Please select the eligibility criteria that correspond to the clinical trial below.
Title: Phase III Multicentric Trial Comparing Accelerated Partial Breast Irradiation (APBI) Versus Standard or Hypofractionated Whole Breast Irradiation in Low Risk of Local Recurrence of Breast Cancer
Brief Summary: The standard treatment for localized breast cancer is based on conservative surgery (when possible) followed by radiation therapy (RT) delivered to the whole breast. The recommended total RT dose is 45 to 50 Gy delivered in 4.5 to 5 weeks followed by a 10 to 16 Gy boost to the tumor bed for 1 to 1.5 weeks. The rationale for the development of APBI was based on the difficulty for many patients to reach RT centers to receive standard whole breast irradiation (WBI) after conservative surgery. APBI offers decreased overall treatment time and several theoretical advantages over WBI, including a decrease in dose delivered to uninvolved portions of the breast and adjacent organs. If equivalence between the two treatments can be shown, then APBI will be considered as a historic evolution in breast cancer management.

In this phase III trial, designed in postmenopausal women \>50 years of age, the objective is to compare the effectiveness and safety of APBI compared with whole breast irradiation. This study is also designed to ensure high quality criteria for surgery, pathology and RT techniques in the 3 arms and will allow to provide data on economics and costs.


Options:
A: 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
B: Inclusion Criteria:

* Age ≥ 48 and \< 75
* Clinical mammographic/ultrasound diagnosis of unicentric carcinoma, with ultrasound diameter ≤2.5 cm. Advisable, but not mandatory, the execution of mammoscintigraphy with MDP-99mTc (Methyl diphosphonate technetium-99m) : this procedure allows the bone staging and the mapping of eventual multi-focality/multi-centricity of the breast neoplasm.
* No previous therapy (biopsy included) for breast cancer in other Institutions.
* Patients with non-palpable lesions will undergo preoperative centering and stereotactic and/or ultrasound-guided cytology (the execution of this last procedure is not mandatory).
* Adequate information to the patient and informed consent.

Exclusion Criteria:

* Ductal or lobular non-infiltrating carcinoma.
* Paget disease.
* Tumor in close proximity to the skin.
* Tumor in the axillary tail.
* Documented multi-centricity/multi-focality of the tumor.
* Patients who underwent excisional biopsy in other Institutions.
* Histology different from carcinoma.
* Personal anamnesis positive for malignancy (basocellular carcinoma, in situ carcinoma of the cervix, contralateral breast cancer free of disease after 15 years of follow-up excluded).
* General contraindications to regular follow-up or radiotherapy.
C: Inclusion Criteria:

* Stage 0, I or II breast cancer.
* Invasive ductal, papillary, mucinous, tubular, medullary or lobular carcinoma.
* Ductal carcinoma in situ (DCIS) alone.
* No lymph invasion (L0) and no hemangiosis (V0).
* Lesions of \> 3 cm diameter, histopathologically confirmed.
* pN0/pNmi (a minimum of 6 nodes in specimen, or a negative sentinel node is acceptable); in the case of DCIS alone axillary staging (e.g. sentinel lymph node biopsy) is optional.
* M0.
* Clear resection margins at least 2 mm in any direction; by lobular histology or DCIS histology only the resection margins must be clear at least 5 mm.
* For DCIS only: lesions must be classified as low or intermediate risk group (Van Nuys Prognostic Index \<8).
* Unifocal and unicentric DCIS or breast cancer.
* Age \>= 40 years.
* Time interval from final definitive breast surgical procedure to the start of external beam therapy or to brachytherapy is less than 12 weeks (84 days). If patients receive chemotherapy the radiotherapy can be started before systemic treatment (within 12 weeks). The radiation therapy can be also given in the interval between the chemotherapy courses. It is also possible to start radiation therapy after chemotherapy is completed according local protocols as soon as possible within 4 weeks after chemotherapy.
* Signed study-specific consent form prior to randomization.

Exclusion Criteria:

* Stage III or IV breast cancer.
* Surgical margins that cannot be microscopically assessed.
* Extensive intraductal component (EIC).
* Paget's disease or pathological skin involvement.
* Synchronous or previous breast cancer.
* Prior malignancy (\< 5 years prior to enrollment in study) except non-melanoma skin cancer or cervical carcinoma FIGO 0 and I if patient is continuously disease-free.
* Pregnant or lactating women.
* Collagen vascular disease.
* The presence of congenital diseases with increased radiation sensitivity, for example Ataxia telangiectatica or similar.
* Psychiatric disorders.
* Patient with breast deemed technically unsatisfactory for brachytherapy.
D: Inclusion criteria

* Age 45 years or older
* Operable invasive breast cancer (T1 and small T2, N0-1, M0) confirmed by cytological or histological examination
* Suitable for breast conserving surgery
* Previously diagnosed and treated contralateral breast cancer may be entered but will be randomised to a separate stratum.
* Available for regular follow-up for at least ten years.

Note: Individual centres may wish to restrict entry to a more exactly defined subset of patients, in which case, only patients with these characteristics may be entered by that particular centre. For example, centres may decide at outset to recruit only women over 50 or even over 65 years of age. Such policies must be pre-defined in writing and approved by the International Steering Committee.

Exclusion criteria

* More than one obvious cancer in the same breast as diagnosed by clinical examination, mammography or ultrasonography.
* Bilateral breast cancer at the time of diagnosis.
* Ipsilateral breast had a previous cancer and/or irradiation.
* Patients known to have BRCA2 gene mutations, but testing for gene mutations is not required
* Lobular cancer or Extensive intraductal Component (EIC =\>25% of the tumour is intraductal) on core biopsy or initial pathology (if performed)
* Patients undergoing primary medical treatment (hormones or chemotherapy) as initial treatment with neoadjuvant intent of reducing tumour size should be excluded; those given short duration (up to 4 weeks) systemic therapy can be included.
* Patients presenting with gross nodal disease, considered to be clinically malignant or proven cytologically or by scanning. In general, 4 or more positive nodes or extranodal spread are not suitable for Targit alone and should receive EBRT as well. However, individual centres may decide that anything more than micrometastasis should receive EBRT.
* Patients with any severe concomitant disease that may limit their life expectancy.
* Previous history of malignant disease does not preclude entry if the expectation of relapse-free survival at 10 years is 90% or greater.
* Any factor included as exclusion criterion in the local centre's Treatment Policy. This is particularly relevant to patients entered into the post pathology stratum.
* No more than 30 days can have elapsed between last breast cancer surgery (not axillary) and entry into the trial for patients in the post-pathology stratification.

Answer: A