Breast Neoplasms: Pierce LJ

Carlson RW, Allred DC, Anderson BO, Burstein HJ, Carter WB, Edge SB, Erban JK, Farrar WB, Goldstein LJ, Gradishar WJ, Hayes DF, Hudis CA, Jahanzeb M, Kiel K, Ljung BM, Marcom PK, Mayer IA, McCormick B, Nabell LM, Pierce LJ, Reed EC, Smith ML, Somlo G, Theriault RL, Topham NS, Ward JH, Winer EP, Wolff AC, Anonymous00042. · No affiliation provided · J Natl Compr Canc Netw. · Pubmed #19200416 No free full text.

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Carlson RW, Anderson BO, Burstein HJ, Cox CE, Edge SB, Farrar WB, Goldstein LJ, Gradishar WJ, Hayes DF, Hudis C, Jahanzeb M, Ljung BM, Marks LB, McCormick B, Nabell LM, Pierce LJ, Reed EC, Silver SM, Smith ML, Somlo G, Theriault RL, Ward JH, Winer EP, Wolff AC, Anonymous00249. · Stanford Hospital & Clinics, USA. · J Natl Compr Canc Netw. · Pubmed #16002000 No free full text.

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Carlson RW, Moench S, Hurria A, Balducci L, Burstein HJ, Goldstein LJ, Gradishar WJ, Hughes KS, Jahanzeb M, Lichtman SM, Marks LB, McClure JS, McCormick B, Nabell LM, Pierce LJ, Smith ML, Topham NS, Traina TA, Ward JH, Winer EP. · No affiliation provided · J Natl Compr Canc Netw. · Pubmed #18597715 No free full text.

Abstract: Breast cancer is common in older women, and the segment of the U.S. population aged 65 years and older is growing rapidly. Consequently, awareness is increasing of the need to identify breast cancer treatment recommendations to assure optimal, individualized treatment of older women with breast cancer. However, the development of these recommendations is limited by the heterogeneous nature of this population with respect to functional status, social support, life expectancy, and the presence of comorbidities, and by the underrepresentation of older patients with breast cancer in randomized clinical trials. The NCCN Breast Cancer in the Older Woman Task Force was convened to provide a forum for framing relevant questions on topics that impact older women with early-stage, locally advanced, and metastatic breast cancer. The task force is a multidisciplinary panel of 18 experts in breast cancer representing medical oncology, radiation oncology, surgical oncology, geriatric oncology, geriatrics, plastic surgery, and patient advocacy. All task force members were from NCCN institutions and were identified and invited solely by NCCN. Members were charged with identifying evidence relevant to their specific expertise. During a 2-day meeting, individual members provided didactic presentations; these presentations were followed by extensive discussions during which areas of consensus and controversy were identified on topics such as defining the "older" breast cancer patient; geriatric assessment tools in the oncology setting; attitudes of older patients with breast cancer and their physicians; tumor biology in older versus younger women with breast cancer; implementation of specific interventions in older patients with breast cancer, such as curative surgery, surgical axillary staging, radiation therapy, reconstructive surgery, endocrine therapy, chemotherapy, HER2-directed therapy, and supportive therapies; and areas requiring future studies.

Buchholz TA, Lehman CD, Harris JR, Pockaj BA, Khouri N, Hylton NF, Miller MJ, Whelan T, Pierce LJ, Esserman LJ, Newman LA, Smith BL, Bear HD, Mamounas EP. · Department of Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcolmbe Blvd, Unit 1202, Houston, TX 77030, USA. · J Clin Oncol. · Pubmed #18258988 No free full text.

Abstract: PURPOSE: To review the state of the science with respect to diagnostic imaging and locoregional therapy for patients with breast cancer receiving preoperative chemotherapy. METHODS: Published data relevant to clinical staging, monitoring of tumor response, and locoregional therapy for patients with breast cancer treated with preoperative chemotherapy were reviewed. RESULTS: High-quality data from prospective randomized trials are limited. Available data suggest that locoregional therapy decisions should be based on both the pretreatment clinical extent of disease and the pathologic extent of the disease after chemotherapy. Accordingly, physical examination and imaging studies that accurately define the initial extent of disease are required before treatment. Sentinel lymph node biopsy can be performed either before or after preoperative chemotherapy for patients with clinical N0 disease. The success of breast conservation after preoperative chemotherapy depends on careful patient selection and achieving negative surgical margins. Adjuvant breast radiation is indicated for all patients treated with breast conservation. For patients treated with mastectomy, chest-wall and regional nodal radiation should be considered for those who present with clinical stage III disease or have histologically positive lymph nodes after preoperative chemotherapy. Additional prospective studies are needed to determine the value of postmastectomy radiation for patients with stage II breast cancer who have negative lymph nodes after chemotherapy. CONCLUSION: The increased use of preoperative chemotherapy has raised new questions concerning the optimal methods to stage and monitor disease response to treatment and how to optimize locoregional treatment. The available evidence suggests that a multidisciplinary approach improves outcomes.

