Anectodical information suggests that flavonoids may be widely used among athletes for their multiple biochemical and pharmacological effects. We have evaluated in vitro the effects of two synthetic isoflavones, methoxyisoflavone and ipriflavone, on the catalytic activity of human aromatase (CYP19), the enzyme catalyzing the conversion of androgens (i.e. testosterone or androstenedione) to estrogens (i.e. estradiol and estrone). The potential inhibitory effect was evaluated by measuring the rate of aromatization of testosterone, monitored by GC-MS, both in the presence and in the absence of methoxyisoflavone or ipriflavone, comparing their effects with those of synthetic aromatase inhibitors (formestane, anastrozole and aminoglutethimide) presently included in the list of prohibited substances and methods, and of natural flavonoids (chrysin, quercetin and daidzein), that are known inhibitors of CYP19. The preliminary results of our in vitro study show that methoxyisoflavone and ipriflavone act as competitive inhibitors of aromatase, the degree of inhibition measured in vitro being of the same order of magnitude of that of the aromatase inhibitors commonly used in anti-estrogenic therapies. Our preliminary in vitro results indicate that, in principle, a sufficiently large intake of isoflavones could alter the kinetics of the dynamic equilibria between androgens and estrogens, suggesting their monitoring in doping control routine analysis.

Purpose To assess pertuzumab plus trastuzumab and an aromatase inhibitor (AI) in patients with human epidermal growth factor receptor 2 (HER2)-positive and hormone receptor-positive metastatic/locally advanced breast cancer (MBC/LABC). Patients and Methods The PERTAIN trial (NCT01491737) is an ongoing randomized, open-label, multicenter-80 sites and eight countries-phase II trial. Patients have HER2-positive, hormone receptor-positive MBC/LABC and no prior systemic therapy with the exception of endocrine. Random assignment was 1:1 to intravenous pertuzumab (840 mg loading dose followed by 420 mg every 3 weeks) plus trastuzumab (8 mg/kg followed by 6 mg/kg every 3 weeks), and oral anastrozole (1 mg every day) or letrozole (2.5 mg every day), or trastuzumab and an AI. Induction intravenous docetaxel every 3 weeks or paclitaxel every week could be administered for 18 to 24 weeks at the investigator's discretion (decided before but given after random assignment). Primary end point was progression-free survival (PFS). Patients were stratified by whether they received induction chemotherapy and their time since adjuvant hormone therapy. Results One hundred twenty-nine patients were randomly assigned per arm (February 2012 to October 2014; intent-to-treat populations); 75 in one arm and 71 in the other were chosen to receive induction chemotherapy. Stratified median PFS was 18.89 months (95% CI, 14.09 to 27.66 months) in the pertuzumab plus trastuzumab arm and 15.80 months (95% CI, 11.04 to 18.56 months) in the trastuzumab arm (stratified hazard ratio, 0.65; 95% CI, 0.48 to 0.89; P = .0070). Serious adverse events (AEs) were reported for 42 (33.1%) of 127 and 24 (19.4%) of 124 patients in the safety populations of the pertuzumab plus trastuzumab and trastuzumab arms, respectively. Rates of grade ≥ 3 AEs were 64 (50.4%) of 127 and 48 (38.7%) of 124, respectively. There were no deaths as a result of AEs. Conclusion PERTAIN met its primary PFS end point. Pertuzumab plus trastuzumab and an AI is effective for the treatment of HER2-positive MBC/LABC. The safety profile was consistent with previous trials of pertuzumab plus trastuzumab.

The present work describes a fast, sensitive and selective procedure for the analyses of aromatase inhibitors including anastrozole, letrozole and exemestane used in the treatment of metastatic breast cancer by high performance liquid chromatography (HPLC) in human whole blood, plasma, and urine samples succeeding an extraction by innovative fabric phase sorptive extraction (FPSE). These drugs were successfully determined using a Luna C18 column at 25 °C using acetonitrile and phosphate buffer. The analytical method was validated, using weighted-matrix matched standard calibration curves. The intra- and inter-day accuracy values (precision and trueness) fulfill the criteria of International Guidelines on Bioanalytical Methods Validation. The analytical performances were further tested on real human biological samples. To the best of our knowledge, this is the first FPSE procedure applied to human whole blood, plasma, and urine samples for the concurrent analysis of aromatase inhibitors possessing a wide range of polarity index values and could be easily adopted as a rapid and green analytical protocol for clinical and pharmaceutical applications. The proposed HPLC method is very innovative since in the literature there are only methods dealing with a single antitumoral drug, and no process has been described so far for these three antitumoral drugs together directly from the whole blood.

