Late-stage Breast Cancer Research Articles

Abstract PO-214: Delay time in the diagnosis and treatment of breast cancer in the California-Mexican Border

Abstract Introduction The delay in the diagnosis and treatment of breast cancer has a direct correlation with more advanced stages of the disease and a lower survival rate. These delays represent an urgent situation in developing countries due to their high prevalence. Objective This study aims to determine the time intervals in the diagnosis and treatment of patients with breast cancer in the main public hospital in the city of Tijuana, to identify the mechanisms through which the different population aspects and Hospitals affect the treatment of patients. Methods A descriptive, observational, and retrospective study was conducted, including patients with breast cancer diagnoses treated at the General Hospital Tijuana in the period from January 2019 to December 2019. We used data from the medical record, including dates, demographics, histopathological, and clinical data from each visit. Descriptive statistics were calculated in SPSS V27. Results A total of 154 patients with breast cancer were treated at the TGH during 2019. Of these, 97 patients included in the study, with an average age of 52.34 ± 9.14 years. The patient delay time was higher than three months in 61% of cases. The diagnosis delay time was between 5 and 13 weeks. Conclusion Mexican breast cancer patients, as Latinas in California, are more likely to exhibit late-stage breast cancers at the time of diagnosis and have lower survival rates. Mexico counts an opportunistic or non-organized mammography screening program, leading to considerable delays in the diagnosis of breast cancer, even in border cities near to the US (where some people use multiple healthcare systems). With this context, it is necessary to recommend the creation of an organized screening program based on a more exceptional ability to cover the target population and, therefore, greater effectiveness at the community, as well as more equitable access. Citation Format: Antonio Galindo-Castañeda, Martín Gonzalez-Corral, Luis Garcia-Armas, Oscar Egurrola-Terán, Luis Martínez-Gómez, Jorge Albert Guadarrama-Orozco. Delay time in the diagnosis and treatment of breast cancer in the California-Mexican Border [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-214.

Abstract PO-019: Delivering cancer prevention programs to Latinx and Korean immigrant communities in Los Angeles through community partnerships and a culturally adapted Cancer 101 Cancer Education and Training Program

Abstract Latinx and Korean immigrants (LKI) in the United States are less likely to incorporate cancer prevention practices (CPP), such as undergoing recommended cancer screening, as compared to white counterparts. Currently lacking are comprehensive, culturally tailored cancer prevention programs for LKI communities. One method of targeting these inequities and increasing CPP is the Cancer 101 Cancer Education and Training Program (CETP). CETP was developed in collaboration with American Indians and Alaska Natives (AI/AN) of Washington state as a cancer education resource to improve cancer knowledge, introduce preventative practices in a tribal setting, and increase survival rates for community members. Participants demonstrated a significant change in knowledge, attitudes and behaviors towards CPP. Given the need to improve CPP among LKI, and the success associated with the AI/AN CETP, the purpose of this study was to explore the impact on CPP through a culturally tailored CETP for LKI communities. We developed partnerships with the leadership of faith-based organizations (FBOs) and federally qualified health centers (FQHCs) serving predominantly LKI populations in neighborhoods with a high concentrations of late-stage cancer diagnoses. We referenced the Center for Disease Control’s (CDC) Community Guide for strategies of implementing tailored cancer programs. We administered our Spanish and Korean language Cancer and Healthcare in Los Angeles Survey (CHILAS) to FBO members to gather baseline awareness and perceptions of CPP. CHILAS data highlighted critical components that were used to modify the CETP. We translated the newly adapted CETP into Spanish and Korean and used it to conduct cancer prevention workshops and organize cancer screening events with our partnered FBOs and FQHCs. Our results include the development of partnerships with 15 FBOs where 12,000 predominantly LKI worshipped, in neighborhoods with a high incidence of late-stage breast cancer diagnoses. The results from 2,100 CHILAS and demographics were used to tailor the CETP for the communities of interest. Using the adapted CETP and strategies from the CDC’s Community Guide, 8,000 congregants received CPP information from the pulpit. Over 2 years, we delivered 63 cancer prevention workshops for 3,000 attendees, with 600 individuals participating in additional organized cancer screening programs and 35 volunteers and navigators trained. Furthermore, participants enrolled in community-based studies including the All of Us research project. Adaptation and application of the Cancer 101 CETP for LKI communities was an effective tool in disseminating cancer awareness and providing accessible cancer screening in high-need neighborhoods. Community partnerships shaped the Cancer 101 CETP to be a tangible and culturally sensitive resource for the communities of interest. We plan to sustain and expand this initiative through the creation of a comprehensive tool kit and training program for community leaders. Citation Format: Zul Surani, Bianca Luna, Dong Hee Kim, Ergueen Herrera, Loraine Escobedo, Robert Haile. Delivering cancer prevention programs to Latinx and Korean immigrant communities in Los Angeles through community partnerships and a culturally adapted Cancer 101 Cancer Education and Training Program [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-019.

