bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of clinical and treatment factors to predict survival outcome in nonmetastatic metaplastic breast cancer.
Authors: Lai L. L. , Luu T. H. , Nelson R. A. 
Published: February 2017

11 Background: Although metaplastic breast cancer (MBC) represents < 1% of breast cancer, stem cell research has stimulated interest in the genetics and biology of MBC. Because prognostic clinical and treatment factors remain ill-defined for this rare breast cancer subtype, we queried a public cancer data registry to identify factors predictive of overall survival (OS) in MBC. Methods: Patients diagnosed with breast cancer from 2001-2008 were identified using the Surveillance, Epidemiology, and End Results (SEER) database. We included only patients with infiltrating ductal carcinoma (IDC) and MBC who had non-metastatic disease. Patients were evaluated by standard demographic, clinicopathologic, and treatment factors including age, race/ethnicity, extent of disease, tumor marker expression and treatment received. Differences between IDC and MBC were assessed using Chi-Square methods. OS across groups was measured using the Kaplan-Meier method and compared using the log-rank test. Cox proportional hazard and stepwise models were used to identify prognostic variables and to adjust for covariates. Median follow-up was 31 months. Results: Of the total 508,071 breast cancer cases, there were 1,246 (0.25%) patients with MBC and 392,809 (77%) with IDC. 5-yr OS for locoregional MBC and IDC was 67% and 84%, respectively (p<0.0001). When compared with IDC, MBC patients were older, had larger ER/PR negative cancers, and were more likely to have nodal disease. Factors predictive of worse OS in MBC on multivariate analysis are listed below. Tumor grade, ER/PR expression, and type of surgery (partial v. total mastectomy) did not impact OS. Of the treatment factors, only radiation affected OS (p=0.0002). Conclusions: To our knowledge this is the largest report of clinical and treatment factors predictive of outcomes in patients with MBC. Studies integrating clinical factors with molecular data may advance therapy that is more specific for this rare breast cancer subtype. [Table: see text]
A prospective study of cancer-related fatigue in women undergoing radiotherapy for breast cancer.
Authors: Torres M. A. , Liu T. , Chen H. , Godette K. D. , Stapleford L. J. , Mister D. , Pace T. , Miller A. H. 
Published: February 2017

110 Background: To investigate potential risk factors for cancer-related fatigue in women with breast cancer undergoing whole-breast radiotherapy (RT), we assessed the contribution of chemotherapy (CTX), RT-induced epidermal thickening, and inflammatory mediators to post RT fatigue. Methods: Following lumpectomy, 30 women received whole breast RT (50 Gy plus a 10 Gy boost). Prior to RT, at week 6 of RT, and 6 weeks post RT, subjects completed a validated questionnaire assessing fatigue (Multidimensional Fatigue Inventory [MFI-20]). At the above visits, patients underwent blood sampling for inflammatory mediators. In addition, breast epidermal thickness was measured using ultrasound tissue characterization. Results: Fatigue scores in the sample as a whole did not increase during RT. Independent multivariate analyses of clinical and demographic factors revealed that prior CTX (p<.001) and age <50 (p=.03) were significant predictors of higher post RT fatigue scores. Before, during, and after RT, CTX-treated patients had significantly higher mean fatigue scores than non-CTX-treated subjects. For example, mean MFI scores post RT in patients previously treated with CTX (n=15) were 28 points higher than patients not treated with CTX (mean 61 vs. 33, p<.001), with a clinically meaningful difference being 10 points. Race, cancer stage, and epidermal thickening (defined as a 50% increase over baseline during or after RT, n=17) did not predict higher post RT fatigue scores. Of the inflammatory mediators, plasma IL-6 prior to RT was the strongest predictor of post RT fatigue (p=.02). In addition, plasma IL-6 concentrations prior to RT were significantly higher in patients who received CTX versus those who did not (mean 5.0 vs. 2.5, p=.01). IL-6 prior to RT was also significantly correlated with RT-induced epidermal thickening (p=.04). Conclusions: Our study suggests that CTX-induced inflammation, measured by plasma IL-6, is independently associated with the development of fatigue as well as epidermal thickening in women undergoing breast RT. Treatments targeting inflammation before RT may reduce both fatigue and epidermal thickening post RT, particularly in patients who have been previously been treated with CTX.
Preoperative radiotherapy in patients with locally advanced breast cancer: Tumor response and patient outcome after 26 years of median follow-up.
Authors: Santos M. , Heymann S. , Fayard F. , Dunant A. , Arriagada R. , Marsiglia H. , Bourgier C. 
Published: February 2017