Carlson RW, Anderson BO, Burstein HJ, Carter WB, Edge SB, Farrar WB, Goldstein LJ, Gradishar WJ, Hayes DF, Hudis CA, Jahanzeb M, Ljung BM, Kiel K, Marks LB, McCormick B, Nabell LM, Pierce LJ, Reed EC, Silver SM, Smith ML, Somlo G, Theriault RL, Ward JH, Winer EP, Wolff AC. · National Comprehensive Cancer Network · J Natl Compr Canc Netw. · Pubmed #17439758 No free full text.

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Pierce LJ. · Department of Radiation Oncology, University of Michigan School of Medicine, Ann Arbor, MI, USA. · J Clin Oncol. · Pubmed #15755979 No free full text.

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Krueger EA, Fraass BA, Pierce LJ. · Department of Radiation Oncology, University of Michigan, Ann Arbor, MI 48109, USA. · Semin Radiat Oncol. · Pubmed #12118390 No free full text.

Abstract: In recent years, interest has grown throughout the radiotherapy community in investigation and clinical application of intensity-modulated radiation therapy (IMRT) for adjuvant treatment of breast cancer. IMRT removes the usual reliance on flat (or uniform-intensity) radiation fields, and instead replaces that simple paradigm with a variable-intensity pattern that is usually determined with the aid of a computerized optimization algorithm. The main goal of much IMRT and optimization work is the delivery of more conformal plans to the patient. Thus, IMRT has the potential to improve target coverage and reduce inhomogeneities observed within the breast (and regional lymph nodes) that are obtained with standard plans. Furthermore, IMRT may be able to reduce doses delivered to the heart and lungs, and may potentially minimize further the probability of complications from radiotherapy.

Pierce LJ. · Department of Radiation Oncology, University of Michigan, Ann Arbor, MI 48109-0010, USA. · Semin Radiat Oncol. · Pubmed #10378970 No free full text.

Abstract: With careful interpretation of existing studies of postmastectomy radiotherapy, much has been learned about the ability of radiotherapy to significantly reduce local failure and potentially impact on survival. With this knowledge, however, has come additional questions about the mechanisms by which radiotherapy could affect systemic control and the extent of that benefit. Therefore, these questions need to be investigated in well-designed, randomized trials that incorporate aggressive surgical techniques and contemporary chemotherapy regimens into the clinical plan. A trial that is currently in progress should give additional insight into whether regional irradiation in the modern era, which incorporates the internal mammary nodes in the radiotherapy field, impacts systemic control. An upcoming trial will investigate whether women at moderate risk for locoregional failure will benefit from comprehensive radiotherapy after aggressive surgery and chemotherapy. And, although no national studies are currently planned to test the optimal sequencing of radiotherapy and chemotherapy, consideration should be given to studying this issue in large, randomized trials.

Morrow M, Jordan VC, Takei H, Gradishar WJ, Pierce LJ. · Northwestern University Medical School, Chicago, Illinois, USA. · Curr Probl Surg. · Pubmed #10089889 No free full text.

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Pinsky RW, Rebner M, Pierce LJ, Ben-David MA, Vicini F, Hunt KA, Helvie MA. · Department of Radiology, University of Michigan Health System, 1500 E Medical Center Dr., Ann Arbor, MI 48109-0302, USA. · AJR Am J Roentgenol. · Pubmed #17579163 links to  free full text

