Breast cancer in elderly women and altered clinico-pathological characteristics: a systematic review.

PURPOSE: Breast cancer is the most common malignancy in women in terms of incidence and mortality. Age is undoubtedly the biggest breast cancer risk factor. In this study we examined clinical, histological, and biological characteristics and mortality of breast cancer in elderly women along with their changes with advancing age. METHODS: We reviewed 63 original articles published between 2006 and 2016 concerning women over 70 years with breast cancer. RESULTS: Compared to patients 70-79 years, patients aged 80 and over had larger tumor size with fewer T1 (42.9% vs 57.7%, p < 0.01) and more T2 lesions (43.5% vs 33.0%, p < 0.01). Lymph nodes and distant metastases were more frequent, with more N + (49.5% vs 44.0%, p < 0.01) and more M1 (8.0% vs 5.9%, p < 0.01). Infiltrating mucinous carcinomas were more frequent (4.3% vs 3.7%, p < 0.01). Tumors had lower grades, with more grade 1 (23.2% vs 19.8%, p = 0.01) and fewer grade 3 (21.5% vs 25.5%, p < 0.01), and were more hormone-sensitive: PR was more often expressed (72.6% vs 67.3%, p < 0.01). Lympho-vascular invasion was less frequent in the 80 years and over (22.9% vs 29.7%, p = 0.01). Breast cancer-specific mortality was higher both at 5 years (25.8% vs 17.2%, p < 0.01) and 10 years (32.7% vs 26.6%, p < 0.01). CONCLUSION: Clinico-pathological characteristics, increased incidence, and mortality associated with aging can be explained on one hand by biological changes of the breast such as increased estrogen sensitivity, epithelial cell alterations, immune senescence, and tumor microenvironment modifications. However, sociologic factors such as increased life expectancy, under-treatment, late diagnosis, and insufficient individual screening, are also involved.

Glycemic management of diabetes by insulin therapy.

Recent technological innovations as insulin analogue formulation, devices for insulin delivery and glucose monitoring have allowed diabetic patients to improve their glycemic control and decrease their level of burden due to diabetes. Intensive insulin therapy via insulin pens, subcutaneous or intraperitoneal insulin infusions using pumps instead of vials and syringes, are associated with improved absorption reproducibility, HbA1c levels, reduced risk of hypo- or hyperglycemia, and increased quality of patient's life. These currently used systems are discussed in this review as well as the future of exogenous insulin therapy: closed loop system, the artificial pancreas, and oral insulin delivery. Glucose homeostasis is directly linked to glycemic regulated by portal insulin administration, thus endogenous insulin therapy might be the most promising treatment to "cure" diabetes. Consequently, pancreas and islet transplantation, and the bioartificial pancreas are described.

[uPA/PAI-1 and EPClin®: Comparison of their impact on the management of intermediate-prognosis breast cancers]. / uPA/PAI-1 et EPClin® : comparaison de leur impact sur la prise en charge des cancers du sein de pronostic intermédiaire.

OBJECTIVE: The uPA/PAI-1 assay and the EPClin® test are useful tools that add to clinico-anatomical characteristics to determine the indication of adjuvant chemotherapy in case of intermediate-prognosis invasive breast cancer. The principal purpose of our study was to analyze the concordance of uPA/PAI-1 and EPClin® in classification of patients into two groups: low and high risk of relapse. METHODS: We prospectively included 63 patients treated for intermediate-prognosis invasive breast cancer. All of these patients received a uPA/PAI-1 assay and an EPClin® test. RESULTS: The uPA/PAI-1 assay and EPClin® test were consistent for 56.2% and inconsistent for 43.8%. In the event of a discrepancy, the treatment decision was based in 95.2% of patients on the EPClin® test result. In total, 38 patients were selected for adjuvant chemotherapy after achievement of the two tests. The mean time to report results after surgery was 9 days for the uPA/PAI-1 assay and 35 days for the EPClin® test. No cases of recurrence or death were found, with an average follow-up of 32 months. CONCLUSION: The EPClin® test resulted in more chemotherapy prescriptions than indicated by uPA/PAI-1. However, we can't conclude to the superiority of one of these two tests, survival data and the effectiveness of our study being insufficient. In general, studies comparing different signatures useful to the therapeutic decision of intermediate prognosis breast cancers should be encouraged.

[Impact of endocrine disrupting pesticides on breast cancer]. / Impact des pesticides perturbateurs endocriniens sur le cancer du sein.

