Breast Neoplasms: White J

Smith BD, Arthur DW, Buchholz TA, Haffty BG, Hahn CA, Hardenbergh PH, Julian TB, Marks LB, Todor DA, Vicini FA, Whelan TJ, White J, Wo JY, Harris JR. · Radiation Oncology Flight, Wilford Hall Medical Center, Lackland AFB, TX, USA. · Int J Radiat Oncol Biol Phys. · Pubmed #19545784 No free full text.

Abstract: PURPOSE: To present guidance for patients and physicians regarding the use of accelerated partial-breast irradiation (APBI), based on current published evidence complemented by expert opinion. METHODS AND MATERIALS: A systematic search of the National Library of Medicine's PubMed database yielded 645 candidate original research articles potentially applicable to APBI. Of these, 4 randomized trials and 38 prospective single-arm studies were identified. A Task Force composed of all authors synthesized the published evidence and, through a series of meetings, reached consensus regarding the recommendations contained herein. RESULTS: The Task Force proposed three patient groups: (1) a "suitable" group, for whom APBI outside of a clinical trial is acceptable, (2) a "cautionary" group, for whom caution and concern should be applied when considering APBI outside of a clinical trial, and (3) an "unsuitable" group, for whom APBI outside of a clinical trial is not generally considered warranted. Patients who choose treatment with APBI should be informed that whole-breast irradiation (WBI) is an established treatment with a much longer track record that has documented long-term effectiveness and safety. CONCLUSION: Accelerated partial-breast irradiation is a new technology that may ultimately demonstrate long-term effectiveness and safety comparable to that of WBI for selected patients with early breast cancer. This consensus statement is intended to provide guidance regarding the use of APBI outside of a clinical trial and to serve as a framework to promote additional clinical investigations into the optimal role of APBI in the treatment of breast cancer.

White J, Joiner MC. · Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI, USA. · Cancer Treat Res. · Pubmed #16335014 No free full text.

This publication has no abstract.

Arthur DW, Winter K, Kuske RR, Bolton J, Rabinovitch R, White J, Hanson WF, Wilenzick RM, McCormick B. · Department of Radiation Oncology, Virginia Commonwealth University, Richmond, VA 23298-0058, USA. · Int J Radiat Oncol Biol Phys. · Pubmed #18294778 No free full text.

Abstract: PURPOSE: Radiation Therapy Oncology Group 95-17 is a prospective Phase II cooperative group trial of accelerated partial breast irradiation (APBI) alone using multicatheter brachytherapy after lumpectomy in select early-stage breast cancers. Tumor control and survival outcomes are reported. METHODS AND MATERIALS: Eligibility criteria included Stage I/II breast carcinoma confirmed to be <3 cm, unifocal, invasive nonlobular histology with zero to three positive axillary nodes without extracapsular extension. APBI treatment was delivered with either low-dose-rate (LDR) (45 Gy in 3.5-5 days) or high-dose-rate (HDR) brachytherapy (34 Gy in 10 twice-daily fractions over 5 days). End points evaluated included in-breast control, regional control, mastectomy-free rate, mastectomy-free survival, disease-free survival, and overall survival. The study was designed to analyze the HDR and LDR groups separately and without comparison. RESULTS: Between 1997 and 2000, 100 patients were accrued and 99 were eligible; 66 treated with HDR brachytherapy and 33 treated with LDR brachytherapy. Eighty-seven patients had T1 lesions and 12 had T2 lesions. Seventy-nine were pathologically N0 and 20 were N1. Median follow-up in the HDR group is 6.14 years with the 5-year estimates of in-breast, regional, and contralateral failure rates of 3%, 5%, and 2%, respectively. The LDR group experienced similar results with a median follow-up of 6.22 years. The 5-year estimates of in-breast, regional, and contralateral failure rates of 6%, 0%, and 6%, respectively. CONCLUSION: Patients treated with multicatheter partial breast brachytherapy in this trial experienced excellent in-breast control rates and overall outcome that compare with reports from APBI studies with similar extended follow-up.

Ibbott GS, Hanson WF, O'Meara E, Kuske RR, Arthur D, Rabinovitch R, White J, Wilenzick RM, Harris I, Tailor RC. · Radiological Physics Center, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA. · Int J Radiat Oncol Biol Phys. · Pubmed #18035213 links to  free full text

Abstract: PURPOSE: The Radiation Therapy Oncology Group (RTOG) protocol 95-17 was a Phase I/II trial to evaluate multicatheter brachytherapy as the sole method of adjuvant breast radiotherapy for Stage I/II breast carcinoma after breast-conserving surgery. Low- or high-dose-rate sources were allowed. Dose prescription and treatment evaluation were based on recommendations in the International Commission on Radiation Units and Measurements (ICRU), Report 58 and included the parameters mean central dose (MCD), average peripheral dose, dose homogeneity index (DHI), and the dimensions of the low- and high-dose regions. METHODS AND MATERIALS: Three levels of quality assurance were implemented: (1) credentialing of institutions was required before entering patients into the study; (2) rapid review of each treatment plan was conducted before treatment; and (3) retrospective review was performed by the Radiological Physics Center in conjunction with the study chairman and RTOG dosimetry staff. RESULTS: Credentialing focused on the accuracy of dose calculation algorithm and compliance with protocol guidelines. Rapid review was designed to identify and correct deviations from the protocol before treatment. The retrospective review involved recalculation of dosimetry parameters and review of dose distributions to evaluate the treatment. Specifying both central and peripheral doses resulted in uniform dose distributions, with a mean dose homogeneity index of 0.83 +/- 0.06. CONCLUSIONS: Vigorous quality assurance resulted in a high-quality study with few deviations; only 4 of 100 patients were judged as representing minor variations from protocol, and no patient was judged as representing major deviation. This study should be considered a model for quality assurance of future trials.

