“Partner”, “Caregiver”, or “Co-Survivor”—Might the Label We Give the Partners of Cancer Patients Affect the Health Outcome of the Patients and Their Partners?

Having a life partner significantly extends survival for most cancer patients. The label given to the partners of cancer patients may, however, influence the health of not just the patients but their partners. “Caregiver” is an increasingly common label for the partners of patients, but it carries an implicit burden. Referring to partners as “caregivers” may be detrimental to the partnerships, as it implies that the individuals are no longer able to be co-supportive. Recognizing this, there has been some effort to relabel cancer dyads as “co-survivors”. However, many cancer patients are not comfortable being called a “survivor”, and the same may apply to their partners. Cancer survivorship, we argue, could be enhanced by helping keep the bond between patients and their partners strong. This includes educating patients and partners about diverse coping strategies that individuals use when facing challenges to their health and wellbeing. We suggest that preemptive couples’ counselling in cancer centers may benefit both patients and their partners.     

Prognostic impact of circulating tumor cells detected with the microfluidic “universal CTC‐chip” for primary lung cancer

Detecting rare circulating tumor cells (CTCs) in the bloodstream is extremely challenging. We had previously developed a novel polymeric microfluidic device, “CTC‐chip,” for capturing CTCs and have shown high capture efficiency in lung cancer cell lines by conjugating Abs against epithelial cell adhesion molecules (EpCAM). This study aimed to optimize the EpCAM‐chip and clarify the prognostic impact of CTCs in lung cancer patients. Of 123 patients with pathologically proven lung cancer, both progression‐free survival (P = .037) and cancer‐specific survival (P = .0041) were predominantly poor when CTCs were detected before treatment. After classification into surgical and chemotherapy groups, progression‐free survival was worse in CTC‐positive patients in both groups (surgery, P = .115; chemotherapy, P = .012), indicating that the detection of baseline CTCs is a risk factor for recurrence and progression. Furthermore, we recovered captured CTCs using micromanipulators and undertook mutation analysis using PCR. Thus, the EpCAM‐chip is a highly sensitive system for detecting CTCs that contributes to the prediction of recurrence and progression and enables genetic analysis of captured CTCs, which could open new diagnostic, therapeutic, and prognostic options for lung cancer patients.     

Towards precision oncology in angiosarcomas using next generation “omic” technologies

Angiosarcomas are a group of aggressive tumors of vascular origin. Although thought to be a rare cancer constituting just 1–2% of all soft tissue sarcomas, recent observations suggest that angiosarcomas are more common amongst Asian populations as compared to the West, suggesting the possibility of distinct genetic or environmental triggers influencing its pathogenesis. Advances in genomic sequencing efforts have led to the discovery of ultraviolet mutation signatures and high tumor mutation burden as common features of angiosarcoma of the head and neck. In addition, multi-omic analyses integrated with clinical data identified 3 subtypes characterized by distinctive etiological and biological phenotypes, with potential implications on precision therapy. The systemic and local immune milieu, as well as the presence of “giant” tumor cells, was also recently demonstrated to influence clinical behavior and patient outcomes, further highlighting complexities of this disease. Improvements in next generation “omic”-based technologies are expected to improve our understanding of angiosarcoma and guide the development of precision oncology in this rare cancer.     

A qualitative exploration of the meaning of the term “survivor” to young women living with a history of breast cancer

There has been a recent increase in research considering the perceptions of the term “cancer survivor” held by individuals who have or have had cancer. This article explores the meaning of the term to young women living with a history of breast cancer. Twenty women participated in semi‐structured interviews about their experience of breast cancer. The methodology was informed by social constructionist grounded theory. Three of the women interviewed said they would use the term survivor to describe themselves, but most of the women felt it did not fit with their experiences. The accounts of those who accepted and rejected the survivor identity are explored, and subthemes in the latter are “survivor as somebody else” and “cancer's ongoing presence.” This article calls into question the basing of intervention strategies on the notion of the “cancer survivor,” and the assumption that younger women favour the survivor identity. Participants struggled with the demand to live up to the ideal of the survivor, which implied a high degree of agency where in reality, cancer was a disempowering experience. Being labelled a survivor obscured ongoing impacts of cancer on the young women's lives.     

