Breast Neoplasms: Strom EA

Taylor ME, Haffty BG, Rabinovitch R, Arthur DW, Halberg FE, Strom EA, White JR, Cobleigh MA, Edge SB. · Washington University, Saint Louis, Missouri 63110-1032, USA. · Int J Radiat Oncol Biol Phys. · Pubmed #19251087 No free full text.

Abstract: This summary focuses on the role of postoperative radiation therapy in patients treated with modified radical mastectomy for invasive breast cancer, particularly in patients receiving systemic therapy.

White JR, Halberg FE, Rabinovitch R, Green S, Haffty BG, Solin LJ, Strom EA, Taylor ME, Edge SB. · Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226-4801 , USA. · J Am Coll Radiol. · Pubmed #18514949 No free full text.

Abstract: BACKGROUND: During the past 2 decades, breast conservation therapy (BCT) has become firmly established as a standard therapeutic approach for eligible women with early-stage breast cancer. Breast radiation after conservative surgery is an integral component of BCT, resulting in comparable local control and equivalent survival to mastectomy. Successful breast conservation relies on understanding key elements for patient selection, evaluation, treatment contraindications, radiation therapy methods, and integration with systemic therapy. METHODS: The Appropriateness Criteria Committee of the American College of Radiology convened an expert panel to examine BCT for early-stage breast cancer. By using a modified Delphi technique to generate consensus, the expert panel responded to questionnaires on 9 clinical cases that address various key elements of breast conservation. A literature review on BCT led to the generation of an evidence table to support the consensus and overview. RESULTS: Consensus for appropriateness criteria for BCT was produced for various clinical scenarios commonly encountered in practice. These topics include radiation oncology management issues related to young patient age, sentinel node biopsy, elderly patients, other histology, positive margins, extensive intraductal component, node-positive breast cancer, genetic breast cancer, partial breast irradiation, and systemic therapy. Radiation methods for BCT are reviewed. CONCLUSION: The Breast Cancer Panel has generated a consensus of up-to-date guidelines for the appropriate use of radiation for BCT by using a modified Delphi process for the American College of Radiology Appropriateness Criteria.

Morrow M, Strom EA, Bassett LW, Dershaw DD, Fowble B, Giuliano A, Harris JR, O'Malley F, Schnitt SJ, Singletary SE, Winchester DP, Anonymous00163, Anonymous00164, Anonymous00165, Anonymous00166. · Northwestern University Medical School, Chicago, IL, USA. · CA Cancer J Clin. · Pubmed #12363326 links to  free full text

Abstract: Multidisciplinary guidelines for management of invasive breast carcinoma from the American College of Radiology, the American College of Surgeons, the College of American Pathology, and the Society of Surgical Oncology have been updated to reflect the continuing advances in the diagnosis and treatment of invasive breast cancer. The guidelines provide a framework for clinical decision-making for patients with invasive breast carcinoma based on review of relevant literature and include information on patient selection and evaluation, technical aspects of surgical treatment, techniques of irradiation, and follow-up care.

Morrow M, Strom EA, Bassett LW, Dershaw DD, Fowble B, Harris JR, O'Malley F, Schnitt SJ, Singletary SE, Winchester DP, Anonymous00159, Anonymous00160, Anonymous00161, Anonymous00162. · Northwestern University Medical School, Chicago, IL, USA. · CA Cancer J Clin. · Pubmed #12363325 links to  free full text

Abstract: The multidisciplinary guidelines for management of ductal carcinoma in situ of the breast from the American College of Radiology, the American College of Surgeons, the College of American Pathology, and the Society of Surgical Oncology have been updated to take into account continuing advances in the diagnosis and treatment of this disease. The continued growth in mammographic evaluation and technology has resulted in an increase in the diagnosis of ductal carcinoma in situ of the breast (DCIS). The resulting guidelines provide a framework for clinical decision-making for patients with DCIS based on review of relevant literature, and includes information on patient selection and evaluation, technical aspects of surgical treatment, techniques of irradiation, and follow-up care.

Strom EA. · No affiliation provided · Int J Radiat Oncol Biol Phys. · Pubmed #12459348 No free full text.

This publication has no abstract.

Buchholz TA, Kuerer HM, Strom EA. · Department of Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA. · Semin Radiat Oncol. · Pubmed #15809931 No free full text.