Everolimus (RAD001) is an oral protein kinase inhibitor of the mTOR (mammalian target of rapamycin) serine/threonine kinase signal transduction pathway. The mTOR pathway regulates cell growth, proliferation and survival, and is frequently deregulated in cancer.The EMA has approved Everolimus as Afinitor® for the treatment of hormone receptor-positive, HER2/neu-negative advanced breast cancer, in combination with exemestane, in postmenopausal women without symptomatic visceral disease after recurrence or progression following a nonsteroidal aromatase inhibitor, for the treatment of unresectable or metastatic, well- or moderately differentiated neuroendocrine tumors of pancreatic origin in adults with progressive disease, and for the treatment of unresectable or metastatic, well-differentiated (Grade 1 or Grade 2) nonfunctional neuroendocrine tumors of gastrointestinal or lung origin in adults with progressive disease, and for the treatment of patients with advanced renal cell carcinoma, whose disease has progressed on or after treatment with VEGF-targeted therapy And as Votubia® for the treatment of adult patients with renal angiomyolipoma associated with tuberous sclerosis complex (TSC), who are at risk of complications (based on factors such as tumor size or presence of aneurysm, or presence of multiple or bilateral tumors) but who do not require immediate surgery, and for the treatment of patients with subependymal giant cell astrocytoma (SEGA) associated with TSC who require therapeutic intervention but are not amenable to surgery, and as an add-on treatment in patients from 2 years of age with seizures related to TSC that have not responded to other treatments ( https://www.novartis.com/news/media-releases/novartis-drug-votubiar-receives-eu-approval-treat-refractory-partial-onset ). The FDA has approved Everolimus as Afinitor® for the treatment of postmenopausal women with advanced hormone receptor-positive, HER2-negative breast cancer in combination with exemestane, after the failure of treatment with letrozole or anastrozole, for the treatment of adult patients with progressive neuroendocrine tumors of pancreatic origin (PNET) with unresectable, locally advanced or metastatic disease, for the treatment of adult patients with advanced RCC after failure of treatment with sunitinib or sorafenib, for the treatment of adult patients with renal angiomyolipoma and tuberous sclerosis complex (TSC), not requiring immediate surgery. for the treatment of adult and pediatric patients, 3 years of age or older, with SEGA associated with TSC who require therapeutic intervention but are not candidates for curative surgical resection. Everolimus shows promising clinical activity in additional indications. Multiple Phase II and Phase III trials of everolimus alone or in combination and will help to further elucidate the role of mTOR in oncology. For a review on everolimus as immunosuppressant, please consult other sources.

Background Gynaecomastia, although rarely related to testicular tumours, in boys with Peutz-Jeghers syndrome (PJS) usually occurs due to large-cell calcifying Sertoli cell tumour (LCCSCT). Case presentation A 4-year-old boy, with a genetic diagnosis of PJS, presented gynaecomastia since the age of 2, associated with increased height velocity (HV). He exhibited bilateral breast enlargement (Tanner-B4) and a testicular volume of 4 mL. Testicular ultrasound revealed multifocal microcalcifications in both testicles. A laboratory evaluation showed undetectable gonadotrophins, testosterone and oestrogen and inhibin A of 4.6 pg/mL (0.9-1.7). The boy was subjected to therapy with anastrozole. In the last follow-up, 2 years after the start of therapy, he experienced a less tense Tanner-B2 and a decrease in HV; serum inhibin A had become negative. Conclusions This is one of the most precocious PJS-related gynaecomastia treated with aromatase inhibitors (AIs) reported in the literature. Oestrogen levels, although under the detection limit, may be sufficient to stimulate breast tissue/growth plates. Inhibin A is a good marker of LCCSCT and an indicator of response to AIs.