bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multivariate analysis of predictors of positive or close margins in breast-conserving therapy.
Authors: Chokechanachaisakul A. , Wesen C. A. , Hall T. M. , Falk J. S. 
Published: February 2017

105 Background: Local recurrence rates after breast-conserving therapy (BCT) are increased with positive or close margin lumpectomy. This group of patients usually requires a re-excision lumpectomy or a completion mastectomy, causing delays in systemic therapy, and a less desirable cosmetic outcome. The objectives of this study were to identify any predictive risk factors that might be associated with positive or close lumpectomy margins (<1mm), and thus have implications for the planning of appropriate primary surgical excision. Methods: This was a retrospective cohort study of 195 consecutive patients from a prospectively collected, single-institution database. Patients who underwent primary lumpectomy for ductal carcinoma in situ (DCIS), invasive ductal carcinoma, and invasive lobular carcinoma from October 2007 to July 2010 were reviewed. Statistical analysis of the data was performed using Chi-squared analyses, multivariate logistic regression and Student’s t-test to identify significant predictors of a close or positive margin following lumpectomy. Results: In this study, 53.8% had positive or close margins. Ninety-two percent of this group underwent re-excision (86.5%) and total mastectomy (13.5%). We also observed that 53.1% of patients who underwent second operation had no residual disease. Factors significantly associated with positive or close margins include a family history of breast cancer (OR=2.3, p=0.01), a non-palpable mass (OR=2.4, p=0.01), or an excisional biopsy (OR=6.02, p=0.022). Age, race, use of hormone replacement therapy, menopausal status, use of preoperative MRI or US, BIRAD, use of neoadjuvant chemotherapy, tumor size, staging, waiting time, histology, receptor status, and axillary status were not significantly correlated with positive or close margins. Conclusions: For patients who were recommended to have a lumpectomy, an increased risk of a positive or close margin was significantly associated with a family history of breast cancer, a nonpalpable mass, or an excisional biopsy. These predictors should be weighed in the decision for attempting lumpectomy with the goal of a negative margin versus the ability to obtain a satisfactory cosmetic outcome.
Accelerated partial breast brachytherapy after lumpectomy as salvage treatment for local recurrences after conservative treatment of breast cancer: Eighteen-year results of a nonrandomized comparison with mastectomy.
Authors: Guix B. , Lejarcegui J. A. , Tello J. I. , Guix I. , Zanon G. , Quinzaños L. , Palombo P. , Del-Campo J. M. , Galdon G. , Espino M. , Milla A. 
Published: February 2017

109 Background: To report the long-term results in a prospective group of patients (pts) treated for local recurrence after conservative treatment of breast cancer by a second conservative surgery or by total mastectomy. Methods: Between 12/1990 and 10/2004, 85 pts with <3 cm, low-risk local recurrence after conservative treatment for breast cancer were offered total mastectomy. 48 of them refused it and were treated by a second lumpectomy followed by HDR brachytherapy implant to the tumor bed+margin. 30 Gy in 12 fractions in 5 days were given. Pts treated by mastectomy had no further radiotherapy. Postmenopausal pts with negative receptors had no systemic tx. The rest of the pts had chemo or hormones. No pts were lost for follow-up. Results: All pts completed treatment. During the 17-year, 1-year minimum follow-up, in the second conservative group there were 8 pts who had regional (2 pts) or distant metastases (6 pts) as their first site of failure. Three of them experienced a differed local recurrence and 1 died from the disease. In the total mastectomy group, there were 2 local recurrences, 1 regional recurrence, and 5 distant metastases as first site of failure. One patient died from the disease. Actuarial results at 17-year for second conservative and total mastectomy were respectively: local control 84.2%-71.7%; disease free survival 65.4%-63.8%; and survival 90.7% and 88.2%. Cosmetic results were satisfactory in 89.4% treated conservatively. No patient experienced arm edema or grade 3-4 early or late complications. Between the 14 pts that were followed-up for at least 10-years, 13 of them were with their breast still in place. Conclusions: Second conservative treatment by HDR brachytherapy was a safe and effective method of treatment for small-size, low-risk, local recurrence after local excision in conservatively treated pts. APBI with wide margins probed to be enough treatment, without significant side-effects in previously intesively irradiated patients. Lumpectomy and partial breast brachytherapy can be conidered the treatment of choice in selected patients with low-risk recurrent breast tumors.
