PURPOSE: Partnering with the largest Federally Qualified Health Center (FQHC) in New Haven, CT, the goal is to implement and test 4 evidence-based interventions (EBI) to increase CRC screening, while evaluating real-world implementation. Here, we report on the six-month (approximate) follow up of a cohort of 3,127 patients overdue for CRC screening who received 1 or more EBIs in October 2021. BACKGROUND: Sociocultural and medical concerns are barriers to colonoscopy uptake contributing to disparities in CRC screening. An additional barrier is system level capacity. COVID-19 associated delays exacerbated the existing backlog of individuals overdue for CRC screening, underscoring the need to expand Fecal Immunochemical Testing (FIT) capacity. This was particularly evident in the safety-net primary care setting that serves lower socio-economic status individuals living in urban New Haven, CT. METHODS: We are testing the unique and additive value of multiple evidence-based interventions (EBIs) for increasing CRC screening. The EBIs include the use of medical reminders, addressing the structural barriers (social determinants of health [SDOH]), and providing assistance from community health workers (CHW). We randomized 3,127 patients overdue for CRC screening to one of 4 arms of the study. All individuals received a reminder from their providers that they were due/overdue for CRC screening with instructions to contact the FQHC. Arm 2 also included information on SDOH barriers, Arm 3 included this same information with offer of navigation from CHW/navigator; and Arm 4 included the offer of CHW educational video and support if needed. Six-month (approximate) outcomes include: 1) Engagement with FQHC resulting in ordered test; 2) completed test. Results by intervention will be assessed at 12 months. RESULTS: Of the 3,127 randomized patients, ages 50-75, 77% were Hispanic (33%) or Black (44%). At 6+ months, a preliminary look at EMR data show that a minimum of 1,275 (40.8%) patients “engaged” with providers resulting in an ordered FIT Kit (n= 1174) or COMPLETED screening colonoscopy that was not associated with a positive FIT result (n = 102). 217 (18.5%) individuals completed the FIT testing with 13 requiring confirmatory colonoscopy (31% completed at this time). Thus, a minimum of 319 (10%) of 3,127 individuals in the cohort completed CRC screening at approximately 6 months post intervention. DISCUSSION: Despite investments in community engagement, stakeholder input, and FIT kit capacity building, the pandemic presented unforeseen challenges. Flexibility and steadfast commitment from FQHC providers and staff were critical to successful implementation during multiple waves of COVID-19, resulting in CRC screening ordered for 41% of cohort within 6 months of intervention. SUMMARY: At 6 months follow up of 3,127 individual who were overdue for CRC screening, one or more of 4 EBIs, in addition to system level efforts to address CRC screening, resulted CRC screening tests ordered for 41% of cohort with at least 10% completed screening. Citation Format: Beth A. Jones, Sakinah C. Suttiratana, Sarah A. DeGiovanni, Steven J. Parra, Levita Robinson, Michael Couturie, Louie Mar Gangcuangco, Denise Stevens. Partnering with primary care to implement evidence based interventions (EBI) to address overdue colorectal cancer (CRC) screening in Connecticut (CT) [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr A104.