Abstract: OBJECTIVE: The purpose of our study was to determine the mammographic appearance, detection method, and stage of ipsilateral breast tumor recurrence in women treated with breast-conserving surgery and whole-breast radiation therapy for ductal carcinoma in situ (DCIS). MATERIALS AND METHODS: Following institutional review board approval, records of women treated with breast-conserving surgery and radiation therapy for DCIS who developed an ipsilateral breast tumor recurrence from 1981 to 2003 were reviewed retrospectively. Multiinstitutional database records showed 513 women were treated, of whom 42 (8.2%) developed local recurrence. Study criteria were fulfilled and complete records were available for 32 women. Mean age at initial diagnosis was 49 years (range, 26-73 years). RESULTS: Of the 32 patients included in our study, 31 (97%) recurrences were mammographically apparent. Twenty-nine (91%) of 32 were diagnosed exclusively by mammography. Mammographic findings at recurrence were calcifications in 24 (75%) of 32, mass in six (19%) of 32, and distortion in one (3%) of 32. The mean time to recurrence was 4.5 years. Twelve (40%) of 30 had the recurrence in a remote quadrant from the original cancer. Recurrences were DCIS in 17 (53%) of 32, DCIS with microinvasion in six (19%) of 32, invasive ductal cancer in three (9%) of 32, invasive lobular cancer in two (6%) of 32, and mixed DCIS and invasive cancer in four (13%) of 32. Six (67%) of nine patients with invasive cancer (excluding microinvasion) had tumors smaller than 1 cm. Ninety-one percent of recurrences were minimal cancers. All recurrences were stage 0 or 1. CONCLUSION: Mammography successfully detected ipsilateral breast tumor recurrence, predominantly as calcifications or masses, after breast-conserving surgery with radiation therapy for DCIS in 97% of cases. The recurrences were located at variable distances from the lumpectomy site. Ninety-one percent of recurrences were minimal cancers and all were early stage, connoting excellent prognosis.

Solin LJ, Fourquet A, Vicini FA, Taylor M, Olivotto IA, Haffty B, Strom EA, Pierce LJ, Marks LB, Bartelink H, McNeese MD, Jhingran A, Wai E, Bijker N, Campana F, Hwang WT. · Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA. · Cancer. · Pubmed #15674853 links to  free full text

Abstract: BACKGROUND: Ductal carcinoma in situ (DCIS) is detected most commonly on routine screening mammography in the asymptomatic patient, and has a long natural history. The objective of the current study was to determine the long-term outcome after breast-conservation surgery followed by definitive breast irradiation for women with mammographically detected DCIS of the breast. METHODS: In total, 1003 women with unilateral, mammographically detected DCIS of the breast underwent breast-conserving surgery followed by definitive breast irradiation. These women were treated in 10 institutions in North America and Europe. The median follow-up was 8.5 years (mean, 9.0 years; range, 0.2-24.6 years). RESULTS: The 15-year overall survival rate was 89%, and the 15-year cause-specific survival rate was 98%. The 15-year rate of freedom from distant metastases was 97%. In total, there were 100 local failures (10%) in the treated breast. The 15-year rate of any local failure was 19%, and the 15-year rate of local only first failure was 16%. Patient age > or = 50 years at the time of treatment and negative final pathology margins from the primary tumor excision both were associated independently with a lower risk of local failure in univariate analysis (P = 0.00062 and P = 0.024, respectively) and in multivariate analysis (P = 0.00057 and P = 0.0026, respectively). For favorable subgroups of patients age > or = 50 years or with negative resection margins, the 10-year risk of local failure was < or = 8%. CONCLUSIONS: The current results support the use of breast-conserving surgery followed by definitive breast irradiation for the treatment of patients with mammographically detected DCIS of the breast. Patient age > or = 50 years at the time of treatment and negative resection margins both were associated independently with a decreased risk of local failure.

Pierce LJ, Hutchins LF, Green SR, Lew DL, Gralow JR, Livingston RB, Osborne CK, Albain KS. · Southwest Oncology Group, San Antonio, TX, USA. · J Clin Oncol. · Pubmed #15545669 No free full text.

Abstract: PURPOSE: Tamoxifen (TAM) is thought to exert a cytostatic effect on hormone-sensitive breast cancer cells. Some preclinical studies show reduced radiosensitivity in irradiated malignant mammary epithelial cells when pretreated with TAM; other studies refute these results. Recent randomized clinical trials suggest an antagonistic effect of TAM on cytotoxic therapy, with improved disease-free survival (DFS) with sequential versus concurrent TAM. An exploratory analysis was undertaken to evaluate the optimal sequencing of TAM and radiotherapy (RT) after breast-conserving surgery. PATIENTS AND METHODS: Southwest Oncology Group trial 8897 (Intergroup 0102) randomly assigned node-negative women with T1-3 breast cancers to cyclophosphamide, doxorubicin, fluorouracil (CAF); CAF --> TAM; cyclophosphamide, methotrexate, fluorouracil (CMF); and CMF --> TAM. For this analysis, data are reported only in the TAM groups. RT was allowed either before adjuvant therapy (sequential [SEQ] RT; 107 patients) or after chemotherapy but concurrent with TAM (concurrent [CONC] RT; 202 patients). Survival data were adjusted for receptor status, age, and tumor size. RESULTS: With a median follow-up of 10.3 years, 10-year DFS values were 83% and 83% for CONC versus SEQ RT groups (log-rank P = .73; P = .76 adjusted for patient characteristics), and 10-year overall survivals were 88% and 90%, respectively (log-rank P = .59; adjusted P = .65). Patterns of failure showed no increase in in-breast recurrence rates between CONC RT and SEQ RT groups, with 10-year local recurrence rates of 7% for CONC RT and 5% for SEQ RT (hazard ratio, 0.73; 95% CI, 0.26 to 2.04; P = .54). CONCLUSION: The current analysis does not suggest an adverse effect on local or systemic control with CONC versus SEQ TAM and RT in node-negative breast cancer. A randomized trial is encouraged to validate these results.

