Mobilizing cross-disciplinary teams to advance translational research using design thinking methods.

Funding agencies are increasingly seeking team-based approaches to tackling complex research questions, but there is a need to mobilize translational teams and create shared visions and strategic action plans long before specific funding opportunities are considered or even released. This is particularly evident for teams who want to pursue large-scale grants, where cross-disciplinary synergy is often required. In response, we created Research Jams, which are engaging yet structured brainstorming sessions that bring together groups for the first time to collectively generate novel research ideas, critically map the future of initiatives, prioritize opportunities and next steps, and build community. Research Jams leveraged various aspects of design thinking, including divergence and convergence, visual thinking, and amplifying diversity. We piloted seven Research Jams for a collective 129 researchers, staff, and partners across 50 University of Michigan units and external organizations. Feedback was overwhelmingly positive, with the vast majority of survey respondents indicating that the sessions were helpful for surfacing shared ideas or visions and that opportunities emerged they would like to pursue. Research Jams were ideal for cross-disciplinary groups who wanted to collaboratively ideate and strategize around complex problems in translational research. Importantly, these models have the potential for implementation with groups in any disciplinary domain who want to spur collaborations to address challenging problems. Our ultimate goal is for Research Jams to be the first intervention within a comprehensive support pathway that extends from early brainstorming all the way to grant submission.

Multiethnic PDX models predict a possible immune signature associated with TNBC of African ancestry.

PURPOSE: Triple-negative breast cancer (TNBC) is an aggressive subtype most prevalent among women of Western Sub-Saharan African ancestry. It accounts for 15-25% of African American (AA) breast cancers (BC) and up to 80% of Ghanaian breast cancers, thus contributing to outcome disparities in BC for black women. The aggressive biology of TNBC has been shown to be regulated partially by breast cancer stem cells (BCSC) which mediate tumor recurrence and metastasis and are more abundant in African breast tumors. METHODS: We studied the biological differences between TNBC in women with African ancestry and those of Caucasian women by comparing the gene expression of the BCSC. From low-passage patient derived xenografts (PDX) from Ghanaian (GH), AA, and Caucasian American (CA) TNBCs, we sorted for and sequenced the stem cell populations and analyzed for differential gene enrichment. RESULTS: In our cohort of TNBC tumors, we observed that the ALDH expressing stem cells display distinct ethnic specific gene expression patterns, with the largest difference existing between the GH and AA ALDH+ cells. Furthermore, the tumors from the women of African ancestry [GH/AA] had ALDH stem cell (SC) enrichment for expression of immune related genes and processes. Among the significantly upregulated genes were CD274 (PD-L1), CXCR9, CXCR10 and IFI27, which could serve as potential drug targets. CONCLUSIONS: Further exploration of the role of immune regulated genes and biological processes in BCSC may offer insight into developing novel approaches to treating TNBC to help ameliorate survival disparities in women with African ancestry.

Androgen Receptor and ALDH1 Expression Among Internationally Diverse Patient Populations.

PURPOSE: Population-based incidence rates of breast cancers that are negative for estrogen receptor (ER), progesterone receptor, and human epidermal growth factor receptor 2/ neu (triple-negative breast cancer [TNBC]) are higher among African American (AA) compared with white American (WA) women, and TNBC prevalence is elevated among selected populations of African patients. The extent to which TNBC risk is related to East African versus West African ancestry, and whether these associations extend to expression of other biomarkers, is uncertain. METHODS: We used immunohistochemistry to evaluate estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2/ neu, androgen receptor and aldehyde dehydrogenase 1 (ALDH1) expression among WA (n = 153), AA (n = 76), Ethiopian (Eth)/East African (n = 90), and Ghanaian (Gh)/West African (n = 286) patients with breast cancer through an institutional review board-approved international research program. RESULTS: Mean age at diagnosis was 43, 49, 60, and 57 years for the Eth, Gh, AA, and WA patients, respectively. TNBC frequency was higher for AA and Gh patients (41% and 54%, respectively) compared with WA and Eth patients (23% and 15%, respectively; P < .001) Frequency of ALDH1 positivity was higher for AA and Gh patients (32% and 36%, respectively) compared with WA and Eth patients (23% and 17%, respectively; P = .007). Significant differences were observed for distribution of androgen receptor positivity: 71%, 55%, 42%, and 50% for the WA, AA, Gh, and Eth patients, respectively ( P = .008). CONCLUSION: Extent of African ancestry seems to be associated with particular breast cancer phenotypes. West African ancestry correlates with increased risk of TNBC and breast cancers that are positive for ALDH1.

Comparative Analysis of Breast Cancer Phenotypes in African American, White American, and West Versus East African patients: Correlation Between African Ancestry and Triple-Negative Breast Cancer.

