title: Breast cancer molecular subtypes: from TNBC to QNBC.
abstract: Treatment protocols for breast cancer depend predominantly on receptor status with respect to estrogen (estrogen receptor alpha), progesterone (progesterone receptor) and human epidermal growth factor [human epidermal growth factor receptor 2 (HER2)]. The presence of one or more of these receptors suggests that a treatment targeting these pathways might be effective, while the absence of, or in the case of HER2, lack of overexpression of, all of these receptors, termed triple negative breast cancer (TNBC), indicates a need for the more toxic chemotherapy. In an effort to develop targeted therapies for TNBC, it will be necessary to differentiate among specific TNBC subtypes. The subset of TNBC that expresses androgen receptor (AR) has been determined to express genes consistent with a luminal subtype and therefore may be amenable to therapies targeting either AR, itself, or other pathways typical of a luminal subtype. Recent investigations of the AR signal pathway within breast cancer lead to AR as a significant target for breast cancer therapy with several clinical trials currently in progress. The subclass of TNBC that lacks AR, which we have termed quadruple negative breast cancer (QNBC) currently lacks a defined targetable pathway. Unlike AR-positive TNBC, QNBC predominantly exhibits a basal-like molecular subtype. Several subtypes and related pathway proteins are preferentially expressed in QNBC that may serve as effective targets for treatment, such as ACSL4, SKP2 and EGFR. ACSL4 expression has been demonstrated to be inversely correlated with expression of hormone/growth factor receptors and may thus serve as a biomarker for QNBC as well as a target for therapy. In the following review we summarize some of the current efforts to develop alternatives to chemotherapy for TNBC and QNBC.
authors.affiliation: Department of Pathology, Rutgers Robert Wood Johnson Medical School Piscataway, NJ, USA.
authors.forename: Jane Date C
authors.initials: JD
authors.lastname: Hon
authors.affiliation: Department of Pathology, New York University School of Medicine New York, NY, USA.
authors.forename: Baljit
authors.initials: B
authors.lastname: Singh
authors.affiliation: Department of Pathology, UT MD Anderson Cancer Center Houston, TX, USA.
authors.forename: Aysegul
authors.initials: A
authors.lastname: Sahin
authors.affiliation: Department of Pediatrics, New York University School of MedicineNew York, NY, USA; Department of NYU Cancer Institute, New York University School of MedicineNew York, NY, USA.
authors.forename: Gang
authors.initials: G
authors.lastname: Du
authors.affiliation: Department of Pediatrics, New York University School of MedicineNew York, NY, USA; Department of NYU Cancer Institute, New York University School of MedicineNew York, NY, USA.
authors.forename: Jinhua
authors.initials: J
authors.lastname: Wang
authors.affiliation: Association of Chinese American Physicians Flushing, NY, USA.
authors.forename: Vincent Y
authors.initials: VY
authors.lastname: Wang
authors.affiliation: Department of Pathology, New York University School of MedicineNew York, NY, USA; Association of Chinese American PhysiciansFlushing, NY, USA.
authors.forename: Fang-Ming
authors.initials: FM
authors.lastname: Deng
authors.affiliation: Association of Chinese American Physicians Flushing, NY, USA.
authors.forename: David Y
authors.initials: DY
authors.lastname: Zhang
authors.affiliation: Department of NYU Cancer Institute, New York University School of MedicineNew York, NY, USA; Department of Neuroscience & Physiology, New York University School of MedicineNew York, NY, USA; New York Harbor Healthcare SystemNew York, NY, USA.
authors.forename: Marie E
authors.initials: ME
authors.lastname: Monaco
authors.affiliation: Department of Pathology, New York University School of MedicineNew York, NY, USA; Department of NYU Cancer Institute, New York University School of MedicineNew York, NY, USA; Association of Chinese American PhysiciansFlushing, NY, USA; New York Harbor Healthcare SystemNew York, NY, USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Lee
keywords: ACSL4; QNBC; TNBC; breast cancer; quadruple negative