Frequent low dose alcohol intake increases gastric cancer risk: the Health Examinees-Gem (HEXA-G) study

Objective:Epidemiological studies indicate that alcohol increases gastric cancer (GC) risk, yet most studies have focused on heavy alcohol intake, leaving other factors understudied. A comprehensive investigation of the effects of the frequency and amount of alcohol intake may help elucidate the GC risk associated with drinking behavior.Methods:The Health Examinees-Gem (HEXA-G) study, a community-based large-scale prospective cohort study, enrolled Korean adults 40–69 years of age between the years 2004 and 2013. Incident GC cases were identified through linkage to Korea Central Cancer Registry data until December 31, 2017. Self-reported questionnaires were used to survey alcohol consumption-related factors (duration, frequency, amount, and type of alcoholic beverages). The frequency and amount of alcohol consumption were combined to explore GC risk according to 4 drinking patterns: “infrequent-light”, “frequent-light”, “infrequent-heavy”, and “frequent-heavy”. We used Cox proportional hazard models to estimate the adjusted hazard ratios (HRs) and 95% confidence intervals (CIs), and investigate the relationship between alcohol intake and GC incidence.Results:A total of 128,218 participants were included in the analysis. During an average follow-up period of 8.6 years, 462 men and 385 women were diagnosed with GC. In men, current drinkers showed a 31% greater risk of GC than non-drinkers (HR 1.31, 95% CI 1.03–1.66), whereas no significant association was observed in women. In men, GC risk was associated with a higher frequency (P trend 0.02) and dose of ethanol intake in grams (P trend 0.03). In men, the “frequent-light” (≥5 times/week and <40 g ethanol/day) drinking pattern was associated with a 46% greater risk of GC (HR 1.46, 95% CI 1.02–2.07) than the “infrequent-light” pattern (<5 times/week and <40 g ethanol/day).Conclusions:This study suggests that frequent intake of alcohol, even in low quantities per session, increases GC risk. Further research is warranted to evaluate the relationship between alcohol and GC in detail.     

Surrogacy Beyond Prognosis: The Importance of “Trial-Level” Surrogacy

Many candidate surrogate endpoints are currently assessed using a 2-level statistical approach, which consists in checking whether (1) the potential surrogate is associated with the final endpoint in individual patients and (2) the effect of treatment on the surrogate can be used to reliably predict the effect of treatment on the final endpoint. In some situations, condition (1) is fulfilled but condition (2) is not. We use concepts of causal inference to explain this apparently paradoxical situation, illustrating this review with 2 contrasting examples in operable breast cancer: the example of pathological complete response (pCR) and that of disease-free survival (DFS). In a previous meta-analysis, pCR has been shown to be a strong and independent prognostic factor for event-free survival (EFS) and overall survival (OS) after neoadjuvant treatment of operable breast cancer. Yet, in randomized trials, the effects of experimental treatments on pCR have not translated into predictable effects on EFS or OS, making pCR an “individual-level” surrogate, but not a “trial-level” surrogate. In contrast, DFS has been shown to be an acceptable surrogate for OS at both the individual and trial levels in early, HER2-positive breast cancer. The distinction between the prognostic and predictive roles of a tentative surrogate, not always made in the literature, avoids unnecessary confusion and allows better understanding of what it takes to validate a surrogate endpoint that is truly able to replace a final endpoint.

Many candidate surrogate endpoints are currently assessed using a two-level statistical approach. This article explores tentative surrogates versus actual outcomes, focusing on the “surrogate paradox”.

Implications for PracticeThe distinction between the prognostic and predictive roles of a tentative surrogate, not always made in the literature, avoids unnecessary confusion and allows better understanding of what it takes to validate a surrogate endpoint that is truly able to replace a final endpoint.     

