From Theory to Practice: Bone Health in Women with Early Breast Cancer Treated with Aromatase Inhibitors

Aromatase inhibitors (AI) are extensively used as adjuvant endocrine therapy in post-menopausal women with hormone receptor-positive early breast cancer (HR+ EBC), but their impact on bone health is not negligible. This work aimed to assess bone loss, fracture incidence, and risk factors associated with these events, as well as the prognostic influence of fractures. We have conducted a retrospective cohort study of women with HR+ EBC under adjuvant therapy with AI, during a 3-year period. Four-hundred-and-fifty-one eligible women were reviewed (median age 68 years). Median time under AI was 40 months. A fracture event occurred in 8.4%, mostly in the radium and femoral neck and in older women (mean 74 vs. 68 years, p = 0.006). Age (OR 1.01, 95% CI 1.01–1.07, p = 0.024) and time under AI (OR 1.02, 95% CI 1.00–1.04, p = 0.037) were independent predictors of fracture, with a fair discrimination (AUC 0.71). Analysis of disease-free survival according to fracture event varied between groups, disfavoring the fracture cohort (at 73 months, survival 78.6%, 95% CI, 47.6–92.4 vs. 95.6%, 95% CI, 91.2–97.8, p = 0.027). The multivariate model confirmed the prognostic impact of fracture occurrence (adjusted HR of 3.17, 95% CI 1.10–9.11; p = 0.032). Bone health is often forgotten, despite its great impact in survivorship. Our results validate the pathophysiologic link between EBC and bone metabolism, which translates into EBC recurrence. Further research in this area may help refine these findings. Moreover, early identification of women at higher risk for fractures is warranted.     

Final results of the double-blind placebo-controlled randomized phase 2 LOTUS trial of first-line ipatasertib plus paclitaxel for inoperable locally advanced/metastatic triple-negative breast cancer

Purpose

In LOTUS (NCT02162719), adding the oral AKT inhibitor ipatasertib to first-line paclitaxel for locally advanced/metastatic triple-negative breast cancer (aTNBC) improved progression-free survival (PFS; primary endpoint), with an enhanced effect in patients with PIK3CA/AKT1/PTEN-altered tumors (FoundationOne next-generation sequencing [NGS] assay). We report final overall survival (OS) results.

Methods

Eligible patients had measurable previously untreated aTNBC. Patients were stratified by prior (neo)adjuvant therapy, chemotherapy-free interval, and tumor immunohistochemistry PTEN status, and were randomized 1:1 to paclitaxel 80 mg/m² (days 1, 8, 15) plus ipatasertib 400 mg or placebo (days 1–21) every 28 days until disease progression or unacceptable toxicity. OS (intent-to-treat [ITT], immunohistochemistry PTEN-low, and PI3K/AKT pathway-activated [NGS PIK3CA/AKT1/PTEN-altered] populations) was a secondary endpoint.

Results

Median follow-up was 19.0 versus 16.0 months in the ipatasertib–paclitaxel versus placebo–paclitaxel arms, respectively. In the ITT population (n?=?124), median OS was numerically longer with ipatasertib–paclitaxel than placebo–paclitaxel (hazard ratio 0.80, 95% CI 0.50–1.28; median 25.8 vs 16.9 months, respectively; 1-year OS 83% vs 68%). Likewise, median OS favored ipatasertib–paclitaxel in the PTEN-low (n?=?48; 23.1 vs 15.8 months; hazard ratio 0.83) and PIK3CA/AKT1/PTEN-altered (n?=?42; 25.8 vs 22.1 months; hazard ratio 1.13) subgroups. The ipatasertib–paclitaxel safety profile was unchanged.

Conclusions

Final OS results show a numerical trend favoring ipatasertib–paclitaxel and median OS exceeding 2 years with ipatasertib–paclitaxel. Overall, results are consistent with the reported PFS benefit; interpretation within biomarker-defined subgroups is complicated by small sample sizes and TNBC heterogeneity.

     

Omentopexy with Glubran®2 for reducing complications after laparoscopic sleeve gastrectomy: results of a randomized controlled study

Background

Gastric fistulas, bleeding, and strictures are commonly reported after laparoscopic sleeve gastrectomy (LSG), that increase morbidity and hospital stay and may put the patient’s life at risk. We report our prospective evaluation of application of synthetic sealant, a modified cyanoacrylate (Glubran®2), on suture rime, associated with omentopexy, to identify results on LSG-related complications.

Methods

Patients were enrolled for LSG by two Bariatric Centers, with high-level activity volume. Intraoperative recorded parameters were: operative time, estimated intraoperative bleeding, conversion rate. We prospectively evaluated the presence of early complications after LSG during the follow up period. Overall complications were analyzed. Perioperative data and weight loss were also evaluated. A control group was identified for the study.

Results

Group A (treated with omentopexy with Glubran®2) included 96 cases. Control group included 90 consecutive patients. There were no differences among group in terms of age, sex and Body Mass Index (BMI). No patient was lost to follow-up for both groups. Overall complication rate was significantly reduced in Group A. Mean operative time and estimated bleeding did not differ from control group. We observed three postoperative leaks in Group B, while no case in Group A (not statistical significancy). We did not observe any mortality, neither reoperation. Weight loss of the cohort was similar among groups. In our series, no leaks occurred applying omentopexy with Glubran®2.

Conclusion

Our experience of omentopexy with a modified cyanoacrylate sealant may lead to a standardized and reproducible approach that can be safeguard for long LSG-suture rime.

Trial registration

Retrospective registration on clinicaltrials.gov PRS, with TRN NCT03833232 (14/02/2019).