Home > Treatments > Biological Therapies > Monoclonal Antibodies > Trastuzumab (Herceptin)

Found this page useful?

Trastuzumab (Herceptin)

Web Resources: Trastuzumab (Herceptin)
Latest Research Publications

Web Resources: Trastuzumab (Herceptin) (6 links)


Latest Research Publications

Khan S, Mikhail S, Xiu J, Salem ME
Molecular biology of gastroesophageal cancers: opportunities and challenges.
Clin Adv Hematol Oncol. 2017; 15(1):75-82 [PubMed] Related Publications
Gastroesophageal (GE) malignancies make up a significant and growing segment of newly diagnosed cancers. Approximately 80% of patients who have GE cancers die within 5 years of diagnosis, which means that effective treatments for these malignancies need to be found. Currently, targeted therapies have a minimal role in this disease group. Intensive study of the molecular biology of GE cancers is a relatively new and ongoing venture, but it has already led to a significant increase in our understanding of these malignancies. This understanding, although still limited, has the potential to enhance our ability to develop targeted therapies in conjunction with the ability to identify actionable gene mutations and perform genomic profiling to predict drug resistance. Several cell surface growth factor receptors have been found to play a prominent role in GE cancer cell signaling. This discovery has led to the approval of 2 agents within the last few years: trastuzumab, an anti-human epidermal growth factor receptor 2 (HER2) monoclonal antibody used in the first-line treatment of HER2-positive GE cancers, and ramucirumab, an anti-vascular endothelial growth factor receptor 2 (VEGFR2) monoclonal antibody that is currently used in later lines of therapy. This review discusses the current state of molecular testing in GE cancers, along with the known molecular biology and current and investigational treatments. The development of trastuzumab and ramucirumab represents a significant advance in our ability to make use of GE tumor molecular profiles. As our understanding of the impact of molecular aberrations on drug effectiveness and disease outcomes increases, we anticipate improved therapy for patients with GE cancers.

Cerqueira-Coutinho C, Missailidis S, Alessandra-Perini J, et al.
Comparison of biodistribution profile of monoclonal antibodies nanoparticles and aptamers in rats with breast cancer.
Artif Cells Nanomed Biotechnol. 2017; 45(3):598-601 [PubMed] Related Publications
The use of monoclonal antibodies and aptamers is growing every single day, as the use of nanoparticle systems. Although most of the products are under investigation, there are a few commercialized products available at the market, for human consume. In this study, we have compared three formulations (aptamer anti-MUC1, monoclonal antibody - Trastuzumab and monoclonal antibodies nanoparticles - PLA/PVA/MMT trastuzumab) to identify their profile as also to understand their behavior into an alive biological system. In this direction the radiolabeling of the products were done and they were all tested in animals (in vivo) in two conditions: healthy rats and breast cancer induced animals. The results showed that the nanoparticle has the better biodistribution profile, followed by the aptamer. We conclude that more studies and a global effort to elucidate the biological behavior of drugs and especially nano-drugs are necessary.

Dekel Y, Machluf Y, Gefen T, et al.
Formation of multimeric antibodies for self-delivery of active monomers.
Drug Deliv. 2017; 24(1):199-208 [PubMed] Related Publications
Proteins and peptides have been used as drugs for almost a century. Technological advances in the past 30 years have enabled the production of pure, stable proteins in vast amounts. In contrast, administration of proteins based on their native active conformation (and thus necessitating the use of subcutaneous injections) has remained solely unchanged. The therapeutic anti-HER2 humanized monoclonal immunoglobulin (IgG) Trastuzumab (Herceptin) is a first line of the treatment for breast cancer. Chicken IgY is a commercially important polyclonal antibody (Ab). These Abs were examined for their ability to self-assemble and form ordered aggregates, by several biophysical methods. Atomic force microscopy analyses revealed the formation of multimeric nanostructures. The biological activity of multimeric IgG or IgY particles was retained and restored, in a dilution/time-dependent manner. IgG activity was confirmed by a binding assay using HER2 + human breast cancer cell line, SKBR3, while IgY activity was confirmed by ELISA assay using the VP2 antigen. Competition assay with native Herceptin antibodies demonstrated that the binding availability of the multimer formulation remained unaffected. Under long incubation periods, IgG multimers retained five times more activity than native IgG. In conclusion, the multimeric antibody formulations can serve as a storage depositories and sustained-release particles. These two important characteristics make this formulation promising for future novel administration protocols and altogether bring to light a different conceptual approach for the future use of therapeutic proteins as self-delivery entities rather than conjugated/encapsulated to other bio-compounds.

Aitelhaj M, Lkhoyaali S, Rais G, et al.
First line chemotherapy plus trastuzumab in metastatic breast cancer HER2 positive - Observational institutional study.
Pan Afr Med J. 2016; 24:324 [PubMed] Free Access to Full Article Related Publications
Breast cancer is the most common malignant disease and among the most frequent causes of cancer mortality in females worldwide. Metastatic breast cancer (MBC) is conventionally considered to be incurable. In first-line treatment of HER-2 positive MBC, randomized trials have demonstrated that trastuzumab when combined with chemotherapy significantly improves progression free survival and overall survival. To evaluate survival and toxicity of chemotherapy with Trastuzumab as first line therapy of human epithermal growth factor receptor 2 positive metastatic breast cancer, in Moroccan population. It is a phase IV observational institutional monocentric study. Including patients with metastatic breast cancer HER2 positive, as first-line chemotherapy combined with Trastuzumab from March 2009 until March 2010. Primary end point: progression free survival, secondary end point response rate and overall survival. A total of 20 patients were enrolled between March 2009 and March 2010. The lung was the first metastatic site in 60% of the cases, followed by bone, liver, nodes, skin and brain. All patients received chemotherapy with Trastuzumab: 9 of them with Docetaxel, 8 with vinorelbine, and 3 with capecitabine. The progression free survival was estimated by the Kaplan-Meier method, from the date of first cycle to the date of progression or at the last consultation, and the median was 12.8 months. Trastuzumab based chemotherapy was generally well tolerated; 5 patients (25%) presented cardiotoxicity. The results of this study join the literature and show the benefit of Trastuzumab to chemotherapy in first line metastatic breast cancer HER-2 positive.

