study finds no disease free survival difference in those women with breast cancer and sentinel node metastasis for axillary lymph node dissection versus no disecction; no difference in overall survival at 10 years also observed.
shortened survival and an increased risk of disease recurrence and metastasis
Currently, four HER2-directed agents are approved for the treatment of patients with HER2+ breast cancer: trastuzumab, pertuzumab, lapatinib, and ado-trastuzumab emtansine (T-DM1)
biosimilars
trastuzumab may provide greater benefit when administered concurrently with chemotherapy rather than after, and this has become the standard approach
concurrent use of anthracyclines (ie, doxorubicin or epirubicin) and trastuzumab is not recommended because of an increased risk for cardiac toxicity
Guidelines also recommend trastuzumab in combination with paclitaxel, docetaxel and carboplatin, or docetaxel and cyclophosphamide, particularly for patients with increased risk for cardiac toxicity or those with small (≤1 cm), node-negative HER2+ tumors
good alternative in patients with increased risk of cardiac toxicity.
guidelines recommend up to 1 year of adjuvant trastuzumab
Neoadjuvant chemotherapy with trastuzumab is associated with higher rates of pathologic complete response (pCR) than chemotherapy alone or in combination with lapatinib
the combination of trastuzumab, lapatinib, and chemotherapy is not recommended because it failed to demonstrate noninferiority versus trastuzumab and chemotherapy in the adjuvant setting
recommend the combination of trastuzumab, pertuzumab, and chemotherapy as neoadjuvant treatment for patients with locally advanced HER2+ breast cancer and for some patients (node-positive or tumor ≥2 cm) with early-stage disease
neoadjuvant chemotherapy in combination with pertuzumab and trastuzumab reduced the risk of progression or death by 31% and recurrence or death by 40% versus trastuzumab alone
Concurrent chemotherapy and HER2-directed therapy improves survival outcomes over chemotherapy alon
dual inhibition of HER2 with trastuzumab and pertuzumab in combination with paclitaxel reduced the risk of death or progression by approximately 40% compared with concurrent trastuzumab and paclitaxel
the combination of trastuzumab, pertuzumab, and taxane chemotherapy is the preferred first-line regimen
The typical onset of TS occurs at 6–7 years of age and is characterized by the appearance of simple, recurrent motor tics, followed by the manifestation of phonic tics after several months [12]. In most children, TS symptoms undergo a progressive exacerbation, which reaches its zenith at the beginning of puberty (11–12 years of age), and is then followed by a gradual remission in the majority of patients
30–40% of TS-affected children retain their symptoms in adulthood
Multiple neurotransmitters have been implicated in TS, including dopamine (DA), serotonin, norepinephrine, acetylcholine, glutamate and γ-amino-butyric acid (GABA)
female gender may predict greater tic severity in adulthood
male gender is a major risk factor for TS (with a male:female prevalence ratio estimated at ~4:1)
the typical age of onset coincides with adrenarche (6–7 years old); symptoms increase in severity until the beginning of puberty (12 years old) and then undergo a spontaneous amelioration, which becomes apparent with the end of puberty (at 18–19 years of age)
TS is diagnosed later in females than males
ample evidence supports the involvement of DAergic dysfunctions in TS
a number of clinical observations showed that tics in TS patients could be exacerbated by anabolic androgens
steroidogenic enzymes and androgen receptors may serve as putative therapeutic targets for this disorder
Unlike males, tic severity is typically increased after puberty in females
26% of females were found to experience exacerbation of tics in the estrogenic phase of the menstrual cycle, and this phenomenon was found to be correlated with increased tic severity at menarche
biochemical hallmark of adrenarche is the acquisition of 17,20 lyase activity by cytochrome P450 C17 (CYP17A1)
increased synthesis of dehydroepiandrosterone (DHEA) and androstenedione, which leads to the growth of axillary and pubic hair as well as enhancement in the oiliness of the skin
interesting read on hormones and tourette's.. Proposed that 5 alpha reductase activity is involved in worsening of tics. This makes sense as Testosterone in men with low T is known to increase dopamine and dopaminergic dysfunction is known to play a role in tourette's; the clinical presentation of girls vs boys is very different. The authors of this article propose that 5 alpha reductase activity controls a back door method where by progesterone is converted to androgens.