To study clinical effectiveness and safety of olaparib monotherapy in metastatic breast cancer patients.

Inclusion Criteria

• 1. Provision of informed consent prior to any study specific procedures. For patients
• aged <20 years and screened in Japan, a written informed consent should be obtained from the patient and his or her legally acceptable representative.
• 2. Patients must be ≥18 years of age.
• 3. Histologically or cytologically confirmed HER2-ve breast cancer with evidence of metastatic disease. Patients can have either TNBC (defined as oestrogen receptor and progesterone receptor negative [immunohistochemistry nuclear staining <1%] and HER2-ve [immunohistochemistry 0, 1+ or 2+ and/or in situ hybridization nonamplified with ratio less than 2.0]) or oestrogen receptor / progesterone receptor positive breast cancer as long as they are HER2-ve.
• 4. Documented BRCA1/2 status
• -To be regarded as BRCA1/2 (+ve), the patient must have a mutation that is predicted to be deleterious or suspected deleterious (known or predicted to be detrimental / lead to loss of function). Mutations that are not clearly pathogenic may be assessed by a committee of genetic specialists to adjudicate if the patient is eligible.
• -Patients with tBRCA mutations: must be confirmed by a validated method (e.g. results from a CLIA-certified laboratory or CE-IVD device)
• 5. Prior treatment with a taxane or an anthracycline in either an adjuvant (may include neoadjuvant) or metastatic breast cancer treatment setting.
• 6. Patients should have received no more than two prior cytotoxic chemotherapy regimens in the metastatic setting. If a patient has oestrogen receptor and/or progesterone receptor positive HER2 negative metastatic breast cancer and has completed a prior line of hormonal treatment, then if the current or currently planned choice of treatment for the patient does not include a hormonal treatment then they would be a suitable patient to enter the study. Previous endocrine therapy
• could be in either an adjuvant or a metastatic setting and include endocrine therapy in combination with a targeted agent such as a CDK4/6 or mTOR inhibitor.
• 7. Be considered suitable, by the Investigator, for further treatment with single-agent chemotherapy for the metastatic disease
• 8. Patients must have normal organ and bone marrow function measured within 14 days prior to administration of study treatment as defined below:
• - Haemoglobin ≥ 10.0 g/dL with no blood transfusion in the past 28 days
• - Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
• - Platelet count ≥ 100 x 109/L
• - Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) unless the patient has documented Gilbert’s Syndrome
• - Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase (SGOT)) / alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase (SGPT)) ≤ 2.5 x institutional ULN unless liver metastases are present in which case they must be ≤ 5x ULN
• - Patients must have creatinine clearance (CrCl) estimated using the Cockcroft- Gault equation of ≥ 51 mL/min or 24 hour urine test may be done if standard of care:
• Estimated CrCl = (140-age [years]) x weight (kg) (x F)a serum creatinine (mg/dL) x 72
• a- where F=0.85 for females and F=1 for males
• 9. Patients must have a life expectancy ≥ 16 weeks
• 10. Postmenopausal or evidence of non-childbearing status for women of childbearing
• potential: negative urine or serum pregnancy test within 28 days of study treatment
• and confirmed prior to treatment on Day 1
• Postmenopausal is defined as (at least one criterion met):
• - amenorrhoeic for 1 year or more following cessation of exogenous hormonal treatments
• - luteinizing hormone and follicle stimulating hormone levels in the postmenopausal range for women under 50
• - radiation-induced oophorectomy with last menses >1 year ago
• - chemotherapy-induced menopause with >1 year interval since last menses
• - surgical sterilisation (bilateral oophorectomy or hysterectomy).
• 11. Women of childbearing potential, who are sexually active, must agree to the use of one highly effective form of contraception and their male partners must use a condom from the signing of the informed consent, throughout the 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.
• 12. Male patients must use a condom during treatment and for 3 months after the last dose of olaparib when having sexual intercourse with a pregnant woman or with a woman of childbearing potential. Female partners of male patients should also use one highly effective form of contraception if they are of childbearing potential.
• 13. Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations for greater than 6 months.