Abstract PURPOSE: We partnered with the largest FQHC in New Haven, CT to address overdue colorectal cancer screening with evidence-based interventions (EBI). We report on the 12-month follow up of a cohort of 3,127 patients overdue for CRC screening who received 1 or more evidence based interventions (EBIs) in October, 2021. BACKGROUND: Sociocultural and medical concerns are barriers to colonoscopy uptake contributing to disparities in CRC screening. An additional barrier is system level capacity. COVID-19 associated delays exacerbated the existing backlog of individuals overdue for CRC screening, underscoring the need to expand Fecal Immunochemical Testing (FIT) screening capacity. At the time of the study, colonoscopy was the front-line cancer screening strategy in this and other primary care settings in this region. METHODS: We tested the unique and additive value of multiple EBIs for increasing CRC screening in this low-income urban population. The EBIs included: medical reminder to all recipients (Arms 1-4), supplemented with information to address social determinants of health [SDOH]) barriers (Arm 2), offer of assistance from trained community health workers (CHW) to address SDOH barriers (Arm 3), and offer of educational intervention (video and pre- and post- survey) (Arm 4). Twelve-month outcomes include: 1) CRC screening test ordered; 2) CRC screening completed. RESULTS: Of the 3,127 randomized patients, ages 50-75, 77% were Hispanic (33%) or Black (44%). At 12 months post-intervention, 1,692 (54.1%) of the cohort received an order for CRC screening, and 541 (17.3%) of the cohort completed screening. With no path to CRC screening other than a provider order, among patients for whom CRC screening was ordered, nearly one-third (32%) completed screening within 12 months of the intervention. There were no differences in either outcome based on intervention Arm. DISCUSSION: Among the 3,127 individuals who were due or overdue for screening at the time of intervention, only 9 had documented CRC cancer screening in the 5 years before randomization. The promotion of stool-based testing may have brought individuals into CRC screening. There were no differences in CRC screening (colonoscopy or FIT) orders or completed tests across the 4 arms of the study, suggesting that the provider endorsed mailed screening reminder with information on in-home, stool-based testing option (FIT), and notice that CRC screening is now recommended beginning at age 45 was key to behavior change. Provider engagement and post-pandemic care-seeking on part of patients, as well as increased awareness of CRC screening following the death of high-profile actor at age 43 likely contributed to increased uptake of CRC screening. SUMMARY: A mailed reminder is a cost effective, scalable intervention that may be effective in safety net primary care settings that serve high-risk individuals. Closing the screening gap in CRC screening should include educating patients about their CRC screening options as well as the change in recommended age to begin CRC screening. Citation Format: Beth A. Jones, Sakinah C. Suttiratana, Sarah A. DeGiovanni, Levita Robinson, Michael Couturie, Steven J. Parra, Louie M. Gangcuangco, Laney Zhang, Denise Stevens, Margarita Vargas-Torres. Implementing on overdue colorectal cancer (CRC) screening in the Federally Qualified Health Center (FQHC) primary care setting: 12-month post intervention results [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C117.

PURPOSE: We partnered with the largest FQHC in New Haven, CT to address overdue colorectal cancer screening with evidence-based interventions (EBI). We report on the 12-month follow up of a cohort of 3,127 patients overdue for CRC screening who received 1 or more evidence based interventions (EBIs) in October, 2021. BACKGROUND: Sociocultural and medical concerns are barriers to colonoscopy uptake contributing to disparities in CRC screening. An additional barrier is system level capacity. COVID-19 associated delays exacerbated the existing backlog of individuals overdue for CRC screening, underscoring the need to expand Fecal Immunochemical Testing (FIT) screening capacity. At the time of the study, colonoscopy was the front-line cancer screening strategy in this and other primary care settings in this region. METHODS: We tested the unique and additive value of multiple EBIs for increasing CRC screening in this low-income urban population. The EBIs included: medical reminder to all recipients (Arms 1-4), supplemented with information to address social determinants of health [SDOH]) barriers (Arm 2), offer of assistance from trained community health workers (CHW) to address SDOH barriers (Arm 3), and offer of educational intervention (video and pre- and post- survey) (Arm 4). Twelve-month outcomes include: 1) CRC screening test ordered; 2) CRC screening completed. RESULTS: Of the 3,127 randomized patients, ages 50-75, 77% were Hispanic (33%) or Black (44%). At 12 months post-intervention, 1,692 (54.1%) of the cohort received an order for CRC screening, and 541 (17.3%) of the cohort completed screening. With no path to CRC screening other than a provider order, among patients for whom CRC screening was ordered, nearly one-third (32%) completed screening within 12 months of the intervention. There were no differences in either outcome based on intervention Arm. DISCUSSION: Among the 3,127 individuals who were due or overdue for screening at the time of intervention, only 9 had documented CRC cancer screening in the 5 years before randomization. The promotion of stool-based testing may have brought individuals into CRC screening. There were no differences in CRC screening (colonoscopy or FIT) orders or completed tests across the 4 arms of the study, suggesting that the provider endorsed mailed screening reminder with information on in-home, stool-based testing option (FIT), and notice that CRC screening is now recommended beginning at age 45 was key to behavior change. Provider engagement and post-pandemic care-seeking on part of patients, as well as increased awareness of CRC screening following the death of high-profile actor at age 43 likely contributed to increased uptake of CRC screening. SUMMARY: A mailed reminder is a cost effective, scalable intervention that may be effective in safety net primary care settings that serve high-risk individuals. Closing the screening gap in CRC screening should include educating patients about their CRC screening options as well as the change in recommended age to begin CRC screening. Citation Format: Beth A. Jones, Sakinah C. Suttiratana, Sarah A. DeGiovanni, Levita Robinson, Michael Couturie, Steven J. Parra, Louie M. Gangcuangco, Laney Zhang, Denise Stevens, Margarita Vargas-Torres. Implementing on overdue colorectal cancer (CRC) screening in the Federally Qualified Health Center (FQHC) primary care setting: 12-month post intervention results [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C117.

