Mosquito control exposures and breast cancer risk: analysis of 1071 cases and 2096 controls from the Ghana Breast Health Study.

Epidemiologic data on insecticide exposures and breast cancer risk are inconclusive and mostly from high-income countries. Using data from 1071 invasive pathologically confirmed breast cancer cases and 2096 controls from the Ghana Breast Health Study conducted from 2013 to 2015, we investigated associations with mosquito control products to reduce the spread of mosquito-borne diseases, such as malaria. These mosquito control products were insecticide-treated nets, mosquito coils, repellent room sprays, and skin creams for personal protection against mosquitos. Multivariable and polytomous logistic regression models were used to estimate odds ratios (ORadj) and 95% confidence intervals (CI) with breast cancer risk-adjusted for potential confounders and known risk factors. Among controls, the reported use of mosquito control products were mosquito coils (65%), followed by insecticide-treated nets (56%), repellent room sprays (53%), and repellent skin creams (15%). Compared to a referent group of participants unexposed to mosquito control products, there was no significant association between breast cancer risk and mosquito coils. There was an association in breast cancer risk with reported use of insecticide-treated nets; however, that association was weak and not statistically significant. Participants who reported using repellent sprays were at elevated risks compared to women who did not use any mosquito control products, even after adjustment for all other mosquito control products (OR = 1.42, 95% CI=1.15-1.75). We had limited power to detect an association with repellent skin creams. Although only a few participants reported using repellent room sprays weekly/daily or < month-monthly, no trends were evident with increased frequency of use of repellent sprays, and there was no statistical evidence of heterogeneity by estrogen receptor (ER) status (p-het > 0.25). Our analysis was limited when determining if an association existed with repellent skin creams; therefore, we cannot conclude an association. We found limited evidence of risk associations with widely used mosquito coils and insecticide-treated nets, which are reassuring given their importance for malaria prevention. Our findings regarding specific breast cancer risk associations, specifically those observed between repellent sprays, require further study.

A Prospective Evaluation of the Quality of Life and Mental Health Implications of Mastectomy Alone on Women in sub-Saharan Africa.

OBJECTIVE: Assess quality of life and mental health implications of mastectomy for breast cancer on sub-Saharan African women. BACKGROUND: Mortality rates amongst women diagnosed with breast cancer in sub-Saharan Africa (SSA) are high, with disparities in survival relative to women in high income countries partly attributed to advanced disease at presentation. Fears of the sequelae of mastectomy are a prominent reason for presentation delays. There is a critical need to better understand the effects of mastectomy on women in SSA to inform preoperative counseling and education for women with breast cancer. METHODS: Women with breast cancer in Ghana and Ethiopia undergoing mastectomy were followed prospectively. Breast related quality-of-life and mental health measures were evaluated preoperatively, 3 and 6 months postoperatively, using BREAST-Q, PHQ-9, and GAD-7. Bivariate and logistic regression analyses evaluated changes in these measures for the total cohort and between sites. RESULTS: A total of 133 women from Ghana and Ethiopia were recruited. The majority of women presented with unilateral disease (99%) and underwent unilateral mastectomy (98%) with axillary lymph node dissection. Radiation was more common in Ghana ( P <0.001). Across most BREAST-Q subscales, women from both countries reported significantly decreased scores at 3 months postoperative. At 6 months, the combined cohort reported decreased scores for breast satisfaction (mean difference, -3.4). Women in both countries reported similar improvements in anxiety and depression scores postoperatively. CONCLUSIONS: Women from Ghana and Ethiopia who underwent mastectomy experienced a decline in breast-related body image while also experiencing decreased levels of depression and anxiety.

Measured body size and serum estrogen metabolism in postmenopausal women: the Ghana Breast Health Study.

