Breast Neoplasms: Buchholz TA

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.

Haffty BG, Buchholz TA, McCormick B. · No affiliation provided · J Clin Oncol. · Pubmed #18285600 No free full text.

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Buchholz TA, Haffty BG, Harris JR. · No affiliation provided · J Surg Oncol. · Pubmed #17221862 No free full text.

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Hunt KK, Buchholz TA, Hortobagyi GN. · No affiliation provided · Ann Surg Oncol. · Pubmed #16041472 No free full text.

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Buchholz TA. · No affiliation provided · Int J Radiat Oncol Biol Phys. · Pubmed #14630253 No free full text.

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Buchholz TA. · No affiliation provided · Cancer. · Pubmed #14508817 links to  free full text

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Buchholz TA. · No affiliation provided · Int J Radiat Oncol Biol Phys. · Pubmed #10704999 No free full text.

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Buchholz TA. · Department of Radiation Oncology, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA. · N Engl J Med. · Pubmed #19118305 No free full text.

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Kronowitz SJ, Kuerer HM, Buchholz TA, Valero V, Hunt KK. · Department of Plastic and Reconstructive Surgery, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA. · Plast Reconstr Surg. · Pubmed #19050516 No free full text.

Abstract: BACKGROUND: In patients undergoing a partial mastectomy, choosing the best method with which to repair the defect is essential to optimizing outcomes and minimizing the potential for postoperative complications. METHODS: The authors present a management algorithm for repairing partial mastectomy defects based on clinically relevant parameters to allow clinicians to better select the most appropriate indications for the various reparative oncoplastic procedures. The clinicopathologic factors considered in surgical decision-making for reconstruction after partial mastectomy include timing of reconstruction in relation to radiation therapy, status of the tumor margin, extent of breast skin resection, breast size, and whether the cosmetic outcome would be better after a total mastectomy with immediate breast reconstruction, thereby avoiding the need for radiation therapy. RESULTS: Most patients with medium or large breasts will likely benefit from immediate repair, whereas some with small breasts may not. Immediate repair of partial mastectomy defects is preferred with the use of local breast tissue (local tissue rearrangement or breast reduction techniques) because of the simplicity of these approaches and because techniques using local tissue maintain the color and texture of the breast. Waiting to repair a large deformity until after whole-breast radiation therapy usually necessitates a complex transfer of a large volume of autologous tissue, which many patients who undergo breast conservation therapy are not willing to pursue. Use of lower abdominal flaps to repair partial breast defects is generally discouraged. CONCLUSION: Although the authors' management algorithm and practical oncoplastic techniques should prove useful, it is up to the multidisciplinary breast team and the patient to determine the best approach.

Jeruss JS, Mittendorf EA, Tucker SL, Gonzalez-Angulo AM, Buchholz TA, Sahin AA, Cormier JN, Buzdar AU, Hortobagyi GN, Hunt KK. · Department of Surgery, Northwestern University Feinberg School of Medicine and Robert H. Lurie Comprehensive Cancer Center, Chicago, Illinois 60611, USA. · Cancer Res. · Pubmed #18701468 No free full text.

Abstract: The use of neoadjuvant chemotherapy has become more prevalent in the treatment of breast cancer patients. The finding of a pathologic complete response to neoadjuvant chemotherapy (no evidence of residual invasive cancer in the breast and lymph nodes at the time of surgical resection) has been shown to correlate with improved survival. The current version of the American Joint Committee on Cancer (AJCC) staging for breast cancer has a pretreatment clinical stage designation that is determined by clinical and radiographic examination of the patient and a postoperative pathologic stage classification based on the findings in the breast and regional lymph nodes removed at surgery. Pathologic staging has not been validated for patients receiving neoadjuvant chemotherapy; thus, prognosis is determined for these patients based on the pretreatment clinical stage. We hypothesized that clinical and pathologic staging variables could be combined with biological tumor markers to provide a novel means of determining prognosis for patients treated with neoadjuvant chemotherapy. Two scoring systems, based on summing binary indicators for clinical and pathologic substages, negative estrogen receptor status, and grade 3 tumor pathology, were devised to predict 5-year patient outcomes. These scoring systems facilitated separation of the study population into more refined subgroups by outcome than the current AJCC staging system for breast cancer, and provide a novel means for evaluating prognosis after neoadjuvant therapy.

Smith BD, Smith GL, Buchholz TA. · Department of Radiation Oncology, 2200 Bergquist Dr, Ste #1, Lackland AFB, TX 78236, USA. · Expert Rev Anticancer Ther. · Pubmed #18366290 No free full text.

