bluuebunny/crossref_metadata_2025_split huggingface dataset:
ZORO: A prospective randomized multicenter study to prevent chemotherapy-induced ovarian failure with the GnRH-agonist goserelin in young hormone-insensitive breast cancer patients receiving anthracycline containing (neo-) adjuvant chemotherapy (GBG 37)
Authors: Gerber B. , Stehle H. , Ricardo F. , Maass N. , Fischer D. , Sommer H. L. , Conrad B. , Mehta K. , Loibl S. 
Published: August 2020

526 Background: Premature ovarian failure due to chemotherapy leads to premature menopause and infertility. To prevent related health problems and to maintain fertility after chemotherapy in patients with hormone insensitive breast cancer, ovarian function might be protected by using a GnRH-agonist. Methods: Patients (pts) < 46 years, with a hormone insensitive breast cancer were randomized to receive an anthracycline/taxane containing chemotherapy with or without goserelin 3.6mg in parallel as subcutaneous injection in the abdominal wall starting at least 2 weeks before chemotherapy, and thereafter every 4 weeks (28 ± 3 days) until the end of the last chemotherapy cycle (EOC). Primary objective is the ovarian function 6 months after EOC. The endpoint normal ovarian function 6 months after EOC is defined by two consecutive menstrual periods within 21–35 days within a time frame of 5–8 months after last application of goserelin. Secondary objectives are treatment compliance, toxicity, quality of life; menopausal symptoms score; ovarian function at 0, 6, 12, 18, and 24 months by menstruation and endocrine function (estradiol, progesterone, FSH, LH, SHBG), duration until recovery of regular menstrual period, pregnancy rate. Results: Between March 2005 and August 2007, 63 pts in16 sites were enrolled. 60 are considered to be evaluable, 3 pts withdrew their informed consent. Nine serious adverse events occurred, which were mainly chemotherapy related and had no relationship to goserelin (3 febrile neutropenias, 2 neutropenias, 2 nauseas, 1 infection of port-catheter, and 1 psychogenic hyperventilation). No treatment related deaths occurred. Two women became pregnant, one in each group. Conclusions: There have been no risks identified related to the safety of the ZORO trial. The treatment with goserelin is feasible in all pts with acceptable hematological and non-hematological tolerability. Final efficacy analysis will be presented at the Meeting. [Table: see text]
MRI tumor volume for predicting response to neoadjuvant chemotherapy in locally advanced breast cancer: Findings from ACRIN 6657/CALGB 150007
Authors: Hylton N. , Blume J. , Gatsonis C. , Gomez R. , Bernreuter W. , Pisano E. , Rosen M. , Marques H. , Esserman L. , Schnall M. 
Published: August 2020

529 Background: American College of Radiology Imaging Network (ACRIN) trial 6657, the imaging component of the I-SPY trial (CALGB 150007/150012), is testing MRI for predicting response to treatment and stratifying risk-of-recurrence in patients with locally-advanced breast cancer. We report preliminary results evaluating MRI for prediction of pathologic response. Methods: Women with ≥3 cm invasive breast cancer receiving neoadjuvant chemotherapy (NACT) with anthracycline-cyclophosphamide (AC) followed by a taxane (T) were enrolled from May 2002 to March 2006. MRI was performed prior to NACT (t1), after 1 cycle AC (t2), between AC and T (t3), and following T prior to surgery (t4). MRI tumor size assessments included longest diameter (MRLD) and tumor volume (MRVol). Clinical size (clinsize) and mammographic longest diameter (MGLD) were also recorded. Linear dimension was measured by the radiologist for MGLD and MRLD; MRVol was calculated by computer using signal enhancement ratio (SER) thresholds. Change in clinical and MRI variables at t2 were compared for ability to predict pathologic complete response (pCR). Results: 237 patients were enrolled at 9 institutions. 216 patients with complete imaging were analyzed. Of tumor size measurements at t4, MRVol showed the strongest correlation with pathsize among clinsize (r = 0.44), MGLD (ns), MRLD (r = 0.28) and MRVol (r = 0.61). Early change in MRVol measured at t2 was the only variable predictive of pCR among clinsize (p = 0.14, 0.15), MRLD (p = 0.40, 0.07), MRVol (p = 0.02, 0.01) and peak SER (p = 0.53, 0.72) in univariate and multivariate logistic regression, respectively. Conclusions: Tumor response measured volumetrically by MRI is a stronger and earlier predictor of pathologic response after NACT than clinical exam or tumor diameter. This work is funded by NIH/ACRIN U01 CA79778; CALGB CA31946, CA33601; NCI SPORE CA58207. [Table: see text]
Use of intraoperative breast cancer sentinel lymph node (SLN) assay to predict of ≥4 positive (+) lymph nodes (LN)
Authors: Chagpar A. B. , Blumencranz P. , Whitworth P. W. , Deck K. B. , Rosenberg A. , Simmons R. M. , Reintgen D. S. , Beitsch P. , Saha S. , Julian T. B. 
