De Angelis C, Fu X, Cataldo ML, Nardone A, et al.

The authors conclude that: Aberrant IFN-signaling predicts resistance to CDK4/6i in both ER+/HER2- BC cell lines and in primary BCs from neoadjuvant clinical trials. Experimentally, acquired resistance to Palbo is associated with activation of the IFN-pathway suggesting its involvement in resistance to CDK4/6i. Future studies are warranted to provide mechanistic insights into the association of IFN-signaling with response to CDK4/6i. 

Cohen O, Mao P, Nayar U, Buendia-Bue JE, et al.

The authors conclude that: This study demonstrated that activating RTKs constitute of prevalent modality of acquired resistance to endocrine therapies, inducing a distinct state with clinical implications - suggesting the potential benefit of combination therapies with specific TKIs over CDK4/6i. The common MAPK activity and our preliminary results - suggests the potential of convergence-node targeting strategy with added MEK or SHP2 inhibition.

[GS2-03] The androgen receptor is a tumour suppressor in estrogen receptor positive breast cancer

Lim E, Hickey TA, Selth LA, Chia KM, et al.

The authors conclude that: Collectively, these findings provide compelling evidence that AR has a tumour suppressor role in ER+ breast cancer and advocate an AR agonist strategy for treatment, even in the context of therapy-resistant, ESR1 mutant disease, and should dispel widespread confusion over the role of AR in ER-driven breast cancer, an issue that currently hinders progress in leveraging modern AR-targeted therapies, including available SARMs that lack the undesirable side-effects of androgens, for clinical benefit.

Pan H, Braybrooke J, Gray R, Peto R, et al.

The authors conclude that: The risk of DR at 20 years after diagnosis for women with node-negative ER+ early stage breast cancer, who discontinue endocrine therapy at 5 years is likely to be about a third lower now than in our previous report. However, long-term follow-up of patients diagnosed more recently is required to accurately characterize long-term recurrence risks.

Satpathy S, Jaehnig E, Karsten K, Kim B-J, et al.

The authors conclude that: In summary, we have developed a robust proteogenomics pipeline well suited for large-scale cancer clinical studies to identify potential resistance mechanism in patients. We conclude that microscaled cancer proteogenomics could improve diagnostic precision in the clinical setting.

Gavilá J, Saura C, Pascual T, Hernando C, et al.

The authors conclude that: Neoadjuvant ribociclib and letrozole in high-risk Luminal B breast cancer achieves similar rates of ROR-low disease at surgery as multi-agent chemotherapy. Future studies in high-risk early breast cancer evaluating the survival outcomes and quality of life of this combination in the absence of cytotoxic therapy are justified.

Martín M, Zielinski C, Ruíz-Borrego M, Carrasco E, Ciruelos E, et al.

The authors conclude that: The PEARL study did not show a statistically superiority in PFS for PAL+ET vs CAPE in MBC pts progressing to AIs. No superiority of PAL+ET was observed in the luminal subgroup either. Treatment with PAL+ET was generally better tolerated than CAPE.