What's new?

A new analysis of worldwide trends reveals that, between 1978 and 2012, liver cancer rates fell in east Asia and Italy, but rose in India, Europe, and the Americas. In this report, the authors analyzed 35 years of liver cancer incidence, the second leading cause of cancer death worldwide. Using data from the CI5plus database, they calculated incidence rates for 5 year intervals. Although liver cancer rates remained high in east Asia and Italy, they decreased, and are expected to continue to decline as HBV prevalence declines. However, liver cancer rates rose elsewhere, possibly due to increased obesity and diabetes.

What's new?

Although many epidemiological studies have reported an association between family history of cancer and concordant cancer risk, the association has not been evaluated in a comprehensive prospective study with adjustment for lifestyle habits. We found that a family history of cancer is associated with increased risk in the incidence of several concordant cancers in an Asian population.

What's new?

The neighborhood where a childhood cancer survivor resides likely influences obesity risk and obesity-related health behaviors. Little is known, however, about the impact of the so-called neighborhood effect, which is driven by factors such as socioeconomic status (SES), access to healthy foods, and exercise opportunities, on obesity risk among survivors of childhood cancer. Here, investigation of survivors in the St. Jude Lifetime cohort shows that obesity risk is significantly increased in particular among survivors living in rural areas or in neighborhoods with relatively low SES. Obesity risk was further linked to age, exposure to cranial radiation, and inadequate physical activity.

What's new?

Foreign and native populations differ in terms of breast cancer outcomes. However, studies rarely distinguish between migrants of the first and second generation, which could shed light on the genetic and environmental factors influencing breast cancer. This research fills the gap by investigating patterns in breast cancer incidence and survival in different groups by migrant generational and menopausal status. Breast cancer incidence was lower among non-European migrants compared to Belgians. Accounting for socioeconomic position and known risk factors partly reduced the observed discrepancies. A risk convergence between second-generation migrants and Belgians for the development of premenopausal breast cancer was observed.

What's new?

Multimorbidity in women with breast cancer increases with age and may influence treatment decisions and outcome. The authors find that in South Africa 44%, of women newly diagnosed with breast cancer also suffered from other chronic conditions, most prevalently obesity, hypertension, HIV and diabetes. Asian and white women were less likely to present with multimorbidity when compared to black women, but multimorbidity was more common in women with higher socioeconomic status. The authors propose to evaluate the effect of multimorbidity on the South African health system and its impact on scarce health care resources.

What's new?

Breast cancers that are detected between regular screening intervals are more aggressive and have poorer outcomes than screen-detected tumors but no valid risk model exists to predict “interval” breast cancers. Here the authors combined breast density with other breast cancer risk factors such as body mass index, family history and a novel measure of age-adjusted hormonal exposure. Applying this to more than 150 women with interval breast cancer, they find that risk discrimination can be doubled with the combination of factors as compared with just using breast density alone, thus improving risk predictions and clinical recommendations for breast screening procedures.

What's new?

Products such as hair dye and hair straightener are widely used. These products contain numerous chemicals, some of which may contribute to cancer risk. The present study evaluated the relationship specifically between breast cancer risk and hair dye and chemical straightener use in a prospective cohort of women ages 35-74. Hair dye use was reported by more than half of study participants. Nearly three-quarters of black women reported use of hair straightener in the past year. Straightener use and personal permanent hair dye use were associated with elevated breast cancer risk. Associations for hair dye were strongest among black women.

What's new?

Immunotherapy has become a key component of non-small cell lung cancer (NSCLC) treatment. However, not all patients benefit from immunotherapy, and there is increasing need to predict immunotherapy response in order to improve treatment efficacy and patient outcomes. In the present investigation of genes involved in endosome-related pathways, which are suspected of serving important immune-guided anti-tumor functions, three variants, located in the genes KIF16B and NEDD4L, were associated with NSCLC survival. The survival-associated variant in KIF16B was specifically associated with reduced KIF16B mRNA expression levels in lung tissue and blood cells, identifying it as a potentially useful biomarker for NSCLC survival.

