Loss of HER2 and disease prognosis after neoadjuvant treatment of HER2+ breast cancer.

INTRODUCTION: HER2 overexpression/amplification occurs in 15-20% breast cancers (BC) and is associated with worse prognosis. The addition of anti-HER2 treatment to neoadjuvant chemotherapy significantly improves the pathological complete response (pCR) rate. Changes in HER2 status after neoadjuvant treatment (NAT) have been reported and may affect prognosis. The aim of this study was to assess the efficacy of NAT in patients with HER2+ BC and its influence on HER2 status and associated prognostic impact. METHODS: Retrospective chart review and pathologic evaluation of all consecutive patients with HER2+ BC (defined as IHC 3+ or IHC 2+ confirmed by SISH) submitted to NAT between 2010-2015 in three Portuguese Hospitals. RESULTS: One hundred eight female patients were included; 40 with stage II, 68 with stage III. Hormone receptors were positive in 70. pCR (ypT0/isN0) was achieved in 48 patients (44%). With a median follow-up of 52 months, there were 5 disease free survival (DFS) events among pCR patients and 19 among non-pCR (P = 0.02). Of the 60 patients with residual disease at surgery, 52 remained HER2+ and 8 (13%) lost HER2 overexpression/amplification. 5y-DFS and 5y-OS was 70% and 84%, respectively, for patients whose residual tumors remained HER2+, and 21% and 50% for patients whose residual tumors became HER2 negative (P = 0.02 and < 0.001). DISCUSSION: We confirmed the negative prognostic impact of NAT-induced HER2 loss on residual tumor leading to worse DFS and OS. Despite the retrospective design and small sample size, these results suggest that it is important to retest HER2 after NAT, to better refine patient outcome.

Differential expression of gonadotropin and estrogen receptors and oocyte cytology during follicular maturation associated with egg viability in European eel (Anguilla anguilla).

In captivity, oogenesis and ovarian follicle maturation in European eel can be induced experimentally using hormonal therapy. The follicle's ability to respond effectively to the induction of maturation and ovulation, resulting in viable eggs, depends on the oocyte stage at the time of induction. We hypothesized that variation in the expression of key hormone receptors in the ovary and size of oocyte lipid droplets are associated with changes in oocyte stage. Thus, we induced ovarian follicle maturation using a priming dose of fish pituitary extract followed by the administration of a 17α, 20ß-dihydroxy-4-pregnen-3-one (DHP) injection. Females were then strip-spawned, the eggs were fertilized in vitro, incubated and larval survival was recorded at 3 days post hatch (dph). The expression of gonadotropin receptors (fshr, lhcgr1 and lhcgr2) and estrogen receptors (esr1, esr2a, esr2b, gpera and gperb) was quantified and the size of oocyte lipid droplets measured. Larval survival at 3 dph was used to differentiate high- and low-quality egg batches. Results showed significantly higher abundance of lhcgr1 and esr2a at priming for high-quality egg batches whereas fshr and gperb transcripts were significantly higher at DHP injection for low-quality egg batches. Therefore, high levels of lhcgr1 and esr2a may be important for attaining follicular maturational competence, while high fshr and gperb mRNA levels may indicate inadequate maturational competence. Furthermore, lipid droplet size at DHP and in ovulated eggs was significantly smaller in high-quality egg batches than in low-quality, which indicates that droplet size may be a useful marker of follicular maturational stage.

Interactive effects of dietary composition and hormonal treatment on reproductive development of cultured female European eel, Anguilla anguilla.

Farmed female eels were fed two experimental diets with similar proximate composition but different n-3 polyunsaturated fatty acid (PUFA) levels. Both diets had similar levels of arachidonic acid (ARA), while levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in one diet were approximately 4.5 and 2.6 times higher compared to the other diet, respectively. After the feeding period, each diet group was divided into two and each half received one of two hormonal treatments using salmon pituitary extract (SPE) for 13 weeks: i) a constant hormone dose of 18.75mg SPE/kg initial body weight (BW) and ii) a variable hormone dosage that increased from 12.5mg SPE/kg initial BW to 25mg SPE/kg initial BW. Results showed a significant interaction between diets and hormonal treatments on gonadosomatic index (GSI), indicating that the effect of broodstock diets on ovarian development depends on both nutritional status and hormonal regime. Females fed with higher levels of n-3 series PUFAs and stimulated with the constant hormonal treatment reached higher GSIs than those receiving the variable hormonal treatment. However, when females were fed lower levels of n-3 series PUFAs there was no difference in the effect of hormonal treatments on GSI. We also found that, independent of hormonal treatment, the diet with higher levels of n-3 series PUFAs led to the most advanced stages of oocyte development, such as germinal vesicle migration. Concentration of sex steroids (E2, T, and 11-KT) in the plasma did not differ between diets and hormonal treatments, but was significantly correlated with ovarian developmental stage. In conclusion, increasing dietary levels of n-3 PUFAs seemed to promote oocyte growth, leading to a more rapid progression of ovarian development in European eel subjected to hormonal treatment.