Radiation Therapy in Treating Women Who Have Undergone Surgery for Early-Stage Invasive Breast Cancer

A Phase III Study of Regional Radiation Therapy in Early Breast Cancer

RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Radiation to the tumor site and surrounding area may kill more tumor cells. It is not yet known if radiation therapy to the breast alone following surgery is more effective than radiation therapy to the breast plus surrounding tissue in treating invasive breast cancer.

PURPOSE: This randomized phase III trial is studying radiation therapy to the breast alone to see how well it works compared to radiation therapy to the breast plus surrounding tissue in treating women who have undergone surgery for early-stage invasive breast cancer.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Radiation: Standard Breast Irradiation; Radiation: Breast Radiation plus Regional Radiation

Detailed Description

OBJECTIVES:

• Compare the overall survival, disease-free survival, isolated local regional disease-free survival, and distant disease-free survival in women with previously resected, early stage, invasive breast cancer treated with breast radiotherapy with or without regional radiotherapy.
• Compare the toxic effects of these regimens in these patients.
• Compare the quality of life of patients (in certain participating centers) treated with these regimens.
• Compare the cosmetic outcomes in patients (in certain participating centers) treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to number of positive nodes (0 vs 1-3 vs more than 3), number of axillary nodes removed (<10, > or equal to 10); type of chemotherapy (anthracycline containing vs other vs none), hormonal therapy (yes vs no), number of axillary lymph nodes excised*, and participating center. Patients are randomized to one of two treatment arms.

NOTE: * Patients with a negative sentinel node dissection with or without an axillary dissection will be stratified according to the total number of nodes removed

• Arm I: Patients undergo standard breast radiotherapy alone 5 days a week for 5 weeks in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients undergo breast and regional radiotherapy 5 days a week for 5 weeks in the absence of disease progression or unacceptable toxicity.

Radiotherapy in both arms begins as soon as possible after randomization. Radiotherapy must begin within 8 weeks after completion of adjuvant IV chemotherapy, unless radiotherapy is administered concurrently with chemotherapy (i.e., cyclophosphamide, methotrexate, and fluorouracil [CMF]), or within 16 weeks after the last breast surgery for patients treated with hormonal therapy alone.

Quality of life is assessed (in patients in certain participating centers) within 2 weeks prior to randomization, during the last week of radiotherapy, at 3 and 9 months after completion of radiotherapy, and then annually until first distant disease recurrence.

Cosmetic outcome is assessed (in patients in certain participating centers) within 2 weeks prior to randomization, and then at 3 and 5 years after completion of radiotherapy or until first distant disease recurrence.

Patients are followed at 3, 6, and 9 months, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: Approximately 1,822 patients will be accrued for this study within approximately 4 years.

• Study Type: Interventional
• Enrollment (Actual): 1832
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Tom Baker Cancer Centre
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute
  • British Columbia
    • Surrey, British Columbia, Canada, V3V 1Z2
      • BCCA - Fraser Valley Cancer Centre
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • BCCA - Vancouver Cancer Centre
    • Victoria, British Columbia, Canada, V8R 6V5
      • BCCA - Vancouver Island Cancer Centre
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 0V9
      • CancerCare Manitoba
  • New Brunswick
    • Moncton, New Brunswick, Canada, E1C 8X3
      • The Vitalite Health Network - Dr. Leon Richard
    • Saint John, New Brunswick, Canada, E2L 4L2
      • Atlantic Health Sciences Corporation
  • Newfoundland and Labrador
    • St. John's, Newfoundland and Labrador, Canada, AIB 3V6
      • Dr. H. Bliss Murphy Cancer Centre
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 1V7
      • QEII Health Sciences Center
  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
      • Juravinski Cancer Centre at Hamilton Health Sciences
    • Kitchener, Ontario, Canada, N2G 1G3
      • Grand River Regional Cancer Centre
    • London, Ontario, Canada, N6A 4L6
      • London Regional Cancer Program
    • Ottawa, Ontario, Canada, K1H 8L6
      • Ottawa Health Research Institute - General Division
    • St. Catharines, Ontario, Canada, L2R 7C6
      • Niagara Health System
    • Sudbury, Ontario, Canada, P3E 5J1
      • Northeast Cancer Center Health Sciences
    • Thunder Bay, Ontario, Canada, P7B 6V4
      • Thunder Bay Regional Health Science Centre
    • Toronto, Ontario, Canada, M4N 3M5
      • Odette Cancer Centre
    • Toronto, Ontario, Canada, M5G 2M9
      • Univ. Health Network-Princess Margaret Hospital
  • Quebec
    • Montreal, Quebec, Canada, H2L 4M1
      • CHUM - Hopital Notre-Dame
    • Montreal, Quebec, Canada, H2W 1S6
      • McGill University - Dept. Oncology
    • Quebec City, Quebec, Canada, G1R 2J6
      • CHUQ-Pavillon Hotel-Dieu de Quebec
    • Quebec City, Quebec, Canada, G1S 4L8
      • CHA-Hopital Du St-Sacrement
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • Centre Hospitalier Universitaire de Sherbrooke
  • Saskatchewan
    • Regina, Saskatchewan, Canada, S4T 7T1
      • Allan Blair Cancer Centre
    • Saskatoon, Saskatchewan, Canada, S7N 4H4
      • Saskatoon Cancer Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 120 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

