Novel estrogen receptor mutations and uses thereof

A method of treating a subject having an Estrogen Receptor positive (ER+) breast cancer, comprising:

• detecting in a sample from the subject a mutant estrogen receptor 1 (ESR1) polypeptide or a nucleic acid molecule encoding the mutant ESR1 polypeptide,
• wherein the mutant ESR1 polypeptide, or the nucleic acid molecule encoding the ESR1 polypeptide, comprises one or more of:
• one or more missense mutations at amino acid position 311, 341, 350, 394, 414, 433, 503, or 538 of the amino acid sequence of SEQ ID NO:2,
• a deletion of nucleotides 1046-1051 of SEQ ID NO:1, or
• an insertion between amino acid positions 344 and 345 of SEQ ID NO:2;
• and
• administering to the subject an effective amount of a Selective Estrogen Receptor Degrader (SERD), thereby treating the ER+ breast cancer in the subject.