Abstract 2622: Paclitaxel directed screening to identify novel anti-cancer drugs

Abstract Among the main challenges for the treatment of breast cancers is disease spread which is often coupled with resistance to chemotherapy. Furthermore, patients with late stage breast cancer go through first- and second-line therapies before they are candidates for new and/or experimental therapies. At such late stages, tumors that might have responded to new therapies have evolved to express multi-drug resistance - conceivably as a consequence of exposure to the initial therapies. Many mechanisms have been proposed to contribute to drug resistance, ranging from (but not limited to) reduced drug penetration and the activity of drug efflux pumps through to cell-adhesion mediated resistance to cell death. To address these challenges we sought to determine whether; a) tumor metastasis to different secondary sites generates location-specific tumor phenotypes that alter sensitivity to chemotherapy and, b) whether pre-treatment of tumors to conventional paclitaxel (PTX) chemotherapy alters their sensitivity to new drugs. First, we implanted 2x10(5) human luciferase-positive LM2-4 human breast cancer cells intracardiacally into SCID mice (n=15), which resulted 2 weeks later in the development of widespread metastases to the lungs, liver, spleen, and bone. For some of the mice bearing such metastases, PTX therapy (20mg/kg, i.p.) was administered 24 hours before the mice were euthanized. Next, we used RNA sequencing of isolated LM2-4 metastatic nodules to determine the impact of the location of metastases on transcriptome profiles (assessed by 40 million reads per each total RNA sample, followed by Principal Component Analysis). This study revealed that lung metastases have similar signatures to metastases to spleen and ovary, and to metastases in those organs following PTX therapy, while such transcriptome profiles are all quite distinct from those of metastases of the same tumor to the liver. These changes presumably are due to different cell-cell interactions of tumor cells in the different organs, as well as a consequence of the different microenvironments. Second, we set up a drug screen of LM2-4 breast cancer cells recovering from 1nM paclitaxel 24hr exposure in vitro to test for drugs that are toxic to the tumor cells following PTX pre-exposure. A screen of 30,000 small molecule drugs thus far identified 7 hit compounds. Our results serve a proof of concept that the location of metastases can alter the tumor cell phenotype, as can pre-treatment with PTX, and suggest that in some cases therapy ought to be tailored to the location of metastasis. Based on those results we identified drugs that may be useful in hampering the tumor cell recovery from PTX chemotherapy. Our work serves as a test ground for stratifying tumors based on their tissue of tumor spread, and provide a rationale for identifying drugs that hamper recovery of tumor cells to chemotherapy agents often incorporated into first and second line therapies, such as paclitaxel. Citation Format: Joseph Wingate, Diana Gonzalez Garcia, Karla Parra, Serina Batson, Joel Martinez, Ivan Sosa Ontiveros, Renato Aguilera, Armando Varela, Paloma Valenzuela, Marcos Armendariz, Chloe Clifton, Arlene Levario, Angelica Chacon, Andres Villagrana, Emmanuel Sanchez, Guido Bocci, Giulio Francia. Paclitaxel directed screening to identify novel anti-cancer drugs [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2622.

Abstract 1303: PRTN3, RGCC and SLCO4C1 are critical SOX9-regulated genes that control TNBC growth

Abstract Background: Breast cancer is the most common cancer in women, and about 12% U.S. women will develop invasive breast cancer over the lifetime. Triple-negative breast cancers (TNBCs) which lack expression of the estrogen and progesterone receptors and the HER2 protein.have a poor prognosis and are typically treated with chemotherapy. Our previous studies have demonstrated that SOX9 is essential for survival and metastasis of TNBCs via suppressing apoptosis and promoting epidermal to mesenchymal transition (EMT). Hypothesis: SOX9-regulated proteins control TNBC growth, and represent promising targets for the treatment of these potentially lethal breast cancers. Material and Methods: Several breast cancer datasets were used to analyze the association between overall survival and SOX9 expression. A doxycycline-inducible Cas9-CRISPR knockout or siRNA knockdown system was used to inhibit SOX9 in cells. RNA-Seq analysis was used to identify SOX9 downstream targets in TNBC cells (MDA MBA-232 and MDA MB-468 with SOX9 knockdown by siRNA transfection) or non-TNBC cells (MCF-7 with SOX9 overexpression by transfection of SOX9-expression plasmid), with support from MD Anderson's genomic biostatistics core. After identification of SOX9 downstream genes, we treated TNBC cells with or without siRNAs of these identified genes to evaluate their effect on TNBC growth. Cell growth was measured using an automated cell counting assay. Protein and mRNA levels were examined by western blotting and qRT-PCR assays. Significant genes are defined by using a false discovery rate (FDR) cut-off of 0.01 and log2 fold change of 2. Significant common genes are defined by using a FDR cut-off of 0.05 and log2 fold change of 1 among the cell lines. Data are presented as mean values ± SD. Statistical significance (p-values) was calculated using the Student's t-test unless otherwise indicated. Results: TNBCs and late stage breast cancers showed higher SOX9 expression compared to non-TNBCs and early stage breast cancers. Using SOX9 inhibited cells, we demonstrated that SOX9 is critical for TNBC cell growth in vitro and in vivo. Using mRNA-seq analysis, we identified downstream genes regulated by SOX9 in breast cancer. 340 genes and 843 genes were suppressed in MDA MB-231 and MDA MB-468 respectively upon SOX9 knockdown, while 250 genes were upregulated in MCF-7 cells upon SOX9 overexpression. Between MDA MB-231 and MDA MB-468 cell line, there were 301 common genes were down-regulated upon SOX9 knockdown. 38 genes were down-regulated upon SOX9 knockdown in TNBC cell lines, and up-regulated upon SOX9 overexpression in MCF-7 cells. Among them, the top 10 genes that show largest difference between TNBCs and MCF-7 cells are MIOX, LAMB2P1, SLCO4C1, RGCC, PRTN3, LINC00173, UCN, LOC100129, VPREB3 and CTF1 genes. We then investigated the effect of these SOX9 downstream targets on cell growth in vitro. Loss of RGCC, PRTN3, and SLCO4C1 reduced cell growth in MDA MBA-231, and MDA MB-468, while having minimal effect on the growth of MCF-7 cells. Conclusion: Our results demostrate that the SOX9-regulated genes RGCC, PRTN3, and SLC04C1 are required for TNBC growth. These genes are critical regulators of TNBC growth and are potential novel targets for the treatment of these aggressive breast cancers. Grant Support: These studies were supported by a Breast Cancer Research Foundation (BCRF) grant (PB). Citation Format: Yanxia Ma, William M. Tahaney, Jing Qian, Jamal Hill, Yun Zhan, Abhijit Mazumdar, Powel H. Brown. PRTN3, RGCC and SLCO4C1 are critical SOX9-regulated genes that control TNBC growth [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1303.