Abstract Purpose: We partnered with a local Federally Qualified Health Center (FQHC) to test implementation of evidence-based interventions (EBI) promoting Fecal Immunochemical Test (FIT) CRC screening in an environment in which colonoscopy has been the prevailing screening strategy. We report on implementation adaptations and preliminary results. Background: Sociocultural and medical concerns are barriers to colonoscopy uptake in some populations. An additional barrier to CRC screening is system level capacity for colonoscopy that results in a back log of cases and long wait times. With Covid-19, the additional backlog in overdue CRC screening has underscored the need to expand FIT testing capacity to address screening needs and to pre-empt further racial/ethnic and SES disparities in CRC outcomes. This trial tests the unique and additive value of multiple EBIs for increasing CRC screening (primarily through FIT testing, but also colonoscopy when indicated) while evaluating the success of implementing these approaches. EBIs include the use of medical reminders, addressing the structural barriers (social determinants of health [SDOH]), and assistance from community health workers. Methods: Participants (3500), ages 45-75, were identified from a large FQHC in New Haven, CT and determined to be overdue for CRC screening. Participants were randomly assigned to one of the four arms of the study: 1) Provider reminder (overdue for CRC screening) only; 2) Provider Reminder + SDOH short message and one-size-fits all link to resources; 3) Provider Reminder + SDOH short message and offer for individualized navigation (trained navigators from local community) to address SDOH and other barriers; 4) Provider Reminder + offer to participate in a CRC educational program as phase 2 of the NCI's Screen to Save program (not an EBI). Preliminary data on uptake of CRC screening will be presented. Results: With input from stakeholders, we have: 1) lowered age eligibility from 50 to 45 to align with new guidelines; 2) expanded the target population to 2 additional satellite clinics, more than doubling the proposed study enrollment; 3) incorporated design changes in the patient reminders. The collaboration between research team and clinician stakeholders has been critical in minimizing disruptions to clinical workflow while assuring fidelity to the evidence-based interventions. Preliminary outcomes (within one month of intervention) on uptake of intervention across the 4 arms of the study, i.e., referral for CRC screening and test completion will be presented. Conclusion: The unique challenges of this urban community of primarily African American/Black, Hispanic/Latinx and/or low socioeconomic status individuals stem from the disproportionate burden of SDOH barriers. Findings will inform primary care setting implementation of EBIs to address the anticipated increase in disparities in CRC screening, exacerbated by COVID-19 changes in health care access and utilization, as well as the increased demand associated with the change in guidelines. Citation Format: Beth A. Jones, Sakinah C. Suttiratana, Sally A. DeGiovanni, Levita Y. Robinson, Michael J. Couturie, Denise Stevens, Monique K. Stefanou, Jose DeJesus, Eduardo Reyes, Jonathan Colon, Maryanne Cosgrove, Steven J. Parra. Implementing evidence-based interventions (EBI) to increase uptake of fecal immunochemical test (FIT) colorectal cancer (CRC) screening in Vulnerable Populations [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-025.

