The "Strong Black Woman" Paradox: Insights from a Cohort of Black Breast and Ovarian Cancer Patients and Family Members.

BACKGROUND: The strong Black woman (SBW) stereotype can be seen as a positive view of Black women and even a standard to uphold. SBW internalization is a coping mechanism for dealing with racism and sexism. However, multiple recent studies have indicated that Black women in the modern era experience the paradox of SBW internalization having negative generational health effects. We interviewed Black women with a personal or relation diagnosis of breast or ovarian cancer to understand their views and experiences, including how the perception of the SBW stereotype influenced their care. METHODS: Qualitative semi-structured interviews were conducted via telephone or video conference and transcribed verbatim. Transcripts were qualitatively analyzed for iterative themes related to cancer care and psychosocial support. RESULTS: Sixty-one Black women completed an interview. Responses in multiple transcripts expressed experiences and sentiments consistent with the SBW stereotype, including the importance of maintaining the appearance of strength during their cancer journey. This resulted in some patients declining assistance during their cancer journeys. Participants shared a hope that there would be more willingness to show vulnerability so that future generations of cancer patients receive adequate support. Key aspects of the SBW stereotype were also cited as potential contributors to ongoing racial disparities in breast and ovarian cancer outcomes. CONCLUSION(S): Participants described a paradox of the SBW stereotype that is ultimately detrimental to health and wellbeing. Healthcare professionals and cancer researchers should be aware of this phenomenon to address cancer care more appropriately in Black women.

Dose delivery reproducibility for PBS proton treatment of breast cancer patients with and without mask immobilization.

BACKGROUND: Setup reproducibility of the tissue in the proton beam path is critical in maintaining the planned clinical target volume (CTV) dose coverage and sparing the organs at risk (OAR). In this study, we retrospectively evaluated radiation therapy dose reproducibility for proton pencil beam scanning (PBS) treatment of breast cancer patients with and without mask immobilization. METHODS: Ninety-four patients treated between January 2019 and September 2022 with at least one verification CT scan (V-CT) in treatment position were included for this study. All patients were set up with arms up using the Orfit AIO patient positioning system, with (69 patients) or without (25 patients) mask immobilization in chin, neck, shoulder, upper arm, and chest areas. Two to three enface or near enface single field uniform dose PBS beams were optimized using a commercial treatment planning system. Prescription doses were 25 to 60 GyRBE in 5 to 45 fractions. Treatment plan doses re-calculated on V-CTs were compared to the corresponding planned doses. Cumulative doses were also calculated for patients with at least 3 V-CTs by deform and weighted sum doses from V-CTs to corresponding P-CTs. CTV D95%, ipsilateral-lung V40%, esophagus D0.01cc, and heart mean dose were evaluated and reported as percentages of prescription doses. Differences were large dose deteriorations (LDD) if: (1) CTV (V-CT/cumulative D95%) - (Planned D95%) < - 5%; or (2) Ipsilateral-lung (V-CT/cumulative V40%) - (Planned V40%) > 5%; or (3) Esophagus (V-CT/cumulative D0.01cc) - (Planned D0.01cc) > 10%; or (4) Heart (V-CT/cumulative mean) - (Planned mean) > 1.5%. RESULTS: On average, V-CT/cumulative and planned CTV/OAR dose parameter differences were less than 2.2%/1.7% and 3.4%/3.7% for masked and maskless patients, respectively. The percentages of patients with at least one CTV or OAR V-CT/cumulative dose LDD were 20.3%/25.0% and 72.0%/54.0% for masked and maskless patients, respectively. CONCLUSIONS: On average, masked/maskless setups achieved delivered and planned CTV/OAR dose parameters agreed within 2.2%/3.7% for PBS treatment of breast cancer patients in this study. Maskless patients had higher rate of CTV/OAR LDDs compared to masked patients. Dosimetric differences large enough to raise clinical concerns in either group were able to be addressed with replannings.

