Axillary staging is commonly performed in patients with clinically node-positive (cN+) breast cancer undergoing neoadjuvant chemotherapy (NACT), regardless of pathological complete response (pCR). Recent evidence has suggested that ypT0 correlates with ypN0 and favorable prognosis, potentially supporting the omission of axillary staging in such cases. This study aimed to evaluate ypT0 as a predictive factor for ypN status and its prognostic significance in cN+ breast cancer treated with NACT.

This retrospective study included 302 patients with cN+ breast cancer treated with NACT at Hiroshima University Hospital between 2006 and 2022. Patients were categorized into non-pCR, ypTis, or ypT0 based on ypT status. Associations between breast pCR, ypN status, recurrence-free survival (RFS), and overall survival (OS) were analyzed.

Among 302 patients (non-pCR, 74.2%; ypTis, 8.9%; ypT0, 16.9%), the ypN+ rates were 63.3%, 15.2%, and 3.9%, respectively. Logistic regression revealed significant associations among ypT0, ypTis, and ypN0. The five-year RFS and OS rates were 78.6% and 85.2% (non-pCR), 83.8% and 95.5% (ypTis), and 98.0% and 100.0% (ypT0), respectively. Cox regression identified ypT0, but not ypTis, as a significant prognostic factor for both RFS and OS.

ypT0 status was associated with a low risk of ypN+ and favorable clinical outcomes in cN+ breast cancer, suggesting the potential feasibility of omitting axillary surgery in select patients.

Dual HER2 blockade with trastuzumab and pertuzumab combined with neoadjuvant chemotherapy improves outcomes in HER2-positive breast cancer. The optimal taxane backbone (paclitaxel vs. docetaxel) remains unclear.

This retrospective study included 220 HER2-positive breast cancer patients treated with anthracycline-based chemotherapy followed by dual HER2 blockade with trastuzumab, pertuzumab, and either paclitaxel (80 mg/m2 for 12 weeks) or docetaxel (75 mg/m2 every three weeks for four cycles). Pathological complete response (pCR), disease-free survival (DFS), overall survival (OS), and toxicity profiles were analyzed.

At the time of diagnosis, 6% of the patients included in the study were at stage I, 70.4% were at stage II, and 23.6% were at stage III. The overall pCR rate was 55%, with no significant difference between the paclitaxel (57.9%) and docetaxel (52.2%) groups (p = 0.418). Higher pCR rates were associated with grade 3 tumors, ER/PR negativity, and Ki- 67 ≥ 20%. Patients achieving pCR had significantly lower relapse rates (2.5% vs. 16.2%, p < 0.001). These factors were significantly associated with pCR in univariate analysis but did not remain independent predictors in multivariate analysis. DFS and OS were higher in the paclitaxel group compared to the docetaxel group (DFS: 96.3% vs. 83.2%, p = 0.025; OS: 100% vs. 95.5%, p = 0.042). Grade 3-4 anemia was more frequent with docetaxel (23% vs. 9%, p = 0.007).

Both paclitaxel and docetaxel are effective in neoadjuvant dual HER2 blockade regimens. Paclitaxel demonstrated better DFS, OS, and a favorable safety profile, supporting its use as a preferred option.

The objective of this systematic review is to investigate the role of imaging in response monitoring during neoadjuvant systemic therapy (NST) for breast cancer and assess whether treatment modifications based on imaging response are implemented in clinical practice.

A systematic review was conducted, analyzing five clinical practice guidelines and 147 clinical trial publications involving NST for breast cancer. The snowballing technique was employed, using a "start set" of clinical guidelines to trace relevant trials. Additionally, a PubMed search was conducted to identify trials published between 2023-2024. The review analyzed the use of imaging modalities, timing, and response criteria, and whether escalation, de-escalation, or change of treatment occurred based on imaging response.

Imaging was utilized in 81 % (119/147) of the trials, with ultrasound, MRI, and mammography being the most frequently employed modalities. Mid-treatment imaging was applied in 56 % (83/147) of the trials. However, only 15 % (22/147) of the trials implemented treatment modifications based on imaging response, highlighting the limited application of imaging response-guided therapy. No standardized imaging protocols or consistent response-guided treatment strategies were identified across the trials or clinical practice guidelines, with considerable variability in imaging methods, timing, and response criteria.

This systematic review underscores the critical need for standardized imaging protocols, response assessment criteria and image-guided treatment decisions. It is therefore evident that imaging for response monitoring during treatment should preferably be performed within clinical trials.

The combination of inetetamab and vinorelbine has demonstrated survival benefits with an acceptable toxicity profile in HER2+ metastatic breast cancer (MBC) patients. This multicenter, single-arm, phase II trial further evaluates the efficacy of inetetamab combined with pertuzumab and nab-paclitaxel as neoadjuvant therapy. Treatment-naïve patients with HER2+ early-stage or locally advanced BC received four cycles of intravenous inetetamab (8 mg/kg loading dose, then 6 mg/kg for subsequent doses), intravenous pertuzumab (840 mg loading dose, then 420 mg for subsequent doses), and weekly nab-paclitaxel (125 mg/m2). The primary endpoint was the total pathological complete response (tpCR) rate, defined as ypT0/is and ypN0, assessed by independent central review. From March 2023 to February 2024, 62 patients were enrolled, with the majority (61/62) completing 4 cycles of neoadjuvant therapy. The tpCR rate was 56.5% (95% CI: 43.3%-69.0%). Further analysis showed that patients with estrogen receptor (ER) negative tumors derived greater benefit, with a tpCR rate of 90.9%. The objective response rate was 90.3% (95% CI: 80.1%-96.4%). The most common grade 3 or higher adverse events were neutropenia (32.3%), decreased white blood cell count (19.4%), infectious pneumonia (3.2%), anemia (3.2%), and diarrhea (3.2%). No death occurred during the neoadjuvant treatment. Neoadjuvant treatment with inetetamab, in combination with pertuzumab and nab-paclitaxel, demonstrates good efficacy and tolerability, especially in ER-negative patients.