Triple-negative breast cancer (TNBC) outcomes with partial breast irradiation and concurrent chemotherapy (PBI-CC) compared with whole breast irradiation and sequential chemotherapy (WBI-SC).
Authors: De Souza Lawrence L. M. , Shah A. , Stearns V. , Asrari F. , Frassica D. A. , Tsangaris T. N. , Fetting J. H. , Lange J. R. , Jacobs L. K. , Zellars R. C. 
Published: February 2017

115 Background: TNBC (ER/PR/HER2-negative) is associated with worse locoregional recurrence (LRR), disease-free survival (DFS), and overall survival (OS) than non-TNBC. MSKCC/Harvard recently reported a 5-yr local recurrence rate of 33% in TNBC patients treated with PBI (Pashtan et. al. ASTRO 2010). Having completed two prospective trials of PBI-CC, one previously reported (Zellars et al. JCO 2009), we reviewed the outcomes of TNBC patients treated with PBI-CC and compared them to those treated with WBI-SC. Methods: TNBC patients treated on 2 phase I/II PBI-CC protocols were compared to a cohort of TNBC patients treated at our institution with WBI-SC with respect to OS, DFS, LRR and in-breast tumor recurrence (IBTR). KM rates of local and distant recurrence, log-rank test of statistical significance are presented. Results: Between 2004 and 2009, 16 patients were treated with PBI-CC and 32 with WBI-SC. PBI-CC was 40.5 Gy (2.7 Gy x 15 QD) to the lumpectomy bed only with cycle 1 of ddAC (60/600 mg/m2 every 14 days with growth factor support x 4 cycles). WBI-SC patients received a med. dose (+ boost) of 60.7 Gy, (42.5 – 66), 5/32 had nodal irradiation. 28/32 recieved AC, and 4/32 C, Docetaxel. Med. follow-up is 38.4 mo (9.2–65.5) and 40.5 mo (5.6–77.8), respectively. There is no statistically significant difference between groups with respect to T/N stage, median age, and menopausal status. No patients died. All 6 recurrences (1 nodal, 4 IBTR, 1 distant) were in the WBI-SC group. Med. time to recurrence was 14.4 months (0.8–38.6). DFS at 3 yr/5 yr were 100% vs. 84.4% (p=0.10) and 100% vs. 81.3%. (p=0.07) in the PBI-CC and WBI-SC groups respectively. There is a trend towards decreased LRR (0% vs. 15.6%, p=0.12) and IBTR (0% vs. 12.5% , p=0.16), in favor of PBI-CC. Conclusions: Our results differ from earlier reports of a high rate of LRR in TNBC patients treated with PBI. This may be due to our use of concurrent chemotherapy with PBI or to undefined factors in our series of WBI-SC. Our data suggest improved DFS, LRR, and IBTR with PBI-CC when compared to retrospectively reviewed contemporary TNBC patients treated WBI-SC and should be externally confirmed.
Patterns of locoregional failure following radiotherapy for breast cancer.
Authors: Chen S. A. , Crocker I. R. , Fox T. , Liu T. , Whitaker D. , Godette K. D. , Torres M. A. 