Suh WW, Schott AF, Hayman JA, Schipper MJ, Shewach DS, Pierce LJ. · Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan 48109, USA. · Breast J. · Pubmed #15125746 No free full text.

Abstract: The purpose of this study was to determine the maximum tolerated dose (MTD) of gemcitabine when given concurrently with standard radiotherapy for the treatment of chest wall recurrences, and to compare actuarial rates of local-regional control with those achieved in historical controls. Patients with unresectable chest wall recurrences were enrolled in a phase I trial of concurrent gemcitabine and radiotherapy. Gemcitabine was increased at 150 mg/m(2)/week increments, starting at 300 mg/m(2)/week. Radiotherapy was delivered to the chest wall and regional nodes to a total of 60 to 70 Gy in 2 Gy daily fractions. Treatment toxicity was assessed and a comparison of treatment outcome was performed between study patients and historical groups treated with either radiotherapy alone or excision followed by radiotherapy. The dose-limiting toxicities of neutropenia and thrombocytopenia occurred at the second planned dose of 450 mg/m(2)/week after accrual of only six patients, resulting in a MTD of 300 mg/m(2)/week. Myelosuppression and skin desquamation were commonly observed. Actuarial rates of local-regional control were 100%, 50%, and 90% at 2 years for the gemcitabine with radiotherapy, radiotherapy alone, and excision followed by radiotherapy groups, respectively (p = 0.105). The difference among the Kaplan-Meier curves for overall local-regional control was statistically significant at p = 0.007 in favor of combined gemcitabine and radiotherapy. The MTD of gemcitabine is 300 mg/m(2)/week when gemcitabine is delivered concurrently with radiotherapy for unresectable chest wall failures. This novel approach suggests excellent local-regional control when compared to historical controls. A phase II trial is warranted.

Olivotto IA, Chua B, Elliott EA, Parda DS, Pierce LJ, Shepherd L, Vallow LA, White JR, Whelan TJ. · Radiation Oncology, British Columbia Cancer Agency and University of British Columbia, Vancouver Island Centre, 2410 Lee Avenue, Victoria, BC V8R 6V5, Canada. · Clin Breast Cancer. · Pubmed #14715112 links to  free full text

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Li XA, Tai A, Arthur DW, Buchholz TA, Macdonald S, Marks LB, Moran JM, Pierce LJ, Rabinovitch R, Taghian A, Vicini F, Woodward W, White JR, Anonymous00081. · Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI 53226, USA. · Int J Radiat Oncol Biol Phys. · Pubmed #19215827 No free full text.

Abstract: PURPOSE: To quantify the multi-institutional and multiobserver variability of target and organ-at-risk (OAR) delineation for breast-cancer radiotherapy (RT) and its dosimetric impact as the first step of a Radiation Therapy Oncology Group effort to establish a breast cancer atlas. METHODS AND MATERIALS: Nine radiation oncologists specializing in breast RT from eight institutions independently delineated targets (e.g., lumpectomy cavity, boost planning target volume, breast, supraclavicular, axillary and internal mammary nodes, chest wall) and OARs (e.g., heart, lung) on the same CT images of three representative breast cancer patients. Interobserver differences in structure delineation were quantified regarding volume, distance between centers of mass, percent overlap, and average surface distance. Mean, median, and standard deviation for these quantities were calculated for all possible combinations. To assess the impact of these variations on treatment planning, representative dosimetric plans based on observer-specific contours were generated. RESULTS: Variability in contouring the targets and OARs between the institutions and observers was substantial. Structure overlaps were as low as 10%, and volume variations had standard deviations up to 60%. The large variability was related both to differences in opinion regarding target and OAR boundaries and approach to incorporation of setup uncertainty and dosimetric limitations in target delineation. These interobserver differences result in substantial variations in dosimetric planning for breast RT. CONCLUSIONS: Differences in target and OAR delineation for breast irradiation between institutions/observers appear to be clinically and dosimetrically significant. A systematic consensus is highly desirable, particularly in the era of intensity-modulated and image-guided RT.