E-cadherin, a CDH1 gene product, is a calcium-dependent cell–cell adhesion molecule playing a critical role in the establishment of epithelial architecture, maintenance of cell polarity, and differentiation. Germline pathogenic variants in the CDH1 gene are associated with hereditary diffuse gastric cancer (HDGC), and large rearrangements in the CDH1 gene are now being reported as well. Because CDH1 pathogenic variants could be associated with breast cancer (BC) susceptibility, CDH1 rearrangements could also impact it. The aim of our study is to identify rearrangements in the CDH1 gene in 148 BC cases with no BRCA1 and BRCA2 pathogenic variants. To do so, a zoom-in CGH array, covering the exonic, intronic, and flanking regions of the CDH1 gene, was used to screen our cohort. Intron 2 of the CDH1 gene was specifically targeted because it is largely reported to include several regulatory regions. As results, we detected one large rearrangement causing a premature stop in exon 3 of the CDH1 gene in a proband with a bilateral lobular breast carcinoma and a gastric carcinoma (GC). Two large rearrangements in the intron 2, a deletion and a duplication, were also reported only with BC cases without any familial history of GC. No germline rearrangements in the CDH1 coding region were detected in those families without GC and with a broad range of BC susceptibility. This study confirms the diversity of large rearrangements in the CDH1 gene. The rearrangements identified in intron 2 highlight the putative role of this intron in CDH1 regulation and alternative transcripts. Recurrent duplication copy number variations (CNV) are found in this region, and the deletion encompasses an alternative CDH1 transcript. Screening for large rearrangements in the CDH1 gene could be important for genetic testing of BC.

Objective: Assess consumer experience and health impact among under-resourced individuals who were enrolled into longitudinal navigation to address social determinants of health (SDOH) needs and health goals related to cancer primary and secondary prevention. Background: The Yale Cancer Disparities Firewall Project is a multi-tiered initiative to address the social determinants of health (SDOH) and other challenges that prevent at-risk communities from receiving the full benefit of the many available cancer prevention and cancer screening options. A communityfacing health navigation program, staffed by community members who have received extensive multidisciplinary training is a central component of this program. Methods: Of the 61 currently enrolled individuals (all of whom are either African American/Black or Hispanic/Latinx), we collected questionnaire data from 24 individuals (39% response rate). In general, participants are enrolled for a minimum of 1 year, but most have been followed for 2 years. Respondents were similar to non-respondents with respect to race (60% were Black/African American vs 61.2%, respectively) and age (mean = 44.8 vs 47.2 years, respectively). Respondents were more likely to be female (85% vs 71.4%, p =.009), Hispanic/Latinx (35% vs 42%), but significantly less likely to be foreign-born (15% vs 26.5 %, p = .021). We assessed satisfaction with assigned navigator(s), uptake of referred services, knowledge gained, health behavior change, and self-rated health (SRH). Results: Per self-report, 79.2% of participants agreed and a further 12.5% somewhat agreed that they were overall satisfied with their experience with the health navigation program. Importantly, two-thirds (66.7%) agreed and a further 20.8% somewhat agreed that they changed their behavior to improve their health and well-being because of the program. Of the 5 health focused services offered, the most commonly reported uptake was physical activity (87.5%), followed by learning how to eat healthier and losing weight. Additionally, one third (33.3%) of participants received assistance with reducing or stopping smoking. In terms of secondary prevention, 62.5% of clients received assistance with cancer screening. Of the 5 SDOH focused services offered, the most common was assistance with finding food to eat (66.7%) followed by assistance with paying utilities (45.8%), a shift from the priority needs at baseline (40% needing food assistance, and 35% with housing concerns), presumably reflecting the additional strains associated with the COVID-19 pandemic. Conclusions: Against the backdrop of COVID-19, these findings suggest that addressing SDOH barriers through individual navigation is an important add-on service when facilitating access to services to maintain healthy lifestyle and adhere to cancer screening guidelines. Although this was a pilot program, we foresee the opportunity to utilize trained non-clinical navigators and/or community health workers and to promote cancer prevention in at risk communities.

