a diagnosis of ER+/HER2- invasive breast carcinoma that is either locally advanced disease not amenable to resection with curative intent (herein called unresectable) or metastatic disease not treatable with curative intent.
2. Has documented radiographic confirmation of disease progression (as assessed by the investigator and/or histology [biopsy required, cytology will not be accepted] for participants presenting with new metastatic lesions) during or after the last administered ET prior to entering the study.
Note: A laboratory report indicating tumor marker elevation cannot be used as
documentation of local or distant disease recurrence.
3. Has locally confirmed ER+/HER2- invasive breast cancer, according to the most recent ASCO/CAP guidelines on the most recent biopsy:
- ER+ as determined by local testing before study entry based on ASCO/CAP guidelines. Tumor will be considered ER+ if the tumor shows ≥1% expression of ER.
- HER2- as determined by local testing before study entry based on ASCO/CAP
guidelines. Tumor will be considered HER2- if the tumor shows HER2 zero or low, defined as IHC 0, 1+ or IHC 2+/ISH-.
Note: The local test results should be performed on a tumor biopsy obtained from a distant metastatic site or a local recurrence that has not been previously irradiated. If a new biopsy is required, it needs to be performed before baseline tumor scan assessment.
An archival tumor tissue sample from the primary tumor may be used, only after Sponsor consultation.
4. Provides additional tissue from the same sample used to determine ER and HER2 status locally.

Medical Conditions
1. Breast cancer amenable to treatment with curative intent.
2. Tumor known to harbor ESR1 mutation (in regions where elacestrant is available and patient has access to it and the administration is not medically contraindicated).
3. Is unable to receive any of the ETs (ie, fulvestrant or exemestane). For example, known bleeding disorder which, in the opinion of the investigator, would prohibit administration
of fulvestrant.
4. Known difficulty in tolerating oral medications, unable to swallow orally administered medication, or conditions which would impair absorption of oral medications such as uncontrolled nausea or vomiting (ie, CTCAE ≥Grade 3 despite antiemetic therapy), ongoing gastrointestinal obstruction, motility disorder, malabsorption syndrome, or prior gastric bypass.
5. Has any of the following:
- A pulse oximeter reading <92% at rest, OR
- Requires intermittent supplemental oxygen, OR
- Requires chronic supplemental oxygen.

Has advanced/metastatic, symptomatic visceral spread at risk of rapidly evolving into life-threatening complications, such as lymphangitic lung metastases, radiographic evidence of intratumoral cavitation or invasion/infiltration of a major blood vessel, bone
marrow replacement, carcinomatous meningitis, significant symptomatic liver metastases, symptomatic pericardial effusion, symptomatic peritoneal carcinomatosis, or
the need to achieve rapid symptom control.
- Participants with symptomatic ascitic effusion caused by peritoneal carcinomatosis which is alleviated after drainage of the ascitic fluid can be enrolled.
- Participants with symptomatic liver metastases include participants with rapidly increasing bilirubin >1.5 × ULN in the absence of biliary obstruction with involvement of over than 50% of liver parenchyma by the disease will be excluded.
7. Patients with only non-measurable lesions other than bone metastasis (eg, pleural effusion, ascites).
Note: Skin only disease is excluded. Participants who have metastatic disease fulfilling the previous criteria in addition to skin disease may be enrolled.
8. Active, bleeding diathesis, or on oral anti-vitamin K medication (except low dose warfarin, LMWH and acetylsalicylic acid or equivalent, as long as the INR is ≤2.0).
9. History of noninfectious pneumonitis/interstitial lung disease including radiation pneumonitis that required steroids or has current pneumonitis/interstitial lung disease.
10. Criterion removed.
11. Has a known germline BRCA mutation (deleterious or suspected deleterious) and has received previous treatment with PARP inhibition either in the adjuvant or metastatic setting (where available and not medically contraindicated).