Would shared decision-making be useful in breast cancer screening programmes? A qualitative study using focus group discussions to gather evidence from French women with different socioeconomic backgrounds.

BACKGROUND: To inform the development of an online tool to be potentially used in shared decision-making about breast cancer screening, French women were questioned about participation in breast cancer screening, the health professional's role, and their perceptions of the proposed tool. METHODS: We organised focus group discussions with 55 French women. Two different strategies were used to recruit women from high and low socioeconomic backgrounds. We applied both inductive and deductive approaches to conduct a thematic analysis of the discussions. We analysed the responses by using the main determinants from different health behaviour models and compared the two groups. RESULTS: Independently of socioeconomic status, the most important determinant for a woman's participation in breast cancer screening was the perceived severity of breast cancer and the perceived benefits of its early detection by screening. Cues to action reported by both groups were invitation letters; recommendations by health professionals, or group/community activities and public events were reported by women from high and low socioeconomic backgrounds, respectively. Among other positive determinants, women from high socioeconomic backgrounds reported making informed decisions and receiving peer support whereas women from low socioeconomic backgrounds reported community empowerment through group/community events. Fear of cancer was reported as a barrier in both groups. Among other barriers, language issues were reported only by women from low socioeconomic backgrounds; women from high socioeconomic backgrounds reported breast cancer screening-related risks other than overdiagnosis and/or overtreatment. Barriers to accessing the online tool to be developed were mainly reported by women from high socioeconomic backgrounds. CONCLUSION: Limitations in implementing shared decision-making for women from low socioeconomic backgrounds were highlighted. An online tool that is suitable for all women, regardless of socioeconomic status, would provide "on-demand" reliable and tailored information about breast cancer screening and improve access to health professionals and social exchanges.

Addressing Cancer Screening Inequities by Promoting Cancer Prevention Knowledge, Awareness, Self-Efficacy, and Screening Uptake Among Low-Income and Illiterate Immigrant Women in France.

Objective: Cancer screening rates are suboptimal for disadvantaged populations in France, yet little evidence exists on their cancer-related knowledge and screening barriers. The main objective of this study was to examine cancer-related knowledge, awareness, self-efficacy, and perceptions of screening barriers among low-income, illiterate immigrant women in France following an 8-weeks cancer educational intervention. Methods: Semi-structured qualitative interviews were conducted with 164 female participants in the Ain department of France between January 2019 and March 2020. Adopting the Health Belief Model as an intervention and analytic framework, salient themes were identified using qualitative thematic analysis. Results: Increased levels of perceived susceptibility to and perceived severity of cancer contributed to higher motivation to get screened. Barriers to screening included low French proficiency, shame surrounding illiteracy, and constant worries due to precarious living conditions. Perceived benefits (e.g., valuing one's health and health-promoting behaviors), cues to action from a trusted source, and greater self-efficacy (e.g., more autonomous in healthcare-seeking) outweighed perceived barriers, including cultural barriers. Conclusions: Implications include developing audience-responsive targeted cancer screening communication strategies and educational materials to increase screening rates and reduce cancer and cancer screening inequities.

Prediction of the severity of colorectal lesion by fecal hemoglobin concentration observed during previous test in the French screening program.

BACKGROUND: The rate of positive tests using fecal immunochemical test (FIT) does not decrease with subsequent campaigns, but the positive predictive value of advanced neoplasia significantly decreases in subsequent campaign after a first negative test. A relationship between the fecal hemoglobin concentration (Fhb) and the opportunity to detect a colorectal cancer in subsequent campaign has been shown. AIM: To predict the severity of colorectal lesions based on Fhb measured during previous colorectal cancer screening campaign. METHODS: This etiological study included 293750 patients aged 50-74, living in Auvergne-Rhône-Alpes (France). These patients completed at least two FIT [test(-1) and test(0)] between June 2015 and December 2019. Delay between test(-1) and test(0) was > 1 year and test(-1) result was negative (< 150 ngHb/mL). The severity of colorectal lesions diagnosed at test(0) was described according to Fhb measured at test(-1) [Fhb(-1)]. The relationship between the severity classified in seven ordinal categories and the predictive factors was analyzed in an ordered multivariate polytomous regression model. RESULTS: The test(0) positive rate was 4.0%, and the colonoscopy completion rate was 97.1% in 11594 patients who showed a positive test(0). The colonoscopy detection rate was 77.7% in those 11254 patients who underwent a colonoscopy. A total of 8748 colorectal lesions were detected (including 2182 low-risk-polyps, 2400 high-risk-polyp, and 502 colorectal cancer). The colonoscopy detection rate varied significantly with Fhb(-1) [0 ngHb/mL: 75.6%, (0-50 ngHb/mL): 77.3%, (50-100 ngHb/mL): 88.7%, (100-150 ngHb/mL): 90.3%; P = 0.001]. People with a Fhb(-1) within (100-150 ngHb/mL) (P = 0.001) were 2.6 (2.2; 3.0) times more likely to have a high severity level compared to those having a Fhb(-1) value of zero. This risk was reduced by 20% in patients aged 55-59 compared to those aged < 55 [adjusted odds ratio: 0.8 (0.6; 1.0)]. CONCLUSION: The study showed that higher Fhb(-1) is correlated to an increased risk of severity of colorectal lesions. This risk of severity increased among first-time participants (age < 55) and the elderly (≥ 70). To avoid the loss of chance in these age groups, the FIT positivity threshold should be reduced to 100 ngHb/mL. The other alternative would be to reduce the time between the two tests in these age groups from the current 2 years to 1 year.

