Background: Antibody-drug conjugates (ADCs) have been the preferred regimens for human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) after trastuzumab. Unfortunately, there is little data showing which ADCs should be chosen for those patients whose treatment with tyrosine kinase inhibitors (TKIs) failed. This study aims to analyze the efficacy and safety between novel anti-HER2 ADCs and trastuzumab emtansine (T-DM1) for those with TKIs failure. Materials and methods: HER2-positive MBC using ADCs from January 2013 to June 2022 were included, and all of them were treated with TKIs. The primary study endpoint was progression-free survival (PFS), and the secondary study endpoints were objective response rate (ORR), clinical benefit rate (CBR), and safety. Results: A total of 144 patients with 73 patients in the novel anti-HER2 ADCs group and 71 patients in the T-DM1 group. In these novel ADCs, 30 patients received trastuzumab deruxtecan (T-Dxd), 43 patients receive other novel ADCs. The median PFS in the novel ADCs group and T-DM1 group were 7.0 months versus 4.0 months, respectively, and ORR was 54.8% versus 22.5%, CBR was 65.8% versus 47.9%, respectively. In subgroups analysis, the PFS were both significantly improved in patients receiving T-Dxd and other novel ADCs compared with T-DM1. The most common grades 3-4 adverse events in the novel anti-HER-2 ADCs group were neutropenia (20.5%) and thrombocytopenia (28.1%) in the T-DM1 group. Conclusions: In patients with HER2-positive MBC previously treated with TKIs, both T-Dxd and other novel anti-HER2 ADCs yielded statistically significant better PFS than T-DM1 did, with tolerable toxicities.

The EGFR-RAS-ERK pathway plays a key role in cancer development and progression. However, the integral assembly of EGFR-RAS-ERK signaling complexes from the upstream component EGFR to the downstream component ERK is largely unknown. Here, we show that hematopoietic PBX-interacting protein (HPIP) interacts with all classical components of the EGFR-RAS-ERK pathway and forms at least two complexes with overlapping components. Experiments of HPIP knockout or knockdown and chemical inhibition of HPIP expression showed that HPIP is required for EGFR-RAS-ERK signaling complex formation, EGFR-RAS-ERK signaling activation, and EGFR-RAS-ERK signaling–mediated promotion of aerobic glycolysis as well as cancer cell growth in vitro and in vivo. HPIP expression is correlated with EGFR-RAS-ERK signaling activation and predicts worse clinical outcomes in patients with lung cancer. These results provide insights into EGFR-RAS-ERK signaling complex formation and EGFR-RAS-ERK signaling regulation and suggest that HPIP may be a promising therapeutic target for cancer with dysregulated EGFR-RAS-ERK signaling.

Background: Taxanes combined with trastuzumab plus either pertuzumab (THP) or pyrotinib (THPy) are standard first‐line treatments for HER2‐positive metastatic breast cancer (HER2+ MBC). Nevertheless, direct comparative evidence remains insufficient. This study compared the efficacy and safety of THP vs. THPy for HER2+ MBC. Methods: The multicenter retrospective study comprised patients treated in first‐line with either THP or THPy from January 2018 to March 2025. Confounding factors were adjusted using 1:1 propensity score matching (PSM) and multivariable Cox regression. Progression‐free survival (PFS) was the primary endpoint, with clinical benefit rate (CBR), objective response rate (ORR), and safety as secondary endpoints. Results: A total of 411 patients were enrolled (THP: 148; THPy: 263). After matching, 139 pairs formed. Before PSM, patients in the THPy group experienced a longer median PFS than those in the THP group (23.6 vs. 19.3 months, HR = 0.72, 95% CI: 0.53–0.97, p = 0.031). After PSM, THPy still provided a PFS benefit (23.6 vs. 17.3 months, HR = 0.68, 95% CI: 0.48–0.97, p = 0.033), with an adjusted HR of 0.44 (95% CI 0.30–0.66, p < 0.001). Before PSM, the THPy group had a lower ORR than the THP group (69.2% vs. 81.1%, p = 0.009), but after PSM, this disparity in ORR was no longer significant (74.1% vs. 79.9%, p = 0.254), and CBR remained comparable between the two groups throughout. THPy showed potential PFS benefit in the subgroup with de novo stage IV disease and liver metastasis. Gastrointestinal toxicities were more common in the THPy group, with diarrhea being the most prominent (any grade: 76.1%; grade ≥ 3: 22.7%). Conclusions: THPy may provide PFS benefit over THP in HER2+ MBC, with suggestive advantages in patients with de novo stage IV disease and liver metastasis. A higher frequency of diarrhea and other gastrointestinal toxicities was observed in the THPy regimen.