Abstract: Ductal carcinoma in situ is a premalignant disease of the breast with a rapidly rising incidence. For women with localized ductal carcinoma in situ, randomized trials have shown that radiation therapy following conservative surgery lowers the relative risk of progression to invasive disease by 60%. Therefore, following conservative surgery, radiation therapy to the breast is generally considered a reasonable standard of care. However, several clinical trials have investigated the safety of conservative surgery alone without radiation for select women with small tumors of low histologic grade excised with widely negative margins. At present, results of these trials are conflicting, and, therefore, radiation therapy is generally recommended following conservative surgery, even for patients with favorable pathologic characteristics.

Woodward WA, Buchholz TA. · Department of Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. · Semin Oncol. · Pubmed #18308149 No free full text.

Abstract: Inflammatory breast cancer (IBC) is the most aggressive form of invasive breast cancer. The disease is associated with extensive local disease at the time of initial diagnosis requiring multidisciplinary treatment including neoadjuvant systemic therapy, surgery and comprehensive locoregional therapy. The clinical and pathological response to induction chemotherapy represents an important prognostic factor. IBC is otherwise associated with a high incidence of locoregional recurrence suggesting a critical role also for local modalities, particularly radiotherapy. The use of different schedules of treatment and possible combination approaches are reviewed and discussed.

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.

Chronowski GM, Buchholz TA. · Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA. · Curr Probl Cancer. · Pubmed #17254900 No free full text.

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Bristol IJ, Buchholz TA. · Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA. · Breast Dis. · Pubmed #16761358 No free full text.

Abstract: Inflammatory breast cancer (IBC) is a very aggressive form of breast carcinoma marked by rapid disease progression and early distant dissemination. Despite this fact, nearly 70% of patients diagnosed with (IBC) will have localized disease at presentation. As survival for patients with IBC has improved with the addition and routine use of doxorubicin-based chemotherapy, local management has emerged as a critical component of the curative management of these patients. Over the last two decades, local control rates for patients with IBC have dramatically improved. Utilization of a combined-modality approach employing neoadjuvant chemotherapy followed by mastectomy and adjuvant chemotherapy with accelerated hyperfractionated radiation to 66 Gy has transformed what was once a disease with local control rates less than 50% to one with local control rates on the order of 70%-80%. In patients whose disease responds to chemotherapy, the 5-year local control rates are even higher. These improvements in local control have translated into improvements in survival. In this paper, we review many of the exciting advances in locoregional management of IBC. We analyze the relevant literature pertaining to those local treatment options, review treatment techniques, and provide evidence-based treatment recommendations fro practicing oncologists.

Truong PT, Woodward WA, Buchholz TA. · British Columbia Cancer Agency, Vancouver Island Center, University of British Columbia, Victoria, BC, Canada. · Expert Rev Anticancer Ther. · Pubmed #16445373 No free full text.

Abstract: For women who opt for mastectomy as primary surgery in breast cancer, indications for adjuvant radiotherapy are also being redefined in light of evidence demonstrating that postmastectomy radiotherapy (PMRT), when given in conjunction with systemic therapy, improves, not only locoregional control, but also survival. However, in certain settings, particularly in patients wih intermediate-risk disease, and in some patients treated with neoadjuvant chemotherapy, the role of PMRT remains controversial. Here, the authors review modern data pertaining to the benefits and risks of PMRT and discuss controversies related to the indications for PMRT, focusing on patients with T1-2 breast cancer with 0-3 positive nodes and patients treated with neoadjuvant chemotherapy. They also summarize key issues related to the integration of PMRT with other treatment modalities.

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.

Chagpar A, Middleton LP, Sahin AA, Meric-Bernstam F, Kuerer HM, Feig BW, Ross MI, Ames FC, Singletary SE, Buchholz TA, Valero V, Hunt KK. · Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. · Cancer. · Pubmed #15747375 links to  free full text

