Receptor 2-positive Early Breast Cancer Research Articles

Cost-Effectiveness Analysis of Adjuvant Pertuzumab and Trastuzumab in Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer in Japan.

Human epidermal growth factor receptor 2 (HER2)-positive breast cancer presents considerable treatment challenges owing to its aggressive nature. Global guidelines have endorsed a full year of HER2-targeted therapy for early-stage breast cancer. However, previous cost-effectiveness analyses of dual HER2-targeted therapies have been limited. This study aimed to examine the cost effectiveness of dual HER2-targeted therapy for early-stage breast cancer within the Japanese healthcare system context. In the Markov model-based study, the cost effectiveness of dual anti-HER2 therapy, combining pertuzumab and trastuzumab, was assessed in comparison to trastuzumab monotherapy. Patients in whom treatment was initiated at a median age of 51 years were included. The study utilized quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs) as comparison units. Subgroup analyses were conducted to explore variations in cost effectiveness, focusing on node-positive and node-negative patients. Both one-way deterministic and broader probabilistic sensitivity analyses using Monte Carlo simulations with 10,000 samples were performed from the Japanese healthcare payers perspective. Dual HER2-targeted therapy led to 0.17 QALYs increment at an additional cost of $US15,289, resulting in an ICER of $US92,232 per QALY. In the subgroup of node-positive patients, the benefit of the dual HER2-targeted therapy was more pronounced, with an increase of 0.64 QALYs and an ICER of $US24,561 per QALY. Sensitivity analyses revealed the model's susceptibility to changes in the transition probabilities from invasive disease-free survival to death, from invasive disease-free survival to first-line metastatic breast cancer, and to costs associated with pertuzumab. Probabilistic sensitivity analysis suggests that for node-positive patients, dual HER2-targeted therapy may be a cost-effective option. The economic viability of dual HER2-targeted therapy was most pronounced in patients with node-positive high-risk early breast cancer. This study highlights the potential of dual HER2-targeted therapy as a cost-effective addition for these cases.

Concurrent epirubicin and trastuzumab use increases complete pathological response rate without additional cardiotoxicity in patients with human epidermal growth factor receptor 2-positive early breast cancer: A meta-regression analysis.

Due to cardiotoxicity concerns, the concurrent use of epirubicin and trastuzumab has not been fully studied. This study aimed to examine the cardiotoxicity and pathological complete response (pCR) rate associated with the concurrent regimens in patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (EBC). We conducted a systematic search for relevant literature in the NCBI/PubMed, the Cochrane database, and international conference abstracts for phase II or III randomized controlled trials between January 1, 2000, and February 28, 2021, focusing on the concurrent regimens in patients with HER2-positive EBC. To compare the risk of cardiotoxicity and the odds of the pCR rate, we performed linear meta-regression analyses to investigate the effects of multiple covariates. We analyzed 7 neoadjuvant trials involving the concurrent use of epirubicin and trastuzumab with 1797 patients. The median cumulative dose of epirubicin used was 300 mg/m2, with a total of 96 reported adverse cardiac events. The concurrent regimens did not result in a significant increase in cardiotoxicity compared to nonconcurrent regimens (risk ratio [RR] = 1.18, 95% confidence interval [CI] = 0.68-2.05). Compared with nonconcurrent or non-anthracycline-containing regimens, concurrent regimens were associated with a significant increase in the pCR rate (odds ratio = 1.48, 95% CI = 1.04-2.12). The linear fixed-effects meta-regression analysis indicated that in trials including more patients with hormone receptor-positive EBC, the RR of cardiotoxicity significantly increased with concurrent regimens, and the pCR rate became less significant. The combination of trastuzumab and a low dose of epirubicin positively impacted the pCR rate without a significant increase in cardiotoxicity. We recommend exploring concurrent regimens for HR-negative, HER2-positive tumors to enhance pCR rates, with caution advised for HR-positive tumors due to potential cardiotoxicity.

Cost-effectiveness analysis of add-on pertuzumab to trastuzumab biosimilar and chemotherapy as neoadjuvant treatment for human epidermal growth receptor 2-positive early breast cancer patients in Singapore