What's new?

Endometrial cancer (EC) treatment recommendations are based on randomized clinical trials and observational studies. In the United States, the extent to which women with EC receive treatment in line with recommendations is unknown. Here, receipt of guideline-concordant treatment was found to vary by histology and geography for U.S. women with EC. In particular, women with stage IIB or stage IV EC and women living in the Northeast were less likely to receive treatment consistent with existing recommendations than stage IA patients and women living in the West or Midwest. Receipt of guideline-concordant treatment was weakly associated with improved overall survival.

What's new?

Endometrial cancers have the highest reported rate of PI3K pathway alterations of any solid tumor. A kinase inhibitor called MK-2206, which blocks the PI3K pathway, has entered Phase II clinical trials. In this study, the authors predicted that tumors with PIK3CA mutations would be more susceptible to MK-2206 than those without. However, this was not the case, and toxicity was also higher than expected. One group of patients did show clinical benefit: those whose tumors had serous histology. MK-2206 is thus being further explored in these patients.

What's new?

Immune checkpoint molecules have been identified as crucial regulators of the immune response against tumors. However, the prognostic significance of the immune checkpoint molecules PD-1, CTLA4, TIM-3, and LAG-3 remains controversial. Using a computational approach, the authors conducted a systematic assessment of the expression of these immune checkpoints across different cancers in relation to treatment response, tumor-infiltrating immune cells, and patient survival. They reveal the potential of these immune checkpoints to serve as prognostic markers and therapeutic targets in some cancers. The findings enhance the current understanding of these checkpoints and identify strategies to promote synergistic activities with other immunotherapies.

What's new?

As the first generation of girls vaccinated against HPV reach adulthood, it's time to re-evaluate screening recommendations. Reducing the frequency of screenings could save money without increasing cervical cancer incidence. Here, the authors collected baseline data on the safety of less frequent cervical cancer screenings. They conducted a randomized trial of Finnish women born in 1992-1994 and vaccinated against HPV16/18, in which participants are screened either once or three times by age 28. At baseline and the first safety interim analyses they found no difference in the incidence of HSIL/CIN3 lesions between the two groups, suggesting that infrequent screening for HPV-vaccinated women does not compromise safety.

What's new?

Owing to the ability of bacteria to elicit powerful immune responses, they are promising carriers for cancer-targeting immunotherapies. However, balancing safety and therapeutic efficacy remains a major challenge for the rational design of bacteria for cancer immunotherapy. In the present study, the authors show that this balance can be achieved in Salmonella by manipulating the spatiotemporal regulation of flagella synthesis. Unexpectedly, abrogating flagella synthesis at an early stage resulted in outer membrane vesicle formation, which enhanced the bacterium's immunogenic properties. The engineered Salmonella strains reported here potentially can serve as vector platforms for various therapies, including immunizations and cancer treatments.

What's new?

While Epstein-Barr virus (EBV) causes almost all nasopharyngeal carcinoma (NPC) in endemic regions, human papillomavirus (HPV) may also cause NPCs in low-incidence, Western populations. Here, the authors used molecular tumor markers to validate EBV and HPV multiplex serology to define the viral status of NPCs in the United Kingdom. IgG antibodies to the EBV antigen LF2 and HPV early antigen serology were highly specific and sensitive to identify EBV- and HPV-positive NPCs, respectively. The results show that both EBV-positive and HPV-positive NPCs are present in a low-incidence country, and that EBV and HPV serum antibodies correlate with the viral status of the tumor.

What's new?

