Table 3 Summary of the gap analysis for the progression of breast cancer
From: Evaluation of the current knowledge limitations in breast cancer research: a gap analysis
| 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. |