BACKGROUND: Several anthropometric measures have been associated with hormone-related cancers, and it has been shown that estrogen metabolism in postmenopausal women plays an important role in these relationships. However, little is known about circulating estrogen levels in African women, and the relevance to breast cancer or breast cancer risk factors. To shed further light on the relationship of anthropometric factors and estrogen levels in African women, we examined whether measured body mass index (BMI), waist-to-hip ratio (WHR), height, and self-reported body size were associated with serum estrogens/estrogen metabolites in a cross-sectional analysis among postmenopausal population-based controls of the Ghana Breast Health Study. METHODS: Fifteen estrogens/estrogen metabolites were quantified using liquid chromatography-tandem mass spectrometry in serum samples collected from postmenopausal female controls enrolled in the Ghana Breast Health Study, a population-based case-control study conducted in Accra and Kumasi. Geometric means (GMs) of estrogens/estrogen metabolites were estimated using linear regression, adjusting for potential confounders. RESULTS: Measured BMI (≥ 30 vs. 18.5-24.9 kg/m2) was positively associated with parent estrogens (multivariable adjusted GM for unconjugated estrone: 78.90 (66.57-93.53) vs. 50.89 (43.47-59.59), p-value < 0.0001; and unconjugated estradiol: 27.83 (21.47-36.07) vs. 13.26 (10.37-16.95), p-value < 0.0001). Independent of unconjugated estradiol, measured BMI was associated with lower levels of 2-pathway metabolites and higher levels of 16-ketoestradriol. Similar patterns of association were found with WHR; however, the associations were not entirely independent of BMI. Height was not associated with postmenopausal estrogens/estrogen metabolite levels in African women. CONCLUSIONS: We observed strong associations between measured BMI and parent estrogens and estrogen metabolite patterns that largely mirrored relations that have previously been associated with higher breast cancer risk in postmenopausal White women. The consistency of the BMI-estrogen metabolism associations in our study with those previously noted among White women suggests that estrogens likely explain part of the BMI-postmenopausal breast cancer risk in both groups. These findings merit evaluation in Black women, including prospective studies.

The oral microbiome and breast cancer and nonmalignant breast disease, and its relationship with the fecal microbiome in the Ghana Breast Health Study.

The oral microbiome, like the fecal microbiome, may be related to breast cancer risk. Therefore, we investigated whether the oral microbiome was associated with breast cancer and nonmalignant breast disease, and its relationship with the fecal microbiome in a case-control study in Ghana. A total of 881 women were included (369 breast cancers, 93 nonmalignant cases and 419 population-based controls). The V4 region of the 16S rRNA gene was sequenced from oral and fecal samples. Alpha-diversity (observed amplicon sequence variants [ASVs], Shannon index and Faith's Phylogenetic Diversity) and beta-diversity (Bray-Curtis, Jaccard and weighted and unweighted UniFrac) metrics were computed. MiRKAT and logistic regression models were used to investigate the case-control associations. Oral sample alpha-diversity was inversely associated with breast cancer and nonmalignant breast disease with odds ratios (95% CIs) per every 10 observed ASVs of 0.86 (0.83-0.89) and 0.79 (0.73-0.85), respectively, compared to controls. Beta-diversity was also associated with breast cancer and nonmalignant breast disease compared to controls (P ≤ .001). The relative abundances of Porphyromonas and Fusobacterium were lower for breast cancer cases compared to controls. Alpha-diversity and presence/relative abundance of specific genera from the oral and fecal microbiome were strongly correlated among breast cancer cases, but weakly correlated among controls. Particularly, the relative abundance of oral Porphyromonas was strongly, inversely correlated with fecal Bacteroides among breast cancer cases (r = -.37, P ≤ .001). Many oral microbial metrics were strongly associated with breast cancer and nonmalignant breast disease, and strongly correlated with fecal microbiome among breast cancer cases, but not controls.

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.

Hereditary Susceptibility for Triple Negative Breast Cancer Associated With Western Sub-Saharan African Ancestry: Results From an International Surgical Breast Cancer Collaborative.

OBJECTIVE: To investigate subtype-specific risk of germline alleles associated with triple negative breast cancer (TNBC) in African ancestry populations. BACKGROUND: Breast cancer (BC) mortality is higher in African American (AA) compared to White American (WA) women; this disparity is partly explained by 2-fold higher TNBC incidence. METHODS: We used a surgically maintained biospecimen cohort of 2884 BC cases. Subsets of the total (760 AA; 962 WA; 910 West African/Ghanaian; 252 East African/Ethiopian) were analyzed for genotypes of candidate alleles. A subset of 417 healthy controls were also genotyped, to measure associations with overall BC risk and TNBC. RESULTS: TNBC frequency was highest in Ghanaian and AA cases (49% and 44% respectively; P < 0.0001) and lowest in Ethiopian and WA cases (17% and 24% respectively; P < 0.0001). TNBC cases had higher West African ancestry than non-TNBC (P < 0.0001). Frequency of the Duffy-null allele (rs2814778; an African ancestral variant adopted under selective pressure as protection against malaria) was associated with TNBC-specific risk (P < 0.0001), quantified West African Ancestry (P < 0.0001) and was more common in AA, Ghanaians, and TNBC cases. Additionally, rs4849887 was significantly associated with overall BC risk, and both rs2363956 and rs13000023 were associated with TNBC-specific risk, although none as strongly as the Duffy-null variant. CONCLUSIONS: West African ancestry is strongly correlated with TNBC status, as well as germline variants related to BC risk. The Duffy-null allele was associated with TNBC risk in our cohort.