Abstract: Partial-breast irradiation (PBI) may prove to be a significant advance in the treatment of selected patients with early-stage breast cancer. However, because PBI treats a much smaller volume of breast tissue than does conventional whole-breast irradiation and the biologic equivalent dose delivered to the tumor may be considerably lower, it is possible that this treatment approach may increase the risk of recurrence. There may also be an increased risk of toxicity using PBI techniques that have significant dose inhomogeneity. Despite these uncertainties, many patients in the United States are currently treated with PBI outside of a clinical study. Showing that PBI is safe and effective requires having results from large clinical trials. If such trials are supported and completed, the benefits and limitations of PBI are likely to be elucidated, and this treatment technique, properly refined, may well prove to be an advance in breast cancer care. If instead PBI is adopted ad hoc within the radiation oncology community without proper testing, it is likely that poor outcomes will be underreported and many patients will receive suboptimal therapy. This would be a big step backward in the role of radiation therapy in breast cancer treatment.

Kuerer HM, Julian TB, Strom EA, Lyerly HK, Giuliano AE, Mamounas EP, Vicini FA. · Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. · Ann Surg. · Pubmed #15075650 links to  free full text

Abstract: OBJECTIVE: To critically review the theoretical and actual risks and benefits of accelerated partial breast irradiation (APBI) after breast-conserving surgery. SUMMARY BACKGROUND DATA: Because of rapid evolution of radiation therapy techniques related to brachytherapy and three-dimensional conformal radiation therapy, APBI has very recently come to the forefront as a potential local treatment option for women with breast cancer. This review aims to give an overview of the biologic rationale for APBI techniques, and benefits and limitations of APBI techniques. METHODS: The authors reviewed the currently available published world medical literature on breast-conserving surgery with and without postoperative irradiation; all studies involving partial breast irradiation, including brachytherapy, for breast cancer; and currently accruing and planned APBI trials. The focus of this review was the early results of treatment in terms of toxicity, complications, cosmesis, and local control. RESULTS: On average, approximately 3% of patients treated with breast-conserving surgery will have an in-breast local recurrence away from the original lumpectomy site with or without postoperative standard whole-breast irradiation. The results of phase I-II studies involving approximately 500 patients treated with APBI after breast-conserving surgery have been published. Although many of the studies have limited long-term follow-up and potential selection bias, early results suggest that toxicity, cosmesis, and local control are comparable to outcomes seen after breast-conserving surgery followed by standard whole-breast irradiation. CONCLUSIONS: Recent advances in radiation delivery and published series of partial breast irradiation support large randomized trials comparing APBI with standard whole-breast irradiation after breast-conserving surgery.

Buchholz TA, Weil MM, Ashorn CL, Strom EA, Sigurdson A, Bondy M, Chakraborty R, Cox JD, McNeese MD, Story MD. · Department of Radiation Oncology, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA. · Cancer. · Pubmed #15042666 links to  free full text

Abstract: BACKGROUND: Mothers of children who have ataxia telangiectasia have been reported to be at increased risk for development of breast carcinoma. To test whether sequence variants in the ataxia telangiectasia, mutated, gene (ATM) are associated with breast carcinoma, the authors compared the frequency of ATM cDNA sequence changes in patients with breast carcinoma with the corresponding frequency in control patients. METHODS: The authors sequenced ATM cDNA from 91 patients with breast carcinoma and compared the frequencies of sequence changes in these patients with the corresponding frequencies in a control sample of 940 individuals with no history of malignant disease. RESULTS: Thirty-five patients with breast carcinoma had one or more single-base changes in ATM. Three genetic variants were found in at least two patients. These variants resulted in Asp1853Asn, Pro1054Arg, or Ser49Cys amino acid substitutions in the ATM protein. The Ser49Cys variant was more common in patients with breast carcinoma than in the control patients, with respective frequencies of 6.7% (5 of 75 patients) and 1.3% (12 of 940 patients; P=0.006; Fisher two-sided exact test). The subgroup of patients with bilateral breast carcinoma had a Ser49Cys frequency of 11.8% (2 of 17 patients), which again was significantly different from what was observed in the control group (P=0.024; Fisher two-sided exact test). The allele frequencies of the other two variants were not different between case patients and control patients. CONCLUSIONS: Patients with breast carcinoma, particularly those with bilateral disease, were more likely to have a variant in the ATM gene that resulted in a Ser49Cys substitution in the gene product. Additional studies are needed to evaluate the potential functional consequences of the Ser49Cys substitution and confirm the relevance of this variant in the development of breast carcinoma.

