadjuvant gemcitabine (G), epirubicin (E) and docetaxel (Doc) for primary breast cancer. Here we report mature survival data and evaluate prognostic factors for disease-free (DFS) and overall survival (OS). Methods: 151 patients were treated in two phase I/II trials of G, E and Doc as neoadjuvant chemotherapy (NAC) for T2-4 N0-2 M0 PBC between Feb. ’02 and Dec. ’04. Patients were treated with six cycles of GEDoc (G 800mg/m2 day (d) 1+8, E 60-90mg/m2 d 1, Doc 60-75mg/m2 d 1 every three weeks) or five cycles of G 1250mg/m2 plus E 90-100mg/m2 every two weeks followed sequentially by four cycles of Doc 80-100mg/m2 every two weeks (GEsDoc). Pathologic complete response (pCR), clinical/pathological factors were correlated with DFS and OS. Results: There was no significant difference in DFS or OS between patients in the GEDoc and GEsDoc trial (DFS: Hazard ratio (HR) 1.13, p=0.67; OS: HR 1.06, p=0.88) with a 5-year DFS and OS of 72 vs 74% and 85 vs 86%, respectively. In an univariate analysis pCR unexpectedly was associated with a worse OS (HR 3.11; p= 0.007). HR for DFS showed a similar but non-significant trend (HR 1.78; p=0.1). Molecular subtypes (OS: HR [lum B] 3.17; [triple negative] 5.81; [HER2] 11.5; p=0.002), negative estrogen receptor (ER) status (OS: HR 3.14; p=0.002) and Ki-67 >20% (OS: HR 5.41; p=0.001) were all significantly associated with DFS and OS. The recently published CPS-EG score (Mittendorf 2011) was also significantly correlated with OS (p=0.006) and DFS (p=0.0006). In a multivariate analysis high Ki-67 was the only significant predictor of OS (HR 10.4; p=0.0026) whereas molecular subtype (p=0.05) and Ki-67 (p=0.04) were significantly associated with DFS. Conclusions: These results raise caution on the reliability of pCR as a single surrogate marker for survival in trials with small sample sizes. Our results emphazise the role of additional factors, esp. Ki-67 and subtypes. Integrative scores based on clinical and pathologic stage as well as tumor biology, might be more reliable predictors of survival.
SPIO-enhanced MR imaging for axillary staging to avoid sentinel node biopsy in patients with breast cancer.
Authors: Motomura Kazuyoshi , Izumi Tetsuta , Tateishi Souichirou , Noguchi Atsushi , Sumino Hiroshi , Kumatani Youji , Ishitobi Makoto , Koyama Hiroki , Horinouchi Takashi , Nakanishi Katsuyuki 
Published: March 2020

1103 Background: We previously demonstrated the usefulness of SPIO-enhanced MR imaging for the detection of metastases in sentinel nodes localized by computed tomography (CT) lymphography (CT-LG) in patients with breast cancer (Ann Surg Oncol, 2011). These techniques have evolved and we report our most recent results of axillary staging using them. Methods: Previously unreported 87 consecutive patients with breast cancer and clinically negative nodes were enrolled in this study. Sentinel nodes identified by CT-LG were evaluated prospectively using SPIO-enhanced MR imaging. A node was considered non-metastatic if it showed a homogenous low signal intensity and metastatic if the entire node or a focal area did not show a low signal intensity on MR imaging. Sentinel nodes located by CT-LG were removed, and imaging results and histopathological findings were compared. Results: The mean patient age was 54.9 years (range, 34-77). Sentinel nodes were identified by CT-LG and removed successfully in all patients. The mean number of sentinel nodes identified by CT-LG was 1.16 (range, 1-2). Twenty of 22 patients with positive sentinel nodes definitively diagnosed by pathology demonstrated metastases on SPIO-enhanced MR imaging. Fifty-eight of 65 patients with negative sentinel nodes definitively diagnosed by pathology were non-metastatic on imaging studies. The sensitivity, specificity and accuracy of MR imaging for the diagnosis of sentinel node metastases were 91%, 89%, and 90%, respectively. Two patients whose metastases were not detected had micrometastases. No adverse events were associated with either CT or MR imaging. Conclusions: SPIO-enhanced MR imaging provided accurate axillary staging, and therefore sentinel node biopsy may not be necessary for most patients with breast cancer.
Prognosis of early breast cancer patients treated with sentinel node biopsy: A prospective study from the Japanese society for sentinel node navigation surgery.
Authors: Imoto Shigeru , Aikou Takashi , Takei Hiroyuki , Wada Noriaki , Aihara Tomohiko , Inaba Masaaki , Motomura Kazuyoshi , Masuda Norikazu , Nagashima Takeshi , Jinno Hiromitsu , Miura Daishu , Saito Mari , Morita Satoshi , Sakamoto Junichi , Kitajima Masaki 
Published: March 2020

