Premenopausal women undergoing chemotherapy are at high risk for premature ovarian failure and its long-term consequences. Data on potential markers to evaluate ovarian reserve pre- and posttreatment ...are limited. Anti-Müllerian hormone (AMH) known for ovarian reserve in reproductive medicine could be a surrogate marker and was assessed in premenopausal breast cancer patients of the SUCCESS A study (EUDRA-CT no. 2005-000490-21).
We identified 170 premenopausal patients, age ≤ 40 years at trial entry, who received FEC-Doc as taxane-anthracylince based chemotherapy. Blood samples were taken at three time points: Before, four weeks after and two years after adjuvant chemotherapy. Serum AMH-levels were evaluated in a central laboratory by a quantitative immunoassay AMH Gen II ELISA (Beckman Coulter, Brea, USA).
Median age was 36 years (21–40 years). Median serum AMH-level before chemotherapy was 1.37 ng/ml (range < 0.1–11.3 ng/ml). Four weeks after chemotherapy AMH-levels dropped in 98.6% of the patients to <0.1 ng/ml (range < 0.1–0.21 ng/ml).
After two years, 73.3% (n = 101) showed no evidence of ovarian function recovery (AMH <0.1 ng/ml, range < 0.1–3.9 ng/ml). Permanent chemotherapy induced amenorrhea occurred only in 50.6% of the patients.
In this analysis, premenopausal patients showed a high rate of ovarian impairment reflected by low AMH-levels after chemotherapy.
•Data on markers to evaluate ovarian reserve in the context of chemotherapy are limited.•We examined AMH-levels in 170 patients ≤40 years who received FEC-Doc chemotherapy.•Low AMH-levels two years after chemotherapy were observed in 73.3% of the patients.•Age was the most important factor on gonadal function after cytotoxic treatment.
We were able to demonstrate a predictive value of serum HER2 (sHER2) in patients receiving trastuzumab in the neoadjuvant GeparQuattro trial. However, the role of sHER2 in patients receiving ...neoadjuvant therapy (NT) with lapatinib is still unclear.
The neoadjuvant GeparQuinto trial compared trastuzumab vs lapatinib in addition to chemotherapy in HER2-positive primary breast cancer patients. The sHER2 levels were measured by enzyme-linked immunosorbant assay in 210 patients, of whom 109 (52%) patients received trastuzumab and 101 (48%) lapatinib at three different time points.
Twenty-two percent of patients had elevated baseline sHER2 levels (>15 ng ml⁻¹). A decrease of sHER2 levels (>20%) in the trastuzumab and lapatinib-treated group during NT was seen in 44% and 24% of the patients, an increase of sHER2 levels (>20%) was seen in 6% and 41% of patients, respectively. Higher pre-chemotherapy sHER2 levels were associated with higher pathological complete remission (pCR) rates in the entire study cohort (OR 1.8, 95% CI 1.02-3.2, P=0.043). A decline of sHER2 levels (>20%) during NT was a predictor for pCR in the lapatinib-treated patient group (OR: 11.7, 95% CI 1.3-110, P=0.031).
Results of this study demonstrate that sHER2 levels change differently during NT depending on the anti-HER2 treatment strategy. Elevated baseline sHER2 levels (>15 ng ml⁻¹) and a decrease of sHER2 levels (>20%) early after therapy initiation are both relevant criteria to predict response to lapatinib-based treatment.
As 80% of intrauterine bone mineralization takes place during the last trimester of pregnancy, preterm infants should be supplemented postnatally with optimal doses of calcium, phosphate and vitamin ...D. Calcium and phosphate excretion in the urine may be used to monitor individual mineral requirements, but are sometimes difficult to interpret. The objective of this study was to assess the value of quantitative ultrasound (QUS) for the analysis of bone status in neonates.
All admissions to three independent tertiary neonatal intensive care units were studied. In 172 preterm and term infants with a gestational age between 23 and 42 weeks (mean 33.8±5.0) and a birth weight from 405 to 5130 g (mean 2132±1091 g) bone status was evaluated prospectively by quantitative ultrasound velocity using a standardized protocol. Infants were followed in regular intervals up to their first discharge home. While measurements were conducted in weekly intervals initially (n=55), 2-week intervals were regarded as sufficient thereafter due to limited changes in QUS values within the shorter period. Infants with a birth weight below 1500 g were followed during outpatient visits until up to 17 months of age.
The intra-individual day-to-day reproducibility was 0.62%. QUS-values from the first week of life correlated significantly with gestational age and birth weight (r=0.5 and r=0.6; P<0.001). Small-for-gestational-age infants showed lower values for QUS than appropriate-for-gestational-age infants allowing for their gestational age. Follow-up measurements correlated positively with age and weight during the week of measurement (r=0.2 and r=0.4; P=0.001). Comparing bone quality at 40 weeks of age in infants born at term versus infants born at 24 to 28 weeks, preterm infants showed significantly lower QUS than term infants (P<.0001).There was a significant correlation of QUS with serum alkaline phosphatase (P=0.003), the supplementation with calcium, phosphate and vitamin D (P< 0.001 each), as well as risk factors for a reduced bone mineralization. No correlation was found between QUS and calcium or phosphate concentration in serum or urine.
