DUBAI MEET 2015

2. HOW TO OPTIMISE ENDOCRINE
THERAPY?
NEW TARGETED AGENTS IN LUMINAL
BC

3.  For Post-menopausal women with early stage ER+ BC
 AIs (as adjuvant, up-front or as a switch therapy)
 Current duration for AIs as an adjuvant therapy  5
yrs (?)
 With Node + or other indicators of late relapse 
extended use of adjuvant therapy
 In pre-menopausal women with ER+ early breast
cancer  the added benefit of ovarian suppression over
and above tamoxifen remains unknown
 In women aged <40 ys, added benefit may exist, but
must be weighed up against both short and
long-term tolerability

4. Weigel MT, Dowsett M. Endocrine Rel Cancer 2010

5. Goldhirsch et al. Ann Oncol June 2011. St Gallen 2011

6. HT in Luminal-B:
 Significant improvement OS for anastrozole compared
to tamoxifen (HR 0.56, 95%CI 0.34–0.92) and this was
replicated in DFS and OS for luminal B subtypes but
not luminal A.
 ‘Subtype shift’ from luminal B to A in progressor
patients treated with neo-adjuvant AIs.

7. With the identification of driving genetic
alterations and signaling pathways  new
developments
E.g. PI3K-AKT-mTOR inhibitors
BOLERO-2 trial marked improvement in
PFS
Other approaches are underway  PI3K
inhibitors, IGF-IR, FGFR

8.  ER signaling is a pivotal but not exclusive
pathway in the complex system of HR+ tumor
proliferation
 PI3K-mTOR is the most common aberrantly
activated pathway in breast cancer, with genetic
defects occurring in >70% of cases
 When deprived of estrogen, hyperactivation of this
pathway can drive resistance to endocrine
monotherapy
 The PI3K-mTOR pathway is a major source of
progression in HR+ advanced breast cancer

9.  Combination of everolimus with exemestane
 Increased efficacy compared with exemestane plus
placebo with respect to PFS in the range of 4–6
months in a pt population of postmenopausal,
hormone receptor positive, advanced breast cancer
patients
 PFS benefit seen is similar to or better than that
of other approved hormonal therapies and
chemotherapies given after initial hormone
resistance

10.  Luminal-B breast cancer (LUM B), which is
associated with higher grade, increased
proliferation rates, and an overall poorer
prognosis.
 LUM B, which is inherently more aggressive,
requires more aggressive therapy and thus is
generally treated with both ET and CT, though
this approach is not always effective.
 Potential alternate or additional treatment
options: targeting of other pathways of importance
in this subgroup. Ann Oncol (2012) 23 (suppl 9): ix27-ix28.

11.  Firstly identification of pathways active in LUM
B, and secondly, development and assessment of
targeted agents against these pathways.
 The utility of inhibitors against mTOR, PI3K or
IGFR-1 is of particular interest.