Prospective genomically guided identification of “early/evolving” and “undersampled” IDH-wildtype glioblastoma leads to improved clinical outcomes

BackgroundGenomic profiling studies of diffuse gliomas have led to new improved classification schemes that better predict patient outcomes compared to conventional histomorphology alone. One example is the recognition that patients with IDH-wildtype diffuse astrocytic gliomas demonstrating lower-grade histologic features but genomic and/or epigenomic profile characteristic of glioblastoma typically have poor outcomes similar to patients with histologically diagnosed glioblastoma. Here we sought to determine the clinical impact of prospective genomic profiling for these IDH-wildtype diffuse astrocytic gliomas lacking high-grade histologic features but with molecular profile of glioblastoma.MethodsClinical management and outcomes were analyzed for 38 consecutive adult patients with IDH-wildtype diffuse astrocytic gliomas lacking necrosis or microvascular proliferation on histologic examination that were genomically profiled on a prospective clinical basis revealing criteria for an integrated diagnosis of “diffuse astrocytic glioma, IDH-wildtype, with molecular features of glioblastoma, WHO grade IV” per cIMPACT-NOW criteria.ResultsWe identified that this diagnosis consists of two divergent clinical scenarios based on integration of radiologic, histologic, and genomic features that we term “early/evolving” and “undersampled” glioblastoma, IDH-wildtype. We found that prospective genomically guided identification of early/evolving and undersampled IDH-wildtype glioblastoma resulted in more aggressive patient management and improved clinical outcomes compared to a biologically matched historical control patient cohort receiving standard-of-care therapy based on histomorphologic diagnosis alone.ConclusionsThese results support routine use of genomic and/or epigenomic profiling to accurately classify glial neoplasms, as these assays not only improve diagnostic classification but critically lead to more appropriate patient management that can improve clinical outcomes.     

Methods of Sentinel Lymph Node Detection and Management in Urinary Bladder Cancer—A Narrative Review

Introduction: Detection of lymph node status in bladder cancer significantly impacts clinical decisions regarding its management. There is a wide range of detection modalities for this task, including lymphoscintigraphy, computed tomography, magnetic resonance imaging, single-photon emission computed tomography, positron emission tomography, and fluoroscopy. We aimed to study the pre- and intraoperative detection modalities of sentinel lymph nodes in urinary bladder cancer. Method: This narrative review was performed by searching the PubMed and EMBASE libraries using the following search terms: (“Transitional cell carcinoma of the bladder” OR “urothelial cancer” OR “urinary bladder cancer” OR “bladder cancer”) AND ((“sentinel lymph node”) OR (“lymphatic mapping”) OR (“lymphoscintigraphy”) OR (“lymphangiography”) OR (“lymph node metastases”)). Studies analysing the effectiveness and outcomes of sentinel lymph node detection in bladder cancer were included, while non-English language, duplicates, and non-article studies were excluded. After analysing the libraries and a further manual search of bibliographies, 31 studies were included in this paper. We followed the RAMESES publication standard for narrative reviews to produce this paper. Results: Of the 31 studies included, 7 studies included multiple detection methods; 5 studies included lymphoscintigraphy; 5 studies included computed tomography and/or single-photon emission computed tomography; 5 studies included fluoroscopy; 4 studies included magnetic resonance imaging; and 5 studies included positron emission tomography. Discussion: Anatomical, radioactive, and functional detection modalities have been studied independently and in combination. The consensus is that preoperative detection with imaging helps guide surgical management and intraoperative detection methods help capture any lymph nodes that may have been missed. Each of these types of detection represent their own set of benefits and drawbacks, but there is currently limited evidence to support any change in overall practice to replace conventional staging.     