Frank SJ, McNeese MD, Strom EA, Perkins G, Salehpour M, Schechter N, Buchholz TA. · Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, 77030, USA. · Clin Breast Cancer. · Pubmed #15023240 No free full text.

Abstract: During the past decade, improvements in treatment-planning tools, computer and imaging technologies, and new therapeutic modalities have allowed radiation to be delivered in a conformal fashion while minimizing treatment toxicity. It is important that physicians involved in breast cancer treatment recognize the numerous advances that have occurred in the delivery of radiation therapy. Changes in 3 specific areas in treatment planning and delivery have revolutionized the way we approach breast cancer treatment: the design of radiation fields using computed tomography (CT) data sets, the development of 3-dimensional dose-calculation algorithms, and the development of new methods to modulate the delivery of radiation dose. With the advent of CT simulators, individual patient anatomy and pathology can be readily visualized and reconstructed in axial, coronal, and sagittal views. With an improved anatomic delineation between the target volumes and critical organ structures, the treatment fields can be designed to be more congruous to the areas at highest risk. In the past few years, new 3-dimensional dose-calculation algorithms have been generated that more accurately calculate dose distributions throughout the treatment-planning volume. Finally, modern linear accelerators allow for modulation of the dose intensity of the radiation beam, which may lead to improved aesthetics and decreased side effects while ensuring that the volumes at high risk receive the prescribed dose. Radiation therapy can be delivered safely and effectively to patients with breast cancer.

Buchholz TA, Strom EA, McNeese MD, Hunt KK. · Department of Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. · Surg Clin North Am. · Pubmed #12875602 No free full text.

Abstract: Radiation therapy is an effective treatment of micrometastatic disease involving lymph nodes. Correspondingly, radiation may be an important adjuvant treatment for selected patients who undergo sentinel lymph node surgery. The specific cohorts for whom radiation maybe of benefit include those at risk for a false-negative surgery, patients with a positive sentinel lymph node who elect to forgo an axillary dissection, and patients with drainage to the internal mammary lymph nodes. For these patients, radiation treatment fields must be specifically designed to include the appropriate nodal regions within the target treatment volumes.

Buchholz TA, Strom EA, Perkins GH, McNeese MD. · Department of Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA. · Oncologist. · Pubmed #12490741 links to  free full text

Abstract: Despite years of clinical study, there are still many unanswered questions regarding postmastectomy radiation. It is clear that radiation therapy plays a critical role in the multidisciplinary management of patients with locally advanced or inflammatory breast cancer. It is also accepted that postmastectomy radiation is not required for most women with noninvasive disease or stage I disease. Randomized clinical trials studying radiation treatments for women with stage II or III breast cancer have shown that the addition of radiation after mastectomy can reduce local-regional recurrence rates, which then improves survival. However, other data have indicated that the risk of local-regional recurrence after mastectomy and chemotherapy is low for patients with small tumors and one to three positive lymph nodes, leading some to question whether postmastectomy radiation is useful for this group. A second controversy regards the sequencing of postmastectomy radiation and breast reconstruction. In this article we discuss these controversies, review the data that are relevant, and provide our institutional approaches to these issues.

Strom EA, McNeese MD. · Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA. · Semin Radiat Oncol. · Pubmed #10378963 No free full text.

Abstract: The goal of postmastectomy irradiation is to eliminate residual viable tumor in tissue remaining after standard mastectomy. Because this subclinical disease is, by definition, not detectable by current technology, the choice of patients and treatment volumes for postmastectomy irradiation must be inferred from a variety of data sources. The absolute risk of locoregional recurrence is related to the stage of disease, the extent of lymphatic involvement, and other treatment received. Patterns of failure analyses consistently identify the chest wall as the most important target for treatment with radiation therapy in high-risk patients. When patients with multiple locoregional sites of recurrence are included, the chest wall may be involved in as many as 60% to 80% of patients. The second most common place for locoregional failure is the undissected lymphatics of the paraclavicular region. The cumulative probability of failure in this region ranges from 10% to 35% of the patients treated for locoregional recurrence. Microscopic tumor metastases in the internal mammary chain are theorized to represent a potential source for distant metastases. Each of the prospective trials of postmastectomy irradiation that have shown survival benefit included the internal mammary chain within their target volume. Nonetheless, local failure in the internal mammary nodes is an uncommon finding. Similarly, after a level I and II axillary dissection, axillary failure is a minor component of local recurrence risk, and it is probable that only a subset of patients may benefit from axillary irradiation.