Cancer Screening Experiences of Black Breast and Ovarian Cancer Patients and Family Members.

Black women experience disproportionate rates of advanced breast cancer diagnoses and mortality. Mammography is a proven and effective tool in early breast cancer detection and impacts patient outcomes. We interviewed Black women with a personal or family history of breast and/or ovarian cancer to understand their screening experiences and views. N = 61 individuals completed an interview. Interview transcripts were qualitatively analyzed for themes regarding clinical experiences, guideline adherence, and family sharing specific to Black women and their families. Most participants were college educated with active health insurance. Women in this cohort were knowledgeable about the benefits of mammography and described few barriers to adhering to annual mammogram guidelines. Some with first-degree family history were frustrated at insurance barriers to mammography before the age of 40. Participants were generally comfortable encouraging family and friends to receive mammograms and expressed a desire for a similar screening tool for ovarian cancer. However, they expressed concern that factors such as screening awareness and education, lack of insurance coverage, and other systematic barriers might prevent other Black women from receiving regular screening. Black women in this cohort reported high adherence to mammography guidelines, but expressed concern about cultural and financial barriers that may impact cancer screening access in the population more generally and contribute to disparities. Participants noted the importance of frank and open discussions of breast cancer screening in their families and community as a means of improving awareness.

Effects of Caffeine and Glucose Supplementation at Birth on Piglet Pre-Weaning Growth, Thermoregulation, and Survival.

Piglet pre-weaning mortality of approximately 15% represents a major economic and welfare concern to the pork industry. Supplementing neonatal piglets with glucose and/or caffeine has the potential to counteract hypoxic stress experienced during parturition and provide an energy substrate, which may improve survival to weaning. This study investigated the effects of caffeine and glucose supplementation at birth, in combination or separately, on piglet growth, thermoregulatory ability, and pre-weaning survival. At birth, 398 piglets were assigned to one of four oral treatments: saline, glucose (300 mg), caffeine (30 mg), or caffeine and glucose combined (30 mg caffeine and 300 mg glucose), dissolved in 6 mL saline. Piglets were tagged at birth, and time taken to reach the udder was recorded. Rectal temperatures were recorded at 4 h and 24 h post-partum, and body weights recorded at birth and 1, 3, and 18 days of age. Colostrum intake was estimated using birth and day 1 weights, and all pre-weaning mortalities were recorded. Treatments did not affect rectal temperature, colostrum intake, or pre-weaning mortality (p > 0.05). Low birth weight piglets (<0.9 kg) treated with caffeine and glucose had increased growth between 1 and 3 days of age (p < 0.05) compared to low birth weight piglets of other treatment groups. Caffeine supplementation alone reduced overall pre-weaning growth in low birth weight piglets compared to all other treatments (p = 0.05). Oral caffeine and glucose had no significant effect on piglet performance except in low birthweight piglets, where it improved growth in the first 3 days of life. Caffeine and glucose supplementation in combination may be beneficial for low birth weight piglets.

"There's not enough studies": Views of black breast and ovarian cancer patients on research participation.

BACKGROUND: Black breast and ovarian cancer patients are underrepresented in clinical cancer trials disproportionate to the prevalence of these cancers in Black females. Historically, lower enrollment has been attributed to individualized factors, including medical mistrust, but more recently structural factors, including systemic racism, have received additional scrutiny. We interviewed Black women with a personal or family history of breast and ovarian cancer to understand their views and experiences related to research participation. METHODS: Qualitative interviews were conducted via telephone or video conference and transcribed verbatim. Transcripts were qualitatively analyzed for iterative themes related to the offer and participation in cancer clinical trials and research studies, impact on cancer care, and recommendations to increase enrollment of Black patients. RESULTS: Sixty-one Black women completed an interview. Participants expressed that Black women are underrepresented in cancer research, and that this negatively impacted their own care. Many cited past historical abuses, including the Tuskegee syphilis trial, as a potential factor for lower enrollment but suggested that lower enrollment was better understood in the context of the entirety of their healthcare experiences, including present-day examples of patient mistreatment or dismissal. Participants suggested that proactive community engagement, transparency, and increased representation of Black research team members were strategies likely to foster trust and bolster research participation. CONCLUSION(S): Medical mistrust is only a partial factor in the lower participation of Black patients in cancer research. Researchers should implement the strategies identified by our participants to promote diverse enrollment and ensure that Black patients are included in future therapeutic advances.