Benitez PR, Keisch ME, Vicini F, Stolier A, Scroggins T, Walker A, White J, Hedberg P, Hebert M, Arthur D, Zannis V, Quiet C, Streeter O, Silverstein M. · Department of Surgery, William Beaumont Hospital, 3577 W. 13 Mile Rd, Suite 201, Beaumont Cancer Center, Royal Oak, MI 48073, USA. · Am J Surg. · Pubmed #17826055 No free full text.

Abstract: OBJECTIVE: Patients with early-stage invasive ductal breast cancer were prospectively evaluated using MammoSite RTS balloon brachytherapy (RTS Cytyc Corp, Marlborough, MA) as the sole modality for delivering accelerated partial breast irradiation to the lumpectomy bed with breast-conserving surgery. This report presents the 5-year results of the treated patients. METHODS: From May 2000 to October 2001, 70 patients were enrolled in this prospective study. Forty-three patients completed accelerated partial breast irradiation with MammoSite brachytherapy following lumpectomy and axillary staging. Thirty-six patients have been followed for a median of 5.5 years (mean 65.2 months). Criteria for entry into the study were unifocal invasive ductal carcinoma, tumor size < or = 2 cm, age > or = 45 years, absence of extensive intraductal component, cavity size > or = 3 cm in 1 dimension, node-negative, and final margins negative per National Surgical Adjuvant Breast and Bowel Project definition. A minimum balloon-to-skin surface distance of 5 mm was required. A dose of 34 Gy was delivered in 10 fractions over 5 days prescribed to 1 cm from the applicator surface using iridium-192 high-dose-rate brachytherapy. Data on infection, seromas, cosmetic outcome, and toxicities were collected at 3 and 6 months and at yearly intervals. Local recurrences, both true recurrences in the lumpectomy bed and failures outside the initially treated target volume (elsewhere failures), were recorded. Contralateral breast failure rates were noted. RESULTS: The catheter was not implanted in 16 of the 70 enrolled patients due to cavity size not amenable to balloon placement (n = 10), ineligible by criteria (n = 4), and skin spacing (n = 2). Fifty-four patients were implanted and 43 were successfully treated with MammoSite balloon brachytherapy. Reasons for catheter explantation in 11 patients were poor cavity conformance in 7, inadequate skin spacing in 2, positive node in 1 and age less than 45 years in 1. Of the 43 patients who completed treatment, the infection rate was 9.3%. Seroma formation occurred in 32.6% of patients, of which 12% were symptomatic requiring aspiration. Asymptomatic fat necrosis was identified in 4 of the 43 patients, noted from time of catheter removal at 11, 14, 42, and 63 months. Good-excellent cosmetic outcomes were achieved in 83.3% of the 36 patients with more than 5 years of follow-up. Cosmetic outcomes were improved, with increased skin spacing having statistical significance at skin spacing > or = 7 mm. The only serious adverse events were 2 infections: mastitis and abscess. Seven of the 43 treated patients have been discontinued from follow-up. None had a local recurrence recorded at last visit. Reasons for exit from the study were death from metastatic disease (n = 3), lost to follow-up (n = 2), and placed in hospice for other medical conditions (n = 2). No local recurrences (either at the tumor bed or elsewhere in the breast) or regional recurrences have occurred in the 36 patients who have been followed for a median of 5.5 years. No contralateral cancers have developed. CONCLUSIONS: MammoSite balloon brachytherapy as a sole modality for delivering radiation to the tumor bed has been successful in achieving excellent local control in this initial clinical study of patients with early-stage invasive ductal breast cancer. This has been achieved with minimal toxicities and good-excellent cosmetic outcomes in 83.3%. Accelerated partial breast irradiation using the MammoSite balloon in a carefully selected group of patients has demonstrated 5-year local recurrence results comparable to those achieved with conventional whole breast radiation therapy and interstitial catheter brachytherapy as reported at 5-year data points in studies of these treatment modalities. Poor cavity conformance and inadequate skin distance were the main factors limiting use of the MammoSite device. Extended follow-up will be required to determine the long-term efficacy of this treatment modality.

Kuske RR, Winter K, Arthur DW, Bolton J, Rabinovitch R, White J, Hanson W, Wilenzick RM. · Arizona Oncology Services and Foundation for Cancer Research and Education, Phoenix, AZ 85013, USA. · Int J Radiat Oncol Biol Phys. · Pubmed #16503383 No free full text.