Background: Breast cancer can be classified based on the immunohistochemistry (IHC) phenotypes, defined by the presence or absence of the main IHC markers. IHC phenotyping is important as it determines the prognosis and guides treatment. For example, human epidermal growth factor receptor 2 (HER2) overexpression, which triggers cell growth and division, is observed in HER2-positive breast cancer. Methods: The standard treatment is based on trastuzumab plus pertuzumab in combination with taxane chemotherapy. The possibility of developing metastases depends on those phenotypes. Approximately 25-50% of patients with HER2-positive breast cancer experience brain metastases. This aspect is especially important, as 20% of those patients die as a result. Results: Through the years, many advanced therapies have been introduced to treat brain metastases, including whole brain radiotherapy, stereotactic radiosurgery, and a tyrosine kinase inhibitor (TKI), neratinib. Nonetheless, this still remains a therapeutic challenge. Conclusions: In this review, we focus on the treatment and efficiency of therapies targeting HER2-positive breast cancer, mainly concentrating on the current and newly developed treatment options for brain metastases, such as trastuzumab deruxtecan and tucatinib.

Previous studies indicate that HER2 protein expression and hormone receptor (HoR) status affect the sensitivity of HER2-positive breast cancer to neoadjuvant therapy, but it is unclear if sensitivity varies among subgroups defined by HER2 and HoR status. We examined 2 cohorts of patients, aged 18 to 80 years, with HER2-positive early breast cancer who underwent neoadjuvant therapy followed by surgery between January 1, 2009, and December 31, 2022: cohort 1 included 2648 patients, and cohort 2 had 141 patients with RNA expression data. Patients were divided into 4 groups based on immunohistochemical HER2 and HoR status: HER2(3+)/HoR-, HER2(3+)/HoR+, HER2(2+)/HoR-, and HER2(2+)/HoR+. We evaluated total pathological complete response (TpCR, defined as ypT0/is ypN0) rates, disease-free survival (DFS), and variations in PAM50 intrinsic subtypes across different subgroups. In cohort 1, HER2(3+)/HoR- had a higher TpCR rate (44.5%) than HER2(3+)/HoR+ (33.8%) (P < .001), HER2(2+)/HoR- (31.7%) (P = .013), and HER2(2+)/HoR+ (13.8%) (P < .001). DFS was similar across groups (P = .445). Trastuzumab or trastuzumab plus pertuzumab significantly improved TpCR rates and DFS in HER2(3+)/HoR- and HER2(3+)/HoR+ but not in HER2(2+)/HoR- and HER2(2+)/HoR+. Cohort 2 showed significant PAM50 subtype differences across these groups (P < .001). In conclusion, the responsiveness of HER2-positive breast cancer to neoadjuvant targeted therapy is significantly influenced by HER2 expression levels and HoR status, emphasizing the necessity of precision medicine approaches to tailor therapeutic strategies for improved clinical outcomes.

Tumor-infiltrating lymphocytes (TILs) have emerged as predictive biomarkers in HER2-positive breast cancer, correlating with treatment response and survival outcomes. This study evaluates the impact of TIL levels and Ki67 suppression on neoadjuvant therapy efficacy in this patient population.

A retrospective analysis of 136 HER2-positive breast cancer patients was conducted. Patients were stratified by TIL levels, and clinical outcomes, including Ki67 expression, pathological complete response (pCR), and disease-free survival (DFS), were assessed.

High TIL levels (≥ 40%) were significantly associated with higher pCR rates (60.32% vs. 39.73%, P = .02) and with TIL ≥ 10% greater Ki67 suppression. In patients with low TIL levels, high Ki67 expression correlated with better pCR rates (57.1% vs 30.8%, P = 0.010), while in high TIL patients, no significant difference was observed between high and low Ki67 groups (P = 0.317). A trend toward improved DFS was noted in the high TIL group, with 3-year survival rates of 91.9% vs. 80.7% in the low TIL group, though this was not statistically significant (P = .062).

TIL levels are robust predictors of pCR and Ki67 suppression in HER2-positive breast cancer, particularly in patients with high initial TILs. These findings highlight the potential for integrating TIL evaluation into personalized treatment strategies to optimize neoadjuvant therapy outcomes. Further research is warranted to validate these results and explore underlying mechanisms.

The efficacy of neoadjuvant therapy (NAT) comprising dual-target drugs has been confirmed among patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC). Therefore, we explored the differences in responses to NAT and prognosis between patients with HER2(3+) and HER2(2+)/fluorescence in-situ hybridization (FISH)-positive BC after TCbHP-based dual-target NAT.

Data from patients with HER2-positive invasive BC who underwent NAT and radical surgery between January 2019 and December 2022 at the Peking University First Hospital and Cancer Hospital of Chinese Academy of Medical Sciences were retrospectively summarized. Propensity score matching (PSM) was used to reduce confounding effects. Pathological complete response (pCR) and invasive disease-free survival (IDFS) were evaluated to respectively reflect therapeutic response and patients' survival status.

We selected 132 BC patients (66 pairs) through PSM form a cohort of 308 patients. The pCR rate of patients in the HER2(3+) group was significantly higher than that in the HER2(2+)/FISH-positive group after NAT (P<0.001). Univariate and multivariate logistic regression analyses determined that pCR was significantly affected by tumor grade, hormone receptor (HR) status, HER2 status (P<0.05). The 3-year IDFS rate of HER2(3+) BC patients was better than that of HER2(2+)/FISH-positive BC patient (P=0.083), although the difference was not statistically significant. Furthermore, multivariable Cox regression analysis exhibited that positive lymph node, HER2(3+), and pCR were independent prognostic factors for IDFS.

