HR positive + HER-2 positive

These mechanisms collectively hinder tumor growth, immune evasion, and metastatic spread. By synthesizing recent findings and analyzing the impact of celecoxib on these pathways, this paper seeks to delineate the integrated approaches necessary for managing metastatic breast cancer effectively.

The binding energy range for these ligands against their respective targets was calculated to be between -15 and -5 kcal/mol. Finally, based on general and common rules in medicinal chemistry, we selected 2, 3, 3, and 8 new ligands with high priority for further studies in the EGFR+HER2, ER, NF-κB, and PR classes, respectively.

MammOnc-DB was developed to provide a unique resource for hypothesis generation and testing, as well as for the discovery of biomarkers and therapeutic targets. The platform also provides pre- and post-treatment data, which can help users identify treatment resistance markers and patient groups that may benefit from combination therapy.

P1/2, N=192, Active, not recruiting, Pfizer | Recruiting --> Active, not recruiting | Trial completion date: Dec 2026 --> Aug 2026 | Trial primary completion date: Dec 2026 --> Aug 2026

Although patients with SPBC have worse prognostic tumor characteristics, OS and CSS rates are better than patients with MPC.

While there is interest in applying local therapies to OM and OP breast cancer, the current randomized data does not back the routine use of surgery or SBRT, particularly when considering the potential for treatment-related toxicities. Future research should refine patient selection through advanced imaging and possibly explore these therapies specifically in patients with hormone receptor-positive or HER2-positive disease.

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.

In this review, we analyze the biology of HR-positive/HER2-positive breast cancer and summarize the evidence concerning the standard of care options both in neoadjuvant/adjuvant settings and in advanced disease. Additionally, we focus on new trials and drugs for HR-positive/HER2-positive breast cancer and the new entity: HER2-low breast cancer.

In our study, a third of patients with stage II-III hormone receptor-negative and HER2-positive breast cancer had a complete pathological response after only three cycles of neoadjuvant systemic therapy. A complete response on breast MRI could help identify early complete responders in patients who had hormone receptor negative tumours. An imaging-based strategy might limit the duration of chemotherapy in these patients, reduce side-effects, and maintain quality of life if confirmed by the analysis of the 3-year event-free survival primary endpoint. Better monitoring tools are needed for patients with hormone receptor-positive and HER2-positive breast cancer.

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

P1, N=43, Terminated, Massachusetts General Hospital | N=120 --> 43 | Recruiting --> Terminated; Interim analysis did not show the required cytokine induction by topical calcipotriene to justify continuation of the trial

Over the last decade, the median OS of patients with brain metastases at initial breast cancer diagnosis remained poor; however, a substantial minority survive 5 or more years, with rates higher in patients with HER2-positive tumors. In addition to tumor subtype, OS varied according to age, extracranial metastases, and sociodemographic factors.

Monochemotherapy (Docetaxel) plus dual-target (Trastuzumab and Pertuzumab) therapy remains the optimal choice among all first-line treatment options for ABC. The combination of trastuzumab with TKIs (Pyrotinib) demonstrated a significant improvement in PFS and ORR, but further data are warranted to confirm the survival benefit.

P1/2, N=240, Recruiting, Pfizer | Phase classification: P1b/2 --> P1/2

Support for third-party writing assistance for this abstract, provided by Content Ed Net (Shanghai) Co., Ltd., was funded by Shanghai Roche Pharmaceuticals Ltd., Shanghai, China; Background: With the approval of pertuzumab (P) in China in 2019, P plus trastuzumab (T) and chemotherapy has become a standard of care in the neoadjuvant setting for patients with HER2-positive (HER2+) early or locally advanced breast cancer (BC). Based on the largest nationwide database, strong representativeness and stability of our data sources, our findings are of great significance to clinical decision-making. The proportion of patients who underwent neoadjuvant therapy of HR+HER2+ BC is much lower than in many other countries, with T plus P in combination with chemotherapy appearing to be the most commonly used targeted regimen. We also found some distinctions between neoadjuvant patterns of early-stage BC in the real world of China and guidelines, which would be further explored in subsequent research.

The combination of anastrozole, palbociclib, trastuzumab, and pertuzumab was well tolerated and effective with a clinical benefit rate of 97% in pts with previously untreated HR-positive, HER2-positive MBC. The combination provides a chemotherapy-free alternative for pts with triple positive breast cancers. Further follow up will determine impact on PFS.

P1/2, N=337, Recruiting, Pfizer | Trial completion date: Feb 2026 --> Sep 2027 | Trial primary completion date: Feb 2026 --> Jul 2026

P1b/2, N=240, Recruiting, Pfizer | N=144 --> 240

According to the SUCRAs, Her2-mAb+Her2-tki+Chem and Her2-mAb+Her2-mAb+Chem ranked highest for PFS and OS, respectively. Subgroup analyses consistently supported these overall findings, indicating that dual-target therapy was the optimal approach irrespective of treatment line.

