bluuebunny/crossref_metadata_2025_split huggingface dataset:
A prospective validation cohort study of a prediction model on non-sentinel lymph node involvement in early breast cancer.
Authors: Yu Xingfei , Zhou Linyan , Yang Chen , Yu Yang , Chen Daobao , Huang Jian , Yang Hongjian , Wang Chen 
Published: May 2019

559 Background: Early breast cancer (cT1-2N0) with one or two sentinel lymph node (SLN) involved may avoid axillary lymph node dissection (ALND) if follow by radiotherapy supported by Z0011 and AMAROS trials. However, only less than one-third of those patients have positive non-sentinel lymph node (nSLN) and can truly benefit from radiotherapy or ALND in those two trials. It is necessary to identify the risk of nSLN metastasis before local treatment decision. We previously developed a predictive model for nSLN involvement using circulating CK19 mRNA level combined with contrast-enhanced ultrasound (CEUS) score (ASCO2017 poster 239, NCT02992067) in a training set. To evaluate the predict effect of this model, we designed a further study using the model prospectively in a validation set (NCT03280134). Methods: We identified early breast cancer cases in Zhejiang Cancer Hospital from July 2017 to June 2018. The level of circulating CK19 mRNA tested by qRT-PCR and CEUS scores were collected before surgery in each case. Patients with 1~2 SLN involved were enrolled and continued for ALND. The estimated percentage of nSLN-involved were calculated both by our model formula and the Memorial Sloan-Kettering Cancer Center (MSKCC) nomogram. The predictive accuracy and false negative rates (FNR) were evaluated and the area under curve (AUC) was compared between two predictive models. Results: Totally, 235 patients diagnosed as early breast cancer with 1~2 SLN involved were enrolled and 35.36% of them were nSLN involved after ALND. The total accuracy and FNR by our model for nSLN-involved prediction was 94.89% and 6.02%, respectively. The AUC was 0.952 (95%CI, 0.922~0.982), significantly higher than that in MSKCC model 0.880 (95%CI, 0.833~0.927). Furthermore, only CK19 mRNA level (HR = 40.091, 95%CI, 13.663~117.635) and CEUS score (HR = 2.009, 95%CI 1.158~3.485) are significantly related to nSLN involvement in both univariate and multivariate analysis, adjusted by age, menopause statue, tumor size, histological grade, estrogen receptor, progesterone receptor and human epidermalgrowth factor receptor-2 expression. Conclusions: Our model using CK19 mRNA and CEUS score showed potential predictive value of nSLN before surgery in early breast cancer patients. Further validation in larger multicenter cohort is warranted before changing clinical practice.
Cognitive impairment in breast cancer patients before surgery?: Results of a subgroup of the French CANTO cohort.
Authors: Lange Marie , Léger Isabelle , Rigal Olivier , Licaj Idlir , Rajpar Shanna , Lefel Johan , Levy Christelle , Capel Aurélie , Luis Ines Maria Vaz Duarte , Meyer Jonathan , Lerebours Florence , Petrucci Jean , Vanlemmens Laurence , Brion Marine , Martin Anne-Laure , Mesleard Christel , Arveux Patrick , Andre Fabrice , Dauchy Sarah , Joly Florence 
Published: May 2019

561 Background: Cognitive impairment has been reported among breast cancer (BC) patients (pts) after adjuvant chemotherapy. However, very few studies focused on cognitive function at diagnosis. Here we aimed to describe cognitive impairment among recently diagnosed BC before any treatment. Methods: A predefined sub-study of the French national prospective cohort of cancer and toxicities performed extensive objective and subjective cognitive assessment before any BC treatment (surgery or neo-adjuvant treatment). This study included a group of pts with newly diagnosed invasive Stage I-III BC and a group of healthy control (HC) women matched on age and education level. Episodic and working memory, executive functions, processing speed, attention, cognitive complaints (FACT-COG), anxiety and depression (HADS) and fatigue dimensions (FA12) were