UNASSIGNED: This study aims to provide a comprehensive assessment of economic and health-related quality of life (HRQoL) outcomes for human epidermal growth factor receptor 2 (HER2)-positive, early-stage breast cancer patients treated with trastuzumab-containing regimens, by focusing on both Incremental Cost-Effectiveness Ratios (ICERs) and quality-adjusted life years (QALYs).
UNASSIGNED: A systematic search was conducted across PubMed, Embase, and Scopus databases without language or publication year restrictions. Two independent reviewers screened eligible studies, extracted data, and assessed methodology and reporting quality using the Drummond checklist and Consolidated Health Economic Evaluation Reporting Standards 2022 (CHEERS 2022), respectively. Costs were converted to US dollars (US$) for 2023 for cross-study comparison.
UNASSIGNED: Twenty-two articles, primarily from high-income countries (HICs), were included, with ICERs ranging from US$13,176/QALY to US$254,510/QALY, falling within country-specific cost-effectiveness thresholds. A notable association was observed between higher QALYs and lower ICERs, indicating a favorable cost-effectiveness and health outcome relationship. EQ-5D was the most utilized instrument for assessing health state utility values, with diverse targeted populations.
UNASSIGNED: Studies reporting higher QALYs tend to have lower ICERs, indicating a positive relationship between cost-effectiveness and health outcomes. However, challenges such as methodological heterogeneity and transparency in utility valuation persist, underscoring the need for standardized guidelines and collaborative efforts among stakeholders.
UNASSIGNED: PROSPERO ID: CRD42021259826.

UNASSIGNED: In recent years, novel therapies targeting specific molecular pathways and immunotherapies have exhibited promising outcomes for treating human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Our work aimed to assess the effectiveness and safety of these emerging treatment regimens for this disease.
UNASSIGNED: We systematically searched databases including PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials their inception to August 2023 to identify relevant randomized controlled trials (RCTs). The quality of eligible RCTs was evaluated with the Cochrane risk-of-bias tool, version 2 (RoB2). Investigated outcomes encompassed progression-free survival (PFS), overall survival (OS), disease-free survival (DFS), pathologic complete remission (pCR), and adverse events (AEs). They were expressed as hazard ratio (HR) with 95% conference intervals (CI) or risk ratio (RR) with 95% CI.
UNASSIGNED: Our analysis identified a total of 28 RCTs suitable for inclusion in the NMA. Regarding the PFS, all these treatment regimens exhibited comparable effectiveness. In terms of OS, Capecitabine+Trastuzumab, Lapatinib+Trastuzumab and Pyrotinib+Capecitabine exhibited better effect compared to other treatments. Regarding pCR and AEs, all these treatment regimens exhibited comparable effectiveness, especially Lapatinib+Trastuzumab and Pyrotinib+Capecitabine.
UNASSIGNED: Our study highlights the prominent role of targeted therapies and immunotherapies in treating HER2-positive breast cancer. The efficacy of trastuzumab-containing regimens was superior to other treatment options, while maintaining a comparable safety profile. Based on these findings, trastuzumab-containing regimens emerge as a preferable and recommended choice in clinical practice for managing HER2-positive breast cancer.
UNASSIGNED: PROSPERO, identifier CRD42023414348.

The tumor biology of human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) promotes the development of central nervous system (CNS) metastases, with 25% of patients with HER2-positive BC developing CNS metastases. Furthermore, the incidence of HER2-positive BC brain metastases has increased in the last decades, likely because of the improved survival with targeted therapies and better detection methods. Brain metastases are detrimental to quality of life and survival and represent a challenging clinical problem, particularly in elderly women, who comprise a substantial proportion of patients diagnosed with BC and often have comorbidities or an age-related decline in organ function. Treatment options for patients with BC brain metastases include surgical resection, whole-brain radiation therapy, stereotactic radiosurgery, chemotherapy, and targeted agents. Ideally, local and systemic treatment decisions should be made by a multidisciplinary team, with input from several specialties, based on an individualized prognostic classification. In elderly patients with BC, additional age-associated conditions, such as geriatric syndromes or comorbidities, and the physiologic changes associated with aging, may impact their ability to tolerate cancer therapy and should be considered in the treatment decision-making process. This review describes the treatment options for elderly patients with HER2-positive BC and brain metastases, focusing on the importance of multidisciplinary management, the different points of view from the distinct disciplines, and the role of oncogeriatric and palliative care in this vulnerable patient group.

