Analysis of Olaparib Response in Patients With BRCA1 and/or 2 Promoter Methylation Diagnosed of Advanced Breast Cancer

Inclusion Criteria: (Any asterisked* are applicable as an inclusion criteria prior to perform the BRCA methylation testing via central testing)

• *The patient has signed and dated the informed consent document and it has been obtained before conducting any procedure specifically for the study.
• Female ≥ 18 years of age on day of signing informed consent.
• Patient with histological confirmation of breast cancer with evidence of advanced disease not amenable to resection or radiation therapy with curative intent.
• Documented Triple Negative (TN) disease by immunohistochemistry (IHC) and/or in situ hybridization based on local testing (preferably assessed on the most recent tumour biopsy available). TN is defined as negative hormone receptor status ( 60 years.
• Age ≤ 60 years and with amenorrhea for 12 or more months in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression and follicle stimulating hormone and estradiol in the postmenopausal range.
• Olaparib is regarded as a compound with medium/high foetal risk, patients of childbearing potential and their partners, who are sexually active, must agree to the use of 2 highly effective forms of contraception in combination as listed below. This should be started from the signing of the informed consent and continue throughout period of taking study treatment and for at least 1 month after last dose of study drug or they must totally/truly abstain from any form of sexual intercourse (see below).

Acceptable non-hormonal birth control methods include:

• Total sexual abstinence. Abstinence must continue for the total duration of the study treatment and for at least 1 month after one dose. Periodic abstinence (e.g., calendar ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
• Vasectomised sexual partner plus male condom. With participant assurance that partner received post-vasectomy confirmation of azoospermia.
• Tubal occlusion plus male condom.
• Intrauterine Device (IUD) plus male condom. Provided coils are copper-banded.

Acceptable hormonal methods:

• Normal and low dose combined oral pills plus male condom.
• Cerazette (desogestrel) plus male condom. Cerazette is currently the only highly efficacious progesterone based pill.
• Hormonal shot or injection (e.g., Depo-Provera) plus male condom.
• Etonogestrel implants (e.g. Implanon or Norplan) plus male condom.
• Norelgestromin/ethinyl estradiol (EE) transdermal system plus male condom.
• Intrauterine system (IUS) device (e.g., levonorgestrel releasing IUS -Mirena®) plus male condom.
• Intravaginal device plus male condom (e.g. EE and etonogestrel).
• *Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits, laboratory tests and examinations and other study procedures including follow up.

Exclusion Criteria: (Any asterisked* are applicable as an inclusion criteria prior to perform the BRCA methylation testing via central testing)

• Involvement in the planning and/or conduct of the study (applies to the sponsor and/or study site staff).
• Previous enrolment in the present study.
• Participation in another clinical study with an investigational product during the last 4 weeks.
• *Any previous treatment with a Poly Adenosine diphosphate-Ribose Polymerase (PARP) inhibitor, including olaparib.
• *Patients with other malignancy within the last 5 years, except: adequately treated non-melanoma skin cancer (basal cell or squamous cell carcinoma), curatively treated in-situ cancer of the cervix, ductal carcinoma in situ (DCIS), stage 1, grade 1 endometrial carcinoma, or other solid tumours including lymphomas (without bone marrow involvement) curatively treated with no evidence of disease for ≥ 5 years prior to study inclusion. Patients with a history of localised breast cancer with a tumor histology different to TN, with no evidence of disease for ≥ 5 years s