A Study of AC Followed by a Combination of Paclitaxel Plus Trastuzumab or Lapatinib or Both Given Before Surgery to Patients With Operable HER2 Positive Invasive Breast Cancer

A Randomized Phase III Trial of Neoadjuvant Therapy for Patients With Palpable and Operable HER2-Positive Breast Cancer Comparing the Combination of Trastuzumab Plus Lapatinib to Trastuzumab and to Lapatinib Administered With Weekly Paclitaxel Following AC Accompanied by Correlative Science Studies to Identify Predictors of Pathologic Complete Response

The primary purpose of this study is to determine whether breast cancer tumors respond (as measured by pathologic complete response: the absence of microscopic evidence of invasive tumor cells in the breast) to combined chemotherapy of AC(doxorubicin and cyclophosphamide) followed by paclitaxel plus trastuzumab or lapatinib or both given before surgery to patients with HER2-positive breast cancer. Trastuzumab will also be given to all patients after surgery. The study will also evaluate the toxic effects of the chemotherapy combination, including effects on the heart, and will determine survival and progression-free survival 5 years after treatment. Also, the study will look at whether there are gene expression profiles in the tumor tissue that can predict pathologic complete response.

Study Overview

• Status: Unknown
• Conditions: Invasive Breast Cancer
• Intervention / Treatment: Drug: doxorubicin; Drug: cyclophosphamide; Drug: paclitaxel; Drug: trastuzumab; Drug: lapatinib

Detailed Description

Women with breast cancers that overexpress HER2 are at greater risk for disease progression and death than women whose tumors do not overexpress HER2. Trastuzumab, a recombinant humanized monoclonal antibody against the extracellular domain of the HER2 protein blocks downstream signaling of HER2 and substantially improves the efficacy of chemotherapy in women with metastatic and early-stage HER2-positive breast cancers. Because resistance to trastuzumab eventually results in progressive disease in the metastatic setting and contributes to recurrence following adjuvant trastuzumab-based therapy, it is important to develop agents other than trastuzumab that target HER2 signaling through different mechanisms of action. Lapatinib is an oral, small molecule, dual tyrosine kinase inhibitor of HER2 and EGFR. Lapatinib has shown a lack of cross-resistance with trastuzumab in preclinical studies and activity in women with HER2-positive, metastatic breast cancer that has progressed during trastuzumab treatment. Trastuzumab blocks the downstream signaling of HER2 by binding to the extracellular domain of the receptor. Lapatinib binds to the intracellular domains of HER2 and EGFR and prevents activation of downstream signaling pathways. Because of this different mechanism of action, lapatinib may be effective in trastuzumab-resistant disease. The study will also provide important safety information on trastuzumab and lapatinib combinations immediately following anthracycline exposure, and also provide an initial direct comparison of cardiac effects of trastuzumab and lapatinib when incorporated into a standard sequential AC followed by weekly paclitaxel (neo)adjuvant regimen.

Availability of a second agent that can interrupt HER2-signaling pathways through completely different mechanisms than those of trastuzumab offers the potential for further improvement in the management of patients with HER2-overexpressing breast cancer in both the adjuvant and metastatic setting. Co-administration of both trastuzumab and lapatinib with chemotherapy may be important in improving outcomes in subsets of HER2-positive breast cancers. However, use of two inhibitors of the HER2 pathway will increase costs and may increase toxicity, so it will be important to identify the subsets of patients who would benefit from the dual therapy. Inhibition of HER2 with a single agent clearly is sufficient for many patients as evidenced by the results of the trastuzumab trials. Therefore, co-administration to unselected populations of women with HER2-positive breast cancers would not represent an optimal approach. Given the activity of lapatinib, it is likely that it will also be sufficiently active in inhibiting HER2-pathway activation in some patients to allow for its use as the sole inhibitor of the HER2 pathway. Different populations may also derive greater benefit from one of the HER2-blocking agents relative to the other. Identification of potential predictive factors for pathologic complete response to the combination or to either agent administered alone in neoadjuvant trials would provide important information for adjuvant trials designed to definitively address these important issues.

