title: Hormone Receptor/Human Epidermal Growth Factor Receptor 2-positive breast cancer: Where we are now and where we are going.
abstract: Near 75% of all breast cancers (BC) express estrogen receptors (ER) and/or progesterone receptors (PgR), while up to 20% of BC show an overexpression/amplification of Human Epidermal Growth Factor Receptor 2 (HER2). Around 50% of all HER2-overexpressing BC show the coexistence of both HER2 overexpression/amplification and ER and/or PgR overexpression. Numerous in vitro and in vivo studies suggest the existence of a cross-talk between their downstream pathways, which seem to affect the natural history, response to therapy and outcome of patients affected by this subset of BC. Meta-analyses or subgroup analysis of numerous neo-/adjuvant trials demonstrated significant clinical implications deriving from ER/HER2 co-existence, consisting in a different pattern of relapse and dissimilar outcome in response to anti-HER2 therapy. However, only two randomized trials in early disease and three in advanced disease specifically addressed the issue whether a combined approach with both hormonal and anti-HER2 therapy would have a better therapeutic impact in this subset of BC compared to the lone anti-HER2 or hormonal therapies (HT). None of these trials demonstrated improvements in overall survival, even though several efficacy end-points such as progression free survival, in advanced setting, or pCR rates in neoadjuvant setting, often favored the combined hormonal and anti-HER2 therapeutic approach. In the next few years, a certain number of ongoing randomized trials, both in neoadjuvant and advanced setting, will evaluate the efficacy of new anti-HER2 drugs, T-DM1 and pertuzumab, in combination with HT, helping to improve the therapeutic strategy for this specific subtype of breast tumors.
authors.affiliation: Medical Oncology, Department of Clinical and Surgical Medicine, University of Naples "Federico II", Naples, Italy. Electronic address: francescoschettini1987@gmail.com.
authors.forename: Francesco
authors.initials: F
authors.lastname: Schettini
authors.affiliation: Medical Oncology, Department of Clinical and Surgical Medicine, University of Naples "Federico II", Naples, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Buono
authors.affiliation: Medical Oncology, Department of Clinical and Surgical Medicine, University of Naples "Federico II", Naples, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Cardalesi
authors.affiliation: Radiotherapy Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy.
authors.forename: Isacco
authors.initials: I
authors.lastname: Desideri
authors.affiliation: Medical Oncology, Department of Clinical and Surgical Medicine, University of Naples "Federico II", Naples, Italy.
authors.forename: Sabino
authors.initials: S
authors.lastname: De Placido
authors.affiliation: Department of Medical Oncology, IRCCS AOU San Martino-IST, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Del Mastro
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000628:therapy*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D020360:Neoadjuvant Therapy; D016032:Randomized Controlled Trials as Topic; D020239:Receptor Cross-Talk; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human
keywords: Breast cancer; Combination therapy; Crosstalk; Estrogen receptor; HER2; Hormone therapy