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Background: Neoadjuvant systemic therapy (NST) is conducted in increased number of patients with breast cancer overexpressing human epidermal growth factor receptor 2 (HER2). Whether the intensity of HER2 protein expression determines response to treatment is challenged. This study aims to analyze the impact of HER2 immunohistochemical (IHC) scores on NST response and survival outcome. Methods: We analyzed a total of 197 patients with HER2-positive breast cancer receiving NST and definite surgery from a prospectively collected database. The analyzed endpoints included pathological complete response (pCR), disease-free survival (DFS), and overall survival (OS). More patients with IHC 2+/in situ hybridization (ISH)-positive tumors presented positive for hormonal receptors, compared with those with IHC 3+ tumors. No clinicopathological features except tumor necrosis were significantly associated with pCR. Results: Both positive hormone receptors and IHC scores stood on the borderline in statistical analysis. IHC 3+ group tends to present a higher pCR rate than IHC 2+/ISH+ groups (52.5% vs. 34.3%). Patients who achieved pCR had better survival outcome than that of non-pCR group. The impact of pCR on survival reached the statistical significance in the IHC 3+ group both in DFS (90.9% vs. 76.5%; p = 0.004) and OS (97.4% vs. 83.2%; p = 0.002). Multivariate analysis demonstrated IHC scores as an independent predictor of survival outcome with the adjustment of tumor staging and pCR. Conclusion: HER2 IHC score is an independent predictor for outcome. IHC 3+ tumors presented a trend of higher pCR rate and better outcome in HER2-positive breast cancer patients who receive NST. [ABSTRACT FROM AUTHOR]

As most erb-b2 receptor tyrosine kinase 2 (HER2)-positive breast cancer (BC) patients currently receive dual HER2-targeting added to neoadjuvant chemotherapy, improved methods for identifying individual response, and assisting postsurgical salvage therapy, are needed. Herein, we evaluated the 41-gene classifier trastuzumab advantage risk model (TRAR) as a predictive marker for patients enrolled in the NeoSphere trial. TRAR scores were computed from RNA of 350 pre- and 166 post-treatment tumor specimens. Overall, TRAR score was significantly associated with pathological complete response (pCR) rate independently of other predictive clinicopathological variables. Separate analyses according to estrogen receptor (ER) status showed a significant association between TRAR score and pCR in ER-positive specimens but not in ER-negative counterparts. Among ER-positive BC patients not achieving a pCR, those with TRARlow scores in surgical specimens showed a trend for lower distant eventfree survival. In conclusion, in HER2-positive/ER-positive BC, TRAR is an independent predictor of pCR and represents a promising tool to select patients responsive to anti-HER2-based neoadjuvant therapy and to assist treatment escalation and de-escalation strategies in this setting. [ABSTRACT FROM AUTHOR]

Background: Multigene assays, such as MammaPrint and BluePrint, provide additional information other than conventional immunohistochemistry (IHC) to help making decision of treatment. This study aims to compare the clinical correlation between molecular subtyping (MS) versus surrogate pathological subtyping (PS). Methods: A database from patients receiving MS evaluation in Taipei Veterans General Hospital from 2013 to 2018 was reviewed retrospectively. Patients were categorized as luminal A, luminal B, human epidermal growth factor receptor 2 (HER2) and basal type from MS results and also centrally assessed according to PS (estrogen receptor [ER], progesterone receptor [PgR], HER2, and Ki-67). The clinical correlation between two different subtyping methodologies was analyzed, and the application of chemotherapy was compared. Results: From 2013 to 2018, a total of 130 patients received MS testing in our institute, and 132 tumor samples were sent for analysis. From MammaPrint, 64 (48.5%) and 55 (41.7%) samples were defined as low and high risks, respectively. The other 13 (9.8%) tumor samples were identified as late recurrence low risk. MS restratified 44 tumors as subtype shifting including 20 tumors from A to B in intrinsic subtypes and 24 tumors from B to A after MS evaluation. Chemotherapy was conducted in only one (1.3%) patient with MS-luminal A but in 87.8% (n = 43) of MS-luminal B subtypes. Conclusion: The MS results restratify the subtypes of hormone receptor positive breast cancer and dominate decision-making of adjuvant therapy. The role of surrogate biomarkers as an alternative tool needs further elucidation. The treatment outcome in different subtypes categorized by MS or PS will be the interesting focus of research. [ABSTRACT FROM AUTHOR]