assessed with neuropsychological tests and the referred self-report questionnaires. Objective and cognitive impairment were defined according to International Cognition and Cancer Task Force recommendations. Results: 264 women (median age 54±11 years) recently diagnosed (average of 37 days after initial diagnosis) with invasive BC (stage I-II, 69%) and 132 matched HC participated in this study. Impaired working memory (20% vs 4%), information processing speed (36% vs 17%), attention (16% vs 1%) and executive function (21% vs 8%) were higher among pts than in HC (p < 0.001). In addition, 24% (n = 64) of pts reported cognitive complaints versus 12% of HC (n = 16, p < 0.01). Emotional and cognitive fatigue were higher in pts than HC (mean 24 vs 15 and 18 vs 11, p < 0.01). Similarly, higher levels of anxiety and depression were observed in patients when compared with HC (respectively in 41% and 3% of patients vs 10 and 1% for HC, p < 0.001). Objective cognitive impairment was not associated with cognitive complains. Both objective and subjective cognitive impairment were not associated with anxiety or depression. However cognitive complain was associated with fatigue (p < 0.001). Conclusions: In this large study, compared to HC, patients recently diagnosed with a localized BC reported more cognitive complains and objective cognitive impairment before surgery, without link with emotional status, but with fatigue. Further understanding of the biology and correlates of cognitive dysfunction at BC diagnosis is needed (CANTO-NCT01993498).
Does the innovative 4R Care Delivery Model improve timing and sequencing of guideline recommended breast cancer care in safety net and non-safety net centers?
Authors: Weldon Christine B. , Trosman Julia Rachel , Makower Della F. , Rapkin Bruce D. , Bozier Moreen , Knightly Eileen , Schaeffer Cathleen M. , Hoskins Kent , Gallagher Christopher , Lo Shelly S. , Grace-Louthen Cathy , Throckmorton Alyssa , Vanderwalde Lindi , Krueger Editha A. , Van Horn Jennifer , Schapira Lidia , Santa-Maria Cesar Augusto , Ravelo Arliene , Benson Al Bowen , Gradishar William John 
Published: May 2019

562 Background: Under the NCI ASCO Teams Project, we proposed a 4R Model which enables patient (pt) and care team to manage timing and sequencing of interdependent care with a novel multimodality 4R Care Project Plan (Trosman JOP ’16). 4R (Right Info/Care/Patient/Time) was previously piloted at 3 Chicago centers (Weldon ASCO ‘18). Methods: A new study tested impact of 4R on timing and sequencing of guideline recommended care at 4 safety net and 3 non safety net US centers. 4R Plans were provided to stage 0-III breast cancer pts Jan-Nov’18, 4R cohort. Clinical and pt reported data analyses compared 4R cohort (N=105) to a historical control cohort of pts who received care pre-4R, Jan - Dec ’17 (N=190). Results: We significantly improved 3 referral metrics and 4 referral completion metrics - receipt of care by pts who were referred (Table). After referrals, safety net pts had a significant increase in 4R vs control cohort in receiving genetic consult (72%, 21/29 vs. 42%, 18/43, p=.02) and dental visit (100%, 6/6 vs. 20%, 1/5, p=.02). They had lower increases in flu shot referrals (41%, 24/58, vs 36%, 37/104, NS) and dental referrals (10%, 6/58, vs 5%, 5/104, NS) than non safety net pts who had significant increases. Other metrics improved at a similar rate for safety net and non safety net pts. Conclusions: 4R markedly improved referral and receipt of interdependent guideline recommended breast cancer care. For most metrics safety net pts benefited from 4R at a similar or higher rate than non safety net pts, indicating that 4R may reduce care disparities. Low increases in referrals for safety net pts and in trial referral/enrollment for all pts must be addressed. An expansion of 4R across the US continues this work. [Table: see text]
TARGIT E(lderly): Prospective phase II trial of intraoperative radiotherapy (IORT) in elderly patients with small breast cancer.