Impact of Phone-Call and Access-Enhancing Intervention on Mammography Uptake among Primary Care Patients at an Urban Safety-Net Hospital: A Randomized Controlled Study

Our urban safety-net hospital (SNH) has very low screening mammogram rates within its primary care clinics. Despite Commission on Cancer (CoC) accreditation, we see ~ 3 × more late-stage breast cancer diagnoses than other CoC sites across the country, and recently showed this to be strongly associated with lack of screening (Ahmadiyeh et al. in J Health Care Poor Underserved, in press, 2020). Here we study whether a two-step intervention (phone calls and assistance scheduling mammograms) increases uptake over usual care. Randomized controlled study of 890 women aged 50-65years who were due for biennial screening mammograms and who were established within one of five primary care clinics at an urban SNH. Each patient in the intervention group was called with overdue status (up to three times, voicemail left if needed) and offered assistance scheduling mammogram appointment. Mammography uptake at 3 and 6months was analyzed. Intervention significantly increased uptake compared with usual care at both timepoints (18% versus 6% at 3months; χ2 = 27.597, p < 0.0001; 23% versus 12% at 6months; χ2 = 18.0, p < 0.0001), with scheduling component driving effectiveness. Of those who were successfully contacted, uptake was significantly greater among those who scheduled appointments versus those who did not (47% versus 9%, χ2 = 95, p < 0.0001), and uptake was no different between contacted but not scheduled patients and usual care controls. Phone call with access-enhancing intervention (facilitating mammogram appointments) increased screening mammogram uptake among primary care patients in an urban safety-net setting and may be applicable to other urban SNHs around the country.

A Study on Acceptance of Mastectomy among Patients Diagnosed with Breast Cancer in Tertiary Hospital in Rivers State, Nigeria

Aim: This study was aimed at ascertaining the acceptance of mastectomy among patients who had breast cancer in a tertiary health facility in Port Harcourt over a 3 year period. Background: The pattern of presentation of breast cancer among Nigerian women is that of prolonged delay, symptomatic breast cancer, advanced breast cancer and poor long-term survival. Seventy percent of cases of breast cancer present in advanced stage. Materials and Methods: The reasons for delayed hospital presentation among patients with breast cancer was assessed using a hospital-based longitudinal study. Data were obtained using a structured proforma. Retrieved data were entered into Microsoft Excel and exported to United States CDC Epi- Info version 7 for statistical analysis. Results: Out of 61 patients counselled for mastectomy, 11 (18%) declined while 50 (82%) accepted. 35 patients with late breast cancer accepted mastectomy while 7patients in the same category did not. Among patients who accepted mastectomy, 15 (30%) were early while 35 (70%) were late breast cancer. Conclusion: The relatively high acceptance of mastectomy seen in this study is tied to patients presenting in late stage of breast cancer. More work is required to improve acceptance of the procedure at early stages of the disease.

High PKCλ expression is required for ALDH1-positive cancer stem cell function and indicates a poor clinical outcome in late-stage breast cancer patients.