This study will compare 3 combined chemotherapy regimens: AC followed by paclitaxel plus trastuzumab and lapatinib, AC followed by paclitaxel plus lapatinib, and AC followed by paclitaxel plus trastuzumab given before surgery to patients with HER2-positive breast cancer.

• Study Type: Interventional
• Enrollment (Actual): 529
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M4N 3M5
      • Odette Cancer Centre
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Jewish General Hospital
    • Montreal, Quebec, Canada, H3A 1A1
      • Royal Victoria Hospital
    • Montreal, Quebec, Canada, H3T 1M5
      • St. Mary's Hospital Center
    • Montreal, Quebec, Canada
      • University of Montreal Hospital Group
    • Quebec City, Quebec, Canada, G1S 4L8
      • Centre Hospitalier Affilie Universitaire De Quebec, Hospital du St-Sacrement
• Puerto Rico
  • San Juan, Puerto Rico, 00936
    • MBCCOP, San Juan, Puerto Rico
• United States
  • Alabama
    • Mobile, Alabama, United States, 36608
      • MBCCOP, Gulf Coast
  • California
    • La Jolla, California, United States, 92037
      • Scripps Cancer Center-San Diego
    • Long Beach, California, United States, 90813
      • Pacific Shores Medical Group
    • Long Beach, California, United States, 90801
      • University of California, Irvine Medical Center
    • Orange, California, United States, 92868
      • St. Joseph Hospital
    • Palm Springs, California, United States, 92262
      • Desert Regional Medical Center Comprehensive Cancer Center
    • Palo Alto, California, United States, 94304
      • Stanford University Medical Center
    • Sacramento, California, United States, 95816
      • Sutter Medical Center
    • San Diego, California, United States, 92120
      • Kaiser Permanente-San Diego
    • Santa Rosa, California, United States, 95403
      • Santa Rosa Memorial Hospital
    • Vallejo, California, United States, 94589
      • Kaiser Permanente-Vallejo
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Cancer Center
    • Colorado Springs, Colorado, United States, 80909
      • Memorial Hospital
    • Denver, Colorado, United States, 80205
      • Kaiser Permanente-Franklin
    • Denver, Colorado, United States, 80224
      • CCOP-Colorado Cancer Research Prog. Inc.(Administrative Only)
    • Lafayette, Colorado, United States, 80026
      • Kaiser Permanente Rock Creek
  • Connecticut
    • Hartford, Connecticut, United States, 06102
      • Hartford Hospital
    • Norwich, Connecticut, United States, 06360
      • Eastern Connecticut Hematology & Oncology Associates
  • District of Columbia
    • Washington, District of Columbia, United States, 20016
      • Sibley Memorial Hospital
  • Florida
    • Orlando, Florida, United States, 32806
      • MD Anderson Cancer Center
  • Georgia
    • Albany, Georgia, United States, 31701
      • Phoebe Putney Memorial Hospital
    • Augusta, Georgia, United States, 30912
      • MBCCOP, Medical College of Georgia Research Institute
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
      • University of Hawaii
    • Honolulu, Hawaii, United States, 96819
      • Kaiser Permanente Hawaii - Moanalua Med Center
  • Idaho
    • Coeur D'Alene, Idaho, United States, 83814
      • Kootenai Cancer Center
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
    • Decatur, Illinois, United States, 62526
      • Decatur Memorial Hospital
    • Elk Grove, Illinois, United States, 60007
      • Cancer Institute at Alexian Brothers Hospital Network
    • Naperville, Illinois, United States, 60566
      • Edward Hospital
    • Plainfield, Illinois, United States, 60585
      • Edward Cancer Center Plainfield
    • Springfield, Illinois, United States, 62526
      • CCOP, Central Illinois
    • Urbana, Illinois, United States, 61801
      • CCOP, Carle Cancer Center
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • St. Vincent Hospital and Health Care Center
    • South Bend, Indiana, United States, 46601
      • CCOP, Northern Indiana Cancer Research Consortium
  • Iowa
    • Des Moines, Iowa, United States, 52501
      • CCOP, Des Moines, IA
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
    • Sioux City, Iowa, United States, 51101
      • CCOP, Sioux Community Cancer consortium
  • Kansas
    • Wichita, Kansas, United States, 67214
      • CCOP, Wichita KS
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky Medical Center
    • Louisville, Kentucky, United States, 40202
      • NortonHealtcare Inc.
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • CCOP, Ochsner Clinic Foundation
  • Maryland
    • Baltimore, Maryland, United States, 21204
      • Greater Baltimore Medical Center
    • Baltimore, Maryland, United States, 21237
      • Franklin Square Hospital Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48106
      • CCOP, Michigan Cancer Research Consortium
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
    • Grand Rapids, Michigan, United States, 49503
      • CCOP, Grand Rapids Clnical Oncology Program