Of the 800 pesticides used worldwide, about 650 can affect the functioning of the endocrine system: endocrine disrupting pesticides (EDPs). Dietary or environmental exposure to EDPs is a concern, as their presence is currently demonstrated in most biological fluids. Some EDPs are prohibited, classified as carcinogenic, others are "probable" or "possible" carcinogens when there is limited evidence of their tumor effect. The impact of EDPs on breasts is not well known to date. However, since most EDPs have a long half-life and are lipophilic, breasts, composed mainly of adipose tissue, are a suitable site for their concentration. The objective of our review was to analyze the impact of EDPs related to our environmental exposure on breast cancer risk, through an analysis of recent literature, including epidemiological and biological data. Our review showed a positive association between the presence of EDPs and breast cancer, especially among women farmers or EDPs users but also in the general population. Studies on breast tumors have found a higher concentration of EDPs in estrogen-sensitive tumors. As for mortality, studies are contradictory, but confirm the dangerousness of some EDPs. The different series analyzed have several limitations, such as the low number of EDPs evaluated, small numbers and insufficient follow up. The potentiating effect of different EDPs used concomitantly and the window of exposure to these substances are parameters to be assessed.

[ASIA syndrome associated with breast implants: Fortuitous link or association?] / Le syndrome ASIA associé aux implants mammaires : lien de causalité ou association fortuite ?

OBJECTIVE: The "Autoimmune/Autoinflammatory Syndrome Induced by Adjuvants" (ASIA syndrome) described in 2011 by Shoenfeld and Agmon-Levin is believed to be the consequence of several immunological dysfunctions triggered by exposure to an adjuvant. Controversies regarding the existence of this syndrome and its possible link to silicone breast implants (SBI) have been growing via social networks and patient groups. The objective of our review was to identify all published cases of ASIA syndromes in SBI carriers to determine the circumstances of onset, key characteristics, and possible biases. METHOD: A literature search of the Pubmed database selecting only original articles written in English between 2011 and 2019 found 126 cases of ASIA syndromes, defined according to the criteria of Shoenfeld and Agmon-Levin, associated with SBI. RESULTS: This syndrome was diagnosed in nearly ¾ cases in a context of prosthetic complications (rupture, effusion, peri-prosthetic shell, infection) with a median time interval of 4 years between SBI implantation and the onset of symptoms. Explantation of the SBI led to an improvement in symptoms in about half of the cases. However, animal, biological and histological studies have provided conflicting results on the links between silicone and dysimmune syndromes. CONCLUSION: Women should be clearly, fairly and appropriately informed of our uncertainties about ASIA syndrome. Mandatory reporting of dysimmune syndromes occurring in silicone MI carriers would increase our knowledge of this still poorly understood condition, for which a genetic predisposition is being investigated.

[Hyperthyroidism and breast cancer: Is there a link?] / Hyperthyroïdie et cancer du sein : y a-t-il une association ?

The objective of this review was to determine whether there is an association between hyperthyroidism and the risk of developing a breast cancer from the analysis of data in the literature. METHOD: The analyzed articles were extracted from the PUBMED database from 2002 to 2017 using the following keywords "hyperthyroidism AND breast cancer" and "thyroid AND breast cancer". RESULTS: A total of 22 studies were selected, including 8 cohort studies, 12 case-control studies and 2 meta-analyzes. Of these 22 studies, 15 have established a significant epidemiological or biological link between hyperthyroidism and breast cancer. Five of them were particularly interested in Graves' disease, and four demonstrated a positive association between this disease and the onset of breast cancer, especially within three years from the thyropathy diagnosis. These different studies also highlighted the increased risk of breast cancer seen in overweight or postmenopausal women. Contradictions persist over the types of mammary cancers observed and their prognosis. CONCLUSION: This review reveals that women with hyperthyroidism appear to have a moderately high risk of breast cancer (RR<2). These data are corroborated by solid physiopathological hypotheses. Regardless of the type of thyropathy responsible for hyperthyroidism, care should be taken to ensure that these patients receive a clinical examination of the breasts on an annual basis and mammographic screening every 2 years from the age of 50 years.

[Breast cancer and diabetes mellitus: Complex interactions]. / Cancer du sein et diabète de type 2 : des interactions complexes.

The aim of this literature review was to quantify the incidence and mortality of breast cancer for women treated for a diabetes mellitus and to analyze the complex relationship between these two common diseases. METHODS: The articles analyzed were extracted from the PubMed database from 2000 to 2015. A total of 22 case/control studies or cohorts were retained, allowing the realization of a meta-analysis. RESULTS: The incidence of breast cancer for women with diabetes is significantly increased for cohorts (RR=1.32; 95% CI: 1.06 to 1.65) and not significantly for case/control studies (RR=1.46; 95% CI: 0.99 to 2.26). Overall, mortality of women with breast cancer is significantly increased for diabetic patients compared with non-diabetic patients (RR=1.53; 95% CI: 1.23 to 1.90). The links between diabetes and breast cancer are explained by common risk factors (overweight/obesity, qualitative and quantitative dietary errors, physical inactivity), biological changes and the impact of some anti-diabetic treatments or hormonotherapy. CONCLUSION: Physicians facing a diabetic patient treated for breast cancer have a role in choosing the best anti-diabetic treatment and implementing lifestyle modifications. Diabetic women without breast cancer should participate in organized breast screening programs and have an annual breast clinical examination.

