Conventional versus reverse sequence of neoadjuvant epirubicin/cyclophosphamide and docetaxel: sequencing results from ABCSG-34.

BACKGROUND: Preoperative chemotherapy containing anthracyclines and taxanes is well established in early-stage breast cancer. Previous studies have suggested that the chemotherapy sequence may matter but definitive evidence is missing. ABCSG trial 34 evaluated the activity of the MUC1 vaccine tecemotide when added to neoadjuvant treatment; the study provided the opportunity for the second randomisation to compare two different anthracycline/taxane sequences. METHODS: HER2-negative early-stage breast cancer patients were recruited to this randomised multicentre Phase 2 study. Patients in the chemotherapy cohort (n = 311) were additionally randomised to a conventional or reversed sequence of epirubicin/cyclophosphamide and docetaxel. Residual cancer burden (RCB) with/without tecemotide was defined as primary study endpoint; RCB in the two chemotherapy groups was a key secondary endpoint. RESULTS: No significant differences in terms of RCB 0/I (40.1% vs. 37.2%; P = 0.61) or pathologic complete response (pCR) rates (24.3% vs. 25%, P = 0.89) were observed between conventional or reverse chemotherapy sequence. No new safety signals were reported, and upfront docetaxel did not result in decreased rates of treatment delay or discontinuation. CONCLUSION: Upfront docetaxel did not improve chemotherapy activity or tolerability; these results suggest that upfront neoadjuvant treatment with anthracyclines remains a valid option.

Hashimoto's thyroiditis affects symptom load and quality of life unrelated to hypothyroidism: a prospective case-control study in women undergoing thyroidectomy for benign goiter.

BACKGROUND: Hashimoto's thyroiditis (HT) is a common disease, and is the most prevalent cause of hypothyroidism. Symptoms and diseases associated with HT are considered to be caused by hypothyroidism. We hypothesized that higher antithyroperoxidase (anti-TPO) antibody levels would be associated with an increased symptom load and a decreased quality of life in a female euthyroid patient collective. METHODS: In a prospective cohort study 426 consecutive euthyroid female patients undergoing thyroid surgery for benign thyroid disease were included. Main outcome measures were preoperative anti-TPO levels, a symptom questionnaire and the SF-36 questionnaire, and lymphocytic infiltration of the thyroid tissue as evaluated by histology. RESULTS: Histology revealed HT in 28/426 (6.6%) subjects. To maximize the sum of the predictive values, a cut-off point for anti-TPO of 121.0 IU/mL was calculated (sensitivity 93.3% [95% confidence interval: 77.9%-99.0%]; specificity 94.7% [95% confidence interval: 92.0%-96.7%]) to predict the presence of histological signs of HT. The mean number of reported symptoms was significantly higher in patients with anti-TPO levels >121.0 IU/mL than in the other group (6.7 ± 2.5 vs. 4.1 ± 2.8; p < 0.001). There were no differences in preoperative thyroid-stimulating hormone levels (1.7 ± 1.3 vs. 1.5 ± 1.4 µU/mL, respectively; p = 0.155). Chronic fatigue, dry hair, chronic irritability, chronic nervousness, a history of breast cancer and early miscarriage, and lower quality-of-life levels were significantly associated with anti-TPO levels exceeding the cut-off point (p < 0.05). CONCLUSIONS: Women with HT suffer from a high symptom load. Hypothyroidism is only a contributing factor to the development of associated conditions.

Younger birth cohort correlates with higher breast and ovarian cancer risk in European BRCA1 mutation carriers.

Mutations in the BRCA1 gene result in an elevated risk of breast cancer (BC) and ovarian cancer (OC). However, risk estimates vary depending on the study population and statistical methodology used, and there are indications that the birth cohort and location of the mutation influence cancer risk. We investigated the risks for BC and OC associated with BRCA1 mutations in a young cohort of female mutation carriers who were identified by molecular genetic testing and belonged to a genetically heterogeneous Central European population. The study included 106 healthy and 158 affected carriers identified at an Austrian risk evaluation center. Risk estimation employed the product limit method. The log rank test was used to compare different strata. The risk of developing cancer to age 70 was found to be 85% for BC (95% CI 75-97%) and 53% for OC (95% CI 37-68%). Female mutation carriers born in 1958 or later were subject to a significantly higher risk of BC (P=0.005; 27% vs. 46% to age 40) and OC (P=0.006; 2% vs. 8% to age 40) than those born earlier. Mutations in exon 11 were associated with lower BC risk than mutations in exons 1-10 (P=0.008) and exons 12-24 (P=0.0006). OC risk was not influenced by mutation location (P=0.86). We conclude that female BRCA1 mutation carriers should be counseled about their cohort-dependent cancer risk. Further research into variables that affect cancer risk and are amenable to modification (e.g., lifestyle-related factors) should be considered a priority.