Genome-wide association studies (GWAS) have to date identified 94 genetic variants (single nucleotide polymorphisms (SNPs)) associated with risk of developing breast cancer. A score based on the combined effect of the 94 risk alleles can be calculated to measure the global risk of breast cancer. We aimed to test the hypothesis that the 94-SNP-based risk score is associated with clinico-pathological characteristics, breast cancer subtypes and outcomes in early breast cancer.A 94-SNP risk score was calculated in 8703 patients in the PHARE and SIGNAL prospective case cohorts. This score is the total number of inherited risk alleles based on 94 selected SNPs. Clinical data and outcomes were prospectively registered. Genotyping was obtained from a GWAS.The median 94-SNP risk score in 8703 patients with early breast cancer was 77.5 (range: 58.1-97.6). The risk score was not associated with usual prognostic and predictive factors (age; tumor, node, metastasis (TNM) status; Scarff-Bloom-Richardson grade; inflammatory features; estrogen receptor status; progesterone receptor status; human epidermal growth factor receptor 2 (HER2) status) and did not correlate with breast cancer subtypes. The 94-SNP risk score did not predict outcomes represented by overall survival or disease-free survival.In a prospective case cohort of 8703 patients, a risk score based on 94 SNPs was not associated with breast cancer characteristics, cancer subtypes, or patients' outcomes. If we hypothesize that prognosis and subtypes of breast cancer are determined by constitutional genetic factors, our results suggest that a score based on breast cancer risk-associated SNPs is not associated with prognosis.PHARE cohort: NCT00381901 , Sept. 26, 2006 - SIGNAL cohort: INCa RECF1098, Jan. 28, 2009.
Carcinomatous meningitis is a rare neuropathological entity in the routine oncology practice, with an estimated frequency of one case in ten metastatic cancers (10% or less). Lung cancer, breast cancer, melanoma, or primary brain tumors usually have the propensity to generate meningeal metastases according to the literature. We herein report unusual cases of Carcinomatous meningitis diagnosed in two young patients of 46 and 38 years old who were primarily followed up for metastatic ovarian cancer and metastatic gastric cancer respectively. Neurological symptoms were prominent at the time of diagnosis. The brain scan was non-contributory. The radiological diagnosis was made by injected brain magnetic resonance imaging (MRI) which showed metastatic meningeal lesions in both cases. Anatomopathological analysis of the cerebrospinal fluid (CSF) was decisive in revealing cancerous cells. The treatment consisted of a doublet of intrathecally (IT) Methotrexate-Depomedrol (patient with ovarian cancer) and a triplet of IT Methotrexate-cytarabine-Depomedrol (patient with gastric cancer). The evolution was marked by a clinical improvement without CSF sterilisation for the patient on the doublet treatment but died 5 months later on the occasion of a new progression. For the other patient on the triplet, the evolution was towards a rapid clinical deterioration with death within 2 months from diagnosis. Carcinomatous meningitis is therefore a serious complication that rapidly threatens the life of patients. Survival rarely exceeds 4 months.
In the Phase III PAOLA-1/ENGOT-ov25 trial (NCT02477644), adding maintenance olaparib to bevacizumab improved progression-free survival (PFS) in patients with advanced ovarian cancer in response after first-line platinum-based chemotherapy plus bevacizumab (HR 0.59; 95% CI 0.49–0.72) (Ray-Coquard et al. NEJM 2019). Outcomes in patients classified by clinical risk according to biomarker status are unknown.
Methods
Patients were classified as higher-risk (stage III patients with upfront surgery and residual disease or who received neoadjuvant chemotherapy, or stage IV patients) or lower-risk (stage III patients with upfront surgery and no residual disease). This exploratory analysis evaluated PFS in higher-risk and lower-risk patients, including by biomarker status: homologous recombination deficiency (HRD)-positive, HRD-negative/unknown and tumour BRCA mutation (BRCAm)-positive.
