Please select the eligibility criteria that correspond to the clinical trial below.
Title: An RCT to Determine if APBI, Utilizing 3D CRT, is as Effective as Whole Breast Irradiation Following Breast Conserving Surgery in Women With Ductal Carcinoma in Situ or Invasive Breast Cancer With Negative Axillary Lymph Nodes
Brief Summary: To determine if Accelerated Partial Breast Irradiation, using 3D CRT, is as effective as Whole Breast Irradiation following breast conserving surgery in women with an new histological diagnosis of ductal carcinoma in situ only or invasive breast cancer without evidence of metastatic disease. Effectiveness will be determined by the rate of ipsilateral breast tumour recurrence.

General objective is to improve the convenience and quality of life of female patients who receive breast irradiation.


Options:
A: Inclusion Criteria:

* 1a. Female patient with a new histological diagnosis of DCIS only. OR

  1b. Female patient with a new histological diagnosis of invasive carcinoma of the breast and no evidence of metastatic disease.

  2. Treated by BCS with microscopically clear resection margins for invasive and non-invasive disease (or no residual disease on re- excision).

  3. Negative axillary node involvement including micrometastasis \<= 0.2mm or positive cells only identified by IHC as determined either by: (i) sentinel node biopsy (ii) axillary node dissection or (iii) clinical exam for patients with DCIS only

Exclusion Criteria:

* 1. Age \< 40 years.

  2. A known deleterious mutation in BRCA 1 and/or BRCA 2.

  3. Tumour size \> 3 cm in greatest diameter on pathological examination (including both the invasive and non-invasive component).

  4. Tumour histology limited to lobular carcinoma only.

  5. History of cancer:
  * Patients with another active malignancy or malignancy treated \< 5 years prior to randomization are excluded.
  * Patients with a prior diagnosis of invasive or non-invasive breast cancer in either breast are excluded regardless of disease free interval. Patients with concurrent invasive or non-invasive contralateral breast cancer are also excluded.
  * Patients with prior or concurrent basal cell or squamous cell skin cancers are eligible for the trial.

    6. More than one primary tumour in different quadrants of the same breast.

    7. Previous irradiation to the ipsilateral breast that would preclude whole breast irradiation.

    8. Presence of an ipsilateral breast implant or pacemaker.

    9. Serious non-malignant disease (e.g. cardiovascular, pulmonary, systemic lupus erythematosus (SLE), scleroderma) which would preclude definitive radiation treatment.

    10. Estrogen receptor status (ER) not known.

    11. For patients not treated with adjuvant chemotherapy: unable to commence radiation therapy within 12 weeks of the last surgical procedure on the breast.

    12. For patients treated with adjuvant chemotherapy: unable to commence within 8 weeks of the last dose of chemotherapy.

    13. Currently pregnant or lactating.

    14. Psychiatric or addictive disorders which would preclude obtaining informed consent or adherence to protocol.

    15. Geographic inaccessibility for follow-up.

    16. Inability to localize surgical cavity on CT (i.e., no evidence of surgical clips or seroma).

    17. Inability to adequately plan the patient for the experimental technique.
B: Inclusion Criteria:

* Age at presentation \>40 y
* Tumor size \<25 mm
* Wide excision or quadrantectomy with clear margins (\>5 mm)
* Clips placed in tumor bed
* Full informed consent from patient

Exclusion Criteria:

* Cardiac dysfunction
* Forced expiratory volume in 1 second (FEV1) \<1 L/m
* Extensive intraductal carcinoma
* Multifocal cancer
* Psychiatric problems
* Recurrent breast cancer
C: DISEASE CHARACTERISTICS:

* Histologically confirmed ductal carcinoma in situ (DCIS\*) or invasive\* adenocarcinoma of the breast

  * Stage 0, I, or II disease

    * Stage II tumors must be ≤ 3 cm
  * Gross disease must be unifocal

    * Microscopic multifocality allowed provided total pathological tumor size is ≤ 3 cm
  * No proven multicentric carcinoma in more than 1 quadrant or separated by ≥ 4 cm
  * No non-epithelial breast malignancies (e.g., sarcoma or lymphoma) NOTE: \*Patients who are 50 years of age and over with DCIS regardless of hormone receptor status AND patients with invasive breast cancer meeting all of the following criteria: ≥ 50 years of age, node-negative, and hormone-receptor positive status will not be enrolled in study after 12/30/2006
* Prior axillary staging required for patients with invasive breast cancer, including 1 of the following:

  * Sentinel node biopsy alone (if sentinel node is negative)
  * Sentinel node biopsy followed by axillary dissection or sampling with ≥ 6 axillary nodes (if sentinel node is positive)
  * Axillary dissection alone with ≥ 6 axillary nodes
* No more than 3 positive axillary nodes