Small tyrosine kinase inhibitors (TKIs) show activity against breast cancer brain metastases (BCBM) of the human epidermal growth factor receptor 2 (HER2)-positive subtype. This meta-analysis aimed to objectively explore the efficacy and safety of TKIs.
Electronic databases were searched for relevant clinical trials. We conducted a pairwise meta-analysis, pooled analysis, and estimated summary survival curves to compare survival outcomes following TKIs therapy for BCBM patients using Stata version 16.0 or R x64 4.0.5.
Thirteen clinical trials involving 987 HER2-positive BCBM patients were analyzed. A trend of longer progression-free survival (PFS) was observed in the TKI-containing arm compared to the non-TKI-containing arm (hazard ratio = 0.64, 95% confidence interval [CI]: 0.35-1.15, p = 0.132), although the difference is not statistically significant. Summary survival curves reported the summary median PFS and overall survival were 7.9 months and 12.3 months. Subgroup analysis revealed that TKIs combined with capecitabine (TKI + Cap) regimens resulted in improved survival outcomes. Tucatinib may be more effective in BCBM patients. The main grade 3-5 adverse events (AEs) were diarrhea (22%, 95% CI: 14%-32%), neutropenia (11%, 95% CI: 5%-18%), hepatic toxicity (7%, 95% CI: 1%-16%), and sensory neuropathy (6%, 95% CI: 2%-12%).
TKIs therapy improved the survival outcomes of HER2-positive BCBM patients, especially when combined with capecitabine and tolerable AEs. We also identified the clinical value of tucatinib, which appears to be the most favorable TKI drug for BCBM patients.

UNASSIGNED: Human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer patients continue to progress despite multiple anti-HER2-targeted treatments. A number of studies have found that Pyrotinib, a small-molecule pan-ErbB receptor tyrosine kinase inhibitor (TKI), is effective in treating patients with HER2-positive metastatic breast cancer. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of Pyrotinib in the treatment of HER2-positive metastatic breast cancer.
UNASSIGNED: PubMed, Embase, Web of Science, and Cochrane Library databases were searched until February 2022. Research on HER2-positive metastatic breast cancer being treated with Pyrotinib in any line of therapy was included, both prospective and retrospective. Statistical pooling and meta-analysis of data from the included studies were performed to explore the efficacy and safety of Pyrotinib in HER2-positive metastatic breast cancer.
UNASSIGNED: In this meta-analysis, 23 studies were included. The overall objective response rate was 0.49 (95% CI: 0.40, 0.58) for Pyrotinib in HER2-positive metastatic breast cancer and 0.52 (95% CI: 0.32, 0.71) in those with brain metastases. The objective response rate of Pyrotinib was superior to that of other second-line therapeutics in comparison (RR =1.38, 95% CI: 1.25, 1.52), but was relatively inferior to trastuzumab emtansine (T-DM1) (RR =0.82, 95% CI: 0.36, 1.85). The combined median progression-free survivals (PFSs) for Pyrotinib in metastatic breast cancer and those with brain metastases were 8.2 (95% CI: 6.8, 9.5) months and 8.9 (95% CI: 6.2, 11.7) months, respectively. The most common adverse reaction was diarrhea with an all-grade incidence of 0.84 (95% CI: 0.74, 0.92), followed by nausea and vomiting of 0.52 (95% CI: 0.36, 0.68).
UNASSIGNED: In any line of treatment for HER2-positive metastatic breast cancer, the Pyrotinib-containing regimens demonstrated considerable tumor response, disease control, and survival with manageable adverse effects.

Approximately 15-20% of breast carcinomas exhibit human epidermal growth factor receptor (HER2) protein overexpression. HER2-positive breast cancer (BC) is a heterogeneous and aggressive subtype with poor prognosis and high relapse risk. Although several anti-HER2 drugs have achieved substantial efficacy, certain patients with HER2-positive BC relapse due to drug resistance after a treatment period. There is increasing evidence that BC stem cells (BCSCs) drive therapeutic resistance and a high rate of BC recurrence. BCSCs may regulate cellular self-renewal and differentiation, as well as invasive metastasis and treatment resistance. Efforts to target BCSCs may yield new methods to improve patient outcomes. In the present review, the roles of BCSCs in the occurrence, development and management of BC treatment resistance were summarized; BCSC-targeted strategies for the treatment of HER2-positive BC were also discussed.

UNASSIGNED: Metaplastic breast cancer (MBC) is an extremely rare malignant breast disease that has rarely been reported. The molecular subtype of MBC is mostly triple-negative, with a high recurrence rate and a worse prognosis. Due to its low HR- and HER2-positive rate, reports on endocrine and targeted therapy are very limited.
UNASSIGNED: We report a case of infrequent triple-negative MBC, which, although at an early stage, quickly developed multiple recurrent lesions in the chest wall. The tumor relapsed repeatedly after comprehensive treatment, including surgery, chemotherapy and radiotherapy. However, pathological results after the third surgery suggested that the molecular subtype had changed from triple-negative to HER2-positive. The previous comprehensive treatment had not been able to effectively control the disease, but the patient achieved a long progression-free survival time through chemotherapy and trastuzumab targeted therapy after the subtype change. To date, there has been no recurrence for over eight years.
UNASSIGNED: Among repeatedly relapsed MBC patients, further investigation should be taken into consideration. As in the case presented in our study, it is possible that the HER2 status can convert from negative to overexpression. Moreover, for HER2-positive MBC patients, anti-HER2 therapy is recommended. The decision-making process requires multidisciplinary involvement.