113 Background: Preoperative radiotherapy (PreopRT) in locally advanced breast cancer patients (LABC) has been rarely reported. The purpose of this study was to determine if pathological response to PreopRT could have prognostic value on locoregional control and survival. Methods: From 1970 to 1984, 203 LABC patients were treated by PreopRT, delivering 45Gy in 25 fractions to the breast, supraclavicular fossa, axilla and ipsilateral internal mammary chain. After a median interval of 38 days (range: 5-121 days), radical mastectomy and axillary dissection was performed independently of radiation response. Chemotherapy or endocrine therapy was prescribed according to physician discretion in 28% and 11% of patients, respectively. Premenopausal patients underwent ovarian ablation. Median follow-up was 26 years. Locoregional control (LRC), disease-free survival (DFS), and overall survival (OS) were estimated using the Kaplan-Meier method, the comparison of survival between groups was performed using the log-rank test, multivariate analysis was performed using the Cox model. Results: Thirty-three patients (16.2%) had a pathologic complete response (pCR) in the breast. The 10- and 20-year Kaplan-Meier LC were 90% (95% confidence interval CI: 85-94%) and 84% (95% CI: 77-89%), respectively. The 10 and 20-years DFS were 49% (CI: 42-55%) and 35% (CI: 29-42%), and the 10 and 20-years OS, 56% (CI: 49-63%) and 41% (CI: 35-48%), in that order. Patients with pCR tended to have better DFS (p=0.06) and OS (p=0.07) when compared to patients with partial response or stable/progressive disease. Having a pCR did not significantly influenced LRC (p=0.44). Multivariate analysis showed that a lower number of positive nodes on axillary dissection and younger age were associated with better DFS (p<0.0001 and p=0.02) and OS (p<0.0001 and p=0.007). Conclusions: LCR achieved by PreopRT followed by radical mastectomy in LABC was excellent in this study, despite few patients having adjuvant systemic therapy. Complete pathologic response defined a subgroup of women with a trend toward better DFS and OS. Older patients and those with a higher number of involved axillary nodes had a worse prognosis.
Role of HER2 status in the treatment of brain metastases arising from breast cancer by stereotactic radiosurgery.
Authors: Novik Y. , Kunnakkat S. , Donahue B. , Rush S. , Golfinos J. , Parker E. , Narayana A. 
Published: February 2017

117 Background: Overexpression of human epidermal growth factor receptor-2 (HER2) in breast cancer has been shown to be an independent risk factor of development of brain metastases (BM). However, the role of HER2 on the radiosensitivity of BM remains controversial. We investigated the efficacy of single fraction stereotactic radiosurgery (SRS) in the treatment of limited BM from breast cancer, based on the HER2 status. Methods: From 2004 to 2010, 57 patients with limited BM were treated with SRS using Leksell Gamma-Knife to a median dose of 20 Gy (range 12-20 Gy) prescribed to the 50% isodose line. The median number of lesions treated were 2 (range 1-7) and the median tumor volume was 92.8 mm3 (range 3.4 -793.7 mm3). There were 27 HER2 positive patients, with 32 ER positive and 22 PR positive patients. Six patients were triple negative. ER/PR information was not available for 4 patients. Overexpression of HER2 was defined as HER2 +++ by immunohistochemistry using the DAKO HercepTest or fluorescent in situ hybridization (FISH) analysis. Time to local recurrence, time to development of new brain metastases, progression-free survival (PFS), and overall survival (OS) were assessed from the date of SRS. Results: With a median follow-up of 11 months (range 1-66 months), 12 patients developed recurrence at the previously treated site (9 HER2 positive patients) and 30 developed new brain metastases (16 HER2 positive patients) The median PFS and OS for all patients were 8 and 16 months respectively. The median PFS for HER2 positive patients compared to HER2 negative patients were 7 and 11 months, respectively (p=0.352). HER2 positive patients had a median OS of 20 months, compared to 14 months in HER2 negative patients (p=0.086). Five patients went on to develop leptomeningeal disease, all of whom were HER2 positive. Conclusions: HER2 overexpression does not increase the risk of recurrence at the site of treatment or appearance of new BM. It does not affect PFS or OS following SRS. However, it remains a risk factor for the development of leptomeningeal disease.
Prognosis by breast cancer subtypes in patients treated with adjuvant chemotherapy in a clinical trial.
Authors: Ali A. M. G. , Provenzano E. , Abraham J. , Bartlett J. M. , Poole C. J. , Hiller L. , Dunn J. , Twelves C. , Earl H. M. , Caldas C. , Pharoah P. 
Published: February 2017

