Treatment
New Recommendations from 2021 Focused Guideline Update
Recommendation 1.1
➤ Alpelisib in combination with endocrine therapy should be offered to
postmenopausal patients in combination with fulvestrant, and to male
patients, with HR-positive, HER2-negative, PIK3CA-mutated, advanced
or metastatic breast cancer following prior endocrine therapy including
an aromatase inhibitor, with or without a CDK4/6 inhibitor. Careful
screening for and management of common toxicities are required.
(Moderate recommendation; EB-B-H)
Recommendation 2.1
➤ To guide the decision to use alpelisib in combination with fulvestrant
in postmenopausal patients, and in male patients, with HR-positive
metastatic breast cancer, clinicians should use next generation
sequencing in tumor tissue or cell-free DNA in plasma to detect PIK3CA
mutations. If no mutation is found in cell free DNA, testing in tumor
tissue, if available, should be used as this will detect a small number of
additional patients with PIK3CA mutations. (Strong recommendation;
EB-B-H)
Recommendation 2.2
➤ There are insufficient data at present to recommend routine testing for
ESR1 mutations to guide therapy for HR-positive, HER2-negative MBC.
Existing data suggest reduced efficacy of aromatase inhibitors compared
to the selective estrogen receptor degrader (SERD) fulvestrant in
patients who have tumor or circulating tumor DNA with ESR1 mutations.
(Moderate recommendation; IC-Ins)
Recommendation 2.3
➤ Patients with metastatic HR-positive but HER2-negative breast cancer
with germline BRCA1 or 2 mutations who are no longer benefiting
from endocrine therapy may be offered an oral PARP inhibitor in the
first- through to third-line setting rather than chemotherapy. (Strong
recommendation; EB-B-I)
Qualifying Statements: Small single-arm studies show that oral PARP inhibitor therapy
demonstrates high response rates in metastatic breast cancer encoding DNA repair defects,
such as germline PALB2 mutation carriers and somatic BRCA mutations. It should also be
noted that the randomized PARP inhibitor trials made no direct comparison with taxanes,
anthracyclines, or platinums; comparative efficacy against these compounds is unknown.
