The efficacy of early breast cancer detection programmes seems to be mainly influenced by the awareness of breast cancer in general among healthy women. This study aimed to provide information about women's understanding of breast cancer incidence and risk of disease. Based on a newly developed questionnaire 2108 healthy women were asked about their knowledge and perceptions in relation to breast cancer incidence, risk factors, risk perception and level of concern. Of these women 78.8% were well aware of breast cancer in general terms. However, there were major aspects such as incidence or risk factors that were poorly understood. Only one-third correctly estimated the incidence of breast cancer; 95% understood breast cancer in the familial history as a risk factor, but only 57% understood the age risk; 37.1% of women perceived hormonal contraceptives and 35.9% hormonal replacement therapy as risk factors of breast cancer. The latter estimation was significantly higher in women above 40 years. Recommendations for the improvement of cancer prevention programmes include targeting understanding of lifetime risk of breast cancer, age as a risk factor, survival from breast cancer or hormonal factors. There is a need to separately address the perceptions of women depending on age, social status and educational levels.

Genome-wide association studies have identified breast cancer risk variants in over 150 genomic regions, but the mechanisms underlying risk remain largely unknown. These regions were explored by combining association analysis with in silico genomic feature annotations. We defined 205 independent risk-associated signals with the set of credible causal variants (CCVs) in each one. In parallel, we used a Bayesian approach (PAINTOR) that combines genetic association, linkage disequilibrium, and enriched genomic features to determine variants with high posterior probabilities (HPPs) of being causal.Potentially causal variants were significantly over-represented in active gene regulatory regions and transcription factor binding sites. We applied our INQUSIT pipeline for prioritizing genes as targets of potentially causal variants, using gene expression (eQTL), chromatin interaction and functional annotations. Known cancer drivers, transcription factors and genes in the developmental, apoptosis, immune system and DNA integrity checkpoint gene ontology pathways, were over-represented among the 178 highest confidence target genes.

The timing of puberty is a highly polygenic childhood trait that is epidemiologically associated with various adult diseases. Here, we analyse 1000-Genome reference panel imputed genotype data on up to ~370,000 women and identify 389 independent signals (all P<5×10 -8 ) for age at menarche, a notable milestone in female pubertal development. In Icelandic data from deCODE, these signals explain ~7.4% of the population variance in age at menarche, corresponding to one quarter of the estimated heritability. We implicate over 250 genes via coding variation or associated gene expression, and demonstrate enrichment across genes active in neural tissues. We identify multiple rare variants near the imprinted genes MKRN3 and DLK1 that exhibit large effects on menarche only when paternally inherited. Disproportionate effects of variants on early or late puberty timing are observed: single variant and heritability estimates are larger for early than late puberty timing in females. The opposite pattern is seen in males, with larger estimates for late than early puberty timing. Mendelian randomization analyses indicate causal inverse associations, independent of BMI, between puberty timing and risks for breast and endometrial cancers in women, and prostate cancer in men. In aggregate, our findings reveal new complexity in the genetic regulation of puberty timing and support new causal links with adult cancer risks.

Background: In the pivotal BOLERO-2 trial, everolimus (EVE) + exemestane (EXE) more than doubled the median progression-free survival (PFS) vs EXE alone in hormone receptor positive (HR+), human epidermal growth factor-receptor 2-negative (HER2-) advanced breast cancer (ABC) recurring/progressing on/after prior non-steroidal aromatase inhibitors (NSAIs). BRAWO is a German non-interventional study conducted in patients (pts) with HR+, HER2–ABC receiving EVE + EXE, according to Summary of Product Characteristics (SmPC), in routine clinical practice. Here we report the final PFS and safety results. Methods: This multicenter study documented 2100 pts between October 2012 and December 2017 across 341 sites in Germany. Postmenopausal women with HR+, HER2– ABC with recurrence or progression after a NSAI were included. Primary observation parameters included the evaluation of the effectiveness of EVE + EXE used in routine care for the entire pt group. Results: In the final analysis, out of the 2100 documented pts, 2074 were included in the full analysis set. The median time since the primary diagnosis was 7.1 years and the median time from first sign of relapse (local recurrence or distant metastases) was 2.1 years. At baseline, 54.1% of pts presented with visceral metastases and 50.1% had an ECOG performance status of 0. Approximately, 63% of pts started with EVE 10 mg (median duration of exposure: 5.1 months; 95% CI, 4.6-5.4), while 34.1% started with EVE 5 mg (median duration of exposure: 4.6 months; 95% CI, 4.1-5.2). The distribution of treatment lines was as follows: first line, 28.7% (n=595); second line, 31.9% (n=662); third line, 18.1% (n=376); fourth line, 10.7% (n=221) and, fifth line and later, 10.6% (n=220). Treatment was discontinued by 55.7% of pts (n=1170) due to progressive disease and 26% of pts (n=546) due to adverse events. The Kaplan-Meier estimate of the median PFS was 6.6 months (95% CI, 6.2-7.0). The best overall responses, based on clinical routine, were complete response, 0.8% (n=17), partial response, 7.4% (n=150), and stable disease, 41.3% (n=842). The general safety profile was consistent with the previously reported safety findings. The most common adverse events were stomatitis (any grade: 42.6%, grade 3: 3.8%, grade 4: &lt;0.1%) and fatigue (any grade: 19.8%, grade 3: 1.5%). Conclusions: Data from BRAWO support EVE + EXE as a suitable treatment option with a reasonable safety profile for HR+, HER2− ABC recurring or progressing on/after prior NSAIs. Citation Format: Lüftner D, Schuetz F, Schneeweiss A, Grischke E-M, Bloch W, Decker T, Uleer C, Salat C, Förster F, Schmidt M, Mundhenke C, Tesch H, Jackisch C, Fischer T, Guderian G, Hanson S, Fasching P. Everolimus + exemestane for HR+ advanced breast cancer in routine clinical practice- Final results from the non-interventional trial, BRAWO [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-18-08.