Reply to: PREDICT underestimates survival of patients with HER2-positive early-stage breast cancer.
Ontology highlight
ABSTRACT:
SUBMITTER: Agostinetto E
PROVIDER: S-EPMC10020562 | biostudies-literature | 2023 Mar
REPOSITORIES: biostudies-literature
Publications
Reply to: PREDICT underestimates survival of patients with HER2-positive early-stage breast cancer.
Agostinetto Elisa E de Azambuja Evandro E Lambertini Matteo M
NPJ breast cancer 20230316 1
Similar Datasets
Project description:The prognostic performance of PREDICT in patients with HER2-positive early breast cancer (EBC) treated in the modern era with effective chemotherapy and anti-HER2 targeted therapies is unclear. Therefore, we investigated its prognostic performance using data extracted from ALTTO, a phase III trial evaluating adjuvant lapatinib ± trastuzumab vs. trastuzumab alone in patients with HER2-positive EBC. Our analysis included 2794 patients. After a median follow-up of 6.0 years (IQR, 5.8-6.7), 182 deaths were observed. Overall, PREDICT underestimated 5-year OS by 6.7% (95% CI, 5.8-7.6): observed 5-year OS was 94.7% vs. predicted 88.0%. The underestimation was consistent across all subgroups, including those according to the type of anti HER2-therapy. The highest absolute differences were observed for patients with hormone receptor negative-disease, nodal involvement, and large tumor size (13.0%, 15.8%, and 15.3%, respectively). AUC under the ROC curve was 73.7% (95% CI 69.7-77.8) in the overall population, ranging between 61.7% and 77.7% across the analyzed subgroups. In conclusion, our analysis showed that PREDICT highly underestimated OS in HER2-positive EBC. Hence, it should be used with caution to give prognostic estimation to HER2-positive EBC patients treated in the modern era with effective chemotherapy and anti-HER2 targeted therapies.
| S-EPMC9300724 | biostudies-literature
Project description:Although human epidermal growth factor receptor 2 (HER2)-positive breast cancer was associated with poor prognosis, it has been changed after the development of trastuzumab. There has been great progress in perioperative HER2-targeting treatment, and investigations of several novel drugs and their combinations are ongoing. Adjuvant trastuzumab with or without pertuzumab for 1 year in combination with concomitant chemotherapy has become a standard treatment in high-risk node-negative tumors or node-positive HER2-positive early breast cancer patients without residual disease or who have not received neoadjuvant treatment. For low-risk HER2-positive early breast cancer patients, adjuvant paclitaxel and 1-year trastuzumab are possible alternatives. For residual disease after neoadjuvant treatment, adjuvant trastuzumab emtansine (T-DM1) for 14 cycles is a standard treatment. Non-anthracycline chemotherapy with dual anti-HER2 targeting of trastuzumab and pertuzumab represents one of the preferred neoadjuvant regimens to achieve higher pathologic complete response (pCR) rates and better clinical outcomes. Further research is needed to develop and validate potential biomarkers to predict pCR, which could help escalate or de-escalate anti-HER2 therapy. Trials incorporating novel agents such as T-DM1, trastuzumab deruxtecan (T-DXd), and immune checkpoint inhibitors and trying to de-escalate treatments in neoadjuvant setting are ongoing. In the future, tailored treatments such as no adjuvant therapy, various HER2-directed therapies alone with chemotherapy, combinations of various HER2-directed therapies and chemotherapy, addition of immune checkpoint inhibitors, and omission of surgery will be individualized in HER2-positive early breast cancer patients.
| S-EPMC9218503 | biostudies-literature
Project description:Background: This study aimed to investigate the impact of early adverse events (AE) following the initiation of lapatinib plus capecitabine on the progression-free survival (PFS) and overall survival (OS) outcomes of human epidermal growth factor receptor 2 (HER2) positive advanced breast cancer (ABC) patients. Methods: A secondary analysis of participants treated with lapatinib plus capecitabine, or ado-trastuzumab emtansine in the clinical trial EMILIA was conducted. Cox proportional hazard analysis was used to assess the impact of AE occurring within the first 42 days of lapatinib plus capecitabine therapy on the PFS and OS outcomes of ABC patients. Results: The study included 488 HER2-positive (ABC) patients initiated on lapatinib plus capecitabine. Rash (Hazard Ratio (HR) [95% Confidence Interval (CI)]: Grade 1 = 0.67 [0.46-0.98], Grade 2+ = 0.71 [0.42-1.19]; p = 0.046) and hand-foot syndrome (HR [95% CI]: Grade 1 = 0.58 [0.43-0.80], Grade 2+ = 0.61 [0.43-0.86]; p = <0.001) occurring within the first 42 days of lapatinib plus capecitabine therapy were significantly associated with improved OS. Conversely, nausea and vomiting occurring within the first 42 days of lapatinib plus capecitabine therapy was significantly associated with worsened OS (HR [95% CI]: Grade 1 = 1.08 [0.82-1.42], Grade 2+ = 1.52 [1.13-2.03]; p = 0.027). Conclusions: Rash and hand-foot syndrome occurring early after the initiation of on lapatinib plus capecitabine were significantly associated with improved OS, while early nausea and vomiting was associated with worse OS. In HER2-positive ABC patients initiating lapatinib plus capecitabine, consideration should be given to more closely monitoring patients at risk of nausea and vomiting, while rash and hand foot syndrome are AE associated with improved survival.