Tsoutsou PG, Vozenin MC, Durham AD, Bourhis J
How could breast cancer molecular features contribute to locoregional treatment decision making?
Crit Rev Oncol Hematol. 2017; 110:43-48 [PubMed] Related Publications
Systemic treatments are tailored to breast cancer (BC) heterogeneity, which is not yet taken into account for radiotherapy (RT) personalization. The primary objective of this review is to summarize existing data suggesting BC subtypes and genetic assays are prognostic and predictive biomarkers useful for RT decision-making and to provide implications for their incorporation into future translational and clinical research. The evidence suggesting that BC subtypes also exhibit distinct "locoregional recurrence (LRR)" patterns is retrospective but consistent and validated in over fifteen studies. The HER-2 positive and triple negative subtypes are the most susceptible to locoregional failure. The high risk of the HER-2 positive subtype can be reversed with trastuzumab administration. Very little is known on the subtypes' intrinsic radiosensitivity properties. Genetic assays have assessed retrospectively signatures' prognostic and predictive value in patients' cohorts (several coming from prospective studies) for LRR risk and radiotherapy (RT) benefit. Further confirmation is needed before their introduction into clinical routine. Evidence on the use of molecular biomarkers for adjuvant RT tailoring is emerging but needs validation and introduction into prospective studies. The plethora of modern RT options (partial breast irradiation, hypofractionation), as well as recent evidence pointing towards more extensive radiotherapy, demand introduction of biological features into clinical trials to improve therapeutic decisions. Open questions, such as tailoring of irradiation after neo-adjuvant chemotherapy in complete responders and the understanding of the interplay between local control, systemic recurrence and survival given modern systemic treatments, need to be addressed under the prism of biology within this heterogeneous disease. Intrinsic radiobiological properties within this heterogeneity need to be highlighted in order to further improve outcomes.

Jacobs I, Ewesuedo R, Lula S, Zacharchuk C
Biosimilars for the Treatment of Cancer: A Systematic Review of Published Evidence.
BioDrugs. 2017; 31(1):1-36 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Biologic treatments for cancer continue to place a significant economic burden on healthcare stakeholders. Biosimilar therapies may help reduce this burden through cost savings, thereby increasing patient access.
OBJECTIVES: The purpose of this study was to collate all published data to assess the weight of available evidence (quantity and quality) for proposed monoclonal antibody biosimilars and intended copies, for the treatment of cancer.
METHODS: MEDLINE(®), Embase(®), and ISI Web of Science(®) databases were searched to September 2015. Conference proceedings (17) were searched (2012 to July 2015). Searches of the United States National Library of Medicine ClinicalTrials.gov registry were also conducted. Risk of bias assessments were undertaken to assess data strength and validity.
RESULTS: Proposed biosimilars were identified in 23 studies (36 publications) in oncology and ten studies in 14 publications in oncology and chronic inflammatory diseases for bevacizumab, rituximab, and trastuzumab originators. Based on our review of the included published studies, and as inferred from the conclusions of study authors, the identified proposed biosimilars exhibit close similarity to their originators. Published data were also retrieved on intended copies of rituximab. It remains unclear what role these agents may have, as publications on rigorous clinical studies are lacking for these molecules.
CONCLUSION: While biosimilar products have the potential to improve patient access to important biologic therapies, robust evidence of outcomes for monoclonal antibody biosimilars in treating cancer patients, including data from comparative efficacy and safety trials, is not yet available in the published literature. Significant data gaps exist, particularly for intended copies, which reinforces the need to maintain a clear differentiation between these molecules and true biosimilars. As more biosimilars become available for use, it will be important for stakeholders to understand fully the robustness of overall evidence used to demonstrate biosimilarity and gain regulatory approval.

Noritake M, Narui K, Kaneta T, et al.
Evaluation of the Response to Breast Cancer Neoadjuvant Chemotherapy Using 18F-FDG Positron Emission Mammography Compared With Whole-Body 18F-FDG PET: A Prospective Observational Study.
Clin Nucl Med. 2017; 42(3):169-175 [PubMed] Related Publications
PURPOSE: The aim of this study was to assess therapeutic response to breast cancer neoadjuvant chemotherapy (NAC) by F-FDG positron emission mammography (PEM) compared with that to whole-body F-FDG PET (WBPET).
METHODS: Twenty patients underwent WBPET and PEM 3 times: the first time was before NAC, the second time was after 2 courses of NAC, and the third time was after all courses of NAC. A pathological complete response (pCR) was defined as no evidence of residual invasive cancer with or without ductal carcinoma in situ. The relationships between each modality's SUVmax and pathological response were evaluated.
RESULTS: Nine patients achieved a pCR, whereas the other 11 patients had a non-pCR. The SUVmax of WBPET after 2 courses of NAC was significantly lower in the pCR group than in the non-pCR group (1.4 ± 0.4 vs 2.7 ± 2.1, P = 0.0334). There were no significant differences in the SUVmax of PEM (ie, PEM uptake value [PUV]) between the groups. The SUVmax of WBPET (area under the ROC curve [AUC] = 0.761) was superior to the PUVmax (AUC, 0.648) for predicting non-pCR at the interim time point. After all courses of chemotherapy, there were no significant differences between the groups in the SUVmax of WBPET; however, PUVmax was significantly lower in the pCR group than in the non-pCR group (1.0 ± 0.2 vs 2.5 ± 2.7, P = 0.0351). After NAC, the PUVmax (AUC, 0.796) was superior to the SUVmax of WBPET (AUC, 0.671).
CONCLUSIONS: There proved to be no apparent superiority of PEM in predicting pCR at the interim time point. Positron emission mammography had greater diagnostic capability for detecting residual cancer after all courses of NAC.

Kroeze SG, Fritz C, Hoyer M, et al.
Toxicity of concurrent stereotactic radiotherapy and targeted therapy or immunotherapy: A systematic review.
Cancer Treat Rev. 2017; 53:25-37 [PubMed] Related Publications
BACKGROUND AND PURPOSE: Both stereotactic radiotherapy (SRT) and immune- or targeted therapy play an increasingly important role in personalized treatment of metastatic disease. Concurrent application of both therapies is rapidly expanding in daily clinical practice. In this systematic review we summarize severe toxicity observed after concurrent treatment.
MATERIAL AND METHODS: PubMed and EMBASE databases were searched for English literature published up to April 2016 using keywords "radiosurgery", "local ablative therapy", "gamma knife" and "stereotactic", combined with "bevacizumab", "cetuximab", "crizotinib", "erlotinib", "gefitinib", "ipilimumab", "lapatinib", "sorafenib", "sunitinib", "trastuzumab", "vemurafenib", "PLX4032", "panitumumab", "nivolumab", "pembrolizumab", "alectinib", "ceritinib", "dabrafenib", "trametinib", "BRAF", "TKI", "MEK", "PD1", "EGFR", "CTLA-4" or "ALK". Studies performing SRT during or within 30days of targeted/immunotherapy, reporting severe (⩾Grade 3) toxicity were included.
RESULTS: Concurrent treatment is mostly well tolerated in cranial SRT, but high rates of severe toxicity were observed for the combination with BRAF-inhibitors. The relatively scarce literature on extra-cranial SRT shows a potential risk of increased toxicity when SRT is combined with EGFR-targeting tyrosine kinase inhibitors and bevacizumab, which was not observed for cranial SRT.
CONCLUSIONS: This review gives a best-possible overview of current knowledge and its limitations and underlines the need for a timely generation of stronger evidence in this rapidly expanding field.