HER2(2+)/FISH-positive BC patients exhibited worse treatment response and prognosis than HER2(3+) BC patients after dual-target NAT, indicating that HER2 expression level is a crucial factor influencing the therapeutic efficacy and prognosis of BC patients after TCbHP-based dual-target NAT.

The area of residual tumor (ART) is a quantitative method for assessing tumors after neoadjuvant chemotherapy (NAC). This study evaluated whether ART can identify a favorable prognosis group in patients with HER2-positive surgically resected breast cancer and residual tumors post-NAC.

We retrospectively reviewed patients with HER2-positive who underwent surgery after NAC, including trastuzumab, from 2005 to 2022 at our institution. ART was assessed at the maximum cut surface of the residual primary tumor using digital pathology images. Receiver operating characteristic curve analysis determined ART-Low and ART-High cutoffs, excluding ART-0 (0 mm2) patients.

Of the 219 patients, 82 had ART greater than 0 mm2. The median follow-up was 90.2 months. The number of patients in the ART-0, ART-Low (0 < ART ≤ 4.0 mm2), and ART-High (> 4.0 mm2) groups were 137, 39, and 43, respectively. The ART-Low group showed significantly shorter event-free survival compared to the ART-0 group (HR 3.50, 95% CI 1.52-8.06), and the ART-High group also tended toward poorer prognosis (HR 2.31, 95% CI 0.89-5.97). However, there was no significant difference in prognosis between the ART-Low and ART-High groups.

The current study suggests that even minimal residual tumor cells in the primary site can significantly impact on prognosis in HER2-positive early breast cancer.

To construct and validate an interpretable machine learning (ML) radiomics model derived from multiparametric magnetic resonance imaging (MRI) images to differentiate between luminal and non-luminal breast cancer (BC) subtypes.

This study enrolled 1098 BC participants from four medical centers, categorized into a training cohort (n = 580) and validation cohorts 1-3 (n = 252, 89, and 177, respectively). Multiparametric MRI-based radiomics features, including T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC), and dynamic contrast-enhanced (DCE) imaging, were extracted. Five ML algorithms were applied to develop various radiomics models, from which the best performing model was identified. A ML-based combined model including optimal radiomics features and clinical predictors was constructed, with performance assessed through receiver operating characteristic (ROC) analysis. The Shapley additive explanation (SHAP) method was utilized to assess model interpretability.

Tumor size and MR-reported lymph node status were chosen as significant clinical variables. Thirteen radiomics features were identified from multiparametric MRI images. The extreme gradient boosting (XGBoost) radiomics model performed the best, achieving area under the curves (AUCs) of 0.941, 0.903, 0.862, and 0.894 across training and validation cohorts 1-3, respectively. The XGBoost combined model showed favorable discriminative power, with AUCs of 0.956, 0.912, 0.894, and 0.906 in training and validation cohorts 1-3, respectively. The SHAP visualization facilitated global interpretation, identifying "ADC_wavelet-HLH_glszm_ZoneEntropy" and "DCE_wavelet-HLL_gldm_DependenceVariance" as the most significant features for the model's predictions.

The XGBoost combined model derived from multiparametric MRI may proficiently differentiate between luminal and non-luminal BC and aid in treatment decision-making.

An interpretable machine learning radiomics model can preoperatively predict luminal and non-luminal subtypes in breast cancer, thereby aiding therapeutic decision-making.

This study aimed to evaluate the efficacy of pyrotinib, an orally administered small molecule tyrosine kinase inhibitor, combined with neoadjuvant chemotherapy in treating patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Pyrotinib works by inhibiting the HER2 signaling pathway, thereby preventing tumor cell growth. This single-arm clinical trial aimed to assess the total pathological complete response (tpCR; ypT0/is and ypN0) rate as the primary endpoint. A total of 27 patients were enrolled, each receiving 4-8 cycles of pyrotinib in combination with neoadjuvant chemotherapy. Pyrotinib combined with neoadjuvant chemotherapy demonstrated notable antitumor activity in patients with HER2-positive breast cancer. Among 26 patients, the tpCR rate was 26% (7/26), while the breast pathological complete response rate was 30% (8/26), indicating complete inhibition of the primary tumor in some cases. Notably, patients with HR-negative breast cancer demonstrated a higher tpCR rate compared with those with HR-positive breast cancer. The treatment regimen was well-tolerated. Diarrhea was the most common adverse event, occurring in 92.3% of patients, with 46.2% experiencing grade 3 or higher diarrhea. No severe adverse events or treatment-related fatalities were reported.

Breast cancer remains the most prevalent malignancy among women globally and ranks as the leading cause of cancer-related mortality in this demographic. Approximately 13 %-15 % of all breast cancer cases are classified as HER2-positive, a subtype associated with a particularly unfavorable prognosis. A large number of patients with HER2-positive breast cancer continue to face disease progression after receiving standardized treatment. Given these challenges, a thorough exploration into the mechanisms underlying drug resistance in HER2-targeted therapy is imperative. This review focuses on the factors related to drug resistance in HER2-targeted therapy, including tumor heterogeneity, antibody-binding efficacy, variations in the tumor microenvironment, and abnormalities in signal activation and transmission. Additionally, corresponding strategies to counteract these resistance mechanisms are discussed, to advance therapeutic efficacy and clinical benefits in the management of HER2-positive breast cancer.

Breast cancer is the most clinically relevant pathology of the mammary gland and is currently the most diagnosed malignant disease among women worldwide. In breast cancer prevention, it is important to consider that the risk of developing the disease is not the same for the entire population. This pathology presents heterogeneous clinical manifestations and the most common classification is related to the following hormonal receptors: estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and triple-negative (TNBC). Currently, a new class of therapy is being used for cancer treatment: anti-body-drug conjugates. A bibliographic search was performed by establishing keywords and then combining them using Boolean operators OR and AND. Thus, the search equation was formulated according to the PICO search question to be used in the PubMed database. Results: Fifteen studies that met the established inclusion criteria were analyzed, and their methodological quality was assessed using the Joanna Briggs Institute approach, demonstrating high reliability in the results obtained, the analyzed studies focus on the combination of adjuvant Pertuzumab + Trastuzumab with chemotherapy for the treatment of HER2-positive breast cancer. Scientific evidence suggests that the combination of pertuzumab and trastuzumab not only improves the survival of patients with HER2-positive breast cancer but also provides a safe and flexible treatment option.

