Breast Cancer Treatment & Management
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12/27/12
Breast Cancer Treatment & Management
Medscape Reference Reference
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Breast Cancer Treatment & Management
Author: Alison T Stopeck, MD; Chief Editor: Jules E Harris, MD more... Updated: Nov 30, 2012
Approach Considerations
Surgery is considered primary treatment for breast cancer, as many patients with early-stage disease are cured with surgery alone. The goals of breast cancer surgery include complete resection of the primary tumor with negative margins to reduce the risk of local recurrences, and pathologic staging of the tumor and axillary lymph nodes for providing necessary prognostic information. Several different types of operations are available for the treatment of breast cancer. Adjuvant treatment for breast cancer involves radiation therapy and a variety of chemotherapeutic and biologic agents.
Treatment of Invasive Breast Cancer
Surgical treatment of invasive breast cancer may consist of lumpectomy or total mastectomy.In breast cancer patients who have clinically negative nodes, surgery typically includes sentinel lymph node dissection for staging the axilla. Go to Surgical Treatment of Breast Cancer for more information on these topics. In addition to surgery, the use of radiation therapy, chemotherapy, or both may be indicated.
Breast-conserving radiation therapy
The purpose of radiation therapy following breast-conserving surgery is to eradicate local subclinical residual disease while reducing local recurrence rates by approximately 75%. Based on results from several randomized controlled studies, radiation to the intact breast is considered standard of care, even in the lowest-risk disease with the most favorable prognostic features. There are 2 general approaches used to deliver radiation therapy: conventional external beam radiotherapy (EBRT) and partial-breast irradiation (PBI). Whole-breast radiotherapy (WBRT) consists of EBRT delivered to the breast at a dose of 50-55 Gy over 5-6 weeks. This is often followed by a boost dose specifically directed to the area in the breast where the tumor was removed. Common side effects of radiation therapy include fatigue, breast pain, swelling, and skin desquamation. Late toxicity (lasting 6 mo or longer following treatment) may include persistent breast edema, pain, fibrosis, and skin hyperpigmentation. Rare side effects include rib fractures, pulmonary fibrosis, cardiac disease (left breast treatment), and secondary malignancies such as radiation-induced sarcoma (0.5%).
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Partial-breast irradiation is employed in early stage breast cancer following breast-conserving surgery as a way of delivering larger fraction sizes while maintaining a low risk of late effects. Several techniques that can deliver this therapy include interstitial brachytherapy (multiple catheters placed through the breast) and intracavitary brachytherapy (a balloon catheter inserted into the lumpectomy site [ie, MammoSite]). Treatment is typically for 5 days, twice daily. These techniques have shown low local recurrence rates comparable to EBRT in several nonrandomized studies. The American Society of Breast Surgeons (ASBrS) recommends the following selection criteria when considering patients for treatment with accelerated partial breast irradiation: Age 45 years and older Invasive ductal carcinoma or DCIS Total tumor size (invasive and DCIS) 3 cm or smaller Negative microscopic surgical margins of excision Axillary lymph node/sentinel lymph node negative Potential complications of partial-breast irradiation are catheter placement, followed by removal secondary to inadequate skin spacing, infection, seroma, fibrosis, chronic pain, or disease recurrence.
Postmastectomy radiation therapy
Clinical practice guidelines developed by ASCO along with several prospective, randomized clinical trials recommend postmastectomy radiation therapy be performed using the following criteria: Positive postmastectomy margins Primary tumors larger than 5 cm Involvement of 4 or more lymph nodes Patients with more than 4 positive lymph nodes should also undergo prophylactic nodal radiation therapy at doses of 4500-5000 cGy to the axillary and supraclavicular regions. For patients who undergo axillary lymph node dissection and are found to have no lymph node involvement, axillary radiation therapy is not recommended. Meta-analyses have shown postmastectomy radiation therapy combined with regional nodal radiation therapy significantly decreases the rate of local relapse and breast cancer mortality. Currently, the benefit of radiation therapy for women with 1-3 positive axillary lymph nodes is uncertain, and studies are ongoing.
Adjuvant Therapy for Breast Cancer
Depending on the model of risk reduction, adjuvant therapy has been estimated to be responsible for 35-72% of the reduction in mortality rate. Adjuvant treatment of breast cancer is designed to treat micrometastatic disease, or breast cancer cells that have escaped the breast and regional lymph nodes but which have not yet had an established identifiable metastasis. Treatment is aimed at reducing the risk of future recurrence, thereby reducing breast cancer-related morbidity and mortality. Go to Adjuvant Therapy for Breast Cancer for more information on this topic.
Treatment of Carcinoma in Situ
Ductal carcinoma in situ
Currently, the standard treatment of DCIS is surgical resection with or without radiation. Adjuvant radiation and hormonal therapies are often reserved for younger women, patients undergoing lumpectomy, or comedo subtype. Approximately 30% of women with DCIS in the US are treated with mastectomy with or without reconstruction, 30% with conservative surgery alone, and 40% with conservative surgery followed by whole-breast radiation therapy. Axillary or sentinel lymph node dissection is not routinely recommended for patients with DCIS. Studies have identified metastatic disease to the axillary nodes in 10% of patients. In DCIS, whole-breast radiotherapy is delivered over 5-6 weeks after surgery, reducing the local recurrence rate by approximately 60%. Roughly 50% of local recurrences are invasive breast cancer. Meta-analyses of randomized controlled trials comparing radiation therapy versus observation after surgery for DCIS have demonstrated slightly higher rates of contralateral breast cancer after radiation therapy (3.85% vs 2.5%). Studies comparing accelerated partial breast radiation given over emedicine.medscape.com/article/1947145-treatment 5 days to standard whole-breast radiotherapy are currently under way.
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partial breast radiation given over 5 days to standard whole-breast radiotherapy are currently under way. Tamoxifen is the only hormonal therapy currently approved for adjuvant therapy in patients treated with breastconserving surgery and radiation for DCIS. Currently, a clinical trial evaluating the role of the aromatase inhibitor anastrozole as adjuvant therapy in DCIS has met its accrual and results are anticipated.
Lobular carcinoma in situ
The National Surgical Adjuvant Breast and Bowel Project (NSABP) P-1 trial prospectively studied the efficacy of tamoxifen in the prevention of breast cancer and included patients with LCIS.[12] The researchers found a 55% risk reduction in women treated with tamoxifen. Overall, treatment options include observation and close follow-up care with or without tamoxifen, and bilateral mastectomy with or without reconstruction. No evidence exists of therapeutic benefit from local excision, axillary dissection, radiotherapy, or chemotherapy. The presence of LCIS in the breast of a woman with ductal or lobular cancer does not require further immediate surgery on the opposite breast. Mirror biopsy of the contralateral breast, once advocated in the treatment of LCIS, is mainly of historic interest.