Rugo HS, Barve A, Waller CF, et al.
Effect of a Proposed Trastuzumab Biosimilar Compared With Trastuzumab on Overall Response Rate in Patients With ERBB2 (HER2)-Positive Metastatic Breast Cancer: A Randomized Clinical Trial.
JAMA. 2017; 317(1):37-47 [PubMed] Related Publications
Importance: Treatment with the anti-ERBB2 humanized monoclonal antibody trastuzumab and chemotherapy significantly improves outcome in patients with ERBB2 (HER2)-positive metastatic breast cancer; a clinically effective biosimilar may help increase access to this therapy.
Objective: To compare the overall response rate and assess the safety of a proposed trastuzumab biosimilar plus a taxane or trastuzumab plus a taxane in patients without prior treatment for ERBB2-positive metastatic breast cancer.
Design, Setting, and Participants: Multicenter, double-blind, randomized, parallel-group, phase 3 equivalence study in patients with metastatic breast cancer. From December 2012 to August 2015, 500 patients were randomized 1:1 to receive a proposed biosimilar or trastuzumab plus a taxane. Chemotherapy was administered for at least 24 weeks followed by antibody alone until unacceptable toxic effects or disease progression occurred.
Interventions: Proposed biosimilar (n = 230) or trastuzumab (n = 228) with a taxane.
Main Outcomes and Measures: The primary outcome was week 24 overall response rate (ORR) defined as complete or partial response. Equivalence boundaries were 0.81 to 1.24 with a 90% CI for ORR ratio (proposed biosimilar/trastuzumab) and -15% to 15% with a 95% CI for ORR difference. Secondary outcome measures included time to tumor progression, progression-free and overall survival at week 48, and adverse events.
Results: Among 500 women randomized, the intention-to-treat population included 458 women (mean [SD] age, 53.6 [11.11] years) and the safety population included 493 women. The ORR was 69.6% (95% CI, 63.62%-75.51%) for the proposed biosimilar vs 64.0% (95% CI, 57.81%-70.26%) for trastuzumab. The ORR ratio (1.09; 90% CI, 0.974-1.211) and ORR difference (5.53; 95% CI, -3.08 to 14.04) were within the equivalence boundaries. At week 48, there was no statistically significant difference with the proposed biosimilar vs trastuzumab for time to tumor progression (41.3% vs 43.0%; -1.7%; 95% CI, -11.1% to 6.9%), progression-free survival (44.3% vs 44.7%; -0.4%; 95% CI, -9.4% to 8.7%), or overall survival (89.1% vs 85.1%; 4.0%; 95% CI, -2.1% to 10.3%). In the proposed biosimilar and trastuzumab groups, 239 (98.6%) and 233 (94.7%) had at least 1 adverse event, the most common including neutropenia (57.5% vs 53.3%), peripheral neuropathy (23.1% vs 24.8%), and diarrhea (20.6% vs 20.7%).
Conclusions and Relevance: Among women with ERBB2-positive metastatic breast cancer receiving taxanes, the use of a proposed trastuzumab biosimilar compared with trastuzumab resulted in an equivalent overall response rate at 24 weeks. Further study is needed to assess safety and long-term clinical outcome.
Trial Registration: clinicaltrials.gov Identifier: NCT02472964; EudraCT Identifier: 2011-001965-42.

Joensuu H
Escalating and de-escalating treatment in HER2-positive early breast cancer.
Cancer Treat Rev. 2017; 52:1-11 [PubMed] Related Publications
The current standard adjuvant systemic treatment of early HER2-positive breast cancer consists of chemotherapy plus 12months of trastuzumab, with or without endocrine therapy. Several trials have investigated modifications of the standard treatment that are shorter and less resource-demanding (de-escalation) or regimens that aim at dual HER2 inhibition or include longer than 12months of HER2-targeted treatment (escalation). Seven randomized trials investigate shorter than 12months of trastuzumab treatment duration. The shorter durations were not statistically inferior to the 1-year duration in the 3 trials with survival results available, but 2 of the trials were small and 1 had a relatively short follow-up time of the patients at the time of reporting. The pathological complete response (pCR) rates were numerically higher in all 9 randomized trials that compared chemotherapy plus dual HER2 inhibition consisting of trastuzumab plus either lapatinib, neratinib, or pertuzumab with chemotherapy plus trastuzumab as neoadjuvant treatments, but the superiority of chemotherapy plus dual HER2-inhibition over chemotherapy plus trastuzumab remains to be demonstrated in the adjuvant setting. One year of adjuvant trastuzumab was as effective as 2years of trastuzumab in the HERA trial, and was associated with fewer side-effects. Extending 1-year adjuvant trastuzumab treatment with 1year of neratinib improved disease-free survival in the ExteNET trial, but the patient follow-up times are still short, and no overall survival benefit was reported. Several important trials are expected to report results in the near future and may modify the current standard.

Kumar A, Lale SV, Aji Alex MR, et al.
Folic acid and trastuzumab conjugated redox responsive random multiblock copolymeric nanocarriers for breast cancer therapy: In-vitro and in-vivo studies.
Colloids Surf B Biointerfaces. 2017; 149:369-378 [PubMed] Related Publications
The study represents synthesis, characterization and biological evaluation of redox responsive polymeric nanoparticles based on random multiblock copolymer for doxorubicin delivery in breast cancer. The random multiblock copolymer was synthesized via ring opening polymerization of lactide with polyethylene glycol to form triblock copolymer followed by isomerization polymerization of the triblock copolymer and 2-hydroxyethyl disulfide with the help of hexamethylene diisocynate in presence of dibutyltin dilaurate as a catalyst. Folic acid was conjugated to hydroxyl group from the multiblock polymer through DCC-NHS coupling. High drug loading content of ∼22% was achieved in the polymeric nanoparticles with size range of ∼110nm and polyethylene glycol fraction of ∼18% in the multiblock copolymer. Drug release profile confirmed the redox responsive behavior of polymeric nanoparticles with ∼72% drug release at pH 5.5 in presence of 10mM GSH as compared to ∼18% drug release at pH 7.4. In vitro cellular uptake studies showed ∼22% cellular uptake with dual (folic acid and trastuzumab) conjugated polymeric nanoparticles as compared to non-targeted polymeric nanoparticles. Fluorescence activated cell sorting (FACS) studies demonstrated higher apoptosis (∼80%) as compared to non-conjugated polymeric nanoparticles (20%) in MCF-7 cell line. In vivo studies showed 91% tumor regression in Ehrlich ascites tumor (EAT) as compared to free doxorubicin treated mice without showing any significant toxicity. Thus, it is envisaged that these redox responsive polymeric nanocarriers act as Trojan horses in cancer therapeutics.

