Metastatic Breast Cancer: Therapeutic Options According to Molecular Subtypes and Prior Adjuvant Therapy

Abstract

In spite of advances in treatment strategies, about 25%-40% of patients with breast cancer still eventually develop metastatic disease that is largely incurable. Treatment goals vary from symptom control to lengthening survival, mainly on the basis of patient age and performance status, tumor biology, site and extent of disease, and prior therapies. In particular, breast cancer molecular characterization allows for the identification of breast cancer subtypes with distinct biological features, a distinct clinical course, and distinct treatment sensitivity.Endocrine manipulation is the cornerstone of therapy in hormone receptor-positive tumors; anti-human epidermal growth factor receptor (HER)-2 agents are essential in the management of HER-2 ؉ tumors; and chemotherapy is the only available option so far for the triple-negative subtype. In each of these subtypes, the more efficacious agents have been progressively incorporated into adjuvant treatment. As a consequence, the choice of the optimal therapeutic strategy for patients with metastatic disease is largely influenced by prior exposure to adjuvant therapies. This review contextualizes the data from clinical trials into different clinical scenarios of metastatic disease, taking into account the molecular subtype and prior adjuvant treatments. The Oncologist 2009;14:645-656

Pivotal Role of Reducedlet-7gExpression in Breast Cancer Invasion and Metastasis

“…In this study, we showed that E2 and EGF, major prometastatic growth factors in breast cancer (44)(45)(46), specifically repress let-7g expression and subsequently increase GAB2 and FN1 expression, which, in turn, cooperatively increased the activity of p44/42 MAPK and MMP-2/MMP-9. It has been reported recently that the p44/42 MAPK cascade may repress let-7 expression either via activating LIN28 transcription to affect primary let-7g processing (47) or via phosphorylating TAR RNA-binding protein, a critical component of miRNA-generating complex, to suppress the expression of let-7 miRNAs (36).…”

Clinicopathological Features of Indonesian Breast Cancers with Different Molecular Subtypes

“…P-53 mutation and cell proliferation rate in breast cancer are important markers for poor prognostic prediction. Luminal A subtype cancers also had lower recurency rate (27.8%) and higher survival rate (median survival rate: 2.2 years) in compare to non luminal cancers (Eroles et al, 2012;Guarneri et al, 2009). A study in Chinese cancer women found that luminal A subtype had the highest locoregional relaps -free survival (93.2%), distant metastasis-free survival (91.5%) and disease free survival rates (87.5%) at 5 years, while Her-2+ subtypes showed the highest rate reccurence (27.5%) and locoregional recurrence (11.4%) (Jia et al, 2014).…”

Biological subtypes of breast cancer: Prognostic and therapeutic implications

“…Patients with luminal-A breast cancer have a good prognosis; the relapse rate is significantly lower than the other subtypes. Recurrence is common in bone, whereas liver, lung and central nervous system metastases occur in less than 10% of patients and treatment is mainly based on hormonal therapy [15,16] .…”