Lin A, Moran JM, Marsh RB, Balter JM, Fraass BA, McShan DL, Kessler ML, Pierce LJ. · Department of Radiation Oncology, University of Michigan, Ann Arbor, MI 48109-0010, USA. · Int J Radiat Oncol Biol Phys. · Pubmed #18793965 No free full text.

Abstract: PURPOSE: Although previous work demonstrated superior dose distributions for left-sided breast cancer patients planned for intensity-modulated radiation therapy (IMRT) at deep inspiration breath hold compared with conventional techniques with free-breathing, such techniques are not always feasible to limit the impact of respiration on treatment delivery. This study assessed whether optimization based on multiple instance geometry approximation (MIGA) could derive an IMRT plan that is less sensitive to known respiratory motions. METHODS AND MATERIALS: CT scans were acquired with an active breathing control device at multiple breath-hold states. Three inverse optimized plans were generated for eight left-sided breast cancer patients: one static IMRT plan optimized at end exhale, two (MIGA) plans based on a MIGA representation of normal breathing, and a MIGA representation of deep breathing, respectively. Breast and nodal targets were prescribed 52.2 Gy, and a simultaneous tumor bed boost was prescribed 60 Gy. RESULTS: With normal breathing, doses to the targets, heart, and left anterior descending (LAD) artery were equivalent whether optimizing with MIGA or on a static data set. When simulating motion due to deep breathing, optimization with MIGA appears to yield superior tumor-bed coverage, decreased LAD mean dose, and maximum heart and LAD dose compared with optimization on a static representation. CONCLUSIONS: For left-sided breast-cancer patients, inverse-based optimization accounting for motion due to normal breathing may be similar to optimization on a static data set. However, some patients may benefit from accounting for deep breathing with MIGA with improvements in tumor-bed coverage and dose to critical structures.

Layman RM, Thomas DG, Griffith KA, Smerage JB, Helvie MA, Roubidoux MA, Diehl KM, Newman LA, Sabel MS, Hayman JA, Pierce LJ, Hayes DF, Schott AF. · Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109-0848, USA. · Clin Cancer Res. · Pubmed #17634534 links to  free full text

Abstract: PURPOSE: Thymidine phosphorylase (TP) induction by docetaxel is a proposed mechanism for the observed preclinical synergy of docetaxel and capecitabine (DC). We evaluated whether TP protein expression is increased by docetaxel and correlates with pathologic complete response (pCR) in breast cancer patients. EXPERIMENTAL DESIGN: Women with stage II to III breast cancer were given four cycles of neoadjuvant docetaxel 36 mg/m(2) i.v. over 30 min on days 1, 8, and 15 and capecitabine 2,000 mg/d, in two divided doses, on days 5 to 21 of a 28-day cycle. Radiology-directed biopsies of the breast tumors were done at baseline and 5 days after the first dose of docetaxel to evaluate TP expression. Following DC therapy, patients had core breast biopsies, and if residual disease was present, received four cycles of standard dose-dense doxorubin and cyclophosphamide (AC). RESULTS: The pCR rate was 26.9% (95% confidence interval, 11.6-47.8). Up-regulation of TP expression was not observed by either quantitative immunofluorescence (QIF) or immunohistochemistry. Radiology-directed core biopsy after neoadjuvant chemotherapy accurately predicted pathologic response in 88% (95% confidence interval, 69.8-97.6) of the cases. Neither level of TP expression nor TP up-regulation correlated with pCR. Significant toxicity resulted in therapy discontinuation in 3 of 26 patients. CONCLUSIONS: DC chemotherapy exhibited a similar pCR rate compared with standard taxane regimens, with increased toxicity. TP expression was not up-regulated after docetaxel and did not correlate with therapeutic response. Core breast biopsy after neoadjuvant chemotherapy accurately predicted pathologic response.

Ben-David MA, Sturtz DE, Griffith KA, Douglas KR, Hayman JA, Lichter AS, Pierce LJ. · Department of Radiation Oncology, Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, Michigan, USA. · Breast J. · Pubmed #17593044 No free full text.

Abstract: The purpose of the study was to review the treatment outcomes of 198 patients treated with breast-conserving surgery (BCS) and whole breast radiation therapy using lung density correction for ductal carcinoma in situ (DCIS). Between April 1985 and December 2002, 198 patients with 200 lesions diagnosed as DCIS (AJCC stage 0) were treated at the University of Michigan. All underwent BCS and whole breast radiotherapy. Median total follow-up was 6.2 years (range: 0.8-18.2). The 5- and 10-year cumulative rates of in-breast only failure were 5.9% (95% CI: 2.6-9.3%) and 9.8% (95% CI: 5.2-14.4%), respectively. Factors that significantly predicted for an increased risk of local failure were family history of breast cancer, positive or close surgical margins and age </= 50 years at diagnosis. Cosmetic outcome was scored as "excellent" or "good" in 94% of the assessed patients. On multivariate analysis, only patient separation significantly predicted cosmetic outcome (p = 0.04). BCS and radiotherapy using lung density correction resulted in high rates of local control at 5 and 10 years with excellent cosmetic results. To the best of our knowledge, this is the first study to report outcome in a series of patients with DCIS treated with lung density correction and results compare favorably with other series in which plans were calculated using unit density.