Treatment of Locally Advanced and Inflammatory Breast Cancer
Originally, the reason for grouping LABC and IBC was the recognition that both diseases had little or no chance of cure from local therapy alone, and they were considered inoperable for that reason. The definition of locally advanced disease has broadened to include patients who are technically operable but who have large primary tumors (>5 cm). It is important to recognize, however, that the reasons for using neoadjuvant therapy are different in women who have large primary tumors, in which the goal is to increase the possibility of breast-conserving surgery, than in those who have disease that meets the original criteria of LABC or IBC, for whom the administration of systemic treatment is essential to make definitive local treatment possible with the intent of cure. Because the prognosis for women with T3N0 (stage IIB) and T3N1 (stage IIIA) breast cancer is better overall than it is for those with classically defined LABC (IIIB, IIIC) or IBC (IIIB, T4d), it is important to know the relative proportions of patients in each category when results of a clinical trial are reported. Not only may one expect better disease-free and overall survival for stage IIB and IIIA patients, but also the likelihood of achieving a pathologic complete response (pCR) from neoadjuvant treatment, a well-recognized surrogate for long-term outcome, is inversely related to tumor size. It is also important to recognize that staging criteria in the sixth edition of the AJCC Cancer Staging Handbook differs from its predecessors in ways that are relevant to the patient groups discussed here: women with T3 tumors were previously considered to have stage III disease and are so reported in the older literature; women with resectable tumors who are found to have 4 or more involved axillary lymph nodes after initial surgery, formerly called stage II, are currently grouped as IIIA. The revised staging system is better for defining prognostic subgroups, but the practical relevance of grouping together all patients who typically receive "up front" chemotherapy remains, as their treatment outcomes are usually reported as a function of the particular neoadjuvant program employed.
Inflammatory breast cancer
IBC is a clinical diagnosis that implies presentation with the cardinal signs of inflammation (calor, rubor, and tumor) involving the breast, although the calor (warmth) may be subtle and the tumor (mass) may not be appreciated as something discrete. Indeed, even when a localized mass is apparent in IBC, the true extent of the disease (as shown by performing skin biopsies from the surrounding, normal-appearing skin) is usually greater than apparent on physical examination. It was originally described as having an erysipeloid border, but only a minority of cases have this component of a raised edge. In Western countries, the frequency of IBC is low, between 1% and 2% of all breast cancers, but it is much higher in some parts of the world, such as northern Africa, for reasons that are not known. IBC tends to occur at a younger age than LABC. Pathologically, it was originally associated with the classic finding of involvement of subdermal lymphatics, although this finding is not in itself diagnostic of IBC (it may occur with LABC as a secondary phenomenon).
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This disease is more likely to stain negatively by IHC for ER and PR, somewhat more likely to be positive for HER2 overexpression, and both angiogenesis and lymphangiogenesis appear to be increased by microvessel density or RNA-based gene expression arrays. Within IBC, however, may be found the same molecular subtypes of breast cancer as originally described for non-inflammatory breast cancer.
Locally advanced breast cancer
LABC is more common in the US than is IBC, and, by the definition used here, may account for 10-15% of patients (this drops to about 5% if one uses the stricter definition of inoperable). Epidemiologically, LABC is associated with lower socioeconomic class and, probably for that reason, with black race in the US. LABC encompasses both relatively indolent neglected tumors and those that have grown rapidly as a result of their inherent biology. It is as heterogeneous as invasive breast cancer in general, and, in most case series, LABC has a better long-term outcome than IBC, even when only inoperable cases are considered.
Evaluation of lymph nodes and response
Patients with LABC or IBC with clinically positive nodes should undergo a core biopsy before initiating chemotherapy. Those with clinically negative nodes may undergo sentinel node biopsy before they start treatment, or sentinel node determination may be delayed until after treatment is completed. Theoretically, it should be preferable to perform sentinel node sampling up front, because chemotherapy might eradicate preexistent disease in the sentinel node and result in a false negative, and/or altered lymphatic drainage in large tumors might affect accuracy of the procedure. However, data from the NSABP B-27 neoadjuvant trial suggest that the false-negative rate for sentinel node biopsies performed after neoadjuvant chemotherapy is about 11%, comparable to the false-negative rate for patients undergoing initial resection.[13] In general, the best single test to evaluate the status of measurable tumor is ultrasonography, preferably done by the same operator to avoid interobserver variability. The mass often appears larger on physical examination than it does on sonogram, which can more effectively discriminate hypoechoic masses from surrounding stroma and/or hematoma. In IBC, MRI may be an important adjunct to response assessment. The role of PET scanning in the routine assessment of response remains to be determined. No current imaging technique appears to be highly accurate for the prediction of complete pathologic response. Thus, the purpose of regular size assessment is to exclude continuation of therapy in a patient with a growing tumor (seen in < 5% with the initial treatment) and to suggest when maximal response of grossly evident disease has been achieved, as this may be the optimal time to proceed to resection.
Systemic Treatment of Metastatic Breast Cancer
Marked advancements are being made in the treatment of early stage breast cancer, but many women still develop recurrence and metastasis. In addition, 5-10% of breast cancer patients have metastatic disease at presentation. Although treatments for metastatic breast cancer continue to improve, there remains no cure once distant metastases develop. Furthermore, although occasional patients with metastatic breast cancer benefit from surgical resection for an isolated recurrence and many require radiation therapy for palliation at a specific site (or definitive treatment of brain metastasis), in general, recurrent or metastatic breast cancer must be approached systemically such that the therapeutic effect reaches all sites of disease. There are 2 main interventions: hormone therapy and chemotherapy. Go to Adjuvant Therapy for Breast Cancer for more information on these topics.
Surgery in Metastatic Breast Cancer Treatment
As modern systemic chemotherapy has become more effective, some patients with intact primary tumors and metastasis can have long-term stable distant disease or even no evidence of residual metastatic disease following treatment. Recently, interest has increased in the role of surgical intervention for the intact primary tumor for these metastatic breast cancer patients. Several single-institution cohort and retrospective studies have examined this question, concluding that surgical resection of the intact primary tumor may provide a survival advantage. It is still unknown whether a selection bias affects the findings of a survival advantage in favor of surgery, and no prospective, randomized control trial has ever been performed to address this question. However, the dogma to never operate in the setting of metastatic emedicine.medscape.com/article/1947145-treatment disease has certainly been dispelled in favor of critical evaluation of
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never operate in the setting of metastatic disease has certainly been dispelled in favor of critical evaluation of whether surgically achieved local control can lead to improved survival as a part of multimodal treatment.