Abstract: BACKGROUND: The ideal pathologic assessment of sentinel lymph nodes (SLNs) in patients with breast carcinoma remains controversial. The authors evaluated how detailed assessment of SLNs using immunohistochemistry (IHC) and serial sectioning would affect treatment decisions and outcomes in patients with breast carcinoma who had negative SLNs on standard hematoxylin and eosin staining. METHODS: The SLNs from patients who were treated between June 1998 and June, 1999 and who had negative lymph node status determined by hematoxylin and eosin staining (n = 84 patients) were evaluated further with serial sectioning and cytokeratin IHC. Patients were offered adjuvant therapy based on primary tumor factors. RESULTS: The median patient age was 57 years, and the median tumor size was 1.2 cm. At a median follow-up of 40.2 months, 81 patients (96%) were alive with no evidence of disease, 1 patient was alive with disease, 1 patient had died of disease, and 1 patient had died of other causes. Fifteen patients (18%) had micrometastases identified on IHC. Of the total 84 patients, information regarding adjuvant therapy was not available for 5 patients. Of the remaining 79 patients, 10 patients (13%) were not offered adjuvant chemotherapy but had positive SLN status determined by IHC. SLN status based on IHC evaluation did not correlate with age (P = 0.077), tumor size (P = 0.717), grade (P = 0.148), estrogen receptor status (P = 1.000), or lymphovascular invasion (P = 0.274). Furthermore, IHC-detected positive SLN status did not correlate with distant metastasis (P = 0.372) or overall or distant metastasis-free survival (P = 0.543 and P = 0.540, respectively). CONCLUSIONS: Although the finding of SLN micrometastases by IHC may change management in > 12% of patients, preliminary results suggested that such micrometastases do not affect outcomes significantly.

Pawlik TM, Buchholz TA, Kuerer HM. · Department of Surgical Oncology, The University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA. · J Am Coll Surg. · Pubmed #15325619 No free full text.

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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.

Sanders KE, Komaki R, Buchholz TA. · Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA. · Rays. · Pubmed #15018312 No free full text.

Abstract: The increased utilization of computed tomography based treatment planning and intensity modulated radiation therapy for treatment of breast cancer has yielded many potential advantages. Yet, a complete understanding of at risk tissues and avoidance structures is necessary to appropriately utilize such a conformal treatment design. Designing a treatment that maximizes dose homogeneity to the whole breast while minimizing dose to the lung parenchyma, coronary vessels, and myocardium has the potential to improve long-term morbidity and cosmetic outcome. In this review we discuss the utilization of three dimensional treatment planning and intensity modulation for the treatment of breast cancer. We focus on the delineation of target and avoidance structures in the setting of breast conserving therapy and the techniques utilized to maximize the therapeutic ratio.

Garg AK, Hortobagyi GN, Aggarwal BB, Sahin AA, Buchholz TA. · Department of Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, 77030, USA. · Curr Opin Oncol. · Pubmed #14624221 No free full text.

Abstract: PURPOSE OF REVIEW: To examine the links of nuclear factor-kappa B (NF-kappa B) to treatment-induced signaling in breast cancer and to propose further studies to elucidate the role of NF-kappa B in breast cancer response to chemotherapy and radiation. RECENT FINDINGS: The authors' group and others have investigated the clinical relevance of ubiquitously expressed NF-kappa B in breast cancer. Possibly through its effects on apoptosis, NF-kappa B has been implicated in tumor resistance to chemotherapy and radiation in many types of tumors. Furthermore, both in vitro and in vivo studies have shown that targeted inhibition of NF-kappa B can sensitize tumor cells to chemotherapy and radiation. SUMMARY: The molecular mechanisms involved in chemotherapy-induced and radiation-induced cell death in breast cancer are not fully known, nor are the mechanisms of treatment resistance. NF-kappa B is a transcription factor for a number of genes involved in tumor progression and resistance to systemic therapies and is a major regulator of the apoptotic pathway. Gaining further insights into molecular factors such as NF-kappa B as biomarkers for treatment response may help clinicians predict treatment outcome and lead to the development of targeted therapeutics.

Buchholz TA, Hunt KK, Whitman GJ, Sahin AA, Hortobagyi GN. · Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. · Cancer. · Pubmed #12973838 links to  free full text

Abstract: BACKGROUND: The majority of patients with breast carcinoma receive chemotherapy as a component of multimodality treatment. Over the past decade, it has become increasingly more common to deliver chemotherapy first, but this has raised new questions within all disciplines of cancer management. METHODS: The authors reviewed published studies on the effect of neoadjuvant chemotherapy for breast carcinoma on the practice of medical oncology, surgical oncology, radiation oncology, pathology, and radiology. RESULTS: Treating breast carcinoma with neoadjuvant chemotherapy has several advantages, such as providing the earliest possible treatment against preexisting micrometastases, offering selected patients breast conservation therapy, and allowing for measurement of disease response, which can then be used to customize subsequent chemotherapy. However, neoadjuvant chemotherapy affects the practice not only of medical oncology, but also has important implications for the specialties of surgery, radiology, pathology, and radiation oncology. The current review addressed the new opportunities and challenges within the multidisciplinary care of breast carcinoma provided by neoadjuvant chemotherapy. CONCLUSIONS: The complexity of the issues led the authors to conclude that patients who receive neoadjuvant chemotherapy are likely to benefit from a coordinated multidisciplinary approach to their care.

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.