UNASSIGNED: Although dual anti-HER2 therapy, namely, pertuzumab plus trastuzumab, has shown promising results in patients with HER2-positive breast cancer (BC), it is still unclear whether dual therapy will increase adverse effects (AEs) while ensuring the efficacy compared with trastuzumab monotherapy. We conducted a systematic review and meta-analysis to compare the efficacy and safety of combined therapy with monotherapy.
UNASSIGNED: A systematic search was performed to identify eligible randomized controlled trials (RCTs) that evaluated the administration of dual anti-HER2 therapy [pertuzumab plus trastuzumab or trastuzumab emtansine (T-DM1)] versus monotherapy (trastuzumab or T-DM1). The primary endpoints were overall survival (OS) and progression-free survival (PFS).
UNASSIGNED: Fourteen RCTs (8,378 patients) were identified. Compared to monotherapy, dual therapy significantly improved the OS (HR = 0.77, 95% CI: 0.59-0.99) and PFS (HR = 0.74, 95% CI: 0.63-0.86) in advanced BC. In neoadjuvant therapy, dual blockade has a higher ORR rate than monotherapy. Grade 3 or higher febrile neutropenia, diarrhea, and anemia as well as heart failure were more frequently reported in dual therapy compared to monotherapy. No significant difference in serious AEs was observed between the two groups. In the subgroup analysis, compared to single-target therapy, dual-target therapy has higher OS and PFS rates in Asian patients with advanced therapy; however, total grade ≥3 AEs and serious AEs were significantly higher in the dual group in Asian patients.
UNASSIGNED: Our study confirms that the combination of pertuzumab and trastuzumab therapy could substantially improve the outcome of patients with HER2-positive breast cancer and was well tolerated compared to trastuzumab monotherapy.

BACKGROUND: Pathogenic variants (PVs) in BRCA1/2 genes account for ∼6% of breast and 20% of ovarian cancers. Most breast tumors developed by BRCA1 carriers are triple negative. BRCA2 tumors have similar rates of estrogen receptor positivity as sporadic controls but are less likely to be human epidermal growth factor receptor 2 (HER2)-positive. Prevalence of HER2 positivity among breast cancers (BCs) in BRCA1/2 mutation carriers is poorly and variably described, ranging from 0% to 10% and 0% to 13% in BRCA1 and BRCA2 carriers, respectively.
METHODS: We assessed the prevalence of HER2 positivity among a single institutional cohort of 398 BCs developed in carriers of BRCA1/2 PVs (240 BRCA1, 158 BRCA2). Subsequently, a systematic review of the literature and pooled analysis was carried out.
RESULTS: In our series we found a 7% HER2 positivity rate among all first BRCA1/2 BCs overall. In BRCA1 carriers, 5.4% of BCs were HER2-positive compared with 9.5% in BRCA2-mutated patients. Among bilateral BCs, HER2-positive cases were 15.2% in the BRCA1 group and 23.1% in the BRCA2 group. Notably, six BRCA1 and eight BRCA2 carriers showed discordant HER2 status between BC and bilateral BC (23.7%, 14/59). The systematic review included 21 083 BRCA1/2 patients from 73 eligible studies. The pooled rate of BRCAmut/HER2-positive BCs is 9.1% (95% confidence interval 7.3% to 11.2%). BRCA1 and BRCA2 when reported as separate data ranged from 0% to 33.3% (mean 8.3%) and from 0% to 86% (mean 10.3%), respectively.
CONCLUSIONS: As compared with sporadic cases, BCs occurring in BRCA1 and/or BRCA2 PVs carriers are less frequently HER2-positive. Prevalence of HER2 positivity in our series was consistent with pooled analysis and did not exceed 10%. Although not common, co-existence of BRCA mutations and HER2 overexpression and/or gene amplification should be acknowledged. More research is needed to better characterize this subgroup of patients who should not be excluded a priori from clinical trials of targeted therapy for BRCA1/2-driven cancers.

Since the advent of anti-HER2 therapies, evidence surrounding adjuvant treatment of small (T1mic, T1a, and T1b), node-negative, HER2-positive breast cancer (HER2+ BC) has remained limited. Practices vary widely between institutions with little known regarding the added benefit of systemic therapy, including cytotoxic chemotherapy and HER2-directed treatments. Our group has set out to perform an extensive review of available literature on this topic.
In this review, we examined HER2 biology, anti-HER therapies, outcome definitions, and available prospective and retrospective data surrounding the use of adjuvant therapy in those with small, node-negative, HER2+ BC. For outcomes, we primarily explored breast cancer-specific survival (BCSS), invasive disease-free survival (iDFS), and overall survival (OS). We also investigated the incidence of adverse events with a particular focus on symptomatic and asymptomatic declines in ejection fraction.
Retrospective data will likely be the main driver for future treatment decisions. Given what we know, high-risk T1b and T1c subgroups derive measurable added benefit from HER2-guided combination therapies but it\'s not clear whether these benefits outweigh known risks associated with this combination therapy. For tumors ≤0.5 cm (T1mic and T1a), treatment remains highly controversial with limited evidence available through retrospective analysis that suggest over-treatment may be occurring.