Neoadjuvant endocrine therapy with or without palbociclib in low-risk patients: a phase III randomized double-blind SAFIA trial.

BACKGROUND: The most prevalent subtype of breast cancer (BC) is luminal hormonal-positive breast cancer. The neoadjuvant chemotherapy regimens have side effects, emphasizing the need to identify new startegies. OBJECTIVE: Analyze the complete pathologic response (pCR) rate and overall response in a low-risk hormone-positive subset of patients receiving neoadjuvant hormone treatment (NAHT) with or without Palbociclib (a CDK4/CDK6 inhibitor) to boost NAHT effectiveness. MATERIALS AND METHODS: Based on the upfront 21-gene Oncotype DX or low-risk Breast Recurrence Score assay (RS™), the SAFIA trial is designed as a prospective multicenter international, double-blind neoadjuvant phase-III trial that selects operable with luminal BC patients that are HER2-negative for the induction hormonal therapy with Fulvestrant 500 mg ± Goserelin (F/G) followed by randomization of responding patients to palbociclib versus placebo. The pCR rate served as the study's main outcome, while the secondary endpoint was a clinical benefit. RESULTS: Of the 354 patients enrolled, 253 initially responded and were randomized to either F/G fulvestrant with palbociclib or placebo. Two hundred twenty-nine were eligible for the evaluation of the pathologic response. No statistically significant changes were observed in the pCR rates for the patients treated with the F/G therapy with placebo or palbociclib (7% versus 2%, respectively) per the Chevallier classification (Class1 + Class2) (p = 0.1464) and 3% versus 10% assessed per Sataloff Classification (TA, NA/NB) (p = 0.3108). Palbociclib did not increase the rate of complete pathological response. CONCLUSION: Neoadjuvant hormonal therapy is feasible in a selected population with a low RS score of < 31 CLINICAL TRIAL: NCT03447132.

Epidemiology of breast cancer in women based on diagnosis data from oncologists and senologists in Algeria.

BACKGROUND: Breast cancer (BC) is a major health issue threatening women's life. No reliable epidemiological data on BC diagnosed by oncologists/senologists are available in Algeria. METHODS: The BreCaReAl study, a non-interventional prospective cohort study, included adult women with confirmed BC in Algeria. Disease incidence, patients and disease characteristics, treatment patterns, and mortality rate were recorded up to 12 months of follow-up. RESULTS: Overall, 1,437 patients were analysed: median age was 48 [41;57] years and 337 (23.5%) women had a family history of BC. BC incidence was 22.3 (95% CI: 21.5; 23.2) cases per 100,000 inhabitants over 8 months. Delayed diagnosis was reported in 400 (29.2%) patients. First line of treatments were mainly chemotherapy and surgery. Twenty-eight serious adverse events were reported including 10 (37.0%) events which led to death. Mortality rate reached 3.2% at 12 months CONCLUSION: A delayed diagnosis highlights the importance of implementing more effective screening strategies.

First description of mutational analysis of MLH1, MSH2 and MSH6 in Algerian families with suspected Lynch syndrome.

Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominant disorder characterized by the early onset of colorectal cancer (CRC) linked to germline defects in Mismatch Repair (MMR) genes. We present here, the first molecular study of the correlation between CRC and mutations occurring in these genes performed in twenty-one unrelated Algerian families. The presence of germline mutations in MMR genes, MLH1, MSH2 and MSH6 genes was tested by sequencing all exons plus adjacent intronic sequences and Multiplex ligand-dependent probe amplification (MLPA) for testing large genomic rearrangements. Pathogenic mutations were identified in 20 % of families with clinical suspicion on HNPCC. Two novel variants described for the first time in Algerian families were identified in MLH1, c.881_884delTCAGinsCATTCCT and a large deletion in MSH6 gene from a young onset of CRC. Moreover, the variants of MSH2 gene: c.942+3A>T, c.1030C>T, the most described ones, were also detected in Algerian families. Furthermore, the families HNPCC caused by MSH6 germline mutation may show an age of onset that is comparable to this of patients with MLH1 and MSH2 mutations. In this study, we confirmed that MSH2, MLH1, and MSH6 contribute to CRC susceptibility. This work represents the implementation of a diagnostic algorithm for the identification of Lynch syndrome patients in Algerian families.

[Acute myocarditis complicating Mediterranean spotted fever. A case report]. / Une myocardite aiguë compliquant une fièvre boutonneuse méditerranéenne. À propos d'un cas.

Mediterranean spotted fever (MSF) due to Rickettsia conorii is the most important tick-borne disease occurring in North Africa. The first description of MSF was made by Conor and Brush in 1910 in Tunisia. Clinical diagnosis relies on the association of fever, rash and inoculation's scar during summertime. Prognosis in MSF is usually good, however malignant forms were described. These forms occur in patients with comorbidities. G6PD deficiency is a classic ground for severe forms of MSF. Myocarditis is an uncommon complication in MSF; only few cases were reported in the literature. We report a new case of myocarditis complicating MSF in a 15-year-old patient with G6PD deficiency. The patient presented with fever and rash, evocative of MSF; he reported chest pain and the electrocardiogram showed ST segment elevation in anterior leads. Troponin level was elevated. Echocardiogram showed left ventricular dysfunction with 40% ejection fraction. Serologic tests confirmed R. conorii recent infection. Antibiotic treatment with vibramycine and rifadine was started. Patient also received classic treatment of myocarditis with left ventricular dysfunction associating CEI, ß-bloquers and diuretics. Evolution was favourable with complete recovery of left ventricular function. Myocarditis is an uncommon but severe complication of MSF. Early diagnosis and treatment allow favorable evolution.

[Percutaneous embolisation of a iatrogenic fistula between the internal mammary artery and the coronary vein]. / Embolisation percutanée d'une fistule iatrogène entre l'artère mammaire interne et la veine coronaire. Revue de la littérature à propos d'une observation.

Latrogenic fistula between the aorta and coronary vein is a rare complication of coronary bypass surgery due to accidental venous or arterial graft onto a coronary vein. The authors report a case of a patient admitted to hospital 2 months after coronary bypass surgery for cardiac failure due to a iatrogenic fistula by implantation of the left internal mammary artery on the great coronary vein. This presentation led to the choice of percutaneous embolisation of the fistula by the release of 6 coils. Based on a review of the literature, this clinical case illustrates the feasibility and value of percutaneous embolisation of iatrogenic fistulae.

Chemical substance kinetics in the case of chronobiological variations of elimination rate.

This study describes an approach permitting the determination of compartmental concentration and drug kinetics in the case of chronobiological variations of elimination rate.