Abstract: PURPOSE: Accelerated partial breast irradiation (APBI) can be delivered with brachytherapy within 4-5 days compared with 5-6 weeks for conventional whole breast external beam radiotherapy. Radiation Therapy Oncology Group 95-17 is the first prospective phase I-II cooperative group trial of APBI alone after lumpectomy in select patients with breast cancer. The toxicity rates are reported for low-dose-rate (LDR) and high-dose-rate (HDR) APBI on this trial. METHODS AND MATERIALS: The inclusion criteria for this study included invasive nonlobular tumors < or =3 cm after lumpectomy with negative surgical margins and axillary dissection with zero to three positive axillary nodes without extracapsular extension. The patients were treated with either LDR APBI (45 Gy in 3.5-5 days) or HDR APBI (34 Gy in 10 twice-daily fractions within 5 days). Chemotherapy (> or =2 weeks after APBI) and/or tamoxifen could be given at the discretion of the treating physicians. RESULTS: Between August 1997 and March 2000, 100 women were enrolled in this study, and 99 were evaluated. Of the 99 women, 33 were treated with LDR and 66 with HDR APBI. The median follow-up for all patients was 2.7 years (range, 0.6-4.4 years) and was 2.9 years for LDR and 2.7 years for HDR patients. Toxicities attributed to APBI included erythema, edema, tenderness, pain, and infection. Of the 66 patients treated with HDR APBI, 2 (3%) had Grade 3 or 4 toxicity. Of the 33 patients treated with LDR, 3 (9%) had Grade 3 or 4 toxicity during brachytherapy. Late toxicities included skin thickening, fibrosis, breast tenderness, and telangiectasias. No patient experienced late Grade 4 toxicity; the rate of Grade 3 toxicity was 18% for the LDR and 4% for the HDR groups. CONCLUSION: Acute and late toxicity for this invasive breast radiation technique was modest and acceptable. Patients receiving chemotherapy, a nonprotocol therapy, had a greater rate of Grade 3 toxicity. The study design did not allow for this to be tested statistically.

Keisch M, Vicini F, Kuske RR, Hebert M, White J, Quiet C, Arthur D, Scroggins T, Streeter O. · Department of Radiation Oncology, Mount Sinai Medical Center, Miami Beach, FL 33140, USA. · Int J Radiat Oncol Biol Phys. · Pubmed #12527040 No free full text.

Abstract: PURPOSE: We present the results of the initial clinical testing of the MammoSite balloon breast brachytherapy applicator in women with early-stage breast cancer treated with breast-conserving therapy. METHODS AND MATERIALS: Seventy patients were enrolled in a multicenter prospective trial testing the applicator for safety and performance. Fifty-four patients were implanted, and 43 patients were ultimately eligible for and received brachytherapy as the sole radiation modality after lumpectomy. Patients were staged T1N0M0 with negative pathologic margins and age >45 years. A dose of 34 Gy was delivered in 10 fractions over 5 days prescribed to 1 cm from the applicator surface using 192Ir high-dose-rate brachytherapy. A minimum skin-to-balloon surface distance of 5 mm was required for treatment. Device performance, complications, and cosmesis were assessed. RESULTS: Computed tomography imaging post-balloon inflation showed 8, 14, and 21 patients with 5-6 mm, 7-9 mm, and >10 mm of skin spacing, respectively. Two patients were explanted because of inadequate skin spacing and 7 because of suboptimal conformance of the surgical cavity to the applicator balloon. One patient was explanted because of positive nodal status and another because of age. The most common side effects related to device placement included mild erythema, drainage, pain, and echymosis. No severe side effects related to implantation, brachytherapy, or explantation occurred. Side effects related to radiation therapy were generally mild with erythema, pain, and dry desquamation being the most common. At 1 month, 88% of patients were evaluated as having good-to-excellent cosmetic results. CONCLUSIONS: The MammoSite balloon breast brachytherapy applicator performed well clinically. All eligible patients completed treatment. Side effects were mild to moderate and self-limiting. Skin-balloon surface distance and balloon-cavity conformance were the main factors limiting the initial use of the device.

White J, Howells A, Jones A, Poole C, Lind M, Stuart N, Carmichael J. · Nottingham City Hospital, Nottingham, UK. · Clin Oncol (R Coll Radiol). · Pubmed #11005696 No free full text.

Abstract: Anthracyclines are the gold standard monotherapy for metastatic breast cancer. Higher response rates are seen with drug combinations, especially with newer agents such as taxanes. The purpose of this study was to evaluate the toxicity and activity of the combination of paclitaxel and epirubicin in patients with advanced breast cancer. Thirty-five women with locally advanced or metastatic breast cancer (first and second relapse) were treated with epirubicin 75 mg/m2 and paclitaxel 200 mg/m2 3-weekly. Six centres recruited 35 patients; 34 (97%) were assessable for response. Eighteen had undergone prior chemotherapy, including six (17%) with anthracycline-containing regimens. Grade 4 neutropenia was found in 33 patients (94%), which was of 4 days' average duration; however, infective complications were rare, with only nine cycles (6%) complicated by neutropenic sepsis. There were two sepsis-related deaths. Symptomatic cardiotoxicity was infrequent, although a >15% decline in cardiac function was recorded in five patients (14%). Grade 3 peripheral neuropathy occurred in three patients (9%). The overall response rate was 50% (95% confidence interval 33-67) (complete response 12%; partial response 38%), with a median duration of response of 31 weeks. The median time to progression was 27 weeks, with a median survival of 48 weeks. This regimen appears to be a relatively safe, tolerable and effective treatment for advanced breast cancer. A United Kingdom Co-ordinating Committee for Cancer Research Phase III trial (AB-01) comparing this combination of epirubicin and paclitaxel with cyclophosphamide and paclitaxel completed accrual in November 1999.

