Purpose The purpose of the study was to investigate if surface guided radiotherapy (SGRT) can decrease setup deviations for tangential and locoregional breast cancer patients compared to conventional laser‐based setup (LBS). Materials and Methods Both tangential (63 patients) and locoregional (76 patients) breast cancer patients were enrolled in this study. For LBS, the patients were positioned by aligning skin markers to the room lasers. For the surface based setup (SBS), an optical surface scanning system was used for daily setup using both single and three camera systems. To compare the two setup methods, the patient position was evaluated using verification imaging (field images or orthogonal images). Results For both tangential and locoregional treatments, SBS decreased the setup deviation significantly compared to LBS (P < 0.01). For patients receiving tangential treatment, 95% of the treatment sessions were within the clinical tolerance of ≤ 4 mm in any direction (lateral, longitudinal or vertical) using SBS, compared to 84% for LBS. Corresponding values for patients receiving locoregional treatment were 70% and 54% for SBS and LBS, respectively. No significant difference was observed comparing the setup result using a single camera system or a three camera system. Conclusions Conventional laser‐based setup can with advantage be replaced by surface based setup. Daily SGRT improves patient setup without additional imaging dose to breast cancer patients regardless if a single or three camera system was used.

The aim of this study was to investigate potential dose reductions to the heart, left anterior descending coronary artery (LAD), and ipsilateral lung for left‐sided breast cancer using visually guided deep inspiration breath‐hold (DIBH) with the optical surface scanning system Catalyst™, and how these potential dosimetric benefits are affected by intrafractional motion in between breath holds. For both DIBH and free breathing (FB), treatment plans were created for 20 tangential and 20 locoregional left‐sided breast cancer patients. During DIBH treatment, beam‐on was triggered by a region of interest on the xiphoid process using a 3 mm gating window. Using a novel nonrigid algorithm, the Catalyst™ system allows for simultaneous real‐time tracking of the isocenter position, which was used to calculate the intrafractional DIBH isocenter reproducibility. The 50% and 90% cumulative probabilities and maximum values of the intrafractional DIBH isocenter reproducibility were calculated and to obtain the dosimetric effect isocenter shifts corresponding to these values were performed in the treatment planning system. For both tangential and locoregional treatment, the dose to the heart, LAD and ipsilateral lung was significantly reduced for DIBH compared to FB. The intrafractional DIBH isocenter reproducibility was very good for the majority of the treatment sessions, with median values of approximately 1 mm in all three translational directions. However, for a few treatment sessions, intrafractional DIBH isocenter reproducibility of up to 5 mm was observed, which resulted in large dosimetric effects on the target volume and organs at risk. Hence, it is of importance to set tolerance levels on the intrafractional isocenter motion and not only perform DIBH based on the xiphoid process.

BackgroundAdjuvant endocrine treatment improves survival after estrogen receptor (ER) positive breast cancer. Recurrences occur, and most patients with metastatic breast cancer develop treatment resistance and incurable disease. An influential factor in relation to endocrine treatment resistance is tumor hypoxia and the hypoxia inducible transcription factors (HIFs). Poor perfusion makes tumors hypoxic and induces the HIFs, which promote cell survival. We previously showed that hypoxic breast cancer cells are tamoxifen-resistant, and that HIF-inhibition restored tamoxifen-sensitivity. We found that HIF-induced tamoxifen-resistance involve cross-talk with epithelial growth factor receptor (EGFR), which itself is linked to tamoxifen resistance. Contralateral breast cancer (CBC), i.e. development of a second breast cancer in the contralateral breast despite adjuvant tamoxifen treatment is in essence a human in vivo-model for tamoxifen-resistance that we explore here to find molecular pathways of tamoxifen-resistance.MethodsWe constructed a tissue-microarray including tumor-tissue from a large well-defined cohort of CBC-patients, a proportion of which got their second breast cancer despite ongoing adjuvant therapy. Using immunohistochemistry >500 patients were evaluable for HIF-1α and EGFR in both tumors, and correlations to treatment, patient outcome, prognostic and predictive factors were analyzed.ResultsWe found an increased proportion of HIF-1α-positive tumors in tamoxifen-resistant (CBC during adjuvant tamoxifen) compared to naïve tumors (CBC without prior tamoxifen). Tumor HIF-1α-positivity correlated to increased breast cancer mortality, and negative prognostic factors including low age at diagnosis and ER-negativity. There was a covariance of HIF-1α- and EGFR-expression and also EGFR-expression correlated to poor prognosis.ConclusionsThe increased percentage of HIF-1α-positive tumors formed during adjuvant tamoxifen suggests a role for HIF-1α in escaping tamoxifen’s restraining effects on breast cancer. Implicating a potential benefit of HIF-inhibitors in targeting breast cancers resistant to endocrine therapy.

BackgroundAlthough 2-20% of breast cancer patients develop a contralateral breast cancer (CBC), prognosis after CBC is still debated. Using a unique patient cohort, we have investigated whether time interval to second breast cancer (BC2) and mode of detection are associated to prognosis.MethodsInformation on patient-, tumour-, treatment-characteristics, and outcome was abstracted from patients' individual charts for all patients diagnosed with metachronous CBC in the Southern Healthcare Region of Sweden from 1977-2007. Distant disease-free survival (DDFS) and risk of distant metastases were primary endpoints.ResultsThe cohort included 723 patients with metachronous contralateral breast cancer as primary breast cancer event. Patients with less than three years to BC2 had a significantly impaired DDFS (p = 0.01), and in sub-group analysis, this effect was seen primarily in patients aged <50. By logistic regression analysis, patients diagnosed with BC2 within routine follow-up examinations had a significantly lower risk of developing metastases compared to those who were symptomatic at diagnosis (p < 0.0001). Chemotherapy given after breast BC1 was a negative prognostic factor for DDFS, whereas endocrine treatment and radiotherapy given after BC2 improved DDFS.ConclusionsIn a large cohort of patients with CBC, we found the time interval to BC2 to be a strong prognostic factor for DDFS in young women and mode of detection to be related to risk of distant metastases. Future studies of tumour biology of BC2 in relation to prognostic factors found in the present study can hopefully provide biological explanations to these findings.