Table 3.

Summary of the gap analysis for the progression of breast cancer

What do we know?	Oestrogen receptor, receptor tyrosine kinase (RTK) and DNA repair pathways have been researched extensively.
	Around 50% of DCIS will progress to invasive disease if untreated, with 12% to 20% recurring at 10 years despite appropriate treatment.
What are the gaps?	Understanding the complexities of breast cancer intracellular signal transduction pathways, paracrine pathways, invasion, angiogenesis and metastasis including relevance of these mechanisms to clinical progression.
	Whether there are inherently migratory stem cells or is metastatic capacity acquired.
	Understanding time-dependent progression events, notably dormancy and reactivation of micrometastasis, at particular secondary sites.
	Understanding the emerging relationship between therapeutic resistance and metastasis.
	Causative factors underlying recurrence of DCIS or progression to invasive disease
	Understanding the interplay between stroma, myoepithelial and epithelial components during early progression and interplay between tumour cells, stroma and the immune system in metastasis.
	The need for improved preclinical models of the influences of the microenvironment, site-specific metastasis and dormancy.
	In vivo imaging technologies to study the dynamics of metastasis and relate this to signalling mechanisms, as well as means to manipulate these mechanisms to evaluate targeting potential.
Problems	Appropriate clinical samples to evaluate biomarkers and cellular endpoints.
	Appropriate preclinical models and improved research reagents.
	Increasingly complex and multidisciplinary research infrastructure.
Translational implications	Identifying patients at increased risk of dissemination.
	Effectively predict therapeutic response with growth inhibitors.
	Improve selection of patients with DCIS for adjuvant radiotherapy or endocrine therapies.
	Identify cellular targets for developing new agents to target breast cancer progression effectively and selectively.
Recommendations	Improve preclinical models, research reagents and technologies (including imaging).
	Enhance access to appropriate clinical material, notably matched samples during progression and sequential samples obtained during treatments including new agents.
	Consider the genetic signature/specific genetic lesions when exploring progression biology and designing clinical trials.