Today, breast cancer (BC) is the most frequently diagnosed malignancy and a leading cause of cancer-related deaths among women worldwide. Brain metastases (BMs) are a common complication among individuals with advanced breast cancer, significantly impacting both survival rates and the overall condition of life of patients. This review systematically analyzes the innovative approaches to drug treatment for breast cancer brain metastases (BCBMs), with particular emphasis placed on treatments targeting molecular mechanisms and signaling pathways and drug delivery strategies targeting the blood brain barrier (BBB). The article discusses various drugs that have demonstrated effectiveness against BCBM, featuring a mix of monoclonal antibodies, nimble small-molecule tyrosine kinase inhibitors (TKIs), and innovative antibody-drug conjugates (ADCs). This study of various drugs and techniques designed to boost the permeability of the BBB sheds light on how these innovations can improve the treatment of brain metastases. This review highlights the need to develop new therapies for BCBM and to optimize existing treatment strategies. With a deeper comprehension of the intricate molecular mechanisms and advances in drug delivery technology, it is expected that more effective personalized treatment options will become available in the future for patients with BCBM.

The potential benefits of pyrotinib for patients with trastuzumab-insensitive, HER2-positive early-stage breast cancer remain unclear. This prospective, multicentre, response-adapted study evaluated the efficacy and safety of adding pyrotinib to the neoadjuvant treatment of HER2-positive breast cancer patients with a poor response to initial docetaxel plus carboplatin and trastuzumab (TCbH). Early response was assessed using magnetic resonance imaging (MRI) after two cycles of treatment. Patients showing poor response, as defined by RECIST 1.1, could opt to receive additional pyrotinib or continue standard therapy. The primary endpoint was the total pathological complete response (tpCR; ypT0/isN0) rate. Of the 129 patients enroled, 62 (48.1%) were identified as MRI-responders (cohort A), 26 non-responders continued with four more cycles of TCbH (cohort B), and 41 non-responders received additional pyrotinib (cohort C). The tpCR rate was 30.6% (95% CI: 20.6-43.0%) in cohort A, 15.4% (95% CI: 6.2-33.5%) in cohort B, and 29.3% (95% CI: 17.6-44.5%) in cohort C. Multivariable logistic regression analyses demonstrated comparable odds of achieving tpCR between cohorts A and C (odds ratio = 1.04, 95% CI: 0.40-2.70). No new adverse events were observed with the addition of pyrotinib. Patients with co-mutations of TP53 and PIK3CA exhibited lower rates of early partial response compared to those without or with a single gene mutation (36.0% vs. 60.0%, P = 0.08). These findings suggest that adding pyrotinib may benefit patients who do not respond to neoadjuvant trastuzumab plus chemotherapy. Further investigation is warranted to identify biomarkers predicting patients' benefit from the addition of pyrotinib.

PARP (poly (ADP-ribose) polymerase) inhibitors (PARPi) have demonstrated significant potential in cancer treatment, particularly in tumors with breast cancer susceptibility gene (BRCA) mutations and other DNA repair deficiencies. However, the development of resistance to PARPi has become a major challenge in their clinical application. The emergence of drug resistance leads to reduced efficacy of the PARPi over time, impacting long-term treatment outcomes and survival rates. PARPi resistance in tumors often arises as cells activate alternative DNA repair pathways or evade the effect of PARPi, diminishing therapeutic effectiveness. Consequently, overcoming resistance is crucial for maintaining treatment efficacy and improving patient prognosis. This paper reviews the strategies to overcome PARPi resistance through combination treatment and nanotechnology therapy. We first review the current combination therapies with PARPi, including anti-angiogenic therapies, radiotherapies, immunotherapies, and chemotherapies, and elucidate their mechanisms for overcoming PARPi resistance. Additionally, this paper focuses on the application of nanotechnology in improving the effectiveness of PARPi and overcoming drug resistance. Subsequently, this paper presents several promising strategies to tackle PARPi resistance, including but not limited to: structural modifications of PARPi, deployment of gene editing systems, implementation of "membrane lipid therapy," and modulation of cellular metabolism in tumors. By integrating these strategies, this research will provide comprehensive approaches to overcome the resistance of PARPi in cancer treatment and offer guidance for future research and clinical practice.

The efficacy of neoadjuvant therapy varies significantly with hormone receptor (HR) status for patients with human epidermal growth factor receptor 2 (HER2) positive breast cancer (BC). Despite extensive research on HER2 + BC, the optimal neoadjuvant strategy for HR+/HER2 + BC remains inconclusive. This study aimed to identify the optimal neoadjuvant regimen for HR+/HER2 + BC treatment. We conducted a systematic search for trials comparing neoadjuvant regimens for HR+/HER2 + BC and a network meta-analysis. Odds ratios for pathological complete response (pCR) and hazard ratios for event-free survival (EFS) were calculated. Treatment regimens were ranked using the surface under the cumulative ranking curve. 20 trials with 2809 patients were included. In pCR analysis, three neoadjuvant regimens sequentially ranked at the top, namely those comprising T-DM1, pertuzumab with trastuzumab, and tyrosine kinase inhibitor with trastuzumab, demonstrating significantly higher pCR rates than monotherapies. In EFS analysis, pertuzumab with trastuzumab ranked the first while T-DM1 containing regimen ranked the last. Anthracycline-free regimens showed a marginally higher pCR rate than anthracycline-containing regimens, while carboplatin-containing regimens demonstrated a numerically higher pCR rate than carboplatin-free regimens. Significant heterogeneity was observed in endocrine therapy analysis, which may be caused by different strategies for incorporating endocrine therapy. In conclusion, trastuzumab plus pertuzumab stands out as the optimal neoadjuvant HER2-targeting regimen for HR+/HER2 + BC Furthermore, anthracycline-free carboplatin-containing chemotherapy emerges as a promising combination treatment. Further investigation is required to clarify the role of endocrine therapy in HR+/HER2 + BC to guide its clinical application.