“We’re on a Merry-Go-Round”: Reflections of Patients and Carers after Completing Treatment for Sarcoma

Sarcoma is a rare cancer that has a significant impact on patients’ and carers’ quality of life. Despite this, there has been a paucity of research exploring the diverse experiences of patients and carers following sarcoma treatment. The aim of this study was to explore patients’ and carers’ reflections on life after treatment for sarcoma. A qualitative research design with a social constructionist epistemology was used. Participants included patients previously treated for sarcoma (n = 21) and family carers of patients treated for sarcoma (n = 16). Participants completed semi-structured interviews which were analysed using thematic analysis. Three primary themes were identified: “This journey is never going to be over”, “But what happens when I am better?”, and finding a silver lining. Participants represented sarcoma as having a long-term, and sometimes indefinite, threat on their life that they had limited control over. Conclusions: This study highlight the heterogeneous and ongoing needs of sarcoma survivors and their families. Patients and carers strove to translate their experiences in a meaningful way, such as by improving outcomes for other people affected by sarcoma. Parental carers in particular attempted to protect the patient from the ongoing stress of managing the disease.     

The association between metabolic syndrome and the risk of prostate cancer,high-grade prostate cancer,advanced prostate cancer,prostate cancer-specific mortality and biochemical recurrence

Background

Although a previous meta-analysis reported no association between metabolic syndrome (MetS) and prostate cancer risk, a number of studies suggest that MetS may be associated with the aggressiveness and progression of prostate cancer. However, these results have been inconsistent. This systematic review and meta-analysis investigated the nature of this association.

Methods

We systematically searched MEDLINE, EMBASE and bibliographies of retrieved studies up to January 2013 using the keywords “metabolic syndrome” and “prostate cancer”. We assessed relative risks (RRs) of the prostate cancer, several parameters of prostate cancer aggressiveness and progression associated with MetS using 95% confidence intervals (95% CIs).

Results

The literature search produced 547 hits from which 19 papers were extracted for the meta-analysis. In cancer-free population with and without MetS, the combined adjusted RR (95% CI) of prostate cancer risk and prostate cancer-specific mortality in longitudinal cohort studies is 0.96 (0.85 ~ 1.09) and 1.12 (1.02 ~ 1.23) respectively. In the prostate cancer patients with and without MetS, the combined unadjusted OR (95% CI) of high grade Gleason prostate cancer is 1.44 (1.20 ~ 1.72), the OR of advanced prostate cancer is 1.37 (1.12 ~ 1.68) and the OR of biochemical recurrence is 2.06 (1.43 ~ 2.96).

Conclusions

The overall analyses revealed no association between MetS and prostate cancer risk, although men with MetS appear more likely to have high-grade prostate cancer and more advanced disease, were at greater risk of progression after radical prostatectomy and were more likely to suffer prostate cancer-specific death. Further primary studies with adjustment for appropriate confounders and larger, prospective, multicenter investigations are required.     

Effects of molecular markers on the treatment decision and prognosis of colorectal cancer: a narrative review

ObjectiveTo summarize the effects of molecular markers on the treatment decision and prognosis of colorectal cancer.BackgroundColorectal cancer is a highly heterogeneous disease. Even colorectal cancers of the same pathological type and clinical stage may have significant differences in treatment efficacy and prognosis. There are three main molecular mechanisms for the occurrence and development of colorectal cancer: chromosomal instability (CIN) pathway, microsatellite instability (MSI), and CpG island methylate phenotype (CIMP). There are multiple molecular markers distributed on each pathway.MethodsWe performed a literature search on the PubMed database for studies published in English (from the date of initiation of the database to the year of 2020) using the following subject terms: “colon cancer”, “rectal cancer”, “colorectal cancer”, “molecular markers”, “biomarkers”, “treatment strategies”, and “prognosis”.ConclusionsThe different expression states of molecular markers have a significant impact on the treatment decision and prognosis of colorectal cancer. Main colorectal cancer molecular markers include MSI and some important genes. Individualized treatments for tumors with different molecular phenotypes have improved the treatment effectiveness for colorectal cancer. The rational use of molecular markers is valuable for treatment decision-making and the prognosis of patients with colorectal cancer.     

Can local ablative techniques replace surgery for locally advanced pancreatic cancer?