Moran JM, Balter JM, Ben-David MA, Marsh RB, Van Herk M, Pierce LJ. · Department of Radiation Oncology, University of Michigan, Ann Arbor, MI 48109-0010, USA. · Int J Radiat Oncol Biol Phys. · Pubmed #17498569 links to  free full text

Abstract: PURPOSE: The short-term displacement and reproducibility of the breast or chest wall, and the internal mammary (IM), infraclavicular (ICV), and supraclavicular (SCV) nodal regions have been assessed as a function of breath-hold state using an active breathing control (ABC) device for patients receiving loco-regional breast radiation therapy. METHODS AND MATERIALS: Ten patients underwent computed tomographic scanning using an ABC device at breath-hold states of end-exhale and 20%, 40%, 60%, and 80% of vital capacity (VC). Patients underwent scanning before treatment and at one third and two thirds of the way through treatment. A regional registration was performed for each target using a rigid-body transformation with mutual information as a metric. RESULTS: Between exhale and 40% of VC, the mean displacement was 0.27/0.34, 0.24/0.31, 0.22/0.19, and 0.13/0.19 cm anterior/superior for the breast or chest wall, and IM, ICV, and SCV nodes, respectively. At 80% of VC, the mean displacement from exhale was 0.84/.88, 0.76/.79, 0.70/0.79, and 0.54/0.56 cm anterior/superior for the breast or chest wall, and IM, ICV, and SCV nodes, respectively. The short-term reproducibility (standard deviation) was <0.3 and <or=0.4 cm for 40% and 80% of VC, respectively. Displacements up to 1.9 cm were observed for individual patients. CONCLUSIONS: The short-term reproducibility of target position is <or=0.4 cm using ABC for all structures for all breath-hold states. This information can be used to guide treatment planning optimization studies that consider the effect of motion on target and normal tissue doses with and without active breathing control.

Jagsi R, Moran JM, Kessler ML, Marsh RB, Balter JM, Pierce LJ. · Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA. · Int J Radiat Oncol Biol Phys. · Pubmed #17448878 links to  free full text

Abstract: PURPOSE: To reduce cardiotoxicity from breast radiotherapy (RT), innovative techniques are under investigation. Information about cardiac motion with respiration and positional reproducibility under active breathing control (ABC) is necessary to evaluate these techniques. METHODS AND MATERIALS: Patients requiring loco-regional RT for breast cancer were scanned by computed tomography using an ABC device at various breath-hold states, before and during treatment. Ten patients were studied. For each patient, 12 datasets were analyzed. Mutual information-based regional rigid alignment was used to determine the magnitude and reproducibility of cardiac motion as a function of breathing state. For each scan session, motion was quantified by evaluating the displacement of a point along the left anterior descending artery (LAD) with respect to its position at end expiration. Long-term positional reproducibility was also assessed. RESULTS: Displacement of the LAD was greatest in the inferior direction, moderate in the anterior direction, and lowest in the left-right direction. At shallow breathing states, the average displacement of LAD position was up to 6 mm in the inferior direction. The maximum displacement in any patient was 2.8 cm in the inferior direction, between expiration and deep-inspiration breath hold. At end expiration, the long-term reproducibility (SD) of the LAD position was 3 mm in the A-P, 6 mm in the S-I, and 4 mm in the L-R directions. At deep-inspiration breath hold, long-term reproducibility was 3 mm in the A-P, 7 mm in the S-I, and 3 mm in the L-R directions. CONCLUSIONS: These data demonstrate the extent of LAD displacement that occurs with shallow breathing and with deep-inspiration breath hold. This information may guide optimization studies considering the effects of respiratory motion and reproducibility of cardiac position on cardiac dose, both with and without ABC.

