Erin Roesch, MD
Efficacy of immunotherapy also depends on breast cancer subtype. Triple-negative and HER2-positive tumors have higher TMB and TILs compared to luminal subtype. A phase 2 study in 88 patients with metastatic HR-positive, ERBB2-negative breast cancer demonstrated no difference in PFS or ORR with pembrolizumab/eribulin versus eribulin alone, including the PD-L1 positive population. There was a trend towards greater immunotherapy benefit in the high TMB subgroup which is encouraging. Future research with novel agents that may augment immune response and/or alter tumor microenvironment are intriguing concepts.
First-line endocrine therapy plus CDK 4/6 inhibitor is considered standard of care for HR-positive metastatic breast cancer. A retrospective chart review evaluating everolimus plus endocrine therapy post-CDK 4/6 inhibitor demonstrated PFS of 4.2 months and ORR of 17%. Although benefit appears modest, mTOR inhibitor combinations remain a valuable treatment option for select patients. Chemotherapy is often reserved for rapidly progressive disease or visceral crisis, however, it is crucial to evaluate for endocrine resistance. Furthermore, additional research is warranted to determine interactions between PI3K/Akt/mTOR and downstream Cyclin D/CDK 4/6/Rb pathways and implications on treatment sequencing.
Trastuzumab therapy for 1 year is standard of care for early-stage HER2-positive breast cancer. A meta-analysis of 5 trials with 11,376 patients showed noninferiority of shorter duration trastuzumab compared to 1 year for DFS and OS and lower congestive heart failure rates with the former. Trastuzumab is well-tolerated, and although cardiac toxicity is often reversible, it can carry more severe consequences in patients with cardiac conditions. Shorter duration may be an option in patients with clinically lower risk disease (ER-positive, node-negative tumors) and significant cardiac risk factors, and represents a method of therapy de-escalation for the appropriate patient.
The COVID-19 pandemic has impacted oncology healthcare delivery models and cancer patients have poorer outcomes from COVID-19. A survey study of Brazilian breast cancer specialists demonstrated changing practices for early-stage breast cancer as the pandemic progressed. For HR-positive tumors with low ki-67, 48% would recommend NET for postmenopausal women, while 34% would recommend NET for those with high ki-67. There is limited data regarding NET for pre-menopausal women. Genomic assays may have an evolving role to identify patients who may be appropriate candidates for neoadjuvant therapy versus upfront surgery. Strategies to decrease treatment complications and effectively utilize resources are essential during the COVID-19 pandemic.