Please select the eligibility criteria that correspond to the clinical trial below.
Title: TARGIT: A Randomised Controlled Trial to Compare Targeted Intra-operative Radiotherapy With Conventional Post-operative Radiotherapy After Conservative Breast Surgery for Women With Early Stage Breast Cancer
Brief Summary: The purpose of this study is to evaluate whether a single fraction of radiotherapy given intra-operatively and targeted to the tissues at the highest risk of local recurrence is equivalent to standard post-operative external beam radiotherapy after breast conserving surgery in women with early stage breast cancer in terms of local relapse within the treated breast.


Options:
A: 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.
B: 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.
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

* 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: D