A Multi-institutional Analysis of Trimodality Therapy for Esophageal Cancer in Elderly Patients.

PURPOSE: The therapeutic gains of neoadjuvant chemoradiation therapy (nCRT) followed by esophagectomy may be offset by increased incidences of morbidity and mortality in elderly patients. This study aimed to determine the impact of age on the risks and benefits of trimodality therapy for esophageal cancer. METHODS AND MATERIALS: We evaluated 571 patients treated with trimodality therapy at 3 high-volume tertiary cancer centers in the United States from 2007 to 2013. Two hundred two of 571 (35%) patients were 65 years or older at diagnosis and were classified as elderly. Toxicity and treatment parameters for the elderly cohort were compared with the younger cohort (ages 22-64) by the use of univariate (UVA) and multivariable (MVA) logistic analyses. Age was analyzed as a continuous hazard for cardiac and pulmonary toxicities. Survival was assessed by the Kaplan-Meier method. RESULTS: Elderly patients had a higher risk for postoperative cardiac toxicities (UVA: odds ratio [OR] 2.2, P<.001; MVA: OR 2.07, P=.004) and pulmonary toxicities (UVA: OR 2.0, P<.001; MVA: OR 2.03, P<.001) and a higher 90-day postoperative mortality (5.4% vs 2.2%, P=.049). Of the elderly patients, 6.9% experienced acute respiratory distress syndrome compared with 3.8% of younger patients (P=.11). Cardiac toxicity was linearly associated with age, and the relative risk increased by 61% for every additional decade of age. There was no difference in postoperative gastrointestinal or wound adverse events or in length of hospital stay. Grade 3+ acute toxicities from nCRT were infrequent and were clinically similar regardless of age. Freedom from esophageal cancer and disease-free survival were similar, but overall survival was significantly shorter in the elderly cohort. CONCLUSIONS: Elderly patients experienced more postoperative cardiopulmonary toxicities and mortality than did younger patients after nCRT. Compared with contemporary outcomes for trimodality therapy, both cohorts had acceptable rates for adverse events and disease control. For appropriately selected elderly patients, trimodality therapy for esophageal cancer is a reasonable treatment option.

Multi-institutional analysis of radiation modality use and postoperative outcomes of neoadjuvant chemoradiation for esophageal cancer.

PURPOSE: Relative radiation dose exposure to vital organs in the thorax could influence clinical outcomes in esophageal cancer (EC). We assessed whether the type of radiation therapy (RT) modality used was associated with postoperative outcomes after neoadjuvant chemoradiation (nCRT). PATIENTS AND METHODS: Contemporary data from 580 EC patients treated with nCRT at 3 academic institutions from 2007 to 2013 were reviewed. 3D conformal RT (3D), intensity modulated RT (IMRT) and proton beam therapy (PBT) were used for 214 (37%), 255 (44%), and 111 (19%) patients, respectively. Postoperative outcomes included pulmonary, GI, cardiac, wound healing complications, length of in-hospital stay (LOS), and 90-day postoperative mortality. Cox model fits, and log-rank tests both with and without Inverse Probability of treatment Weighting (IPW) were used to correct for bias due to non-randomization. RESULTS: RT modality was significantly associated with the incidence of pulmonary, cardiac and wound complications, which also bore out on multivariate analysis. Mean LOS was also significantly associated with treatment modality (13.2days for 3D (95%CI 11.7-14.7), 11.6days for IMRT (95%CI 10.9-12.7), and 9.3days for PBT (95%CI 8.2-10.3) (p<0.0001)). The 90day postoperative mortality rates were 4.2%, 4.3%, and 0.9%, respectively, for 3D, IMRT and PBT (p=0.264). CONCLUSIONS: Advanced RT technologies (IMRT and PBT) were associated with significantly reduced rate of postoperative complications and LOS compared to 3D, with PBT displaying the greatest benefit in a number of clinical endpoints. Ongoing prospective randomized trial will be needed to validate these results.