In the treatment of pancreatic ductal adenocarcinoma (PDAC) the best chance at long term survival or cure has to date always included the complete surgical removal of the tumor. However, locally advanced pancreatic cancer (LAPC), about 25% of all newly diagnosed PDAC, is defined by its primary technical unresectability due to infiltration of visceral arteries and absence of metastasis. Induction therapies, especially FOLFIRINOX treatment, together with technical surgical advancement have increased the numbers for conversion to secondary resectability. Recent data on resections after induction therapy show promising, almost doubled survival compared to palliative treatment. Yet, around 70% of LAPC remain unresectable after induction therapy, often due to persistent local invasion. As locally ablative techniques are becoming more widely available this review examines their possible applicability to substitute for surgery in these cases which we propose to group under the new term “Inconvertible LAPC”. The need for defining this novel subgroup who might benefit from ablative treatment is based on the findings in our review that high-level evidence on ablative techniques for PDAC is largely lacking and the latest effective, harmonized treatment guidelines for LAPC are not often incorporated in these studies. The “inconvertible LAPC” label requires persistent unresectability after staging and induction therapy of LAPC according to current guidelines followed by liberal indication for aggressive surgical exploration at a center equipped for extended pancreatic resections. Ideally, this specification of a new, distinct patient group will also put it in the spotlight more, hopefully prompt more trials designed to generate robust evidence and optimize transferability of study results.     

Diagnosis of “cribriform” prostatic adenocarcinoma: an interobserver reproducibility study among urologic pathologists with recommendations

Accurate diagnosis of cribriform Gleason pattern 4 (CrP4) prostate adenocarcinoma (PCa) is important due to its independent association with adverse clinical outcomes and as a growing body of evidence suggests that it impacts clinical decision making in PCa management. To identify reproducible features for diagnosis of CrP4, we assessed interobserver agreement among 27 experienced urologic pathologists of 60 digital images from 44 radical prostatectomies (RP) that represented a broad spectrum of potential CrP4. The following morphologic features were correlated with the consensus diagnosis (defined as 75% agreement) for each image: partial vs. transluminal glandular bridging, intraglandular stroma, <12 vs. ≥12 lumina, well vs. poorly formed lumina, mucin (mucinous fibroplasia, extravasation, or extracellular pool), size (compared to benign glands and number of lumina), number of attachments with gland border by tumor cells forming a “glomeruloid-like” pattern, a clear luminal space along the periphery of gland occupying <50% of glandular circumference, central nerve, dense (cell mass occupying >50% of luminal space) vs. loose, and regular vs. irregular contour. Interobserver reproducibility for the overall diagnostic agreement was fair (k=0.40). Large CrP4 had better agreement (k=0.49) compared to small CrP4 (k=0.40). Transluminal bridging, dense cellular proliferation, a clear luminal space along the periphery of gland occupying <50% of gland circumference, lack of intraglandular mucin, and lack of contact between the majority of intraglandular cells with stroma were significantly associated with consensus for CrP4. In contrast, partial bridging, majority of intraglandular cells in contact with stroma, mucinous fibroplasia, only one attachment to the gland border by tumor cells forming a “glomeruloid-like” pattern, and a clear luminal space along the periphery of gland accounting for >50% of the glandular circumference were associated with consensus against CrP4. In summary, we identified reproducible morphological features for and against CrP4 diagnosis, which could be used to refine and standardize the diagnostic criteria for CrP4.     

Use of screening tests,diagnosis wait times,and wait-related satisfaction in breast and prostate cancer

Background

Understanding factors relating to the perception of wait time by patients is key to improving the patient experience.

Methods

We surveyed 122 breast and 90 prostate cancer patients presenting at clinics or listed on the cancer registry in Newfoundland and Labrador and reviewed their charts. We compared the wait time (first visit to diagnosis) and the wait-related satisfaction for breast and prostate cancer patients who received regular screening tests and whose cancer was screening test–detected (“screen/screen”); who received regular screening tests and whose cancer was symptomatic (“screen/symptomatic”); who did not receive regular screening tests and whose cancer was screen test–detected (“no screen/screen”); and who did not receive regular screening tests and whose cancer was symptomatic (“no screen/symptomatic”).