Pharmacologic Breast Cancer Risk Reduction
Two selective estrogen receptor modulators (SERMs), tamoxifen and raloxifene (Evista), are approved for reduction of breast cancer risk in high-risk women. Two NSABP trials (NSABP P1 and P2) showed that tamoxifen reduced the risk of DCIS and invasive breast cancer by 30-50%. In the NSABP P2 prevention trial, raloxifene was as effective as tamoxifen in reducing the risk of invasive breast cancer but was 30% less effective than tamoxifen in reducing the risk of DCIS. ACOG has updated its practice guidelines regarding pharmacologic intervention (eg, tamoxifen, raloxifene, aromatase inhibition) for breast cancer risk reduction.[14] Some of the highlights of the expert panel's literature review are as follows: Tamoxifen use for 5 years reduces risk of breast cancer for at least 10 years in premenopausal women, particularly ER-positive invasive tumors. Women 50 years or younger have few adverse effects with tamoxifen, and vascular/vasomotor adverse effects do not persist post treatment. Tamoxifen and raloxifene are equally effective in reducing risk of ER-positive breast cancer in postmenopausal women. Raloxifene is associated with lower rates of thromboembolic disease, benign uterine conditions, and cataracts than tamoxifen. Evidence does not exist on whether either agent decreases mortality from breast cancer. Recommendations include the following: For women with increased risk for breast cancer, offer tamoxifen (20 mg/d for 5 y) to reduce the risk of invasive ER-positive breast cancer In postmenopausal women, raloxifene (60 mg/d for 5 y) may also be considered Aromatase inhibitors (eg, anastrozole, exemestane, letrozole), fenretinide, or other SERMs are not recommended for use outside of a clinical trial
Long-term Monitoring
Follow-up guidelines
There is no consensus among oncologists as to the appropriate and optimal follow-up for long-term breast cancer survivors. The majority of relapses, both local and distant, occur within the first 3 years, especially in higher risk and ER-negative patients. The 2007 ASCO guidelines do not support the use of tumor biomarkers, including CEA, CA15.3, and CA27.29, for monitoring patients for recurrence after primary breast cancer therapy. Table 6, below, lists the NCCN’s recommendations for breast cancer patients in the adjuvant setting. Table 6. Follow-up Recommendations for Breast Cancer Survivors per NCCN Guidelines (Open Table in a new window) Intervention* Mammography Year 1 Year 2 Year 3-5 Year 6+ q4 mo q6 mo Annually
History and physical examination q3-4 mo
Annually (or 6 mo after Annually Annually Annually
post-BCS irradiation)
Chest x-ray Pelvic examination† Bone density ‡
NR Annually q1-2 y
NR
NR
NR
Annually Annually Annually
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BCS = breast-conserving surgery; NR = not recommended.
*
Bone scan, blood counts, LFTs, and tumor markers are not routinely recommended
and should be performed if clinically indicated.
†
For patients with an intact uterus on tamoxifen.
‡
For patients at risk for osteoporosis.
Postsurgical imaging
Women who have had surgery for breast cancer may still require breast cancer screening with mammography. If a woman had a total mastectomy, then the other breast requires yearly follow-up, because she is still at higher risk of developing cancer in the remaining breast. If she had subcutaneous mastectomy, partial mastectomy, or lumpectomy, then that breast itself requires follow-up mammography. The first mammogram is best performed 6 months postoperatively to provide a baseline for the new postoperative and radiation changes. Thereafter, mammography may be performed every 6-12 months for screening and followup. Go to Postsurgical Breast Imaging for more information on this topic. Monitoring of metastatic disease Recommendations for monitoring disease response in the metastatic setting vary. In general, monthly evaluations consisting of a history and physical examination to evaluate progression of disease and toxicities are reasonable. Tumor markers, such as CEA, CA15.3, and CA27.29, can be used in conjunction with diagnostic imaging, history, and physical examination for monitoring while on active therapy. CA15.3 and CA27.29 levels correlate with the course of disease in 60-70% of patients, whereas CEA levels correlate in 40% of patients. However, data are insufficient to recommend the use of CEA, CA15.3, or CA27.29 alone for monitoring response to treatment. Caution should be used when interpreting rising CEA, CA15.3, or CA27.29 levels during the first 4-6 weeks of a new therapy, as spurious early rises may occur. Standardized guidelines for imaging are not yet established and should be tailored to each patient. In general, CT scanning (chest, abdomen, and pelvis), MRI, bone scanning, or PET/CT scanning are performed when symptoms change or tumor markers rise. Circulating tumor cells are cells present in the blood that possess antigenic or genetic characteristics similar to a primary tumor type. The FDA has recently approved the CellSearch System (Veridex, Raritan, NJ) for the detection of circulating tumor cells in patients with metastatic breast cancer. This system captures circulating tumor cells using an immunomagnetic process with an epithelial cell adhesion molecule coated with magnetic beads and cytokeratin antibodies. A circulating tumor cell is identified when it is cytokeratin- and DAPI-positive but CD45-negative. Studies done by Cristofanilli using the CellSearch System have shown a prognostic utility and predictive use for circulating tumor cells in metastatic breast cancer patients.[15] Circulating tumor cell–positive patients (>5 CTCs/7.5 mL blood) were shown to have a worse progression-free survival (17%) and overall survival than the circulating tumor cell–negative patients (36%). The presence of more than 5 circulating tumor cells before hormonal or chemotherapy treatment and following the first cycle of treatment also predict a worse outcome. However, studies to date have used small sample sizes, and no data have shown that use of circulating tumor cell testing affects overall survival or improves on quality of life. Per ASCO guidelines, the use of circulating tumor cell testing in breast cancer is not recommended for the diagnosis of breast cancer, nor should test results influence treatment decisions. The Southwest Oncology Group (SWOG) is conducting a large, prospective trial to address the clinical use of circulating tumor cells in breast cancer. emedicine.medscape.com/article/1947145-treatment 6/10
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cancer.
