Background. Currently, there have been no reports of clear‐cut beneficial effects of regular screening with mammography at a mean screening interval of 2 years in women younger than 50 years of age. It may be that, because of a higher growth rate of breast cancer, more frequent screening is necessary if any effect is to be observed in this age group. However, good quantitative estimates for the growth rate in different age groups are lacking. Methods. The study group consisted of cancers diagnosed in women who participated in a screening program with serial mammography available. The growth rate, expressed as the tumor volume doubling time, was calculated on the assumption of exponential growth. The analysis was based, not only on the increase in tumor volume for cancers with at least two mammograms showing a measurable tumor nucleus shadow (n = 85), but also on censored values, calculated for cancers showing no growth (n = 6) and for cancers showing only a measurable tumor nucleus shadow on the mammogram at diagnosis (n = 109). In calculating these latter growth rates, the density of the breast parenchyma was taken into account. Results. The median volume doubling time of the primary breast cancers diagnosed in women aged 50–70 years was 157 days (95% confidence limits, 121–204 days). This was significantly longer than in women younger than 50 years of age at diagnosis (80 days; 95% confidence limits, 44–147 days). Primary breast cancer in women older than 70 years of age at diagnosis grew even more slowly (median, 188 days; 95% confidence limits, 120–295). Conclusions. To observe a beneficial effect of screening, if any, for women younger than age 50 years, more frequent screening than in the older age group is necessary.

Spermatozoa of subfertile men contain significantly higher thiol concentrations as compared with those of fertile men. The detrimental effect on embryo quality of a high Hcy concentration in the ejaculate and in follicular fluid is intriguing and may suggest that Hcy is inversely associated with fertility outcome.

Context: Noonan syndrome (NS) is characterized by short stature, typical facial dysmorphology and congenital heart defects. Short-term effect of GH therapy in NS is beneficial, reports on the effect on adult height are scarce. Objective: To determine the effect of long-term GH therapy in children with NS. Design: Twenty-nine children with NS were treated with GH until final height was reached. Setting: Hospital endocrinology departments. Patients: Children with the clinical diagnosis of NS, with mean age at the start of therapy of 11.0 years, 22 out of 27 tested children had a mutation in the protein tyrosine phosphatase, non-receptor-type 11 gene (PTPN11 gene). Interventions: GH was administered subcutaneously at 0.05 mg/kg per day until growth velocity was 1 cm/6 months. Main outcome measure: Linear growth (height) was measured at 3-month intervals in the first year and at 6-month intervals thereafter until final height. Results: At the start of treatment, median height SDS (H-SDS) was K2.8 (K4.1 to K1.8) and 0.0 (K1.4 to C1.2), based on national and Noonan standards respectively. GH therapy lasted for 3.0-10.3 years (median, 6.4), producing mean gains in H-SDS of C1.3 (C0.2 to C2.7) and C1.3 (K0.6 to C2.4), based on national and Noonan standards respectively. In 22 children with a mutation in PTPN11 mean gain in H-SDS for National standards was C1.3, not different from the mean gain in the five children without a mutation in PTPN11C1.3 (PZ0.98). Conclusion: Long-term GH treatment in NS leads to attainment of adult height within the normal range in most patients.

Summary Background Increasing the dose intensity of cytotoxic therapy by shortening the intervals between cycles, or by giving individual drugs sequentially at full dose rather than in lower-dose concurrent treatment schedules, might enhance efficacy. Methods To clarify the relative benefits and risks of dose-intense and standard-schedule chemotherapy in early breast cancer, we did an individual patient-level meta-analysis of trials comparing 2-weekly versus standard 3-weekly schedules, and of trials comparing sequential versus concurrent administration of anthracycline and taxane chemotherapy. The primary outcomes were recurrence and breast cancer mortality. Standard intention-to-treat log-rank analyses, stratified by age, nodal status, and trial, yielded dose-intense versus standard-schedule first-event rate ratios (RRs). Findings Individual patient data were provided for 26 of 33 relevant trials identified, comprising 37 298 (93%) of 40 070 women randomised. Most women were aged younger than 70 years and had node-positive disease. Total cytotoxic drug usage was broadly comparable in the two treatment arms; colony-stimulating factor was generally used in the more dose-intense arm. Combining data from all 26 trials, fewer breast cancer recurrences were seen with dose-intense than with standard-schedule chemotherapy (10-year recurrence risk 28·0% vs 31·4%; RR 0·86, 95% CI 0·82–0·89; p<0·0001). 10-year breast cancer mortality was similarly reduced (18·9% vs 21·3%; RR 0·87, 95% CI 0·83–0·92; p<0·0001), as was all-cause mortality (22·1% vs 24·8%; RR 0·87, 95% CI 0·83–0·91; p<0·0001). Death without recurrence was, if anything, lower with dose-intense than with standard-schedule chemotherapy (10-year risk 4·1% vs 4·6%; RR 0·88, 95% CI 0·78–0·99; p=0·034). Recurrence reductions were similar in the seven trials (n=10 004) that compared 2-weekly chemotherapy with the same chemotherapy given 3-weekly (10-year risk 24·0% vs 28·3%; RR 0·83, 95% CI 0·76–0·91; p<0·0001), in the six trials (n=11 028) of sequential versus concurrent anthracycline plus taxane chemotherapy (28·1% vs 31·3%; RR 0·87, 95% CI 0·80–0·94; p=0·0006), and in the six trials (n=6532) testing both shorter intervals and sequential administration (30·4% vs 35·0%; RR 0·82, 95% CI 0·74–0·90; p<0·0001). The proportional reductions in recurrence with dose-intense chemotherapy were similar and highly significant (p<0·0001) in oestrogen receptor (ER)-positive and ER-negative disease and did not differ significantly by other patient or tumour characteristics. Interpretation Increasing the dose intensity of adjuvant chemotherapy by shortening the interval between treatment cycles, or by giving individual drugs sequentially rather than giving the same drugs concurrentl...

A high percentage of patients with HR+ disease received initial palliative chemotherapy, which was associated with worse outcome, even after adjustment of relevant prognostic factors.

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