HR positive + HER-2 negative

Among T2N1M0 stage HR + /HER2- patients, OS and BCSS of NACT were inferior to ACT. Patients who attained non-pCR after NACT demonstrated significantly worse survival outcomes compared with those who received ACT.

Our study demonstrates an increasing trend in use of pretherapy genomic profiling over time, which is consistent with observed clinical trends. Over 50% of patients underwent upfront surgery when pretherapy genomic profiling was used to guide decision-making, who would have otherwise been offered neoadjuvant chemotherapy. We observed de-escalation of breast specific surgery in more patients with pretherapy genomic profiles.

Implementation of the standardized practice for the operative surgeon to order genomic testing following the release of the pathology report has led to a significant decrease in TAT of genomic testing results, by 7.9 days. The increase in volume in reports ordered amongst breast surgeons has not adversely affected TAT. This protocol can easily be implemented and replicated at other institutions to decrease the time from surgery until final treatment plan.

The rate of chemotherapy use for HR+HER2-BC is higher in patients age 18-40 compared to patients older than 40, with patients age 18-30 receiving chemotherapy at the highest rate. In our cohort of young adults, chemotherapy use was associated with larger tumors, higher clinical stage, and higher ODX score. We suspect that increased use of ODX scores may have contributed to the decrease in chemotherapy utilization in this population.

Among patients with a solitary extracranial metastasis from breast cancer, TNBC was associated with the poorest OS and DPFS rates. Identification of other significant prognostic factors for oligometastatic breast cancer patients may inform guidelines for metastasis directed treatments.

Elevated stiffness indicates a more aggressive tumor biology in HR + HER2-BC, but is less significant in other subtypes. High TIL levels consistently correlate with lower tumor stiffness across all subtypes.

HR-positive/HER2-negative breast cancer with BRCA2 mutations differs from those without mutations in clinical behaviour and reflects more aggressive tumour behaviour. Our results indicate that BRCA2 mutations have no significant effect on the survival of Chinese women with HR-positive/HER2-negative breast cancer.

Our research established links between tumor calcifications and molecular features, thus proposing potential precision treatment strategies for HR+/HER2- breast cancer.

The incidence of new AA also decreased with subsequent draws in the TN and HER2+ cohorts (TN: 25% to 0-9%, HER2 + : 38% to 14-15%). While the incidence of new AA in serial cfDNA decreased with subsequent draws across all MBC subtypes, new alterations with a potential impact on treatment selection continued to emerge, particularly for patients with HR+/HER2- MBC.

P1/2, N=240, Recruiting, Pfizer | Trial completion date: Sep 2026 --> Dec 2026 | Trial primary completion date: Sep 2026 --> Dec 2026

P1/2, N=337, Recruiting, Pfizer | Trial completion date: Oct 2027 --> May 2028 | Trial primary completion date: Aug 2026 --> Mar 2027

In the phase III CAPItello-291 trial, capivasertib in combination with fulvestrant (C+F) demonstrated improved progression-free survival (PFS) (7.3 vs 3.1 months) compared with placebo-fulvestrant (P+F) cohort in AKT-altered pathway patients who had progressed through prior aromatase inhibitor. Capivasertib is a viable treatment option for patients with PIK3CA/AKT1/PTEN activating mutations following progression on endocrine-based regimens in the metastatic setting or recurrence within 12 months of completing adjuvant therapy. Integration of capivasertib into clinical practice is ongoing; intermittent dosing and favorable toxicity are attractive for future novel combination prospective trials.

Gedatolisib plus palbociclib and endocrine therapy showed a promising objective response rate compared with the published results for standard-of-care therapies and had an acceptable safety profile.

Among patients with surgically resected BrM, a high proportion of those with metastatic triple-negative BC and HR+/HER2- disease have HER2-low BrM with potential to benefit from HER2-targeted therapy.

Throughout this timeframe, a typical patient undergoes many treatments that have effects on the bone microenvironment. Therefore, this review explores the clinical course of a representative patient with hormone receptor-positive bone metastatic breast cancer, examining key treatment options at each stage and their effects on preventing and treating bone metastases.

These real-life data show that everolimus in combination with AI in patients with HER2-negative, HR-positive advanced breast cancer is an effective treatment with an acceptable toxicity profile.

Factors associated with shorter overall survival were advanced age, unmarried marital status, lower household income, and grade III disease, among others. Brain metastases remains an unmet medical need for patients with breast cancer; the development of new drugs may provide an improvement in overall survival for male patients in the future.

Analysis of the tumor microenvironment after combination immunotherapy did not show a significant change in immune cell subsets from baseline. There was limited benefit for dual checkpoint blockade administered prior to NACT in our study of 8 patients with HR+/HER2-negative breast cancer.

Our RWD suggests that elderly patients, when compared to those under 70, experience similar survival outcomes and exhibit comparable tolerance for CDK4/6i therapy.

Pharmacovigilance and experimental studies are warranted to confirm any causative relationship and to explore the underlying pathophysiology, respectively.

A cut-off of ≤5 ultrasound-detected abnormal nodes can distinguish between patients with limited versus high nodal burden, with high specificity. Hence, incorporating the number of abnormal ultrasound-detected nodes into clinical practice may prove useful in guiding between upfront surgery and gene assay testing or neoadjuvant chemotherapy in this group of patients.

