Higher Per Daily Treatment-Dose Radiation Therapy or Standard Per Daily Treatment Radiation Therapy in Treating Patients With Early-Stage Breast Cancer That Was Removed by Surgery
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Standard fractionation whole breast irradiation; Hypofractionated whole breast irradiation; Concurrent boost; Sequential boost
Intervention description: Target-based radiation using three-dimensional conformal radiation therapy (3D-CRT) or intensity-modulated radiation therapy (IMRT) to deliver 25 fractions of 2.0 Gy for a total dose of 50.0 Gy or 16 fractions of 2.67 Gy for a total dose of 42.7 Gy. Must begin within 9 weeks of last surgery or chemotherapy delivery.; Target-based radiation using three-dimensional conformal radiation therapy (3D-CRT) or intensity-modulated radiation therapy (IMRT) to deliver 15 fractions of 2.67 Gy for a total dose of 40.0 Gy. Must begin within 9 weeks of last surgery or chemotherapy delivery.; 15 fractions of 3.2 Gy for a total dose of 48 Gy to the lumpectomy cavity. Given concurrently with treatment to the entire breast. May be given by either electron beam or photon beams using either 3D-CRT or IMRT.; 6 fractions of 2.0 Gy per fraction for a total dose of 12 Gy or 7 fractions of 2.0 Gy for a total dose of 14 Gy to the lumpectomy cavity. May be given by either electron beam or photon beams using either 3D-CRT or IMRT. Begins without a treatment break after completion of the treatment to the entire breast.
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 2354.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: stage IA breast cancer; stage IB breast cancer; stage II breast cancer; estrogen receptor-negative breast cancer; estrogen receptor-positive breast cancer; progesterone receptor-negative breast cancer; progesterone receptor-positive breast cancer; ductal breast carcinoma in situ

Summary:

      RATIONALE: It is not yet know whether higher per daily radiation therapy is equally as
      effective as standard per daily radiation therapy in treating breast cancer.

      PURPOSE: This randomized phase III trial studies how well an accelerated course of higher per
      daily radiation therapy with concomitant boost works compared to standard per daily radiation
      therapy with a sequential boost in treating patients with early-stage breast cancer that was
      removed by surgery.
    

Eligibility criteria:

        Inclusion criteria:

          1. Pathologically proven diagnosis of breast cancer resected by lumpectomy and whole
             breast irradiation with boost without regional nodal irradiation planned

          2. The patient must be female

          3. The patient must meet at least one of the three following criteria:

               -  A. Pathological stage I, II Breast Cancer AND at least one of the following:

                    -  Age < 50 years or

                    -  Positive axillary nodes or

                    -  Lymphovascular space invasion or

                    -  2 or more close resection margins (> 0 mm to ≤ 2 mm) or

                    -  1 close resection margin and extensive intraductal component (EIC) [Per
                       College of American Pathologist (CAP) Recommendation] or

                    -  Focally positive resection margins or

                    -  Non-hormone sensitive breast cancer (estrogen receptor (ER)- and
                       progesterone receptor(PR)-negative) or

                    -  Grade III histology or

                    -  Oncotype recurrence score > 25 or

               -  B. Pathological stage 0 breast cancer with nuclear grade 3 ductal carcinoma in
                  situ (DCIS) and patient age <50 years or

               -  C. Post-neoadjuvant pathological 0, I, II breast cancer resected by lumpectomy
                  after neoadjuvant systemic therapy

          4. Study entry must be within 50 days from whichever comes later: last surgery (breast or
             axilla) or last chemotherapy. The day of surgery is Day "0".

          5. If multifocal breast cancer, then it must have been resected through a single
             lumpectomy incision with negative margins

          6. Breast-conserving surgery with margins defined as follows: (also see 3.1.3 for
             eligibility)

               -  Negative margins defined as no tumor at the resected specimen edge.

               -  Close resection margins > 0 mm to ≤ 2 mm. as follows:

                    -  One close resection margin and EIC (per College of American Pathologist
                       (CAP) Recommendation)

                    -  2 or more close resection margins.

               -  A focally positive resection margin

          7. For invasive breast cancer the axilla must be staged by one of the following:

               -  Sentinel node biopsy alone, if sentinel node is negative, i.e. any of the
                  following:

                    -  pN0: no regional lymph node metastasis identified histologically,

                    -  pN0(i-): pN0 and immunohistochemical (IHC) negative, or

                    -  pN0(i+): pN0 and IHc positive;

               -  Sentinel node biopsy alone, OR followed by axillary node dissection per
                  investigator discretion, for clinically node negative patients as described
                  below:

                    -  microscopic sentinel node positive (pN1mic)

                    -  one or two sentinel nodes positive (pN1) without extracapsular extension

                    -  negative sentinel node biopsy after neoadjuvant chemotherapy

               -  Axillary node dissection is required following sentinel node (SN) biopsy with a
                  minimum total of 6 axillary nodes if any of the following exist:

                    -  for > 2 positive SN

                    -  any positive SN biopsy after neoadjuvant chemotherapy

                    -  for clinically (by either imaging or examination) T3 disease

                    -  for extracapsular extension

               -  Axillary dissection alone (with a minimum of 6 axillary nodes)

          8. Age ≥ 18

          9. CT-imaging of the ipsilateral breast within 28 days prior to study entry for the
             radiation treatment planning. Must be able to delineate on CT scan the extent of the
             target lumpectomy cavity for boost

         10. Appropriate stage for protocol entry, including no clinical evidence for distant
             metastases, based upon the following minimum diagnostic workup:

               -  History/physical examination, including breast exam (inspection and palpation of
                  the breasts) and documentation of weight and Zubrod Performance Status of 0-2
                  within 28 days prior to study entry;

               -  Right and left mammography within 90 days of diagnostic biopsy establishing
                  diagnosis

         11. Patients must have had ER analysis performed on the primary breast tumor prior to
             study entry according to current American Society of Clinical Oncology (ASCO)/ College
             of American Pathologists (CAP) Guideline Recommendations for hormone receptor testing.
             If negative for ER, assessment of PR must also be performed according to current
             ASCO/CAP Guideline Recommendations for hormone receptor testing (http://www.asco.org)

         12. Complete blood count (CBC)/differential obtained within 14 days prior to study entry,
             with adequate bone marrow function defined as follows:

               -  Absolute neutrophil count (ANC) ≥ 1,800 cells/mm3

               -  Platelets ≥ 75,000 cells/mm3

               -  Hemoglobin ≥ 8.0 g/dl (Note: The use of transfusion or other intervention to
                  achieve Hgb ≥ 8.0 g/dl is acceptable.)

         13. Women of childbearing potential must have a negative urine or serum pregnancy test
             within 14 days of study entry

         14. Women of childbearing potential must be non-pregnant and non-lactating and willing to
             use medically acceptable form of contraception during radiation therapy

         15. Patient must provide study specific informed consent prior to study entry

         16. Breast implants allowed

        Exclusion criteria:

          1. American Joint Committee on Cancer (AJCC) pathologic T4, N2 or N3, M1 pathologic
             stages III or IV breast cancer

          2. Treatment plan that includes regional node irradiation

          3. Prior invasive non-breast malignancy (except non-melanomatous skin cancer, carcinoma
             in situ of the cervix) unless disease free for a minimum of 5 years prior to study
             entry

          4. Prior invasive or in-situ carcinoma of the breast [-prior lobular carcinoma in situ
             (LCIS) is eligible]

          5. Two or more breast cancers not resectable through a single lumpectomy incision

          6. Bilateral breast cancer

          7. DCIS only (without an invasive component) and age ≥ 50 years

          8. DCIS nuclear grade 1 or 2 only (without an invasive component) and age < 50 years

          9. Invasive breast cancer and low risk for 5-year in breast recurrence after lumpectomy
             with negative margins that does not meet one of the eligibility factors in 3.1.3.

         10. Unable to delineate on CT scan the extent of the target lumpectomy cavity for boost
             (Placement of surgical clips to assist in treatment planning of the boost is strongly
             recommended, see Section 6.4.2 for details)

         11. Suspicious unresected microcalcification, densities, or palpable abnormalities (in the
             ipsilateral or contralateral breast) unless biopsied and found to be benign

         12. Non-epithelial breast malignancies such as sarcoma or lymphoma

         13. Paget's disease of the nipple

         14. Male breast cancer

         15. Prior radiotherapy to the breast or prior radiation to the region of the ipsilateral
             breast that would result in overlap of radiation therapy fields

         16. Intention to administer concurrent chemotherapy for current breast cancer.

         17. Severe, active co-morbidity, defined as follows:

               -  Unstable angina and/or congestive heart failure requiring hospitalization within
                  the last 6 months

               -  Transmural myocardial infarction within the last 6 months

               -  Acute bacterial or fungal infection requiring intravenous antibiotics at the time
                  of registration;

               -  Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness
                  requiring hospitalization or precluding study therapy within 30 days before
                  registration;

               -  Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects;
                  note, however, that laboratory tests for liver function and coagulation
                  parameters are not required for entry into this protocol

               -  Acquired Immune Deficiency Syndrome (AIDS) based upon current Centers for Disease
                  Control and Prevention (CDC) definition; note, however, that HIV testing is not
                  required for entry into this protocol. The need to exclude patients with AIDS
                  from this protocol is necessary because the treatments involved in this protocol
                  may be significantly immunosuppressive

         18. Pregnancy or women of childbearing potential who are sexually active and not
             willing/able to use medically acceptable forms of contraception

         19. Active systemic lupus, erythematosus, or any history of scleroderma, dermatomyositis
             with active rash

         20. Medical, psychiatric or other condition that would prevent the patient from receiving
             the protocol therapy or providing informed consent