Caldas-Lopes E, Cerchietti L, Ahn JH, Clement CC, Robles AI, Rodina A, Moulick K, Taldone T, Gozman A, Guo Y, Wu N, de Stanchina E, White J, Gross SS, Ma Y, Varticovski L, Melnick A, Chiosis G. · Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. · Proc Natl Acad Sci U S A. · Pubmed #19416831 No free full text.

Abstract: Triple-negative breast cancers (TNBCs) are defined by a lack of expression of estrogen, progesterone, and HER2 receptors. Because of the absence of identified targets and targeted therapies, and due to a heterogeneous molecular presentation, treatment guidelines for patients with TNBC include only conventional chemotherapy. Such treatment, while effective for some, leaves others with high rates of early relapse and is not curative for any patient with metastatic disease. Here, we demonstrate that these tumors are sensitive to the heat shock protein 90 (Hsp90) inhibitor PU-H71. Potent and durable anti-tumor effects in TNBC xenografts, including complete response and tumor regression, without toxicity to the host are achieved with this agent. Notably, TNBC tumors respond to retreatment with PU-H71 for several cycles extending for over 5 months without evidence of resistance or toxicity. Through a proteomics approach, we show that multiple oncoproteins involved in tumor proliferation, survival, and invasive potential are in complex with PU-H71-bound Hsp90 in TNBC. PU-H71 induces efficient and sustained downregulation and inactivation, both in vitro and in vivo, of these proteins. Among them, we identify downregulation of components of the Ras/Raf/MAPK pathway and G(2)-M phase to contribute to its anti-proliferative effect, degradation of activated Akt and Bcl-xL to induce apoptosis, and inhibition of activated NF-kappaB, Akt, ERK2, Tyk2, and PKC to reduce TNBC invasive potential. The results identify Hsp90 as a critical and multimodal target in this most difficult to treat breast cancer subtype and support the use of the Hsp90 inhibitor PU-H71 for clinical trials involving patients with TNBC.

Kainz K, White J, Herman J, Li XA. · Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI, USA. · Int J Radiat Oncol Biol Phys. · Pubmed #19362247 No free full text.

Abstract: PURPOSE: To investigate whether helical tomotherapy can provide conformal, uniform target-dose coverage for partial-breast irradiation (PBI) of patients positioned prone while achieving organ-at-risk sparing compliant with National Surgical Adjuvant Breast and Bowel Project (NSABP) B-39/Radiation Therapy Oncology Group (RTOG) 0413 guidelines; and to report our initial experience with the delivery of prone-breast PBI treatments using tomotherapy. METHODS AND MATERIALS: For our pilot study, we generated helical tomotherapy plans upon the images of 10 prone-positioned patients previously treated using conventional techniques. We also generated plans for 4 left-breast prone-positioned PBI patients who were treated using helical tomotherapy, and recalculated the planned sinograms upon the pretreatment megavoltage computed tomographic images. Of the planning target volume (PTV), 95% was prescribed to receive 38.5 Gy, administered twice daily for 5 days. RESULTS: For our pilot study, on average the maximum point dose to the PTV was 41.3 Gy, and 99% or more of the PTV received 90% or more of the prescribed dose. RTOG 0413 dose-volume histogram objectives were fulfilled for all organs at risk except the contralateral breast, which received a maximum point dose as high as 3.2 Gy in 1 case. For the prospective prone-positioned tomotherapy PBI plans, all objectives were met except the contralateral-breast maximum dose, which was 3.7 Gy on average. Dose calculation using the planned sinogram upon the pretreatment megavoltage computed tomographic images indicated consistency with the planned dose distributions. CONCLUSIONS: Helical tomotherapy can provide conformal and uniform target-dose coverage simultaneous with adequate sparing of critical structures; in this study only the contralateral breast dose exceeded RTOG 0413 guidelines. Dosimetric results for our 4 prospective patient cases were consistent with those for our 10-case pilot study.

Casey T, Bond J, Tighe S, Hunter T, Lintault L, Patel O, Eneman J, Crocker A, White J, Tessitore J, Stanley M, Harlow S, Weaver D, Muss H, Plaut K. · Animal Science, University of Vermont, Burlington, VT 05405, USA. · Breast Cancer Res Treat. · Pubmed #18373191 No free full text.

Abstract: BACKGROUND: Breast cancer invasion and metastasis involves both epithelial and stromal changes. Our objective was to delineate the pivotal role stroma plays in invasion by comparing transcriptomes among stromal and epithelial cells in normal tissue and invasive breast cancer. METHODS: Total RNA was isolated from epithelial and stromal cells that were laser captured from normal breast tissue (n = 5) and invasive breast cancer (n = 28). Gene expression was measured using Affymetrix U133A 2.0 GeneChips. Differential gene expression was evaluated and compared within a model that accounted for cell type (epithelial [E] versus stromal [S]), diagnosis (cancer [C] versus normal [N]) as well as cell type-diagnosis interactions. RESULTS: Compared to NE, the CE transcriptome was highly enriched with genes in proliferative, motility and ECM ontologies. Differences in CS and NS transcriptomes suggested that the ECM was being remodeled in invasive breast cancer, as genes were over-represented in ECM and proteolytic ontologies. Genes more highly expressed in CS compared to CE were primarily ECM components or were involved in the remodeling of ECM, suggesting that ECM biosynthesis and remodeling were initiated in the tumor stroma. CONCLUSION: Based on identified molecular cross-talk between the two contiguous cell populations, a mechanistic model that spurs invasion is proposed, that shows breast cancer invasion proceeds through the acquisition of a motile phenotype in tumor epithelial cells and a reactive phenotype in cancer associated fibroblasts.