Published: February 2017

118 Background: To determine the influence of radiotherapy (XRT) technique on local control in breast cancer (BRCA) patients, we evaluated the relationship between PET/CT-identified locoregional recurrences (LRR) and prior definitive XRT treatment plans. Methods: Twenty-two consecutive LRRs of BRCA were identified by PET/CT in 19 patients treated from 2004-2011 with definitive post-operative radiation for their BRCA. PET/CT and original XRT CT simulation images were fused using a B-spline deformable registration algorithm (VelocityAI, Velocity Medical Solutions, Atlanta, GA) to correct for posture and soft tissue changes. Prior XRT dose to the FDG avid LRR region was calculated. LRR was classified as in-field, marginal or out-of-field. In-field LRRs were defined as ≥95% of the LRR volume receiving ≥95% of the prescribed dose (45–50.4 Gy). Marginal misses were LRRs at the field edge and/or not receiving ≥95% of the prescribed dose. Out-of-field LRRs were LRRs intentionally not treated with the original XRT plan. Results: Four LRRs were in-field, 8 were marginal and 10 were out-of-field, with two patients having both in-field and out-of-field LRRs and one having a marginal and out-of-field LRRs. Three in-field, 3 marginal and 6 out-of-field LRRs occurred simultaneously with distant metastasis (DM). In-field LRRs received a median dose of 48.4Gy (range 45-50Gy). Two in-field LRRs were marginal misses of the additional 15 Gy boost dose (median dose received 53.5 Gy); both patients had high grade, ER/PR-, and HER2 + tumors. In the 7 patients with triple negative tumors, there were 4 marginal, 4 out-of-field, and no in-field LRRs. Among marginal LRRs, a median dose of 33Gy (range 2–45.6Gy) was delivered. Out-of-field LRRs occurred in 5 supraclavicular and 5 internal mammary lymph nodes. With a median follow-up period of 3.7 yrs, the 5-yr disease-free survival (DFS) in patients with an isolated LRR is 55.6%, while in those recurring with DM, the DFS is 22.5%. Conclusions: Our study is one of the first to systematically evaluate the influence of XRT technique over local control in BRCA. Due to the number of marginal and out-of-field LRRs, our data suggest that XRT field design and dose are important factors in preventing LRRs in addition to tumor biology.
Preliminary results of a prospective trial of image-guided 3D conformal accelerated partial breast irradiation (APBI).
Authors: Pham H. T. , Yao M. , Song G. , Badiozamani K. R. , Salcedo - Wasicek C. , Wechter D. 
Published: February 2017

125 Background: External beam APBI is noninvasive and may offer better coverage of tumor sites in proximity to skin or chest wall than brachytherapy. To improve conformality and accuracy of treatment, we conducted a prospective IRB-approved clinical trial of APBI with implanted gold markers for image guidance. Cosmetic assessments through patient and physician questionnaires were collected. Adverse events were graded according to Common Terminology Criteria for Adverse Events v3.0. This is our preliminary report on toxicity and cosmetic outcomes. Methods: Thirty-four pts were enrolled from 12/06 to 4/10. Eligibility criteria included age > 40, unifocal disease, ductal histology, tumor ≤ 3 cm, surgical margin ≥ 2 mm, and planning target volume: breast volume ratio < 0.2. Vascular invasion, positive axillary nodes, high-grade ductal carcinoma in situ, and extensive intraductal component were excluded. Three gold fiducials were sutured into the operative site at the time of partial mastectomy. The clinical target volume comprised the surgical cavity including all surgical clips and gold fiducials + 10-15 mm. Prescribed dose was 3.85 Gy b.i.d. to 38.5 Gy, using 4–5 non-coplanar beams. Special breathing technique and image guidance with electronic portal imaging were used. Results: Median follow-up is 18 months (range 7-47 months). Most pts had mild acute reactions with only 6% grade 2 erythema. Late toxicities include hyperpigmentation (71% grade 1), fibrosis (26% grade 1, 32% grade 2), skin dimpling or indentation (38% grade 1, 3% grade 2), telangiectasias (12% grade 1), rib fractures in the treatment area (3% grade 2). The only grade 3 toxicity was a seroma requiring surgical excision in one pt. Cosmesis was rated by the pt versus (v.) physician as excellent/good in 85% v. 94%, 80% v. 90%, and 84% v. 85% of the pts at prior to treatment, 6 months, and one year respectively. Ninety-one percent of patients were “totally satisfied with the treatment and results.” No breast recurrences have been observed. Conclusions: Image-guided APBI is well-tolerated, with high patient satisfaction. Early cosmesis results, as assessed by both pts and physicians, are comparable to whole-breast radiotherapy.