DISEASE CHARACTERISTICS:

• Histologically proven invasive carcinoma of the breast

  • No evidence of T4, N2-3, or M1 disease prior to surgery
  • Node positive or high-risk node negative

• Prior breast-conserving therapy (BCT) (e.g., lumpectomy, partial mastectomy, or segmental mastectomy) and axillary node dissection or sentinel node biopsy required and must be a candidate for breast radiotherapy after BCT

  • Normally patients should have microscopically clear resection margins and those with positive margins should undergo reexcision
  • Patients with microscopically focally positive margins (defined as no greater than 3 times high power fields) are candidates for breast radiotherapy plus a boost to the lumpectomy site

  • Patients with prior sentinel node dissection eligible if node negative, but still meet high-risk criteria

    • If node positive, then a level I and II axillary dissection must be performed
  • No evidence of residual disease in axilla after dissection
• Must be treated with currently accepted adjuvant systemic chemotherapy and/or hormonal therapy

• High risk of regional and systemic recurrence due to one of the following:

  • Pathologically positive axillary lymph nodes

  • Pathologically negative axillary lymph nodes with one of the following:

    • Primary tumor greater than 5 cm

    • Primary tumor greater than 2 cm and less than 10 axillary lymph nodes excised and one of the following:

      • Estrogen receptor negative
      • Skarf-Bloom-Richardson grade 3
      • Lymphovascular invasion

• Hormone receptor status:

  • Estrogen and progesterone receptor status known

PATIENT CHARACTERISTICS:

Age:

• 16 and over

Sex:

• Female

Menopausal status:

• Premenopausal or postmenopausal

Performance status:

• ECOG 0-2

Life expectancy:

• At least 5 years

Hematopoietic:

• Not specified

Hepatic:

• SGOT and/or SGPT no greater than 3 times upper limit of normal (ULN)*
• Alkaline phosphatase no greater than 3 times ULN* NOTE: * Patients with laboratory values greater than 3 times ULN may still be eligible if no metastatic disease by imaging examinations

Renal:

• No serious nonmalignant renal disease

Cardiovascular:

• No serious nonmalignant cardiovascular disease

Pulmonary:

• No serious nonmalignant pulmonary disease

Other:

• Not pregnant or nursing
• Fertile patients must use effective contraception
• No other serious nonmalignant disease (e.g., systemic lupus erythematosus or scleroderma) that would preclude definitive surgery or radiotherapy

• No other malignancy except:

  • Nonmelanomatous skin cancer
  • Carcinoma in situ of the cervix or endometrium
  • Contralateral noninvasive breast cancer (unless prior radiotherapy to the contralateral breast)
  • Invasive carcinoma of the cervix, endometrium, colon, thyroid, or melanoma that was curatively treated at least 5 years prior to study participation
• No psychiatric or addictive disorder that would preclude informed consent or study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• See Disease Characteristics
• Concurrent standard adjuvant chemotherapy allowed

