The impact of loco-regional recurrences on metastatic progression in early-stage breast cancer: a multistate model

To study whether the effects of prognostic factors associated with the occurrence of distant metastases (DM) at primary diagnosis change after the incidence of loco-regional recurrences (LRR) among women treated for invasive stage I or II breast cancer. The study population consisted of 3,601 women, enrolled in EORTC trials 10801, 10854, or 10902 treated for early-stage breast cancer. Data were analysed in a multivariate, multistate model by using multivariate Cox regression models, including a state-dependent covariate. The presence of a LRR in itself is a significant prognostic risk factor (HR: 3.64; 95%-CI: 2.02-6.5) for the occurrence of DM. Main prognostic risk factors for a DM are young age at diagnosis (</=40: HR: 1.79; 95%-CI: 1.28-2.51), larger tumour size (HR: 1.58; 95%-CI: 1.35-1.84) and node positivity (HR: 2.00; 95%-CI: 1.74-2.30). Adjuvant chemotherapy is protective for a DM (HR: 0.66; 95%-CI: 0.55-0.80). After the occurrence of a LRR the latter protective effect has disappeared (P = 0.009). The presence of LRR in itself is a significant risk factor for DM. For patients who are at risk of developing LRR, effective local control should be the main target of therapy

Dose to level I and II axillary lymph nodes and lung by tangential field radiation in patients undergoing postmastectomy radiation with tissue expander reconstruction

<p>Abstract</p> <p>Background</p> <p>To define the dosimetric coverage of level I/II axillary volumes and the lung volume irradiated in postmastectomy radiotherapy (PMRT) following tissue expander placement.</p> <p>Methods and Materials</p> <p>Twenty-three patients were identified who had undergone postmastectomy radiotherapy with tangent only fields. All patients had pre-radiation tissue expander placement and expansion. Thirteen patients had bilateral expander reconstruction. The level I/II axillary volumes were contoured using the RTOG contouring atlas. The patient-specific variables of expander volume, superior-to-inferior location of expander, distance between expanders, expander angle and axillary volume were analyzed to determine their relationship to the axillary volume and lung volume dose.</p> <p>Results</p> <p>The mean coverage of the level I/II axillary volume by the 95% isodose line (V_D95%) was 23.9% (range 0.3 - 65.4%). The mean Ipsilateral Lung V_D50%was 8.8% (2.2-20.9). Ipsilateral and contralateral expander volume correlated to Axillary V_D95%in patients with bilateral reconstruction (p = 0.01 and 0.006, respectively) but not those with ipsilateral only reconstruction (p = 0.60). Ipsilateral Lung V_D50%correlated with angle of the expander from midline (p = 0.05).</p> <p>Conclusions</p> <p>In patients undergoing PMRT with tissue expanders, incidental doses delivered by tangents to the axilla, as defined by the RTOG contouring atlas, do not provide adequate coverage. The posterior-superior region of level I and II is the region most commonly underdosed. Axillary volume coverage increased with increasing expander volumes in patients with bilateral reconstruction. Lung dose increased with increasing expander angle from midline. This information should be considered both when placing expanders and when designing PMRT tangent only treatment plans by contouring and targeting the axilla volume when axillary treatment is indicated.</p

2. Survival Impact of HER-2/Neu, Cox-2, Urokinase Plasminogen Activator (upa), Cytokeratin 17/5,6 and other Markers with Long-Term Outcome of Early Breast Cancer. Report from the British Columbia Tissue Micro-Array Project (BCTMAP)

Tumor samples are available from over 19,600 Stage I-III breast cancer patients treated according to evolving British Columbia guidelines from 1978 to 1990. A tissue mico-array (TMA) was constructed from 930 of these patients, all of whom participated in randomized or phase II studies. Outcome was defined as 20-year Breast Cancer specific Survival (BrCaSS), with events defined as Breast Ca death. Follow up was median 17.8 years (ranges 11–28). Multiple tumor markers were tested, and results correlated with 20-year BrCaSS for markers expressed versus non-expressed. No difference in BrCaSS was found for aromatase, integrin-linked kinase (ILK), IGF-1 and Topo-isomerase-2. The negative predictive value of IHC versus FISH and ACIS-IHC versus FISH was 96 and 97%, respectively. The positive predictive value of IHC versus FISH and ACIS-IHC versus FISH was 84 and 84%, respectively. All tests, with the exception of HER-2 FISH were done by IHC. Results of other markers (VEGF, ER/PgR, hypoxia markers, etc.), and an interactive multivariate analysis adjusting for conventional prognostic factors and for all above markers, are in progress.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44215/1/10549_2004_Article_5127209.pd