  * No axillary nodes with definite evidence of microscopic or macroscopic extracapsular extension
  * No positive non-axillary sentinel nodes (intramammary nodes are staged as axillary nodes)
  * No palpable or radiographically suspicious ipsilateral or contralateral axillary, supraclavicular, infraclavicular, or internal mammary nodes unless there is histologic confirmation that these nodes are negative for tumor
* Must have undergone lumpectomy

  * Resected margins histologically free of tumor
  * Re-excision of surgical margins allowed
  * Target lumpectomy cavity clearly delineated AND target lumpectomy/whole breast reference volume ≤ 30% based on postoperative pre-randomization CT scan
  * Final surgery (i.e., lumpectomy, re-excision of margins, or axillary staging procedure) within the past 42 days
* No suspicious microcalcifications, densities, or palpable abnormalities in the ipsilateral or contralateral breast unless biopsied and found to be benign
* No Paget's disease of the nipple
* No history of invasive breast cancer or DCIS

  * Prior lobular carcinoma in situ treated by surgery alone allowed
* No synchronous bilateral invasive or non-invasive breast cancer
* Partial breast irradiation deemed technically deliverable by radiation oncologist at a credentialed facility
* Must have undergone a history and physical exam within the past 4 months AND a bilateral mammogram within the past 6 months
* Hormone receptor status:

  * Estrogen receptor (ER) status known
  * Progesterone status known if ER analysis is negative
  * Marginal or borderline results are considered positive

PATIENT CHARACTERISTICS:

Age

* 18 and over

Sex

* Female

Menopausal status

* Premenopausal or postmenopausal

Performance status

* Not specified

Life expectancy

* At least 10 years, excluding diagnosis of breast cancer

Hematopoietic

* Not specified

Hepatic

* Not specified

Renal

* Not specified

Other

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective non-hormonal contraception
* No other malignancy within the past 5 years except previously treated carcinoma in situ of the cervix or colon, melanoma in situ, or basal cell or squamous cell skin cancer

  * Deemed to be at low risk for recurrence
* No collagen vascular disease (e.g., systemic lupus erythematosus or scleroderma), specifically dermatomyositis with a creatine phosphokinase (CPK) level above normal, or active skin rash
* No psychiatric or addictive disorder that would preclude study therapy

PRIOR CONCURRENT THERAPY:

Biologic therapy

* No prior biologic therapy for this malignancy

Chemotherapy

* No prior chemotherapy for this malignancy
* No concurrent chemotherapy during study radiotherapy

Endocrine therapy

* No prior hormonal therapy for this malignancy unless total duration of hormonal therapy was no more than 28 days before randomization
* Concurrent hormonal therapy allowed provided it is not administered during chemotherapy
* No concurrent raloxifene, tamoxifen, or other selective estrogen receptor modulating drugs
* No concurrent hormone replacement therapy
* No concurrent Femring\^®

Radiotherapy

* No prior radiotherapy for this malignancy
* No prior breast or thoracic radiotherapy
* No concurrent brachytherapy boosts
* No concurrent intensity modulated radiotherapy
* No concurrent regional nodal irradiation

Surgery

* See Disease Characteristics
* No prior breast implants

  * Patients who have had implants removed are eligible

Other

* No other concurrent anticancer therapy
D: Inclusion Criteria:

* Women aged ≥50 years
* Menopausal status confirmed
* Pathology confirmation of invasive carcinoma (all types)
* Complete tumor removal and conservative surgery
* Pathologic tumor size of invasive carcinoma ≤2 cm (including the in situ component) pT1
* All histopathologic grades
* Clear lateral margins for the invasive and in situ disease (\>2 mm)
* pN0 or pN(i+)
* No metastasis
* Radiotherapy should be started more than 4 weeks and less than 12 weeks after last surgery
* Surgical clips (4 to 5 clips in the tumor bed)
* No prior breast or mediastinal radiotherapy
* Eastern Cooperative Oncology Group (ECOG) 0-1
* Information to the patient and signed informed consent

Exclusion Criteria:

* Multifocal invasive ductal carcinoma defined as the presence of at least two distinct tumors that are separated by normal tissue or when the distance between the two lesions does not permit conservative surgery
* Bilateral breast cancer
* No or less than 4 surgical clips in the tumor bed
* Nodal involvement : pN1 (including micrometastasis, mi+), pN2, pN3
* Metastatic disease
* internal mammary node involvement or supraclavicular lymph node involvement
* Indication of chemotherapy or trastuzumab
* Involved or close lateral margins for the invasive and /or in situ components (\<2 mm) AND impossibility to re-operate or impossible to perform another conservative surgery
* Patients with known BRCA1 or BRCA2 mutations
* Previous mammoplasty
* Previous homolateral breast and/or mediastinal irradiation
* Previous invasive cancer (except basocellular epithelioma or in situ carcinoma of the cervix)
* No geographical, social or psychologic reasons that would prevent study follow

Answer: A