The combination of pyrotinib (Py) with cytotoxic agents proved to be effective in early human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC). However, the optimal chemotherapy regimen is unknown. This study attempts to explore it from real-world research data.

Information was collected from patients with early-stage HER2-positive BC from 23 centers across the country. They were categorized into the anthracycline group (A group) and non-anthracycline group (non-A group). Patients in the non-A group were further categorized into the platinum group and non-platinum group and the short-cycle (≤4 cycles) taxane group and long-cycle (>4 cycles) taxane group. Total pathological complete response (tpCR, ypT0/is ypN0) and breast pathological complete response (bpCR, ypT0/is) rates were assessed.

A total of 107 patients were enrolled. Postoperative pathology indicated a tpCR rate of 36.8 %, a bpCR rate of 42.1 % in the A group, the non-A group had a tpCR rate of 47.8 %, and a bpCR rate of 53.6 %, with P-values of 0.273 and 0.254, respectively. In the long-cycle taxane group, the tpCR and bpCR rates were 60.8 % and 66.7 %, respectively. In the short-cycle taxane group, the tpCR and bpCR rates were 11.1 % and 16.7 %, respectively (both P<0.001). The platinum group had higher tpCR rate (62.9 % vs. 32.4 %, respectively; P = 0.011) and bpCR rate (65.7 % vs. 41.2 %, respectively; P = 0.041).

As for a neoadjuvant therapy regimen with Py, an anthracycline-free regimen is feasible. Besides, platinum-containing, long-cycle taxane regimens appear to achieve superior efficacy under anthracycline-removed conditions.

Breast cancer (BRCA) is the most common malignant tumor among women, characterized by high incidence rates and mortality rates. Oxidative stress and immunity, particularly in relation to mitochondria, have emerged as pivotal factors in breast carcinogenesis. Nonetheless, limited research has explored the specific contribution of mitochondrial oxidative stress to the prognosis of BRCA.

In this study, we conducted univariate and multivariate Cox regression analyses to pinpoint independent prognostic genes associated with mitochondrial oxidative stress (MOSRGs) and their correlation with BRCA clinical outcomes. Subsequently, we developed a robust and accurate MOS scoring system for BRCA patients based on these identified independent prognostic MOSRGs.

Our findings were further substantiated by immune infiltration and somatic mutation analyses, providing additional evidence that the MOS scoring system holds predictive value for clinical outcomes in patients and correlates directly with three subtypes of BRCA. In vitro experiments in the MCF7 cell and breast tissue further verified the mRNA and protein expression level of independent prognostic genes, validating the consistency of the MOS prognostic signatures in BRCA.

This research has unveiled a novel prognostic scoring system, providing valuable insights for improving patient prognosis assessment and developing individualized treatment strategies in BRCA patients.

Trastuzumab (TRA) is a key drug in human epidermal growth factor receptor type 2 (HER2)-positive breast cancer treatment. Infusion reactions (IR) with TRA are frequently observed in practice. Although the efficacy of premedication has been previously reported, it remains uncommon. The probability of severe IR due to TRA is low; however, when it does occur, it is associated with patient discomfort and expenditure of medical resources. This study aimed to analyze the factors associated with the occurrence of IR in patients with breast cancer who received TRA.

We retrospectively studied 204 patients who underwent TRA for breast cancer treatment between September 2008 and June 2023, identifying factors influencing the occurrence of IR at the time of TRA administration.

A total of 182 patients were included in this study, and the incidence of IR was 25.8% (47/182 patients). Multiple logistic regression analysis showed that pertuzumab (PER) use, high alkaline phosphatase (ALP), and low high-density lipoprotein (HDL) cholesterol levels were associated with IR.

IR should be considered when PER is combined with TRA. ALP and HDL cholesterol levels may be predictive markers of TRA-induced IR in patients with breast cancer.

Human epidermal growth factor receptor 2-positive (HER2+) breast cancer is an aggressive subtype of breast cancer associated with a poor prognosis when sub-optimally treated. Recent advances include new and effective targeted therapies that have significantly improved outcomes for patients. Despite these advances, there are significant gaps across Canada, underscoring the need for evidence-based consensus guidance to inform treatment decisions. Addressing these gaps is crucial to ensuring that effective therapies are integrated into clinical practice, so as to improve the lives of patients affected by this aggressive form of breast cancer. The Research Excellence, Active Leadership (REAL) Canadian Breast Cancer Alliance is a standing nucleus committee of clinical-academic oncologists across Canada and Breast Cancer Canada, a patient organization. The mandate of this group is to provide evidence-based guidance on best practices in the management of patients with breast cancer. These consensus recommendations were developed using a modified Delphi process with up to three rounds of anonymous voting. Consensus was defined a priori as ≥75% of voters agreeing with the recommendation as written. There are 9 recommendations in the early setting; 7 recommendations in the metastatic setting; and 10 recommendations for patients with brain metastases.