| S-EPMC7097941 | biostudies-literature
Project description:Advances in HER2-targeted therapies have improved the survival of patients with HER2-positive breast cancer. The standard-of-care treatment for localized disease has been chemotherapy and 1 year of adjuvant HER2-targeted therapy, typically with the anti-HER2 antibody trastuzumab. Despite the effectiveness of this treatment, disease relapse occurs in a subset of patients; thus, focus has been placed on escalating treatment by either combining different HER2-targeted agents or extending the duration of HER2-targeted therapy. Indeed, dual HER2-targeted therapies and extended-duration anti-HER2 therapy, as well as adjuvant therapy with the anti-HER2 antibody-drug conjugate T-DM1, have all been approved for clinical use. Emerging evidence suggests, however, that some patients do not derive sufficient benefit from these additional therapies to offset the associated toxicities and/or costs. Similarly, the universal use of chemotherapy might not benefit all patients, and treatment de-escalation through omission of chemotherapy has shown promise in clinical trials and is currently being explored further. The future of precision medicine should therefore involve tailoring of therapy based on the genetics and biology of each tumour and the clinical characteristics of each patient. Predictive biomarkers that enable the identification of patients who will benefit from either escalated or de-escalated treatment will be crucial to this approach. In this Review, we summarize the available HER2-targeted agents and associated mechanisms of resistance, and describe the current therapeutic landscape of early stage HER2-positive breast cancer, focusing on strategies for treatment escalation or de-escalation.
| S-EPMC8023395 | biostudies-literature
Project description:Breast cancer (BC) has the second highest incidence among cancers and is the leading cause of death among women worldwide. The human epidermal growth factor receptor 2 (HER2) is overexpressed in approximately 20%-30% of BC patients. The development of HER2-targeted drugs, including monoclonal antibodies (mAbs), tyrosine kinase inhibitors (TKIs) and antibody-drug conjugates (ADCs), has improved the operation rate and pathological remission rate and reduced the risk of postoperative recurrence for HER2-positive early-stage BC (HER2+ EBC) patients. This review systematically summarizes the mechanisms, resistance, therapeutic modalities and safety of HER2-targeted drugs and helps us further understand these drugs and their use in clinical practice for patients with HER2+ EBC.
| S-EPMC11439691 | biostudies-literature
Project description:BackgroundIn premenopausal patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer, the gonadotoxicity of trastuzumab and lapatinib remains largely uncertain, and the prognostic effect of treatment-related amenorrhea (TRA) is unknown.MethodsIn the Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization (BIG 2-06) phase III trial, HER2-positive early breast cancer patients were randomized (1:1:1:1) to receive one year of trastuzumab, lapatinib, their sequence, or their combination. As per study protocol, menopausal status was collected in all patients at random assignment and at week 37 visit. We investigated TRA rates and whether TRA in patients with hormone receptor-positive and -negative tumors would impact disease-free survival (DFS) and overall survival (OS). Landmark and time-dependent modeling were used to account for guarantee-time bias. All statistical tests were two-sided.ResultsA total of 2862 premenopausal women were included, of whom 1679 (58.7%) had hormone receptor-positive disease. Median age was 43 (interquartile range = 38-47) years. Similar TRA rates were observed in the trastuzumab (72.6%), lapatinib (74.0%), trastuzumab→lapatinib (72.1%), and trastuzumab+lapatinib (74.8%) arms (P = .64). The association between TRA and survival outcomes differed according to hormone-receptor status (Pinteraction for DFS = .007; Pinteraction for OS = .003). For hormone receptor-positive patients, the TRA cohort had statistically significantly better DFS (adjusted hazard ratio [aHR] = 0.58, 95% confidence interval [CI] = 0.45 to 0.76) and OS (aHR = 0.63, 95% CI = 0.40 to 0.99) than the no TRA cohort. No difference was observed in hormone receptor-negative patients.ConclusionsIn this unplanned analysis, no association between TRA rate and type of anti-HER2 treatment was observed. TRA was associated with statistically significant survival benefits in premenopausal hormone receptor-positive/HER2-positive early breast cancer patients.