Background: Hormone receptor-positive, human epidermal growth factor receptor II (HER2)-negative luminal B1 breast cancer is associated with a higher risk of disease relapse than luminal A breast cancer. Therefore, we assessed and compared the distant metastasis pattern and clinical outcomes associated with luminal B1 and luminal A breast cancer in an Asian population. Methods: In this observational study, we assessed patients with estrogen receptor-positive, HER2-negative breast cancer who underwent surgery from 2009 to 2016. Patients were classified into luminal A or luminal B1 subsets via immunohistochemical analysis. Disease-free survival, post-metastasis survival, and overall survival were estimated; time to disease relapse and patterns of distant metastasis were compared. Risk of relapse and mortality were assessed using Cox proportional hazards model. Results: Patients with luminal B1 breast cancer (n = 677) were significantly younger and had larger tumors and a higher degree of affected axillary lymph nodes, lymphovascular invasion, and tumor necrosis than those with luminal A breast cancer (n = 630). Higher rates of local recurrence and distant metastasis were observed for luminal B1 (both p < 0.05); however, no difference was observed in the specific distant metastatic sites. We observed a significant increase in disease relapse risk in luminal B1 patients compared with that in luminal A (hazard ratio: 2.157, 95% CI: 1.340-3.473, p < 0.05). Patient age, tumor size, stage, lymphovascular invasion, and receiving chemotherapy and hormone therapy were independent risk factors for metastasis and recurrence. Only the luminal B1 subtype (hazard ratio: 5.653, 95% CI: 1.166-27.409, p < 0.05) and stage (hazard ratio: 3.400, 95% CI: 1.512-7.649, p < 0.05) were identified as independent risk factors for post metastatic mortality. Conclusion: Luminal B1 breast cancer has aggressive tumor biology compared with luminal A breast cancer in the follow-up period. However, there was no significant difference in the disease relapse pattern between the groups. [ABSTRACT FROM AUTHOR]

Background: To assess the clinical outcomes and metastatic behavior between de novo versus recurrent human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) based on a single-institution database in Taiwan. Methods: We retrospectively identified patients diagnosed between January 2000 and December 2017 with de novo stage IV or recurrent HER2-positive MBC. Several variables were recorded in patients with recurrent disease: age at diagnosis, metastatic site, hormone receptor (HR) status, HER2 status, and disease-free interval (DFI). Treatments and metastatic patterns were compared between de novo stage IV and recurrent MBC cohorts. Post-metastasis survival (PMS) was estimated using the Kaplan-Meier method with log-rank tests. Hazard ratios and 95% CIs were estimated using Cox regression analysis. Results: In total, 1360 patients were diagnosed with breast cancer with HER2 overexpression. At baseline, de novo stage IV patients were older than recurrent MBC patients (median age 58 vs 53). The majority of the de novo stage IV patients were diagnosed after 2010, while most of the recurrent MBC patients were diagnosed during 2000-2009. An increased number of de novo stage IV patients underwent targeted therapy than recurrent MBC patients was also noted. PMS in patients with de novo stage IV and recurrent MBC was 79.2 months and 61.8 months, respectively, which indicated significant better survival in de novo stage IV than those with recurrent MBC disease. Longer survival was also noted in de novo stage IV and recurrent MBC with DFI >24 months than in those with recurrent MBC with DFI <24 months and in patients receiving HER2-targeted therapy after MBC diagnosis than in those not receiving the therapy. However, median PMS showed no significant difference between patients with the luminal B2 (HR-positive, HER2-negative) and HER2-enriched (HR-negative, HER2-positive) subtypes. After adjustment in multivariate analysis, a low risk of BC-specific death was observed in patients aged >50 years, those receiving HER2-targeted therapy for MBC, and those with oligometastasis, while patients with first metastases to the liver or brain showed a higher risk of BC-specific death than those without metastases. Conclusion: De novo and recurrent MBC have distinct characteristic, metastatic patterns and outcomes in Asian HER2-positive breast cancer patients. The age distribution and survivals between HR+/– status were different to non-Asian group. These differences should be further investigated in the future considering ethnic factor. [ABSTRACT FROM AUTHOR]

This study aimed to explore the symptom profiles and predominant symptoms in newly diagnosed breast cancer women before and after receiving docetaxel chemotherapy. A pre-post study recruited adult women with stage I-III breast cancer undergoing docetaxel chemotherapy using convenience sampling. The 13-item symptom severity subscale of the M. D. Anderson Symptom Inventory-Taiwan Form was used to measure symptoms. The study employed latent profile analysis to identify subgroups based on symptom severity before and after docetaxel chemotherapy. Descriptive statistics, including mean and frequency, were used to compare and contrast the most prevalent and severe symptoms within each subgroup to confirm the predominant symptoms. The study identified four and two symptom profiles before and after docetaxel treatment, respectively. Disturbed sleep was identified as a prevalent symptom for all participants, regardless of their chemotherapy status. The predominant symptoms before treatment were disturbed sleep, dry mouth, difficulty remembering, and fatigue, while disturbed sleep and numbness were the predominant symptoms after treatment. The findings of this study are significant, as they contribute to the current understanding of the symptom experience of breast cancer individuals undergoing docetaxel chemotherapy. Healthcare professionals should prioritize assessing and managing these symptoms, including identifying contributing factors to poor sleep. Addressing symptom profiles related to sleep can improve the quality of life of breast cancer individuals undergoing docetaxel chemotherapy. • Provide a unique and comprehensive method to identify symptom profiles. • Identify disturbed sleep as a predominant symptom throughout docetaxel chemotherapy. • Docetaxel chemotherapy often leads to numbness, a key symptom of chemotherapy-induced neuropathy. [ABSTRACT FROM AUTHOR]