Purpose: We aimed to investigate whether estrogen receptor (ER) status affects the predictive role of the human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC) score on the efficacy of neoadjuvant treatment for HER2-positive breast cancer. Methods: This retrospective study comprised 167 individuals diagnosed with HER2-positive invasive breast cancer who had undergone neoadjuvant treatment and surgery. Uni- and multivariable logistic regression analyses were performed on the relationship between the HER2 IHC score and total pathological complete response (tpCR), breast pathological complete response (bpCR), or axillary partial response (apCR). Subgroup analyses were used to investigate whether the relationship between the HER2 IHC score and tpCR, bpCR, or apCR differed by ER or PR status. Results: The overall tpCR rate for HER2-positive breast cancers treated with neoadjuvant treatment was 41.32% (69 of 167). The tpCR, bpCR, and apCR rates were greater in the HER2 IHC 3+ group (tpCR: IHC 3 + 47.69% vs. IHC 2 + 18.92%, p=0.009). Significant interactions between HER2 IHC score and tpCR or bpCR were found in subgroup analyses based on ER status (tpCR: p for interaction = 0.001; bpCR: p for interaction = 0.001). Among ER-positive patients, the HER2 IHC 2+ group had substantially decreased tpCR, bpCR, and apCR rates than the HER2 IHC 3+ group (tpCR rate: p=0.003; bpCR rate: p=0.002; apCR rate: p=0.002). For ER-negative individuals, the tpCR, bpCR, and apCR rates did not differ significantly among the HER2 IHC 3+ versus HER2 IHC 2+ groups. Similarly, interactions between HER2 IHC score and tpCR, bpCR, or apCR were found in subgroup analyses based on PR status. Conclusion: HER2 IHC 2+ may indicate a decreased tpCR rate, bpCR rate, and apCR rate to neoadjuvant treatment in HR-positive patients having HER2-positive breast cancer, but not in HR-negative patients.

Breast cancer is the most common malignancy in terms of incidence and is the leading cause of cancer deaths among women worldwide. In the Philippines, 33,079 new cases of breast cancer were documented in 2020 comprising 17.5% of all new cancer diagnoses. With a rate of 27 deaths per 100,000 people, the Philippines is the frontrunner in Asia for breast cancer mortality. HER2/neu-positive breast cancer, a more aggressive subtype associated with poorer survival outcomes, is present in about 23.5%. Fortunately, the emergence of HER2-targeted therapies has considerably improved disease-free survival and overall survival. This article reviews the most recent data in the HER2+ early breast cancer space.

Different hormone receptor (HR) expression patterns have significant biological and therapeutic implications in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer. However, the distinction between HR-positive /HER2-positive (HR+/HER2+) and HR-negative/HER2-positive (HR-/HER2+) subtypes remains unclear.

This retrospective study analyzed 828 patients with HER2-positive breast cancer at the First Affiliated Hospital of Xi'an Jiaotong University from 2012 to 2022. Baseline characteristics were compared by chi-square test. Survival outcomes were estimated by Kaplan-Meier method.

In total, 56.3% (n = 466) had HR-positive and 43.7% (n = 362) had HR-negative disease. Comparatively, HR+/HER2 + breast cancers presented favorable clinicopathological features. At a median follow-up of 49 months, 199 disease-free survival (DFS) events and 99 deaths were observed. HR+/HER2 + patients had significantly better survival outcomes than HR-/HER2 + patients. HR-positive status was an independent protective factor for overall survival (OS) [P = 0.032; hazard ratio, 0.61; 95% confidence interval (CI), 0.39-0.96] and DFS (P = 0.001; hazard ratio, 0.61; 95% CI, 0.46-0.81). HR+/HER2 + patients were significantly less sensitive to neoadjuvant therapy than HR-/HER2 + patients. In the first-line treatment for HR+/HER2 + advanced breast cancer, receiving endocrine therapy significantly improved advanced-OS (P < 0.001; hazard ratio, 0.33; 95% CI, 0.18-0.59) and progression-free survival (PFS) (P < 0.001; hazard ratio, 0.38; 95% CI, 0.25-0.58) compared with not receiving endocrine therapy. Moreover, maintenance endocrine therapy after HER2-targeted therapy and chemotherapy is associated with significant advanced-OS and PFS benefits compared with no maintenance endocrine therapy (advanced-OS: P < 0.001; hazard ratio, 0.05; 95% CI, 0.03-0.12; PFS: P < 0.001; hazard ratio, 0.35; 95% CI, 0.21-0.57).

This study reveals the high heterogeneity of HER2-positive breast cancer related to HR status in clinicopathological features, metastasis patterns, and outcomes. Large randomized controlled trials are warranted to optimize treatment strategies for the HER2-positive breast cancer population.

HER2-positive breast cancer is highly aggressive, with a significant risk of recurrence and metastasis, leading to a poor prognosis. While most early-stage HER2-positive breast cancer patients benefit from combining trastuzumab monoclonal antibody with chemotherapy, the therapeutic response to various drug combinations varies across the HER2+ patient population. Therefore, predicting the prognosis and treatment response of HER2+ breast cancer patients to specific regimens is crucial for selecting appropriate precision individualized therapies. HER2DX is the first genomic tool designed to guide the treatment of HER2+ breast cancer patients. The three scores provided by HER2DX inform the entire treatment process, including predicting survival outcomes, recurrence, metastasis, and treatment responses like Pathological Complete Response Rate (pCR). It offers recommendations on follow-up intervals, treatment plans, and the duration of drug therapy. This review examines the literature and analyzes studies applying HER2DX to guide the comprehensive treatment and predict prognosis in HER2+ breast cancer patients, aiming to promote the widespread use of HER2DX in individualized treatment.

This randomized, parallel-controlled, double-blinded, phase III equivalence study evaluated the equivalence of a proposed pertuzumab biosimilar QL1209 to the pertuzumab (Perjeta®) each with trastuzumab and docetaxel in neoadjuvant treatment of early or locally advanced breast cancer patients with HER2-positive, ER/PR-negative.

Eligible patients were randomly (1:1) assigned to receive 4 cycles of neoadjuvant QL1209 or pertuzumab each with trastuzumab and docetaxel, and adjuvant treatment. The primary endpoint was total pathologic complete response (tpCR), with equivalence margins of 0.76 to 1.32.