Authors: Wenz Frederik ,   TARGIT E Trialists
Published: May 2019

563 Background: TARGIT E is a prospective, multicentric single-arm phase II trial (NCT01299987; Neumaier et al. BMC Cancer 2012) that is based on the experimental arm of the protocol of the international randomized TARGIT A study. The trial was designed to investigate the efficiency of a risk-adapted approach consisting of a single dose of intraoperative radiotherapy (IORT) followed by whole breast radiotherapy (WBRT) only when risk factors are present in elderly patients. Methods: Patients with low-risk breast cancer (≥70 years, cT1, cN0, cM0, invasive carcinoma of no special type) were enrolled between February 2011 and September 2014. During breast conserving surgery, a single dose of 20 Gy of low-energy IORT was given (Intrabeam, Carl Zeiss Meditec, Germany). Additional postoperative WBRT (46 – 50 Gy) was applied in case risk factors (larger size, other histology, free margin < 1 cm, lymphatic vessel invasion (L1), positive nodes, multifocality/multicentricity, extensive intraductal component (EIC)) were present. Systemic therapy was applied according to international standards and guidelines. The primary outcome was the local relapse rate. Discontinuation of the trial was judged to be necessary if the local relapse rates exceed 3/4/6% at 2.5/5/7.5 years. Results: A total of 541 patients were screened. Of those 474 patients were enrolled, whereas 347 (73.1%) received IORT only, 99 (10.8%) IORT plus WBRT, 22 (4.6 %) WBRT only and 7 (1.5%) surgery only with no subsequent adjuvant therapies. After a median follow-up of 3.25 years, four ipsilateral in-breast recurrences were observed (after 11, 33, 42 and 43 months) resulting in an actuarial local relapse-free survival of 99.8% after 2.5 years and 98.5% after 5 years. Conclusions: The results of the prospective TARGIT E trial consolidate earlier reports from the randomized TARGIT A trial, supporting the use of accelerated partial breast radiotherapy (APBI) in selected patients. The observed local relapse rates at 2.5 and 5 years are far below the predefined stopping rules. Clinical trial information: NCT01299987.
Prediction of occult axillary metastases in treatment-naïve patients with breast cancer: A transSENTINA analysis.
Authors: Kolberg-Liedtke Cornelia , Kolberg Hans-Christian , Bauerfeind Ingo , Fehm Tanja N. , Fleige Barbara , Lebeau Annette , Schwentner Lukas , Staebler Annette , Loibl Sibylle , Untch Michael , Kühn Thorsten 
Published: May 2019

566 Background: Prediction of occult axillary metastases through clinical / biological parameters may allow reduction of axillary staging. This is particularly important, as systemic therapies have become more efficient. We have conducted a systematic analysis among patients undergoing axillary sentinel lymph-node biopsy (SLNB) before initiation of primary systemic therapy as part of a clinical trial (SENTINA) with the goal to identify predictors of sentinel lymph node status in a well-defined patient cohort. Methods: Patients with a clinically negative axillary status who underwent SLNB as part of the prospective SENTINA trial were included. Univariate and multivariate analyses were carried out to identify clinical / pathological parameters associated with SLN status, using logistic regression models. Model performance was assessed by ROC analyses. Calculations were performed using R version 3.5.2. Results: Arms A and B of the SENTINA study contained 1022 patients. Among 805 cN0 patients, all parameters considered relevant for this analysis were available. 527 and 278 patients presented with negative and positive lymph nodes upon SLN biopsy, respectively. Univariate regression models identified largest tumor diameter (odds ratio (OR) 1.016, p-value 0.0041), tumor type (ductal vs. lobular, OR 2.004, p 0.00234), tumor grading (low vs. high, OR 0.537, p < 0.001), hormone receptor (HR) status (negative vs. positive, OR 2.668, p < 0.001), HER2 status (negative vs. positive, OR 1.462, p 0.0158) as being associated with SLN status with an a < 0.1. Multivariate analysis resulted in tumor diameter, HR status, HER2 status and tumor type being independently associated. These parameters were combined using stepwise (backward and forward) selection into a prediction model. This model predicted SLN status with an AUC of only 0.65. Conclusions: Using data obtained as part of the SENTINA trial we were able to build a prediction model that was able to predict SLN metastases in treatment naïve cN0 patients with limited accuracy. Additional (biological) parameters, such as response to systemic therapies (i.e. axillary conversion through PST) may be more appropriate to predict presence of occult sentinel lymph node metastases among patients with breast cancer.
