HER2 Negative Breast Cancer

Low-dose apatinib combined with oral vinorelbine demonstrates potential efficacy and well tolerated for pretreated HER2-negative mBC.

P3, N=378, Not yet recruiting, Shanghai Escugen Biotechnology Co., Ltd

Moreover, preliminary evidence regarding the use of genomic assays to inform de-escalation of endocrine treatment, such as shorter durations or omission, for low risk patients are reviewed. Overall, gene expression assays are emerging as potential tools to further personalize adjuvant treatment for patients with HR+/HER2- breast cancers.

P3, N=500, Not yet recruiting, AstraZeneca

P=N/A, N=550, Recruiting, Novartis Pharmaceuticals | Not yet recruiting --> Recruiting

P3, N=240, Not yet recruiting, MedSIR

P3, N=3100, Suspended, Novartis Pharmaceuticals | Recruiting --> Suspended

In conclusion, the identified systemic immune signatures indicate an immune-suppressed environment in mBC patients who had progressed/relapsed on standard treatments, and is consistent with ongoing chronic inflammation. These activated immuno-suppressive mechanisms may be investigated as therapeutic targets, and for use as biomarkers of response or treatment resistance.

P=N/A, N=50, Recruiting, Fondazione Policlinico Universitario Agostino Gemelli IRCCS | Trial completion date: Feb 2024 --> Feb 2025 | Trial primary completion date: Jan 2024 --> Jan 2025

P2, N=367, Active, not recruiting, Sanofi | Trial completion date: Mar 2024 --> Sep 2024

Although the AEs of palbociclib and abemaciclib affected the treatment considerably, the treatment duration and RDI were similar. CDK4/6 inhibitors should be selected based on the tolerability and manageability of each AE.

In patients with heavily pretreated advanced HR+/HER2- BC and TNBC, Dato-DXd demonstrated promising clinical activity and a manageable safety profile. Dato-DXd is currently being evaluated in phase III studies.

Analysis of somatic mutations by whole exome sequencing showed that counter-intuitively, the cluster of HR + /HER2- samples exhibiting higher immune scores was associated with lower tumour mutational burden, lower homologous recombination deficiency scores, and fewer copy number aberrations, implicating the involvement of non-canonical tumour immune pathways. Further investigations are warranted to determine the underlying mechanisms of these pathways, with the potential to develop innovative immunotherapeutic approaches tailored to this specific patient population.

This clinical trial population of similarly treated TNBC patients showed no racial differences in breast cancer outcomes. Disease extent, rather than race, was associated with disease events.

P1, N=96, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Apr 2024 --> Apr 2026 | Trial primary completion date: Apr 2024 --> Apr 2026

P1, N=42, Recruiting, Nanjing Chia-tai Tianqing Pharmaceutical | Not yet recruiting --> Recruiting

We summarized the ctDNA and cancer tissue mutational landscape, including overall neoplastic burden and PIK3CA and ESR1 hotspot mutations in abemaciclib-treated patients with HR+/HER2- MBC. The data provide insights that could help optimize treatment strategies in this population.

Despite the significant gains of abemaciclib as adjuvant treatment in terms of progression-free survival, this treatment is not cost-effective for the Spanish National Health System at published prices. It may be cost-effective with an appropriate discount on the official price.

Breast cryoablation for palliative and curative treatment of breast cancer has been performed for decades. Although there is a recent resurgence of interest in breast cryoablation with curative intent for unifocal, hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer, this report highlights the essential role that cryoablation can play in the palliative treatment of multicentric oestrogen and progesterone receptor-negative and human epidermal growth factor receptor 2-negative (triple-negative) breast cancer, meeting the select pretreatment objectives such as breast or nipple pain relief and prevention of tumour erosion through the skin or nipple in patients who have failed or cannot tolerate the standard of care treatment.

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.

The addition of palbociclib to ET was effective for treating HR+/HER2- ABC in Japanese routine clinical practice.

Our model showed a high specificity with a low false positive rate (8.1%) for identifying low-risk 21-gene RS. As a result, there is a possibility of minimizing the need for testing in low-risk patients. These findings suggest the potential utility of the developed clinical-pathological models in identifying a subset of patients aged 50 and above who may safely omit the 21-gene RS assay.