Despite development of markers for identification of cancer stem cells, the mechanism underlying the survival and division of cancer stem cells in breast cancer remains unclear. Here we report that PKCλ expression was enriched in basal-like breast cancer, among breast cancer subtypes, and was correlated with ALDH1A3 expression (p = 0.016, χ2-test). Late stage breast cancer patients expressing PKCλhigh and ALDH1A3high had poorer disease-specific survival than those expressing PKCλlow and ALDH1A3low (p = 0.018, log rank test for Kaplan-Meier survival curves: hazard ratio 2.58, 95% CI 1.24–5.37, p = 0.011, multivariate Cox regression analysis). Functional inhibition of PKCλ through siRNA-mediated knockdown or CRISPR-Cas9-mediated knockout in ALDH1high MDA-MB 157 and MDA-MB 468 basal-like breast cancer cells led to increases in the numbers of trypan blue-positive and active-caspase 3-positive cells, as well as suppression of tumor-sphere formation and cell migration. Furthermore, the amount of CASP3 and PARP mRNA and the level of cleaved caspase-3 protein were enhanced in PKCλ-deficient ALDH1high cells. An Apoptosis inhibitor (z-VAD-FMK) suppressed the enhancement of cell death as well as the levels of cleaved caspase-3 protein in PKCλ deficient ALDH1high cells. It also altered the asymmetric/symmetric distribution ratio of ALDH1A3 protein. In addition, PKCλ knockdown led to increases in cellular ROS levels in ALDH1high cells. These results suggest that PKCλ is essential for cancer cell survival and migration, tumorigenesis, the asymmetric distribution of ALDH1A3 protein among cancer cells, and the maintenance of low ROS levels in ALDH1-positive breast cancer stem cells. This makes it a key contributor to the poorer prognosis seen in late-stage breast cancer patients.

Molecular Cytogenomic Characterization of the Murine Breast Cancer Cell Lines C-127I, EMT6/P and TA3 Hauschka.

Background: To test and introduce effective and less toxic breast cancer (BC) treatment strategies, animal models, including murine BC cell lines, are considered as perfect platforms. Strikingly, the knowledge on the genetic background of applied BC cell lines is often sparse though urgently necessary for their targeted and really justified application. Methods: In this study, we performed the first molecular cytogenetic characterization for three murine BC cell lines C-127I, EMT6/P and TA3 Hauschka. Besides fluorescence in situ hybridization-banding, array comparative genomic hybridization was also applied. Thus, overall, an in silico translation for the detected imbalances and chromosomal break events in the murine cell lines to the corresponding homologous imbalances in humans could be provided. The latter enabled a comparison of the murine cell line with human BC cytogenomics. Results: All three BC cell lines showed a rearranged karyotype at different stages of complexity, which can be interpreted carefully as reflectance of more or less advanced tumor stages. Conclusions: Accordingly, the C-127I cell line would represent the late stage BC while the cell lines EMT6/P and TA3 Hauschka would be models for the premalignant or early BC stage and an early or benign BC, respectively. With this cytogenomic information provided, these cell lines now can be applied really adequately in future research studies.

Patient Delay in Breast Cancer Diagnosis in Two Hospitals in Karachi, Pakistan: Preventive and Life-Saving Measures Needed

PURPOSEPatients with breast cancer in Pakistan commonly present with advanced disease. The objectives of this study were to evaluate the frequency and length of delays in seeking medical consultation and to assess the factors associated with them.METHODSFour hundred ninety-nine patients with newly diagnosed breast cancer were enrolled and interviewed over the period from February 2015 to August 2017. Information on sociodemographic factors, delay to medical consultation, stage of breast cancer at presentation, and tumor characteristics of the breast cancer were collected through face-to-face interviews and medical file review.RESULTSThe mean (standard deviation) age of patients with breast cancer was 48.0 (12.3) years. The mean (standard deviation) patient delay was 15.7 (25.9) months, with 55.2% of women detecting a breast lump but not seeking a medical consultation because of a lack of awareness about the significance of the lump. A total of 9.4% of the women decided to seek treatment initially using complementary and alternative medicine and traditional treatment; 9.4% of the women presented to a health care provider with a breast lump but no action was taken, and they were wrongly reassured about the lump without mammography or biopsy. For 26% of the women, the delay in presentation was caused by anxiety, fears and misconceptions regarding diagnosis and treatment, and other social factors including possible adverse effects on their relationship with their husband. Multivariable analysis showed a strong association of lower socioeconomic status (odds ratio [OR], 8.11 [95% CI, 2.46 to 26.69]) and late stage of breast cancer (OR, 4.83 [95% CI, 1.74 to 13.39]) with a patient delay of ≥ 3 months.CONCLUSIONPatient delay is a serious problem in Pakistan. There is an urgent need for intensive and comprehensive breast cancer education that addresses the myths and misconceptions related to breast cancer.