1106 Background: Sentinel node biopsy (SNB) is a new standard of care for clinically node-negative breast cancer patients. Our society conducted a prospective study on SNB for early breast cancer patients from Jul 2004 to Oct 2005 (UMIN000006126). A preliminary result regarding with success rates of multiple mapping methods and the adverse events was presented at the 2007 ASCO. We observed patient’s outcome for 5 years. Methods: Of the 1,411 cases registered, the objects were 1,107 cases excluding cases with bilateral breast cancer, non-invasive breast cancer, past history of other malignancy or failure of SNB and cases treated with primary chemotherapy or endocrine therapy. Adjuvant therapy and breast irradiation were decided by physician’s discretion and patient’s preference. To evaluate the risk of isolated tumor cells or micrometastases in sentinel lymph nodes (SLN), clinicopathological factors were analyzed using the Cox regression model. Results: After a median follow-up of 62 months, there were 85 recurrences and 14 deaths. 5-year Kaplan-Meire estimates for disease-free survival and overall survival (OS) were 92.6% and 97.5% in 848 cases with pN0(sn), 96.2% and 100% in 26 with pN0(i+)(sn), 89.3% and 95.3% in 68 with pN1mi(sn) and 82.8% and 92.0% in 165 with pN1(sn) or greater nodal metastases. No axillary lymph node dissection (ALND) was performed in 809 cases (95.4%), 18 (69.2%), 38 (55.9%), and 24 (14.5%), respectively. Regional node recurrence was found in 8 cases (0.9%), 0 (0%), 2 (2.9%) and 2 (1.2%), respectively. Univariate analysis showed that pN1(sn) or greater nodal metastases, pT2-4, nuclear grade 3, lymphovascular invasion, negative hormone receptor status, SNB followed by ALND, chemotherapy therapy were significant risk factors for OS. However, from multivariate analysis, nuclear grade 3, lymphovascular invasion and SNB followed by ALND were independent unfavorable prognostic factors (hazard ratio: 3.21, 2.61 and 3.93). Conclusions: Although a non-randomized prospective study, isolated tumor cells and micrometastases in SLN did not affect patient’s survival. ALND should be omitted for early breast patients with those metastases.
Role of breast surgery in T1-T3 breast cancer patients with synchronous bone metastases.
Authors: Botteri Edoardo , Munzone Elisabetta , Bagnardi Vincenzo , Intra Mattia , Rotmensz Nicole , Bazolli Barbara , Montanari Bruno , Aurilio Gaetano , Sciandivasci Angela , Esposito Angela , Pagani Gianmatteo , Adamoli Laura , Nole Franco , Goldhirsch Aron 
Published: March 2020

1115 Background: The role of breast surgery in advanced breast cancer (ABC) is controversial. The main potential advantage of removing the primary tumor is to eliminate the source of further metastatic spread. While previous studies addressed the question in very heterogeneous populations (e.g. patients with any local and distant extension), we have focused on a homogeneous series of ABC patients. Methods: From our institutional Tumor Registry we selected 191 consecutive women diagnosed between 2000 and 2008 with locally operable (T1-T3) ABC, synchronous bone metastases and no other distant sites involved. The progression free survival (PFS) was calculated from diagnosis to the date of progression, defined as either a new site of metastatic disease or clinical/radiographic evidence of increasing tumor burden at a previously known bone metastatic site. Results: Median age was 51 years and 92% of the women had an endocrine-responsive tumor. One-hundred and thirty patients out of 191 (68%) underwent surgery at the time of diagnosis, while 61 (32%) did not. Twenty-six of the operated patients (20%) had previously undergone neoadjuvant chemotherapy; 15 (12%) had positive or undetermined surgical margins. Operated and non-operated patients were similar with respect to age, tumor size, nodal involvement, estrogen and progesterone receptor status, HER2 overexpression and Ki-67, but differed in terms of number of bone metastatic sites: a single metastasis was detected in 34 (26%) operated and 7 (11%) non-operated cases (P=0.02). First-line treatment strategies with endocrine therapy, chemotherapy and Trastuzumab were similarly distributed between the two groups. The 5-year PFS was 22.0% and 10.4% in operated and non-operated patients, respectively. The multi-adjusted hazard ratio was 0.62 (95% confidence interval 0.39-0.98) in favor of surgery. The exclusion of the patients who had received neoadjuvant chemotherapy and patients with positive or undetermined surgical margins did not alter the results. Conclusions: In this large and homogeneous series of ABC patients with synchronous bone metastases, the role of breast surgery had a favorable impact on the progression of the disease, indicating a potential survival benefit.
The APC I1307K polymorphism as a significant risk factor for CRC in average-risk Ashkenazi Jews.
Authors: Boursi Ben , Sella Tal , Liberman Eliezer , Geva Ravit , Shmueli Einat , Sagiv Eyal , Kazanov Dina , Kraus Sarah , Arber Nadir 
Published: March 2020