Buchholz TA, Weil MM, Story MD, Strom EA, Brock WA, McNeese MD. · Department of Radiation Oncology, M.D. Anderson Cancer Center, Houston, Texas 77030, USA. · Radiat Oncol Investig. · Pubmed #10333246 No free full text.

Abstract: The genetic determinants for most breast cancer cases remain elusive. However, a mutation in a tumor suppressor gene, such as p53, BRCA1, BRCA2, or ATM, has been determined to be one mechanism of breast carcinogenesis. It has been established that inherited mutations in p53, BRCA1, and BRCA2 significantly contribute to breast cancer risk, although the importance of an inherited ATM mutation is controversial. Sporadic mutations in p53 are also common in breast cancer cells. The precise deficiencies that result from these genetic mutations have yet to be fully described. Although the functions of these genes are different, they are all involved in the maintenance of genomic stability after DNA damage. Mutations that impair the function of these four genes may adversely affect the manner in which DNA damage is processed. It is likely that the risk of breast cancer development is increased through this mechanism. In this article, we review the relevancy of p53, BRCA1, BRCA2, and ATM mutations to breast cancer development, and review the in vitro, in vivo, and clinical data exploring the mechanisms by which these mutations affect genomic integrity and DNA damage repair.

Gonzalez-Angulo AM, Walters R, Broglio K, Frye DK, Strom EA, Theriault RL, Booser DJ, Valero V, Buzdar AU, Hortobagyi GN. · Department of Breast Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX 77230-1439, USA. · Clin Breast Cancer. · Pubmed #19073507 No free full text.

Abstract: PURPOSE: This study sought to quantify the extent of downstaging after preoperative chemotherapy for stage III breast cancer, to assess the feasibility of breast-conserving therapy (BCT) after preoperative chemotherapy, to determine the effectiveness of this multimodal treatment as measured by disease-free survival (DFS) and overall survival (OS), and to evaluate toxicities. PATIENTS AND METHODS: Patients were treated with 4 preoperative courses of 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC). They were then evaluated for response to go to mastectomy or BCT. After local therapy, patients with an excellent response were treated with 4 additional cycles of FAC, whereas patients with a moderate response received 4 cycles of MV (methotrexate and vinblastine). A total of 203 patients were registered; 194 patients (96%) underwent surgery after chemotherapy. RESULTS: The 5-year OS and progression-free survival rates were 89.8% and 81.6%, respectively, for patients with an excellent response to therapy compared with 67.2% and 63.5%, respectively, for patients with a moderate response and 55.3% and 48.8%, respectively, for patients considered nonresponders (P=.0005 for OS; P<.0001 for DFS). Cytopenia, nausea/vomiting, and stomatitis were the most common toxicities. Preoperative chemotherapy with FAC downstaged 88.6% of patients, and BCT was possible in >25%. CONCLUSION: Response to preoperative chemotherapy was a prognostic factor in improved long-term survival.

Buchholz TA, Strom EA, Oswald MJ, Perkins GH, Oh J, Domain D, Yu TK, Woodward WA, Tereffe W, Singletary SE, Thomas E, Buzdar AU, Hortobagyi GN, McNeese MD. · Department of Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA. · Int J Radiat Oncol Biol Phys. · Pubmed #16750325 No free full text.

Abstract: PURPOSE: To analyze the results of a Phase III clinical trial that investigated whether a hyperfractionated radiotherapy (RT) schedule could reduce the risk of locoregional recurrence in patients with locally advanced breast cancer treated with chemotherapy and mastectomy. METHODS AND MATERIALS: Between 1985 and 1989, 200 patients with clinical Stage III noninflammatory breast cancer were enrolled in a prospective study investigating neoadjuvant and adjuvant chemotherapy. Of the 179 patients treated with mastectomy after neoadjuvant chemotherapy, 108 participated in a randomized component of the trial that compared a dose-escalated, hyperfractionated (twice-daily, b.i.d.) chest wall RT schedule (72 Gy in 1.2-Gy b.i.d. fractions) with a once-daily (q.d.) schedule (60 Gy in 2-Gy q.d. fractions). In both arms of the study, the supraclavicular fossa and axillary apex were treated once daily to 50 Gy. The median follow-up period was 15 years. RESULTS: The 15-year actuarial locoregional recurrence rate was 7% for the q.d. arm and 12% for the b.i.d. arm (p=0.36). The rates of severe acute toxicity were similar (4% for q.d. vs. 5% for b.i.d.), but moist desquamation developed in 42% of patients in the b.i.d. arm compared with 28% of the patients in the q.d. arm (p=0.16). The 15-year actuarial rate of severe late RT complications did not differ between the two arms (6% for q.d. vs. 11% for b.i.d., p=0.54). CONCLUSION: Although the sample size of this study was small, we found no evidence that this hyperfractionation schedule of postmastectomy RT offered a clinical advantage. Therefore, we have concluded that it should not be further studied in this cohort of patients.