| S-EPMC6335113 | biostudies-literature
Project description:Despite evidence from clinical trials showing the efficacy of shorter durations of therapy, most HER2-positive early breast cancer (EBC) patients receive a year of anti-HER2 therapy. A survey of Canadian oncologists was conducted online, with electronic data collection, and the analysis is reported descriptively. Measures collected included current practices with respect to the duration of adjuvant anti-HER2 therapy, perspectives on data regarding shorter durations of treatment, and interest in further trials on this subject. Responses were received from 42 providers across Canada. Half (50%, 21/42) reported having never recommended 6 months of anti-HER2 therapy. The primary reason physicians consider a shorter duration is in response to treatment-related toxicities (76%, 31/41). Most participants (79%, 33/42) expressed the need for more data to determine which patients can be safely and effectively treated with shorter durations. Patient factors such as young age, initial stage, hormone receptor status, and type of neoadjuvant chemotherapy were attributed to reluctance to offer shorter durations of treatment. Many respondents (83%, 35/42) expressed interest in participating in the proposed clinical trial of 6 months of anti-HER2 therapy. In contemporary Canadian practice, 12 months of anti-HER2 therapy remains the primary practice. Future trials are required to better define the role of shorter treatment durations.
| S-EPMC10742686 | biostudies-literature
Project description:We found that MCF-7 and T-47D or MDA-MB-157 and MDA-MB-231 are rBC2LCN-positive or -negative breast cancer cell lines, respectively. To examine a global gene expression comparison between the rBC2LCN-positive and -negative breast cancer cell lines, DNA microarray analysis was performed.
2020-06-08 | GSE139670 | GEO
Project description:AimThe main objective of the current study was to explore the value of risk-adjustment when comparing (i.e. benchmarking) long-term overall survival (OS) in breast cancer (BC) between Swedish regions. We performed risk-adjusted benchmarking of 5- and 10-year OS after HER2-positive early BC diagnosis between Sweden's two largest healthcare regions, constituting approximately a third of the total population in Sweden.MethodsAll patients diagnosed with HER2-positive early-stage BC between 01-01-2009 and 31-12-2016 in healthcare regions Stockholm-Gotland and Skane were included in the study. Cox proportional hazards model was used for risk-adjustment. Unadjusted (i.e. crude) and adjusted 5- and 10-year OS was benchmarked between the two regions.ResultsThe crude 5-year OS was 90.3% in the Stockholm-Gotland region and 87.8% in the Skane region. The crude 10-year OS was 81.7% in the Stockholm-Gotland region and 77.3% in the Skane region. However, when adjusted for age, menopausal status and tumour biology, there was no significant OS disparity between the regions, neither at the 5-year nor 10-year follow-up.ConclusionThis study showed that risk-adjustment is relevant when benchmarking OS in BC, even when comparing regions from the same country that share the same national treatment guidelines. This is, to our knowledge, the first published risk-adjusted benchmarking of OS in HER2-positive BC.
| S-EPMC10272493 | biostudies-literature
Project description:Over the last decades, a better understanding of breast cancer heterogeneity provided tools for a biologically based personalization of anticancer treatments. In particular, the overexpression of the human epidermal growth factor receptor 2 (HER2) by tumor cells provided a specific target in these HER2-positive tumors. The development of the monoclonal antibody trastuzumab, and its approval in 1998 for the treatment of patients with metastatic disease, radically changed the natural history of this aggressive subtype of breast cancer. These findings provided strong support for the continuous research in targeting the HER2 pathway and implementing the development of new anti-HER2 targeted agents. Besides trastuzumab, a series of other anti-HER2 agents have been developed and are currently being explored for the treatment of breast cancer patients, including those diagnosed with early-stage disease. Among these agents, neratinib, an oral tyrosine kinase inhibitor that irreversibly inhibits HER1, HER2, and HER4 at the intracellular level, has shown promising results, including when administered to patients previously exposed to trastuzumab-based treatment. This article aims to review the available data on the role of the HER2 pathway in breast cancer and on the different targeted agents that have been studied or are currently under development for the treatment of patients with early-stage HER2-positive disease with a particular focus on neratinib.
| S-EPMC5513878 | biostudies-literature