SciCombinator

We show that elevated levels of Ret receptor are found in different sub-types of human breast cancers and that high Ret correlates with decreased metastasis-free survival. The role of Ret in ER+ breast cancer models was explored combining in vitro and in vivo approaches. Our analyses revealed that ligand-induced Ret activation: (i) stimulates migration of breast cancer cells; (ii) rescues cells from anti-proliferative effects of endocrine treatment and (iii) stimulates expression of cytokines in the presence of endocrine agents. Indeed, we uncovered a positive feed-forward loop between the inflammatory cytokine IL6 and Ret that links them at the expression and the functional level. In vivo inhibition of Ret in a metastatic breast cancer model inhibits tumour outgrowth and metastatic potential. Ret inhibition blocks the feed-forward loop by down-regulating Ret levels, as well as decreasing activity of Fak, an integrator of IL6-Ret signalling. Our results suggest that Ret kinase should be considered as a novel therapeutic target in subsets of breast cancer.

The objective of this study was to determine whether the 21-gene Recurrence Score (RS) provides clinically meaningful information in patients with de novo stage IV breast cancer enrolled in the Translational Breast Cancer Research Consortium (TBCRC) 013.

Despite reported benefits, many women do not attend breast cancer support groups. Abundant online resources for support exist, but information regarding the effectiveness of participation is lacking. We report the results of a Twitter breast cancer support community participant survey.

To assess the influence of stage at breast cancer diagnosis, tumour biology, and treatment on survival in contemporary times of better (neo-)adjuvant systemic therapy.

A growing number of studies have examined associations between night shift work and the risks of common cancers among women, with varying conclusions. We did a meta-analysis to identify whether long-term night shift work increased the risks of common cancers in women. We enrolled 61 articles involving 114,628 cases and 3,909,152 participants from Europe, North America, Asia, and Australia. Risk estimates were performed with a random-effect model or a fixed-effect model. Subgroup analyses and meta-regression analyses about breast cancer were conducted to explore possible sources of heterogeneity. In addition, we carried out a dose-response analysis to quantitatively estimate the accumulative effect of night shift work on the risk of breast cancer. A positive relationship was revealed between long-term night shift work and the risks of breast [OR = 1.316; 95% confidence interval (CI), 1.196-1.448], digestive system (OR = 1.177; 95% CI, 1.065-1.301), and skin cancer (OR = 1.408; 95% CI, 1.024-1.934). For every 5 years of night shift work, the risk of breast cancer in women was increased by 3.3% (OR = 1.033; 95% CI, 1.012-1.056). Concerning the group of nurses, long-term night shift work presented potential carcinogenic effect in breast cancer (OR = 1.577; 95% CI, 1.235-2.014), digestive system cancer (OR = 1.350; 95% CI, 1.030-1.770), and lung cancer (OR = 1.280; 95% CI, 1.070-1.531). This systematic review confirmed the positive association between night shift work and the risks of several common cancers in women. We identified that cancer risk of women increased with accumulating years of night shift work, which might help establish and implement effective measures to protect female night shifters. Cancer Epidemiol Biomarkers Prev; 27(1); 25-40. ©2018 AACR.

There have been calls to remove ‘carcinoma’ from terminology for in situ cancers such as ductal carcinoma in situ (DCIS), to reduce overdiagnosis and overtreatment. We investigated the effect of describing DCIS as ‘abnormal cells’ versus ‘pre-invasive breast cancer cells’ on women’s concern and treatment preferences.

Background: Periodontal pathogens have been isolated from precancerous and cancerous lesions and also shown to promote a procarcinogenic microenvironment. Few studies have examined periodontal disease as a risk factor for total cancer, and none have focused on older women. We examined whether periodontal disease is associated with incident cancer among postmenopausal women in the Women’s Health Initiative Observational Study.Methods: Our prospective cohort study comprised 65,869 women, ages 54 to 86 years. Periodontal disease information was obtained via self-report questionnaires administered between 1999 and 2003, whereas ascertainment of cancer outcomes occurred through September 2013, with a maximum follow-up period of 15 years. Physician-adjudicated incident total cancers were the main outcomes and site-specific cancers were secondary outcomes. HRs and 95% confidence intervals (CI) were calculated using Cox proportional hazards regression. All analyses were conducted two-sided.Results: During a mean follow-up of 8.32 years, 7,149 cancers were identified. Periodontal disease history was associated with increased total cancer risk (multivariable-adjusted HR, 1.14; 95% CI, 1.08-1.20); findings were similar in analyses limited to 34,097 never-smokers (HR, 1.12; 95% CI, 1.04-1.22). Associations were observed for breast (HR, 1.13; 95% CI, 1.03-1.23), lung (HR, 1.31; 95% CI, 1.14-1.51), esophagus (HR, 3.28; 95% CI, 1.64-6.53), gallbladder (HR, 1.73; 95% CI, 1.01-2.95), and melanoma skin (HR, 1.23; 95% CI, 1.02-1.48) cancers. Stomach cancer was borderline (HR, 1.58; 95% CI, 0.94-2.67).Conclusions: Periodontal disease increases risk of total cancer among older women, irrespective of smoking, and certain anatomic sites appear to be vulnerable. Impact: Our findings support the need for further understanding of the effect of periodontal disease on cancer outcomes. Cancer Epidemiol Biomarkers Prev; 26(8); 1255-65. ©2017 AACR.

The intra-tumor diversity of cancer cells is under intense investigation; however, little is known about the heterogeneity of the tumor microenvironment that is key to cancer progression and evolution. We aimed to assess the degree of microenvironmental heterogeneity in breast cancer and correlate this with genomic and clinical parameters.

Microcalcifications can be the early and only presenting sign of breast cancer. One shared characteristic of breast cancer is the appearance of mammographic mammary microcalcifications that can routinely be used to detect breast cancer in its initial stages, which is of key importance due to the possibility that early detection allows the application of more conservative therapies for a better patient outcome. The mechanism by which mammary microcalcifications are formed is still largely unknown but breast cancers presenting microcalcifications are more often associated with a poorer prognosis.

The triterpene glycoside actein from the herb black cohosh preferentially inhibits the growth of breast cancer cells and activates the ER stress response. The ER IP3 receptor and Na,K-ATPase form a signaling microdomain. Since actein is lipophilic, its action may be limited by bioavailability.