Concordance between the 21-gene recurrence score (RS) and the 70-gene profile (MP) in breast cancer (BC) patients (pts).
Authors: Denduluri N. , Rugo H. S. , Davis S. E. , Favret A. , Hong R. , Au A. , Moore D. H. , Esserman L. 
Published: February 2017

13 Background: Genomic assays are increasingly incorporated into treatment planning for pts with early stage BC to provide prognostic and/or predictive information. MP is a validated predictor of recurrence risk (RR) in pts without any treatment and RS is a validated predictor of RR in pts treated with 5 years of hormonal therapy (HT). Because concordance between RS and MP is largely unknown, we analyzed concordance in untreated pts that had both tests performed. Methods: Data are from 50 early stage BC pts treated at 4 US Oncology practices and the University of California, San Francisco. We used linear regression to test whether clinical features were related to discordance, measured as part of the gamma statistic. Results: Median age was 52.5 years, 16% (8 pts) had micro or macroscopic nodal involvement, and 66%, 30%, and 4% of pts had stage I, II, and III disease, respectively. All pts had estrogen receptor positive disease and 2 pts had HER2 overexpression by IHC or FISH. Concordance of MP and RS is shown below. Clinical features, including tumor size, grade, and HER2 were not significantly related to discordance. Gamma concordance was 0.64 (95% CI 0.28 to 0.98, p=0.0013). Conclusions: Concordance is high, mostly due to agreement in low risk scores. Five cases are truly discordant (MP low/RS intermediate or high) based on predicted outcomes. The 11 cases with high-risk MP with low risk RS may reflect endocrine sensitivity to 5 years of HT, or true discordance. Our identification of discordance should stimulate research to further clarify biology and elucidate the drivers of different types of risk. Large studies are underway to refine risk definition and treatment recommendations. [Table: see text]
Association between race and BMI with response to neoadjuvant endocrine therapy in postmenopausal women with large estrogen receptor-positive breast cancers.
Authors: Ambros T. , Sujoy V. , Fernandez C. G. , Reis I. , Wright J. L. , Jorda M. , Saigal K. , Hurley J. 
Published: February 2017

132 Background: Neoadjuvant endocrine therapy is increasingly used in the treatment of breast cancer. There is a need to define which patients will benefit the most from this form of therapy. Methods: Retrospective review of medical records from University of Miami/Jackson Memorial Hospital from 1998 to 2011. Response to neoadjuvant endocrine therapy was evaluated through comparison of palpable breast mass size at presentation with pathological tumor size in surgical specimens. Response was stratified as “No Response” (NR), indicating no change or increase in size, “Moderate Response” (MR) as up to 50% decrease in size, and “Good Response” (GR) > 50% decrease in size. Data was analyzed by body mass index (BMI), type of endocrine therapy, race and histology. Results: Data from 62 postmenopausal, estrogen receptor-positive women who received neoadjuvant hormonal therapy was analyzed. Median age was 62 (range 50-91). Clinical stage: II 24.2%, IIIA 25.8%, IIIB 35.5%, IIIC 6.5%. Endocrine therapy used was tamoxifen (14.5%) or aromatase inhibitor (AI) (85.5%). Response rate was NR in 22.6%, MR in 43.5% and GR in 33.9%. Fifty two patients had available height and weight information. In patients receiving AI, BMI was significantly higher in the NR group vs. GR group (mean BMI 38.68 vs. 27.56, p=0.041). Mean BMI in MR was 32.18, not statistically different from either group. Analysis of both AI and tamoxifen treated patients yielded similar results (results not included). The rate of GR was higher in the Caucasian vs. African American population (40.4% vs. 14.3%, p=0.017). Inversely, the rate of NR was higher in African Americans (50.0% vs. 14.9%, p=0.017). There was a trend towards more favorable tumor size change in Caucasian vs. African American women (mean 36.19% reduction vs. 11.69% increase in tumor size, p=0.058). The mean tumor size change was more favorable in ductal vs. lobular carcinomas (34.75% decrease vs 8.69% increase, p=0.184). Conclusions: Lower BMI and Caucasian ethnicity were associated with higher frequency of GR (> 50% decrease in tumor size) to neoadjuvant endocrine therapy. No association was found between response and stage, PR status or HER2 expression.