Background/Objectives: Hormone receptor-positive, HER2-negative breast cancer is the most common subtype, with endocrine therapy as the standard treatment. Despite the advancements in adjuvant endocrine therapy, recurrence remains a challenge, particularly in high-risk patients. Recent trials on cyclin D kinase 4/6 (CDK4/6) inhibitors in adjuvant therapy have shown promise in reducing early recurrence and improving survival. Methods: This review analyzes the clinical evidence supporting the use of CDK4/6 inhibitors, focusing on the NATALEE and monarchE trials, which demonstrate comparable efficacy and manageable safety profiles for ribociclib and abemaciclib. Results and Conclusions: Ribociclib, with its broader applicability and impact on the decision making for axillary lymph node surgery, may be the preferred option in high-risk populations. The review also addresses unanswered clinical questions and highlights the need for ongoing research to optimize the adjuvant therapy strategies.

In this study, we aimed to explore the safety and vaccination coverage data of Chinese patients with breast cancer receiving coronavirus disease 2019 (COVID-19) vaccination. The patients were recruited from 41 hospitals across 20 Chinese provinces. The vaccination coverage was approximately 22.4%, and the frequency of total adverse events was 13.3% after the first dose and 9.9% after the second dose. The most frequent adverse reaction within 14 days of the first dose was local pain (5.7%). Unvaccinated patients were very likely to reject the vaccine rather than be hesitant in patients with old age (odds ratio [OR], 1.238; 95% confidence interval [CI], 1.101–1.391), chronic disease history (OR, 1.189; 95% CI, 1.057–1.337), and cancer relapse (OR, 1.398; 95% CI, 1.233–1.585). Of the unvaccinated patients with breast cancer, 54.1% opted to receive COVID-19 vaccines if more data were available. Considering the safety but low vaccination coverage for breast cancer, increased positive attitudes and acceptance toward COVID-19 vaccines are important.

Journal of Medical Internet Research - International Scientific Journal for Medical Research, Information and Communication on the Internet #Preprint #PeerReviewMe: Warning: This is a unreviewed preprint. Readers are warned that the document has not been peer-reviewed by expert/patient reviewers or an academic editor, may contain misleading claims, and is likely to undergo changes before final publication, if accepted, or may have been rejected/withdrawn. Readers with interest and expertise are encouraged to sign up as peer-reviewer, if the paper is within an open peer-review period. Please cite this preprint only for review purposes or for grant applications and CVs (if you are the author). Background: `The widespread vaccination of the novel coronavirus vaccine (COVID-19 vaccine) has become one of the most likely effective means to end the COVID-19 pandemic. Tumor patients with high risk of infection, high incidence of serious events and high mortality should be the focus of epidemic prevention and treatment in the setting of COVID-19. But real-world data on the safety of vaccination for breast cancer patients are still unknown. Objective: This study aims to further analyze the safety of COVID-19 vaccine in vaccinated breast cancer patients. Methods: In the CSCO BC NCP-02 study, breast cancer patients who seek medical advice from October 2021 to December 2021were screened, from whom the vaccinated patients were enrolled in order to analysis the safety of vaccination. Results: The CSCO BC NCP-02 study screened 5766 patients who received COVID-19 vaccine, 45.1% (2599/5766) of the population were vaccinated before diagnosis of breast cancer, 41.3% (2379/5766) of the population were vaccinated after diagnosis of breast cancer, and the time of vaccination or diagnosis in 13.6% (784/5766) of the patients was unknown. Among breast cancer patients, 85.4% (2032/2379) were vaccinated one year after breast cancer diagnosis, and 95.4% (2270/2379) were vaccinated in the early breast cancer stage. Of all patients, 93.9% (5415/5766) received inactivated vaccine, 3.7% received recombinant subunit vaccine, 2.4% received other vaccines, including adenovirus and mRNA vaccine. In the first dose, the highest incidence of AE was 24.4% (95%CI, 11.2-37.5) for these received adenovirus vaccine. The lowest was 12.5% (95%CI: 11.6-13.4) for these received inactivated vaccines. In the second dose, both inactivated vaccines (8.7%, 95%CI:8.0-9.5) and recombinant vaccine (8.7%, 95%CI:5.5-12.0) showed the same incidence of AEs. Patients with metastatic breast cancer had the highest incidence of AEs (16.5%, 95%CI:9.5-23.5) at the first dose. The total incidence of AE vaccinated before and after diagnosis of breast cancer was 16.4% and 16.9%, respectively. The most common AEs were local pain (11.1% vs 9.1%), fatigue (5.5% vs 6.3%) and muscle soreness (2.3% vs 3.6%). The type of vaccines (OR=0.937,95% CI：0.689-1.273) and time window of vaccination (OR=0.919,95% CI：0.785-1.077) did not affect the incidence of AEs. Conclusions: Compared with the patients vaccinated before diagnosis of breast cancer, the incidence of AEs of COVID-19 vaccine in breast cancer patients was not significantly increased. It is safe for these breast cancer patients to receive COVID-19 vaccines. Clinical Trial: ChiCTR2200055509