Estadio clínico tardío de cáncer de mama en el estado de Jalisco: magnitud y variaciones espaciotemporales

Los registros oficiales indican que, en Jalisco, México, el diagnóstico de cáncer de mama (Cama) en mujeres generalmente se realiza en fases avanzadas. Mediante datos georreferenciados de pacientes atendidas en un hospital de tercer nivel, se identificó la magnitud y variación espaciotemporal asociada a estadio clínico tardío (IIb, IIIa, IIIb, IIIc, IV) por municipio de residencia en el trienio 2013-2015. Los municipios Acatic, Atoyac y Zapotlanejo mostraron un incremento en la tasa estimada para este periodo, cuyo valor fue 44.6, 17.7 y 19.2 por cada cien mil mujeres mayores de 20 años, respectivamente. Además, el riesgo de estadio tardío se incrementó hasta cuatro veces según el municipio de residencia. Los resultados sugieren cuáles son los municipios donde se requiere mejorar la detección y diagnóstico de Cama, pero sobre todo garantizar un tratamiento oportuno para las mujeres que residen en los lugares de mayor riesgo, en apego a lineamientos establecidos en la NOM 041-SSA2-2011.

Tumour Size and Age in Early Versus Advanced Breast Cancer in Kuwait

Background: In the Middle East, Kuwait in particular, the rate of incidence of breast cancer has increased in the past recent years. The objective of this study was to obtain information about the relationship between tumour size and age in early vs. late stage breast cancer in Kuwaiti female patients. Method: A total of 259 files of Kuwaiti women with breast cancer in 2012 were obtained from the Kuwait Cancer Control Center Registry (KCCC). Data were obtained was evaluated and divided into different prognostic variables including patient characteristics, tumour size, tumour grade, TNM, laterality, and treatments. Results: The results showed that the mean age at diagnosis was 54± 11.2. The mean tumour size was 3.4± 2.1 cm. The most frequent stage observed throughout the study, according to TNM staging, was T2N0M0. One hundred and thirty cases were diagnosed as an early stage while sixty-eight cases were diagnosed as a late stage. Conclusion: Larger tumour size, high lymph node involvement and negative ER/PR receptors were observed more in the older age group compared with other studies. An early-stage disease can present with large tumour size >3 cm and late-stage disease can present with small tumour size. More studies are required to find the aetiologies. Women should be encouraged to do screening programs.

Abstract B127: Hispanic-White residential segregation and stage at diagnosis among female residents of Texas

Abstract Background: Breast cancer is the second leading cause of cancer-related deaths among females in the United States. Individual and neighborhood-level characteristics have been associated with breast cancer-related disparities. There is a paucity of literature about Hispanic-White residential segregation and stage at diagnosis of breast cancer, and whether residential segregation explains or moderates disparities in stage at diagnosis among Hispanics. Objectives: To explore whether Hispanic-White residential segregation is associated with late-stage breast cancer, and how it explains or moderates disparities in stage at diagnosis of breast cancer associated with Hispanic ethnicity. To explore whether health insurance coverage and census tract (CT) poverty level explains or moderates disparities associated with residential segregation. Methods: This is a retrospective data analysis using the Texas Cancer Registry. The analyses were restricted to non-Hispanic White and Hispanic females ages 18 and older diagnosed with breast cancer from 2007-2014, and who had only one primary tumor. The dependent variable was stage at diagnosis (early, late). The independent variables of interest were Hispanic-White residential segregation, race/ethnicity, type of insurance coverage and CT poverty level. Multilevel logistic regression models with individuals nested within CT were used for analyses. The final sample size was 80,149 individuals nested within 5,023 CT. Results: Hispanics were more likely to be diagnosed with late-stage breast cancer (OR=1.14; 95% CI=1.10-1.19). Increasing Hispanic-White residential segregation was associated with increased likelihood of late-stage diagnosis (OR=1.46; 95% CI=1.04-2.05). Type of health insurance explained some of the association between residential segregation and late-stage diagnosis. Residential segregation did not explain or moderate the association between Hispanic ethnicity and breast cancer stage at diagnosis. Predicted probability estimates showed that individuals who were uninsured or insured through Medicaid had similar probabilities of late-stage diagnosis. These disparities were worse for uninsured or Medicaid-insured Hispanic residents of highly segregated CTs. Conclusion: Hispanic-White residential segregation was associated with increased likelihood of late-stage breast cancer diagnosis. Interventions to increase early-stage breast cancer diagnosis are needed among residents of CTs with high residential segregation, especially among Medicaid insured and uninsured women. Interventions aimed at raising awareness of the association between Hispanic residential segregation and breast cancer stage at diagnosis among healthcare providers should be explored. Citation Format: Chinedum Ojinnaka. Hispanic-White residential segregation and stage at diagnosis among female residents of Texas [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 B127.