Green MC, Buzdar AU, Smith T, Ibrahim NK, Valero V, Rosales MF, Cristofanilli M, Booser DJ, Pusztai L, Rivera E, Theriault RL, Carter C, Frye D, Hunt KK, Symmans WF, Strom EA, Sahin AA, Sikov W, Hortobagyi GN. · The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Box 424, Houston, TX 77030, USA. · J Clin Oncol. · Pubmed #16087943 No free full text.

Abstract: PURPOSE: To determine the impact a change in schedule of paclitaxel administration from once every 3 weeks to frequent administration would have on the pathologic complete response (pCR) rate in the breast and lymph nodes for patients with invasive breast cancer treated with primary systemic chemotherapy (PST). PATIENTS AND METHODS: Patients with clinical stage I-IIIA breast cancer were randomly assigned to receive PST of paclitaxel doses administered either weekly (for a total of 12 doses of paclitaxel) or once every 3 weeks (four cycles), followed by four cycles of fluorouracil/doxorubicin/cyclophosphamide (FAC) in standard doses every 3 weeks. Two different doses of paclitaxel were used based on lymph node status defined by ultrasound and fine needle aspiration. Clinical response and extent of residual disease in the breast and lymph nodes was assessed after completion of all chemotherapy. RESULTS: A total of 258 patients were randomly assigned to receive doses of paclitaxel administered either weekly or once every 3 weeks, followed by FAC. Of these 258 patients, 110 patients had histologic lymph node involvement and 148 patients had clinical N0 disease. Weekly paclitaxel followed by FAC was administered to 127 patients and once-every-3-weeks paclitaxel followed by FAC was administered to 131 patients. Clinical response to treatment was similar between groups (P = .25). Patients receiving weekly paclitaxel had a higher pCR rate (28.2%) than patients treated with once-every-3-weeks paclitaxel (15.7%; P = .02), with improved breast conservation rates (P = .05). CONCLUSION: The change in schedule of paclitaxel from once every 3 weeks to a more frequent administration significantly improved the ability to eradicate invasive cancer in the breast and lymph nodes.

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.

Yu TK, Whitman GJ, Thames HD, Buzdar AU, Strom EA, Perkins GH, Schechter NR, McNeese MD, Kau SW, Thomas ES, Hortobagyi GN, Buchholz TA. · Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA. · J Natl Cancer Inst. · Pubmed #15547180 links to  free full text

Abstract: BACKGROUND: Taxane-based chemotherapy has been associated with an increased risk of radiation pneumonitis in patients with breast cancer. To obtain additional information about this association, we investigated the association between paclitaxel chemotherapy and radiation pneumonitis in patients participating in a phase III randomized study. METHODS: Five hundred and twenty-four breast cancer patients were prospectively and randomly assigned to receive either four cycles of paclitaxel followed by four cycles of 5-fluorouracil, doxorubicin, cyclophosphamide (FAC) or eight cycles of FAC. One hundred and eighty-nine of these patients (100 in the paclitaxel-FAC group and 89 in the FAC group) subsequently underwent radiation therapy in our institution and had medical records available to review for pulmonary symptoms. In addition, a radiologist who was unaware of the type of treatment scored chest x-ray changes after radiation treatment. Crude rates of radiation pneumonitis were compared with chi-square or Fisher's exact test, and actuarial rates were assessed with Kaplan-Meier and log-rank tests. All statistical tests were two-sided. RESULTS: No difference in the rate of clinically relevant radiation pneumonitis was observed between the two groups (5.0% in the paclitaxel-FAC group versus 4.5% in the FAC group; difference = 0.5%, 95% CI = -6.6% to 5.5%; P = 1.00). Oral steroids for pneumonitis were taken by two patients in the paclitaxel-FAC group but by none in the FAC group, and no patient was hospitalized for or died of radiation pneumonitis. The paclitaxel-FAC group (39.3%) had a higher rate of radiographic changes after irradiation than the FAC group (23.7%; difference = 15.6%, 95% CI = -0.11% to 28.8%; P = .034). CONCLUSION: Patients with breast cancer treated with sequential paclitaxel, FAC, and radiation therapy appeared to have a very low rate of clinically relevant radiation pneumonitis that was no different from that of patients treated with FAC alone.