Evaluation of threshold selection methods for adaptive kernel density estimation in disease mapping.

BACKGROUND: Maps of disease rates produced without careful consideration of the underlying population distribution may be unreliable due to the well-known small numbers problem. Smoothing methods such as Kernel Density Estimation (KDE) are employed to control the population basis of spatial support used to calculate each disease rate. The degree of smoothing is controlled by a user-defined parameter (bandwidth or threshold) which influences the resolution of the disease map and the reliability of the computed rates. Methods for automatically selecting a smoothing parameter such as normal scale, plug-in, and smoothed cross validation bandwidth selectors have been proposed for use with non-spatial data, but their relative utilities remain unknown. This study assesses the relative performance of these methods in terms of resolution and reliability for disease mapping. RESULTS: Using a simulated dataset of heart disease mortality among males aged 35 years and older in Texas, we assess methods for automatically selecting a smoothing parameter. Our results show that while all parameter choices accurately estimate the overall state rates, they vary in terms of the degree of spatial resolution. Further, parameter choices resulting in desirable characteristics for one sub group of the population (e.g., a specific age-group) may not necessarily be appropriate for other groups. CONCLUSION: We show that the appropriate threshold value depends on the characteristics of the data, and that bandwidth selector algorithms can be used to guide such decisions about mapping parameters. An unguided choice may produce maps that distort the balance of resolution and statistical reliability.

Design considerations for identifying breast cancer risk factors in a population-based study in Africa.

Although breast cancer is becoming more prevalent in Africa, few epidemiologic studies have been undertaken and appropriate methodologic approaches remain uncertain. We therefore conducted a population-based case-control study in Accra and Kumasi, Ghana, enrolling 2,202 women with lesions suspicious for breast cancer and 2,161 population controls. Biopsy tissue for cases prior to neoadjuvant therapy (if given), blood, saliva and fecal samples were sought for study subjects. Response rates, risk factor prevalences and odds ratios for established breast cancer risk factors were calculated. A total of 54.5% of the recruited cases were diagnosed with malignancies, 36.0% with benign conditions and 9.5% with indeterminate diagnoses. Response rates to interviews were 99.2% in cases and 91.9% in controls, with the vast majority of interviewed subjects providing saliva (97.9% in cases vs. 98.8% in controls) and blood (91.8% vs. 82.5%) samples; lower proportions (58.1% vs. 46.1%) provided fecal samples. While risk factor prevalences were unique as compared to women in other countries (e.g., less education, higher parity), cancer risk factors resembled patterns identified elsewhere (elevated risks associated with higher levels of education, familial histories of breast cancer, low parity and larger body sizes). Subjects with benign conditions were younger and exhibited higher socioeconomic profiles (e.g., higher education and lower parity) than those with malignancies, suggesting selective referral influences. While further defining breast cancer risk factors in Africa, this study showed that successful population-based interdisciplinary studies of cancer in Africa are possible but require close attention to diagnostic referral biases and standardized and documented approaches for high-quality data collection, including biospecimens.

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.

Research Ethics Education in the STEM Disciplines: The Promises and Challenges of a Gaming Approach.

While education in ethics and the responsible conduct of research (RCR) is widely acknowledged as an essential component of graduate education, particularly in the STEM disciplines (science, technology, engineering, and math), little consensus exists on how best to accomplish this goal. Recent years have witnessed a turn toward the use of games in this context. Drawing from two NSF-funded grants (one completed and one on-going), this paper takes a critical look at the use of games in ethics and RCR education. It does so by: (a) setting the development of research and engineering ethics games in wider historical and theoretical contexts, which highlights their promise to solve important pedagogical problems; (b) reporting on some initial results from our own efforts to develop a game; and (c) reflecting on the challenges that arise in using games for ethics education. In our discussion of the challenges, we draw out lessons to improve this nascent approach to ethics education in the STEM disciplines .

Global surgical oncology disease burden: addressing disparities via global surgery initiatives: the University of Michigan International Breast Cancer Registry.