Published: August 2020

530 Background: Predicting which patients will have ≥4 +LN and may need radiation therapy affects immediate breast reconstruction. We hypothesized that model s to predict the likelihood of ≥4+LN may be improved by incorporation of quantitative real time RT-PCR analysis of SLN. Methods: 728 patients were enrolled in 2 prospective studies of the GeneSearch BLN Assay (Veridex LLC) for SLN metastases. 205 (28.2%) were found to have +SLN by hematoxylin-eosin staining. Of these, 115 pts (15.8%) had tumors ≤5 cm in size with >4 total LN removed, forming the cohort of interest for this study. Quantitative cycle times (CT) for mammaglobin (MG) and CK19 were correlated with finding ≥4+LN on final pathology. Results: Median tumor size was 2.0 cm (range; 0.2–5.0 cm). Median number of SLN removed was 3 (range; 1–11). 18 patients (15.7%) had ≥4 +LN on final pathology. Median CT for MG was 29.1 (interquartile range (IQR): 24.7–39.0) in patients with <4 +LN vs. 21.4 (IQR: 18.5–26.8) in those with ≥4 +LN, p<0.001. Median CT for CK19 was 23.7 (IQR: 20.9–28.2) in patients with <4 +LN vs. 19.6 (IQR: 17.8–20.7) in those with ≥4 +LN, p<0.001. Tumor size ≥2cm, proportion of SLN+ >50%, MG CT <25.8 and CK19 <20.8 were correlated with ≥4 +LN on final pathology. On multivariate analysis, tumor size, MG CT and CK19 CT were significant (see table). A simplified CPR was created with 1 point given if tumor size was ≥2cm, 1 point if MG CT <25.8 and 2 points if CK19 CT<20.8. Of the 24 patients (20.9%) with 0 points, only 1 (4.2%) had ≥4 +LN; of the 12 patients (10.4%) with 3 points, 8 (66.7%) had ≥4 +LN on final pathology, p<0.001. Area under the receiver-operator curve was 86.2% (95% CI: 76.1%-96.2%). Conclusions: Intraoperative quantitative RT-PCR of SLN improves prediction of ≥4 +LN; further validation of this model will have clinical utility regarding the use of immediate, delayed, or delayed-immediate reconstruction approaches. [Table: see text] [Table: see text]
Outcome prediction by the 70-gene profile in the context of the National Comprehensive Cancer Network (NCCN) guidelines
Authors: de Snoo F. A. , Knauer M. , Bender R. A. , Stork-Sloots L. , Rutgers E. J. , Glas A. M. , Linn S. C. , Van 't Veer L. J. 