Morrow NV, Stepaniak C, White J, Wilson JF, Li XA. · Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI 53226, USA. · Int J Radiat Oncol Biol Phys. · Pubmed #17889272 No free full text.

Abstract: PURPOSE: Intra- and interfractional errors for breast cancer patients undergoing breast irradiation in the prone position were analyzed. METHODS AND MATERIALS: To assess intrafractional error resulting from respiratory motion, four-dimensional computed tomography scans were acquired for 3 prone and 3 supine patients, and the respiratory motion was compared for the two positions. To assess the interfractional error caused by daily set-up variations, daily electronic portal images of one of the treatment beams were taken for 15 prone-positioned patients. Portal images were then overlaid with images from the planning system that included the breast contour and the isocenter, treatment beam portal, and isocenter. The shift between the planned and actual isocenter was recorded for each portal image, and descriptive statistics were collected for each patient. The margins were calculated using the 2Sigma + 0.7sigma recipe, as well as 95% confidence interval based on the pooled standard deviation of the datasets. RESULTS: Respiratory motion of the chest wall is drastically reduced from 2.3 +/- 0.9 mm in supine position to -0.1 +/- 0.4 mm in prone position. The daily set-up errors vary in magnitude from 0.0 cm to 1.65 cm and are patient dependent. The margins were defined by considering only the standard deviation to be 1.1 cm, and 2.0 cm when the systematic errors were considered using the 2Sigma + 0.7sigma recipe. CONCLUSIONS: Prone positioning of patients for breast irradiation significantly reduces the uncertainty introduced by intrafractional respiratory motion. The presence of large systematic error in the interfractional variations necessitates a large clinical target volume-to-planning target volume margin and indicates the importance of image guidance for partial breast irradiation in the prone position, particularly using imaging modality capable of identifying the lumpectomy cavity.

Bovi J, Qi XS, White J, Li XA. · Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI 53226, USA. · Radiother Oncol. · Pubmed #17692980 No free full text.

Abstract: BACKGROUND AND PURPOSE: Accelerated partial breast irradiation (APBI) is being studied in a phase III randomized trial as an alternative to whole breast irradiation (WBI) for early stage breast cancer patients. There are three methods for APBI: multi-catheter brachytherapy (MCT), MammoSite brachytherapy (MST), or 3D conformal (3DCRT). There is a paucity of data comparing among methods. Using a linear-quadratic (LQ) model, we evaluated the anticipated efficacy among the APBI methods for equivalent uniform dose (EUD), Tumor Control Probability (TCP), and Normal Tissue Complication Probability (NTCP). MATERIALS AND METHODS: Treatment plans from five patients treated by each APBI modality were retrospectively selected. Dose-volume-histograms (DVH) for planning target volume (PTV), breast, and lung were generated. The LQ parameters alpha=0.3Gy(-1) and alpha/beta=10Gy were used for calculations. The values of EUD, TCP, and NTCP were calculated based on DVHs. RESULTS: The average EUD (normalized to 3.4Gy BID) for the MCT, MST, and 3DCRT APBI was 35, 37.2, and 37.6Gy. When normalized to 2Gy fractionation these become, 42.2, 46.4, and 46.9Gy. Average TCP for MCT, MST, and 3DCRT PBI was 94.8%, 99.1%, and 99.2%. The NTCP values for breast and lung were low for all three methods. CONCLUSIONS: The EUD for PTV and TCP were most similar in MST and 3DCRT APBI and were lower in MCT APBI. This questions the equivalence of the three APBI modalities that are currently being evaluated in the NSABP-B39/RTOG 0413 protocol.

Casey TM, Eneman J, Crocker A, White J, Tessitore J, Stanley M, Harlow S, Bunn JY, Weaver D, Muss H, Plaut K. · Department of Animal Science, Michigan State University, B290 Anthony Hall, East Lansing, MI 48824, USA. · Breast Cancer Res Treat. · Pubmed #17674196 No free full text.

Abstract: Cancer associated fibroblasts (CAFs) are believed to promote tumor growth and progression. Our objective was to measure the effect of TGF-beta1 on fibroblasts isolated from invasive breast cancer patients. Fibroblasts were isolated from tissue obtained at surgery from patients with invasive breast cancer (CAF; n = 28) or normal reduction mammoplasty patients (normal; n = 10). Myofibroblast activation was measured by counting cells immunostained for smooth muscle alpha actin (ACTA2) in cultures +/- TGF-beta 1. Conditioned media (CM) was collected for invasion assays and RNA was isolated from cultures incubated in media +/- TGF-beta1 for 24 h. Q-PCR was used to measure expression of cyclin D1, fibronectin, laminin, collagen I, urokinase, stromelysin-1, and ACTA2 genes. Invasion rate was measured in chambers plated with MDA-MB-231 cells and exposed to CM in the bottom chamber; the number of cells that invaded into the bottom chamber was counted. Wilcox Rank Sum tests were used to evaluate differences in CAFs and normal fibroblasts and the effect of TGF-beta 1. There was no difference in percent myofibroblasts or invasion rate between normal and CAF cultures. However, TGF-beta1 significantly increased the percent of myofibroblasts (P < 0.01) and invasion rate (P = 0.02) in CAF cultures. Stromelysin-1 expression was significantly higher in normal versus CAF cultures (P < 0.01). TGF-beta 1 significantly increased ACTA2 expression in both normal and CAF cultures (P < 0.01). Expression of fibronectin and laminin was significantly increased by TGF-beta in CAF cultures (P < 0.01). CAFs were measurably different from normal fibroblasts in response to TGF-beta 1, suggesting that TGF-beta stimulates changes in CAFs that foster tumor invasion.