Utility of 18F-FDG PET for Predicting Histopathologic Response in Esophageal Carcinoma following Chemoradiation.

INTRODUCTION: For patients with esophageal cancer undergoing neoadjuvant chemoradiation (CRT) followed by surgical resection, complete histopathologic response (pCR) is associated with favorable overall survival (OS). The aim of this study was to evaluate the correlation between 18F-fluorodeoxyglucose positron emission tomography (FDG PET) response to neoadjuvant CRT and pCR. METHODS: Maximum standardized uptake values and standardized uptake ratios (SURs) were measured before and after CRT. SUR was normalized to liver uptake and mediastinal blood pool uptake. FDG PET complete response was defined as metabolic activity normalization to hepatic and blood pool activity. The correlation between FDG PET parameters and pCR was examined through logistic regression analyses. RESULTS: In total, 193 patients were monitored for a median of 3.6 years after initiation of CRT. Most tumors were adenocarcinoma (85%) and stage T3 (75%). Complete FDG PET response and pCR occurred in 27% and 34% of patients, respectively. Histologic findings, chemotherapy type, tumor stage, and radiation dose were not significantly associated with complete radiographic response. The rates of pCR in patients with and without radiographic complete response were 42% and 31% (p = 0.17), respectively. No predictive correlation was found between pCR and change in maximum standardized uptake value (p = 0.25), in SUR normalized to blood pool uptake (p = 0.20), or in SUR normalized to liver uptake (p = 0.15). The 5-year OS rate was 46% for patients with a complete FDG PET response versus 44% without a complete response (p = 0.78). The 5-year OS rate of patients who achieved pCR was 49% versus 43% for patients with residual tumor (p = 0.04). CONCLUSION: For patients with esophageal cancer who received neoadjuvant chemoradiation, pretreatment and posttreatment FDG PET parameters did not correlate with pCR or OS.

Failure patterns and survival outcomes in triple negative breast cancer (TNBC): a 15 year comparison of 448 non-Hispanic black and white women.

PURPOSE: Triple negative breast cancer (TNBC) is a distinct subtype of breast cancer with unique pathologic, molecular and clinical behavior. It occurs more frequently in young blacks and has been reported to have a shorter disease-free interval. We undertook this study to analyze the demographic characteristics, failure patterns, and survival outcomes in this disease. METHODS: A total of 448 non-Hispanic black and white women were identified over a 15 year period from 1996 to 2011. Demographic and clinical information including age, race, menopausal status, stage, tumor characteristics, and treatments were collected. Fisher's exact test and multivariable Cox regression were used to compare failure patterns and survival outcomes between races. RESULTS: 49 % (n = 223) were black. 59 % patients were between 41 and 60 years, with 18 % ≤40 years. 57 % were premenopausal and 89 % had grade 3 tumors. Stage II (47 %) was most frequent stage at diagnosis followed by stage III (28 %). 32 % had lymphovascular invasion. Adjusting for age, stage, and grade, there was no difference in survival outcomes (OS, DFS, LFFS, and DFFS) between the two races. 62 (14 %) patients failed locally either in ipsilateral breast or chest wall, and 19 (4 %) failed in the regional lymphatics. Lung (18 %) was the most frequent distant failure site with <12 % each failing in brain, liver and bones. CONCLUSION: Failure patterns and survival outcomes did not differ by race in this large collection of TNBC cases. Lung was the predominate site of distant failure followed by brain, bone, and liver. Few patients failed in the regional lymphatics.