Abstract Background Patient navigation is proving an effective evidenced based strategy for cancer screening, diagnosis and treatment. Novel solutions are needed to provide community members with local cancer screening and prevention resources. The Yale Cancer Disparities Firewall (Firewall) recently launched a “health” navigation program that combines health navigators, technology and screening for social determinants of health (SDOH) to initiate ongoing wellness relationships with people in need of cancer screening and risk reduction support. Health navigation utilizes a digital platform, NowPow, LLC, to connect community members to cancer screening, prevention and social resources. Health navigation, powered by NowPow, LLC, is a key component as we build a cancer disparities firewall around at–risk populations by addressing patient cancer risk reduction, screening and social needs using health navigators. Methodology Health navigators recruited community members for health navigation at Yale Cancer Center community outreach and engagement events. Participants identified one or more self-management goals of interest: tobacco treatment, weight management, eating healthier food, physical activity and cancer prevention. With telephone follow-up, health navigators screened individuals using NowPow, LLC, a digital platform that can tailor zip code specific screening and prevention and SDOH resources to individual needs. Resource lists were populated for each participant based on SDOH screenings and participant self-management goals and sent via text message and/or email. Health navigators tracked participant engagement with resources at 1 week, 2 week and 3-4 week intervals via telephone. Results Navigators contacted 511 individuals in a 2-month period: 141 demonstrated interest and 42 entered the program (71.4% female, 65% AA, 20%H/L, 6% other). Health Prevention Priorities: healthier food: 71.4%, physical activity: 66.7%, weight management: 61.9%, cancer prevention: 40.5%, finding healthy food: 31%, tobacco treatment: 11.9%. The top 3 SDOH needs were housing instability (32%), food insecurity (24%), and utilities (23%). Distances to referred services ranged 4.7 to 11.1 miles from the participants’ zipcode. Within 4 weeks of follow-up, 54% of individuals contacted at least 1 resource. The major reason given for not accessing referred resources was “too busy”. Conclusions In this pilot project, we are using NowPow, LLC, a digital interface to facilitate health navigators in linking community members to both cancer screening and SDOH resources. Although interest in receiving navigation has been relatively high, accessing the resources that have been provided lags. Understanding the barriers to uptake will be key to the development of strategies to overcome lifestyle barriers such as time constraints and competing priorities to ensure the utilization of local cancer screening and prevention and SDOH resources by all participants. Citation Format: Monique Killins, Sakinah Suttiratana, Roy Herbst, Jacqueline Prinz, Briyana Green, Jose DeJesus, Denise Stevens, Beth A Jones. Utilizing health navigators and technology to increase cancer screening and healthy lifestyle: Preliminary findings from the Yale Cancer Disparities Firewall Project [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr C118.

Abstract Background: Cancer incidence rates in Connecticut are well above the national average with the greatest burden on African Americans, Hispanic/Latinos, and those with low socioeconomic status. In 2018, we launched the Yale Cancer Center’s (YCC) Cancer Disparities Firewall Project with the goal of providing a protective firewall around our catchment’s at-risk populations, specifically targeting breast, prostate, lung, and colorectal cancer. Methods: The Aims of the Cancer Disparities Firewall Project are to: 1) expand community outreach & education; 2) establish a “health” navigation program; 3) create infrastructure to support sustainable change. Strategies to accomplish Aims 1 & 2 require our presence in communities, workplaces, and other venues that are not always associated with health care institutions. Focusing on 2 key components of the cancer control continuum, prevention and early detection, and adapting for individual settings (e.g., minority populations are concentrated in mostly urban areas of the state), we conduct health fairs, provide “Ask the Doctor” forums, and hold free screening events on a regular basis. Supported by a bicultural/bilingual male and female staff, we provide outreach in Spanish and English. For Aim 2, we established a “health” navigation program that provides geo-coded linkages to care in the communities where people live by combining skilled health navigators with a digital platform, NowPow. As accessing services to support lifestyle change (e.g., tobacco treatment, weight management) and timely cancer screening may be low priority, we screen for social determinants of health (SDOH), as well as cancer prevention barriers and tailor referrals to services accordingly. Based on multiple points of contact beginning with in-person enrollment at a community based event, we facilitate access by building relationships that continue as needed. The third aim is to build sustainability into our efforts through internal and external partnerships. Results: Since June, 2018, community outreach and education events (Aim 1) have increased by 80%, as has documented outreach to individuals (from 3345 to 5500), with racial/ethnic profiles that reflect the target population. In its first 2 months, the health navigation arm of the project (Aim 2) has recruited 141/511 individuals into navigation with 30% (42/141) currently followed (71.4% female, 65% AA, 20%H/L, 6% other). Now working with almost 100 community and institutional partners in order to assure sustainability (Aim 3), as one example, we partner with a local community college to build a cancer track into a patient navigation program, adapting the curriculum as needed. Summary: Addressing the four cancers that drive observed cancer disparities, our approach uses outreach and technology to increase our navigation in-reach to vulnerable communities, and is an important step toward establishing linkages to care. Further, this work lays the foundation for new implementation strategies and research. Citation Format: Beth A Jone, Roy Herbst, Sakinah C Suttiratana, Monique Killins, Denise Stevens, Briyana Green, Jacqueline Prinz, Jose DeJesus. Yale Cancer Disparities Firewall Project: Taking lifestyle change and cancer screening into the community to reduce cancer disparities [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr C115.