Verstovsek S, Verschraegen CF, Edwards CL, Malpica A, Kavanagh JJ, Ross MI, Strom EA, Jhingran A, Theriault RL, Kudelka AP. · Division of Medicine, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA. · Am J Clin Oncol. · Pubmed #10683089 No free full text.

Abstract: Multiple metachronous primary malignancies are becoming increasingly frequent; however, multiple synchronous primary malignancies are still unusual. We report the case of a 61-year-old woman with synchronous stage IIIB ductal carcinoma of the left breast and FIGO stage IB2 squamous cell carcinoma of the cervix. The patient was treated initially every 4 weeks with a 24-h intravenous infusion of paclitaxel (175 mg/m2) followed by a 1-h infusion of carboplatin (area under the curve of 5 mg/ml x min) with concurrent irradiation of the pelvis. Significant toxic reactions including nausea, vomiting, and diarrhea required hospitalization or outpatient intravenous fluids and antiemetics. After four cycles of chemotherapy, the breast cancer was in complete clinical remission, and the patient underwent a modified radical mastectomy with axillary lymph node dissection. Pathologic findings revealed a few microscopic foci of residual infiltrating ductal carcinoma exhibiting a marked treatment effect; none of the 14 axillary lymph nodes removed showed evidence of metastatic tumor. A near-complete pathologic response of the breast cancer and a complete clinical response of the cervical cancer were obtained. Adjuvant chemotherapy for the breast cancer was then initiated, followed by radiation and hormonal therapy.

Hortobagyi GN, Buzdar AU, Theriault RL, Valero V, Frye D, Booser DJ, Holmes FA, Giralt S, Khouri I, Andersson B, Gajewski JL, Rondon G, Smith TL, Singletary SE, Ames FC, Sneige N, Strom EA, McNeese MD, Deisseroth AB, Champlin RE. · Department of Breast Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA. · J Natl Cancer Inst. · Pubmed #10655439 links to  free full text

Abstract: BACKGROUND: Uncontrolled studies have reported encouraging outcomes for patients with high-risk primary breast cancer treated with high-dose chemotherapy and autologous hematopoietic stem cell support. We conducted a prospective randomized trial to compare standard-dose chemotherapy with the same therapy followed by high-dose chemotherapy. PATIENTS and METHODS: Patients with 10 or more positive axillary lymph nodes after primary breast surgery or patients with four or more positive lymph nodes after four cycles of primary (neoadjuvant) chemotherapy were eligible. All patients were to receive eight cycles of 5-fluorouracil, doxorubicin (Adriamycin), and cyclophosphamide (FAC). Patients were stratified by stage and randomly assigned to receive two cycles of high-dose cyclophosphamide, etoposide, and cisplatin with autologous hematopoietic stem cell support or no additional chemotherapy. Tamoxifen was planned for postmenopausal patients with estrogen receptor-positive tumors and chest wall radiotherapy was planned for all. All P values are from two-sided tests. RESULTS: Seventy-eight patients (48 after primary surgery and 30 after primary chemotherapy) were registered. Thirty-nine patients were randomly assigned to FAC and 39 to FAC followed by high-dose chemotherapy. After a median follow-up of 6.5 years, there have been 41 relapses. In intention-to-treat analyses, estimated 3-year relapse-free survival rates were 62% and 48% for FAC and FAC/high-dose chemotherapy, respectively (P =.35), and 3-year survival rates were 77% and 58%, respectively (P =.23). Overall, there was greater and more frequent morbidity associated with high-dose chemotherapy than with FAC; there was one septic death associated with high-dose chemotherapy. CONCLUSIONS: No relapse-free or overall survival advantage was associated with the use of high-dose chemotherapy, and morbidity was increased with its use. Thus, high-dose chemotherapy is not indicated outside a clinical trial.

Beadle BM, Woodward WA, Middleton LP, Tereffe W, Strom EA, Litton JK, Meric-Bernstam F, Theriault RL, Buchholz TA, Perkins GH. · Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. · Cancer. · Pubmed #19204903 No free full text.