Published: August 2020

535 Background: According to the NCCN consensus guidelines molecular profiling for breast cancer prognosis may be used in patients with ER-positive, Her2-negative and LN-negative disease. Current proposed NCCN clinical risk assessment suggests adjuvant treatment for the majority of these patients. The 70-gene profile (MammaPrint) is validated as an independent prognostic indicator for patients with lymph node-negative and positive disease. Prognosis prediction by MammaPrint may be more suitable to indicate who needs adjuvant chemotherapy in addition to endocrine therapy. Methods: 566 tumor samples of women with ER-positive, Her2-negative and LN- negative breast cancer from 5 previously reported studies were analyzed and classified by MammaPrint as good or poor prognosis. 10-year breast cancer-specific survival (BCSS) was analyzed according to MammaPrint and the NCCN guidelines. Results: Median follow-up was 3.5 years (range 0.1–21.1). 380 of 566 patients (67%) were classified as good and 186 (33%) as poor prognosis by MammaPrint. Using the NCCN guidelines, 7% were classified as low and 93% as high risk respectively. 349 patients (62%) received no adjuvant treatment, 17% received hormonal treatment only, 2% chemotherapy only and 20% both respectively. At 10 years, BCSS was 91% vs. 67% for the good and poor prognosis groups (HR 4.0 [95%CI 2.0–7.9], p<0.001) whith MammaPrint risk assessment. If the NCCN guidelines were used, BCSS was 86% vs. 83% for the low and high risk groups (HR 1.11 [0.3–4.6), p=0.888). In multivariate analysis, adjusted for known prognostic factors and adjuvant therapy, only MammaPrint and histological grade were independent predictors for 10-year-BCSS with HRs of 2.8 (1.3–6.1, p=0.008) and 1.9 (1.1–3.1, p=0.015), respectively. Conclusions: MammaPrint is a strong and independent prognostic indicator in ER-positive, Her2-negative, LN-negative breast cancer and is discordant in 62% of cases when compared with the NCCN guidelines. MammaPrint identifies approximately 66% of NCCN high risk patients as having a good prognosis. Integration of MammaPrint into clinical risk assessment and adjuvant treatment selection can provide a large benefit for management of patients with endocrine-responsive early breast cancer. [Table: see text]
Use of progesterone receptor (PR) expression to predict benefit from prolonged adjuvant tamoxifen (TAM) in breast cancer: Results of a biomarker study from the TAM01 randomized Trial
Authors: Mathieu M. , De la Cruz J. , Veilllard A. S. , Koscielny S. , Bourgier C. , Rimareix F. , Spielmann M. , Delozier T. , Andre F. , Delaloge S. 
Published: August 2020

536 Background: The optimal duration of endocrine therapy ranges between 5 and 7 years. Recent data suggest that a subset of patients could benefit from extended adjuvant TAM. The goal of this biomarker study was to identify potential candidates for extended TAM. Methods: After 2–3 yrs of adjuvant TAM, 3793 patients (pts) were randomized to continue TAM up to 10 yrs, or to stop treatment (Delozier, J Clin Oncol. 2000). The tumor blocks of 587/988 pts included at the Institut Gustave-Roussy, were used to construct a tissue micro-array (TMA). Immunohistochemical stainings were performed for ER, PR, bcl2, p53 (+: > 10% of stained cells), HER-2 (+: score 3+), EGFR1 (+: any positivity), PAK1, IGFR1 (+: intensity = 2 or 3). Median follow-up was 12 years. The prognostic values of biomarkers were assessed by a Cox model adjusted for clinical prognostic parameters and predictive values by interaction tests. Only statistical tests with P<0.01 were considered significant because of multi-hypothesis testing. Time-to-relapse (TTR), excluding contralateral cancer, was the main study endpoint. Results: Median age of the cohort included in the TMA was 63. Tumor characteristics : 54% node-positive, 85% ER+, 64% PR+, 7% HER-2+, 68% bcl2+, 14% p53+, 8% EGFR1+, 46% PAK1, 45% IGFR1. None of the biomarkers were prognostically significant. However, PR expression was strongly predictive for the efficacy of extended TAM on TTR (interaction test, p = 0.003). Long-term TAM was associated with a hazard ratio of 0.56, (95% CI: 0.30–1.03) and 1.94 (95%CI = 0.80–4.70) for PR+ and PR- pts respectively. A trend towards interaction between ER (p = 0.04), HER-2 (p = 0.05) and Bcl2 (p = 0.03) expression and a benefit from TAM was also observed, with a trend towards greater efficacy of prolonged TAM in ER+/HER-2-/ bcl2+ tumors. P53, EGFR1, PAK1, IGFR1 expression had no predictive value. Conclusions: PR expression, probably reflective of ER activation and functionality, strongly predicts benefit from continuation of TAM after 2–3 yrs. These data could provide a rationale for evaluating the efficacy of TAM after 5 years of anti-aromatase therapy in post-menopausal women with ER+/PR+/bcl2+/Her2-tumors. No significant financial relationships to disclose.