Clinical pharmacogenomic testing impacts therapy decisions and supportive medication choices in breast cancer.
Authors: Harnden Kathleen Kiernan , Deeken John F. , Stankowicz Matthew , Stafford Arielle , Cocilovo Costanza , Khromykh Alina , Iyer Ramaswamy K , Barnett Scott , Lawrence Grace , Moeckel Franziska , Vogt Brittany , Philips Sheila , Solares Andrea , Edmiston Kirsten H. 
Published: May 2019

569 Background: Pharmacogenomics, the study of the interaction between the patient’s genome and therapeutic drug response, evaluates the associations between efficacy and toxicity through analysis of drug metabolizing enzymes. As personalized medicine advances to the forefront of cancer care, pharmacogenomics can evaluate the individual’s ability to metabolize key medications in breast cancer treatment including anti-emetics, opioids, and tamoxifen. Women who do not achieve optimal levels of the active metabolites of tamoxifen are at higher risk of recurrence. Patients on chemotherapy who do not respond to anti-emetics can suffer from nausea and vomiting resulting in dehydration and hospitalization. This project evaluates the feasibility and therapeutic impact of real time pharmacogenomics in a selection of patients at the Inova Schar Cancer Institute (ISCI). Methods: An interdisciplinary team was created through the ISCI and the Inova Translational Medicine Institute to implement cheek swab based pharmacogenomic testing in 50 new patients undergoing mastectomy or neoadjuvant chemotherapy for breast cancer. Study patients were assessed for genotypic variability of key CYP enzymes and resulting impact on anti-emetic choices, perioperative pain control, and tamoxifen use. Results: Data was collected in a RedCap database. The 50 women enrolled were ages 28-83. Cheek swabs were performed in clinic and median turn around time was 7 days. 24 distinct genotypes were found in the 50 patients. 20% had abnormal CYP2D6 phenotypes indicating abnormalities in tamoxifen metabolism. 28% of patients had results leading to changes in dose or medication choice of perioperative pain control. 6% of patients had a CYP2D6 ultra-rapid metabolizer phenotype and were given granisetron in lieu of ondansetron. These patients had no documented nausea or vomiting requiring dose adjustments to the treatment plan or medical intervention. 40% of patients had results recommending avoidance of tamoxifen, 75% of which have ER+ breast cancer. 25% of patients had recommended changes to the dose of tamoxifen. Conclusions: Pharmacogenomic testing is feasible and available real-time for immediate use in the clinic. CYP mutations impact treatment decisions in a significant proportion of patients. Individualized treatment plans tailored to pharmacogenomic recommendations can be created in the multi-disciplinary setting and may decrease side effects of treatment and improve efficacy of curative therapy.
On-treatment changes in tumor-infiltrating lymphocytes (TIL) during neoadjuvant HER2 therapy (NAT) and clinical outcome.