INTRODUCTION: Triple-negative breast cancer (TNBC) is more common among African American (AA) and western sub-Saharan African breast cancer (BC) patients compared with White/Caucasian Americans (WA) and Europeans. Little is known about TNBC in east Africa. METHODS: Invasive BC diagnosed 1998-2014 were evaluated: WA and AA patients from the Henry Ford Health System in Detroit, Michigan; Ghanaian/west Africans from the Komfo Anokye Teaching Hospital in Kumasi, Ghana; and Ethiopian/east Africans from the St. Paul's Hospital Millennium Medical College in Addis Ababa, Ethiopia. Histopathology and immunohistochemistry for estrogen receptor (ER), progesterone receptor (PR), and HER2/neu expression was performed in Michigan on formalin-fixed, paraffin-embedded samples from all cases. RESULTS: A total of 234 Ghanaian (mean age 49 years), 94 Ethiopian (mean age 43 years), 272 AA (mean age 60 years), and 321 WA (mean age 62 years; p = 0.001) patients were compared. ER-negative and TNBC were more common among Ghanaian and AA compared with WA and Ethiopian cases (frequency ER-negativity 71.1 and 37.1 % vs. 19.8 and 28.6 % respectively, p < 0.0001; frequency TNBC 53.2 and 29.8 % vs. 15.5 and 15.0 %, respectively, p < 0.0001). Among patients younger than 50 years, prevalence of TNBC remained highest among Ghanaians (50.8 %) and AA (34.3 %) compared with WA and Ethiopians (approximately 16 % in each; p = 0.0002). CONCLUSIONS: This study confirms an association between TNBC and West African ancestry; TNBC frequency among AA patients is intermediate between WA and Ghanaian/West Africans consistent with genetic admixture following the west Africa-based trans-Atlantic slave trade. TNBC frequency was low among Ethiopians/East Africans; this may reflect less shared ancestry between AA and Ethiopians.

Breast Cancer and African Ancestry: Lessons Learned at the 10-Year Anniversary of the Ghana-Michigan Research Partnership and International Breast Registry.

Women with African ancestry in western, sub-Saharan Africa and in the United States represent a population subset facing an increased risk of being diagnosed with biologically aggressive phenotypes of breast cancer that are negative for the estrogen receptor, the progesterone receptor, and the HER2/neu marker. These tumors are commonly referred to as triple-negative breast cancer. Disparities in breast cancer incidence and outcome related to racial or ethnic identity motivated the establishment of the International Breast Registry, on the basis of partnerships between the Komfo Anokye Teaching Hospital in Kumasi, Ghana, the University of Michigan Comprehensive Cancer Center in Ann Arbor, Michigan, and the Henry Ford Health System in Detroit, Michigan. This research collaborative has featured educational training programs as well as scientific investigations related to the comparative biology of breast cancer in Ghanaian African, African American, and white/European American patients. Currently, the International Breast Registry has expanded to include African American patients throughout the United States by partnering with the Sisters Network (a national African American breast cancer survivors' organization) and additional sites in Ghana (representing West Africa) as well as Ethiopia (representing East Africa). Its activities are now coordinated through the Henry Ford Health System International Center for the Study of Breast Cancer Subtypes. Herein, we review the history and results of this international program at its 10-year anniversary.

Factors associated with receipt of breast cancer adjuvant chemotherapy in a diverse population-based sample.

PURPOSE: Disparities in receipt of adjuvant chemotherapy may contribute to higher breast cancer fatality rates among black and Hispanic women compared with non-Hispanic whites. We investigated factors associated with receipt of chemotherapy in a diverse population-based sample. PATIENTS AND METHODS: Women diagnosed with breast cancer between August 2005 and May 2007 (N = 3,252) and reported to the Detroit, Michigan, or Los Angeles County Surveillance, Epidemiology, and End Results (SEER) registry were recruited to complete a survey. Multivariable analyses examined factors associated with chemotherapy receipt. RESULTS: The survey was sent to 3,133 patients; 2,290 completed a survey (73.1%), and 1,403 of these patients were included in the analytic sample. In multivariable models, disease characteristics were significantly associated with the likelihood of receiving chemotherapy. Low-acculturated Hispanics were more likely to receive chemotherapy than non-Hispanic whites (odds ratio [OR], 2.00; 95% CI, 1.31 to 3.04), as were high-acculturated Hispanics (OR, 1.43; 95% CI, 1.03 to 1.98). Black women were less likely to receive chemotherapy than non-Hispanic whites, but the difference was not significant (OR, 0.83; 95% CI, 0.64 to 1.08). Increasing age (even in women age < 50 years) and Medicaid insurance were associated with lower rates of chemotherapy receipt. CONCLUSION: In this population-based sample, disease characteristics were strongly associated with receipt of chemotherapy, indicating that clinical benefit guides most treatment decisions. We found no compelling evidence that black women and Hispanics receive chemotherapy at lower rates. Interventions that address chemotherapy use rates according to age and insurance status may improve quality of systemic treatment.