Endocrine therapy:

• See Disease Characteristics
• Concurrent standard adjuvant hormonal therapy allowed

Radiotherapy:

• See Disease Characteristics

Surgery:

• See Disease Characteristics

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard Breast Irradiation	Radiation: Standard Breast Irradiation; Standard Breast Irradiation - A dose of 5000 cGy in 25 fractions at a rate of 200 cGy per day, 5 days a week for 5 weeks will be prescribed to the standard tangent fields.
Experimental: Breast Radiation plus regional radiation; regional radiation therapy (to the ipsilateral supraclavicular, axillary and internal mammary nodes)	Radiation: Breast Radiation plus Regional Radiation; Breast Radiation plus Regional Radiation - A dose of 5000 cGy in 25 fractions at a rate of 200 cGy per day, 5 days a week for 5 weeks will be prescribed to the modified wide tangent fields.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Duration of study	10 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease-free Survival	Disease-free survival (including locoregional and distant disease)	10 years

Collaborators and Investigators

• Sponsor: NCIC Clinical Trials Group
• Collaborators: National Cancer Institute (NCI); Radiation Therapy Oncology Group; North Central Cancer Treatment Group; NSABP Foundation Inc; Trans Tasman Radiation Oncology Group; SWOG Cancer Research Network
• Investigators: Study Chair: Timothy J. Whelan, MD, Margaret and Charles Juravinski Cancer Centre; Study Chair: David S. Parda, Allegheny Cancer Center at Allegheny General Hospital; Study Chair: Julia R. White, MD, Medical College Of Wisconsin; Study Chair: Lori J. Pierce, MD, University of Michigan Rogel Cancer Center; Study Chair: Boon Chua, MD, Peter MacCallum Cancer Centre, Australia; Study Chair: Laura A. Vallow, MD, Mayo Clinic

Publications and helpful links

General Publications

• Whelan TJ, Olivotto IA, Parulekar WR, Ackerman I, Chua BH, Nabid A, Vallis KA, White JR, Rousseau P, Fortin A, Pierce LJ, Manchul L, Chafe S, Nolan MC, Craighead P, Bowen J, McCready DR, Pritchard KI, Gelmon K, Murray Y, Chapman JA, Chen BE, Levine MN; MA.20 Study Investigators. Regional Nodal Irradiation in Early-Stage Breast Cancer. N Engl J Med. 2015 Jul 23;373(4):307-16. doi: 10.1056/NEJMoa1415340.
• Gross JP, Whelan TJ, Parulekar WR, Chen BE, Rademaker AW, Helenowski IB, Donnelly ED, Strauss JB. Development and Validation of a Nomogram to Predict Lymphedema After Axillary Surgery and Radiation Therapy in Women With Breast Cancer From the NCIC CTG MA.20 Randomized Trial. Int J Radiat Oncol Biol Phys. 2019 Sep 1;105(1):165-173. doi: 10.1016/j.ijrobp.2019.05.002. Epub 2019 May 11.

Study record dates

Study Major Dates

• Study Start (Actual): March 9, 2000
• Primary Completion (Actual): November 20, 2014
• Study Completion (Actual): April 19, 2017

Study Registration Dates

• First Submitted: July 5, 2000
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimated): January 27, 2003

Study Record Updates

• Last Update Posted (Actual): August 21, 2023
• Last Update Submitted That Met QC Criteria: August 3, 2023
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: stage II breast cancer; stage I breast cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: MA20; CAN-NCIC-MA20; NSABP-CAN-NCIC-MA20 (Other Identifier: NSABP); NCCTG-CAN-NCIC-MA20 (Other Identifier: NCCTG); RTOG-CAN-NCIC-MA20 (Other Identifier: RTOG); SWOG-CAN-NCIC-MA20 (Other Identifier: SWOG); TROG-CAN-NCIC-MA20 (Other Identifier: TROG); CDR0000067938 (Other Identifier: PDQ)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No