Contributor Information and Disclosures
Author Alison T Stopeck, MD Associate Professor of Medicine, Arizona Cancer Center, University of Arizona Health Sciences Center; Director of Clinical Breast Cancer Program, Arizona Cancer Center; Medical Director of Coagulation Laboratory, University Medical Center; Director of Arizona Hemophilia and Thrombosis Center Alison T Stopeck, MD is a member of the following medical societies: American Association for Cancer Research, American College of Physicians, American Society of Clinical Oncology, American Society of Hematology, Hemophilia and Thrombosis Research Society, and Southwest Oncology Group Disclosure: Genentech Honoraria Speaking and teaching; AstraZeneca Honoraria Speaking and teaching; AstraZeneca Grant/research funds Other Coauthor(s) Patricia A Thompson, PhD Assistant Professor, Department of Pathology, University of Arizona, Tucson Disclosure: Nothing to disclose. Chief Editor Jules E Harris, MD Clinical Professor of Medicine, Section of Hematology/Oncology, University of Arizona College of Medicine, Arizona Cancer Center Jules E Harris, MD is a member of the following medical societies: American Association for Cancer Research, American Association for the Advancement of Science, American Association of Immunologists, American Society of Hematology, and Central Society for Clinical Research Disclosure: Nothing to disclose. Additional Contributors Leona Downey, MD Assistant Professor of Internal Medicine, Section of Oncology and Hematology, University of Arizona, Arizona Cancer Center Leona Downey, MD is a member of the following medical societies: American Geriatrics Society, American Society of Clinical Oncology, and Southwest Oncology Group Disclosure: Nothing to disclose. Manjit Singh Gohel, MD, MRCS, MB, ChB Specialist Registrar, Division of Breast and Endocrine Surgery, Northwick Park Hospital Disclosure: Nothing to disclose. Harold Harvey, MD Professor, Department of Medicine, Pennsylvania State University Disclosure: Nothing to disclose. Kanchan Kaur, MBBS, MS (General Surgery), MRCS (Ed) Consulting Breast and Oncoplastic Surgeon, Medanta, The Medicity, India Disclosure: Nothing to disclose. Julie Lang, MD Assistant Professor of Surgery and the BIO5 Institute, Director of Breast Surgical Oncology, University of Arizona College of Medicine Julie Lang, MD is a member of the following medical societies: American College of Surgeons, American Society of Breast Surgeons, American Society of Clinical Oncology, Association for Academic Surgery, and Society of Surgical Oncology
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Society of Surgical Oncology Disclosure: Genomic Health Grant/research funds Speaking and teaching; Agendia Grant/research funds Speaking and teaching; Surgical Tools Grant/research funds Research; Sysmex Grant/research funds Research Robert B Livingston, MD Professor of Clinical Medicine and Director, Clinical Research Shared Services, Arizona Cancer Center Robert B Livingston, MD is a member of the following medical societies: American Association for Cancer Research, American Federation for Clinical Research, and American Society of Clinical Oncology Disclosure: Nothing to disclose. Hanan Makhoul, MD Staff Physician, Department of Internal Medicine, University of Arkansas School of Medicine Disclosure: Nothing to disclose. Issam Makhoul, MD Associate Professor, Department of Medicine, Division of Hematology/Oncology, University of Arkansas for Medical Sciences Issam Makhoul, MD is a member of the following medical societies: American Society of Clinical Oncology and American Society of Hematology Disclosure: Nothing to disclose. Robert C Shepard, MD, FACP Associate Professor of Medicine in Hematology and Oncology at University of North Carolina at Chapel Hill; Vice President of Scientific Affairs, Therapeutic Expertise, Oncology, at PRA International Robert C Shepard, MD, FACP is a member of the following medical societies: American Association for Cancer Research, American College of Physician Executives, American College of Physicians, American Federation for Clinical Research, American Federation for Medical Research, American Medical Association, American Medical Informatics Association, American Society of Hematology, Association of Clinical Research Professionals, Eastern Cooperative Oncology Group, European Society for Medical Oncology, Massachusetts Medical Society, and Society for Biological Therapy Disclosure: Nothing to disclose. Hemant Singhal, MD, MBBS, FRCSE, FRCS(C) Senior Lecturer, Director of Breast Service, Department of Surgery, Imperial College School of Medicine; Consultant Surgeon, Northwick Park and St Marks Hospitals, UK Hemant Singhal, MD, MBBS, FRCSE, FRCS(C) is a member of the following medical societies: Royal College of Physicians and Surgeons of Canada and Royal College of Surgeons of Edinburgh Disclosure: Nothing to disclose. Carl V Smith, MD The Distinguished Chris J and Marie A Olson Chair of Obstetrics and Gynecology, Professor, Department of Obstetrics and Gynecology, Senior Associate Dean for Clinical Affairs, University of Nebraska Medical Center Carl V Smith, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists, American Institute of Ultrasound in Medicine, Association of Professors of Gynecology and Obstetrics, Central Association of Obstetricians and Gynecologists, Council of University Chairs of Obstetrics and Gynecology, Nebraska Medical Association, and Society for Maternal-Fetal Medicine Disclosure: Nothing to disclose. Wiley Souba, MD Chairman, Professor, Department of General Surgery, Pennsylvania State College of Medicine; Chief Surgeon, The Milton S Hershey Medical Center Disclosure: Nothing to disclose. Rachel Swart, MD, PhD Assistant Professor of Medicine, Department of Hematology and Oncology, Arizona Cancer Center, University of Arizona
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Rachel Swart, MD, PhD is a member of the following medical societies: American Association for Cancer Research, American Society of Clinical Oncology, Arizona Medical Association, and Southwest Oncology Group Disclosure: Roche Grant/research funds Other Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference Disclosure: Medscape Salary Employment Simon Thomson, MB, BCh, MD, FRCS Specialist Registrar, Department of Breast and Endocrine Surgery, Northwick Park Hospital, UK Simon Thomson, MB, BCh, MD, FRCS is a member of the following medical societies: British Medical Association Disclosure: Nothing to disclose.
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13. Bear HD, Anderson S, Smith RE, et al. Sequential preoperative or postoperative docetaxel added to preoperative doxorubicin plus cyclophosphamide for operable breast cancer:National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol. May 1 2006;24(13):2019-27. [Medline]. 14. [Best Evidence] [Guideline] Visvanathan K, Chlebowski RT, Hurley P, Col NF, Ropka M, Collyar D, et al. American Society of Clinical Oncology clinical practice guideline update on the use of pharmacologic interventions including tamoxifen, raloxifene, and aromatase inhibition for breast cancer risk reduction. J Clin Oncol. Jul 1 2009;27(19):3235-58. 15. Cristofanilli M. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. Semin Oncol. Jun 2006;33(3 Suppl 9):S9-14. 16. Xeloda [package insert]. South San Francisco, Calif: Genentech; November 2009. 17. Ellence [package insert]. New York, NY: Pfizer; February 2007. 18. Baselga J, Cortés J, Kim SB, Im SA, Hegg R, Im YH, et al. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med. Jan 12 2012;366(2):109-19. [Medline]. 19. The U.S. Food and Drug Administration. FDA begins process to remove breast cancer indication from Avastin label. FDA NEWS RELEASE: Dec. 16, 2010. Available at http://www.fda.gov/newsevents/newsroom/pressannouncements/ucm237172.htm. Accessed July 15, 2011. 20. The U.S. Food and Drug Administration. Postmarket Drug Safety Information: Avastin (bevacizumab) Information, Update, 6/29/2011. Accessed July 15, 2011. [Full Text]. 21. Herceptin [package insert]. South San Francisco, Calif: Genentech; October 2010. 22. Tykerb [package insert]. Research Triangle Park, NC: GlaxoSmithKline; January 2010. 23. Femara [package insert]. East Hanover, NJ: Novartis; April 2010. 24. Fareston [package insert]. Memphis, Tenn: GTX; December 2004. Medscape Reference © 2011 WebMD, LLC 25. James TA, Mace JL, Virnig BA, et al. Preoperative needle biopsy improves the quality of breast cancer surgery. J Am Coll Surg. Oct 2012;215(4):562-8. [Medline]. 26. Mulcahy N. Breast cancer needle biopsy in 'granular' detail. Medscape Medical News. Available at http://www.medscape.com/viewarticle/772152. Accessed Oct 15 2012.