Authors: Luen Stephen James , Griguolo Gaia , Nuciforo Paolo , Campbell Christine , Fasani Roberta , Cortes Javier , Untch Michael , Lin Suling Joyce , Savas Peter , Fox Stephen B. , Di Cosimo Serena , Llombart Cussac Antonio , de Azambuja Evandro , Piccart-Gebhart Martine J. , Pusztai Lajos , Sotiriou Christos , Salgado Roberto , Prat Aleix , Loi Sherene 
Published: May 2019

574 Background: Higher quantity of pretreatment TIL (PT) is associated with improved pCR and EFS in HER2+ early breast cancer (BC). The value of on-treatment TIL is unknown. Methods: The NeoALTTO trial randomized 455 women with HER2+ BC to 12 weeks NAT with trastuzumab, lapatinib or combination with paclitaxel, followed by FEC after surgery. In the PAMELA trial 151 women received 18 weeks NAT with lapatinib and trastuzumab (±hormonal therapy). TIL were quantified on PT and on-treatment (W2) biopsies using the published method on H&E slides, and tested for associations with pCR (logistic regression), EFS and OS (Cox models) in univariate (UV) and multivariate (MV) analyses. The likelihood ratio test assessed added prognostic value to clinicopathological (CP) variables. pCR associations were validated in PAMELA. We investigated enrichment of immune cell subsets using previously published RNAseq data from NeoALTTO. Results: In NeoALTTO, PT and W2 TIL were evaluable in 277/455 (61%). We defined two groups: immune-poor (L+F) and immune-enriched (II+P), see Table. Immune-enriched (41%; 134) vs poor (59%; 164) patients had significantly higher pCR rates (40% vs 21%; UV OR 2.24; 95%CI 1.31-3.85; P = .003; MV P = .009), and added significant value to CP + PT TIL for prediction of pCR (P = .003). This was further confirmed in PAMELA (N = 94/151) (26% vs 6%; UV P = .021; MV P = .028). In NeoALTTO, the immune-enriched vs poor patients had significantly improved EFS (5 yr est 85% vs 60%; UV HR 0.31; 95%CI 0.18-0.54; P < .001; MV P < .001) and OS (5 yr est 91% vs 77%; UV HR 0.40; 95%CI 0.20-0.82; P = .012; MV P = 0.026), and provided significant added prognostic value beyond CP + pCR + PT TIL (EFS P < .001) In NeoALTTO PT samples, II vs F patients had enrichment of DCs, NKs and CD8+ including tissue resident memory cells (P = .009) suggesting requirement of key immune subsets. Further validation by IHC is ongoing. Conclusions: On-treatment TIL identifies patients more likely to achieve pCR and have improved EFS in early-stage HER2+ BC, beyond CP + PT TIL. This information could aid future trial design. Clinical trial information: NCT00553358, NCT01973660. [Table: see text]
Phase II randomized study of neoadjuvant metformin plus letrozole versus placebo plus letrozole for ER-positive postmenopausal breast cancer [METEOR Study].
Authors: Kim Jisun , Han Wonshik , Kim Eun-Kyu , Jung Yongsik , Kim Hyun-Ah , Chae Soo Min , Lee Eun Sook , Ahn Sei-Hyun , Kim Tae Hyun , Jeong Joon , Choi Su Yun , Nam Seok Jin , Paik Nam-Sun , Kim Lee Su , Gong Gyungyub , Yu Jong Han , Jung So-Youn , Kim Hee Jeong , Ahn Sung Gwe , Kim Min Kyoon 
Published: May 2019

576 Background: Neoadjuvant endocrine therapy with an aromatase inhibitor has shown efficacy comparable to that of neoadjuvant chemotherapy in postmenopausal breast cancer. Pre-/Clinical data have shown that metformin, a widely used anti-diabetic drug also one of mTOR inhibitor have shown anti-tumor activity. We report the result of prospective, multicenter, phase II randomized, placebo controlled trial aiming to evaluate the direct anti-tumor effect of metformin in non-diabetic postmenopausal women with hormone-receptor (HR) positive breast cancer. Methods: 203 postmenopausal women diagnosed with hormone receptor positive, T1-3/N0-2 invasive breast cancer were randomized to 24 weeks of neoadjuvant letrozole (2.5 mg/day) and either metformin (2000 mg/day) or placebo. Women with history of diabetes were excluded. Primary endpoint was clinical response rate (complete, partial response by caliper). Secondary endpoint was pathologic complete response rate, breast conservation rate, percent mammographic density change. PEPI score and toxicity profile were compared between two groups. Results: 153 intention-to treat population were analyzed (72 metformin, 75 placebo group). Overall clinical response rate was 61.4% (94/153) by caliper and did not reach statistical significance between metformin versus placebo groups (66.7% versus 56.4%, p = 0.193). Breast conservation rate was 68.0% (100/147) (66.7% versus 69.3%). Overall, 87.3% (103/118) displayed Ki67 < 10% at surgical specimen and 16.7% (21/126) had zero PEPI score. Neither Ki67% nor PEPI score was different between two groups. However, among the 20 patients with core-needle biopsy after 4 weeks of medication, greater number of patients displayed Ki67 < 10% in metformin group than in placebo group (87.5% versus 33.3%, p = 0.017). Patients with 4week Ki67 < 10% had higher clinical response rate (100% versus 57.1%, p = 0.038). Grade 3 side effects were reported in three patients (vomiting, high blood pressure, weight loss) and no hypoglycemia event was observed. Conclusions: 61.7% overall clinical response was achieved with 24-weeks of neoadjuvant letrozole, with numerically > 10% higher response rate in letrozole+metformin group (66.7% versus 56.4%). 4-weeks Ki67 < 10% level was predictive of clinical response. With < 2% grade 3 side effects, preoperative letrozole (with/without metformin) followed by 4-week Ki67 evaluation may indeed serve as primary choice to postmenopausal hormone receptor positive breast cancers. Clinical trial information: NCT01589367.
