Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase III, Open Label, Randomised, Controlled, Multi-centre Study to Assess the Efficacy and Safety of Olaparib Monotherapy Versus Physicians Choice Chemotherapy in the Treatment of Metastatic Breast Cancer Patients With Germline BRCA1/2 Mutations.
Brief Summary: This open label, randomised, controlled, multi-centre phase III study will assess the efficacy and safety of single agent olaparib vs standard of care based on physician's choice of capecitabine, vinorelbine or eribulin in metastatic breast cancer patients with gBRCA 1/2 mutations.


Options:
A: Inclusion Criteria:

1. Histologically confirmed invasive breast cancer by core needle or incisional biopsy (excisional biopsy is not allowed). Clinical stage T2-3 N0-2 or T1 N1-2 by physical exam or radiologic studies.
2. Documented Breast Cancer Gene (BRCA) germline mutation testing.
3. Estrogen Receptor (ER)-, Progesterone Receptor (PR)-, and Human Epidermal Growth Factor Receptor (HER)2-negative (triple-negative) cancer of the breast.
4. ECOG Performance status of 0 to 1.
5. Women must be determined to be not of childbearing potential (surgically sterile, or postmenopausal defined as amenorrheic for at least 12 months) by the Investigator OR they must have a negative serum pregnancy test prior to randomization.

Exclusion Criteria:

1. Previous anti-cancer treatment (cytotoxic chemotherapy, immunotherapy, biologic therapy radiotherapy or investigational agents) with therapeutic intent for current breast cancer.
2. Previous treatment with carboplatin, paclitaxel, doxorubicin, cyclophosphamide and a Poly-(ADP-ribose)-Polymerase (PARP) inhibitor.
3. Concurrent treatment with an ovarian hormonal replacement therapy or with hormonal agents such as raloxifene, tamoxifen or other selective estrogen receptor modulator (SERM). Subjects must have discontinued use of such agents prior to beginning study treatment.
4. A history of seizure within 12 months prior to study entry.
5. Pre-existing neuropathy from any cause in excess of Grade 1.
B: Inclusion Criteria:

* Germline mutation in BRCA1 or BRCA2 that is predicted to be deleterious or suspected deleterious.
* Histologically or cytologically confirmed breast cancer with evidence of metastatic disease.
* Prior therapy with an anthracycline and a taxane in either an adjuvant or metastatic setting.
* Prior platinum allowed as long as no breast cancer progression occurred on treatment or if given in adjuvant/neoadjuvant setting at least 12 months from last dose to study entry elapsed.
* ER/PR breast cancer positive patients must have received and progressed on at least one endocrine therapy (adjuvant or metastatic), or have disease that the treating physician believes to be inappropriate for endocrine therapy.
* ECOG performance status 0-1.
* Adequate bone marrow, kidney and liver function.

Exclusion Criteria:

* Prior treatment with PARP inhibitor.
* Patients with HER2 positive disease.
* More than 2 prior lines of chemotherapy for metastatic breast cancer.
* Untreated and/or uncontrolled brain metastases.
* Prior malignancy unless curatively treated and disease-free for \> 5 years prior to study entry. Prior adequately treated non-melanoma skin cancer, in situ cancer of the cervix, DCIS or stage I grade 1 endometrial cancer allowed.
* Known HIV (Human Immunodeficiency Virus) infection.
* Pregnant or breast-feeding women.
C: Inclusion Criteria:

* At least 18 years of age;
* Metastatic breast cancer (Stage IV) with measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria;
* 0-2 prior chemotherapy regimens in the metastatic setting;
* Histologically documented (either primary or metastatic site) breast cancer that was ER-negative, PR-negative, and HER-2 nonoverexpressing by immunohistochemistry (0,1) or non-gene amplification by fluorescence in situ hybridization (FISH);
* Completion of prior chemotherapy at least 2 weeks prior to trial entry and recovery from toxicity of prior chemotherapy;
* Radiation therapy must have been completed at least 2 weeks prior to trial entry, and radiated lesions may not have served as measurable disease;
* Patient may have had central nervous system (CNS) metastases if he/she did not require steroids, whole brain radiation therapy (XRT), gamma/cyber knife, and brain metastases were clinically stable without symptomatic progression;
* Eastern Cooperative Oncology Group (ECOG) performance status 0-1;
* Adequate organ function defined as: absolute neutrophil count (ANC)≥1,500/mm3, platelets ≥100,000/mm3, creatinine clearance \>50mL/min, ALT and AST \<2.5 x upper limit of normal (ULN) (or \<5 x ULN in case of liver metastases); total bilirubin \<1.5 mg/dL.
* Tissue block (primary or metastatic) available for PARP and PG studies was recommended, although its absence did not exclude subjects from participating;
* Woman of child bearing potential must have had documented negative pregnancy test within two weeks of trial entry and agreed to acceptable birth control during the duration of the trial therapy;
* Signed, IRB approved written informed consent.