    • Kalamazoo, Michigan, United States, 49007
      • CCOP, Kalamazoo, MI
    • Lansing, Michigan, United States, 48910
      • Michigan State University - Breslin Cancer Center
    • Royal Oak, Michigan, United States, 48073
      • CCOP, William Beaumont Hospital
    • Southfield, Michigan, United States, 48075-9975
      • Providence Hospital - Southfield
  • Minnesota
    • Minneapolis, Minnesota, United States, 55415
      • Hennepin County Medical Center
    • Minneapolis, Minnesota, United States, 55416
      • CCOP, Metro-Minnesota
  • Missouri
    • Columbia, Missouri, United States, 65203
      • University of Missouri-Ellis Fischel
    • Kansas City, Missouri, United States, 64131
      • CCOP, Kansas City (Administrative Only)
    • Springfield, Missouri, United States, 65804
      • CCOP, Ozark Health Ventures LLC
    • St. Louis, Missouri, United States, 63110
      • Saint Louis UniversityHealth Sciences Center
    • St. Louis, Missouri, United States, 63131
      • CCOP, Heartland Cancer Research
  • Montana
    • Billings, Montana, United States, 59101
      • CCOP, Montana Cancer Consortium
  • Nebraska
    • Omaha, Nebraska, United States, 74136
      • CCOP, Missouri Valley Consortium
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Cancer Institute Of New Jersey
    • Newark, New Jersey, United States, 07112
      • Newark Beth Israel Medical Center
  • New York
    • Albany, New York, United States, 12206
      • New York Oncology Hematology PC-Albany
    • Glens Falls, New York, United States, 12801
      • Cancer Center at Glens Falls Hospital
    • Syracuse, New York, United States, 13057
      • CCOP, Hematology-Oncology Associates of CNY
  • North Carolina
    • Burlington, North Carolina, United States, 27215
      • Alamance Regional Medical Center
    • Chapel Hill, North Carolina, United States, 28302
      • University of North Carolina at Chapel Hill
    • Charlotte, North Carolina, United States, 28203
      • CCOP, Southeast Cancer Control Consortium
    • Mebane, North Carolina, United States, 27302
      • Alamance Regional Medical Center - Off site Clinic
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University School of Medicine
  • Ohio
    • Akron, Ohio, United States, 44304
      • Akron City Hospital
    • Canton, Ohio, United States, 44710
      • Aultman Hospital
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve/University Hospitals-Ireland Cancer Cntr.
    • Columbus, Ohio, United States, 43017
      • Ohio State University
    • Columbus, Ohio, United States, 43215
      • CCOP, Columbus, OH
    • Dayton, Ohio, United States, 45429
      • CCOP, Dayton, OH
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74136
      • CCOP, Oklahoma
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18105
      • Lehigh Valley Hospital
    • Danville, Pennsylvania, United States, 17882-2170
      • Geisinger Clinic
    • Hershey, Pennsylvania, United States, 17033
      • Hershey Medical Center
    • Philadelphia, Pennsylvania, United States, 19141-3098
      • Albert Einstein Healthcare Network
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh
    • Pittsburgh, Pennsylvania, United States, 15224
      • Western Pennsylvania Hospital
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny General Hospital/Allegheny-Singer Research Institute
    • Pittsburgh, Pennsylvania, United States, 15212
      • NSABP Foundation, Inc.
    • Scranton, Pennsylvania, United States, 18501
      • Mercy Hospital
    • West Reading, Pennsylvania, United States, 19612
      • Reading Hospital & Medical Center
    • Wynnewood, Pennsylvania, United States, 19096
      • CCOP, Main Line Health
  • South Carolina
    • Spartanburg, South Carolina, United States, 29303
      • CCOP, Upstate Carolina
  • South Dakota
    • Souix Falls, South Dakota, United States, 57104
      • Sanford Cancer Center
  • Tennessee
    • Knoxville, Tennessee, United States, 37909
      • Thompson Cancer Survival Center-Dowell Springs
  • Texas
    • Lubbock, Texas, United States, 79410
      • Joe Arrington Cancer Research & Treatment Center
    • San Antonio, Texas, United States, 78229
      • University of Texas Health Science Center at San Antonio
  • Virginia
    • Richmond, Virginia, United States, 23298
      • MBCCOP, Virginia Commonwealth University
  • Washington
    • Seattle, Washington, United States, 98109
      • Puget Sound Oncology Consortium
    • Seattle, Washington, United States, 99519
      • CCOP, Virginia Mason
    • Tacoma, Washington, United States, 83706
      • CCOP, Northwest
  • West Virginia
    • Morgantown, West Virginia, United States, 26506-9162
      • West Virginia University Hospitals Inc.
    • Parkersburg, West Virginia, United States, 26101
      • Camden-Clark Memorial Hospital
    • Wheeling, West Virginia, United States, 26003
      • Wheeling Hospital
  • Wisconsin
    • Marshfield, Wisconsin, United States, 54449
      • CCOP, Marshfield Clinic
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion criteria:

• Female
• 18 years or older
• ECOG performance status of 0 or 1
• Primary breast tumor palpable and measures greater than or equal to 2.0 cm by physical exam
• Diagnosis of invasive adenocarcinoma made by core needle biopsy
• Breast cancer determined to be HER2-positive
• LVEF assessment by MUGA scan or ECG within 3 months prior to randomization

• Blood counts must meet the following criteria:

  • ANC greater than or equal to 1200/mm3
  • Platelet count greater than or equal to 100,000/mm3
  • Hemoglobin greater than or equal to 10 g/dL
• Serum creatinine less than or equal to ULN for the lab

• Adequate hepatic function by these criteria:

  • Total bilirubin less than or equal to the ULN for the lab unless the patient has a bilirubin elevation greater than ULN to 1.5 x ULN resulting from Gilbert's disease or similar syndrome due to slow conjugation of bilirubin; and
  • Alkaline phosphatase less than or equal to 2.5 x ULN; and
  • AST less than or equal to 1.5 x ULN for the lab.
• If skeletal pain present or alkaline phosphatase greater than ULN (but less than or equal to 2.5 x ULN), bone scan or PET scan must not demonstrate metastatic disease
• If AST or alkaline phosphatase greater than ULN , liver imaging (CT, MRI or PET scan) must not demonstrate definitive metastatic disease and the requirements in criterion for hepatic function must be met
• Able to swallow oral medications

Exclusion criteria:

• FNA alone to diagnose the primary tumor
• Excisional biopsy or lumpectomy was performed prior to randomization
• Surgical axillary staging procedure prior to randomization. Exceptions: 1) FNA or core biopsy of an axillary node for any patient, and 2) although not recommended, a pre-neoadjuvant therapy SN biopsy for patients with clinically negative axillary nodes.
• Tumors clinically staged as T4
• Ipsilateral cN2b or cN3 disease (Patients with cN1 or cN2a disease are eligible)
• Definitive clinical or radiologic evidence of metastatic disease
• Synchronous bilateral invasive breast cancer
• Requirement for chronic use of any of the medications or substances specified in the protocol
• Treatment including RT, chemotherapy, and/or targeted therapy for the currently diagnosed breast cancer prior to randomization
• Any sex hormonal therapy, e.g., birth control pills, ovarian hormone replacement therapy, etc. (These patients are eligible if therapy is discontinued prior to randomization)
• Continued therapy with any hormonal agent such as raloxifene, tamoxifen, or other SERM. (Patients are eligible only if these medications are discontinued prior to randomization)
• Prior history of breast cancer, including DCIS (Patients with a history of LCIS are eligible)
• Prior therapy with anthracyclines, taxanes, trastuzumab, or lapatinib for any malignancy
• Other malignancies unless the patient is considered to be disease-free for 5 or more years prior to randomization and is deemed by her physician to be at low risk for recurrence. Patients with the following cancers are eligible if diagnosed and treated within the past 5 years: carcinoma in situ of the cervix, carcinoma in situ of the colon, melanoma in situ, and basal cell and squamous cell carcinoma of the skin.

• Cardiac disease that would preclude the use of the drugs included in the B-41 treatment regimens. This includes but is not confined to:

  • Active cardiac disease:

    • angina pectoris requiring the use of anti-anginal medication;
    • ventricular arrhythmias except for benign premature ventricular contractions controlled by medication;
    • conduction abnormality requiring a pacemaker;
    • supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication; and
    • clinically significant valvular disease.

  • History of cardiac disease:

    • myocardial infarction;
    • congestive heart failure; or
    • cardiomyopathy.
• Uncontrolled hypertension, defined as blood pressure greater than 150/90 mm/Hg on antihypertensive therapy
• History of or current symptomatic interstitial pneumonitis or pulmonary fibrosis or definitive evidence of interstitial pneumonitis or pulmonary fibrosis described on CT or chest x-ray in asymptomatic patients
• Sensory/motor neuropathy greater than or equal to grade 2, as defined by the NCI's CTCAE v3.0
• Malabsorption syndrome, ulcerative colitis, resection of the stomach or small bowel, or other disease significantly affecting gastrointestinal function
• Other non-malignant systemic disease that would preclude treatment with any of the treatment regimens or would prevent required follow-up
• Conditions that would prohibit administration of corticosteroids
• Administration of any investigational agents within 30 days before randomization
• Pregnancy or lactation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group 1: AC then paclitaxel + trastuzumab; AC followed by paclitaxel plus trastuzumab	Drug: doxorubicin; 60 mg/m2 IV every 21 days for cycles 1-4; Drug: cyclophosphamide; 600 mg/m2 IV every 21 days for cycles 1-4; Drug: paclitaxel; 80 mg/m2 IV on days 1, 8, and 15 every 28 days for cycles 5-8; Drug: trastuzumab; First dose: 4 mg/kg IV, subsequent doses: 2 mg/kg IV weekly beginning on day 1 of the first paclitaxel cycle until 1-7 days before surgery
Experimental: Group 2: AC then paclitaxel + lapatinib; AC followed by paclitaxel plus lapatinib	Drug: doxorubicin; 60 mg/m2 IV every 21 days for cycles 1-4; Drug: cyclophosphamide; 600 mg/m2 IV every 21 days for cycles 1-4; Drug: paclitaxel; 80 mg/m2 IV on days 1, 8, and 15 every 28 days for cycles 5-8; Drug: lapatinib; Group 2: 1250 mg PO daily beginning on day 1 of the first paclitaxel cycle until 1 day before surgery. Group 3: 750 mg PO daily beginning on day 1 of the first paclitaxel cycle until 1 day before surgery.
Experimental: Group 3: AC then paclitaxel + trastuzumab + lapatinib; AC followed by paclitaxel plus trastuzumab plus lapatinib	Drug: doxorubicin; 60 mg/m2 IV every 21 days for cycles 1-4; Drug: cyclophosphamide; 600 mg/m2 IV every 21 days for cycles 1-4; Drug: paclitaxel; 80 mg/m2 IV on days 1, 8, and 15 every 28 days for cycles 5-8; Drug: trastuzumab; First dose: 4 mg/kg IV, subsequent doses: 2 mg/kg IV weekly beginning on day 1 of the first paclitaxel cycle until 1-7 days before surgery; Drug: lapatinib; Group 2: 1250 mg PO daily beginning on day 1 of the first paclitaxel cycle until 1 day before surgery. Group 3: 750 mg PO daily beginning on day 1 of the first paclitaxel cycle until 1 day before surgery.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Determination of pathologic complete response (pCR), defined by the absence of microscopic evidence of invasive tumor cells in the post chemotherapy surgical breast specimen.	surgery following chemotherapy