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Medscape Reference Reference
News Reference Education MEDLINE
Breast Cancer Treatment & Management
Author: Alison T Stopeck, MD; Chief Editor: Jules E Harris, MD more... Updated: Nov 30, 2012
Approach Considerations
Surgery is considered primary treatment for breast cancer, as many patients with early-stage disease are cured with surgery alone. The goals of breast cancer surgery include complete resection of the primary tumor with negative margins to reduce the risk of local recurrences, and pathologic staging of the tumor and axillary lymph nodes for providing necessary prognostic information. Several different types of operations are available for the treatment of breast cancer. Adjuvant treatment for breast cancer involves radiation therapy and a variety of chemotherapeutic and biologic agents.
Treatment of Invasive Breast Cancer
Surgical treatment of invasive breast cancer may consist of lumpectomy or total mastectomy.In breast cancer patients who have clinically negative nodes, surgery typically includes sentinel lymph node dissection for staging the axilla. Go to Surgical Treatment of Breast Cancer for more information on these topics. In addition to surgery, the use of radiation therapy, chemotherapy, or both may be indicated.
Breast-conserving radiation therapy
The purpose of radiation therapy following breast-conserving surgery is to eradicate local subclinical residual disease while reducing local recurrence rates by approximately 75%. Based on results from several randomized controlled studies, radiation to the intact breast is considered standard of care, even in the lowest-risk disease with the most favorable prognostic features. There are 2 general approaches used to deliver radiation therapy: conventional external beam radiotherapy (EBRT) and partial-breast irradiation (PBI). Whole-breast radiotherapy (WBRT) consists of EBRT delivered to the breast at a dose of 50-55 Gy over 5-6 weeks. This is often followed by a boost dose specifically directed to the area in the breast where the tumor was removed. Common side effects of radiation therapy include fatigue, breast pain, swelling, and skin desquamation. Late toxicity (lasting 6 mo or longer following treatment) may include persistent breast edema, pain, fibrosis, and skin hyperpigmentation. Rare side effects include rib fractures, pulmonary fibrosis, cardiac disease (left breast treatment), and secondary malignancies such as radiation-induced sarcoma (0.5%).
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Partial-breast irradiation is employed in early stage breast cancer following breast-conserving surgery as a way of delivering larger fraction sizes while maintaining a low risk of late effects. Several techniques that can deliver this therapy include interstitial brachytherapy (multiple catheters placed through the breast) and intracavitary brachytherapy (a balloon catheter inserted into the lumpectomy site [ie, MammoSite]). Treatment is typically for 5 days, twice daily. These techniques have shown low local recurrence rates comparable to EBRT in several nonrandomized studies. The American Society of Breast Surgeons (ASBrS) recommends the following selection criteria when considering patients for treatment with accelerated partial breast irradiation: Age 45 years and older Invasive ductal carcinoma or DCIS Total tumor size (invasive and DCIS) 3 cm or smaller Negative microscopic surgical margins of excision Axillary lymph node/sentinel lymph node negative Potential complications of partial-breast irradiation are catheter placement, followed by removal secondary to inadequate skin spacing, infection, seroma, fibrosis, chronic pain, or disease recurrence.
Postmastectomy radiation therapy
Clinical practice guidelines developed by ASCO along with several prospective, randomized clinical trials recommend postmastectomy radiation therapy be performed using the following criteria: Positive postmastectomy margins Primary tumors larger than 5 cm Involvement of 4 or more lymph nodes Patients with more than 4 positive lymph nodes should also undergo prophylactic nodal radiation therapy at doses of 4500-5000 cGy to the axillary and supraclavicular regions. For patients who undergo axillary lymph node dissection and are found to have no lymph node involvement, axillary radiation therapy is not recommended. Meta-analyses have shown postmastectomy radiation therapy combined with regional nodal radiation therapy significantly decreases the rate of local relapse and breast cancer mortality. Currently, the benefit of radiation therapy for women with 1-3 positive axillary lymph nodes is uncertain, and studies are ongoing.
Adjuvant Therapy for Breast Cancer
Depending on the model of risk reduction, adjuvant therapy has been estimated to be responsible for 35-72% of the reduction in mortality rate. Adjuvant treatment of breast cancer is designed to treat micrometastatic disease, or breast cancer cells that have escaped the breast and regional lymph nodes but which have not yet had an established identifiable metastasis. Treatment is aimed at reducing the risk of future recurrence, thereby reducing breast cancer-related morbidity and mortality. Go to Adjuvant Therapy for Breast Cancer for more information on this topic.
Treatment of Carcinoma in Situ
Ductal carcinoma in situ
Currently, the standard treatment of DCIS is surgical resection with or without radiation. Adjuvant radiation and hormonal therapies are often reserved for younger women, patients undergoing lumpectomy, or comedo subtype. Approximately 30% of women with DCIS in the US are treated with mastectomy with or without reconstruction, 30% with conservative surgery alone, and 40% with conservative surgery followed by whole-breast radiation therapy. Axillary or sentinel lymph node dissection is not routinely recommended for patients with DCIS. Studies have identified metastatic disease to the axillary nodes in 10% of patients. In DCIS, whole-breast radiotherapy is delivered over 5-6 weeks after surgery, reducing the local recurrence rate by approximately 60%. Roughly 50% of local recurrences are invasive breast cancer. Meta-analyses of randomized controlled trials comparing radiation therapy versus observation after surgery for DCIS have demonstrated slightly higher rates of contralateral breast cancer after radiation therapy (3.85% vs 2.5%). Studies comparing accelerated partial breast radiation given over emedicine.medscape.com/article/1947145-treatment 5 days to standard whole-breast radiotherapy are currently under way.
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partial breast radiation given over 5 days to standard whole-breast radiotherapy are currently under way. Tamoxifen is the only hormonal therapy currently approved for adjuvant therapy in patients treated with breastconserving surgery and radiation for DCIS. Currently, a clinical trial evaluating the role of the aromatase inhibitor anastrozole as adjuvant therapy in DCIS has met its accrual and results are anticipated.
Lobular carcinoma in situ
The National Surgical Adjuvant Breast and Bowel Project (NSABP) P-1 trial prospectively studied the efficacy of tamoxifen in the prevention of breast cancer and included patients with LCIS.[12] The researchers found a 55% risk reduction in women treated with tamoxifen. Overall, treatment options include observation and close follow-up care with or without tamoxifen, and bilateral mastectomy with or without reconstruction. No evidence exists of therapeutic benefit from local excision, axillary dissection, radiotherapy, or chemotherapy. The presence of LCIS in the breast of a woman with ductal or lobular cancer does not require further immediate surgery on the opposite breast. Mirror biopsy of the contralateral breast, once advocated in the treatment of LCIS, is mainly of historic interest.
