In Reply
Authors: Lyndsay Harris, Deborah Toppmeyer, Bruce G. Haffty
Journal: Journal of Clinical Oncology (2007)

luminal and normal-like cancers.Another neoadjuvant study 6 suggested that the clinical response to doxorubicin and cyclophosphamide was markedly higher among patients with triple negative tumors than among those with nontriple negative tumors.Pathologic complete response to neoadjuvant chemotherapy was higher in patients with triple negative tumors than in those with nontriple negative-like tumors.Unfortunately, in this study, 34% of triple negative patients did not receive chemotherapy, and among the patients who received adjuvant chemotherapy (66%) only 41% and 6% of them received anthracycline and taxanes as an adjuvant treatment, respectively.Therefore, lack of effective adjuvant treatment in this study may further lead to poorer prognosis.The authors also mentioned potential chemotherapeutic agents that may be effective in the management of triple negative breast cancer, such as epidermal growth factor receptor inhibitors.It is worth mentioning other possible agents that may be effective in this specific subgroup.BRCA1 pathway activity may be impaired in many triple negative breast cancers.BRCA1 functions in DNA repair and cell cycle checkpoint responses may result in sensitivity to DNA damaging agents, such as cisplatin, and resistance to spindle poisons. 7 Recently Moyana et al 8 reported that small heat-shock protein alpha-basic crystallin was commonly expressed in triple negative tumors and predicted poor survival in breast cancer patients independently of other prognostic markers.Alpha B crystallin overexpression also induced epidermal growth factor-and anchorage-independent growth, increased cell migration and invasion, and constitutively activated the mitogen-activated protein kinase/ERK (mitogenactivated extracellular signal regulated kinase/ERK) pathway.Therefore mitogen-activated extracellular signal regulated kinase inhibitors may be an effective therapy for triple negative breast tumors expressing alpha B crystallin.Recent study by Pinilla et al 9 showed that caveolin-1 (CAV1) expression is associated with a triple negative phenotype in sporadic and hereditary breast cancer.ABI-007 (Abraxane; American BioScience Inc, Santa Monica, CA) is a novel, biologically interactive, nanometer-sized albumin-bound paclitaxel particle initially developed to avoid the toxicities associated with polyethylated castor oil.In their phase III study, Gradishar et al 10 compared albumin-bound nanoparticle paclitaxel, ABI-007 with polyethylated castor oil-based paclitaxel in women with metastatic breast cancer.This study showed greater efficacy and a favorable safety profile of ABI-007 though no subgroup analysis of molecular phenotypes for differential efficacy of the treatment was performed.After the incorporation of ABI-007 with albumin in blood circulation, ABI-007 is preferentially transported from blood to tumor site in two ways.One way is through leaky junction of endothelial cells that are highly pronounced around the tumor tissue by induction of angiogenesis.The second way and perhaps more prominent way is acting through receptor-mediated transcytosis of this albumin-bound This second mechanism is mediated by CAV-1.Breast cancer patients with higher CAV-1 expression, as in the cases of breast cancer with triple negative phenotype, may show better efficacy with more favorable safety profile if they receive ABI-007.In conclusion, standard adjuvant chemotherapy seems to be less effective in breast cancer with triple negative type and new therapeutic approaches are indicated.Greater understanding of the pathologic and molecular characteristics of this phenotype may lead us to tailor the treatment for these patients.