1507 Background: The I1307K adenomatous polyposis coli gene variant, prevalent among Ashkenazi Jews, may increase risk for colorectal neoplasia. We studied the clinical importance of screening for this polymorphism in 3305 Israelis undergoing colonoscopic assessment. Methods: Blood samples and risk factor information were collected from individuals undergoing colonoscopic examination at our medical center. Germline genetic analysis for the APC I1307K variant was performed using real-time PCR for DNA extracted from peripheral mononuclear cells. Results: The overall prevalence of the I1307K polymorphism was 8.0% (10.1% among Ashkenazi while only 2.7% among Sephardic Jews, p<0.001). The overall adjusted odds ratio (OR) for CR neoplasia among carriers was 1.51(95% CI, 1.16 –1.98). Among average risk Ashkenazi Jews, the OR was 1.76 (95% CI 1.26-2.45). On the contrary, among Sephardi subjects the OR was 0.996 (95% CI, 0.51-1.93). A multiplicative interaction was identified between Ashkenazi ethnicity and APC I1307K carrier status (PINTERACTION=0.055). The histopathological features of adenomas and cancers did not differ between carriers and non-carriers. Conclusions: The APC I1307K gene variant is an important risk factor for CRC in average risk Ashkenazi jews and should be considered for screening in this population.
MEN1 gene mutations with different phenotypic presentations in two families: Is it a time to grade MEN1 mutations as high-risk and low-risk?
Authors: Shifrin Alexander L. , Bale Allen E , Dykas Dan , Fay Angela Musial , Belitsis Kenneth , Fomin Svetalna , Lann Danielle , Villanueva Ronald , Zheng Min , Govil Sushama , Erler Brian , Matulewicz Theodore , Topilow Arthur , Krasna Mark , Vernick Jerome 
Published: March 2020

1540 Background: MEN1 syndrome results from MEN1 gene mutations and is characterized by primary hyperparathyroidism (PHPT), pancreatic endocrine tumors (PET), pituitary adenomas, thymic and other tumors. About 600 different mutations have been reported on Human Gene Mutation Database and 30 of them presented as Familial Isolated Hyperparathyroidism (FIHP); however, no genotype-phenotype correlations have been identified. Methods: We characterized 2 independent families with newly diagnosed MEN1. Mutation analyses were performed in Dept of Genetics Yale University. Diagnostic tests, surgical treatment were implemented. Results: Family 1 has 21 members. 5 presented with early onset of PHPT and no other tumors. 3 ½ parathyroidectomies were performed. A proband had direct sequencing that showed a mutation in Exon 7, consisting of single base insertion in codon 319 (TAC to TTAC)(c1065_1066insT). There were no deaths in the family. Family 2 has 20 members. 7 were tested and showed a mutation in Exon 2, consisting of single base deletion in codon 103 (CTG to _TG)(c417delC). One 1st generation member died from PET at age 79, three 3rd generation members had multifocal metatstatic malignant gastrinomas (ages 32, 39, 41). The proband had total pancreatectomy at age 32. Five members had PHPT, angiofibromas. Three 2nd generation members had thymic carcinomas (ages 20, 54, 60). Conclusions: Phenotypic presentation of MEN1 syndrome may vary with the same mutation suggesting a lack of genotype-phenotype correlation and the effect of modifying factors. On the other hand, these two families—one with a mutation predicted to truncate the menin protein close to its terminus and the other with a truncating mutation early in the coding sequence—have dramatically different severity of the syndrome. Our findings suggest that the exon 7 mutation has a milder effect on protein function resulting in FIHP. The management may be heavily influenced by the predicted clinical phenotype, we are proposing the development of a grading system for MEN1 gene mutations as low-risk and high-risk and to attempt to identify other modifying genetic and environmental factors to improve screening and timing for surgery.
Genetic testing referral, uptake, and results in a program for women age 40 or younger with breast cancer.
Authors: Ali Asma , Warner Ellen , Hill Kimberley 
Published: March 2020

