Most common breast cancer susceptibility variants have been identified through genome-wide association studies (GWAS) of predominantly estrogen receptor (ER)-positive disease1. We conducted a GWAS using 21,468 ER-negative cases and 100,594 controls combined with 18,908 BRCA1 mutation carriers (9,414 with breast cancer), all of European origin. We identified independent associations at P < 5 × 10−8 with ten variants at nine new loci. At P < 0.05, we replicated associations with 10 of 11 variants previously reported in ER-negative disease or BRCA1 mutation carrier GWAS and observed consistent associations with ER-negative disease for 105 susceptibility variants identified by other studies. These 125 variants explain approximately 14% of the familial risk of this breast cancer subtype. There was high genetic correlation (0.72) between risk of ER-negative breast cancer and breast cancer risk for BRCA1 mutation carriers. These findings may lead to improved risk prediction and inform further fine-mapping and functional work to better understand the biological basis of ER-negative breast cancer.

BackgroundSocial media can act as an important platform for debating, discussing, and disseminating information about vaccines. Our objectives were to map and describe the roles played by web-based mainstream media and social media as platforms for vaccination-related public debates and discussions during the Polio crisis in Israel in 2013: where and how did the public debate and discuss the issue, and how can these debates and discussions be characterized?MethodPolio-related coverage was collected from May 28 to October 31, 2013, from seven online Hebrew media platforms and the Facebook groups discussing the Polio vaccination were mapped and described. In addition, 2,289 items from the Facebook group “Parents talk about Polio vaccination” were analyzed for socio-demographic and thematic characteristics.ResultsThe traditional media mainly echoed formal voices from the Ministry of Health. The comments on the Facebook vaccination opposition groups could be divided into four groups: comments with individualistic perceptions, comments that expressed concerns about the safety of the OPV, comments that expressed distrust in the Ministry of Health, and comments denying Polio as a disease.In the Facebook group “Parents talk about the Polio vaccination”, an active group with various participants, 321 commentators submitted 2289 comments, with 64 % of the comments written by women. Most (92 %) people involved were parents. The comments were both personal (referring to specific situations) and general in nature (referring to symptoms or wide implications). A few (13 %) of the commentators were physicians (n = 44), who were responsible for 909 (40 %) of the items in the sample. Half the doctors and 6 % of the non-doctors wrote over 10 items each. This Facebook group formed a unique platform where unmediated debates and discussions between the public and medical experts took place.ConclusionThe comments on the social media, as well as the socio-demographic profiles of the commentators, suggest that social media is an active and versatile debate and discussion-facilitating platform in the context of vaccinations. This paper presents public voices, which should be seen as authentic (i.e. unmediated by the media or other political actors) and useful for policy making purposes. The policy implications include identifying social media as a main channel of communication during health crises, and acknowledging the voices heard on social media as authentic and useful for policy making. Human and financial resources need to be devolved specifically to social media. Health officials and experts need to be accessible on social media, and be equipped to readily provide the information, support and advice the public is looking for.

Purpose: Bisphosphonates are used for treatment or prevention of osteoporosis and of bone metastases. The use of oral bisphosphonates was suggested to be associated with reduced risk of developing breast cancer, and their positive influence on breast cancer survival was only demonstrated with third-generation bisphosphonates. We studied the association of use of oral bisphosphonates after breast cancer diagnosis on overall and breast cancer survival.Experimental Design: A nested case-control analysis was performed using data from the population-based Breast Cancer in Northern Israel Study (BCINIS). Participants were postmenopausal women with newly diagnosed breast cancer insured by Clalit. Use of second-generation bisphosphonates (alendronate and/or risedronate) was identified using computerized prescription records. The analysis was restricted to women who did not use bisphosphonates prior to diagnosis.Results: In a cohort of 3,731 postmenopausal women with breast cancer, followed up for an average of 70 months, there were 799 cases of death which were matched to 15,915 control periods of living breast cancer cases. Use of bisphosphonates after diagnosis for at least 18 months was significantly more common among survivors than among their matched controls who died, adjusted for tumor stage/grade (overall survival: OR ¼ 0.63, 0.41-0.96, P ¼ 0.03; breast cancer-specific survival: OR ¼ 0.28, 0.09-0.91, P ¼ 0.035). A similar advantageous effect, but statistically underpowered, was found in estrogen receptor (ER)-positive, ERnegative, and HER2neu-positive tumors.Conclusions: The use of oral bisphosphonates, by postmenopausal, probably osteoporotic, women initiated after diagnosis of breast cancer was associated with a significant improvement in overall and breast-specific odds of survival.