Among the 585 patients enrolled, 257 and 259 patients were assigned to the QL1209 and pertuzumab groups, respectively. The tpCR rates were comparable in the QL1209 (109/255, 42.75%; 90% CI 37.65 to 47.84) and pertuzumab (117/259, 45.17%; 90% CI 40.09 to 50.26) groups. The tpCR risk ratio was 0.95 (90% CI, 0.80 to 1.11), and the 90% CI fell within the predefined equivalence margin. The most common grade ≥3 treatment-related adverse event was decreased neutrophil count (10. 9% vs. 12.7%) in the QL1209 and pertuzumab groups.

QL1209 demonstrated equivalent efficacy and comparable safety profile to the reference pertuzumab in neoadjuvant treatment of HER2-positive, ER/PR-negative, early, or locally advanced breast cancer.

Chinadrugtrials.org CTR20201073; ClinicalTrials.gov NCT04629846.

This perspective underscores the evolution and significance of neoadjuvant therapy in breast cancer, tracing its history and efficacy in improving outcomes. It delves into the correlation between achieving complete response and long-term survival, emphasizing the predictive value of treatment response estimation. Neoadjuvant chemotherapy in HER2-positive early breast cancer, particularly with taxanes and anti-HER2 therapies, emerges as a cornerstone, offering enhanced breast conservation rates and prognostic insights. The focus on individualized care, tailored to treatment response, underscores the need for adaptive strategies. Additionally, the article discusses the ongoing debate surrounding anthracyclines' role and the benefits of dual HER2 blockade. Ultimately, advocating for a personalized approach, guided by treatment response assessment, ensures optimal outcomes in HER2-positive breast cancer management.

TCbHP (taxane + carboplatin + trastuzumab + pertuzumab) is the preferred neoadjuvant therapy regimen for human epidermal growth factor receptor 2 (HER2)-positive breast cancer. However, no consensus exists regarding whether specific populations may be exempt from carboplatin, allowing for de-escalation to the THP (taxane + trastuzumab + pertuzumab) regimen. Additionally, the optimal number of cycles for neoadjuvant THP remains unclear. We compared the efficacy and safety of neoadjuvant TCbHP and THP regimens, providing clinicians with a nuanced perspective to guide their treatment regimen selection.

This multicenter real-world study included patients with HER2-positive breast cancer undergoing neoadjuvant TCbHP or THP between March 2019 and February 2023. Efficacy was assessed through the pathological complete response (pCR) rate, while safety was evaluated through monitoring adverse events.

Among 220 patients, 103 received 6 cycles of TCbHP (TCbHP×6), 83 received 6 cycles of THP (THP×6), and 34 received 4 cycles of THP (THP×4). The TCbHP×6 cohort exhibited a 66% pCR rate compared with 53% in the THP×6 cohort (P = 0.072). Subgroup analysis revealed that in patients aged ≤ 50 years, those with hormone receptor (HR)-negative status, and those with clinical stage T2, the pCR rate of the TCbHP×6 regimen was significantly higher than the THP×6 regimen (P < 0.05). The TCbHP×6 cohort reported higher frequencies of any-grade adverse events (99% versus 86.7%) and grade 3-4 events (49.5% versus 12%) than the THP×6 cohort. Propensity score matching identified 27 patient pairs between the THP×6 and THP×4 cohorts, indicating a significantly higher pCR rate for the THP×6 regimen than the THP×4 regimen (63% versus 29.6%, P = 0.029).

The TCbHP×6 regimen is favored for individuals aged ≤ 50 years and those aged > 50, ≤60 years with HR-negative status or clinical stage T2-4. For patients in compromised general condition or lacking the specified indications, the THP×6 regimen emerges as a lower-toxicity alternative with satisfactory efficacy. To ensure treatment efficacy, a minimum of 6 cycles of neoadjuvant THP is required.

This study aimed to retrospectively analyse the pathological response and safety of combining albumin-bound paclitaxel (nab-paclitaxel) or docetaxel with anti-HER2 therapy as a neoadjuvant treatment for HER2-positive breast cancer.

From June 2020 to August 2023, 225 HER2-positive breast cancer patients who underwent radical surgery following neoadjuvant treatment were enrolled in this study. The patients were divided into two groups based on the drugs they received: the nab-paclitaxel group (n=166, receiving nab-paclitaxel + platinum along with trastuzumab and pertuzumab) and the docetaxel group (n=59, receiving docetaxel + platinum along with trastuzumab and pertuzumab). The pathological response and adverse events related to the drugs were collected and evaluated in both groups.

In the nab-paclitaxel group, the rates of breast and total pathological complete response (bpCR and tpCR) were significantly greater than those in the docetaxel group (69.27% vs. 47.45%, P=0.003; 68.67% vs. 45.76%, P=0.002). For patients who did not achieve pCR after chemotherapy, the pathological response of chemotherapy was analysed using MP grading and RCB grading. The results showed that there was a statistically significant difference between the two groups (P<0.05). Multivariate analysis revealed that therapeutic drugs, clinical stage, ER status, and Ki-67 level were independent predictors of pCR. The nab-paclitaxel group had a significantly greater proportion of patients with peripheral sensory neuropathy than did the docetaxel group (58.43% vs. 38.98%, P=0.035), while the docetaxel group had a greater proportion of patients with allergies and elevated ALT (31.93% vs. 69.49%, P=0.000; 23.49% vs. 40.68%, P=0.021).

Our real-world study revealed that nab-paclitaxel combined with anti-HER2 therapy was an effective neoadjuvant therapy for HER2-positive breast cancer. The multivariate analysis revealed that chemotherapy drugs, clinical stage, ER status, and Ki-67 level was the significant factor influencing treatment outcome. These findings offer a valuable reference for the neoadjuvant treatment of patients with HER2-positive breast cancer.