Zolata H, Afarideh H, Davani FA
Triple Therapy of HER2(+) Cancer Using Radiolabeled Multifunctional Iron Oxide Nanoparticles and Alternating Magnetic Field.
Cancer Biother Radiopharm. 2016; 31(9):324-329 [PubMed] Related Publications
By using radio-labeled multifunctional superparamagnetic iron oxide nanoparticles (SPIONs) and an alternating magnetic field (AMF), we carried out targeted hyperthermia, drug delivery, radio-immunotherapy (RIT), and controlled chemotherapy of cancer tumors. We synthesized and characterized Indium-111-labeled, Trastuzumab and Doxorubicin (DOX)-conjugated APTES-PEG-coated SPIONs in our previous work. Then, we evaluated their capability in SPECT/MRI (single photon emission computed tomography/magnetic resonance imaging) dual modal molecular imaging, targeting, and controlled release. In this research, AMF was introduced to evaluate therapeutic effects of magnetic hyperthermia on radionuclide-chemo therapy of HER2(+) cells and tumor (HER2(+))-bearing mice. In vitro and in vivo experiments using synthesized complex were repeated under an AMF (f: 100 KHz, H: 280 Gs). Instead of an intra-tumor injection in most hyperthermia experiments, SPIONs were injected to the tail vein, based on our delivery strategies. For magnetic delivery, we held a permanent Nd-B-Fe magnet near the tumor region. The results showed that simultaneous magnetic hyperthermia enhanced SKBR3 cancer cells, killing by 24%, 28%, 33%, and 80% at 48 hours post-treatment for treated cells with (1) bare SPIONs; (2) antibody-conjugated, DOX-free, surface-modified SPIONs; (3) (111)In-labeled, antibody-conjugated surface-modified SPIONs; and (4) (111)In-labeled, antibody- and DOX-conjugated surface-modified SPIONs, respectively. Moreover, tumor volume inhibitory rate was 85% after a 28 day period of treatment. By using this method, multimodal imaging-guided, targeted hyperthermia, RIT, and controlled chemotherapy could be achievable in the near future.

Meng Q, Li Z, Li S
Prediction and Early Evaluation of Anticancer Therapy Response: From Imaging of Drug Efflux Pumps to Targeted Therapy Response.
Curr Med Chem. 2016; 23(41):4625-4638 [PubMed] Related Publications
Multidrug resistance (MDR) describes the resistance of tumor cells to chemotherapy and has been ascribed to the overexpression of drug efflux pumps. Molecular imaging of drug efflux pumps is helpful to identify the patients who may be resistant to the chemotherapy and thus will avoid the unnecessary treatment and increase the therapeutic effectiveness. Imaging probes targeting drug efflux pumps can non-invasively evaluate the Pgp function and play an important role in identification of MDR, prediction of response, and monitoring MDR modulation. On the other hand, new anticancer agents based on molecular targets such as epidermal growth factor receptor (EGFR) and angiogenic factor receptor may potentially be combined with chemotherapeutic drugs to overcome the MDR. Imaging of molecular targets visualize treatment response of patients at molecular level vividly and help to select right patients for certain targeted anticancer therapy. Among all the imaging modalities, nuclear imaging including positron emission tomography (PET) and single photon emission computed tomography (SPECT) imaging has the greatest promise for rapid translation to the clinic and can realize quantitative visualization of biochemical processes in vivo. In this review, we will summarize the nuclear imaging probes utilized for predicting and evaluating the early anticancer therapy response.99mTc labeled agents and PET based radiopharmaceuticals like 18F-Paclitaxel, 11C-Verapamil for drug efflux pumps imaging will be discussed here. Moreover, molecular imaging probes used for targeted therapy response evaluation like 18F-Tamoxifen,89Zr-Trastuzumab will also be introduced in this review.

Koskas M, Depreeuw J, Moens S, et al.
Genomic Characterisation and Response to Trastuzumab and Paclitaxel in Advanced or Recurrent HER2-positive Endometrial Carcinoma.
Anticancer Res. 2016; 36(10):5381-5384 [PubMed] Related Publications
BACKGROUND/AIM: Human epidermal growth factor receptor 2 (HER2) positivity is associated with a worse prognosis in endometrial cancer (EC). Trastuzumab as a single agent did not demonstrate activity in such cases but there are no reports on its combined use with taxanes. We report the outcome in patients treated simultaneously with trastuzumab and paclitaxel for advanced or recurrent HER2-positive endometrial carcinoma and compared it to their microsatellite instability (MSI) status and PIK3CA mutational profiles.
PATIENTS AND METHODS: Patients with advancedor recurrent endometrial carcinoma showing HER2 overexpression (2+ or 3+ immunohistochemical staining) or HER2 amplification (fluorescence in situ hybridization (FISH) HER2/chromosome 17 centromere (CEP 17) ratio >2.0) were treated with trastuzumab (8 mg/kg) and paclitaxel (90 mg/m(2)) every three weeks. Evaluation of the response was assessed according to the response evaluation criteria in solid tumors (RECIST) guidelines. Endometrial tumors, sampled before the beginning of trastuzumab, were genotyped for PIK3CA hot spot mutations using Sequenom iPLEX Assay technology.
RESULTS: Two uterine serous adenocarcinomas and one grade 3 endometrioid adenocarcinoma showing HER2 positivity were treated with trastuzumab and paclitaxel. Between three and seven months of treatment, the three cases showed progressive disease. The genomic analysis of the three cases showed different mutational profiles. One case was found to have MSI and had one PIK3CA mutation. The two others showed no hot spot mutation for PIK3CA.
CONCLUSION: Even associated with paclitaxel, HER2-positive endometrial carcinomas poorly responded to trastuzumab. This report underlines the low accuracy of HER2 positivity to predict response of endometrial cancer to combined targeted therapy using trastuzumab and paclitaxel.