Abstract: BACKGROUND: Some evidence suggests that women with pregnancy-associated breast cancers (PABC) have a worse outcome compared with historical controls. However, young age is a worse prognostic factor independently, and women with PABC tend to be young. The purpose of the current study was to compare locoregional recurrence (LRR), distant metastases (DM), and overall survival (OS) in young patients with PABC and non-PABC. METHODS: Data for 668 breast cancers in 652 patients aged<or=35 years were retrospectively reviewed. One hundred four breast cancers (15.6%) were pregnancy-associated; 51 cancers developed during pregnancy and 53 within 1 year after pregnancy. RESULTS: The median follow-up for all living patients was 114 months. Patients who developed PABC had more advanced T classification, N classification, and stage group (all P<.04) compared with patients with non-PABC. Patients with PABC had no statistically significant differences in 10-year rates of LRR (23.4% vs 19.2%; P=.47), DM (45.1% vs 38.9%; P=.40), or OS (64.6% vs 64.8%; P=.60) compared with patients with non-PABC. For those patients who developed breast cancer during pregnancy, any treatment intervention during pregnancy provided a trend toward improved OS compared with delaying evaluation and treatment until after delivery (78.7% vs 44.7%; P=.068). CONCLUSIONS: Young patients with PABC had no statistically significant differences in LRR, DM, or OS compared with those with non-PABC; however, pregnancy contributed to a delay in breast cancer diagnosis, evaluation, and treatment. Primary care and reproductive physicians should be aggressive in the workup of breast symptoms in the pregnant population to expedite diagnosis and allow multidisciplinary treatment.

Reed VK, Woodward WA, Zhang L, Strom EA, Perkins GH, Tereffe W, Oh JL, Yu TK, Bedrosian I, Whitman GJ, Buchholz TA, Dong L. · Department of Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA. · Int J Radiat Oncol Biol Phys. · Pubmed #18804333 No free full text.

Abstract: PURPOSE: To compare interobserver variations in delineating the whole breast for treatment planning using two contouring methods. METHODS AND MATERIALS: Autosegmented contours were generated by a deformable image registration-based breast segmentation method (DEF-SEG) by mapping the whole breast clinical target volume (CTVwb) from a template case to a new patient case. Eight breast radiation oncologists modified the autosegmented contours as necessary to achieve a clinically appropriate CTVwb and then recontoured the same case from scratch for comparison. The times to complete each approach, as well as the interobserver variations, were analyzed. The template case was also mapped to 10 breast cancer patients with a body mass index of 19.1-35.9 kg/m(2). The three-dimensional surface-to-surface distances and volume overlapping analyses were computed to quantify contour variations. RESULTS: The median time to edit the DEF-SEG-generated CTVwb was 12.9 min (range, 3.4-35.9) compared with 18.6 min (range, 8.9-45.2) to contour the CTVwb from scratch (30% faster, p = 0.028). The mean surface-to-surface distance was noticeably reduced from 1.6 mm among the contours generated from scratch to 1.0 mm using the DEF-SEG method (p = 0.047). The deformed contours in 10 patients achieved 94% volume overlap before correction and required editing of 5% (range, 1-10%) of the contoured volume. CONCLUSION: Significant interobserver variations suggested a lack of consensus regarding the CTVwb, even among breast cancer specialists. Using the DEF-SEG method produced more consistent results and required less time. The DEF-SEG method can be successfully applied to patients with different body mass indexes.

Beadle BM, Woodward WA, Tucker SL, Outlaw ED, Allen PK, Oh JL, Strom EA, Perkins GH, Tereffe W, Yu TK, Meric-Bernstam F, Litton JK, Buchholz TA. · Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. · Int J Radiat Oncol Biol Phys. · Pubmed #18707822 No free full text.