QUS is a highly reproducible, easily applicable and radiation-free technique that can be used to monitor bone quality in individual newborns. Further prospective randomized-trials are necessary to evaluate, if therapeutic interventions based on QUS are able to prevent osteopenia of prematurity.
Introduction Adjuvant anthracycline-based chemotherapy (AbCTX) is a standard treatment for patients with primary breast cancer. Its main target is topoisomerase IIα (TopIIa), a nuclear protein which ...is important for DNA replication and mitosis. We propose that the overexpression of the TopIIa protein or amplification of the TopIIa gene may be useful in predicting increased responsiveness towards AbCTX. Methods Tumor tissues of 118 patients who received adjuvant AbCTX were examined by immunohistochemistry (IHC) and fluorescence in situ hybridisation (FISH) for TopIIa and HER2. For IHC, the primary antibodies 485 (Dako) and NCL-TOPOIIA (Novocastra) were used. FISH analysis was performed with the SPEC HER2/CEP 17 Dual Color Probe (Zytovision) and LSI TOP 2A Spectrum Orange/CEP 17 Spectrum Green probe (Abbott). TopIIa IHC was evaluated by the immunoreactive score (IRS). FISH amplification was stated at an HER2-TopIIa/CEP 17 ratio ≥2, deletion of TopIIa at a ratio <0.8. Results The median age of the patient population was 50 years (range 23-77), 76 (64%) had tumors >2 cm in size, 98 (85%) were nodal positive, and 72 (66%) estrogen-receptor positive. Chemotherapy regimes consisted of epirubicin-cyclophosphamide (EC 40 pts), EC-CMF (18 pts), FAC/FEC (33 pts), anthracycline-taxane combinations (23 pts) and others (4 pts). After IHC, it was found that 19% of the tumors were positive for HER2 (3+) and the median IRS for TopIIa staining was 2 (49% positive); 28 (24%) tumors showed HER2 amplification, therefrom 20/22 (91%) within the HER2 3+ group. TopIIa gene was amplified in 17 cases (16%) and deletion was seen in 6 (5%) tumors. Of all cases with HER2 gene amplification, 14 (50%) cases of TopIIa co-amplification and one case of deletion were seen. Looking at histological parameters, TopIIa IHC correlated with nodal status (P = 0.018) and high grading (G3) (P = 0.047). After a median follow-up of 42 months (range 1-242), a significant prognostic factor for local recurrence was HER2 positivity (IHC P = 0.013 and FISH P = 0.023). Thirty-two patients developed metastasis (27%), which was correlated with HER2 FISH positivity (P = 0.024) and, as a trend, Top IIa IHC negativity (P = 0.094); 25 (21%) patients died from the disease. Negative prognostic parameters were the lack of estrogen-receptor expression (P = 0.008), lymphangiosis (P = 0.02), and TopIIa IHC negativity (P = 0.03). Conclusion In this cohort of patients, HER2 positivity indicated higher rates of local and distant recurrence. In contrast, TopIIa IHC positivity predicted lower risk of metastases and death, thus being a positive-predictive factor for the responsiveness to AbCTX. TopIIa gene amplification did not add predictive information. Therefore, we conclude that TopIIa protein expression might rather be the target of anthracyclines independent from gene copy number.
Background. Evidence is accumulating that circulating tumor cells (CTC) out of peripheral blood can serve as prognostic marker not only in metastatic but also in early breast cancer (BC). Various ...methods are available to detect CTC. Comparisons between the different techniques, however, are rare. Material and Methods. We evaluate two different methods for CTC enrichment and detection in primary BC patients: the FDA-approved CellSearch System (CSS; Veridex, Warren, USA) and a manual immunocytochemistry (MICC). The cut-off value for positivity was ≥1 CTC. Results. The two different nonoverlapping patient cohorts evaluated with one or the other method were well balanced regarding common clinical parameters. Before adjuvant CHT 21.1% (416 out of 1972) and 20.6% (247 out of 1198) of the patients were CTC-positive, while after CHT 22.5% (359 out of 1598) and 16.6% (177 out of 1066) of the patients were CTC-positive using CSS or MICC, respectively. CTC positivity rate before CHT was thus similar and not significantly different ( P = 0.749 ), while CTC positivity rate immediately after CHT was significantly lower using MICC compared to CSS ( P < 0.001 ). Conclusion. Using CSS or MICC for CTC detection, we found comparable prevalence of CTC before but not after adjuvant CHT.
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