Background Avoiding axillary lymph node dissection (ALND) for invasive breast cancers with isolated tumor cells or micrometastatic sentinel node biopsy (SNB) could decrease morbidity with minimal clinical significance. Purpose The aim of this study is to simulate the medico-economic impact of the routine use of the MSKCC non-sentinel node (NSN) prediction nomogram for ER+ HER2- breast cancer patients. Methods We studied 1036 ER+ HER2- breast cancer patients with a metastatic SNB. All had a complementary ALND. For each patient, we calculated the probability of the NSN positivity using the MSKCC nomogram. After validation of this nomogram in the population, we described how the patients' characteristics spread as the threshold value changed. Then, we performed an economic simulation study to estimate the total cost of caring for patients treated according to the MSKCC predictive nomogram results. Results A 0.3 threshold discriminate the type of sentinel node (SN) metastases: 98.8% of patients with pN0(i+) and 91.6% of patients with pN1(mic) had a MSKCC score under 0.3 (false negative rate = 6.4%). If we use the 0.3 threshold for economic simulation, 43% of ALND could be avoided, reducing the costs of caring by 1 051 980 EUROS among the 1036 patients. Conclusion We demonstrated the cost-effectiveness of using the MSKCC NSN prediction nomogram by avoiding ALND for the pN0(i+) or pN1(mic) ER+ HER2- breast cancer patients with a MSKCC score of less than or equal to 0.3.

Background: A better understanding of the molecular profile of anal squamous cell carcinomas (ASCCs) is necessary to consider new therapeutic approaches, and the identification of prognostic and predictive factors for response to treatment. Methods: We retrospectively analysed tumours from ASCC patients for mutational analysis of KRAS , NRAS , HRAS , BRAF , PIK3CA , MET , TP53 and FBXW7 genes by HRM and Sanger sequencing analysis. Results: Specimens from 148 patients were analysed: 96 treatment-naive tumours and 52 recurrences after initial radiotherapy (RT) or chemoradiotherapy (CRT). Mutations of KRAS , PIK3CA , FBXW7 and TP53 genes were present in 3 (2.0%), 30 (20.3%), 9 (6.1%) and 7 tumours (4.7%), respectively. The distribution of the mutations was similar between treatment-naive tumours and recurrences, except for TP53 mutations being more frequent in recurrences ( P =0.0005). In patients treated with abdominoperineal resection (APR) after relapse ( n =38, median follow-up of 18.2 years), overall survival (OS) was significantly correlated with HPV16 status ( P =0.048), gender ( P =0.045) and PIK3CA mutation ( P =0.037). The PIK3CA status retained its prognostic significance in Cox multivariate regression analysis ( P =0.025). Conclusions: Our study identified PIK3CA mutation as an independent prognostic factor in patients who underwent APR for ASCC recurrence, suggesting a potential benefit from adjuvant treatment and the evaluation of targeted therapies with PI3K/Akt/mTor inhibitors in PIK3CA- mutated patients.