Relative dose intensity (RDI) assessment in an academic center.
Authors: Arnaout A. , Leblebjian H. , Bartel S. , Hassett M. J. 
Published: February 2017

139 Background: Patients with early breast cancer treated in the adjuvant setting realize maximum benefit as to disease- free and overall survival when they receive their full planned dose of chemotherapy. Due to the aggressive treatment regimens, patients are at increased risk of dose delays and reductions, which result in reduced RDI. Studies have shown that at RDI < 85%, treatment outcomes are compromised. We sought to calculate the RDI attained in our breast cancer clinic and identify factors contributing to decreased RDI. Methods: We retrospectively reviewed records of 383 patients treated between January 2008 and December 2009. Treatment blocks were reviewed separately to better identify contributing factors to decreased RDI. Regimens were dose-dense doxorubicin and cyclophosphamide (ddAC), dd-paclitaxel (ddT), paclitaxel and trastuzumab (TH), and TH post ddAC. G-CSF support was noted when present. Dose reductions and dose delays (in days) with reason(s) were recorded for patients with RDI < 85%. Patients who switched care or regimen were excluded from this study. Results: Of the 383 patients, 150 received ddAC; 101 ddT; 67 TH and 65 TH post ddAC. Of these, the percentage of patients with RDI < 85% was 10.4%. RDI was <85% in 8.7%, 6.9%, 14.9%, and 15.4% in the ddAC, ddT, TH, and TH post ddAC regimens, respectively. The major impediments were neutropenia in the anthracycline containing regimen, neuropathy with taxanes, and cardiotoxicity with trastuzumab. No dose delays were seen for administrative issues. Conclusions: Our results show that 10.4% of treated patients had RDI < 85%. These results were superior when compared to historic data for same regimens. Major reasons for decreased RDI were neutropenia, neuropathy, and cardiotoxicity. Improving risk assessment of neutropenia before initiating treatment could improve RDI in this patient population. Prophylaxis with vitamin B6 may help reduce incidence of neuropathy. Efforts to assure on-schedule treatments should be maintained. This includes comprehensive paramedical support to overcome any hurdles to on-time treatment. Proper education of patients on the importance of RDI can increase awareness of the value of cooperating with the provider and encourage them to persevere with the treatment.
Risk of having BRCA mutations in women with triple-negative breast cancer: A systematic review and meta-analysis.
Authors: Tun N. M. , Villani G. M. , Ong K. 
