Phase III Study to Evaluate the Safety, Efficacy, and Impact on Quality of Life of Capivasertib Alongside Standard-of-care Endocrine Treatment in Patients With HR+/HER2- Advanced Breast Cancer and Progression on Prior Endocrine-based Treatment

Inclusion Criteria: 1. Females (≥18 years, pre-, peri- or post-menopausal) and males (≥18 years) at the time of signing the informed consent form a. Pre-menopausal (and peri-menopausal, i.e., those that do not meet the criteria for post menopausal defined below) women can be enrolled if amenable to treatment with an GNRH agonist. Patients are to have commenced concomitant treatment with GNRH agonist prior to or on Cycle 1, Day 1 and must be willing to continue it for the duration of the study. b. Post-menopausal women are defined as: i. aged ≥60 years of age, OR ii. aged \<60 years of age and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments/chemotherapy/ovarian suppression/tamoxifen or similar. These patients should also have serum oestradiol and follicle stimulating hormone (FSH) levels confirmed as being within the standard laboratory reference range for post-menopausal females, OR iii. documented bilateral oophorectomy. 2. Histologically confirmed HR+/HER2- breast cancer determined from the most recent tumour sample (primary or metastatic) as per WHO classification. To fulfil the requirement of HR+ disease, a breast cancer must express ER with or without co-expression of progesterone receptor. Therefore, tumours must be: a. ER+ defined as ≥1% of tumour cells stain positive for ER on immunohistochemistry (IHC) or, if no percentage is available, then an Allred IHC score of ≥3/8, b. Progesterone receptor positive defined as ≥1% of tumour cells stain positive for progesterone receptor on IHC or, if no percentage is available, then an Allred IHC score of ≥3/8; or progesterone receptor negative defined as \<1% of tumour cells stain positive for progesterone receptor on IHC or, if no percentage is available, then an Allred IHC score of ≤2/8; or progesterone receptor unknown, and c. HER2- defined as 0 or 1+ intensity on IHC, or 2+ intensity on IHC and no evidence of amplification on in situ hybridisation (ISH), or if IHC not done, no evidence of amplification on ISH. 3. Metastatic or locally advanced disease with radiological or objective evidence of recurrence or progression (the cancer should have shown progression during or after most recent therapy); locally advanced disease must not be amenable to resection with curative intent (patients who are considered suitable for surgical or ablative techniques following potential down-staging with study treatment are not eligible). 4. Patients are to have received treatment with an ET (endocrine-based therapy) containing regimen (single agent or in combination) and have: a. Radiological evidence of breast cancer recurrence or progression while on, or within 12 months of the end of (neo)adjuvant treatment with an ET, OR b. Radiological evidence of progression while on prior ET administered as a treatment line for locally advanced or metastatic breast cancer (this does not need to be the most recent therapy). 5. Presence of one or more of the PIK3CA/AKT1/PTEN biomarkers, preferably determined in tumour tissue\* 6. Decision to newly initiate capivasertib 7. Informed consent provided by patient prior to participation in the trial and before initiation of any study-specific measures 8. A. Female patients of childbearing potential at inclusion must have a negative pregnancy test (serum) and additionally, - surgically sterile, - carry an intrauterine device (combined with a barrier method), * having received a bilateral tubal ligation/occlusion (combined with a barrier method), * or using a highly effective method of contraception for the duration of the study (from the time they sign consent) and for 3 months after the last dose of capivasertib / GNRH and for 2 years after the last dose of fulvestrant to prevent pregnancy. * Total/true abstinence When the patient refrains from any form of sexual intercourse and this is in line with their usual and/or preferred lifestyle; this must continue for the duration of the study and for 3 months after the last dose of capivasertib/ GNRH and for 2 years after the last dose of fulvestrant to prevent pregnancy. * Vasectomised sexual partner (with participant assurance that partner received post-vasectomy confirmation of azoospermia) combined with a barrier method or sexual partner with bilateral orchiectomy * Hormonal contraception is not acceptable. 8\. B. Male patients must either be * surgically sterile * or using an highly effective method of contraception for the duration of the study (from the time they sign consent) and for 4 months after the last dose of capivasertib/ GNRH and for 2 years after the last dose of fulvestrant to prevent pregnancy in a partner. * Sexually abstinent men (i.e., refraining from heterosexual intercourse during the entire study duration) must continue for 4 months after the last dose of capivasertib/ GNRH and for 2 years after the last dose of fulvestrant to prevent pregnancy in a partner. * Male patients who intend to be sexually active with a woman of childbearing potential, must use a condom plus spermicide upon entering the study and until 4 months after the last dose of capivasertib and for 2 years after the last dose of fulvestrant to prevent pregnancy in a partner. * Highly effective methods of contraception should be considered in female partners of men taking capivasertib plus fulvestrant who are of childbearing potential. 9\. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 with no deterioration over the previous 2 weeks and life expectancy of ≥12 weeks \*A list of eligible alterations and test procedures is provided in the protocol. Exclusion Criteria: * Patients eligible for inclusion in this study must not meet any of the following criteria: 1. Absence of an alteration in the PIK3CA/AKT1/PTEN biomarkers 2. Previous enrolment in the present study 3. Participation in another clinical study with any investigational medicinal product and still on IMP treatm