Results

Although there were no group differences with respect to having a long wait (greater than the median of 47.5 days) for breast cancer patients (47.8% screen/screen, 54.7% screen/symptomatic, 50.0% no screen/ screen, 40.0% no screen/symptomatic; p = 0.814), a smaller proportion of the screen/symptomatic patients were satisfied with their wait (72.5% screen/ screen, 56.4% screen/symptomatic, 100% no screen/ screen, 90.9% no screen/symptomatic; p = 0.048).A larger proportion of screen/symptomatic prostate cancer patients had long waits (>104.5 days: 41.3% screen/screen, 92.0% screen/symptomatic, 46.0% no screen/screen, 40.0% no screen/symptomatic; p = 0.011) and a smaller proportion of screen/ symptomatic patients were satisfied with their wait (71.2% screen/screen, 30.8% screen/symptomatic, 76.9% no screen/screen, 90.9% no screen/symptomatic; p = 0.008).

Conclusions

Diagnosis-related wait times and satisfaction were poorest among patients who received regular screening tests but whose cancer was not detected by those tests.     

Diet and supplements and their impact on colorectal cancer

Background

Colorectal cancer is the third commonest cancer and the third leading cause of cancer death among men and women. It has been proposed that dietary factors are responsible for 70-90% of colorectal cancer and diet optimization may prevent most cases.

Aim

To evaluate the role of dietary components and supplements in colorectal cancer.

Methods

Bibliographical searches were performed in Pubmed for the terms “diet and colorectal cancer”, “diet and colon cancer”, “diet and rectal cancer”, “nutrition and colorectal cancer”, “probiotics and colorectal cancer”, “prebiotics and colorectal cancer”, “alcohol and cancer” and “colorectal cancer epidemiology”.

Results

Consumption of processed or red meat, especially when cooked at high temperatures may be associated with increased risk of colorectal cancer. The evidence for dietary fibre is unclear but foods that contain high amounts of fibre are usually rich in polyphenols which have been shown to alter molecular processes that can encourage colorectal carcinogenesis. Meta-analyses provide evidence on the benefits of circulating, diet-derived and supplemented, vitamin D and Calcium. We also found that diets rich in Folate may prevent colorectal carcinoma. The evidence on dietary micronutrients such as Zinc and Selenium in association with colorectal cancer is not conclusive. It has been suggested that there may be a direct association between alcohol intake and colorectal cancer. In vitro and in vivo studies have highlighted a possible protective role of prebiotics and probiotics.

Conclusions

The lack of randomized trials and the presence of confounding factors including smoking, physical activity, obesity and diabetes may often yield inconclusive results. Carefully designed randomized trials are recommended.Key Words: Colorectal cancer, nutrition, diet, carcinogenesis     

Novel Hsp90 inhibitor NVP-AUY922 radiosensitizes prostate cancer cells

Outcomes for poor-risk localized prostate cancers treated with radiation are still insufficient. Targeting the “non-oncogene” addiction or stress response machinery is an appealing strategy for cancer therapeutics. Heat-shock-protein-90 (Hsp90), an integral member of this machinery, is a molecular chaperone required for energy-driven stabilization and selective degradation of misfolded “client” proteins, that is commonly overexpressed in tumor cells. Hsp90 client proteins include critical components of pathways implicated in prostate cancer cell survival and radioresistance, such as androgen receptor signaling and the PI3K-Akt-mTOR pathway. We examined the effects of a novel non-geldanamycin Hsp90 inhibitor, AUY922, combined with radiation (RT) on two prostate cancer cell lines, Myc-CaP and PC3, using in vitro assays for clonogenic survival, apoptosis, cell cycle distribution, γ-H2AX foci kinetics and client protein expression in pathways important for prostate cancer survival and radioresistance. We then evaluated tumor growth delay and effects of the combined treatment (RT-AUY922) on the PI3K-Akt-mTOR and AR pathways in a hind-flank tumor graft model. We observed that AUY922 caused supra-additive radiosensitization in both cell lines at low nanomolar doses with enhancement ratios between 1.4–1.7 (p < 0.01). RT-AUY922 increased apoptotic cell death compared with either therapy alone, induced G₂-M arrest and produced marked changes in client protein expression. These results were confirmed in vivo, where RT-AUY922 combination therapy produced supra-additive tumor growth delay compared with either therapy by itself in Myc-CaP and PC3 tumor grafts (both p < 0.0001). Our data suggest that combined RT-AUY922 therapy exhibits promising activity against prostate cancer cells, which should be investigated in clinical studies.     