Mukai H, Saeki T, Aogi K, et al.
Patritumab plus trastuzumab and paclitaxel in human epidermal growth factor receptor 2-overexpressing metastatic breast cancer.
Cancer Sci. 2016; 107(10):1465-1470 [PubMed] Free Access to Full Article Related Publications
Human epidermal growth factor receptor 3 (HER3) expression in lung and breast cancers has a negative impact on survival. Patritumab, a human anti-HER3 mAb, has shown anticancer activity in preclinical models. This study examined the safety and pharmacokinetics of patritumab in combination with trastuzumab and paclitaxel in patients with HER2-overexpressing metastatic breast cancer. In this open-label, multicenter, dose-escalation, phase Ib study, patients received patritumab 9 or 18 mg/kg plus trastuzumab and paclitaxel at known tolerated doses. Safety and tolerability were assessed based on dose-limiting toxicities and other non-life threatening adverse events. The pharmacokinetic profile for patritumab was determined based on the target trough level. Clinical efficacy was evaluated based on the overall response rate and progression-free survival. Six patients received patritumab 9 mg/kg and 12 received 18 mg/kg. The most common adverse events were diarrhea, alopecia, leukopenia, neutropenia, and maculopapular rash. No dose-limiting toxicities were observed. The target trough serum concentration was achieved in all patients at a dose of 18 mg/kg. Overall response rate was 38.9% and median progression-free survival was 274 days. In conclusion, patritumab plus trastuzumab and paclitaxel was tolerable and efficacious at both doses. We recommend the dose level of 18 mg/kg for future phase II studies. (Clinical trial registration: JapicCTI-121772.).

Orlando L, Schiavone P, Calvani N, et al.
Response of extensive breast cancer skin metastases to rechallenge with trastuzumab together with low-dose chemotherapy and insulin.
Tumori. 2016; 102(Suppl. 2) [PubMed] Related Publications
INTRODUCTION: Cutaneous metastasis occurs in about 29% of breast cancer patients and has a deep impact on patient quality of life.
METHODS: A 60-year-old woman with cutaneous metastases from heavily pretreated HER2-positive breast cancer received CMFVP (oral cyclophosphamide 100 mg daily; oral prednisone 12.5 mg daily for 2 weeks, then 7.5 mg daily; intravenous weekly methotrexate 25 mg/m2, 5-5-fluorouracil 400 mg/m2 and vincristine 0.5 mg) with weekly trastuzumab and subcutaneous insulin until disease progression.
RESULTS: From March 2009 to November 2009 the patient was treated with the described regimen. At the best response, we observed the disappearance of some lesions and cessation of bleeding and thoracic pain. Time to progression was 8 months.
CONCLUSIONS: Our patient had clinical benefit from reintroduction of trastuzumab, low-dose chemotherapy and insulin. The explanation of this prolonged response is only speculative and requires further clinical confirmation in the treatment strategy of HER2-positive breast cancer.

Matyszewski A, Czarnecka AM, Stachowiak P, et al.
Cardiac safety of systemic therapy in breast cancer patients with high risk of atherosclerosis complications.
Future Oncol. 2017; 13(7):593-602 [PubMed] Related Publications
AIM: This study was designed to verify the efficacy of breast cancer treatment and its cardiac toxicity in population with significant cardiac comorbidities.
MATERIALS & METHODS: Prospective observational study was conducted in 48 patients.
RESULTS: The increase and dependence of echocardiographic parameter early/late were observed on hemoglobin level in all patients, and white blood cells and cholesterol in patients with diabetic were reported. Patients undergo left ventricle diameter change on treatment.
CONCLUSION: Use of potentially cardiotoxic chemo regimens in breast cancer patients with cardiac comorbidities, with optimized cardiac therapy accordingly can save patients from development of early myocardial dysfunction induced by chemotherapy - limiting factor to minimize the risk is optimization of lipid level, red blood cell count and platelets count.

Endo Y, Dong Y, Kondo N, et al.
HER2 mutation status in Japanese HER2-positive breast cancer patients.
Breast Cancer. 2016; 23(6):902-907 [PubMed] Related Publications
BACKGROUND: Human epidermal growth factor receptor 2 (HER2) gene amplification/overexpression is a major therapeutic target in breast cancer, and has been introduced as a predictive biomarker to identify patients who may benefit from therapy with anti-HER2 agents. HER2 somatic mutations have been reported, and these may influence the effect of HER2-targeted drugs.
METHODS: Here, we sought HER2 mutations in a group of 135 Japanese breast cancer patients with HER2-positive tumors. We analyzed HER2 mutations by direct Sanger sequencing of two major areas, the extracellular domain at position 309-310 and the kinase domain between 755 and 781.
RESULTS: Two patients with the HER2 somatic mutation S310F in the extracellular domain were found in this series. One patient with the S310F mutation had a node-negative invasive ductal carcinoma classified as HER2 2+ by the HercepTest and fluorescence in situ hybridization (FISH) positive, and which was estrogen receptor (ER)-negative and progesterone receptor (PgR)-negative. Another patient with the S310F mutation had an apocrine carcinoma with seven lymph nodes positive for metastasis, classified as HER2 3+ by the HercepTest, but which was FISH-negative, as well as ER-negative and PgR-negative. Both patients had received adjuvant single-agent trastuzumab therapy, and had no local recurrence or distant metastasis for five and three years after surgery, respectively.
CONCLUSIONS: Our data show that HER2 mutations are rare in HER2-positive Japanese breast cancer patients. The two mutations found in this study were identical, S310F. We suggest that in vitro experiments to determine whether the S310F mutation could be involved in resistance to anti-HER2 drugs are worthwhile in future.