Inflammatory TNBC Breast Cancer: Demography and Clinical Outcome in a Large Cohort of Patients With TNBC.

INTRODUCTION: Inflammatory breast cancer (IBC) is a rare and aggressive form of breast cancer with poor 5-year survival. Knowledge and information about IBC with the triple negative (TNBC) phenotype are limited. Here, we report the characteristics and outcome of inflammatory TNBC (I-TNBC) cancer cohorts from a large TNBC dataset. PATIENTS AND METHODS: After obtaining institutional review board approval, we collected information on 476 women with a diagnosis of TNBC from 1996 to 2011. Data on patient characteristics, tumor, and treatment were collected. Overall survival (OS) was computed from the date of diagnosis to the date of death or last follow-up. For disease-free survival (DFS), patients were scored if they failed. Statistical analysis was performed using SAS v9.3. RESULTS: A total of 34 (7%) patients were diagnosed with inflammatory TNBC. The median age was 52 years, and 56% were white. The median follow-up was 13 months (interquartile range, 2-126 months). Twenty-one percent (n = 7) presented with stage IV disease, while 91% had axillary nodal involvement. All but 2 (94%; n = 32) patients had neoadjuvant chemotherapy, with 6% (n = 2) achieving complete response. Twenty-one (62%) patients underwent mastectomy; 71% (n = 24) received radiation. The 2- and 5-year OS and DFS were 34%, 26% (vs. 65%, 46%) and 27%, 23% (vs. 53%, 40%), respectively, for I-TNBC and non-inflammatory stage III-IV TNBC. Compared with the non-inflammatory group, the 2- and 5-year OS (P < .0005) and DFS (P < .0073) were significantly inferior for I-TNBC. CONCLUSION: IBC with the triple negative phenotype is an aggressive disease with a significantly inferior outcome compared with non-inflammatory locally advanced TNBC. Newer strategies are required to improve survival outcome.

14-3-3ɛ/ζ Affects the stability of δ-catenin and regulates δ-catenin-induced dendrogenesis.

Accumulated evidence suggests that aberrant regulation of δ-catenin leads to pathological consequences such as mental retardation and cognitive dysfunction. This study revealed that 14-3-3ɛ/ζ stabilizes δ-catenin, with different binding regions involved in the interaction. Furthermore, the specific inhibition of the interaction of 14-3-3 with δ-catenin reduced levels of δ-catenin and significantly impaired the capacity of δ-catenin to induce dendritic branching in both NIH3T3 fibroblasts and primary hippocampal neurons. However, the S1094A δ-catenin mutant, which cannot interact with 14-3-3ζ, still retained the capability of inducing dendrogenesis. Taken together, these results elucidate the underlying events that regulate the stability of δ-catenin and δ-catenin-induced dendrogenesis.

Rho kinase inhibitor Y-27632 facilitates recovery from experimental peripheral neuropathy induced by anti-cancer drug cisplatin.

Chemotherapy drugs have neurotoxicity associated with treatment, which can become a dose-limiting problem when clinical presentation is severe. However, there is no effective therapy to circumvent the neurotoxicity of anti-cancer drug treatment. In this study, we utilized a newly designed mouse model of cisplatin-induced peripheral neuropathy to determine both the severity of neurotoxicity induced by drug treatment and the effectiveness of the Rho kinase inhibitor Y-27632 in post-treatment recovery. Sensory nerve conduction studies revealed a significant increase in mean distal (peak) latency with cisplatin treatment, indicating a deterioration of sensory nerve function. Also, hind paw touch sensitivity decreased steadily with increasing cumulative dose of cisplatin. Histological and immunohistochemical analyses of the sural nerve using neuronal marker protein gene product 9.5 (PGP 9.5) demonstrated abnormal nerve fiber morphology in cisplatin-treated mice. Remarkably, post-treatment with Y-27632 improved the sural nerve distal (peak) latency and sensory threshold to return to pre-treatment levels. Sural nerve histology worsened in the absence of Y-27632 during recovery. These studies suggest that Rho kinase inhibitor Y-27632 can initiate regeneration of damaged nerves following cisplatin treatment.