12 Background: Breast cancer can be classified into molecular subtypes that have distinct survival patterns. The purpose of this study was i) to evaluate the prognostic significance of breast cancer subtypes in a cohort of women taking part in the NEAT and BR9601 clinical trials comparing CMF with ECMF, and ii) to evaluate whether the subtypes were predictive of the added benefit of epirubicin in these trials. Methods: Tumor tissue microarrays were stained and scored for ER, PR, HER2, EGFR and CK5/6. These were used to classify the tumors into six intrinsic subtypes (1). We used Cox regression to compare overall survival (OS), breast cancer specific survival (BSS) and relapse free survival (RFS) in the different subgroups. We also compared the effect of ECMF with CMF by subgroup. Results: IHC data were available for 1725 cases of whom 805 were Luminal 1-basal negative, 153 were Luminal 1-basal positive, 174 were Luminal 2, 192 were HER2-like, 230 were core basal phenotype and 171 were 5-negative phenotype. Median follow-up time was 7 years. The prognostic effects of the subtypes were similar to those reported for unselected breast cancer cases irrespective of adjuvant therapy (Blows FM, et al. PLoS Med 2010;75:e1000279.). In particular, the luminal 1-basal negative tumors were associated with the best prognosis in five years after surgery and the HER2-like tumors were associated with the poorest prognosis. ECMF has previously shown to be associated with a 33% relative risk reduction for OS compared to CMF (Poole CJ et al. N Engl J Med 2006;35518:1851-62.). There was little evidence for significant heterogeneity of effect by tumor subtype for any end point (OS P= 0.40, BSS P=0.53 RFS P=0.50). However, there was an observed trend towards the largest additional benefit from ECMF being in women with tumors of the 5-negative phenotype (OS HR=0.39 95% CI 0.21-0.73) and the smallest being in Luminal 1-basal negative tumors (OS HR=0.86 95% CI 0.64-1.16). Conclusions: In a clinical trial in which all patients received chemotherapy, we confirmed that breast cancer subtypes show distinct behaviour with differences in short and long term survival. The benefit of ECMF over CMF was statistically similar in all disease subtypes.
Stereotactic radiosurgery for early-stage breast cancer: A new paradigm.
Authors: Yu C. X. , Regine W. , Zheng M. , Zhang J. , Feigenberg S. J. 
Published: February 2017

120 Background: Stereotactic radiosurgery (SRS) has not been widely used for breast cancer partly due to: 1) the lack of a suitable immobilization device; and 2) the lack of a delivery system that can concentrate a high radiation dose noninvasively. We have developed a SRS system that effectively addresses these obstacles and demonstrated the dosimetric feasibility of simultaneously ablating the intact tumor and sterilizing the tumor bed. Methods: A breast immobilization device consists of a solid outer cup with embedded stereotactic frame and a porous inner cup; the two cups join at the chest wall side by a soft goggle-like lip for comfort. A negative pressure is applied to the space between the two cups to immobilize the breast tissues. 15 patients with surgical clips in their breast underwent a geometric reproducibility trial, in which the patients received two CT scans spaced 10-60 minutes while wearing the cup. A SRS delivery system uses 36 Co-60 sources that rotate around a focal point to produce 36 non-coplanar arcs. The breast cup is locked on the treatment couch with the patient in prone position. The couch moves dynamically during treatment, allowing the focal spots to “paint” the desired 3D dose distribution. Results: The reproducibility of the 42 available clips was 1.83 mm ± 1.08 mm (2 std) and patients reported good comfort. 8 treatment plans simultaneously delivering an ablative dose of 18Gy to an intact tumor plus a 3mm margin (CTV1) and 10Gy to the tumor bed (CTV2 = CTV1+1cm) have been developed and verified with measurements. The dose-volume histograms showed very uniform dose coverage with 98% of CTV1 receiving 18Gy and 100% of tumor bed receiving 10Gy. On average, only 21% of the normal breast receives greater than 5Gy, safe to deliver 3 fractions of such doses. Conclusions: A breast-specific SRS system has been developed. Dosimetric studies illustrated the feasibility of managing early-stage breast cancer with SRS. Clinical studies that will identify patients in whom current forms of surgery and postoperative radiation may be eliminated are planned, allowing completion of local therapies noninvasively within a few days rather than months.
MammoSite partial breast irradiation following breast-conserving surgery for early-stage breast cancer.
Authors: Shokek O. , Yacoub S. , Bauer T. L. , Bell T. , Fortier G. A. , Grim R. , Hempling R. E. , Johnson D. E. , Kassas B. , Lasher D. , Mudge K. , Pandelidis S. , Pramanik R. , Watson M. , Wojcicka J. , Shah A. 
Published: February 2017