Treatment of Locally Advanced and Inflammatory Breast Cancer
Originally, the reason for grouping LABC and IBC was the recognition that both diseases had little or no chance of cure from local therapy alone, and they were considered inoperable for that reason. The definition of locally advanced disease has broadened to include patients who are technically operable but who have large primary tumors (>5 cm). It is important to recognize, however, that the reasons for using neoadjuvant therapy are different in women who have large primary tumors, in which the goal is to increase the possibility of breast-conserving surgery, than in those who have disease that meets the original criteria of LABC or IBC, for whom the administration of systemic treatment is essential to make definitive local treatment possible with the intent of cure. Because the prognosis for women with T3N0 (stage IIB) and T3N1 (stage IIIA) breast cancer is better overall than it is for those with classically defined LABC (IIIB, IIIC) or IBC (IIIB, T4d), it is important to know the relative proportions of patients in each category when results of a clinical trial are reported. Not only may one expect better disease-free and overall survival for stage IIB and IIIA patients, but also the likelihood of achieving a pathologic complete response (pCR) from neoadjuvant treatment, a well-recognized surrogate for long-term outcome, is inversely related to tumor size. It is also important to recognize that staging criteria in the sixth edition of the AJCC Cancer Staging Handbook differs from its predecessors in ways that are relevant to the patient groups discussed here: women with T3 tumors were previously considered to have stage III disease and are so reported in the older literature; women with resectable tumors who are found to have 4 or more involved axillary lymph nodes after initial surgery, formerly called stage II, are currently grouped as IIIA. The revised staging system is better for defining prognostic subgroups, but the practical relevance of grouping together all patients who typically receive "up front" chemotherapy remains, as their treatment outcomes are usually reported as a function of the particular neoadjuvant program employed.
Inflammatory breast cancer
IBC is a clinical diagnosis that implies presentation with the cardinal signs of inflammation (calor, rubor, and tumor) involving the breast, although the calor (warmth) may be subtle and the tumor (mass) may not be appreciated as something discrete. Indeed, even when a localized mass is apparent in IBC, the true extent of the disease (as shown by performing skin biopsies from the surrounding, normal-appearing skin) is usually greater than apparent on physical examination. It was originally described as having an erysipeloid border, but only a minority of cases have this component of a raised edge. In Western countries, the frequency of IBC is low, between 1% and 2% of all breast cancers, but it is much higher in some parts of the world, such as northern Africa, for reasons that are not known. IBC tends to occur at a younger age than LABC. Pathologically, it was originally associated with the classic finding of involvement of subdermal lymphatics, although this finding is not in itself diagnostic of IBC (it may occur with LABC as a secondary phenomenon).
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This disease is more likely to stain negatively by IHC for ER and PR, somewhat more likely to be positive for HER2 overexpression, and both angiogenesis and lymphangiogenesis appear to be increased by microvessel density or RNA-based gene expression arrays. Within IBC, however, may be found the same molecular subtypes of breast cancer as originally described for non-inflammatory breast cancer.
Locally advanced breast cancer
LABC is more common in the US than is IBC, and, by the definition used here, may account for 10-15% of patients (this drops to about 5% if one uses the stricter definition of inoperable). Epidemiologically, LABC is associated with lower socioeconomic class and, probably for that reason, with black race in the US. LABC encompasses both relatively indolent neglected tumors and those that have grown rapidly as a result of their inherent biology. It is as heterogeneous as invasive breast cancer in general, and, in most case series, LABC has a better long-term outcome than IBC, even when only inoperable cases are considered.
Evaluation of lymph nodes and response
Patients with LABC or IBC with clinically positive nodes should undergo a core biopsy before initiating chemotherapy. Those with clinically negative nodes may undergo sentinel node biopsy before they start treatment, or sentinel node determination may be delayed until after treatment is completed. Theoretically, it should be preferable to perform sentinel node sampling up front, because chemotherapy might eradicate preexistent disease in the sentinel node and result in a false negative, and/or altered lymphatic drainage in large tumors might affect accuracy of the procedure. However, data from the NSABP B-27 neoadjuvant trial suggest that the false-negative rate for sentinel node biopsies performed after neoadjuvant chemotherapy is about 11%, comparable to the false-negative rate for patients undergoing initial resection.[13] In general, the best single test to evaluate the status of measurable tumor is ultrasonography, preferably done by the same operator to avoid interobserver variability. The mass often appears larger on physical examination than it does on sonogram, which can more effectively discriminate hypoechoic masses from surrounding stroma and/or hematoma. In IBC, MRI may be an important adjunct to response assessment. The role of PET scanning in the routine assessment of response remains to be determined. No current imaging technique appears to be highly accurate for the prediction of complete pathologic response. Thus, the purpose of regular size assessment is to exclude continuation of therapy in a patient with a growing tumor (seen in < 5% with the initial treatment) and to suggest when maximal response of grossly evident disease has been achieved, as this may be the optimal time to proceed to resection.
Systemic Treatment of Metastatic Breast Cancer
Marked advancements are being made in the treatment of early stage breast cancer, but many women still develop recurrence and metastasis. In addition, 5-10% of breast cancer patients have metastatic disease at presentation. Although treatments for metastatic breast cancer continue to improve, there remains no cure once distant metastases develop. Furthermore, although occasional patients with metastatic breast cancer benefit from surgical resection for an isolated recurrence and many require radiation therapy for palliation at a specific site (or definitive treatment of brain metastasis), in general, recurrent or metastatic breast cancer must be approached systemically such that the therapeutic effect reaches all sites of disease. There are 2 main interventions: hormone therapy and chemotherapy. Go to Adjuvant Therapy for Breast Cancer for more information on these topics.
Surgery in Metastatic Breast Cancer Treatment
As modern systemic chemotherapy has become more effective, some patients with intact primary tumors and metastasis can have long-term stable distant disease or even no evidence of residual metastatic disease following treatment. Recently, interest has increased in the role of surgical intervention for the intact primary tumor for these metastatic breast cancer patients. Several single-institution cohort and retrospective studies have examined this question, concluding that surgical resection of the intact primary tumor may provide a survival advantage. It is still unknown whether a selection bias affects the findings of a survival advantage in favor of surgery, and no prospective, randomized control trial has ever been performed to address this question. However, the dogma to never operate in the setting of metastatic emedicine.medscape.com/article/1947145-treatment disease has certainly been dispelled in favor of critical evaluation of
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never operate in the setting of metastatic disease has certainly been dispelled in favor of critical evaluation of whether surgically achieved local control can lead to improved survival as a part of multimodal treatment.