Implication of MYH in colorectal polyposis.

OBJECTIVE: The aim of this study was to determine the frequency of MYH mutations in one large population of polyposis patients without APC mutation identified. SUMMARY BACKGROUND DATA: Familial adenomatous polyposis (FAP) is the most known inherited colorectal cancer syndrome. In 70% to 80% of polyposis patients, an APC mutation is found. Patients with polyposis but no APC mutation are considered as APC-muted patients and followed as their relatives accordingly. Biallelic mutation of MYH has been found to responsible of colorectal polyposis and cancer in an autosomal recessive pattern of inheritance. METHODS: Between 1978 and 2004, 433 patients were operated for polyposis. A mutation on APC was identified in 322 patients. Among the remaining patients, 44 were identified as possible MYH-muted patients and contacted, and 31 signed informed consent. Clinical data were obtained from the patients' medical notes. Germline mutation of MYH was searched by sequencing the whole gene. To confirm the deleterious effects of biallelic MYH mutation, transversions on K-ras and APC were searched. RESULTS: There were 9 women and 22 men with a mean age of 53.9 years (range, 22-68 years) at the time of diagnosis. The mean number of polyps was 62.8 (range, 11-266). Eighteen patients (58.1%) had a colorectal cancer. We found biallelic MYH mutation in 6 patients (19.3%; 95% confidence interval, 5.2%-33.5%) and 5 (83.3%) had transversions in K-ras and/or APC. CONCLUSION: MYH is a new gene responsible for about 1.4% of all adenomatous polyposis and about 20% of adenomatous polyposis without APC mutation identified. Search for MYH biallelic mutation in these patients should be systematic as it changes their and relatives'surveillance.

Inhibition of vascular endothelial growth factor (VEGF)-165 and semaphorin 3A-mediated cellular invasion and tumor growth by the VEGF signaling inhibitor ZD4190 in human colon cancer cells and xenografts.

We recently showed by DNA microarray analysis that vascular endothelial growth factor (VEGF) receptor (VEGFR) is expressed in HCT8/S11 human colon cancer cells, suggesting that several angiogenic factors may target colon cancer cells themselves. In this study, transcripts encoding the VEGF-165 and semaphorin 3A (Sema3A) receptors and coreceptors Flt-1, KDR/Flk-1, plexin A1, and neuropilins NP-1 and NP-2 were identified by reverse transcription-PCR in the human colon cancer cell lines HCT8/S11, HT29, HCT116, and PCmsrc. Collagen invasion induced by VEGF-165 and Sema3A in HCT8/S11 cells (EC(50), 0.4-1 nmol/L) required p42/44 mitogen-activated protein kinase and signaling through RhoA/Rho-kinase-dependent and -independent pathways, respectively. As expected, the VEGFR signaling inhibitor ZD4190 selectively abrogated the proinvasive activity of VEGF in collagen gels (IC(50), 10 nmol/L) and chick heart fragments. We identify a novel function for VEGF-165 and Sema3A as proinvasive factors for human colorectal cancer cells. Interestingly, oral administration of the single drug ZD4190 to athymic mice (50 mg/kg/d, once daily) inhibited by 70% the growth of HCT8/S11 tumor cell xenografts. Combinations between the src tyrosine kinase inhibitor M475271 and ZD4190 or cisplatin resulted in additive therapeutic activity against LNM35 human lung tumor xenografts. Our data have significant implications for new therapeutic approaches and individualized treatment targeting VEGFR and src signaling pathways in combination with established clinical drugs at primary tumors and distant metastases in colon and lung cancer patients.

The cancer chemopreventive agent resveratrol induces tensin, a cell-matrix adhesion protein with signaling and antitumor activities.

During a search to identify resveratrol (3,5,4'-trihydroxy-trans-stilbene, RV) target genes in the human erythroleukemic K562 cell line, we show here that the tensin gene and protein levels are remarkably induced by this dietary polyphenol. Tensin, a cell-matrix adhesion protein binding the integrins and cytoskeletal actin filaments also interacts with PI3-kinase and JNK signaling pathways. Tensin induction by RV is associated with increased K562 cell adhesion to fibronectin, cell spreading and actin polymerization. The same responses were observed in the tensin-deficient MCF7 human breast cancer cell line. In K562 and MCF7 cells treated by RV, tensin was found in punctate and intracytoplasmic areas. In MCF7 epithelial cells, induction of tensin is not exclusively associated with plasma membrane-bound vinculin, suggesting a dual localization of tensin in both focal and fibrillar adhesions. Pharmacological blockade of PI3-kinase and Rho GTPases/Rho-kinase resulted in selective depletion of focal adhesions, disorganization of tensin localization and disruption of stress fibers. RV increased cell motility and attachment to fibronectin in MCF7 cells submitted to mechanical laminar flow stress, and abrogated estrogen-induced MCF7 cancer cell invasion. Our data support the conclusion that induction of tensin by RV contributes to the chemopreventive and anti-invasive activity of this natural dietary compound in tensin-negative and -deficient leukemic cells or epithelioid cancers.