BackgroundThe impact of adjuvant chemotherapy on breast cancer prognosis has been demonstrated in randomized trials, but its impact is unknown in real-world populations. The aim of this study was to evaluate the effect of adjuvant chemotherapy on the survival of breast cancer patients in an unselected population.MethodsThis prospective cohort study included 32,502 women treated at the Institut Curie between 1981 and 2008 for a first invasive breast cancer without metastasis. The patients were matched based on their propensity score to receive adjuvant chemotherapy.ResultsThe matching generated a subsample of 9,180 patients with an overlapping propensity score. In the group without chemotherapy, the overall survival (OS) rates at 5 and 10 years of follow-up were 87.6% (95% CI [86.7-88.6]) and 75.0% (95% CI [73.6-76.5]), respectively, versus 92.1% (95% CI [91.3-92.9]) and 81.9% (95% CI [80.6-83.2]), respectively, in the chemotherapy group. Distant disease-free survival (DDFS) was significantly improved in the five first years (absolute benefit of 3.5%). In a multivariate analysis, adjuvant chemotherapy was associated with better OS (HR = 0.75, 95% CI [0.69-0.83], p<0.0001) and DDFS (HR = 0.82, 95% CI [0.75-0.90], p<0.0001).ConclusionAdjuvant chemotherapy significantly improves OS and DDFS rates in an unselected population, in accordance with previous results reported by randomized trials.

AIM:The objective of the present study was to describe the biological characteristics of each lesion in patients with bifocal/bicentric (BF/BC) breast cancer.PATIENTS AND METHODS:We retrospectively reviewed the charts of 205 patients diagnosed with BF/BC cancer. The degree of concordance between the two lesions was assessed using Pearson product-moment correlation coefficients.RESULTS:A total of 205 patients were included. Both tumors displayed the same histological type in 182 patients (89%). The same grade was found for both tumors in 178 of the cases (96.7% and 100% for grade 3 lesions). Immunohistochemical concordance between the two tumors was excellent, with correlation coefficients of 0.98, 0.96 and 0.99 for estrogen receptors (ER), progesterone receptors (PR) and Ki67, respectively. Human Epidermal growth factor Receptor 2 (HER2) status was available for both tumors in 177 cases (86%), with a perfect concordance. We did not find any differences in molecular sub-type between tumor foci.CONCLUSION:Immunohistochemistry should be performed only on the main tumor in cases of BF/BC cancer.

There are knowledge gaps regarding the needs of cancer survivors in Connecticut and their utilization of supportive services.

PURPOSE:To evaluate the effect of postmastectomy radiotherapy (PMRT) in Stage II-III breast cancer patients with negative lymph nodes (pN0) after neoadjuvant chemotherapy (NAC).PATIENTS AND MATERIALS:Of 1,054 breast cancer patients treated with NAC at our institution between 1990 and 2004, 134 had pN0 status after NAC and mastectomy. The demographic data, tumor characteristics, metastatic sites, and treatments were prospectively recorded. The effect of PMRT on locoregional recurrence-free survival and overall survival (OS) was evaluated by multivariate analysis, including known prognostic factors.RESULTS:Of the 134 eligible patients, 78 (58.2%) received PMRT and 56 (41.8%) did not. At a median follow-up time of 91.4 months, the 5-year locoregional recurrence-free survival and OS rate was 96.2% and 88.3% with PMRT and 92.5% and 94.3% without PMRT, respectively (p = NS). The corresponding values at 10 years were 96.2% and 77.2% with PMRT and 86.8% and 87.7% without PMRT (p = NS). On multivariate analysis, PMRT had no effect on either locoregional recurrence-free survival (hazard ratio, 0.37; 95% confidence interval, 0.09-1.61; p = .18) or OS (hazard ratio, 2.06; 95% confidence interval, 0.71-6; p = .18). This remained true in the subgroups of patients with clinical Stage II or Stage III disease at diagnosis. A trend was seen toward poorer OS among patients who had not had a pathologic complete in-breast tumor response after NAC (hazard ratio, 6.65; 95% confidence interval, 0.82-54.12; p = .076).CONCLUSIONS:The results from the present retrospective study showed no increase in the risk of distant metastasis, locoregional recurrence, or death when PMRT was omitted in breast cancer patients with pN0 status after NAC and mastectomy. Whether the omission of PMRT is acceptable for these patients should be addressed prospectively.