Published: February 2017

160 Background: Increased prevalence of BRCA1 mutations (BRCA1) has been associated with the occurrence of triple-negative breast cancer (TNBC) (estrogen receptor [ER]- and progesterone receptor [PR]-negative, HER2-negative) in independent clinical studies. However, BRCA2 mutation (BRCA2) has not been found to overrepresent in women with TNBC. We have performed a meta-analysis of these studies to provide further statistical evidence of the association between BRCA positivity and TNBC. Methods: A Medline search of the MeSH terms “BRCA”, “triple”, and “negative” yielded 37 articles. A search of ASCO abstracts yielded 18 relevant articles. Random effects model was used for analysis due to heterogeneity among the proportions of included studies (Cochran’s Q = 18.52 and 15.18, tau2 = 0.61 and 1.29, I2 = 73% and 80% for BRCA1 and BRCA2 respectively). Mantel-Haenszel method was applied to calculate the pooled event-based odds ratio (OR) with 95% confidence interval (CI). Results: 6 studies including 1,602 BC patients were eligible for analysis of BRCA1 and 4 studies including 1297 BC patients for BRCA2. 172 patients with BRCA1 mutations and 79 patients with BRCA2 mutations were analyzed. Among these 6 studies, 1 included Ashkenazi Jewish women exclusively and 1 included only women of Chinese descent. The overall prevalence of BRCA1 was 10.05% (172 out of 1,602), and for TNBC patients 21.94% (95 out of 433) with an odds ratio of 5.90 (CI: 2.75, 12.66, p < 0.00001). TNBC was not a risk for BRCA2 (OR = 0.67, CI: 0.19, 2.39, p = 0.53). Chinese women with TNBC did not have an elevated risk of BRCA1 (OR = 0.94, CI: 0.24, 3.66) in contrast to Jewish women with TNBC who had the highest risk of BRCA1 among the populations studied (OR = 21.79, CI: 9.03, 52.55). Conclusions: Women with TNBC carry a significantly high risk of having BRCA1 but not BRCA2 mutations. We recommend genetic testing for BRCA1 mutations in women with TNBC especially in Ashkenazi Jewish population. Further studies on Chinese population are needed to further establish the relationship between TNBC and BRCA1 mutations in this cohort.
Assessing the added value of breast tumor markers in breast cancer genetic risk prediction model BRCAPRO.
Authors: Arun B. , Biswas S. , Tankhiwale N. , Blackford A. L. , Gutierrez-Barrera A. M. , Litton J. K. , Hortobagyi G. N. , Amos C. I. , Parmigiani G. 
Published: February 2017

164 Background: BRCAPRO is a widely used genetic risk prediction model for estimating the carrier probabilities of mutations in BRCA1/2 genes. BRCAPRO has been enhanced to utilize information on molecular markers ER, PR, CK5/6, and CK14. However, no independent validation study on the utility of these markers in risk prediction exists to support using these in actual clinical settings. Further, an important predictive and prognostic marker for breast cancer, Her-2/neu (Her2) is not utilized in BRCAPRO. Therefore, the aim of our study was to: 1) incorporate Her2 in BRCAPRO; 2) conduct a validation study of the markers. Methods: Patients with breast cancer at the UT M. D. Anderson Cancer Center’s breast clinic who were referred for genetic evaluation were included. Separate sets of cohort were used for model building with Her2 and validation to avoid bias. This study was approved by the IRB. For the model building, we estimated the joint probabilities of ER and Her2 status for carriers and non-carriers of BRCA1/2 mutations. For the validation, BRCAPRO was run at two settings: 1) no marker data used and 2) ER/PR used. We calculated the Area Under the receiving operator characteristic Curve (AUC) using the probabilities of carrying any of BRCA1 or BRCA2 and conditional probabilities of carrying BRCA1 (CondBRCA1) and BRCA2 (CondBRCA2) given a proband is carrier. Results: The model-building set for Her2 was based on 409 probands and validation set on 796 probands wherein 23% of the probands were carriers. In the model-building step, we found that joint consideration of Her2 and ER/PR is useful in discriminating between carriers and non-carriers in some subgroups, e.g., a proband with ER-, Her2+ is much more likely to be a non-carrier than a carrier. In the validation step, the AUC for CondBRCA1 and CondBRCA2 improved substantially when ER/PR was used. We are in the process of coding Her2 in BRCAPRO and then validating its utility. Conclusions: Breast tumor markers are useful for prediction of BRCA1/2 mutation status in the BRCAPRO model. ER/PR helps discriminate between BRCA1 and BRCA2 mutation carriers. In our ongoing validation study Her2 is expected to improve discrimination between carriers and non-carriers in certain sub-groups.