Biomarkers in Her2- Positive Disease

Abstract

<b><i>Background:</i></b> Breast cancer is a heterogeneous disease with well-known characteristics such as hormone receptor (HR) status and human epidermal growth factor (Her)2 status. Although Her2 represents an established treatment target, the development of resistance mechanisms during treatment, cardiotoxicity, and a worse response to standard therapies lead to worse outcomes. <b><i>Summary:</i></b> Therefore, we investigated various biomarkers in breast cancer such as Her2 mutations, Her2 heterogeneity, HR, PIK3CA, PTEN, programmed death receptor ligand 1 (PD-L1), tumor-infiltrating lymphocytes (TIL), micro RNA (miRNA), and BRCA mutations with regard to their clinical impact in Her2-positive disease. HR status and Her2 status, such as the presence of PIK3CA mutations, already play a role in treatment decision-making processes, whereas other biomarkers like PD-L1 status or TIL represent promising future markers. The influence of BRCA mutations in Her2-positive disease, Her2 mutations, and the impact of miRNA is vague to date. Antibody-drug conjugates (ADC) such as T-DM have been established as important treatment strategies, especially in Her2-positive disease. <b><i>Key Message:</i></b> However, up-to-date biomarkers appropriate for clinical practice are missing. Further studies are needed.

Intratumoral Heterogeneity and Immune Response Indicators to Predict Overall Survival in a Retrospective Study of HER2-Borderline (IHC 2+) Breast Cancer Patients

“…Novel prognostic BC biomarkers have been intensively investigated as recently reviewed by Wu et al (4). In particular, robust biomarkers are in demand for HER2-positive disease to improve selection of patients for current and emerging therapies of HER2-positive metastatic BC (5) as well as for prediction of resistance for anti-HER2 therapies, recurrence (6,7), and particular consequences of the disease (8). Novel approaches based on pathology image analytics and machine learning methods open new perspectives for predictive modeling and clinical decision support (9,10).…”

Inetetamab in combination with rapamycin and chemotherapy for trastuzumab‐treated metastatic human epidermal growth factor receptor 2‐positive breast cancer with abnormal activation of PI3K/Akt/mTOR pathway

“…Accumulating evidence suggests that PIK3CA mutations are associated with a poorer prognosis and are more likely to lead to drug resistance. 17 Preclinical studies have implicated that the combination of PI3K/ AKT/mTOR pathway inhibitors can enhance the antiproliferative activity of anti-HER-2 therapy and overcome resistance to anti-HER-2 therapy. [18][19][20][21] The BOLERO-3 study showed that everolimus (mTOR inhibitors) in combination with trastuzumab and vincristine significantly prolonged the PFS of HER2-positive, trastuzumab-resistant patients who previously received paclitaxelbased chemotherapy (7.00 months vs. 5.78 months, p = .0067).…”

“…PIK3CA mutations are associated with activation of the PI3K/AKT/mTOR pathway, leading to abnormal activation of this pathway and in turn stimulates tumor proliferation, metastasis, and invasion. Accumulating evidence suggests that PIK3CA mutations are associated with a poorer prognosis and are more likely to lead to drug resistance 17 …”

Does the 21-gene recurrence score have clinical utility in HR+/HER2+ breast cancer?

“…HER2 is one of four transmembrane growth factors that comprise the epidermal growth factor receptor (EGFR) family (4). Tumors that overexpress HER2 constitute around one fifth of breast cancers.…”

“…Alternatively, aromatase inhibitors decrease the natural conversion of androgens to estrogens in the body – effectively ‘starving’ neoplastic cells of the hormones that would otherwise stimulate their growth. HER2 is one of four transmembrane growth factors that comprise the epidermal growth factor receptor (EGFR) family [ 4 ]. Tumors that overexpress HER2 constitute around one fifth of breast cancers.…”