Purpose: To determine whether Ki67 expression and breast cancer subtypes could predict locoregional recurrence (LRR) and influence the postmastectomy radiotherapy (PMRT) decision in breast cancer (BC) patients with pathologic negative lymph nodes (pN0) after modified radical mastectomy (MRM).Methods and Materials: A total of 699 BC patients with pN0 status after MRM, treated between 2001 and 2008, were identified from a prospective database in a single institution. Tumors were classified by intrinsic molecular subtype as luminal A or B, HER2+, and triple-negative (TN) using estrogen, progesterone, and HER2 receptors. Multivariate Cox analysis was used to determine the risk of LRR associated with intrinsic subtypes and Ki67 expression, adjusting for known prognostic factors.Results: At a median follow-up of 56 months, 17 patients developed LRR. Five-year LRR-free survival and overall survival in the entire population were 97%, and 94.7%, respectively, with no difference between the PMRT (nZ191) and no-PMRT (n=508) subgroups. No constructed subtype was associated with an increased risk of LRR. Ki67 >20% was the only independent prognostic factor associated with increased LRR (hazard ratio, 4.18; 95% CI, 1.11-15.77; P<.0215). However, PMRT was not associated with better locoregional control in patients with proliferative tumors.Conclusions: Ki67 expression but not molecular subtypes are predictors of locoregional recurrence in breast cancer patients with negative lymph nodes after MRM. The benefit of adjuvant RT in patients with proliferative tumors should be further investigated in prospective studies. (C) 2012 Elsevier Inc.

Neoadjuvant chemotherapy (NAC) generally induces significant changes in the pathologic extent of disease. This potential down-staging challenges the standard indications of adjuvant radiation therapy. We assessed the utility of lymph node irradiation (LNI) in breast cancer (BC) patients with pathologic N0 status (pN0) after NAC and breast-conserving surgery (BCS).Among 1,054 BC patients treated with NAC in our institution between 1990 and 2004, 248 patients with clinical N0 or N1 to N2 lymph node status at diagnosis had pN0 status after NAC and BCS. Cox regression analysis was used to identify factors influencing locoregional recurrence-free survival (LRR-FS), disease-free survival (DFS), and overall survival (OS).All 248 patients underwent breast irradiation, and 158 patients (63.7%) also received LNI. With a median follow-up of 88 months, the 5-year LRR-FS and OS rates were respectively 89.4% and 88.7% with LNI and 86.2% and 92% without LNI (no significant difference). Survival was poorer among patients who did not have a pathologic complete primary tumor response (hazard ratio, 3.05; 95% confidence interval, 1.17-7.99) and in patients with N1 to N2 clinical status at diagnosis (hazard ratio = 2.24; 95% confidence interval, 1.15-4.36). LNI did not significantly affect survival.Relative to combined breast and local lymph node irradiation, isolated breast irradiation does not appear to be associated with a higher risk of locoregional relapse or death among cN0 to cN2 breast cancer patients with pN0 status after NAC. These results need to be confirmed in a prospective study.

BACKGROUND:Data from the Surveillance, Epidemiology, and End Results program and the European Concerted Action on survival and Care of Cancer Patients (EUROCARE) project indicate that about 6% of women newly diagnosed with breast cancer have stage IV disease, representing about 12 600 new cases per year in the United States in 2005. Historically, local therapy of the primary tumor in this setting has been aimed solely at symptom palliation. However, several studies suggest that surgical excision of the primary tumor can prolong these patients' survival.DISCUSSION:Exclusive locoregional radiotherapy is an alternative form of locoregional treatment in this setting and may represent an effective alternative to surgery in this setting. Here we discuss current issues regarding exclusive and adjuvant locoregional radiotherapy in breast cancer patients with synchronous metastases.SUMMARY:Several studies suggest that surgery or exclusive irradiation of the primary tumor is associated with better survival in breast cancer patients with synchronous metastases and that exclusive locoregional radiotherapy may represent an effective alternative to surgery in this setting. Results of well-designed prospective studies are needed to re-evaluate treatment of the primary breast tumor in patients with metastases at diagnosis, and to identify those patients who are most likely to benefit.