Rodríguez-Serrano F, Mut-Salud N, Cruz-Bustos T, et al.
Functionalized immunostimulating complexes with protein A via lipid vinyl sulfones to deliver cancer drugs to trastuzumab-resistant HER2-overexpressing breast cancer cells.
Int J Nanomedicine. 2016; 11:4777-4785 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Around 20%-30% of breast cancers overexpress the proto-oncogene human epidermal growth receptor 2 (HER2), and they are characterized by being very invasive. Therefore, many current studies are focused on testing new therapies against tumors that overexpress this receptor. In particular, there exists major interest in new strategies to fight breast cancer resistant to trastuzumab (Tmab), a humanized antibody that binds specifically to HER2 interfering with its mitogenic signaling. Our team has previously developed immunostimulating complexes (ISCOMs) as nanocapsules functionalized with lipid vinyl sulfones, which can incorporate protein A and bind to G immunoglobulins that makes them very flexible nanocarriers.
METHODS AND RESULTS: The aim of this in vitro study was to synthesize and evaluate a drug delivery system based on protein A-functionalized ISCOMs to target HER2-overexpressing cells. We describe the preparation of ISCOMs, the loading with the drugs doxorubicin and paclitaxel, the binding of ISCOMs to alkyl vinyl sulfone-protein A, the coupling of Tmab, and the evaluation in both HER2-overexpressing breast cancer cells (HCC1954) and non-overexpressing cells (MCF-7) by flow cytometry and fluorescence microscopy. Results show that the uptake is dependent on the level of overexpression of HER2, and the analysis of the cell viability reveals that targeted drugs are selective toward HCC1954, whereas MCF-7 cells remain unaffected.
CONCLUSION: Protein A-functionalized ISCOMs are versatile carriers that can be coupled to antibodies that act as targeting agents to deliver drugs. When coupling to Tmab and loading with paclitaxel or doxorubicin, they become efficient vehicles for the selective delivery of the drug to Tmab-resistant HER2-overexpressing breast cancer cells. These nanoparticles may pave the way for the development of novel therapies for poor prognosis resistant patients.

Niraula S, Ocana A
Mechanism of drug resistance in relation to site of metastasis: Meta-analyses of randomized controlled trials in advanced breast cancer according to anticancer strategy.
Cancer Treat Rev. 2016; 50:168-174 [PubMed] Related Publications
BACKGROUND: Breast cancer is heterogeneous at different levels: biologic subtypes, intratumoral areas, and sites of metastases. Randomized controlled trials (RCTs) classify metastatic sites as visceral or non-visceral, but this has little influence in treatment decisions, particularly in the absence of clinical urgency. Indeed, it is unclear if response to treatments differs among sites of metastases.
PATIENTS AND METHODS: RCTs investigating 3 different anticancer strategies in metastatic breast cancer were identified: (1) new hormonal therapy, (2) new targeted therapies in hormone receptor positive tumours (everolimus or palbociclib), and (3) new anti-HER2 therapies. RCTs reporting hazard ratios (HR) for Progression Free Survival (PFS) and Overall Survival (OS) for sub-groups based on sites of metastases were weighted using generic inverse variance approach, and pooled in meta-analyses using Revman 5.3. Subgroup difference was tested with Chi(2) statistics.
RESULTS: Eleven RCTs (6701pts.) qualified. There was a significant difference in PFS between women with visceral versus non-visceral metastases when two endocrine strategies were compared, with benefits limited to women with visceral metastases [Pooled HR 0.85; 95% CI, 0.77-0.95 versus 1.02 (0.88-1.18) for non-visceral; p(difference)=0.05]. However, combination of an endocrine therapy and a targeted therapy was associated with better PFS compared to endocrine therapy alone for both groups [HR 0.51 (0.43-0.60) versus 0.45 (0.36-0.56) for non-visceral; p(difference)=0. 36]. Novel HER-2 targeted therapies were associated with significantly better PFS and OS only in visceral metastases [HR 0.59 (0.52-0.66) versus 0.71(0.44-1.13) for non-visceral, p(difference)=0.45, for PFS; and 0.64 (0.56-0.73) versus 0.82 (0.57=1.19) for non-visceral, p(difference)=0.20, for OS].
CONCLUSION: Combination of targeted agents and endocrine therapy results in concordant, superior PFS suggesting targetable endocrine resistance across metastatic sites. Discordant responses with endocrine strategy alone support use of targeted therapy, rather than change in endocrine agent at disease progression. HER2 targeted therapies may be less effective in areas of poor vascularization.

Ozen M, Gunduz M, Ates O, et al.
Trastuzumab 1-year vs 9-week in early-stage HER2-positive, lymph node negative breast cancer patients.
J BUON. 2016 Jul-Aug; 21(4):799-808 [PubMed] Related Publications
PURPOSE: Optimal duration of adjuvant trastuzumab therapy in early-stage HER2-positive, lymph node-negative breast cancer is unknown. To establish this, we compared 1-year and 9-week trastuzumab regimens in HER2-positive, lymph node-negative early-stage breast cancer patients.
METHODS: We retrospectively analyzed 4374 breast cancer patients. There were 181 early-stage, lymph node-negative breast cancer patients who were treated with adjuvant trastuzumab for either 9-week or 1-year schedule. A total of 101 patients received trastuzumab for 9 weeks and the remaining 80 patients received this adjuvant therapy for 1 year. Disease free survival (DFS) and overall survival (OS) rates of both groups were calculated.
RESULTS: There was no difference between groups according to OS. Five-year OS rates were 95.5% in the 9-week group and 93.3% in the 1-year group (p=0.78). DFS was affected by age, having tamoxifen therapy and disease stage. Nine-week trastuzumab group was superior to 1-year group and 5-year DFS rates were 91% in 9-week group and 81.2% in 1-year group (p=0.02). However, the 1-year group had more stage II patients than the 9-week group. We did not find any difference between groups regarding developing congestive heart failure.
CONCLUSION: It appeared that 9-week trastuzumab treatment was not inferior to 1-year trastuzumab treatment in early-stage, lymph node-negative breast cancer patients.

Wang Y, Liu J, Jia W, et al.
Comparison of the Therapeutic Efficacy of the Early and the Delayed Use of Vinorelbine-Based Regimens for Patients with Advanced Breast Cancer.
Chemotherapy. 2017; 62(1):71-79 [PubMed] Related Publications
BACKGROUND: The aim of this study was to evaluate the efficacy of vinorelbine-based regimens as first-, second- and more-line therapies in advanced breast cancer (ABC) and to analyze the best timing of vinorelbine treatment.
METHODS: A total of 71 ABC patients were retrospectively reviewed. Of these, 35 patients were treated with vinorelbine-based regimens as first-line chemotherapy, and 36 patients were treated with vinorelbine-based regimens as second-line or more-line therapy. The primary end point of the study was progression-free survival (PFS).
RESULTS: No difference was found in baseline characteristics between the two groups (p > 0.1 for all comparisons). There was a significant difference in the objective response rate (ORR; p = 0.006) and clinical benefit rate (CBR; p = 0.013) between the first-line group and the second- or more-line groups. In the vinorelbine first-line group, the ORR was 68.6% (24 patients), and in the second-line or more-line groups the ORR was 36.1% (13 patients). A significant difference in PFS between the first-line group and the second-line or more-line groups was also observed (p = 0.030). The median PFS in the overall population was 6.3 ± 1.32 months (95% CI 3.69-8.90). The median PFS was 11.1 ± 3.76 months (95% CI 3.73-18.47) in the first-line group compared with 5.2 ± 1.35 months (95% CI 2.54-7.85) in the second-line or more-line groups. In patients treated with vinorelbine-trastuzumab combination as the first-line therapy, a complete response was observed in 1 patient (12.5%) and partial response in 5 patients (62.5%), giving an ORR of 75.0%. Progressive disease was observed in 1 patient (12.5%), and stable disease in 1 patient (12.5%), leading to a CBR of 87.5%. The median PFS was 13.8 ± 2.75 months (95% CI 8.42-19.18), and median OS was 37.0 ± 11.6 months (95% CI 14.18-59.82). No significant difference was found in overall survival (OS) between the groups (p = 0.612).
CONCLUSION: For ABC patients, no significant difference in median OS was found between the early use and delayed use of vinorelbine-based regimens, but the short-term efficacy and PFS of vinorelbine-based regimens were significantly better in the early use group than in the delayed use group.