Jagsi R, Griffith KA, Koelling T, Roberts R, Pierce LJ. · Radiation Oncology Department, University of Michigan School of Medicine, Ann Arbor, Michigan 48109, USA. · Cancer. · Pubmed #17238178 links to  free full text

Abstract: BACKGROUND: Radiation therapy (RT), a critical component of breast-conserving therapy for breast cancer, has been associated with coronary artery disease (CAD) in numerous older studies, but the risk may be lower with modern techniques. METHODS: Observed rates of cardiac events in 828 patients treated with breast-conserving surgery and RT at the University of Michigan were compared with expected rates. Relations between potential risk factors and actuarial rates of first CAD event were analyzed. RESULTS: Observed risks of cardiac events were lower than expected. The standardized incidence ratio (SIR) of myocardial infarction (MI) was 0.44 (95% confidence interval [CI]: 0.21-0.70). The SIR of MI or CAD requiring intervention was 0.50 (95% CI: 0.27-0.68). With a median follow-up of 6.8 years, 12 (1.4%) patients had at least 1 MI on follow-up and 20 (2.4%) had at least 1 MI or CAD requiring intervention. Median age at first cardiac event was 75.9 years (range, 43.1-91.5). Median interval from RT to occurrence of the first cardiac event was 3.7 years (range, 13 days to 15.4 years). The 10-year cumulative incidence of MI was 1.2% and cumulative incidence of MI or CAD requiring intervention was 2.7%. On multivariate analysis, age, diabetes mellitus, active smoking, and laterality of RT were significant predictors of MI. Age and active smoking were significant predictors of MI or CAD requiring intervention. CONCLUSIONS: Patients in this series had lower risk of ischemic cardiac events than expected. Although small in absolute magnitude, patients radiated to the left side did have a statistically significant increased risk of MI. These findings support further investigation of techniques to minimize the long-term cardiac risks faced by breast cancer patients.

Oh KS, Kong FM, Griffith KA, Yanke B, Pierce LJ. · Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI 48109, USA. · Int J Radiat Oncol Biol Phys. · Pubmed #16863683 No free full text.

Abstract: PURPOSE: The aims of this study were to determine the changes in breast and excision cavity volumes after whole-breast irradiation and the adequacy of using the surgical scar to guide boost planning. METHODS AND MATERIALS: A total of 30 women consecutively treated for 31 breast cancers were included in this study. Simulation CT scans were performed before and after whole-breast irradiation. CT breast volumes were delineated using clinically defined borders. Excision cavity volumes were contoured based on surgical clips, the presence of a hematoma, and/or other surgical changes. Hypothetical electron boost plans were generated using the surgical scar with a 3-cm margin and analyzed for coverage. RESULTS: The mean CT breast volumes were 774 and 761 cc (p = 0.22), and the excision cavity volumes were 32.1 and 25.1 cc (p < 0.0001), before and after 40 Gy (39-42 Gy) of whole-breast irradiation, respectively. The volume reduction in the excision cavity was inversely correlated with time elapsed since surgery (R = 0.46, p < 0.01) and body weight (R = 0.50, p < 0.01). The scar-guided hypothetical plans failed to cover the excision cavity adequately in 62% and 53.8% of cases using the pretreatment and postradiation CTs, respectively. Per the hypothetical plans, the minimum dose to the excision cavity was significantly lower for tumors located in the inner vs. outer quadrants (p = 0.02) and for cavities >20 cc vs. <20 cc (p = 0.01). CONCLUSIONS: This study demonstrates a significant reduction in the volume of the excision cavity during whole-breast irradiation. Scar-guided boost plans provide inadequate coverage of the excision cavity in the majority of cases.

Jagsi R, Griffith KA, Koelling T, Roberts R, Pierce LJ. · Radiation Oncology Department, University of Michigan Cancer Center Biostatistics Core, and the University of Michigan School of Medicine, Ann Arbor, MI 48109-0010, USA. · J Clin Oncol. · Pubmed #16702581 No free full text.

Abstract: PURPOSE: To examine whether stroke risk is elevated in American breast cancer patients treated with modern techniques, as well as whether supraclavicular radiation therapy (RT) is associated with increased risk. METHODS: Observed rates of stroke in 820 eligible early-stage breast cancer patients treated at the University of Michigan Hospital (Ann Arbor, MI) were compared with expected rates. Relationships between potential risk factors and actuarial rate of first stroke were analyzed. RESULTS: Median follow-up was 6.8 years. Twenty patients had at least one cerebrovascular accident (CVA) in follow-up; 35 patients had at least one CVA or transient ischemic attack (CVA/TIA). The standardized incidence ratios were 1.74 (0.94 to 2.37) for CVA and 1.68 (1.003 to 2.06) for CVA/TIA. The absolute excess risk per 1,000 patients per year was 1.67 for CVA and 2.76 for CVA/TIA. On bivariate analysis, factors significantly associated with actuarial rate of first CVA included hypertension (P = .002), age (P < .0001), coronary artery disease (P = .001), atrial fibrillation (P = .009), and supraclavicular RT (P = .021). Factors associated with CVA/TIA were hypertension (P < .001), coronary artery disease (P = .002), and age (P < .0001). Tamoxifen use alone was not significant (P = .19), but tamoxifen combined with baseline hypertension led to increased risk of CVA/TIA (log-rank P < .0001). On multivariate analysis, only age (P < .001) and hypertension (P = .003) remained significant predictors of CVA/TIA. Age was the only significant predictor of CVA alone (P < .001). CONCLUSION: American breast cancer survivors may have an elevated risk of stroke compared with the general population, but the absolute excess risk is low. This study found no significant association between supraclavicular RT and stroke after controlling for other factors.