Patterns and correlates of postmastectomy breast reconstruction by U.S. Plastic surgeons: results from a national survey.

BACKGROUND: : Concern exists that plastic surgeons have lost interest in postmastectomy breast reconstruction, which has helped enable the oncoplastic movement by general surgery. The authors evaluated patterns and correlates of postmastectomy breast reconstruction among U.S. plastic surgeons. METHODS: A survey was mailed to a national sample of 500 randomly selected members of the American Society of Plastic Surgeons (73 percent of eligible subjects responded; n = 312). The dependent variable was surgeon's annual volume of breast reconstructions (dichotomized into >50 and ≤ 50 cases per year). Logistic regression was used to evaluate factors associated with annual volume, including surgeon demographic and practice characteristics, community support for reconstruction, and surgeons' attitudes toward insurance reimbursement. RESULTS: Ninety percent found doing breast reconstruction personally rewarding, and nearly all enjoyed the technical aspects of the procedure. The majority of surgeons, however, were low-volume to moderate-volume providers, and 43 percent reported decreasing their volume over the past year due to poor reimbursement. Resident availability was significantly associated with high volume (odds ratio, 4.93; 95 percent CI, 2.31 to 10.49); years in practice and perceived financial constraints by third-party payers were inversely associated with high volume (>20 years compared with ≤ 10 years: odds ratio, 0.23. 95 percent CI, 0.07 to 0.71; odds ratio, 0.22, 95 percent CI, 0.08 to 0.56, respectively). CONCLUSIONS: Although plastic surgeons find breast reconstruction professionally rewarding, many are decreasing their practice. Factors associated with low volume include lack of resident coverage and perceived poor reimbursement. Advocacy efforts must be directed at facilitating reconstructive services for this highly demanding patient population.

Receipt of delayed breast reconstruction after mastectomy: do women revisit the decision?

BACKGROUND: Postmastectomy breast reconstruction is an important component of breast cancer care, but few receive it at the time of the mastectomy. Virtually nothing is known about receipt of reconstruction after initial cancer therapy and why treatment might be delayed. MATERIALS AND METHODS: A 5-year follow-up survey was mailed to a population-based cohort of mastectomy-treated breast cancer patients who were initially surveyed at time of diagnosis in 2002 and reported to the Los Angeles and Detroit SEER registries (N = 645, response rate 60%). Outcomes were receipt of reconstruction (immediate [IR], delayed [DR], or none) and patient appraisal of their treatment decisions. RESULTS: About one-third (35.9%) had IR, 11.5% had DR, and 52.6% had no reconstruction. One-third delayed reconstruction because they focused more on other cancer interventions, and nearly half were concerned about surgical complications and interference with cancer surveillance. Two-thirds of those with no reconstruction said that the procedure was not important to them. A large proportion of all patients were satisfied with their reconstruction decision-making (89.4% IR, 78.4% DR, 80.4% no reconstruction, P = NS). However, only 59.3% of those with no reconstruction felt that they were adequately informed about their reconstructive options (vs 82.7% IR and 78.4% DR, P < .01). CONCLUSIONS: There was modest uptake of breast reconstruction after initial cancer treatment. Factors associated with delayed reconstruction were primarily related to uncertainty about the procedure, concern about cancer surveillance, and low priority. Those without reconstruction demonstrated significant informational needs, which should be addressed with future research efforts.

Plastic surgeons' satisfaction with work-life balance: results from a national survey.

BACKGROUND: Plastic surgery demographics are transforming, with a greater proportion of women and younger physicians who desire balance between their career and personal lives compared with previous generations. The authors' purpose was to describe the patterns and correlates of satisfaction with work-life balance among U.S. plastic surgeons. METHODS: A self-administered survey was mailed to a random sample of American Society of Plastic Surgeons members (n = 708; 71 percent response rate). The primary outcome was satisfaction with work-life balance. Independent variables consisted of surgeon sociodemographic and professional characteristics. Logistic regression was used to evaluate correlates of satisfaction with work-life balance. RESULTS: Overall, over three-fourths of respondents were satisfied with their career; however, only half were satisfied with their time management between career and personal responsibilities. Factors independently associated with diminished satisfaction with work-life balance were being female (odds ratio = 0.63; 95 percent CI, 0.42 to 0.95), working more than 60 hours per week (versus < 60 hours per week; odds ratio = 0.44; 95 percent CI, 0.28 to 0.72), having emergency room call responsibilities (versus no emergency room call, odds ratio = 0.42; 95 percent CI, 0.27 to 0.67), and having a primarily reconstructive practice (versus primarily aesthetic practice; odds ratio = 0.53; 95 percent CI, 0.30 to 0.93). CONCLUSIONS: While generational differences were minimal, surgeons who were female, worked longer hours, and had emergency room call responsibilities and primarily reconstructive practices were significantly less satisfied with their work-life balance.