SEOM–GEICAM–SOLTI clinical guidelines in advanced breast cancer (2022)

Advanced breast cancer; Anti-HER2 therapy; Endocrine therapyCàncer de mama avançat; Teràpia anti-HER2; Teràpia endocrinaCáncer de mama avanzado; Terapia anti-HER2; Terapia endocrinaAdvanced breast cancer represents a challenge for patients and for physicians due its dynamic genomic changes yielding to a resistance to treatments. The main goal is to improve quality of live and survival of the patients through the most appropriate subsequent therapies based on the knowledge of the natural history of the disease. In these guidelines, we summarize current evidence and available therapies for the medical management of advanced breast cancer

Baseline Mutations and ctDNA Dynamics as Prognostic and Predictive Factors in ER-Positive/HER2-Negative Metastatic Breast Cancer Patients

Purpose: Prognostic and predictive biomarkers to cyclindependent kinases 4 and 6 inhibitors are lacking. Circulating tumor DNA ( ctDNA) can be used to profile these patients and dynamic changes in ctDNA could be an early predictor of treatment efficacy. Here, we conducted plasma ctDNA profiling in patients from the PEARL trial comparing palbociclib+fulvestrant versus capecitabine to investigate associations between baseline genomic landscape and on-treatment ctDNA dynamics with treatment efficacy. Experimental Design: Correlative blood samples were collected at baseline [cycle 1-day 1 (C1D1)] and prior to treatment [cycle 1-day 15 (C1D15)]. Plasma ctDNA was sequenced with a custom error-corrected capture panel, with both univariate and multivariate Cox models used for treatment efficacy associations. A prespecified methodology measuring ctDNA changes in clonal mutations between C1D1 and C1D15 was used for the on-treatment ctDNA dynamic model. Results: 201 patients were profiled at baseline, with ctDNA detection associated with worse progression-free survival (PFS)/ overall survival (OS). Detectable TP53 mutation showed worse PFS and OS in both treatment arms, even after restricting population to baseline ctDNA detection. ESR1 mutations were associated with worse OS overall, which was lost when restricting population to baseline ctDNA detection. PIK3CA mutations confer worse OS only to patients on the palbociclib+fulvestrant treatment arm. ctDNA dynamics analysis (n = 120) showed higher ctDNA suppression in the capecitabine arm. Patients without ctDNA suppression showed worse PFS in both treatment arms. Conclusions: We show impaired survival irrespective of endocrine or chemotherapy-based treatments for patients with hormone receptor-positive/HER2-negative metastatic breast cancer harboring plasma TP53 mutations. Early ctDNA suppression may provide treatment efficacy predictions. Further validation to fully demonstrate clinical utility of ctDNA dynamics is warranted

Evaluation of the prognostic and predictive value of tumor-infiltrating lymphocytes (TILs) in a phase III randomized adjuvant breast cancer (BC) trial (BIG 2-98) of node-positive (N1) BC comparing the addition of docetaxel to doxorubicin (A-T) with doxorubicin (A)-only chemotherapy (CT).

info:eu-repo/semantics/nonPublishe

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.Clinical Trial, Phase IIIJournal ArticleRandomized Controlled TrialResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

Evaluation of the prognostic and predictive value of tumor-infiltrating lymphocytes (TILs) in a phase III randomized adjuvant breast cancer (BC) trial (BIG 2-98) of node-positive (N+) BC comparing the addition of docetaxel to doxorubicin (A-T) with doxorubicin (A)-only chemotherapy (CT)

Abstract nr 556 - General Poster Sessioninfo:eu-repo/semantics/publishe

Overall survival benefit for sequential doxorubicin-docetaxel compared with concurrent doxorubicin and docetaxel in node-positive breast cancer-8-year results of the breast international group 02-98 phase III trial

Background: In women with node-positive breast cancer, the Breast International Group (BIG) 02-98 tested the incorporation of docetaxel (Taxotere) into doxorubicin (Adriamycin)-based chemotherapy, and compared sequential and concurrent docetaxel. At 5 years, there was a trend for improved disease-free survival (DFS) with docetaxel. We present results at 8-year median follow-up and exploratory analyses within biologically defined subtypes. Methods: Patients were randomly assigned to one of four treatments: (i) sequential control: doxorubicin (A) (75 mg/m. 2) × 4 → classical cyclophosphamide, methotrexate, 5-fluorouracil (CMF); (ii) concurrent control: doxorubicin, cyclophosphamide (AC)(60/600 mg/m. 2) × 4 →CMF; (iii) sequential docetaxel: A (75 mg/m. 2) × 3 → docetaxel (T) (100 mg/m. 2) × 3 → CMF and (iv) concurrent docetaxel: AT(50/75 mg/m. 2) × 4 →CMF. The primary comparison evaluated docetaxel efficacy regardless of the schedule. Exploratory analyses were undertaken within biologically defined subtypes. Results: Two thousand eight hundred and eighty-seven patients were enrolled. After 93.4 months of median follow-up, there were 916 DFS events. For the primary comparison, there was no significant improvement in DFS from docetaxel [hazard ratio (HR) = 0.91, 95% confidence interval (CI) = 0.80-1.05, P = 0.187]. In secondary comparisons, sequential docetaxel significantly improved DFS compared with sequential control (HR = 0.81, 95% CI = 0.67-0.99, P = 0.036), and significantly improved DFS (HR = 0.84, 95% CI = 0.72-0.99, P = 0.035) and overall survival (OS) (HR = 0.79, 95% CI = 0.65-0.98, P = 0.028) compared with concurrent doxorubicin-docetaxel. Luminal-A disease had the best prognosis. HRs favored addition of sequential docetaxel in all subtypes, except luminal-A; but this observation was not statistically supported because of limited numbers. Conclusion: With further follow-up, the sequential docetaxel schedule resulted in significantly better OS than concurrent doxorubicin-docetaxel, and continued to show better DFS than sequential doxorubicin-based control. © The Author 2013. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Supplementary Table S13 from Baseline Mutations and ctDNA Dynamics as Prognostic and Predictive Factors in ER-Positive/HER2-Negative Metastatic Breast Cancer Patients

Supplementary Table 13. Alternative methodologies used for the calculation of CDR and PFS predictions.</p

Supplementary Table S2 from Baseline Mutations and ctDNA Dynamics as Prognostic and Predictive Factors in ER-Positive/HER2-Negative Metastatic Breast Cancer Patients

Supplementary Table 2. Complete table results for all patients (n=201) involved in baseline (C1D1) analysis.</p