Robotic radical hysterectomy for stage 1B1 cervical cancer: A case series of survival outcomes from a leading UK cancer centre.

BACKGROUND: We present the largest UK single institute robotic radical hysterectomy (RRH) case series for the management of cervical cancer (CC). METHODS: Data were collected on women who had a RRH as primary treatment for stage 1b1 CC between December 2009 and December 2018. RESULTS: Ninty women had a robotic hysterectomy. Five-year follow-up data were available for 30%. The disease-free survival at 5 years was 89.6%. Overall survival at 3 and 5 years for death from any cause was 96.1% and 91.4%, respectively. The overall 5-year survival for death from disease only was 92.8%. Overall survival by tumour size alone showed that women with tumours less than 2 cm had a 98.3% 5-year survival compared to 83.4% for tumour size greater than 2 cm. Irrespective of tumour size, those that had no evidence of lymphovascular space invasion had a 100% 5-year survival. CONCLUSION: Our preliminary data supports the oncological safety of RRH in a selective cohort of patients with stage 1b1 CC.

Crosstalk between ERα and Receptor Tyrosine Kinase Signalling and Implications for the Development of Anti-Endocrine Resistance.

Although anti-endocrine therapies have significantly advanced the treatment of breast cancer, they pose the problem of acquired drug resistance. The oestrogen receptor (ER)-expressing breast cancer cell lines MCF-7 and T47D alongside their in vitro derived resistant counterparts MCF-7-TR (tamoxifen-resistant) and T47D-FR (fulvestrant-resistant) showed dual resistance to fulvestrant and tamoxifen in the presence of upregulated HER1 and HER2 growth factor receptors. Our study demonstrated that tamoxifen resistance and fulvestrant resistance are associated with collateral sensitivity to the tyrosine kinase inhibitors (TKIs) lapatinib (p < 0.0001) and afatinib (p < 0.0001). Further, we found that over time, the TKIs reactivated ERα protein and/or mRNA in tamoxifen- and fulvestrant-resistant cells. Combinations of anti-endocrine agents with afatinib gave rise to significantly enhanced levels of apoptosis in both T47D-FR and MCF-7-TR in a synergistic manner versus additive effects of agents used singly. This was associated with p27kip1 induction for anti-endocrine-resistant cells versus parental cells. Our data supports the use of combination treatment utilising dual HER1/2 inhibitors in breast cancer patients showing resistance to multiple anti-endocrine agents.