Exclusion Criteria:

* Lesions identifiable only by positron emission tomography (PET);
* Prior treatment with gemcitabine, carboplatin, cisplatin or iniparib;
* Major medical conditions that might have affected trial participation (uncontrolled pulmonary, renal, or hepatic dysfunction, uncontrolled infection);
* Significant history of uncontrolled cardiac disease; i.e. uncontrolled hypertension, unstable angina, recent myocardial infarction (within prior 6 months), uncontrolled congestive heart failure, and cardiomyopathy that was either symptomatic or asymptomatic but with decreased ejection fraction \<45%;
* Other significant comorbid condition which the investigator felt might compromise effective and safe participation in the trial;
* Patient enrolled in another investigational device or drug trial, or was receiving other investigational agents;
* Concurrent or prior (within 7 days of trial day 1) anticoagulation therapy (low dose for port maintenance allowed);
* Concurrent radiation therapy was not permitted throughout the course of the trial;
* Inability to comply with the requirements of the trial;
* Pregnant or lactating woman;
* Leptomeningeal disease or brain metastases requiring steroids or other therapeutic intervention.
D: Inclusion Criteria:

- Histologically documented breast cancer (either primary or metastatic site) that is ER-negative, PR-negative, and HER2 non-overexpressing by immunohistochemistry (0, 1) or fluorescence in situ hybridization (FISH).

Triple-negative tumors were defined by the following criteria:

* HER2-non-overexpressing: FISH-negative (defined by ratio \<2.2) or, immunohistochemical (IHC) 0, IHC 1+ or, IHC 2+ or IHC 3+ and FISH-negative.
* ER- and PR-negative: \<10% tumor staining by immunohistochemistry (IHC).

  * Never having received chemotherapy for metastatic disease or, having received 1 or 2 prior chemotherapy regimens in the metastatic setting (Prior adjuvant/neoadjuvant therapy was allowed);
  * Metastatic breast cancer (Stage IV) with measurable disease by RECIST 1.1 criteria;
  * Female, ≥18 years of age;
  * Eastern Cooperative Oncology Group (ECOG) performance status of 0-1;
  * Organ and marrow function as follows: absolute neutrophil count (ANC) ≥1500/mm3, platelets ≥100,000/dL, hemoglobin ≥9 g/dL, bilirubin ≤1.5 mg/dL, serum creatinine ≤1.5 mg/dL or creatinine clearance ≥60 mL/min, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 times the upper limit of normal if no liver involvement or ≤5 times the upper limit of normal with liver involvement;
  * Radiation therapy completed at least 14 days before study dosing on day 1; radiated lesions may not have served as measurable disease;
  * Central nervous system metastases allowed if subject did not require steroids, whole brain radiation therapy (XRT), gamma/cyber knife, and brain metastases were clinically stable without symptomatic progression;
  * For women of child bearing potential, documented negative pregnancy test within two weeks of study entry and agreement to acceptable birth control during the duration of the study therapy;
  * Tissue block (primary or metastatic) or readily available fresh frozen tumor tissue for PARP expression and other pharmacogenomic studies recommended (although its absence will not exclude subjects from participating);
  * No other diagnosis of malignancy (with exception of non melanoma skin cancer or a malignancy diagnosed ≥5 years ago);
  * Obtained informed consent;
  * Capability to understand and comply with the protocol and signed informed consent document.

Exclusion Criteria:

* Systemic anticancer therapy within 14 days of the first dose of study drug;
* Prior treatment with gemcitabine, carboplatin, cisplatin or iniparib
* Had not recovered to grade ≤1 from adverse events (AEs) per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v3.0 or to within 10% of baseline values due to investigational drugs or other medications administered more than 30 days prior to study enrollment;
* Major medical conditions that might have affected study participation (e.g. uncontrolled pulmonary, renal, or hepatic dysfunction, uncontrolled infection, cardiac disease);
* Concurrent radiation therapy intended to treat primary tumor not permitted throughout the course of the study; palliative radiation was acceptable;
* Leptomeningeal disease or brain metastases requiring steroids or other therapeutic intervention;
* Pregnancy or breastfeeding;
* Inability or unwillingness to abide by the study protocol or cooperate fully with the investigator or designee.

Answer: B