1542 Background: PYNK: Breast Cancer Program for Young Woman is a novel program started in 2008 at our center to optimize management and promote research for women ≤ age 40 newly diagnosed with breast cancer. Clinical and epidemiological data including cancer family history (FH) is prospectively collected on each consenting patient. As Toronto’s population is uniquely multiethnic we sought to determine BRCA testing eligibility, uptake and results for PYNK patients. Methods: Of the 145 consecutive patients, data were available for 109, of whom 2 had testing prior to diagnosis. Our provincial BRCA testing criteria are age < 35 at diagnosis; suspicious FH; or Ashkenazi Jewish (AJ) and age < 50 at diagnosis. Results: Of the 107 previously untested patients, 40 were < 35 at diagnosis. In 5 of the other 67 testing eligibility could not be assessed. 66 of the 102 (65%) were eligible and of those 65 (98%) were offered referral for counseling. One declined counseling, 9 were not yet seen, 2 declined testing, and 53 were tested. Test results are available for 47 as follows: 30 (64%) no mutation, 4 (8%) variant of uncertain significance (VUS), 7(15%) BRCA1 mutations and 6 (13%) BRCA2 mutations including 1 of the 4 AJ women. Ethnicity of the other 12 mutation carriers was: 1 Hispanic, 2 European, 2 African, 4 Asians, 1 mix, 1 unknown and 1 not recorded. Two (15%) of the mutation carriers had no FH of breast or ovarian cancer. Four additional women opted for counseling and testing despite ineligibility and none had mutations. Conclusions: A specialized program for young women facilitates appropriate referral for genetic testing and encourages high testing uptake, which is important given the high prevalence of mutations (28% of tested women). Further research is necessary to assess the psychological and management impact of having a VUS on young women compared to their older counterparts.
Predictors of contralateral prophylactic mastectomy among patients with ductal carcinoma in situ (DCIS) who underwent evaluation for BRCA genetic testing.
Authors: Elsayegh Nisreen , Gutierrez-Barrera Angelica M. , Muse Kimberly I. , Lin Heather , Turco Diana L. , Litton Jennifer Keating , Kuerer Henry Mark , Arun Banu 
Published: March 2020

1549 Background: Patients with DCIS are at increased risk for developing contralateral breast cancer (CBC). Therefore, an increasing number of women with DCIS are electing for contralateral prophylactic mastectomy (CPM). In a previous study involving 2072 women with DCIS, 13.5% chose CPM. In this study, we aimed to evaluate factors associated with CPM in patients with DCIS who underwent genetic counseling for BRCA. Methods: 165 women with pure DCIS, who underwent genetic counseling, were included in the study. Patients’ characteristics were obtained from a prospectively maintained research database at UT M.D. Anderson Cancer Center. Univariate and multivaraite logistic regression analysis were used to determine predictive factors associated with CPM. Patients’ characteristics included age, marital and educational status, tumor markers, nuclear grade, family history with breast (BC) and ovarian cancer (OC), race, Ashkenazi Jewish ancestry, and BRCA genetic test results. Results: Out of 165 patients, 17(10.3%) were found to have a BRCA deleterious mutation. 44(26.7%) underwent CPM. Younger patients (median ≤ 45 yr) were more likely to elect for CPM than older patients (p= 0.0098). Patients who tested positive for a BRCA mutation were more likely to elect for CPM than those who tested negative or were not tested (p= 0.0001). Patients who had a family history of OC (15 (57.7%) were more likely to choose CPM than those who did not (p= 0.0004). These three factors remained significant in the multivariate model (p <0.008). Marital and educational status, tumor markers, nuclear grade, and family history of breast cancer were not significant predictors of CPM. Conclusions: The rate of CPM in patients with DCIS is high. Factors associated with increased likelihood of undergoing CPM include family history of OC, age, and BRCA positivity. Further studies are needed to evaluate patients perception of CBC risk, and if this may play a role in the high number of CPM.