Ahunbay EE, Chen GP, Thatcher S, Jursinic PA, White J, Albano K, Li XA. · Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI 53226, USA. · Int J Radiat Oncol Biol Phys. · Pubmed #17275205 No free full text.

Abstract: PURPOSE: To investigate the technical and dosimetric advantages and the efficacy of direct aperture optimized intensity-modulated radiation therapy (DAO-IMRT) over standard (e.g., beamlet optimized) IMRT and conventional three-dimensional conformal radiotherapy (3D-CRT) for whole breast irradiation in supine and prone positions. METHODS AND MATERIALS: We retrospectively designed DAO-IMRT plans for 15 breast cancer patients in supine (10 patients) and prone (5 patients) positions with a goal of uniform dose coverage of the whole breast. These DAO-IMRT plans were compared with standard IMRT using beamlet optimization and conventional 3D-CRT plans using wedges. All plans used opposed tangential beam arrangements. RESULTS: In all cases, the DAO-IMRT plans were equal to or better than those generated with 3D-CRT and standard beamlet-IMRT. For supine cases, DAO-IMRT provided higher uniformity index (UI, defined as the ratio of the dose to 95% of breast volume to the maximum dose) than either 3D-CRT (0.88 vs. 0.82; p = 0.026) or beamlet-IMRT (0.89 vs. 0.85; p = 0.003). Direct aperture optimized IMRT also gave lower lung doses than either 3D-CRT (V20 = 7.9% vs. 8.6%; p = 0.024) or beamlet-IMRT (V20 = 8.4% vs. 9.7%; p = 0.0008) for supine patients. For prone patients, DAO-IMRT provided higher UI than either 3D-CRT (0.89 vs. 0.83; p = 0.027) or beamlet-IMRT (0.89 vs. 0.85; p = 0.003). The planning time for DAO-IMRT was approximately 75% less than that of 3D-CRT. The monitor units for DAO-IMRT were approximately 60% less than those of beamlet-IMRT. CONCLUSION: Direct aperture optimized IMRT improved the overall quality of dose distributions as well as the planning and delivery efficiency for treating whole breast in both supine and prone positions.

Jones RB, Pearson J, Cawsey AJ, Bental D, Barrett A, White J, White CA, Gilmour WH. · Faculty of Health and Social Work, University of Plymouth, Drake Circus, Plymouth PL4 8AA. · BMJ. · Pubmed #16597660 links to  free full text

Abstract: OBJECTIVE: To explore the hypothesis that different methods of selecting and printing information for cancer patients could improve emotional support by affecting interaction with others, and so lead to improved psychological wellbeing. DESIGN: Randomised trial with eight groups (three factors, 2x2x2). Data collected at recruitment and three month follow-up. PARTICIPANTS: 400 patients starting radiotherapy, of whom 325 with breast or prostate cancer and complete anxiety and depression data were included in the analysis. INTERVENTIONS: Printed booklets: half had only general information from CancerBACUP about each patient's cancer and half had personalised information from the patient's medical record plus selected general information; half were composed of information chosen interactively by the patient and half were produced automatically with a larger volume of material; and half had additional advice on anxiety management and half did not. MAIN OUTCOME MEASURES: Patients' views of the information, use of their booklets with others; change in reported social support; change in anxiety and depression. RESULTS: The larger booklets produced automatically were more likely to be found useful and to tell patients something new and less likely to be seen as too limited than the booklets produced interactively, but they were also more likely to overwhelm some patients. Personalised booklets were more likely than general booklets to tell patients something new. There was no difference in patients' perceived understanding of their cancer by any of the intervention factors. Patients with personalised information were more likely to show their booklets to others and to think it helped in discussing their cancer or its treatment. There were no major differences in social support, anxiety, or depression by any intervention factors. CONCLUSIONS: Patients were more likely to show personalised information to their confidants than general information. Further research is needed into the effects of sharing information on patients' social support and anxiety. Trial registration US Government Clinical Trials Database NCT00127465.

Dubner S, Bovi J, White J, Susnik B. · Department of Pathology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA. · Breast J. · Pubmed #16509846 No free full text.

Abstract: We present the case of a 52-year-old woman who underwent lumpectomy and radiation therapy for breast carcinoma and 2 years later presented with changes limited to the breast radiation field including hyperpigmentation, retraction, and skin thickening. These clinical features, along with pathologic findings, were diagnostic of postirradiation morphea. It is important to be aware of this rare complication of radiation therapy because it clinically presents with symptoms mimicking malignancy and may be misinterpreted as recurrent carcinoma or even angiosarcoma.