Secondary Outcome Measures

Outcome Measure	Time Frame
The determination of pCR in the surgical breast and lymph node specimens following chemotherapy.	surgery following chemotherapy
Clinical tumor measurement as assessed by physical exam of the breast and lymph nodes	baseline (prior to starting protocol therapy), at the completion of AC (before starting paclitaxel and trastuzumab and/or lapatinib), and at the conclusion of the sequential regimens (prior to surgery).
Determination of cardiac toxicity as measured by the incidence of cardiac events defined as definite or probable cardiac death	two year cumulative incidence
Determination of non-cardiac toxicities as measured by frequencies of adverse events categorized using CTCAE v3.0.	through 5 years after entry
Overall survival as measured by time from randomization until death from any cause.	through 5 years after entry
Recurrence-free interval as measured by occurrence of inoperable progressive disease, or from time of surgery to occurrence of local, regional, or distant recurrence in patients with operable disease.	through 5 years after entry
In tumor tissue, a comparison of array comparative genomic hybridization (CGH) data with gene expression profile data to examine coordinated overexpression of amplified genes, especially in HER2 and cMYC loci.	Tissue sample collected at surgery following chemotherapy

Collaborators and Investigators

• Sponsor: NSABP Foundation Inc
• Collaborators: GlaxoSmithKline

Publications and helpful links

General Publications

• Robidoux A, Tang G, Rastogi P, Geyer CE Jr, Azar CA, Atkins JN, Fehrenbacher L, Bear HD, Baez-Diaz L, Sarwar S, Margolese RG, Farrar WB, Brufsky AM, Shibata HR, Bandos H, Paik S, Costantino JP, Swain SM, Mamounas EP, Wolmark N. Lapatinib as a component of neoadjuvant therapy for HER2-positive operable breast cancer (NSABP protocol B-41): an open-label, randomised phase 3 trial. Lancet Oncol. 2013 Nov;14(12):1183-92. doi: 10.1016/S1470-2045(13)70411-X. Epub 2013 Oct 4.

Study record dates

Study Major Dates

• Study Start: July 1, 2007
• Primary Completion (Actual): June 1, 2012
• Study Completion (Anticipated): March 1, 2017

Study Registration Dates

• First Submitted: June 13, 2007
• First Submitted That Met QC Criteria: June 13, 2007
• First Posted (Estimate): June 15, 2007

Study Record Updates

• Last Update Posted (Estimate): June 6, 2016
• Last Update Submitted That Met QC Criteria: June 3, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Keywords: neoadjuvant; paclitaxel; cyclophosphamide; trastuzumab; lapatinib; HER2 positive breast cancer; invasive breast cancer; doxorubicin; NSABP
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Protein Kinase Inhibitors; Antibiotics, Antineoplastic; Cyclophosphamide; Paclitaxel; Trastuzumab; Doxorubicin; Lapatinib
• Other Study ID Numbers: NSABP B-41