Prospective randomized trial evaluating weekly paclitaxel (WP) versus docetaxel in combination with capecitabine (DC) in operable breast cancer
Authors: Buzdar A. U. , Green M. C. , Broglio K. R. , Carter C. D. , Valero V. , Ibrahim N. K. , Hunt K. K. , Hortobagyi G. N. 
Published: August 2020

542 Background: Paclitaxel has scheduled-dependant efficacy, and WP is associated with better therapeutic index (J Clin Oncol. 2005;23:5983–5992). The DC combination had higher response rate, longer control of disease, and improved survival in metastatic disease (J Clin Oncol. 2002;20:2812–2823). This randomized study compared the efficacy and safety of WP to DC in patients (pts) with operable breast cancer. Methods: Pts were randomized 1:1 and stratified by the timing of therapy (preoperative vs adjuvant). The primary endpoint was disease-free survival (DFS), and the secondary endpoint in pts receiving preoperative therapy was complete pathologic response (pCR). WP arm was paclitaxel 80 mg/m2 weekly for 12 weeks, followed by 4 cycles of FEC. DC arm included docetaxel 75 mg/m2 day 1, and capecitabine 1500mg/m2 daily for 14 days of each 3 week cycle for a planned 4 cycles of DC followed by 4 cycles of FEC. The study was designed to include 930 pts to have 80% power to detect a difference in 4 year DFS from 85% on the WP arm to 92% on the DC arm, based on a two-sided test at the 0.05 significance level. Results: 601 pts were randomized, 304 on WP arm and 297 on DC arm. 37% of pts on each arm received therapy in the preoperative setting. Pts characteristics were balanced between the two arms. Median follow-up was 38 months. 4-year DFS on DC arm was 91.0% (95% confidence interval [CI], 84.8- 94.1) and the 4-year DFS on the WP arm was 89.3% (95% CI, 84.8- 94.1) (p = 0.957). A total of 107 pts have been treated with DC and 109 have been treated with WP in the preoperative setting and are evaluable for pCR. The pCR rates were 18.7% and 17.4% on each arm respectively (p = 0.81). The DC arm had higher incidence of hand foot syndrome, and myelosuppression, and WP treatment was associated with higher neurotoxicity. Interim data was presented June 2008 to the institutional data monitoring committee and the study was closed due to futility. If the trial had continued as planned, the predictive probability of concluding in favor of the DC arm for DFS and pCR were 0.005 and 0.001, respectively. Conclusions: WP and DC as utilized in this study had similar efficacy in pts with early stage breast cancer. WP was a better tolerated therapy, associated with little myelotoxicity. [Table: see text]
ASCO-recommended prognostic factors uPA/PAI-1 in node-negative (N0) breast cancer patients (pts) compared to clinicopathological risk assessment within the NNBC 3-Europe trial
Authors: Thomssen C. , Vetter M. , Schmidt M. , Veyret C. , Meisner C. , von Minckwitz G. , Martin P. , Sweep F. C. , Paepke D. , Harbeck N. 