White J. · Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI 53226, USA. · Brachytherapy. · Pubmed #16182217 No free full text.

This publication has no abstract.

Pierce LJ, Moughan J, White J, Winchester DP, Owen J, Wilson JF. · Department of Radiation Oncology, University of Michigan School of Medicine, Ann Arbor, MI 48109-0010, USA. · Int J Radiat Oncol Biol Phys. · Pubmed #15850920 No free full text.

Abstract: PURPOSE: The Patterns of Care Study survey process evaluation has been an effective means of assessing the evaluation and treatment practices used by radiation oncologists in the United States for Stage I-II breast cancer. The current 1998-1999 report updates the previous 1989 and 1993-1994 analyses and reflects the recent changes in surgery and systemic therapy observed nationally in the management of early-stage disease. METHODS AND MATERIALS: A weighted sample size of 71,877 patient records of women treated with breast-conserving surgery and radiotherapy (RT) was obtained from a stratified two-stage sampling of 353 patient records. These cases were centrally reviewed from academic and private radiation oncology practices across the United States. The data collected included patient characteristics, clinical and pathologic factors, and surgical and RT details. The results were compared with those of previous Patterns of Care Study survey reports. RESULTS: Of the patients in the current survey, 97% had undergone mammography before biopsy. A review of the primary tumor pathologic findings indicated improved quantification of an intraductal component from 7.0% in 1993-1994 to 20.4% in 1998-1999 (p = 0.01). The tumor characteristics were better defined, with estrogen and progesterone receptor measurement performed in 91.4% and 91.3% in the 1998-1999 survey vs. 83.7% and 80.3% in the 1989 survey, respectively (p = 0.03 and p = 0.002, respectively). Axillary dissection was performed in 82.2% in the present survey compared with 93.6% in the 1993-1994 survey (p = 0.0004); sentinel node biopsy was performed in 20.1% of the present cases. The use of CT for planning was increased in the current survey, with 22.9% cases CT planned vs. 9% in 1993-1994 (p = 0.10). In the present survey, 100% had received whole breast RT. When a supraclavicular field was added, the dose was prescribed to a specified depth in 67.5% of cases, most commonly 3 cm. When an axillary field was added, the dose was generally prescribed to the mid-plane. Chemotherapy and tamoxifen was used in 36% and 55.8% of patients, respectively, in the 1998-1999 survey, representing a statistically significant increase compared with the 1993-1994 survey, despite comparable pathologic tumor size and nodal involvement. CONCLUSION: The present results demonstrate a high level of compliance of the sampled radiation oncology practices with current breast conservation standards and continued improvement in many categories compared with prior patterns of care study surveys. The estimates in the current survey after whole breast RT will serve as a benchmark against newer trends in breast cancer RT, such as partial breast RT.

White J, Moughan J, Pierce LJ, Morrow M, Owen J, Wilson JF. · Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI 53226, USA. · Int J Radiat Oncol Biol Phys. · Pubmed #15337542 No free full text.

Abstract: PURPOSE: The Patterns of Care Study performed this first known practice survey to establish a national profile of the delivery of postmastectomy radiotherapy (RT) in operable breast cancer. METHODS AND MATERIALS: A Patterns of Care Study research associate collected data from 55 randomly selected institutions. The survey data included 132 items describing the patient, pathologic features, and treatment course for patients with clinical Stage I, II, and IIIA breast cancer undergoing postmastectomy RT in 1998 and 1999. A multivariate analysis was performed to determine the impact of tumor factors and type of treatment facility on the radiation fields used. RESULTS: A weighted sample size of 13,720 was obtained from a sampling of 405 patient records. The mean tumor size was 3.5 cm, and the mean number of axillary nodal metastases was 4.55. Lymphatic vascular invasion was noted in 34%, microscopic skin or dermal lymphatic invasion in 16%, positive or close margins in 36%, and extracapsular nodal extension in 23%. Radiotherapy included the chest wall in all cases and the regional nodes in 78%. When nodal RT was delivered, it included a supraclavicular field, supplemental axillary field, and/or an internal mammary field in 98%, 46%, and 23% of cases, respectively. Chest wall and supraclavicular RT was delivered in >90% of instances with 6-MV photons to doses between 45 and 50 Gy. More variation was seen in the delivery of the axillary and internal mammary RT. On multivariate analysis, the presence of four or more positive nodes and treatment at a large-volume facility were the factors most frequently associated with the use of regional radiation fields. CONCLUSION: This Patterns of Care Study survey has demonstrated that breast cancer patients undergoing postmastectomy RT in 1998 and 1999 had a high proportion of factors associated with an increased risk of locoregional failure. The practice patterns established in this study provide a baseline for comparison with future survey results.