Pharmacologic Breast Cancer Risk Reduction
Two selective estrogen receptor modulators (SERMs), tamoxifen and raloxifene (Evista), are approved for reduction of breast cancer risk in high-risk women. Two NSABP trials (NSABP P1 and P2) showed that tamoxifen reduced the risk of DCIS and invasive breast cancer by 30-50%. In the NSABP P2 prevention trial, raloxifene was as effective as tamoxifen in reducing the risk of invasive breast cancer but was 30% less effective than tamoxifen in reducing the risk of DCIS. ACOG has updated its practice guidelines regarding pharmacologic intervention (eg, tamoxifen, raloxifene, aromatase inhibition) for breast cancer risk reduction.[14] Some of the highlights of the expert panel's literature review are as follows: Tamoxifen use for 5 years reduces risk of breast cancer for at least 10 years in premenopausal women, particularly ER-positive invasive tumors. Women 50 years or younger have few adverse effects with tamoxifen, and vascular/vasomotor adverse effects do not persist post treatment. Tamoxifen and raloxifene are equally effective in reducing risk of ER-positive breast cancer in postmenopausal women. Raloxifene is associated with lower rates of thromboembolic disease, benign uterine conditions, and cataracts than tamoxifen. Evidence does not exist on whether either agent decreases mortality from breast cancer. Recommendations include the following: For women with increased risk for breast cancer, offer tamoxifen (20 mg/d for 5 y) to reduce the risk of invasive ER-positive breast cancer In postmenopausal women, raloxifene (60 mg/d for 5 y) may also be considered Aromatase inhibitors (eg, anastrozole, exemestane, letrozole), fenretinide, or other SERMs are not recommended for use outside of a clinical trial
Long-term Monitoring
Follow-up guidelines
There is no consensus among oncologists as to the appropriate and optimal follow-up for long-term breast cancer survivors. The majority of relapses, both local and distant, occur within the first 3 years, especially in higher risk and ER-negative patients. The 2007 ASCO guidelines do not support the use of tumor biomarkers, including CEA, CA15.3, and CA27.29, for monitoring patients for recurrence after primary breast cancer therapy. Table 6, below, lists the NCCN’s recommendations for breast cancer patients in the adjuvant setting. Table 6. Follow-up Recommendations for Breast Cancer Survivors per NCCN Guidelines (Open Table in a new window) Intervention* Mammography Year 1 Year 2 Year 3-5 Year 6+ q4 mo q6 mo Annually
History and physical examination q3-4 mo
Annually (or 6 mo after Annually Annually Annually
post-BCS irradiation)
Chest x-ray Pelvic examination† Bone density ‡
NR Annually q1-2 y
NR
NR
NR
Annually Annually Annually
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BCS = breast-conserving surgery; NR = not recommended.
*
Bone scan, blood counts, LFTs, and tumor markers are not routinely recommended
and should be performed if clinically indicated.
†
For patients with an intact uterus on tamoxifen.
‡
For patients at risk for osteoporosis.
Postsurgical imaging
Women who have had surgery for breast cancer may still require breast cancer screening with mammography. If a woman had a total mastectomy, then the other breast requires yearly follow-up, because she is still at higher risk of developing cancer in the remaining breast. If she had subcutaneous mastectomy, partial mastectomy, or lumpectomy, then that breast itself requires follow-up mammography. The first mammogram is best performed 6 months postoperatively to provide a baseline for the new postoperative and radiation changes. Thereafter, mammography may be performed every 6-12 months for screening and followup. Go to Postsurgical Breast Imaging for more information on this topic. Monitoring of metastatic disease Recommendations for monitoring disease response in the metastatic setting vary. In general, monthly evaluations consisting of a history and physical examination to evaluate progression of disease and toxicities are reasonable. Tumor markers, such as CEA, CA15.3, and CA27.29, can be used in conjunction with diagnostic imaging, history, and physical examination for monitoring while on active therapy. CA15.3 and CA27.29 levels correlate with the course of disease in 60-70% of patients, whereas CEA levels correlate in 40% of patients. However, data are insufficient to recommend the use of CEA, CA15.3, or CA27.29 alone for monitoring response to treatment. Caution should be used when interpreting rising CEA, CA15.3, or CA27.29 levels during the first 4-6 weeks of a new therapy, as spurious early rises may occur. Standardized guidelines for imaging are not yet established and should be tailored to each patient. In general, CT scanning (chest, abdomen, and pelvis), MRI, bone scanning, or PET/CT scanning are performed when symptoms change or tumor markers rise. Circulating tumor cells are cells present in the blood that possess antigenic or genetic characteristics similar to a primary tumor type. The FDA has recently approved the CellSearch System (Veridex, Raritan, NJ) for the detection of circulating tumor cells in patients with metastatic breast cancer. This system captures circulating tumor cells using an immunomagnetic process with an epithelial cell adhesion molecule coated with magnetic beads and cytokeratin antibodies. A circulating tumor cell is identified when it is cytokeratin- and DAPI-positive but CD45-negative. Studies done by Cristofanilli using the CellSearch System have shown a prognostic utility and predictive use for circulating tumor cells in metastatic breast cancer patients.[15] Circulating tumor cell–positive patients (>5 CTCs/7.5 mL blood) were shown to have a worse progression-free survival (17%) and overall survival than the circulating tumor cell–negative patients (36%). The presence of more than 5 circulating tumor cells before hormonal or chemotherapy treatment and following the first cycle of treatment also predict a worse outcome. However, studies to date have used small sample sizes, and no data have shown that use of circulating tumor cell testing affects overall survival or improves on quality of life. Per ASCO guidelines, the use of circulating tumor cell testing in breast cancer is not recommended for the diagnosis of breast cancer, nor should test results influence treatment decisions. The Southwest Oncology Group (SWOG) is conducting a large, prospective trial to address the clinical use of circulating tumor cells in breast cancer. emedicine.medscape.com/article/1947145-treatment 6/10
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cancer.