[Cyclooxygenase 2 and carcinogenesis]. / Cyclo-oxygénase 2 et carcinogenèse.

The membrane glycoprotein Cox2 is regulated at transcriptional and post-transcriptional levels by pro-inflammatory agents, cytokines, growth factors, oncogenes, and tumor-promoters. Cox2 is expressed during early stages of colorectal carcinogenesis from the premalignant adenoma stage, and adenocarcinomas of stomach, colon, breast, lung and prostate. Its expression is detected in neoplastic, inflammatory, endothelial and stromal cells. Cox2 is involved in the conversion of arachidonic acid into prostaglandins and thromboxanes, as well as the synthesis of malonaldehyde (MDA, a mutagen) and the production of hydrogen peroxide, which promotes carcinogenesis. The Cox2 products act in turn on serpentine receptors coupled to heterotrimeric G-proteins (R-TXA2, R-PG) that are connected to signaling elements implicated in oncogenesis. Thus, Cox2 plays a key role in early stages of carcinogenesis by promoting the proliferation of tumoral cells and their resistance to apoptosis, as well as angiogenesis. tumor cell invasion and setting up of the metastatic process. These mechanisms establish the rationale behind the therapeutic targeting of Cox2 in human solid tumors.

Trefoil factor family (TFF) peptides and cancer progression.

TFF peptides are involved in mucosal maintenance and repair through motogenic and antiapoptotic activities. These peptides are overexpressed during inflammatory processes and cancer progression. They also function as scatter factors, proinvasive and angiogenic agents. Such a divergence is related to the pathophysiological state of tissues submitted to persistent aggressive situations during digestive processes in the normal gastrointestinal tract, inflammatory and neoplastic diseases. In agreement with this model, TFF peptides are connected with multiple oncogenic pathways. As a consequence, the TFF signaling pathways may serve as potential targets in the control of chronic inflammation and progression of human solid tumors.

[Cyclooxygenase 2 and carcinogenesis]. / Cyclo-oxygénase 2 et carcinogenèse.

The membrane glycoprotein Cox2 is regulated at transcriptional and post-transcriptional levels by pro-inflammatory agents, cytokines, growth factors, oncogenes, and tumor-promoters. Cox2 is expressed during early stages of colorectal carcinogenesis from the premalignant adenoma stage, and adenocarcinomas of stomach, colon, breast, lung and prostate. Its expression is detected in neoplastic, inflammatory, endothelial and stromal cells. Cox2 is involved in the conversion of arachidonic acid into prostaglandins and thromboxanes, as well as the synthesis of malonaldehyde (MDA, a mutagen) and the production of hydrogen peroxide, which promotes carcinogenesis. The Cox2 products act in turn on serpentine receptors coupled to heterotrimeric G-proteins (R-TXA2, R-PG) that are connected to signaling elements implicated in oncogenesis. Thus, Cox2 plays a key role in early stages of carcinogenesis by promoting the proliferation of tumoral cells and their resistance to apoptosis, as well as angiogenesis, tumor cell invasion and setting up of the metastatic process. These mechanisms establish the rationale behind the therapeutic targeting of Cox2 in human solid tumors.

Selective abrogation of the proinvasive activity of the trefoil peptides pS2 and spasmolytic polypeptide by disruption of the EGF receptor signaling pathways in kidney and colonic cancer cells.

Trefoil peptides (TFFs) are now considered as scatter factors, proinvasive and angiogenic agents acting through cyclooxygenase-2 (COX-2)- and thromboxane A2 receptor (TXA2-R)-dependent signaling pathways. As expression and activation levels of the epidermal growth factor receptor (EGFR) predict the metastatic potential of human colorectal cancers, the purpose of this study was to establish whether the EGF receptor tyrosine kinase (EGFR-TK) contributes to cellular invasion induced by TFFs in kidney and colonic cancer cells. Both the dominant negative form of the EGFR (HER-CD533) and the EGFR-TK inhibitor ZD1839 (Iressa) abrogated cellular invasion induced by pS2, spasmolytic polypeptide (SP) and the src oncogene, but not by ITF and the TXA2-R. Similarly, EGFR-TK inhibition by ZD1839 reversed the invasive phenotype promoted by the constitutively activated form of the EGFR (EGFRvIII) and the EGFR agonists transforming growth factor alpha (TGFalpha), amphiregulin and EGF. We also provide evidence that TFFs, EGFRvIII, and TGFalpha trigger common proinvasive pathways using the PI3'-kinase and Rho/Rho- kinase cascades. These findings identify the EGFR-TK as a key signaling element for pS2- and SP-mediated cellular invasion. It is concluded that although pS2, SP and ITF belong to the same family of inflammation- and cancer-associated regulatory peptides, they do not control identical signaling networks.