122 Background: Partial breast irradiation (PBI) remains investigational until comparisons to whole-breast external beam radiotherapy (EBRT) confirm noninferiority. Methods: From 2004 to 2010, 103 patients at York Cancer Center (Pennsylvania) who underwent margin-negative breast-conserving surgery for early-stage invasive or in situ breast carcinoma were enrolled on a prospective MammoSite PBI protocol. NSABP B39 stage and planning criteria were utilized, with unicentric tumors up to 3 cm and pN0-1 axillary staging for invasive carcinomas. PBI was prescribed to 1 cm from the applicator surface in 10 twice-daily fractions to 34 Gy. Results: With a median follow-up of 27 months, three patients experienced recurrence: one with isolated local in-breast tumor recurrence (local IBTR), one with IBTR remote from the surgical cavity (non-local IBTR) plus regional and distant recurrence, and one with regional and distant recurrence only 3- and 5-year freedom from local IBTR are 100% and 96% (non-local IBTR: 100% and 95%). Physician-reported cosmesis evaluations are available for 25 patients at 2-3 years after treatment, with a median score of “excellent.” 26 additional patients on protocol underwent insertion of the MammoSite applicator but had it removed without treatment, most commonly due to unsatisfactory cavity conformance (24 patients), uncommonly due to infection or seroma (two patients). Their characteristics (invasive vs. in situ disease, T/N stage, negative vs. close margins, age) were not statistically different than the 103 MammoSite-treated patients. All except one received EBRT, and none experienced IBTR, which is not statistically different than the IBTR rates of the 103 MammoSite-treated patients (p=0.84). Conclusions: MammoSite PBI in well-selected patients was associated with low rates of IBTR and not significantly different than a comparison cohort selected for MammoSite PBI but treated instead with EBRT. Randomized comparisons of PBI vs. EBRT are required to confirm PBI as standard.
Lymphedema and arm symptoms following three-dimensional conformal radiation therapy (3DCRT) for node-positive breast cancer (BC) patients.
Authors: Sparks I. , Prior P. , Xiang Q. , Li X. A. , Yen T. W. , White J. R. 
Published: February 2017

130 Background: Regional nodal irradiation for lymph node (LN) positive BC after lumpectomy/mastectomy can be subject to controversy due to the potential for treatment morbidity particularly lymphedema. Little is known about lymphedema and other arm morbidity rates after 3DCRT approaches. Methods: 172 LN positive BC cases treated from 2000 to 2007 using 3-DCRT and Dose Volume Histogram analyses were studied. All cases underwent axillary node dissection (AND). Axillary target volumes (ATV) were delineated on all treatment planning CT scans. Field arrangement and beam modifications were selected to deliver a min of 45 Gy to 90% of the ATV. Post-treatment bilateral arm circumference measurements (96%) and patient reported ipsilateral arm symptoms (thickness, heaviness, tingling, numbness) were recorded. Results: Median follow-up was 83.7 months. Median (med) patient age was 50. 52% were premenopausal. 76/66% had positive estrogen/progesterone receptors and 16% were HER2+. 52% underwent lumpectomy and 46% mastectomy. Median number of LN removed was 17 (1-46), number +LN was 3 (1-29), and tumor size was 3.7 cm. For 79 patients with separate AND the mean resected axillary volume was 157.8 cc (med 171 cc, range 25-472 ). The mean contoured ATV was 69 cc (med 58cc, range 16-608). On average 95% of the ATV was covered by a med of 44.7 Gy. Local control was achieved in 94.7% regional LN control in 99.4%. 16.7% met criteria for lymphedema (> 2 cm difference in circumference). Arm symptoms were reported by 51 (30%) of these 20 (39%) had measured circumference change > 2 cm. Referral to physical therapy was documented for 15% for reduced ROM but at last follow-up noted in 2.3%. The measured lymphedema rate was higher in patients who had mastectomy – 22 v. 11% (p=0.042) and worse with increasing resected axillary dissection volumes (p=0.032), ATV volume (p=0.883), and RT dose inhomgeneity coefficient (p = 0.049). Conclusions: Measured lymphedema rates following AND and 3-DCRT in this study were similar to those reported for AND in randomized studies compared to sentinel node. Careful attention to 3DCRT methods may help optimize lymphedema rates.
Neoadjuvant therapy and rates of margin re-excision in patients with invasive breast cancer.
Authors: Hanna E. M. , Musunuru S. , Flippo-Morton T. , Sarantou T. , Norton H. J. , Calhoun M. , White R. L. 
Published: February 2017