Methodology to obtain a mixed sural nerve recording in mice.

OBJECTIVE: There is an increasing interest in using mouse models for electrodiagnostic research. Studying transgenic mice with various pathologies adds to our knowledge of the natural history of a disease. It is imperative, however, to compare disease models with the appropriate control. DESIGN: For these animals to be used in electrodiagnostic research, reference values must be set. If reference values are not available, the validity of data are highly questionable. We propose a method of obtaining mixed nerve action potentials and collect reference values from the sural nerve of mice. RESULTS: The results were a mean peak latency of 1.74 msecs on the right and 1.89 msecs on the left. The mean amplitude was 17.0 microV on the left and 21.6 microV on the right. CONCLUSIONS: In future studies, these reference values can be useful tools in analysis of murine subjects.

Anti-cancer drug induced neurotoxicity and identification of Rho pathway signaling modulators as potential neuroprotectants.

Many chemotherapy drugs are known to cause significant clinical neurotoxicity, which can result in the early cessation of treatment. To identify and develop more effective means of neuroprotection it is important to understand the toxicity of these drugs at the molecular and cellular levels. In the present study, we examine the effects of paclitaxel (taxol), cisplatin, and methotrexate on primary rat neurons including hippocampal, cortical, and dorsal horn/dorsal root ganglion neuronal cultures. We found that all of these anti-cancer drugs induce substantial neurotoxicity evidenced by neurite degeneration. The neurons are capable of recovering after treatment withdrawal, but taxol exerts a biphasic effect that results in the collapse of processes days after treatment is withdrawn. After cisplatin and methotrexate treatment, we observed the degeneration of neuronal processes including the reduction of dendritic branching, length, and altered growth cone formation, indicating an abnormal arrangement of the actin cytoskeleton consistent with the involvement of Rho family small GTPases. Inhibiting RhoA downstream effector p160 ROCK/Rho kinase using Y-27632, or activating p75 neurotrophin receptor (p75 NTR) using non-peptide mimetic LM11A-31, were able to reverse the degeneration caused by cisplatin and methotrexate. Therefore, the neurotoxicity resulting from exposure to the anti-cancer drugs cisplatin and methotrexate can be alleviated by inhibiting Rho signaling pathway.

Delta-catenin-induced dendritic morphogenesis. An essential role of p190RhoGEF interaction through Akt1-mediated phosphorylation.

Delta-catenin was first identified through its interaction with Presenilin-1 and has been implicated in the regulation of dendrogenesis and cognitive function. However, the molecular mechanisms by which delta-catenin promotes dendritic morphogenesis were unclear. In this study, we demonstrated delta-catenin interaction with p190RhoGEF, and the importance of Akt1-mediated phosphorylation at Thr-454 residue of delta-catenin in this interaction. We have also found that delta-catenin overexpression decreased the binding between p190RhoGEF and RhoA, and significantly lowered the levels of GTP-RhoA but not those of GTP-Rac1 and -Cdc42. Delta-catenin T454A, a defective form in p190RhoGEF binding, did not decrease the binding between p190RhoGEF and RhoA. Delta-catenin T454A also did not lower GTP-RhoA levels and failed to induce dendrite-like process formation in NIH 3T3 fibroblasts. Furthermore, delta-catenin T454A significantly reduced the length and number of mature mushroom shaped spines in primary hippocampal neurons. These results highlight signaling events in the regulation of delta-catenin-induced dendrogenesis and spine morphogenesis.