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. |
|
|
|
|
|
Thompson et al. Breast Cancer Research 2008 10:R26 doi:10.1186/bcr1983 |
|