Abstract B122: Spatial analysis of ductal carcinoma in situ, locoregional, and distant metastatic breast cancer in North Carolina: Evidence for rural-urban disparities

Abstract Introduction: A projected 8870 women will be diagnosed with breast cancer in North Carolina (NC) in 2019, with 1390 estimated deaths. However, breast cancer is a heterogenous disease, and investigating total incidence may hide differences in how sociodemographic factors impact the development of different subtypes of breast cancer, in particular early vs late stage aggressive phenotypes. The objective of this study was to investigate geographical variation of breast cancer in NC by stage, and to determine stage-specific associations with race and urbanicity. Methods: Breast cancer patient data were obtained from the NC Central Cancer Registry (NC CCR 2009-14) and stratified by stage and comprised of patients diagnosed with ductal carcinoma in situ (7975; DCIS), locoregional (38,200; combined localized, regional, and regional with direct extensions), or distant metastatic breast cancer (2073) based on derived summary staging defined by the Surveillance, Epidemiology, and End Results (SEER) program. Spatial distribution maps were generated in ArcMap 10.5.1 software for age-standardized incidence ratios (SIRs) by county using the NCCCR patient dataset described and age distributions from 2014 U.S. Census population estimates. Additionally, we stratified patients by rural-urban continuum code (RUCC), condensed for our purposes into three rural-urban categories: metropolitan urbanized, non-metro urbanized, and less populated. Results: DCIS, locoregional, and distant metastatic breast cancers all exhibited patterns of significantly different SIRs than expected based on state incidence rates in the northeastern region of NC, while DCIS and total breast cancer also had significantly different SIRs in the western region. Approximately 70% of patients inhabited metropolitan urbanized areas regardless of breast cancer stage, however, the highest incidence rates for all stages were consistently observed in less populated counties. Mean age at diagnosis for all stages was slightly higher in less populated areas, for example 61.4yrs DCIS and 62.8yrs distant metastatic breast cancer, than metropolitan areas, at 60.0yrs DCIS and 60.1yrs distant metastatic breast cancer. A higher percentage of distant metastatic breast cancer patients (29%) versus locoregional or DCIS patients (both 20%) in the dataset self-identified as Black, a pattern consistent across rural-urban categories. The percentage of current smokers was also higher for distant metastatic breast cancer cases (10%) than locoregional (6%) or DCIS cases (5%) across all rural-urban categories. Conclusions: Our results indicate that breast cancer incidence in NC varies geospatially by stage with incidence often higher in less populated areas. There were also age, race, and smoking status disparities across rural-urban stratifications and in patients with late stage breast cancer, which have the potential to contribute to poor survival outcomes in high risk patients. Citation Format: Larisa M Gearhart-Serna, Kate Hoffman, Gayathri R Devi. Spatial analysis of ductal carcinoma in situ, locoregional, and distant metastatic breast cancer in North Carolina: Evidence for rural-urban 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 B122.

Abstract B111: Previous mammography experience as a predictor of mammography adherence among Hispanic/Latinas living in the Northeast United States

Abstract Background: Similar to non-Hispanic Black women, Hispanic/Latino women are more likely to be diagnosed with later-stage breast cancer than White women, and their mammography screening rates are lower than those of both groups. Although the literature generally focuses on women's behavior to identify predictors of mammography screening, we hypothesized that selected factors associated with prior mammography experience would impact future screening. From a large prospective study of cancer screening in Hispanic/Latinas living in the Northeast US, the purpose of this investigation was to determine how previous mammography experiences influenced adherence to mammography screening guidelines over 2.5-4 years of follow-up. Methods: Among 1,456 community-living Hispanic/Latinas ages 40 to 75 who had received at least one screening mammogram at the time of their baseline interview and consented to medical record review, we considered “mammography experience” in predicting annual screening mammography (documented screening mammogram within 12 months + 1-month lag time), in accordance with recommendations promulgated by the American Cancer Society (and widely followed) during the study period. Using multivariate logistic regression, we identified independent predictors of adherence to recommended guidelines after adjusting for core sociodemographic, access to care, and medical factors. Key predictors included characteristics of provider (gender, race/ethnicity), ease of communication and use of interpreters, being treated with respect, believing that mammography-related pain was minimized as much as possible, communication of results, and general satisfaction. Odds Ratios (ORs) and 95% Confidence Intervals (CI) are reported. Results: 54% of Hispanic/Latino women were adherent to recommended mammography screening guidelines over the follow up period. Although needing help with communicating with medical staff and not speaking the same language as the radiologic technologist were significant in bivariate analyses, only 2 “experience” variables were significant predictors after multivariate adjustment: 1) Women who were told the results of their earlier mammogram at the time of the test were less likely (OR= 0.80; 95% CI 0.63, 0.97) to adhere to annual screening guidelines compared to patients who were not told their results; and 2) compared to women who did not have a usual care provider, having a female doctor increased a woman's odds of being compliant with recommended guidelines (OR = 1.40, 95% CI 1.05, 1.77), whereas having a male usual care provider did not (OR = 0.86, 95% CI 1.05, 1.77). Conclusion: In a prospective look at adherence to mammography screening guidelines in Hispanic/Latino women living in the Northeast US, having a female usual care provider was associated with adherence to mammography screening guidelines. This finding requires further study, particularly in this subpopulation. Citation Format: Beth A. Jones, Krisha Patel, Inginia Genao, Marcella Nunez-Smith, Claus Elizabeth, Hosanna Soler-Vila, Markowski Justin. Previous mammography experience as a predictor of mammography adherence among Hispanic/Latinas living in the Northeast United States [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr B111.