Supported by Pierre Fabre Background: Neratinib is an oral pan-HER tyrosine kinase inhibitor approved in Europe in adult patients with early-stage hormone receptor-positive (HR+) HER2-positive (HER2+) breast cancer who completed adjuvant trastuzumab-based therapy ≤ 1 year ago. This study will further characterize neratinib-related diarrhoea in patients with early breast cancer treated with extended adjuvant neratinib in Europe. It will also assess the impact of the educational materials provided. Additionally, the ancillary study will describe clinical outcomes at 2 years in a real-world setting.

All molecular subtypes of MBC had a poorer prognosis compared with IDC, NOS. The different molecular subtypes of MBC did not affect the BCSD. HR-positive MBC patients had a significantly higher high-risk RS than IDC, NOS patients.

P1b/2, N=144, Recruiting, Pfizer | Trial completion date: Jul 2027 --> Sep 2026

Prominent status of dual-targeted therapy for patients with HR+/HER2+ metastatic breast cancer was revealed. Compared with chemotherapy-containing regimens, the ET-containing ones showed better efficacy and similar safety profiles, which could be recommended in clinical practice.

Our preliminary results suggested that pyrotinib plus letrozole is feasible for the first-line treatment of patients with HR-positive and HER2-positive MBC, with manageable toxicities.

P1, N=16, Active, not recruiting, NantBioScience, Inc. | Unknown status --> Active, not recruiting | Trial completion date: Dec 2020 --> Dec 2025 | Trial primary completion date: Dec 2019 --> Jul 2025

P2, N=185, Recruiting, Baylor Breast Care Center | Not yet recruiting --> Recruiting

Combined HER2/ER blockade may be an effective treatment strategy for patients with HR+/HER2+ BC in the appropriate clinical setting(s). In this review, we provide an overview of crosstalk between the ER and HER2 pathways, summarize data from recently published and ongoing clinical trials, and discuss clinical implications for targeted treatment of HR+/HER2+ BC.

MpBCs are associated with poorer prognoses than IDC-NSTs. They are heterogeneous with different clinicopathological features and clinical outcomes between histological subtypes. Pure and with heterologous mesenchymal differentiation subtypes have more survival benefits than the mixed subtype.

P1b/2, N=144, Recruiting, Pfizer | Trial completion date: Dec 2027 --> Jul 2027 | Trial primary completion date: Dec 2026 --> Jul 2026

P1/2, N=337, Recruiting, Pfizer | N=198 --> 337

Regarding PFS, significant differences were detected between dual HER2 blockade plus endocrine therapy versus endocrine therapy alone (HR 0.45, 95% CrI 0.25-0.83; HR 0.47, 95% CrI 0.27-0.87), and trastuzumab, pertuzumab plus chemotherapy versus trastuzumab plus chemotherapy (HR 0.69, 95% CrI 0.47-0.96). Prominent status of dual-targeted therapy for patients with HR+/HER2+ metastatic breast cancer was revealed. Compared with chemotherapy-containing regimens, the endocrine therapy-containing regimens showed better efficacy and similar safety profile, which could be recommended in practice.

P1/2, N=198, Recruiting, Pfizer | N=337 --> 198

P1/2, N=337, Recruiting, Pfizer | Phase classification: P1 --> P1/2 | N=118 --> 337 | Trial completion date: Apr 2025 --> Feb 2026 | Trial primary completion date: Apr 2025 --> Feb 2026

The biological subtype of breast cancer with regional metastasis in most cases remains stable among the cases of the entire sample. Discordance of the subtype is most often observed in cases with a hormone receptor-negative Her2-positive subtype of the primary tumor.

We included in this analysis 784 patients with HR-positive/HER2-positive BC from the randomized ShortHER trial of adjuvant trastuzumab (1 year vs 9 weeks) + chemotherapy...In this post-hoc analysis of the ShortHER trial adjuvant treatment with AI was independently associated with improved DFS. Subgroup analysis in premenopausal patients suggests benefits with ovarian suppression.Trial registration: NCI ClinicalTrials.gov number: NCT00629278.

P2, N=144, Ongoing, Pfizer Inc.

P2, N=185, Not yet recruiting, Baylor Breast Care Center | Trial completion date: Jan 2028 --> Sep 2029 | Trial primary completion date: Oct 2025 --> Jun 2027

Recent research and clinical trials have revealed that a combination of endocrine therapy and anti-HER2 approaches without chemotherapy provides along-term disease control for some patients, but the challenge lies in how to accurately identify the subsets of patients who can benefit from such a de-chemotherapy treatment strategy. In this review, we aim to summarize the results of preclinical and clinical studies in HR+/HER2+ MBC and discuss the possibility of sparing chemotherapy in this subgroup of patients.

p-AKT1 (Ser473) is a prognostic marker for poor outcomes in patients with HR-positive/HER2-positive breast cancer and may have a potential value as a therapeutic target.

HR+HER2+ BC patients with BM treated with radiotherapy show a better prognosis than other subtypes. For HER2-positive patients with good prognosis, it may be important to continue HER2-targeted therapy appropriately after radiotherapy for BM.

Capecitabine maintenance treatment is associated with longer PFS in patients with MBC, especially those receiving first-line capecitabine-based chemotherapy and those with HR positivity/HER2 positivity. TP53 aberrations may be responsible for the poor response to capecitabine maintenance treatment.