Race and response to neoadjuvant chemotherapy according to MammaPrint risk.
Authors: Nunes Raquel , De Snoo Femke , Stork-Sloots Lisette , Treece Hong-Khanh (Tina) Dinh , Dreezen Christa , Audeh M. William 
Published: May 2019

578 Background: African-American (AA) women with breast cancer have a less favorable prognosis, likely due to differences in tumor biology. This is not only driven by the higher rate of triple negative/basal tumors in patients with AA ancestry, as worse outcome has also been seen in patients with luminal tumors. The Neoadjuvant BReast Cancer Symphony Trial (NBRST, NCT01479101) was a prospective trial that has shown an association of MammaPrint/BluePrint (MP/BP) with a rate of pathologic Complete Response (pCR) of 2% in Luminal A with 95% Distant Metastasis Free Interval at 3 years. Here, we determine the MP/BP risk distribution, response to therapy, and outcome in African American (AA) and Caucasian (Cau) patients. Methods: NBRST enrolled 1,072 breast cancer patients (pts) in the US (June 2011 and December 2014), median follow-up 34.9 months. The current unplanned analysis compared clinicopathological characteristics, molecular risk assignment and outcome with neoadjuvant chemotherapy (NACT) in AA and Cau pts. Molecular subtyping groups were assessed by MP/BP as follows: Luminal A (MammaPrint Low Risk), Luminal B (MammaPrint High Risk), HER2 and Basal types. Results: Out of 1,072 pts, 157 (15%) were AA, and 780 (73%) were Cau. AA patients were younger at diagnosis (52 vs 54 yrs; p = 0.016), had a higher likelihood of having higher grade (gr 3, 65% vs 53%; p = 0.005), ER-negative (45% vs 33%; p = 0.005) and lymph node positive tumors (71% vs 51; p < 0.001). MP/BP classified more AA patients as Basal type, 45% compared to 33% of Cau patients (p = 0.004). Fewer AA patients were classified as Luminal A (15%) compared to Cau pts (33%; p = 0.004). In multivariate analysis race was a significant factor for higher pCR rates to NACT in AA compared to Cau pts, together with PR, HER2, T-stage and Grade (HR = 1.679, 95% CI = (1.057, 2.67), p = 0.028). The pCR rate to NACT in patients with Basal tumors was 38% and similar in AA and Cau patients. In patients with hormone receptor positive and HER2 negative tumors, patients classified by MP/BP as Luminal A had lower pCR (2%) compared to non-luminal A (13%) (p = 0.0015). MP low risk patients had higher 3 yr DMFS (97%) than MP high risk patients (86%; p = 0.010). DMFS for AA MP Low Risk patients was 100%. Conclusions: In this study, MP was able to identify patients with hormone receptor positive tumors with low sensitivity to chemotherapy and good outcome, irrespective of race, suggesting that this test can be helpful to characterize the tumor’s biology and select patients who will not benefit from chemotherapy independently of their ancestry. Clinical trial information: NCT01479101.