P2, N=30, Recruiting, Massachusetts General Hospital | Trial completion date: Jul 2024 --> Dec 2025 | Trial primary completion date: Dec 2023 --> Jul 2025

Furthermore, differences in AEs emerged between patients with PIK3CA-mutated breast cancer and those with PROS. This study provides vital insights for healthcare professionals to navigate AEs in clinical practice and informs future research for enhancing alpelisib 's safety profile.

This study suggested that HER2-low expression may predict the efficacy of ET but not that of CDK4/6 inhibitor plus ET in HR-positive/HER2-negative MBC patients. The results of this study highlight the importance of integrating HER2 status in tailoring personalized treatment strategies for HR-positive MBC.

P=N/A, N=25, Enrolling by invitation, OHSU Knight Cancer Institute | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

This study provided real-world data for the use of chidamide in patients with HoR-positive and HER2-negative MBC. Our data endorsed the use of chidamide in patients pretreated with CDK4/6 inhibitors and patients treated with different endocrine combinations.

In TNBC, cfDNA concentrations during therapy were not strongly correlated with response or prognosis. In the HR-positive/HER2-negative group, pretreatment cfDNA concentration was prognostic for DRFS. Overall, the predictive and prognostic value of cfDNA concentration was more limited than that of ctDNA.

Despite the rate of PEPI score 0 was not high, tucidinostat plus exemestane as a neoadjuvant therapy might be well tolerated and showed promising clinical responses in patients with early hormone receptor-positive, HER2-negative breast cancer. To clarify the safety and efficacy of this strategy, further investigation is warranted.

No abstract available

The identification of BRCA1/2 alterations in ctDNA could guide the use of germline testing. The VAF cutoff identified for the likelihood of a germinal mutation is lower than expected, suggesting that a wider population should be screened for germinal mutation with relevant impact on the therapeutic choices and family screening.

The nationwide survey revealed significant variability across laboratories in terms of sampling methodology, technical assessment and clinical report signing healthcare figures for PIK3CA molecular testing in diagnostic routine practice. This study provides insights into the real-world routine of PIK3CA testing in HR+/HER2- MBC and highlights the need for standardization and networking in predictive pathology.

Conclusion Tissue-based biomarkers with significant prognostic output were identified from the immune and OncoMasTR panels. A mIF panel incorporating both types of markers is being developed, aiming to offer improved prognostic prediction for early-stage breast cancer beyond current approaches.

Among patients with BC and CNS metastases accessible for intracranial response at 3 months, intracranial activity was observed with capecitabine. These patients have a poor prognosis regardless of the BC subtype, especially in scenarios where newer therapeutic options are unavailable.

Median age was 49 years (19-86), 28.3% (30) had de novo stage IV disease; 63% received palbociclib with ET as first line, 54% of them with aromatase inhibitor over fulvestrant. Multivariate analysis showed that the year at diagnosis and CDKi timing (first line versus ≥second line) were significantly associated with OS. Our real-world data show that first-line CDKi + ET provides a statistically significant benefit in OS versus ≥second line in HR+/HER2- ABC patients.

In conclusion, our work uncovers opportunities for further treatment personalization and stresses the need for effective combination treatments to address the altered tumor genomic landscape following AI+CDK4/6i exposure. Further, we demonstrated the potential of RWD for refining patient treatment strategy and guiding clinical trial design.

Treatment of patients with visceral metastatic HR-positive, HER2-negative BC with ribociclib in combination with ET showed a tendency toward a more favorable clinical outcome. Despite small numbers of patients and sites, this head-to-head comparison with chemotherapy supports the use of ribociclib with ET in patients with visceral metastasis at risk of fast disease progression.

In this randomized phase II trial, single-agent metronomic oral vinorelbine was effective and well tolerated as first-line chemotherapy for patients with HR-positive/HER2-negative ABC. Formal comparisons are not done in this phase II study and one can simply observe that confidence intervals of all endpoints overlap. When deciding for a chemotherapy after failure of endocrine therapy and CDK 4/6 inhibitors, oral vinorelbine might be an option to be given with either schedule.

The customized 19-gene assay has a high concordance with MammaPrint in predicting recurrent risk and evaluating effects of adjuvant chemotherapy, especially in the low- and medium-risk groups that can be exempted from chemotherapy. A larger cohort is warranted to further validate this assay.

P=N/A, N=419, Recruiting, Ipsen | Trial primary completion date: Jun 2024 --> Dec 2025

P1, N=100, Recruiting, Taiho Oncology, Inc. | N=242 --> 100 | Trial completion date: Jun 2024 --> Jul 2027 | Trial primary completion date: Oct 2023 --> Jul 2024

The literature data and bioinformatic tools provide an underlying molecular rationale for most of these miRNAs, mainly involving the PI3K/AKT/mTOR pathway and cell-cycle machinery as cyclin D1, CDKN1B, and protein p27Kip1 and autophagy. Our findings propose a novel panel of miRNAs associated with a higher likelihood of early progression in patients treated with ET and Palbociclib and may contribute to shed some light on the mechanisms of de novo resistance to CDK4/6i, but this should be considered exploratory and evaluated in larger cohorts.

P2, N=201, Active, not recruiting, Priscilla McAuliffe | Recruiting --> Active, not recruiting | Trial completion date: Mar 2023 --> Mar 2025 | Trial primary completion date: Mar 2023 --> Mar 2024