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Deals with a study which analyzed cell cycle regulatory proteins from breast cancer patients. Results; Discussion; Materials and methods.

Background NeoRes I is a randomized phase II trial comparing neoadjuvant chemoradiotherapy with neoadjuvant chemotherapy in the treatment of resectable oesophageal cancer. Methods Patients with biopsy-proven adenocarcinoma or squamous cell carcinoma in the oesophagus or gastro-oesophageal junction (Siewert type I and II), T1N1 or T2–3N0–1 and M0-M1a (AJCC 6th edition) were randomized to receive three 3-weekly cycles of cisplatin 100 mg/m2 day 1 and fluorouracil 750 mg/m2/24 hours, days 1–5 with or without the addition of concurrent radiotherapy 40 Gy, 2 Gy/fraction, 5 days a week, followed by oesophageal resection with two-field lymphadenectomy. Primary endpoint was complete histopathological response rate. Survival and recurrence patterns were evaluated as secondary endpoints. Results Between 2008 and 2013, 181 patients were enrolled in 10 participating institutions in Sweden and Norway. Patients were well matched for pre-treatment characteristics T3: 64,1%, T2: 34,8%, T1: 1,1%. Adenocarcinoma: 72,4%, squamous cell carcinoma: 27,6%. Proximal/middle: 16,6%, distal: 65,2%, cardia (Siewert type II): 18,2%. < 60 years: 36,5%, 60–75 years: 63,5%. Treatment-related complications have previously been described with no significant differences between the treatment groups although postoperative complications were more severe in the chemoradiotherapy group. At the time of this analysis, median follow-up time for living patients was 63 months. Overall 5-year survival was better among those who achieved complete histopathological response (74,9%, 95% CI 54,2–87,2% versus 39,3%, 95% CI 30,6–47,8%, P  = 0002). Despite the previously reported higher rate of tumour tissue response in those who received neoadjuvant chemoradiotherapy, this was not translated into better survival. Five-year progression-free survival was 38,6%, 95% CI 28,4–48,6% (chemoradiotherapy) versus 32,4%, 95% CI 22,9–42,4% (chemotherapy), P  = 0,48. Five-year overall survival was 41,2%, 95% CI 30,9–51,3% (chemoradiotherapy) versus 38,9%, 95% CI 28,7- 49,0% (chemotherapy), P  = 0,95. There were no differences in recurrence patterns between the two treatment-groups. Conclusion This is to our knowledge the largest completed randomized trial comparing neoadjuvant chemotherapy with neoadjuvant chemoradiotherapy followed be oesophageal resection in patients with cancer in the oesophagus or gastro-oesophageal junction. We found no overall or progression-free survival advantages by adding radiotherapy, despite better tumour tissue response. Disclosure All authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]

The oestrogen receptor-alpha (ER alpha) differs in expression and regulation in breast cancer and, by studying the co-factor cyclin D1 as well as changes in the microenvironment, we here delineate two conditions that potentially cause regional down-regulation of the receptor. Heterogeneously expressed ER alpha was observed in 24 out of 134 of the studied breast cancer samples. In 6 out of 24 of the heterogeneous tumours, there was a clear inverse association between cyclin D1 protein/gene amplification and presence of ER alpha. In a subset of 120 tumours, analysed by Western blotting and ELISA, we further showed disparity in differentiation grade and proliferation between tumours with varied cyclin D1/ER alpha content. In another fraction (9 out of 24) of the heterogeneous tumours, there was an inverse association between the ER alpha and Hypoxia-Inducible Factor-1 alpha (HIF-1 alpha) suggesting that ER alpha was down-regulated during hypoxic conditions. These results were verified by culturing ER alpha breast cancer cell lines under hypoxic conditions showing a prominent down-regulation of the ER alpha. The two factors linked to ER alpha down-regulation can also be used to design new treatment approaches interfering with key proteins in these ER alpha regulatory pathways, thereby hopefully increasing the effect of anti-hormonal treatment.

Background: C-erbB2 is overexpressed in approximately one-fourth of human breast cancers. In spite of numerous reports suggesting a connection of c-erbB2 overexpression with cell cycle regulation through p27, D cyclins and c-myc, the relationship between c-erbB2 and proliferation through de-regulation of the pRb pathway in primary breast cancer has not been fully clarified., Materials and Methods: For this purpose we compared the expression of c-erbB2 in a total of 105 primary breast tumours with a variety of cell cycle proteins and clinical parameters., Results: C-erbB2 was strongly correlated with down-regulation of p27 and overexpression of c-erbB2 was, as expected, associated with poor survival. However, there was no correlation with proliferation. There was, nevertheless, an association between c-erbB2 and proliferation in certain subtypes of breast cancer, as in oestrogen-receptor-positive tumours, tumours with high cyclin D1, and in tumours with an overall linear pRb pathway, i.e. tumours with a preserved linearity between cyclin D1, pRb phosphorylation and proliferation., Conclusion: Our results suggest that c-erbB2 may have alternative functions in different subtypes of breast cancer, and further stress that c-erbB2, in addition to promoting proliferation, also functions through other mechanisms in breast cancer.