Common drugs and treatments for cancer and age-related diseases: revitalizing answers to NCI's provocative questions

In 2011, The National Cancer Institute (NCI) has announced 24 provocative questions on cancer. Some of these questions have been already answered in “NCI''s provocative questions on cancer: some answers to ignite discussion” (published in Oncotarget, 2011, 2: 1352.) The questions included “Why do many cancer cells die when suddenly deprived of a protein encoded by an oncogene?” “Can we extend patient survival by using approaches that keep tumors static?” “Why are some disseminated cancers cured by chemotherapy alone?” “Can we develop methods to rapidly test interventions for cancer treatment or prevention?” “Can we use our knowledge of aging to enhance prevention or treatment of cancer?” “What is the mechanism by which some drugs commonly and chronically used for other indications protect against cancer?” “How does obesity contribute to cancer risk?” I devoted a single subchapter to each the answer. As expected, the provocative questions were very diverse and numerous. Now I choose and combine, as a single problem, only three last questions, all related to common mechanisms and treatment of age-related diseases including obesity and cancer. Can we use common existing drugs for cancer prevention and treatment? Can we use some targeted “cancer-selective” agents for other diseases and … aging itself.     

Correlation between targeted RNAseq signature of breast cancer CTCs and onset of bone-only metastases

Background Bone is the most frequent site of metastases from breast cancer (BC), but no biomarkers are yet available to predict skeletal dissemination.Methods We attempted to identify a gene signature correlated with bone metastasis (BM) onset in circulating tumour cells (CTCs), isolated by a DEPArray-based protocol from 40 metastatic BC patients and grouped according to metastasis sites, namely “BM” (bone-only), “ES” (extra-skeletal) or BM + ES (bone + extra-skeletal).Results A 134-gene panel was first validated through targeted RNA sequencing (RNAseq) on sub-clones of the MDA-MB-231 BC cell line with variable organotropism, which successfully shaped their clustering. The panel was then applied to CTC groups and, in particular, the “BM” vs “ES” CTC comparison revealed 31 differentially expressed genes, including MAF, CAPG, GIPC1 and IL1B, playing key prognostic roles in BC.Conclusion Such evidence confirms that CTCs are suitable biological sources for organotropism investigation through targeted RNAseq and might deserve future applications in wide-scale prospective studies.Subject terms: Breast cancer, Molecular medicine     

Reproductive Outcomes in Young Breast Cancer Survivors Treated (15–39) in Ontario,Canada

We conducted a population-based, retrospective, matched-cohort study to examine the impact of breast cancer diagnosis and treatment on fertility outcomes. Relative risks of infertility, childbirth, premature ovarian insufficiency (POI; age < 40) and early menopause (age < 45) were calculated using modified Poisson regression. Our primary cohort included young women (15–39) with early stage BC diagnosed 1995–2014. Five cancer-free patients were matched to each BC patient by birth year and census subdivision. The BC cohort was further divided by treatment with chemotherapy vs. no chemotherapy treatment. 3903 BC patients and 19,515 cancer-free women. BC patients treated with chemotherapy were at increased risk of infertility (RR 1.81; 95% CI 1.60–2.04), and POI (RR 6.25; 95% CI 5.15–7.58) and decreased childbirth (RR 0.85; 95% CI 0.75–0.96), compared to women without cancer. BC patients who did not receive chemotherapy were also at increased risk of infertility (RR 1.80 95% CI 1.48–2.18) and POI (RR 2.12 95% CI 1.37–3.28). All young BC survivors face an increased risk of diagnosed infertility and POI relative to women without cancer, independent of chemotherapy. These results emphasize the importance of pre-treatment fertility counselling for young women diagnosed with BC.