4
Diagnosis
Recommendation 3.2
➤ There is insufficient evidence to support a recommendation either for or
against testing for a germline PALB2 pathogenic variant for the purpose
of determining eligibility for treatment with PARP inhibitor therapy in the
metastatic setting. This recommendation is independent of the indication
for testing to assess cancer risk. (Moderate recommendation; IC-L)
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 pathogenic variants and somatic BRCA1/2 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.
Recommendation 4.1
➤ There are insufficient data at present to recommend routine testing of
tumors for homologous recombination deficiency (HRD) to guide therapy
for metastatic breast cancer. (Moderate recommendation; IC-L)
Recommendation 5.1
➤ Patients with locally recurrent unresectable or metastatic hormone
receptor-negative and HER2-negative breast cancer who are candidates
for a treatment regimen that includes an immune checkpoint inhibitor
should undergo testing for expression of PD-L1 in the tumor and
immune cells with an FDA-approved test to determine eligibility for
treatment with the immune checkpoint inhibitor pembrolizumab plus
chemotherapy. (Strong recommendation; EB-B-I)
Recommendation 6.1
➤ Patients with metastatic cancer who are candidates for a treatment
regimen that includes an immune checkpoint inhibitor should
undergo testing for dMMR/microsatellite instability-high (MSI-H) to
determine eligibility for dostarlimab-gxly or pembrolizumab. (Moderate
recommendation; IC-L)
Recommendation 7.1
➤ Patients with metastatic cancer who are candidates for treatment
with an immune checkpoint inhibitor should undergo testing for TMB
to determine eligibility for pembrolizumab monotherapy. (Moderate
recommendation; IC-L)