ABSTRACT Objectives The Asian PEONY trial showed that add-on pertuzumab to trastuzumab and chemotherapy significantly improved pathological complete response in the neoadjuvant treatment of patients with human epidermal growth factor receptor 2-positive (HER2+) early breast cancer (EBC). This study evaluated the cost-effectiveness of pertuzumab as an add-on therapy to trastuzumab and chemotherapy for neoadjuvant treatment of patients with HER2+ EBC in Singapore. Methods A six-state Markov model was developed from the Singapore healthcare system perspective, with a lifetime time horizon. Model outputs were: costs; life-years (LYs); quality-adjusted LYs (QALYs); incremental cost-effectiveness ratios (ICERs). Sensitivity/scenario analyses explored model uncertainties. Results The base case projected the addition of pertuzumab to be associated with improved outcomes by 0.277 LYs and 0.271 QALYs, increased costs by S$1,387, and an ICER of S$5,121/QALY. The ICER was most sensitive to the pCR rate, and the probabilistic sensitivity analysis showed that add-on pertuzumab had an 81.3% probability of being cost-effective at a willingness-to-pay threshold of S$45,000/QALY gained. Conclusions This model demonstrated that the long-term clinical impact of early pertuzumab use, particularly the avoidance of metastatic disease and thus avoidance of higher costs and mortality rates, make neoadjuvant pertuzumab a cost-effective option in the management of patients with HER2+ breast cancer in Singapore.

Body Mass Index As A Prognostic Factor In HER-2 Positive Early Breast Cancer Patients And Its Effect On Duration Of Treatment With Trastuzumab: A Retrospective Study.

To evaluate prognostic value of body mass index in human epidermal growth factor receptor 2-positive early breast cancer, and to evaluate the duration of trastuzumab administration. The retrospective study was conducted from March 2020 to December 2021 at Kafrelsheikh University Hospital and Zagazig University Hospital, Egypt, and comprised data of women diagnosed between 2015 and 2017 with stage III human epidermal growth factor receptor 2-positivebreast cancer, who were treated with adjuvant chemotherapy and trastuzumab for a year. Body massindex had been calculated at the time of diagnosis, and data was divided into 3 groups: average weight group A, overweight group B and obese group C. Disease-free survival, distant disease-free survival and overall survival were estimated for all the three groups. Data was analysed using SPSS 26. The mean age of 160 cases was 44.99±11.35 years(range: 25-66 years). There were 93(58.1) postmenopausal women, 60(37.5%) had positive family history and 128 (80%) underwent modified radical mastectomy. There were 60(37.5%) patients in group A, 49(30.6%) in group B and 51(31.9%) in group C. There was significant association of body mass index with disease-free survival and distant disease-free survival (p<0.05), but not with overall survival (p>0.05). Significant difference was noted between body mass index and duration of trastuzumab (p<0.001). Body massindex wasfound to be an independent prognostic factor for human epidermal growth factor receptor 2-positiveearly breast cancer.

100P Cost-effectiveness analysis of trastuzumab emtansine as adjuvant treatment for patients in Singapore with human epidermal growth factor receptor 2-positive early breast cancer

100P Cost-effectiveness analysis of trastuzumab emtansine as adjuvant treatment for patients in Singapore with human epidermal growth factor receptor 2-positive early breast cancer

Safety and efficacy of adjuvant subcutaneous trastuzumab in human epidermal growth factor receptor 2-positive early breast cancer: Final results of the SafeHER study

AimTo report the final results of the 5-year follow-up of the non-randomized SafeHER Phase III study (NCT01566721) describing the safety, tolerability, and efficacy of subcutaneous (SC) trastuzumab alone and in combination with concurrent or sequential chemotherapy. MethodsPatients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (EBC) with no prior anti-HER2 therapy were included. SC trastuzumab was administered every 3 weeks for 18 cycles as adjuvant therapy with or without chemotherapy (concurrent or sequential). The primary objective was overall safety and tolerability of SC trastuzumab; efficacy was a secondary objective. ResultsNo new safety signals were observed during the final evaluation. The majority of adverse events (AEs) were grade 1 or 2 across the chemotherapy subgroups. Treatment discontinuation due to AEs was 5.1% for the intent-to-treat (ITT) population and similar for all chemotherapy subgroups. The overall disease-free survival (DFS) 5-year event-free rate in the ITT population (n = 2573) was 86.6% (95% CI, 85.2%–87.9%) with a median follow-up of 72 months. Based on chemotherapy timing, the no (n = 235), concurrent (n = 1533), and sequential (n = 805) chemotherapy subgroups had DFS 5-year event-free rates (95% CI) of 88.5% (83.4%–92.2%), 88.4% (86.6%–89.9%), and 82.6 (79.7%–85.2%), respectively. ConclusionsThe 5-year follow-up analysis of the SafeHER trial demonstrating that SC trastuzumab has an acceptable safety profile, including cardiac toxicity, and efficacy for the treatment of HER2-positive EBC with and without chemotherapy, corresponding with historical data with trastuzumab.