Epithelial-mesenchymal transition (EMT) likely contributes to chemoresistance in triple-negative breast cancers (TNBC), but the underlying mechanisms remain unclear. Here, the expression of Notch1 positively associated with melanoma cell adhesion molecule (MCAM), a unique EMT activator, in TNBC tissue samples. High expression of Notch1 and MCAM predicted poor survival, particularly in patients treated with chemotherapy. Notch1 and MCAM levels were significantly higher in cisplatin-resistant than wild-type TNBC cells. The findings suggest that Notch1 regulates MCAM in EMT and contributes to cisplatin resistance in TNBC. Targeting the Notch1/MCAM axis might be a potential avenue to enhance therapeutic efficacy in patients with TNBC.

What's new?

Chronic inflammation at tumor sites is linked to the emergence of ectopic formations known as tertiary lymphoid structures (TLSs), which combat tumor progression. Here, analyses of human colorectal cancer (CRC) tissue show that high expression of a previously identified 12-chemokine signature predicts high TLS expression at tumor sites and is associated with increased presence of tumor infiltrating immune cells and reduced CRC recurrence rate. High 12-chemokine signature status was further linked to key clinicopathological and molecular features of CRC. The findings indicate that the 12-chemokine signature is informative for host immune status and may have a prognostic role in CRC.

What's new?

Stromal infiltrating immune cells play a crucial role in tumor proliferation, invasion, and metastasis. However, few studies have investigated the prognostic potential of an overall stromal immune-cell signature in triple-negative breast cancer (TNBC). Here, the authors developed an immune index that classified patients into two immune phenotypes with different prognoses. Among the stromal infiltrating immune cells in TNBC, CD4+ T cells, γδ T cells, and M1 macrophages predicted a better prognosis, while monocytes and M2 were worse indicators. The classification was an independent prognostic indicator for TNBC and might serve as a potential predictor for the tumor microenvironment immune activity.

What's new?

This study explored the effects of (chemo)radiotherapy on the tumor immunome and the potential of tumor-infiltrating immune cells as predictive or prognostic biomarkers in a unique cervical cancer population treated with (chemo)radiotherapy and subsequent surgery. Analysis of pre- and post-treatment immune cell markers, and their changes during treatment showed correlations with pathological response, survival, and metastasis. The CD8/CD3 ratio, CD8/CD4 ratio, IL33-tumor cells, IL33-immune cell/tumor cell ratio, and PD-L1-tumor cells may predict pathological complete response and thus radiosensitivity in cervical cancer. Investigation of these markers in future trials may thus lead to more personalized care for cervical cancer patients.

What's new?

About 20% of women with high-grade serous epithelial ovarian carcinoma do not respond to platinum-based chemotherapy but molecular parameters are lacking to predict if a tumor is responsive or not. The authors compared transcriptomic data of more than a thousand tumor biopsies and show that differences in the expression profile of five functionally related pathways distinguish the biology of platinum-sensitive from resistant cases. Three genes in these networks, SDF2L1, PPP1R12A and PRKG1, were independently associated with survival, and may thus provide a molecular signature for patients' stratification at diagnosis.

What's new?

Altered expression of the CEACAM1 adhesion molecule has been linked to adverse tumor features in various cancer types. The role of CEACAM1 in prostate cancer is poorly understood, however. Studying a large set of more than 13,000 cancers, here the authors found that loss of CEACAM1 expression was strongly linked to high Gleason grade, lymph node metastasis, advanced tumor stage, positive surgical margin, frequent genomic deletions, and early biochemical recurrence, especially in ERG-fusion positive cancers. Furthermore, loss of CEACAM1 expression characterized a subset of tumors with a particularly poor prognosis, independently from established histo-morphological features, with potential clinical applications.

What's new?

Non-small-cell lung cancer often metastasizes to the brain. Are there specific genes that increase this tendency? In this study, the authors used gene-set enrichment analysis, RNA sequencing, and immunohistochemical assays to develop a model to predict brain metastasis. The resulting “brain metastasis score” (BMS) identified five genes that are highly predictive. Further analyses indicated that a high BMS is associated with cell-cycle and DNA-repair pathways. Determining which patients have a high-risk BMS may guide special prophylactic management.