Deciphering the impact of STAT3 activation mediated by PTPRT promoter hypermethylation as biomarker of response to paclitaxel-plus-cetuximab in patients with recurrent or metastatic squamous cell carcinoma of the head and neck.

BACKGROUND: Squamous cell carcinoma of the head and neck (SCCHN) is an aggressive disease with poor prognosis. It is known that the activation of STAT3 signaling pathways promotes the development and progression of this neoplasia and it has been described the role of PTPRT as a negative regulator of STAT3. Then, we have evaluated the impact of them as biomarkers of outcome in a series of patients with recurrent and/or metastatic SCCHN treated with weekly paclitaxel-plus-cetuximab (ERBITAX) regimen. PATIENTS AND METHODS: Between 2008 and 2017, 52 patients with recurrent/metastatic SCCHN were treated with ERBITAX at our center, 34 of whom had available tumor samples. Phosphorylated STAT3 (pSTAT3) protein expression was analyzed by immunohistochemistry, STAT3 mRNA expression by qPCR, and PTPRT promoter methylation by methylation-specific PCR. Molecular results were correlated with response rate (RR), progression-free survival (PFS), and overall survival (OS). RESULTS: pSTAT3 overexpression was detected in 67% and PTPRT promoter hypermethylation in 41% of tumor samples. PTPRT promoter hypermethylation showed a trend towards an association with lower RR (21% vs. 60%; p = 0.06). A lower RR was also observed in patients with pSTAT3 overexpression (36% vs. 54%) and in those with high STAT3 mRNA levels (43% vs. 64%), but these differences did not reach statistical significance. PTPRT promoter hypermethylation correlated with pSTAT3 overexpression (p = 0.009) but not with STAT3 mRNA overexpression. OS and PFS was shorter in patients with activated STAT3, but the difference did not reach statistical significance. CONCLUSIONS: Although this was a relatively small retrospective study, it provides preliminary indications of the potential role of the STAT3 pathway on outcome in SCCHN and confirms that PTPRT acts as a negative regulator of STAT3. Our findings warrant investigation in a larger patient cohort to determine if inactivating this pathway through specific targeted treatments could improve outcomes in recurrent/metastatic SCCHN patients.

Psychosocial aspects and life project disruption in young women diagnosed with metastatic hormone-sensitive HER2-negative breast cancer.

Metastatic breast cancer (MBC) diagnosis in young women negatively impacts on quality of life (QoL) and daily activities, disrupting their life project and forcing them to face new psychosocial challenges. The recently published results on the improvement of the overall survival of pre- or perimenopausal women with hormone-receptor-positive, HER2-negative MBC treated with CDK4/6 inhibitors plus endocrine therapy, while preserving, and in some items improving their QoL, will change the landscape of the management of this patient population. Their extended survival and potential improvement in QoL will, therefore, modify their specific needs in terms of psychosocial support. The complexity of the care of young women with MBC is described herein, based on an extensive literature review. Further research about the specific psychosocial requirements of these women and a new multidisciplinary holistic approach is paramount to properly address their concerns and preferences. The communication with and support of their partners, parents and children is an important factor affecting the QoL of these patients. Altogether, a multidisciplinary care, open communication and personalized support is required to address the psychosocial implications of the new prognostic expectations on these patients with the incorporation of new targeted therapies.

Nanoparticle albumin-bound paclitaxel in a patient with locally advanced breast cancer and taxane-induced skin toxicity: a case report.

INTRODUCTION: Taxanes have demonstrated effectiveness in the treatment of breast cancer, the most common type of cancer in women. The toxicity profile of taxanes (including skin toxicities) induces dose adjustment, delay, or discontinuation, which prevents a sufficient dose intensity to achieve a response. Nanoparticle albumin-bound paclitaxel, a solvent-free form of paclitaxel, prevents toxicities and reduces the pharmacokinetic interferences between paclitaxel and other drugs. CASE PRESENTATION: We describe the case of a 55-year-old Caucasian woman with locally advanced breast cancer treated with neoadjuvant therapy who developed secondary skin toxicity due to delayed hypersensitivity to taxanes. She received Adriamycin® (doxorubicin), cyclophosphamide and docetaxel and developed toxicity that promoted treatment delay and a switch to weekly paclitaxel. After the third and fourth weeks of treatment, paclitaxel toxicities also induced treatment delay and paclitaxel was switched to nanoparticle albumin-bound paclitaxel. She completed the five planned nanoparticle albumin-bound paclitaxel cycles with acceptable tolerability (including persistent grade 2 neuropathy) and without dose delay or adjustments. Clinical response was achieved although pathological response was not good. CONCLUSIONS: Nanoparticle albumin-bound paclitaxel treatment is a good option for patients with breast cancer with taxanes-related skin toxicity. This drug allows the treatment to be completed with acceptable tolerance in our case.

The effect of body mass index on overall and disease-free survival in node-positive breast cancer patients treated with docetaxel and doxorubicin-containing adjuvant chemotherapy: the experience of the BIG 02-98 trial.

BACKGROUND: Obesity has been shown to be an indicator of poor prognosis for patients with primary breast cancer (BC) regardless of the use of adjuvant systemic therapy. PATIENTS AND METHODS: This is a retrospective analysis of 2,887 node-positive BC patients enrolled in the BIG 02-98 adjuvant study, a randomised phase III trial whose primary objective was to evaluate disease-free survival (DFS) by adding docetaxel to doxorubicin-based chemotherapy. In the current analysis, the effect of body mass index (BMI) on DFS and overall survival (OS) was assessed. BMI was obtained before the first cycle of chemotherapy. Obesity was defined as a BMI >or= 30 kg/m2. RESULTS: In total, 547 (19%) patients were obese at baseline, while 2,340 (81%) patients were non-obese. Estimated 5-year OS was 87.5% for non-obese and 82.9% for obese patients (HR 1.34; P = 0.013). Estimated 5-years DFS was 75.9% for nonobese and 70.0% for obese patients (HR 1.20; P = 0.041). Ina multivariate model, obesity remained an independent prognostic factor for OS and DFS. CONCLUSIONS: In this study,obesity was associated with poorer outcome in node-positive BC patients. Given the increasing prevalence of obesity worldwide, more research on improving the treatment of obese BC patients is needed.