Combined Estrogen Receptor and Progesterone Receptor Level Can Predict Survival Outcome in Human Epidermal Growth Factor Receptor 2-positive Early Breast Cancer

BackgroundIn human epidermal growth factor receptor 2 (HER2)-positive breast cancer, emerging evidence imply that clinical behaviors differ according to hormone receptor (HR) status. However, there is no conclusion about the relevance between estrogen receptor (ER) or progesterone receptor (PR) expression and clinical outcome of HER2+ breast cancer. Our study aimed to determine the influence of different ER/PR levels on survival outcome of HER2+ early breast cancer. Patients and MethodsNine hundred and nineteen early HER2+ breast cancer patients treated between 2009 and 2016 were retrospectively reviewed and HR+/HER2+ patients were further divided based on ER level (Low/L: 1%-9%; Median/M: 10%-79%; High/H: 80%-100%) and PR level (Low/L: 0%-19%; High/H: 20%-100%) according to restricted cubic spline (RCS) smoothing curve. Disease-free survival (DFS) and overall survival (OS) were estimated by Kaplan–Meier method and log rank test. ResultsFour hundred and forty two HR+/HER2+ and 477 HR-/HER2+ breast cancer patients were included in our study and 73.2% received target therapy (HR+ 69.7%, HR- 76.5%). While HR+/HER2+ breast cancer showed better survival than HR-/HER2+ subtype in 5-year disease free survival (DFS, 93.0% vs. 86.8%, P < .001), no significant difference was observed between DFS in ER+/PR+ and ER+/PR- subgroup (94.4% vs. 90.4%, P = .22). However, a potential correlation was found between ER/PR levels and DFS in HR+/HER2+ (P = .074) tumors. In HR+/HER2+ breast cancer, all subgroups showed DFS improvement trend versus M-ER/L-PR. In all HER2+ patients, hazard ratio of H-ER/H-PR compared with HR- subtype was 0.10 (95%CI 0.01-0.74, P = .024) in all patients and 0.14 (95%CI, 0.02-1.02, P = .053) in patients receiving anti-HER2 therapy. ConclusionER/PR expression may become a predictor of survival benefit in HER2+ early breast cancer and a higher ER/PR level might be associated with better DFS.

Optimum duration of adjuvant trastuzumab in treatment of human epidermal growth factor receptor-2 positive early breast cancer: protocol for a network meta-analysis of randomised controlled trials

IntroductionControversy regarding optimum duration of trastuzumab treatment remains in patients with human epidermal growth factor receptor-2 (HER2) positive early breast cancer. The objective of applying network meta-analysis (NMA) is to...

Safety and tolerability of subcutaneous trastuzumab for the adjuvant treatment of human epidermal growth factor receptor 2-positive early breast cancer: SafeHer phase III study's primary analysis of 2573 patients

AimTo assess the safety and tolerability of adjuvant subcutaneous trastuzumab (Herceptin® SC, H SC), delivered from an H SC Vial via hand-held syringe (Cohort A) or single-use injection device (Cohort B), with or without chemotherapy, for human epidermal growth factor receptor 2 (HER2)-positive stage I to IIIC early breast cancer (EBC) in the phase III SafeHer study (NCT01566721). MethodsPatients received 600 mg fixed-dose H SC every 3 weeks for 18 cycles. The chemotherapy partner was at the investigators' discretion (H SC monotherapy was limited to ≤10% of the population). Data from the first H SC dose until 28 days (plus a 5-day window) after the last dose are presented. Results are descriptive. ResultsIn the overall population, 2282/2573 patients (88.7%) experienced adverse events (AEs). Of the above, 128 (5.0%) patients experienced AEs leading to study drug discontinuation; 596 (23.2%) experienced grade ≥ 3 AEs and 326 (12.7%) experienced serious AEs. Grade ≥ 3 cardiac disorders were reported in 24 patients (0.9%), including congestive heart failure in eight (0.3%).As expected, the AE rates varied according to the timing of chemotherapy in both cohorts, with higher rates in concurrent versus sequential chemotherapy subgroups. In the concurrent chemotherapy subgroup, AEs were more common during the actual period of concurrent chemotherapy compared with the period when patients did not receive concurrent chemotherapy. ConclusionSafeHer confirms the safety and tolerability of the H SC 600 mg fixed dose for 1 year (every 3 weeks for 18 cycles) as adjuvant therapy with concurrent or sequential chemotherapy for HER2-positive EBC. These primary analysis results are consistent with the known safety profile for intravenous H and H SC.

Trastuzumab in Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer: Results of a Prospective, Noninterventional Study on Routine Treatment Between 2006 and 2012 in Germany.