Pierce LJ, Levin AM, Rebbeck TR, Ben-David MA, Friedman E, Solin LJ, Harris EE, Gaffney DK, Haffty BG, Dawson LA, Narod SA, Olivotto IA, Eisen A, Whelan TJ, Olopade OI, Isaacs C, Merajver SD, Wong JS, Garber JE, Weber BL. · Department of Radiation Oncology, University of Michigan School of Medicine, Ann Arbor, MI 48109-0010, USA. · J Clin Oncol. · Pubmed #16636335 No free full text.

Abstract: PURPOSE: We compared the outcome of breast-conserving surgery and radiotherapy in BRCA1/2 mutation carriers with breast cancer versus that of matched sporadic controls. METHODS: A total of 160 BRCA1/2 mutation carriers with breast cancer were matched with 445 controls with sporadic breast cancer. Primary end points were rates of in-breast tumor recurrence (IBTR) and contralateral breast cancers (CBCs). Median follow-up was 7.9 years for mutation carriers and 6.7 years for controls. RESULTS: There was no significant difference in IBTR overall between carriers and controls; 10- and 15-year estimates were 12% and 24% for carriers and 9% and 17% for controls, respectively (hazard ratio [HR], 1.37; P = .19). Multivariate analyses for IBTR found BRCA1/2 mutation status to be an independent predictor of IBTR when carriers who had undergone oophorectomy were removed from analysis (HR, 1.99; P = .04); the incidence of IBTR in carriers who had undergone oophorectomy was not significantly different from that in sporadic controls (P = .37). CBCs were significantly greater in carriers versus controls, with 10- and 15-year estimates of 26% and 39% for carriers and 3% and 7% for controls, respectively (HR, 10.43; P < .0001). Tamoxifen use significantly reduced risk of CBCs in mutation carriers (HR, 0.31; P = .05). CONCLUSION: IBTR risk at 10 years is similar in BRCA1/2 carriers treated with breast conservation surgery who undergo oophorectomy versus sporadic controls. As expected, CBCs are significantly increased in carriers. Although the incidence of CBCs was significantly reduced in mutation carriers who received tamoxifen, this rate remained significantly greater than in controls. Additional strategies are needed to reduce contralateral cancers in these high-risk women.

Ben-David MA, Kleer CG, Paramagul C, Griffith KA, Pierce LJ. · Department of Radiation Oncology, Cancer and Geriatrics Center, University of Michigan Medical School, Ann Arbor, Michigan 48109-0010, USA. · Cancer. · Pubmed #16329136 links to  free full text

Abstract: BACKGROUND: The goals of the current study were to compare the clinicopathologic presentations of patients with lobular carcinoma in situ (LCIS) as a component of breast carcinoma who were treated with breast conserving surgery (BCS) and radiation therapy (RT) with those of patients without LCIS as part of their primary tumor and to report rates of local control by overall cohort and specifically in patients with positive margins for LCIS and multifocal LCIS. METHODS: Sixty-four patients with Stages 0-II breast carcinoma with LCIS (LCIS-containing tumor group, LCTG) that had received BCS+RT treatment at the University of Michigan between 1989 and 2003 were identified. These patients were matched to 121 patients without LCIS (control group) in a 1:2 ratio. RESULTS: The median follow-up time was 3.9 years (range, 0.3-18.9 yrs). There were no significant differences between the two groups with regard to clinical, pathologic, or treatment-related variables or in mammographic presentation, with the exception of a higher proportion of the LCTG patients who received adjuvant hormonal therapy (P = 0.01). The rates of local control at 5 years were 100% in the LCTG group and 99.1% in the control group (P = 0.86). The presence of LCIS at the margins and the size and presence of multifocal LCIS did not alter the rate of local control. CONCLUSIONS: The extent of LCIS and its presence at the margins did not reduce the excellent rates of local control after BCS+RT. The data suggest that LCIS in the tumor specimen, even when multifocal, should not affect selection of patients for BCS and whole-breast RT.