131 Background: Many patients with invasive breast cancer receive neoadjuvant chemotherapy (NACT) prior to undergoing definitive surgical management in an effort to facilitate breast conservation. This study compares the re-excision rates of patients undergoing NACT with those who proceed directly to surgical treatment. A retrospective review of all breast cancer patients treated with neoadjuvant chemotherapy between November 2007 and June 2010 was performed. Re-excision rates were calculated for patients who received NACT and were then compared to a group of contemporaneous patients who did not receive neoadjuvant treatment (non-NACT). Re-excisions were routinely performed for disease <2mm from the margin. Patients with DCIS or LCIS were excluded. For statistical analysis, t-test and chi square tests were performed using SAS v9.2. Results: During the study period, 152 patients received neoadjuvant chemotherapy and then underwent surgical treatment of breast cancer. Of these patients, 108 (71.0%) underwent partial mastectomy as primary treatment, 44 (29.0%) underwent mastectomy. As a comparison group, we evaluated 188 consecutive patients diagnosed with invasive breast cancer who underwent initial treatment in the form of partial mastectomy. Table 1 demonstrates the characteristics of NACT and non-NACT patients and margin re-excision rates. Conclusions: Neoadjuvant chemotherapy is often administered in an effort to allow women with larger tumors to pursue breast conservation therapy. This study demonstrates that the rate of margin re-excision in NACT patients is not statistically different from those patients who undergo partial mastectomy as their primary treatment. [Table: see text]
Neoadjuvant endocrine therapy with exemestane in locally advanced breast cancer: The initial results from a Brazilian breast cancer center.
Authors: Marziona F. , Mattar A. , Hegg R. , Belloni S. J. , Rocha S. B. , Tavares E. G. , Monteiro W. M. , Carneiro A. Q. , Kuwamoto S. M. , Gebrim L. H. 
Published: February 2017

135 Background: Endocrine therapy is a well-established treatment for hormone-positive breast cancer, both in the adjuvant and the metastatic setting. Neoadjuvant chemotherapy has been used to increase the number of patients who are eligible for breast-conservation therapy (BCT) by inducing tumor downstaging. Neoadjuvant endocrine therapy (NET) is mostly used in patients who are not eligible for chemotherapy (almost reserved to postmenopausal patients). The clinical response with NET in postmenopausal patients with locally advanced breast cancer (LABC) and positive hormonal receptors is almost 75% with aromatase inhibitors (AI). The comparison among tamoxifen and the three AI (anastrozole, letrozole, and exemestane) shows a superiority to AI regarding BCT. There are few data in premenopausal women and NET. Methods: 29 women with rich positive hormone receptor were enrolled in the study between January to September of 2010. Patients received exemestane 25mg/day (EXE) and as we included both pre (12 patients) and postmenopausal (17 patients) women, the premenopausal ones were submitted to ooforectomy. Results: All patients were clinical stage III. In the premenopausal group 6 patients were submitted to surgery and 5 are still taking EXE. Between the two groups 9 patients were submitted to surgery, 4 showed response and are scheduling to surgery, 10 are still taking exemestane. Five patients had serious comorbidities and were submitted to radiotherapy after 9 months of EXE (one without clinical tumor) and are asymptomatic for at least 4 months. Just one patient (premenopausal) had tumor progression after 5 months of EXE and was switched to chemotherapy. Most common side effects were arthralgia/myalgia grade 1/2. Conclusions: In Brazil LABC is frequent and neoadjuvant chemotherapy is the standard treatment. We offered a treatment with a lower cost and especially lower side effects. Because of the initial stage, BCS was not possible, but we had clinical response in about 75% of the patients. This approach was good for patients with comorbidities, and despite the NET is not established for premenopausal patients our initial results encourage us to recommend it.