Systemic Targeted Therapy for her2-Positive Early Female Breast Cancer: A Systematic Review of the Evidence for the 2014 Cancer Care Ontario Systemic Therapy Guideline

Abstract

BackgroundThis systematic review addresses the question “What is the optimal targeted therapy for female patients with early-stage human epidermal growth factor receptor 2 (her2)–positive breast cancer?”MethodsThe medline and embase databases were searched for the period January 2008 to May 2014. The Standards and Guidelines Evidence directory of cancer guidelines and the Web sites of major guideline organizations were also searched.ResultsSixty publications relevant to the targeted therapy portion of the systematic review were identified. In four major trials (hera, National Surgical Adjuvant Breast and Bowel Project B-31, North Central Cancer Treatment Group N9831, and Breast Cancer International Research Group 006), adjuvant trastuzumab for 1 year was superior in disease-free survival (dfs) and overall survival (os) to no trastuzumab; trastuzumab showed no benefit in one trial (pacs 04). A shorter duration of trastuzumab (less than 1 year compared with 1 year) was evaluated, with mixed results for dfs: one trial showed superiority (finher), one trial could not demonstrate noninferiority (phare), another trial showed equivalent results (E 2198), and one trial is still ongoing (persephone). Longer trastuzumab duration (hera: 2 years vs. 1 year) showed no improvement in dfs or os and a higher rate of cardiac events. Newer her2-targeted agents (lapatinib, pertuzumab, T-DM1, neratinib) have been or are still being evaluated in both adjuvant and neoadjuvant trials, either by direct comparison with trastuzumab alone or combined with trastuzumab. In the neoadjuvant setting (neoaltto, GeparQuinto, Neosphere), trastuzumab alone or in combination with another anti-her2 agent (lapatinib, pertuzumab) was compared with either lapatinib or pertuzumab alone and showed superior or equivalent rates of pathologic complete response. In the adjuvant setting, lapatinib alone or in combination with trastuzumab, compared with trastuzumab alone (altto) or with placebo (teach), was not superior in dfs. The results of the completed aphinity trial, evaluating the role of dual her2 blockade with trastuzumab and pertuzumab, are highly anticipated. Ongoing trials are evaluating trastuzumab as a single agent without adjuvant chemotherapy (respect) and in patients with low her2 expression (National Surgical Adjuvant Breast and Bowel Project B-47).ConclusionsTaking into consideration disease characteristics and patient preference, 1 year of trastuzumab should be offered to all patients with her2-positive breast cancer who are receiving adjuvant chemotherapy. Cardiac function should be regularly assessed in this patient population.

Immunohistochemical Expression of the Promising Therapeutic Target (Human Epidermal Growth Factor Receptor 2/Neu) in Iraqi Patients With Medulloblastoma

“…After antigen retrieval was performed, the tissue sections were covered with peroxide block solution for 5 min followed by incubation of primary antibody for 30 min, then the tissue sections covered with poly excel poly HRP and incubate for 30 min at room temperature, working solution and incubate for 5 min at room temperature, and finally hematoxyline stain was applied. Immunohistochemically stained sections were evaluated under a light microscope(leica DM500) independently by three pathologists by using the same scoring system established to evaluate HER2/NEU in breast cancer [18]. Score 0 no staining or membranous staining is observed in <10% of the tumor cells.…”

The renaissance of anti‐neoplastic immunity from tumor cell demise

“…Other TKI selectively target non‐receptor tyrosine kinases, such as the Abelson murine leukemia viral oncogene homolog 1 (Abl) family of kinases c‐Abl and Bcr‐Abl . Tumor outgrowth can also be restrained by limiting oxygen, nutrients, and growth‐stimulating signals with specific monoclonal antibodies (mAb) against VEGF and human epidermal growth factor receptor 2 (HER‐2) …”

“…18 Tumor outgrowth can also be restrained by limiting oxygen, nutrients, and growth-stimulating signals with specific monoclonal antibodies (mAb) against VEGF and human epidermal growth factor receptor 2 (HER-2). 19,20 Alternatively, targeted drugs can be designed against genetic mutations in cancer cells. A dominant mutation at the V600E amino acid of the v-raf murine sarcoma viral oncogene homolog B1 (BRAF) causes aberrant activation of mitogen-activated protein kinase (MAPK).…”

Precision medicine in cancer: beyond wishful thinking?

“…In the nineties of the last century, the monoclonal antibody trastuzumab, targeted against the Her2 receptor, was introduced into the clinic and usually combined with paclitaxel. Since then, therapy of female breast cancer improved a lot, with a high 5-year survival (>90%), especially when the patients are estrogen or HER2 receptor positive [4].…”