Table 1 Lessons learned over the past decade of target-directed research in breast cancer
Lesson | Examples |
|---|---|
Trial populations | Â |
 Conduct trials in either positively-selecteda or target-matchedb populations | Identification of 6 intrinsic biological BC subtypes (luminal A; luminal B; HER2-enriched; basal-like; normal breast-like; and claudin-low) (Perou et al. 2000; Sorlie et al. 2001; Carey et al. 2006; Prat et al. 2010) Recurrence scores (e.g. OncotypeDX, PAM50, MammaPrint or IHC4) to help select patients that can forego adjuvant CT (Paik et al. 2006; Albain et al. 2010; Paik et al. 2004; Parker et al. 2009; Chia et al. 2012; Barton et al. 2012; Dowsett et al. 2008; Cuzick et al. 2011; van ‘t Veer et al. 2002; Cardoso et al. 2008; Rutgers et al. 2011; van de Vijver et al. 2002) Positive trial outcomes HER2-inhibitors in HER2-positive populations (Slamon et al. 2001; Guan et al. 2013; Goldhirsch et al. 2013; Marty et al. 2005; Perez et al. 2011; Vogel et al. 2002) ET in HR-positive populations (Fisher et al. 1989; Early Breast Cancer Trialists’ Collaborative Group 2005) Negative trial outcomes Bevacizumab combinations in HER2-negative populations (Miller et al. 2005, 2007; Miles et al. 2010; Robert et al. 2011; Brufsky et al. 2011) Cetuximab combinations in non-KRAS wild-type (Carey et al. 2012; Baselga et al. 2010; O’Shaughnessy et al. 2007) Inaparib in triple-negative populations (O’Shaughnessy et al. 2011a) |
Interventions | Â |
 Consider combining T-D with CT | Trastuzumab plus CT (Goldhirsch et al. 2013; Marty et al. 2005; Perez et al. 2011; Slamon et al. 2001; Inoue et al. 2010; Swain et al. 2013) in HER2-positive populations T-DM1 (Verma et al. 2012) in HER2-positive populations |
 Consider multi-T-D strategies based on a biological rationale | Everolimus plus ET in HR-positive (Baselga et al. 2012b) Dual HER2-inhibition in HER2-positive (Baselga et al. 2012c; Swain et al. 2013; Gianni et al. 2012) |
 Consider continued T-D therapy | Early setting Positive trial outcomes Additional 5 years of tamoxifen (Davies et al. 2013; Gray et al. 2013) or letrozole (Goss et al. 2005) in HR-positive populations Negative trial outcomes An additional year of trastuzumab in HER2-positive populations (Goldhirsch et al. 2013) Advanced setting Sequential ET in HR-positive populations (Baselga et al. 2012b) Continued HER2-inhibition in HER2-positive across multiple lines of therapy (Cameron et al. 2008; Verma et al. 2012; von Minckwitz et al. 2009) |
Trial design | Â |
 Consider the neo-adjuvant setting as a platform for accelerated testingc | Pertuzumab (Gianni et al. 2012, 2015), trastuzumab plus FEC and paclitaxel (Buzdar et al. 2013) in HER2-positive NAT populations Trastuzumab plus lapatinib (Baselga et al. 2012a; Robidoux et al. 2012) in HER2-positive patient NAT populations |
 Utilize phase III trials to arrive at conclusive findings | Negative trial outcomes Iniparib in TN populations (O’Shaughnessy et al. 2011a, b) Positive trial outcomes The majority of currently established T-D agents (Baselga et al. 2012b, c; Buzdar et al. 1996, 1998; Cameron et al. 2008; Fisher et al. 1989; Slamon et al. 2001; The Nolvadex Adjuvant Trial Organisation 1985; Verma et al. 2012) |
 Are powered to assess improved survivald | Negative trial outcomes Bevacizumab combinations in first-line (Miles et al. 2010; Miller et al. 2007; Robert et al. 2011) Positive trial outcomes EGF104535 (Guan et al. 2013), CLEOPATRA (Swain et al. 2012; Verma et al. 2012), EMILIA (Baselga et al. 2012c; Swain et al. 2013) |