Abstract C107: Surveillance mammography and Ffllow-up care in Black and White breast cancer survivors

Abstract Purpose Adherence to surveillance mammography following a breast cancer (BC) diagnosis is a pivotal way to mitigate late stage BC recurrences and ultimately mortality for breast cancer survivors (BCS); yet there are stark racial disparities in adherence to routine follow-up care post-treatment. This study seeks to address disproportionately low adherence rates to breast surveillance guidelines among Black BCS, when compared to White counterparts, by evaluating environmental, social, and psychosocial factors (e.g., attitudes, knowledge) that may influence survivor’s adherence to surveillance mammography. Methods The mixed method designs involve recruiting and screening Black and White BCS concurrently through an epidemiologic survey and online focus groups via social media platforms (e.g., Facebook, Instagram Quora reddit). Data from survey will employ descriptive and bivariate statistics to assess the relationship between environmental, social and psychosocial factors with surveillance mammography and follow-up care. Guided by the Integrated Behavioral Prediction conceptual framework, thematic and linguistic analyses will be conducted for the online focus group text data to find emergent themes and subthemes. Results This study will provide preliminary results highlighting primary factors (e.g., barriers, facilitators) that influence adherence, by race. Our findings will focus on associated factors for women’s adherence to surveillance mammography, to inform survivorship guidelines and clinical practice. Conclusion Knowledge gained from the study will provide clinicians crucial points of communication; identify important modifiable factors needed in survivorship behavioral interventions, and inform strategies for screening messages. Furthermore, understanding factors that support adherence to surveillance mammography among Black BCS will uncover novel approaches to educate and reach this group in efforts to reduce survival disparities. Citation Format: Megan C Edmonds, Sunny J Kim, Vanessa B Sheppard. Surveillance mammography and Ffllow-up care in Black and White breast cancer survivors [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 C107.

Taking Care of Yourself and Your Risk for Breast Cancer (CUIDARSE): A Randomized Controlled Trial of a Health Communication Intervention for Latinas

Latinas in the United States are more likely to be diagnosed with late-stage breast cancer (BC) compared to non-Latinas. Literacy-appropriate and culturally sensitive cancer communication interventions can help address existing racial/ethnic BC disparities. We formatively developed a new BC prevention brochure for Spanish-speaking Latinas (≥35 years). Eligible women (n = 240) from a large public hospital in California were randomly assigned to one of three study arms: Group 1 received the new brochure, Group 2 included a community health worker (CHW) who delivered the new brochure's content, and a control group received a standard educational brochure. Participants completed three surveys (baseline, postintervention, 3-month follow-up) with a 100% completion rate for the first two surveys and 80.4% completion after 3 months. We assessed the difference in outcomes for BC risk knowledge, perceived BC susceptibility, and BC information self-efficacy between groups. Participant mean age was 52.3 years, and 82.1% reported low English proficiency. Mean knowledge scores increased and perceived BC susceptibility improved for all groups (p ≤ .05), yet treatment effects were not significant between groups for these outcomes. BC information self-efficacy also increased from baseline to postintervention for all groups to >80%. After 3 months, only Group 2 and the control group retained their increases and treatment effects were significant only for Group 2 compared to other groups in unadjusted and adjusted models. A CHW-delivered intervention may be more effective in improving BC information self-efficacy among Latinas compared to print material alone. More research is needed to examine the efficacy of CHW-delivered interventions.

Prognostic and predictive effects of circulating and disseminated tumor cells in breast cancer: A National Cancer Database (NCDB) analysis.

1029 Background: Alongside other biomarkers, circulating tumor cells (CTCs) and disseminated tumor cells (DTCs) could contribute to our growing understanding of the breast cancer (BC) “liquid biopsy”. This study evaluated 1) clinicopathologic factors associated with CTCs and DTCs, 2) the prognostic value of CTCs and DTCs by disease stage, 3), the efficacy of chemotherapy by CTC and DTC status. Methods: We conducted a retrospective analysis of BC using the 2004-2016 National Cancer Database (NCDB). The NCDB defines CTCs as isolated tumor cells (ITCs) found in the blood (using assays such as reverse transcriptase polymerase chain reaction or immunohistochemistry) distant from the breast. DTCs are ITCs found in the bone marrow or other non-regional tissues. To evaluate variables associated with CTCs or DTCs, we used chi-squared and Wilcoxon rank-sum tests (univariate), followed by multivariate logistic regression. Consequently, we included CTC or DTC status in a multivariate, stage-by-stage Cox regression analysis for overall survival (OS). After adjusting for receptor status and staging, we used the Kaplan-Meier method to explore chemotherapy efficacy in CTC- or DTC-positive vs. CTC- or DTC-negative subsets. Results: 4,846 cases reported CTC-status, 1,454 (21.1%) of which were positive. 4,993 cases reported DTC-status, 1,400 (20.3%) of which were positive. Factors associated with positive CTC status were HER2-positivity, progesterone receptor-positivity, lobular histology and N-staging. Factors associated with positive DTC status were being White, HER2-positivity, lobular histology and N-staging. Positive CTC-status was associated with poor OS overall in late-stage (III and IV) (HR 1.477, 95% CI: 1.129-1.931, p = 0.004) but not early-stage BC (0, I, II) (p = 0.110) disease. DTC-status was not associated with OS in early-stage or late-stage subsets. In hormone receptor (HR)-positive disease, chemotherapy was associated with better OS when CTC-status was also positive both in early-stage (p = 0.003) and late-stage (p = 0.023) disease. In a subset of the same BC subtype with negative CTC-status, however, chemotherapy conferred no survival benefit (p = 0.638 for early-stage, p = 0.501 for late-stage). DTC status was not a significant predictor of chemotherapy efficacy in early or late-stage, HR+ disease. Conclusions: This study suggests that CTC-status is a stronger prognostic factor at later stages of BC; yet it can also help guide management of early-stage disease as it appears predictive for chemotherapy benefit.