Results
Of 806 randomized patients, 74% were higher risk and 26% were lower risk, with median follow-up of 22.4 and 23.8 months, respectively. PFS significantly favoured olaparib plus bevacizumab versus placebo plus bevacizumab in higher-risk and lower-risk patients. In both higher- and lower-risk patients, the greatest PFS benefit was seen with olaparib plus bevacizumab versus bevacizumab alone in the HRD-positive subgroup (figures 1 and 2) and the subgroup with a tumour BRCAm (figure 2). Outcomes in the higher- and lower-risk HRD-negative/unknown subgroups are shown in figure 2.
Conclusions
In PAOLA-1, maintenance olaparib plus bevacizumab provided a substantial PFS benefit over bevacizumab alone in higher-risk and lower-risk patients, especially in the HRD-positive and BRCAm populations.
Abstract Introduction Predictive markers of LV5FU2 maintenance benefit after first-line induction with FOLFIRINOX in patients with metastatic pancreatic cancer are necessary to select patients who will not be harmed by this strategy. Patients and Methods We focused on patients who received 12 cycles of FOLFIRINOX (arm A, N = 88) or 8 cycles of FOLFIRINOX followed by LV5FU2 maintenance in controlled patients (arm B, N = 91) from the PRODIGE-35 trial. Prognostic factors and predictors of efficiency were identified by using Cox regression. Median progression-free survival (PFS), overall survival (OS), and time to deterioration of quality of life (TTD-QoL) were evaluated. Results Poor independent prognostic factors were primary tumor in place, age <65 years and the presence of liver metastases for PFS, a baseline neutrophil/lymphocyte ratio (NLR) ≥5 and CA19.9 ≥500 UI/L for OS, independent of the treatment arm. Patients with one metastatic site had a longer PFS in arm A, whereas patients with ≥2 metastatic sites had a longer PFS in arm B. We also identified predictors of OS and TTD-QoL in arm B but these differences were not statistically significant. Conclusion Except for patients with one metastatic site who benefited more from 12 cycles of FOLFIRINOX, a maintenance strategy with LV5FU2 should be widely offered to mPC patients whose survival and QoL are preserved after 4 months of FOLFIRINOX. (ClinicalTrials.gov: NCT02352337).
PurposeCombining bevacizumab with paclitaxel significantly improves progression-free survival (PFS) versus paclitaxel alone in HER2-negative metastatic breast cancer (MBC). Eribulin is active and tolerable in pretreated MBC. To assess whether eribulin may offer a more tolerable yet effective combination partner for bevacizumab, we evaluated a bevacizumab/eribulin combination regimen as first-line therapy for MBC.MethodsIn this single-arm phase II study, patients with histologically confirmed HER2-negative MBC and no prior chemotherapy for MBC received eribulin 1.23 mg/m2 on days 1 and 8 every 3 weeks for ≥6 cycles plus bevacizumab 15 mg/kg on day 1 every 3 weeks until disease progression. The primary endpoint was non-progression rate at 1 year. Secondary endpoints included objective response rate (ORR), PFS, and safety.ResultsThe median age of the 61 treated female patients was 59 years, 16% had triple-negative MBC, 30% had ≥3 metastatic sites, and 71% had received prior (neo)adjuvant chemotherapy. Patients received a median of six eribulin and nine bevacizumab cycles. The non-progression rate at 1 year was 32% (95% confidence interval [CI]: 20–43%), ORR was 47% (95% CI: 34–60%), and median PFS was 8.3 months (95% CI: 7.0–9.6 months). The only grade ≥3 clinical adverse events in >5% of patients were hypertension (39%), neutropenia (26%), thrombosis (10%), and paresthesia/dysesthesia (7%).ConclusionFirst-line eribulin/bevacizumab combination therapy showed interesting activity in MBC with an acceptable safety profile, including a particularly low incidence of high-grade neuropathy.