Abstract: PURPOSE: Young women with breast cancer have higher locoregional recurrence (LRR) rates than older patients. The goal of this study is to determine the impact of locoregional treatment strategy, breast-conserving therapy (BCT), mastectomy alone (M), or mastectomy with adjuvant radiation (MXRT), on LRR for patients 35 years or younger. METHODS AND MATERIALS: Data for 668 breast cancers in 652 young patients with breast cancer were retrospectively reviewed; 197 patients were treated with BCT, 237 with M, and 234 with MXRT. RESULTS: Median follow-up for all living patients was 114 months. In the entire cohort, 10-year actuarial LRR rates varied by locoregional treatment: 19.8% for BCT, 24.1% for M, and 15.1% for MXRT (p = 0.05). In patients with Stage II disease, 10-year actuarial LRR rates by locoregional treatment strategy were 17.7% for BCT, 22.8% for M, and 5.7% for MXRT (p = 0.02). On multivariate analysis, M (hazard ratio, 4.45) and Grade III disease (hazard ratio, 2.24) predicted for increased LRR. In patients with Stage I disease, there was no difference in LRR rates based on locoregional treatment (18.0% for BCT, 19.8% for M; p = 0.56), but chemotherapy use had a statistically significant LRR benefit (13.5% for chemotherapy, 27.9% for none; p = 0.04). CONCLUSIONS: Young women have high rates of LRR after breast cancer treatment. For patients with Stage II disease, the best locoregional control rates were achieved with MXRT. For patients with Stage I disease, similar outcomes were achieved with BCT and mastectomy; however, chemotherapy provided a significant benefit to either approach.

Garg AK, Frija EK, Sun TL, Strom EA, Perkins GH, Oh JL, Yu TK, Woodward WA, Tereffe WA, Salehpour M, Buchholz TA. · Department of Radiation Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA. · Int J Radiat Oncol Biol Phys. · Pubmed #18676090 No free full text.

Abstract: PURPOSE: To determine the differences in dosimetric coverage of the Level III axillary node target as a function of the superior tangential/supraclavicular match line in breast cancer patients undergoing with tangential breast and supraclavicular fossa radiotherapy. METHODS AND MATERIALS: The data from 20 consecutive breast cancer patients who were treated with breast conservation surgery and Level I and II axillary dissection followed by radiotherapy to the undissected Level III axilla/supraclavicular fossa were retrospectively analyzed. The nodal volumes were delineated from the computed tomography simulation data set. Three composite treatment plans were generated for each patient according to the placement of the match line. RESULTS: Coverage of the contoured Level III/axillary apex varied significantly with respect to the ipsilateral clavicular head, depending on the placement of the superior tangential/supraclavicular match line. The mean volume of the Level III/axillary apex covered by the 90% isodose line (45 Gy) was 100% for caudal placement of the match line, significantly greater than the 92% for intermediate placement (bisecting the clavicular head; p = 0.001) and the 68% for cranial placement with respect to the clavicular head (p < 0.001). CONCLUSION: Placement of the superior tangential/supraclavicular match line caudal to the clavicular head results in statistically improved dosimetric coverage of the Level III axilla/axillary apex in breast cancer patients undergoing tangential/supraclavicular radiotherapy.

Bristol IJ, Woodward WA, Strom EA, Cristofanilli M, Domain D, Singletary SE, Perkins GH, Oh JL, Yu TK, Terrefe W, Sahin AA, Hunt KK, Hortobagyi GN, Buchholz TA. · Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA. · Int J Radiat Oncol Biol Phys. · Pubmed #18439768 No free full text.

Abstract: PURPOSE: The aims of this study were to determine outcomes for patients with inflammatory breast cancer (IBC) treated with multimodality therapy, to identify factors associated with locoregional recurrence, and to determine which patients may benefit from radiation dose escalation. METHODS AND MATERIALS: We retrospectively reviewed 256 consecutive patients with nonmetastatic IBC treated at our institution between 1977 and 2004. RESULTS: The 192 patients who were able to complete the planned course of chemotherapy, mastectomy, and postmastectomy radiation had significantly better outcomes than the 64 patients who did not. The respective 5-year outcome rates were: locoregional control (84% vs. 51%), distant metastasis-free survival (47% vs. 20%), and overall survival (51% vs. 24%) (p < 0.0001 for all comparisons). Univariate factors significantly associated with locoregional control in the patients who completed plan treatment were response to neoadjuvant chemotherapy, surgical margin status, number of involved lymph nodes, and use of taxanes. Increasing the total chest-wall dose of postmastectomy radiation from 60 Gy to 66 Gy significantly improved locoregional control for patients who experienced less than a partial response to chemotherapy, patients with positive, close, or unknown margins, and patients <45 years of age. CONCLUSIONS: Patients with IBC who are able to complete treatment with chemotherapy, mastectomy, and postmastectomy radiation have a high probability of locoregional control. Escalation of postmastectomy radiation dose to 66 Gy appears to benefit patients with disease that responds poorly to chemotherapy, those with positive, close, or unknown margin status, and those <45 years of age.