Substitution of insulin by exenatide in bad controlled type 2 diabetic patients: efficacy and predictive factors.

AIM: Exenatide therapy is indicated in type 2 diabetes after failure of oral antidiabetic agents (OAD). The aim of this observational prospective study was to assess efficacy of exenatide, in improving HbA1c of at least of 1% (responders) in type 2 diabetic patients treated previously with insulin. METHODS: Thirty-six patients (HbA1c >7.5%), with chronic bad glycemic control, were hospitalized to improve glycemia using transient continuous insulin infusion followed by administration of exenatide and OAD agents. In these patients, insulin had been introduced previously because of OAD failure without any sign of severe insulin deficiency. RESULTS: On the 27 patients analyzed at 3 months, 19 patients were responders (HbA1c: M0: 9.9±1.7%; M3: 7.6±1.2%). Among the 8 non-responders, only 4 deteriorated their HbA1c. After 9 months, 10 patients remained Responders (HbA1c: 7±0.9%). Predictive factors for an improvement of glycemic control were: diabetes duration shorter than 12 years, ratio fasting glycemia/C-peptide less than 1, fasting C-peptide higher than 2.0 µg/L and mean capillary blood glucose after 3 days of exenatide lower than 200 mg/dL. These criteria remained valid in case of a high HbA1c at baseline. CONCLUSION: In patients with no signs of insulin dependence and in case of insulin failure, exenatide associated to OAD may be tried in order to improve glycemic control, this objective was reached by 70% of our patients. Predictive factors for good response, easily available in clinical practice, may help therapeutic choices.

[Acute hepatopathy caused by amiodarone. Study of a case and review of the literature]. / Hépatopathie aiguä due à l'amiodarone. Etude d'un cas et revue de la littérature.

The authors report the case of a non-alcoholic 73-year-old man, treated for arrhythmia with amiodarone for 2 months, and hospitalized because of jaundice and hepatomegaly. There was an important increase in serum alkaline phosphatase activity (4 times the normal value) and a moderate increase in the serum activity of transaminases (3-4 times the normal value). Endoscopic retrograde cholangiography was normal. Serum markers of virus B and tissue antibodies were absent. Histological examination of a liver specimen disclosed portal and periportal fibrosis, mixed inflammatory infiltrate of the portal spaces, and ductular proliferation. Lamellar lysosomal inclusions were demonstrated on electron microscopy. Outcome was favorable after withdrawal of amiodarone. This report, as well as the 7 previously published cases, cannot explain the pathogenesis of amiodarone-induced liver changes.

[Puncture of solid tumors of the liver with large caliber needle guided by ultrasonography. Study of 70 punctures]. / Ponction des tumeurs solides du foie à l'aiguille de gros calibre guidée par l'échographie. Etude de 70 ponctions.

Seventy specimens of solid hepatic tumors were obtained for histologic examination with a 18 G (1.2 mm) diameter needle under real-time ultrasound control. Overall sensitivity was 95.6 p. 100 while specificity was 100 p. 100. Distinction between primitive and secondary malignant tumor was possible in 91 p. 100 of cases. Transient hemorrhage at the puncture site occurred in one patient. These results attest to the superiority of guided puncture with a needle of sufficient caliber, thus allowing for correct histologic study. Side effects did not occur more frequently than with fine caliber needles.

[Hepatocellular carcinoma invading the right atrium: clinical, echographic and angiographic study]. / Carcinome hépatocellulaire envahissant l'oreillette droite: étude clinique, échographique et angiographique.

The authors report the case of a 54 year old woman suffering from hepatocellular carcinoma with tumor growth into right hepatic vein, inferior vena cava and right atrium. On cardiac examination, a pansystolic bruit and a diastolic rumble were audible at the tricuspid focus. Diagnosis was confirmed by inferior vena cavography and two-dimensional echocardiography, which demonstrated a large mobile mass in the right atrium moving to and fro through the tricuspid valve. This case report emphasizes the value of routine cardiac examination during the course of hepatocellular carcinoma.

Gastric bezoar: another side effect of endoscopic variceal sclerotherapy.

Gastric bezoars were observed after esophageal variceal injection of polidocanol in 5 of 56 patients with alcoholic cirrhosis treated by endoscopic sclerosis. We suggest that endoscopic sclerotherapy could have induced a transient vagal injury resulting in delayed gastric emptying and subsequent bezoar formation. Although the volume of sclerosant (25-35 ml per session) and the length of the injector needle (4 mm) were the same in all patients, two reasons could explain the occurrence of bezoars in these five patients: a deeper injection of sclerosant, and a worsening of a preexistent vagal neuropathy due to diabetes mellitus and/or alcoholism.