Contributor Information and Disclosures
Author Alison T Stopeck, MD Associate Professor of Medicine, Arizona Cancer Center, University of Arizona Health Sciences Center; Director of Clinical Breast Cancer Program, Arizona Cancer Center; Medical Director of Coagulation Laboratory, University Medical Center; Director of Arizona Hemophilia and Thrombosis Center Alison T Stopeck, MD is a member of the following medical societies: American Association for Cancer Research, American College of Physicians, American Society of Clinical Oncology, American Society of Hematology, Hemophilia and Thrombosis Research Society, and Southwest Oncology Group Disclosure: Genentech Honoraria Speaking and teaching; AstraZeneca Honoraria Speaking and teaching; AstraZeneca Grant/research funds Other Coauthor(s) Patricia A Thompson, PhD Assistant Professor, Department of Pathology, University of Arizona, Tucson Disclosure: Nothing to disclose. Chief Editor Jules E Harris, MD Clinical Professor of Medicine, Section of Hematology/Oncology, University of Arizona College of Medicine, Arizona Cancer Center Jules E Harris, MD is a member of the following medical societies: American Association for Cancer Research, American Association for the Advancement of Science, American Association of Immunologists, American Society of Hematology, and Central Society for Clinical Research Disclosure: Nothing to disclose. Additional Contributors Leona Downey, MD Assistant Professor of Internal Medicine, Section of Oncology and Hematology, University of Arizona, Arizona Cancer Center Leona Downey, MD is a member of the following medical societies: American Geriatrics Society, American Society of Clinical Oncology, and Southwest Oncology Group Disclosure: Nothing to disclose. Manjit Singh Gohel, MD, MRCS, MB, ChB Specialist Registrar, Division of Breast and Endocrine Surgery, Northwick Park Hospital Disclosure: Nothing to disclose. Harold Harvey, MD Professor, Department of Medicine, Pennsylvania State University Disclosure: Nothing to disclose. Kanchan Kaur, MBBS, MS (General Surgery), MRCS (Ed) Consulting Breast and Oncoplastic Surgeon, Medanta, The Medicity, India Disclosure: Nothing to disclose. Julie Lang, MD Assistant Professor of Surgery and the BIO5 Institute, Director of Breast Surgical Oncology, University of Arizona College of Medicine Julie Lang, MD is a member of the following medical societies: American College of Surgeons, American Society of Breast Surgeons, American Society of Clinical Oncology, Association for Academic Surgery, and Society of Surgical Oncology
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Society of Surgical Oncology Disclosure: Genomic Health Grant/research funds Speaking and teaching; Agendia Grant/research funds Speaking and teaching; Surgical Tools Grant/research funds Research; Sysmex Grant/research funds Research Robert B Livingston, MD Professor of Clinical Medicine and Director, Clinical Research Shared Services, Arizona Cancer Center Robert B Livingston, MD is a member of the following medical societies: American Association for Cancer Research, American Federation for Clinical Research, and American Society of Clinical Oncology Disclosure: Nothing to disclose. Hanan Makhoul, MD Staff Physician, Department of Internal Medicine, University of Arkansas School of Medicine Disclosure: Nothing to disclose. Issam Makhoul, MD Associate Professor, Department of Medicine, Division of Hematology/Oncology, University of Arkansas for Medical Sciences Issam Makhoul, MD is a member of the following medical societies: American Society of Clinical Oncology and American Society of Hematology Disclosure: Nothing to disclose. Robert C Shepard, MD, FACP Associate Professor of Medicine in Hematology and Oncology at University of North Carolina at Chapel Hill; Vice President of Scientific Affairs, Therapeutic Expertise, Oncology, at PRA International Robert C Shepard, MD, FACP is a member of the following medical societies: American Association for Cancer Research, American College of Physician Executives, American College of Physicians, American Federation for Clinical Research, American Federation for Medical Research, American Medical Association, American Medical Informatics Association, American Society of Hematology, Association of Clinical Research Professionals, Eastern Cooperative Oncology Group, European Society for Medical Oncology, Massachusetts Medical Society, and Society for Biological Therapy Disclosure: Nothing to disclose. Hemant Singhal, MD, MBBS, FRCSE, FRCS(C) Senior Lecturer, Director of Breast Service, Department of Surgery, Imperial College School of Medicine; Consultant Surgeon, Northwick Park and St Marks Hospitals, UK Hemant Singhal, MD, MBBS, FRCSE, FRCS(C) is a member of the following medical societies: Royal College of Physicians and Surgeons of Canada and Royal College of Surgeons of Edinburgh Disclosure: Nothing to disclose. Carl V Smith, MD The Distinguished Chris J and Marie A Olson Chair of Obstetrics and Gynecology, Professor, Department of Obstetrics and Gynecology, Senior Associate Dean for Clinical Affairs, University of Nebraska Medical Center Carl V Smith, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists, American Institute of Ultrasound in Medicine, Association of Professors of Gynecology and Obstetrics, Central Association of Obstetricians and Gynecologists, Council of University Chairs of Obstetrics and Gynecology, Nebraska Medical Association, and Society for Maternal-Fetal Medicine Disclosure: Nothing to disclose. Wiley Souba, MD Chairman, Professor, Department of General Surgery, Pennsylvania State College of Medicine; Chief Surgeon, The Milton S Hershey Medical Center Disclosure: Nothing to disclose. Rachel Swart, MD, PhD Assistant Professor of Medicine, Department of Hematology and Oncology, Arizona Cancer Center, University of Arizona
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Rachel Swart, MD, PhD is a member of the following medical societies: American Association for Cancer Research, American Society of Clinical Oncology, Arizona Medical Association, and Southwest Oncology Group Disclosure: Roche Grant/research funds Other Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference Disclosure: Medscape Salary Employment Simon Thomson, MB, BCh, MD, FRCS Specialist Registrar, Department of Breast and Endocrine Surgery, Northwick Park Hospital, UK Simon Thomson, MB, BCh, MD, FRCS is a member of the following medical societies: British Medical Association Disclosure: Nothing to disclose.
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13. Bear HD, Anderson S, Smith RE, et al. Sequential preoperative or postoperative docetaxel added to preoperative doxorubicin plus cyclophosphamide for operable breast cancer:National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol. May 1 2006;24(13):2019-27. [Medline]. 14. [Best Evidence] [Guideline] Visvanathan K, Chlebowski RT, Hurley P, Col NF, Ropka M, Collyar D, et al. American Society of Clinical Oncology clinical practice guideline update on the use of pharmacologic interventions including tamoxifen, raloxifene, and aromatase inhibition for breast cancer risk reduction. J Clin Oncol. Jul 1 2009;27(19):3235-58. 15. Cristofanilli M. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. Semin Oncol. Jun 2006;33(3 Suppl 9):S9-14. 16. Xeloda [package insert]. South San Francisco, Calif: Genentech; November 2009. 17. Ellence [package insert]. New York, NY: Pfizer; February 2007. 18. Baselga J, Cortés J, Kim SB, Im SA, Hegg R, Im YH, et al. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med. Jan 12 2012;366(2):109-19. [Medline]. 19. The U.S. Food and Drug Administration. FDA begins process to remove breast cancer indication from Avastin label. FDA NEWS RELEASE: Dec. 16, 2010. Available at http://www.fda.gov/newsevents/newsroom/pressannouncements/ucm237172.htm. Accessed July 15, 2011. 20. The U.S. Food and Drug Administration. Postmarket Drug Safety Information: Avastin (bevacizumab) Information, Update, 6/29/2011. Accessed July 15, 2011. [Full Text]. 21. Herceptin [package insert]. South San Francisco, Calif: Genentech; October 2010. 22. Tykerb [package insert]. Research Triangle Park, NC: GlaxoSmithKline; January 2010. 23. Femara [package insert]. East Hanover, NJ: Novartis; April 2010. 24. Fareston [package insert]. Memphis, Tenn: GTX; December 2004. Medscape Reference © 2011 WebMD, LLC 25. James TA, Mace JL, Virnig BA, et al. Preoperative needle biopsy improves the quality of breast cancer surgery. J Am Coll Surg. Oct 2012;215(4):562-8. [Medline]. 26. Mulcahy N. Breast cancer needle biopsy in 'granular' detail. Medscape Medical News. Available at http://www.medscape.com/viewarticle/772152. Accessed Oct 15 2012.
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