Objectives. To quantify and characterize hypnotics consumption habits among adult patients insured by Clalit Health Services (CHS), the largest health care provider in Israel, in 2000 and 2010. Methods. A retrospective analysis of CHS computerized pharmacy records. Data were collected for all patients over the age of 18 years who were prescribed hypnotics in 2000 and in 2010. Results. Sleep medications were consumed by 8.7% of the adult CHS population in 2000 and by 9.6% in 2010. About one-quarter of consumers were treated for more than 6 months in both years. Multiple sleeping drugs were consumed more often in 2010 (45.2%) than a decade before (22%). While in 2000 benzodiazepines accounted for 84.5% of hypnotics, in 2010 this was reduced to 73.7% (p < 0.05). Of all patients treated for longer than 6 months only 11% in 2000 and 9% in 2010 required a dose escalation suggesting the absence of tolerance. Conclusions. Nine percent of the Israeli population consumes hypnotics. There is a major increase in prescription of combination of medications between 2000 and 2010, with an increase in Z class medications use and reduction in benzodiazepines. Most patients chronically treated did not escalate dosage, suggesting the absence of tolerance.

Introduction: Israel led a rapid vaccine rollout against COVID-19, leading to a local remission of the epidemic and rolling back of most public health measures. Further vaccination of 12-15-year-olds may be hindered by public perceptions of the necessity and safety of vaccination. Methods: we examined the considerations of vaccine hesitant parents (VHPs) regarding vaccination of children against COVID-19. The responses of 456 parents were surveyed and analyzed before FDA authorization of vaccination of children. Results: parents who were vaccinated against COVID-19 were more likely to intend to vaccinate their children (r=-0.466, p<0.01). Low accessibility of vaccination may be a dissuading factor for VHPs more inclined to vaccinate. Vaccine efficacy and gaining a "Green Pass" were positively associated with an intention to vaccinate and statistically significant. VHPs inclined not to vaccinate indicated short development time and possible long term effects as dissuading factors. Discussion: vaccine promotion should be tailored for VHPs' positive and negative considerations for higher uptake.

Bisphosphonates are traditionally used for treatment of osteoporosis and more recently for treatment and prevention of bone metastases in various malignancies. The use of 2nd-generation oral bisphosphonates has been reported to reduce the risk of developing breast and colon cancer but their influence on cancer survival has not been studied. Methods Two large cohorts of consecutively diagnosed cases with breast or colorectal cancer were studied for the association between use of 2nd-generation oral bisphosphonates and cancer survival. Using computerized prescription records, sustained use of alendronate/risedronate was assessed in postmenopausal women with newly diagnosed breast (n = 2,843) or colorectal cancer (n = 1,706). Overall survival and cancer-specific survival were evaluated using time dependent analysis. Results Postmenopausal women with breast cancer previously unexposed to bisphosphonates who used 2nd-generation bisphosphonates after diagnosis for at least one year had a significantly better survival than non-users, adjusted for age, tumor stage and grade (Overall survival: HR = 0.53, 0.33-0.86, breast cancer-specific survival: HR = 0.26, 0.10-0.71, p = 0.009). A similar advantageous hazard ratio was found in users with ER positive, ER negative and HER2neu positive tumors. A similar significantly better survival was noted for colorectal cancer after adjustment for age, tumor stage and grade (Overall survival: HR = 0.53, 0.33-0.85, colorectal cancer-specific survival: HR = 0.44, 0.21-0.88, p = 0.02). Women who used bisphosphonates before diagnosis did not exhibit a significant survival benefit. Pharmacogenetic studies of F(D)PPS (Farnesyl Pyrophosphate Synthase), a gene coding a key step in the mevalonate pathway revealed direct correlation between a minor homozygous status and survival in bisphosphonate users. Conclusions The use of 2nd-generation bisphosphonates initiated after diagnosis was associated with a significant improvement in overall and in cancer-specific survival of postmenopausal women with breast or colon cancers. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-06-03.

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Withdrawn by Author Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-13-06.