HR positive

The biological basis arises from the dual function of monocytes in promoting tumor-supportive environments and lymphocytes in facilitating immune monitoring. Through the capture of this immunological interaction, MLR acts as a low-risk and affordable method for risk assessment and treatment choices adapted to molecular subtype traits.

We summarize intensive treatment methods for T1N0M0 HR+/HER2- breast cancer patients, which extend beyond the standard 5-year tamoxifen (TAM)-based adjuvant ET. These methods include intensive ET, poly(ADP-ribose) polymerase (PARP) inhibitors, other targeted therapies, antibody-drug conjugates, oral chemotherapy, immunotherapy, and enhanced prevention of bone metastasis. This review provides a foundation for developing personalized adjuvant treatment strategies for patients with T1N0M0 HR+/HER2- breast cancer.

The discovered LPP phenotype defines a small, high-risk subset warranting external validation. Given the retrospective, single-system design of the study, it is imperative to interpret the discovered phenotype features as hypothesis-generating, rather than as definitive evidence.

Conversely, T-DXd administered due to the presence of HER2-low showed excellent effectiveness. Performing a re-biopsy is crucial due to the possible loss of estrogen receptors, which would require a change in therapeutic strategy no longer based on endocrine therapy. In cases that remain luminal, knowledge of the mutational profile may help to offer patients novel targeted treatments.

We demonstrate that optimal efficacy requires biomarker-guided patient selection integrating genetic and TME features, precise sequencing, and a mechanistic understanding of drug-specific immunomodulatory effects. The integration of platform trial designs (I-SPY2, CheckMate-7FL) with composite biomarker algorithms represents a paradigm shift toward precision neoadjuvant immunotherapy, offering a conceptual framework for transforming outcomes in molecularly defined HR+ breast cancer subsets.

P1, N=168, Completed, AbbVie | Active, not recruiting --> Completed | Trial completion date: Jun 2025 --> Sep 2025 | Trial primary completion date: Jun 2025 --> Sep 2025

Patients with metastatic HR+HER2- IBC demonstrated a shorter time on treatment suggesting shorter duration of response on CDKI + HT, which is markedly inferior to reported data for non-IBC patients from phase III trials.

nal-IRI demonstrated IC activity in HER2[-] BC with BMs. While overall efficacy was limited and long-term outcomes remain poor, these results highlight the unmet need in this challenging population and support the importance of developing more treatment strategies.

P3, N=474, Active, not recruiting, Bayer | Trial completion date: Jun 2027 --> Jun 2028

Patients with HR+HER2- ABC showed impaired cognitive function at initial diagnosis compared to cancer-free controls. During first-line endocrine treatment with aromatase inhibitors, cognitive function declined in a small group of patients, regardless of the addition of CDK4/6i.

Tucatinib addition to trastuzumab and pertuzumab demonstrated improvement in PFS with no new safety signals identified and may be an option for 1L maintenance therapy in patients with HER2+ MBC.

We analyzed pre- and on-treatment biopsies from patients with HR+ breast cancer treated with letrozole to induce estrogen deprivation (ED)...Finally, deletion combined with silencing of the CXCL11 receptors CXCR3 and CXCR7 in MCF7 cells impaired proliferation in response to exogenous CXCL11 and to co-culture with CD8+ T cells in estrogen-free conditions. These findings suggest that CD8+ T cell-associated CXCL11 in the TIME modulates the response of HR+ breast cancer cells to estrogen suppression.