Identification of a regulatory Vδ1 gamma delta T cell subpopulation expressing CD73 in human breast cancer.

γδ T cells contribute to the immune response against many cancers, notably through their powerful effector functions that lead to the elimination of tumor cells and the recruitment of other immune cells. However, their presence in the tumor microenvironment has been associated with poor prognosis in breast, colon, and pancreatic cancer, suggesting that γδ T cells may also display pro-tumor activities. Here, we identified in blood from healthy donors a subpopulation of Vδ1T cells that represents around 20% of the whole Vδ1 population, expresses CD73, and displays immunosuppressive phenotype and functions (i.e., production of immunosuppressive molecules, such as IL-10, adenosine, and the chemotactic factor IL-8, and inhibition of αβT cell proliferation). We then found that in human breast tumors, γδ T cells were present particularly in late stage breast cancer samples, and that ∼20% of tumor-infiltrating γδ T cells expressed CD73. Taken together, these results suggest that regulatory γδ T cells are present in the breast cancer microenvironment and may display immunosuppressive functions through the production of immunosuppressive molecules, such as IL-10, IL-8, and adenosine, thus promoting tumor growth.

LncRNA GAS5 affects epithelial-mesenchymal transition and invasion of breast cancer cells by regulating miR-216b.

To study the mechanism of lncRNA GAS5 affecting epithelial-mesenchymal transition and invasion of breast cancer cells by regulating miR-216b. Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to detect the expressions of GAS5 and miR-216b in breast cancer and paracancerous tissues. The relationship between GAS5 and clinicopathological parameters of breast cancer patients was analyzed. The Dual-Luciferase reporter gene was used to detect the interaction between GAS5 and miR-216b and the transwell invasion assay was used to detect the invasive ability of lung cancer cells after GAS5 inhibition. Apoptosis assay was used to detect the apoptosis of breast cancer cells after GAS5 inhibition. Western blotting and immunofluorescence staining were used to detect the inhibition of GAS5 epithelial-mesenchymal transition. Compared with paracancerous tissues, in breast cancer tissues, the expression of GAS5 was increased and the expression of miR-216b was decreased. As the patients enter the later stages of breast cancer, the expression level of GAS5 in breast cancer patients was significantly elevated. The expression of GAS5 in the tissues with lymph node metastasis of breast cancer was markedly increased. The inhibition of GAS5 can promote the apoptosis of breast cancer cells; GAS5 can specifically bind to the 3' UTR of miR-216b. The expression of GAS5 inhibited the expression of E-cadherin in breast cancer cells and significantly upregulated N-cadherin, which has been confirmed by immunofluorescence staining experiments. GAS5 plays an important role in the development of breast cancer. GAS5 can target on miR-216b to regulate the biological behavior and epithelial-mesenchymal transition of breast cancer cells.

A Mini-review on HER2 Positive Breast Cancer and its Metastasis: Resistance and Treatment Strategies

HER2 positive breast cancer is an aggressive breast cancer followed by brain metastasis, which emerges at the later stage of breast cancer or after a few years of treatment. HER2+ breast cancer brain metastasis is a complex fatal disease with short survival and resistance to first-line drugs such as Trastuzumab, lapatinib, etc. The resistance can be due to the upregulation/downregulation of various proteins of downstream pathways mainly PI3K/AKT pathway and MAPK pathway. In addition, the Blood-brain Barrier (BBB) and Blood Tumor Barrier (BTB) also hinder the delivery to brain metastases. Thus controlling the altered proteins of the downstream pathway can be a targeted approach to control breast cancer and its brain metastasis. At the same time, targeted delivery to metastatic sites can give a synergistic effect in controlling brain metastasis and increasing the survival period. Various type of targeted nanocarriers such as single, dual, or multitargeted, pH specific, or stimuli sensitive nanocarriers can be employed for providing specific delivery to HER2+ cancer cells. Furthermore, combinations such as Trastuzumab with tyrosine kinase inhibitors (lapatinib, neratinib, afatinib), chemotherapeutic drugs (paclitaxel, doxorubicin, capecitabine), or some natural compounds (curcumin, Lycorine, berberine) with anti-apoptotic activity can provide an additional effect in the management of HER2 positive breast cancer and its metastasis.