Trastuzumab is part of the standard treatment in patients with human epidermal growth factor receptor 2-positive early breast cancer in addition to (neo)adjuvant chemotherapy. This German prospective noninterventional study, which included major patient cohorts underrepresented in the pivotal randomized studies, examined the generalizability of the results of those studies. Between 2006 and 2012, 4,027 patients were enrolled and treated with trastuzumab; they were unselected regarding age or concomitant/sequential adjuvant chemotherapy. Long-term outcome data were obtained in yearly intervals. All analyses were descriptive in nature. Among 3,940 evaluable patients, 26% were elderly (older than 65 years of age). More than half of the population had pN0 tumor stage. Ninety-four percent received chemotherapy: 78% as adjuvant treatment and 14% as neoadjuvant treatment, 2% both. Anthracyclines were administered in 87% and taxanes in 66%. Trastuzumab was stopped prematurely in 9% (because of cardiotoxicity in 3.5%). Recurrence-free survival was 90.0% (95% confidence interval [CI], 88.9%-91.1%) and 82.8% (95% CI, 81.2%-84.4%) after 3 and 5 years, respectively. The corresponding figures for overall survival were 96.8% (95% CI, 96.1%-97.6%) and 90.0% (95% CI, 88.6%-91.4%). Pathological primary tumor size, lymph node involvement, and hormone receptor status had the greatest independent effect on recurrence risk. Cardiac function toxicity of National Cancer Institute common toxicity criteria grade ≥2 and ≥3 was observed in 2.5% and less than 1% of patients, respectively. The maturing follow-up data seem to confirm the beneficial results of trastuzumab treatment for early breast cancer from the randomized studies. Moreover, these findings support use of trastuzumab-based therapy in patients groups less commonly included in the phase III trials (e.g., elderly patients and those with stage I disease). The Oncologist 2017;22:131-138Implications for Practice: On the basis of the results of large pivotal phase III studies, the inclusion of trastuzumab in adjuvant treatment regimens for human epidermal growth factor receptor 2-positive breast cancer is standard of care. However, in these trials, elderly patients, those with comorbidities, and/or those with contraindications or refusal of cytotoxic chemotherapy are typically underrepresented. This study provides data on observed treatment options, outcomes, and risks in a wider, unselected patient population (including more than 1,000 patients with stage I disease), treated routinely in several institutions of varying size and location across Germany.

Efficacy of Adjuvant Trastuzumab for Patients With Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer and Tumors ≤ 2 cm: A Meta-Analysis of the Randomized Trastuzumab Trials.

We compared efficacy of trastuzumab versus no trastuzumab in patients with small (≤ 2 cm) human epidermal growth factor receptor 2 (HER2) -positive breast cancer treated in randomized trials. A meta-analysis was conducted using data from five of the six adjuvant trastuzumab trials. Efficacy end points were disease-free survival (DFS) and overall survival (OS). Separate analyses were prospectively planned for hormone receptor (HR) -positive and HR-negative cohorts. Random effect models and Yusuf-Peto fixed effects models assessed the impact of heterogeneity on baseline hazards and treatment effects across studies. Peto-Pike cumulative incidence estimates were stratified by study and nodal status. Median follow-up time was 8 years. For 2,263 patients with HR-positive disease, 8-year cumulative incidence rates comparing trastuzumab versus no trastuzumab were 17.3% versus 24.3% (P < .001) for DFS and 7.8% versus 11.6% (P = .005) for OS, respectively; for 1,092 HR-positive patients with zero or one positive lymph nodes, results were 12.7% versus 19.4% (P = .005) for DFS and 5.3% versus 7.4% (P = .12) for OS, respectively. For 1,957 patients with HR-negative disease, 8-year cumulative incidence rates were 24.0% versus 33.4% (P < .001) for DFS and 12.4% versus 21.2% (P < .001) for OS, respectively; for 1,040 HR-negative patients with zero or one positive lymph nodes, results were 20.4% versus 26.3% (P = .05) for DFS and 8.2% versus 12.2% (P = .084) for OS, respectively. Women with HER2-positive tumors ≤ 2 cm in the randomized trastuzumab trials derived substantial DFS and OS benefit from adjuvant trastuzumab. Trastuzumab-treated patients with HR-positive disease and ≤ one positive lymph node may be candidates for trials assessing less aggressive treatment approaches.

Two Years versus One Year of Trastuzumab in Patients with Early Breast Cancer

The 2005 results of large randomized trials, including the Trastuzumab in Treating Women with Primary Breast Cancer [HERA; NCT00045032] trial, demonstrated statistically significant disease-free survival benefit for 1 year of treatment with trastuzumab compared with observation in patients with human epidermal growth factor receptor 2-positive early breast cancer. After 2005, the HERA trial focused on the secondary objective of comparing 2 years of trastuzumab treatment with 1 year of treatment, and this article discusses the results of this analysis.