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.

This study demonstrated the feasibility of omitting Oncotype Dx® assay in postmenopausal women with node negative, T1, Nottingham Grade 1, HR positive, HER2 negative breast carcinoma with Magee 2 equation score ≤ 18. Using comparable tools such as Magee 2 equation may reduce financial toxicity to this population and overall cost to the system. Larger study recommended.

Our preliminary results suggest that gene expression profiling holds more weight than nodal status in determining adjuvant therapy. Our study is limited by sample size, and data collection is still ongoing. Premenopausal patients were included for the purpose of this report, but ultimately will be evaluated separately from postmenopausal patients, as in other similar studies.

Patients < 50 with pT1-2N1 HR+/HER2- breast cancer and RS≤25 have an OS benefit from combined adjuvant chemoendocrine therapy regardless of the number of +LNs. However, the OS benefit is least among patients with 1 +LN, and there may be a subset of these patients who derive a limited benefit from chemotherapy, and for whom risks outweigh benefits. Correlation of these findings with disease-free survival and other clinicopathologic features unavailable in this analysis may help to identify a subset of patients with low-risk disease who could safely avoid adjuvant chemotherapy.

Clinicopathologic features including patient age, race, clinical T category, grade, Ki67, ER/PR expression, and tumor location are associated with nodal positivity in women 50-69 years of age with cT1N0, ER+HER2- breast cancer. The 21-gene RS is not associated with nodal positivity. This predictive model is able to identify women at high risk for nodal metastasis and may help multidisciplinary teams as they look to consider de-escalating SLN surgery in breast cancer.

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.

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.

The nomogram, integrating CESM deep learning with clinical-pathological features, proved valuable for predicting NAC response in patients with ER-positive/HER2-negative breast cancer. Nomogram outperformed deep learning-based and clinical models.

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.

Patients with clinical stage II/III TNBC were treated with 5 cycles of anlotinib (12 mg, d1-14, q3w) plus 6 cycles of taxanes (docetaxel 75 mg/m2 ,d1, q3w or nab-paclitaxel 125 mg/m2, d1 and d8, q3w) and lobaplatin (30 mg/m2, d1, q3w), followed by surgery. The addition of anlotinib to neoadjuvant chemotherapy showed manageable toxicity and encouraging antitumor activity for patients with clinical stage II/III TNBC. Chongqing Talents Project, Chongqing Key Project of Technology Innovation and Application Development and Chongqing Outstanding Youth Natural Science Foundation.

P1/2, N=15, Completed, M.D. Anderson Cancer Center | Active, not recruiting --> Completed | Trial completion date: Dec 2025 --> Apr 2024 | Trial primary completion date: Dec 2025 --> Apr 2024

The SUVmax ratio of HER2-positive breast cancer brain metastases was significantly greater than that of HER2-negative lesions (3.98 vs 1.79, U = 38.00, p = 0.008). The SUVmax ratio may help to identify the HER2 status of breast cancer brain metastases, if validated prospectively.

P3, N=300, Recruiting, Institut Curie | Not yet recruiting --> Recruiting

P1, N=35, Active, not recruiting, M.D. Anderson Cancer Center | Phase classification: P1b --> P1

P2, N=23, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Feb 2024 --> Aug 2024

P1, N=33, Recruiting, Mayo Clinic | Trial completion date: Aug 2024 --> Aug 2027 | Trial primary completion date: Aug 2024 --> Aug 2027

P1/2, N=138, Not yet recruiting, Washington University School of Medicine

P2, N=100, Active, not recruiting, Sermonix Pharmaceuticals Inc. | Trial completion date: Feb 2024 --> Dec 2024 | Trial primary completion date: Feb 2024 --> Dec 2024

Pembrolizumab monotherapy achieved durable treatment responses. Patients with a high baseline T-cell clonality had prolonged disease control with pembrolizumab.

P2, N=46, Active, not recruiting, SOLTI Breast Cancer Research Group | Trial completion date: Nov 2024 --> May 2024 | Trial primary completion date: Dec 2023 --> Apr 2024