Motallebnezhad M, Younesi V, Aghebati-Maleki L, et al.
Antiproliferative and apoptotic effects of a specific anti-insulin-like growth factor I receptor single chain antibody on breast cancer cells.
Tumour Biol. 2016; 37(11):14841-14850 [PubMed] Related Publications
Insulin-like growth factor I receptor (IGF-IR) is expressed on breast cancer cells and involves in metastasis, survival, and proliferation. Currently, application of IGF-IR-targeting monoclonal antibodies (mAbs), alone or in combination with other drugs, is a promising strategy for breast cancer therapy. Single-chain fragment variable (scFv) antibodies have been introduced as appropriate tools for tumor-targeting purposes because of their advantages over whole antibodies. In the present study, we employed a naïve phage library and isolated scFvs against a specific epitope from extracellular domain of IGF-IR by panning process. The selected scFvs were further characterized using polyclonal and monoclonal phage ELISA, soluble monoclonal ELISA, and colony PCR and sequencing. Antiproliferative and apoptotic effects of selected scFv antibodies on breast cancer cell lines were also evaluated by MTT and Annexin V/PI assays. The results of ELISA indicated specific reactions of the isolated scFvs against the IGF-IR peptide, and analyses of PCR product and sequencing confirmed the presence of full length VH and Vκ inserts. Treatment of MCF7 and SKBR3 cells with anti-IGF-IR scFv led to a significant growth inhibition. The results also showed that scFv treatment significantly augmented trastuzumab growth inhibitory effects on SKBR3 cells. The percentage of the apoptotic MCF7 and SKBR3 cells after 24-h treatment with scFv was 39 and 30.70 %, respectively. Twenty-four-hour treatment with scFv in combination with trastuzumab resulted in 44.75 % apoptosis of SKBR3 cells. Taken together, our results demonstrate that the targeting of IGF-IR by scFv can be an effective strategy in the treatment of breast cancer and provide further evidence for effectiveness of dual targeting of HER2 and IGF-IR in breast cancer therapy.

Furrer D, Jacob S, Caron C, et al.
Tissue Microarray Is a Reliable Tool for the Evaluation of HER2 Amplification in Breast Cancer.
Anticancer Res. 2016; 36(9):4661-6 [PubMed] Related Publications
AIM: We examined an economical method for evaluating the amplification of the human epidermal growth factor receptor 2 (HER2) gene in breast cancer specimens.
MATERIALS AND METHODS: We compared HER2 amplification determined by fluorescence in situ hybridization (FISH) on whole-tissue (WT) blocks used for diagnostic and on tissue microarray (TMA) sections for a cohort of 521 consecutive patients with breast cancer. In a subset of 116 patients, we examined HER2 concordance from the WT section and a TMA section from a randomly chosen additional block (a proxy of the core biopsy).
RESULTS: Overall concordance for HER2 amplification between WT and TMA sections was 98.2%, and between sections from WT and from the additional block was 99.0%.
CONCLUSION: The high concordance rates support the use of TMA for the evaluation of HER2 amplification in breast cancer and suggest that FISH can be used to assess HER2 using core biopsies.

Uneno Y, Yokoyama A, Nishikawa Y, et al.
Paraneoplastic Limbic Encephalitis in a Human Epidermal Growth Factor Receptor-2-positive Gastric Cancer Patient Treated with Trastuzumab-combined Chemotherapy: A Case Report and Literature Review.
Intern Med. 2016; 55(18):2605-9 [PubMed] Related Publications
Paraneoplastic neurological syndromes (PNSs) are rare nervous system dysfunctions in cancer patients, which are primarily observed with small-cell lung cancer, gynecological cancer, and thymoma. We herein present an uncommon case of PNS in an anti-Hu antibody-positive patient with human epidermal growth factor receptor (HER)-2-positive gastric cancer (GC), who developed limbic encephalitis and a worsening cognitive function. Trastuzumab-combined chemotherapy was initiated and appeared to be partially effective for controlling the neurological symptoms and tumor volume. Chemotherapy failure eventually led to uncontrollable neurological symptoms. This is the first case demonstrating that trastuzumab-combined chemotherapy may be effective for controlling neurological symptoms of PNS in HER2-positive GC patients.

Li Y, Zhang R, Han Y, et al.
Comparison of the types of candidate reference samples for quality control of human epidermal growth factor receptor 2 status detection.
Diagn Pathol. 2016; 11(1):85 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Human epidermal growth factor receptor 2 (HER2) is as a target gene for trastuzumab in patients with breast cancer. Accurate determination of HER2 status and strict quality control are necessary to ensure reproducibility and accuracy of the techniques used for the determination of HER2 status.
METHODS: We used three different types of samples: formalin-fixed and paraffin-embedded (FFPE) samples prepared from cell lines, agarose gel samples using cell lines, and xenograft tumor samples. One cell line for FFPE or xenografts did not overexpress HER2, while the others showed different levels of HER2 overexpression. We compared the morphology, HER2 gene amplification status, and HER2 protein expression status of these samples with those of clinical specimens.
RESULTS: We successfully produced three kinds of samples for quality control. Cells from the cell line-sample sections were dispersed while those from the agarose gel-sample sections and xenograft tumor sample sections (prepared from the both cell lines) were concentrated in one area. The FISH results for all three kinds of samples were as expected. The IHC results of the cell line samples and xenograft tumor samples were as expected, but the staining level of the agarose gel samples, using HER2-overexpressed cell lines was weak which might be regarded as a false negative result.
CONCLUSIONS: Xenograft tumor samples might be used as an additional option for quality control in FISH and IHC. However, it might not replace the clinical specimen quality controls directly.