Inetetamab is the first domestically developed innovative anti-HER2 monoclonal antibody in China, proven effective and safe in HER2-positive advanced breast cancer. However, its efficacy and safety in neoadjuvant treatment of HER2-positive locally advanced breast cancer (LABC) remain to be validated.

This prospective cohort study aimed to evaluate the efficacy and safety of inetetamab combined with pertuzumab, taxanes, and carboplatin (TCbIP) in neoadjuvant therapy for HER2-positive LABC, comparing it to data from patients treated with the TCbHP regimen (trastuzumab combined with pertuzumab, taxanes, and carboplatin) using propensity score matching (PSM). The primary endpoint was total pathological complete response (tpCR). Adverse events (AEs), objective response rate (ORR), and near-pCR were key secondary endpoints.

Forty-four patients with clinical stage IIA-IIIC HER2-positive LABC were prospectively enrolled and treated with the TCbIP regimen. The tpCR rate among 28 patients who completed surgery was 60.7%, comparable to and slightly higher than the TCbHP group in PSM (60.7% vs. 53.6%, P = 0.510). The ORR was 96.4%, and the DCR reached 100.0%. The most common ≥ grade 3 AE was neutropenia (21.4% vs. 11.9%, P = 0.350). No significant reduction in left ventricular ejection fraction was observed, and no patient withdrew from treatment due to AEs.

Neoadjuvant therapy with TCbIP showed good efficacy and safety in patients with HER2-positive LABC and might be another promising option for neoadjuvant treatment.

NCT05749016 (registration date: Nov 01, 2021).

There has been significant progress made in developing novel targeted therapies in the neoadjuvant setting for non-metastatic HER2-positive breast cancer, which may be used in combination with conventional chemotherapy to optimise pathological responses at surgery. However, these therapies, particularly the chemotherapeutic components, may portend significant and long-lasting toxicity. Hence, de-escalation of treatment intensity has been an area of interest and was evaluated in the phase II NeoSphere study. Herein, we report the real-world pathological and survival outcomes from neoadjuvant taxane and dual HER2 blockade recorded at our centre.

This was a retrospective cohort study of patients receiving neoadjuvant pertuzumab, trastuzumab and taxane chemotherapy for non-metastatic HER2-positive breast cancer at a single centre in Sydney, Australia. We collected data pertaining to baseline demographic characteristics, pathological response rates, post-surgical prescribing patterns and also undertook survival analyses for invasive disease-free survival (iDFS) as well as exploratory analyses for correlations between pre-specified clinicopathologic factors and pathological response at surgery.

Our population was largely similar at baseline to the NeoSphere study. 71 patients were included in the final analysis. 61% achieved a pathological complete response (pCR). Three patients received conventional chemotherapy in the adjuvant setting. 92% of included patients were alive and disease-free at 3 years of follow-up. Only 3 events of recurrence or death were recorded at a median follow-up of 32 months. No significant difference in iDFS was noted between patients achieving pCR and those with residual disease at surgery.

This study demonstrates that de-escalated adjuvant treatment for HER2-positive early breast cancer achieved favourable pathological and long-term outcomes comparable to large trials, some utilising more intensive chemotherapeutic components.

In this study, we evaluated the feasibility of the sentinel lymph node (SLN) identification rate (SLN-IR) of fluorescein-guided sentinel lymph node biopsy (SLNB) in combination with methylene blue dye (MBD) and factors which can lead to a false negative rate (FNR) threshold of 10%.

This was a prospective cross-sectional non-randomized validation study in patients with post-neoadjuvant chemotherapy (NACT) clinically node negative axilla who were node positive prior to start of NACT. Patients underwent validation of SLNB using fluorescein (and blue LED light) and MBD. Axillary dissection was performed irrespective of SLNB histology. SLIN-IR and FNR were assessed and compared with various molecular subtypes.

The SLNs were identified in 102 out of 120 (85%) post-NACT patients. The median number of sentinel lymph nodes identified was 2 (range 1-3). The SLN-IR using MBD was 85%, FD was 82.5%, and combined MBD FD was 85%. Two or more SLNs were removed in 72 patients and 11 patients had tumor in the rest of the axilla, resulting in an FNR of 17.4%. An FNR was 25% in case only one SLN was found, and it was 11.42% if two or more than two SLNs were excised.

This cohort study found that use of low-cost dual dyes in patients with positive axillary disease, rendered cN0 with NACT, with 2 or more negative SLNs with SLNB alone, results in an FNR of 11.4%. Her 2 positive and TNBC with 2 or more negative SLNs are associated with an FNR of <10%. However, the number of such patients was small and further studies with larger sample size are warranted to confirm these findings.

There remains an unmet need for targeted therapies against advanced non-small-cell lung cancer (NSCLC) with HER2 mutations. To improve the antitumor activity of single anti-HER2 agent, this prospective, single-arm clinical trial (NCT05016544) examined the safety profile and efficacy of anti-HER2 antibody inetetamab and pan-HER TKI pyrotinib in HER2-posivite advanced NSCLC patients. Enrolled patients received inetetamab every 3 weeks and pyrotinib once per day (pyrotinib, dose-escalation part, 240 mg, 320 mg; dose-expansion part, 320 mg). Primary endpoints were dose-limiting toxicity (DLT) dosage and safety. Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). A total of 48 patients were enrolled. During the dose-escalation period, no DLT occurred. Diarrhea was the most commonly reported treatment-related adverse event (TRAE). Grade 3 TRAEs occurred in seven patients. The median PFS (mPFS) was 5.5 months [95% confidence interval (CI): 4.4-8.6 months]. The confirmed ORR and DCR reached 25% (11/44) and 84.1% (37/44), respectively. Responses were shown in patients with distinct HER2 aberrations. In summary, inetetamab in combination with pyrotinib demonstrated acceptable safety and antitumor activity among patients with advanced HER2-mutant NSCLC.