White J, Morrow M, Moughan J, Owen J, Pajak T, DesHarnais S, Winchester DP, Wilson JF, Anonymous00346, Anonymous00347. · Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA. · Cancer. · Pubmed #12569588 links to  free full text

Abstract: BACKGROUND: Multiple treatment guidelines and practice standards have been developed regarding the management of patients with breast carcinoma. Few evaluations of the penetration and utility of these practice standards have been performed. In 1992, the American College of Surgeons (ACOS), the American College of Radiology, the College of American Pathologists, and the Society of Surgical Oncology collaborated in establishing standards for breast-conservation treatment (BCT). The authors sought to determine whether practice patterns for patients with breast carcinoma who underwent BCT were consistent with these standards 2 years after their dissemination and to establish whether compliance varied by the same patient and hospital variables that predicted for the amount of BCT performed. METHODS: A study specific questionnaire was circulated to cancer registrars through the Commission on Cancer of the ACOS asking them to submit reports on patients with Stage I and II breast carcinoma who were diagnosed in 1994. Eight hundred forty-two predominantly community hospitals throughout the United States responded, yielding a total of 16,643 analyzable patients. The frequency of compliance to the 1992 published practice standards for 7097 patients who received BCT was determined. The variation in compliance rates by patient age, race, and insurance status and the treating hospital's geographic locations and cancer programs were evaluated. RESULTS: Of the 22 standards that were evaluated in the areas of preoperative mammography (2 standards), labeling of the surgical specimen (3 standards), pathology report content (10 standards), radiation after lumpectomy (6 standards), and systemic therapy for patients with positive lymph nodes (1 standard), treatment adherence was > or = 80% for 16 standards (73%). Poor compliance was demonstrated for six standards: the documentation of an abnormality's size in the mammogram report, labeling the lumpectomy specimen with the affected quadrant of the breast, spatial orientation of the lumpectomy specimen and inclusion of lymphatic/vascular invasion, ductal carcinoma in situ, and macroscopic margin assessment in the pathology report. Variation in compliance to a standard occurred frequently across the type of hospital cancer program and geographic region (77% for both), and variation occurred less across the patient variables of age (32%), race (41%), and payer (23%). There was not a pattern of more frequent compliance among variables associated with more BCT use. CONCLUSIONS: Large-scale evaluation of the penetration of treatment standards is feasible. For patients who underwent lumpectomy, practice appeared to be consistent (> or = 80% compliance), with 73% of 22 treatment standards evaluated. The standards with poor compliance represent areas for targeted physician education and reevaluation. Significant differences in adherence to a standard were seen frequently based on a hospital's geographic location and type of cancer program. This emphasizes the importance of adequate dissemination of treatment standards to ensure penetration into medical practices of all types.

Morrow M, White J, Moughan J, Owen J, Pajack T, Sylvester J, Wilson JF, Winchester D. · American College of Surgeons Commission on Cancer, Chicago, IL, USA. · J Clin Oncol. · Pubmed #11304779 No free full text.

Abstract: PURPOSE: To define patterns of care for the local therapy of stage I and II breast cancer and to identify factors used to select patients for breast-conserving therapy (BCT). PATIENTS AND METHODS: A convenience sample of 16,643 patients with stage I and II breast cancer treated in 1994 was obtained from hospital-based tumor registries. Histologic variables were determined from original pathology reports. RESULTS: BCT was performed in 42.6% of patients. Multivariate analysis demonstrated that living in the Northeast United States (odds ratio [OR], 2.48; 95% confidence interval [CI], 2.16 to 2.84), having a clinical T1 tumor (OR, 2.51; 95% CI, 2.27 to 2.78), and having a tumor without an extensive intraductal component (OR, 2.07; 95% CI, 1.81 to 2.37) were the strongest predictors of breast-conserving surgery. Radiation therapy was given to 86% of patients who had breast-conserving surgery. Age less than 70 years was the most significant predictor of receiving radiation (OR, 2.11; 95% CI, 1.77 to 2.25). Tumor variables did not correlate with the use of radiation, but favorable tumor characteristics were associated with the use of breast-conserving surgery. CONCLUSION: Despite strong evidence supporting the use of BCT, the majority of women continue to be treated with mastectomy. Predictors of the use of BCT do not correspond to those suggested in guidelines.

Cochran SD, Mays VM, Bowen D, Gage S, Bybee D, Roberts SJ, Goldstein RS, Robison A, Rankow EJ, White J. · Department of Epidemiology, School of Public Health, Center for Health Sciences, University of California, Los Angeles, Box 951772, Los Angeles, CA 90095-1772, USA. · Am J Public Health. · Pubmed #11291371 links to  free full text

Abstract: OBJECTIVES: This study examined whether lesbians are at increased risk for certain cancers as a result of an accumulation of behavioral risk factors and difficulties in accessing health care. METHODS: Prevalence estimates of behavioral risk factors (nulliparity, obesity, smoking, and alcohol use), cancer screening behaviors, and self-reported breast cancer histories derived from 7 independently conducted surveys of lesbians/bisexual women (n = 11,876) were compared with national estimates for women. RESULTS: In comparison with adjusted estimates for the US female population, lesbians/bisexual women exhibited greater prevalence rates of obesity, alcohol use, and tobacco use and lower rates of parity and birth control pill use. These women were also less likely to have health insurance coverage or to have had a recent pelvic examination or mammogram. Self-reported histories of breast cancer, however, did not differ from adjusted US female population estimates. CONCLUSIONS: Lesbians and bisexual women differ from heterosexual women in patterns of health risk. These women would be expected to be at especially greater risk for chronic diseases linked to smoking and obesity.

Sparber A, Jonas W, White J, Derenzo E, Johnson E, Bergerson S. · Department of Nursing, National Institutes of Health, Bethesda, Maryland, USA. · Cancer Invest. · Pubmed #10834028 No free full text.

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White J. · No affiliation provided · J Natl Cancer Inst. · Pubmed #10716955 links to  free full text

This publication has no abstract.