van Netten JP, Hoption Cann S, Thornton I, Finegan R
Growing concern following compression mammography.
BMJ Case Rep. 2016; 2016 [PubMed] Related Publications
A patient without clinical symptoms had a mammogram in October 2008. The procedure caused intense persistent pain, swelling and development of a haematoma following mediolateral left breast compression. Three months later, a 9×11 cm mass developed within the same region. Core biopsies showed a necrotizing high-grade ductal carcinoma, with a high mitotic index. Owing to its extensive size, the patient began chemotherapy followed by trastuzumab and later radiotherapy to obtain clear margins for a subsequent mastectomy. The mastectomy in October 2009 revealed an inflammatory carcinoma, with 2 of 3 nodes infiltrated by the tumour. The stage IIIC tumour, oestrogen and progesterone receptor negative, was highly HER2 positive. A recurrence led to further chemotherapy in February 2011. In July 2011, another recurrence was removed from the mastectomy scar. She died of progressive disease in 2012. In this article, we discuss the potential influence of compression on the natural history of the tumour.

Esclovon JW, Ponder M, Aydin N, Misra S
Challenges of treating incidental synchronous bilateral breast cancer with differing tumour biology.
BMJ Case Rep. 2016; 2016 [PubMed] Related Publications
A 59-year-old woman with right breast mass was diagnosed with invasive ductal carcinoma (IDC). Workup consisted of bilateral diagnostic mammogram and ultrasound (US); both showed a right breast mass with normal left breast. Core biopsy showed IDC with estrogen receptor negative (ER-)/progesterone receptor negative (PR-) and HER2/neu positive receptor status. The patient underwent carboplatin-based chemotherapy with Herceptin. The mass completely resolved. The patient desired to proceed with bilateral total mastectomy with right sentinel lymph node biopsy (SLNB). Pathology showed complete resolution of the right-sided breast mass without malignancy in right SLN. Incidentally, IDC was found in the left breast specimen, which was ER+/PR+ and HER 2/neu negative. Tumour board consensus was to obtain a left axilla US with MRI in 6 months if the US was unremarkable. Biologically different synchronous bilateral breast cancer poses a difficult clinical challenge for management due to differing responses to treatment. Use of MRI may be a diagnostic option in women who choose contralateral prophylactic mastectomy.

Cao L, Cai G, Xu F, et al.
Trastuzumab improves locoregional control in HER2-positive breast cancer patients following adjuvant radiotherapy.
Medicine (Baltimore). 2016; 95(32):e4230 [PubMed] Free Access to Full Article Related Publications
The benefit of adjuvant trastuzumab in disease-free and overall survival for human epidermal receptor 2-positive (HER2+) breast cancer patients is well established. However, the effect of trastuzumab on locoregional control remains unclear, particularly in patients treated with adjuvant radiotherapy (RT). In this study, we investigated the locoregional benefit of trastuzumab in patients with HER2+ breast cancer after adjuvant RT.Using a single institutional database, we identified 278 patients with stage II/III invasive HER2+ breast tumors receiving adjuvant RT between January 2008 and July 2011. We compared the locoregional outcomes of 134 patients who received trastuzumab to 144 patients without trastuzumab within the same period. Clinical and biological factors that might impact on the locoregional benefit of trastuzumab were also assessed.At the median follow-up of 45 months, trastuzumab significantly lowered the risk of locoregional recurrence (LRR) with a 3-year LRR rate of 2.4% versus 7.5% for the cohort with and without trastuzumab (P = 0.019). Trastuzumab was associated with a more significant locoregional benefit in the hormone receptor-positive (HR+)/HER2+ subgroup, with a 3-year LRR of 0% versus 6.7% in the cohort with and without trastuzumab (P = 0.027). For HR-/HER2+ breast tumor patients, the 3-year LRR rate was still lower for the cohort with trastuzumab (4.7% vs 8.6%). However, statistical significance was not found (P = 0.179). Both univariate and multivariate analyses confirmed that trastuzumab treatment was the only significant predictive factor for LRR (hazard ratio, 4.05; 95% confidence interval, 1.07-15.35; P = 0.039).Adjuvant trastuzumab in addition to RT is associated with significant reduced LRR risk in HER2+ breast cancer.

Rasmy A, Abozeed W, Elsamany S, et al.
Correlation of Preoperative Ki67 and Serum CA15.3 Levels with Outcome in Early Breast Cancers a Multi Institutional Study.
Asian Pac J Cancer Prev. 2016; 17(7):3595-600 [PubMed] Related Publications
BACKGROUND: To investigate the association between preoperative pathological Ki67 labeling index and serum tumor marker cancer antigen 153 (CA 153) with clinicpathological parameters and treatment outcomes in early breast cancer.
MATERIALS AND METHODS: A retrospective study at 4 cancer centers in Saudi Arabia and Egypt was performed. Data were collected for female patients diagnosed with unilateral early breast cancer between March 2010 and October 2013. Cases treated with neoadjuvant chemotherapy (NACT) followed by surgery and radiotherapy were included. NACT included 68 cycles of anthracycline and taxane based regimens. Trastuzumab and hormonal treatments were added according to HER2 and hormone receptor status. Baseline serum CA15.3 and pathological Ki67 levels were evaluated and correlated with disease free survival (DFS) and overall survival (OS).
RESULTS: A total of 280 pts was included. The median age was 49 years (3866 y) and median overall survival was 35 (2038) months (mo). Estrogen receptors (ER), progesterone receptors (PR) and HER 2 receptors were positive in 233 (83.2%), 198 (70%) and 65 cases (23.2%), respectively. High preoperative Ki67 and CA15.3 were noted in 177 (63.2%) and 131 (46.8%). A total of 45 (16%) patients had distal or local recurrence and 24 (8.6%) died of their disease. Most of the relapsed cases had high preoperative Ki67 (n=41, 91%) and CA15.3 (n=28, 62%) values. All of the patients who died had a high Ki67 but CA15.3 was high in 9 (37%) only. Mean DFS/OS in patients with high preoperative Ki67 was 32 months /32 months as compared to 37 months/35 months in those with normal Ki67 (p<0.001). Correlation of preoperative CA15.3 and survival was statistically not significant.
CONCLUSIONS: Preoperative Ki67 can be a predictive and prognostic marker. Higher levels are associated with poor DFS and OS in patients with early BC.

CancerIndex.org
Disclaimer: This site is for educational purposes only; it can not be used in diagnosis or treatment.
About

[Home]    Page last updated: 07 March, 2017     © CancerIndex, Established 1996