Published: August 2020

544 Background: ASCO Tumor Marker Guidelines 2007 recommended clinical routine use of the invasion markers uPA (urokinase-type plasminogen activator) and its inhibitor PAI-1 for risk assessment in N0 breast cancer pts (Harris et al, J Clin Oncol. 2007;25:5287). Ten-year follow-up data of the confirmatory prospective clinical uPA/PAI-1 trial (CHEMO-N0) will be presented at the ASCO 2009 Meeting (Harbeck et al.). We conducted a further prospective trial (NNBC 3-Europe) addressing the direct comparison between risk-assessment by uPA/PAI-1 (UP) and clinico-pathological factors (C), and optimization of adjuvant chemotherapy for high-risk N0 pts: FEC*3-Doc*3 vs. standard FEC*6. Methods: From December 2002 to January 2009, 4,040 pts were recruited by 151 centres. For uPA and PAI-1 ELISA, tumors samples were snap frozen und processed. Risk assessment was based on grade and in G2 tumors, either by UP or by a St. Gallen adapted C algorithm. High-risk pts were randomized for adjuvant chemotherapy. All laboratories took part in central quality assurance (QA) for uPA/PAI-1 determination. Results: Risk assessment was performed for 1,590 pts based on C and for 2,445 pts based on UP. End of accrual was planned when 2,572 high risk pts were randomised for chemotherapy and thus ends Jan 31, 2009. Current status shows 1,291 high-risk pts in the FEC-Doc and 1,294 in the FEC arm. In the low-risk arm, 1,450 pts have endocrine therapy, only. By both risk stratifications, 42% of the G2 tumors were assigned as low risk, but in total, more pts were classified as low-risk by UP (39%) than by C (31%). Median uPA level were at 2.40 ng/mg protein (below cutoff), median PAI-1 at 15.9 (above cutoff). In the QA programm, mean coefficients of variations are 12% for uPA and PAI-1 determination. Conclusions: The prospective biomarker trial using uPA/PAI-1 has just ended accrual with more than 4,000 patients. Routine uPA/PAI-1 determination is reliable and feasible even in core needle specimens. Using tumor grade and uPA/PAI-1, adjuvant chemotherapy may be avoided in about 39% of N0 breast cancer pts. Cooperation: EORTC Patho-Biology Group, AGO Breast Group, GBG, Unrestricted grants by Sanofi-Aventis, Pfizer, American Diagnostica, Martin-Luther-Universitaet Halle-Wittenberg. [Table: see text]
Modeling bone mineral density (BMD) evolution in postmenopausal patients treated by letrozole (L), tamoxifen (T), and sequences of T and L (SAKK 21/07)
Authors: Zaman K. , Thürlimann B. , Huober J. , Schönenberger A. , Pagani O. , Lüthi J. , Simcock M. , Giobbie-Hurder A. , Genton C. , Aebi S. 
Published: August 2020

545 Background: Osteoporosis and fractures are long term complications of aromatase inhibitor use in the adjuvant therapy of breast cancer. Early detection of patients (pts) at risk of treatment-induced osteoporosis may allow preventive therapy and selection of the most appropriate endocrine therapy. We developed a statistical model describing the evolution of BMD in pts treated with T, L and sequences of T and L. Methods: Available dual-energy x-ray absorptiometry exams (DXA) of pts treated in trial BIG 1–98 were retrospectively collected from Swiss centers. Treatment arms: A) T for 5 years; B) L for 5 years; C) 2 years of T followed by 3 years of L; and D) 2 years of L followed by 3 years of T. Pts without DXA were used as a control for detecting selection bias. A repeated measures model using the first-order autoregressive covariance structure to allow for different times between DXA was used to model BMD (g/cm2) since trial randomisation. Prospectively defined covariates were considered as fixed effects in a multivariable model using an intention to treat analysis. Covariates at trial randomization were: age, height, weight, race, known osteoporosis, tobacco use, prior bone fracture, prior hormone replacement therapy (HRT), bisphosphonate use and previous neo-/adjuvant chemotherapy (ChT). Results: A total of 247 out of 546 pts had between 1 and 5 DXA; a total of 576 DXA were collected. Arm A contained 67 pts, B 63 pts, C 55 pts and D 62 pts. Median follow-up was 5.8 years. Factors correlated with BMD in the multivariate analysis were weight (0.003/kg, p < 0.0001), height (0.003/cm, p = 0.0083), osteoporosis (-0.130, p < 0.0001), tobacco (current / previously vs. never: -0.057, p = 0.0011 / -0.042, p = 0.0798), previous HRT (0.030, p = 0.0244), ChT (0.032, p = 0.0174), time since endocrine therapy start (-0.009/year, p = 0.0164) and treatment arm (B / C / D vs. A: -0.068, p = 0.0002 / -0.091, p < 0.0001 / -0.064, p = 0.003). Conclusions: Our statistical model describes the BMD evolution for pts treated with L and/or T. All treatment regimens affect BMD. Contrary to expectation, the switch schedule T followed by L does not seem to result in better bone protection compared to L monotherapy. [Table: see text]
Ductal carcinoma in situ of the breast and gene expression markers for prediction of invasive recurrence
Authors: McKean H. A. , Reynolds C. , Hoskin T. L. , Suman V. J. , Grant C. S. , Erlander M. G. , Ma X. , Ingle J. , Goetz M. P. 
Published: August 2020

550 Background: Ductal carcinoma in situ (DCIS) is a heterogeneous group of non-invasive cancers with varying propensity for recurrence. There are no validated markers that identify patients at risk for invasive recurrence following lumpectomy. HOXB13/IL17BR (H/I) is expressed in both DCIS and invasive cancer (Ma Cancer Cell. 2004) and associated with recurrence in stage I cancer. A 5-gene molecular grade index (MGI) distinguishes outcome in grade II disease (Ma Clin Cancer Res. 2008). We sought to determine whether H/I or MGI was associated with invasive recurrence in resected DCIS. Methods: We identified patients at Mayo Rochester who underwent lumpectomy ± radiation for DCIS between 1988 and 2001 and performed a nested case/control study. Cases were patients with ipsilateral invasive recurrence, matched to controls based on age, surgery date, length of follow-up, and adjuvant radiation. DCIS was macrodissected from paraffin sections and RNA extracted to obtain H/I and MGI RT-PCR profiles. The association of H/I and MGI with case-control status was assessed with conditional logistic regression; results reported are odds ratios (OR) with 95% confidence intervals (CI). The association of H/I and MGI as continuous variables with nuclear grade (low, intermediate, high) was estimated with Spearman's rank correlation. Results: 427 patients underwent lumpectomy for DCIS, and 33 were identified as possible cases. Histologic review excluded 8 (non-sufficient tissue or DCIS recurrence without invasion). 25 cases were matched to 48 controls (2 controls for 23 cases, 1 control for 2 cases). Both H/I (r = 0.43, p = 0.0001) and MGI (r = 0.41, p = 0.0004) were significantly correlated with nuclear grade. Positive H/I was associated with trend towards higher recurrence (OR 1.9; p = 0.22) that was most pronounced in cases/controls (15/28) treated with lumpectomy alone (OR 3.3; CI: 0.8–13.2, p = 0.09). Similarly, positive MGI was associated with a trend towards higher recurrence risk in patients treated with surgery alone (OR 2.0; CI: 0.6–6.4, p = 0.27). Conclusions: These data suggest that both HOXB13/IL17BR and MGI can identify a subset of patients with surgically resected DCIS who are at risk for invasive recurrence. Further studies in larger cohorts are needed to confirm these findings. [Table: see text]