BACKGROUND: Disparities in breast cancer incidence and outcome between African American and white American women are multifactorial in etiology. The increased frequency of triple-negative breast cancers (TNBC) in African American patients suggests the possible contribution of hereditary factors related to African ancestry. METHODS: The University of Michigan (UM)-Komfo Anoyke Teaching Hospital (KATH) Breast Cancer Research Collaborative and International Breast Registry was established in 2004. It features epidemiologic information, tumor tissue, and germline DNA specimens from African American, white American, and Ghanaian women. RESULTS: This research collaborative has generated valuable findings regarding the pathogenesis and patterns of TNBC while concomitantly improving the standard of breast oncology care in Ghana. This partnership has also yielded important opportunities for academic and educational exchange. It has expanded to involve other sites in Africa and Haiti. CONCLUSIONS: The UM-KATH collaborative is a model for demonstrating the research and academic exchange value of international partnerships.

Characterizing Breast Cancer in a Population with Increased Prevalence of Triple-Negative Breast Cancer: Androgen Receptor and ALDH1 Expression in Ghanaian Women.

BACKGROUND: The androgen receptor (AR) is a commonly-expressed hormone receptor in breast cancer and may be a marker of response to targeted anti-androgen therapy, a particularly attractive option for triple-negative breast cancer (TNBC). Gene expression studies suggest that ARs may distinguish a luminal/AR TNBC subtype from stem cell-like subtypes. TNBC frequency is two to three times higher in African American and African breast cancers compared with White American and European breast cancers, yet little is known regarding TNBC subtypes in high-frequency African-ancestry populations. We evaluated ARs and the mammary stem cell marker aldehyde dehydrogenase 1 (ALDH1) among breast cancers from Ghana, Africa. METHODS: Overall, 147 formalin-fixed, paraffin-embedded invasive breast cancers from the Komfo Anoyke Teaching Hospital in Ghana were studied at the University of Michigan, and analyzed immunohistochemically for estrogen receptor (ER), progesterone receptor (PR), HER2/neu, ALDH1, and AR expression. RESULTS: The median age of patients was 45 years. Only 31 cases (21 %) were ER-positive, and 14 (10 %) were HER2-positive; 89 (61 %) were TNBCs. For the entire group, 44 % were AR-positive and 45 % were ALDH1-positive. ER/PR-positive tumors were more likely to be AR-positive compared with ER/PR-negative tumors (87 vs. 26 %; p < 0.0001), but there was no association between ALDH1 and AR expression. Among the TNBC cases, 45 % were ALDH1-positive and 24 % were AR-positive. ALDH1 positivity was associated with AR positivity within the subset of TNBC (36 vs. 14 %; p = 0.019). CONCLUSION: We confirmed other studies showing a high frequency of TNBC in Africa. Surprisingly, ALDH1 was found to correlate with AR expression among TNBC, suggesting that novel TNBC subtypes may exist among populations with African ancestry.

Cancer incidence in Ghana, 2012: evidence from a population-based cancer registry.

BACKGROUND: Data on cancers is a challenge in most developing countries. Population-based cancer registries are also not common in developing countries despite the usefulness of such registries in informing cancer prevention and control programmes. The availability of population-based data on cancers in Africa varies across different countries. In Ghana, data and research on cancer have focussed on specific cancers and have been hospital-based with no reference population. The Kumasi Cancer Registry was established as the first population-based cancer registry in Ghana in 2012 to provide information on cancer cases seen in the city of Kumasi. METHODS: This paper reviews data from the Kumasi Cancer Registry for the year 2012. The reference geographic area for the registry is the city of Kumasi as designated by the 2010 Ghana Population and Housing Census. Data was from all clinical departments of the Komfo Anokye Teaching Hospital, Pathology Laboratory Results, Death Certificates and the Kumasi South Regional Hospital. Data was abstracted and entered into Canreg 5 database. Analysis was conducted using Canreg 5, Microsoft Excel and Epi Info Version 7.1.2.0. RESULTS: The majority of cancers were recorded among females accounting for 69.6% of all cases. The mean age at diagnosis for all cases was 51.6 years. Among males, the mean age at diagnosis was 48.4 compared with 53.0 years for females. The commonest cancers among males were cancers of the Liver (21.1%), Prostate (13.2%), Lung (5.3%) and Stomach (5.3%). Among females, the commonest cancers were cancers of the Breast (33.9%), Cervix (29.4%), Ovary (11.3%) and Endometrium (4.5%). Histology of the primary tumour was the basis of diagnosis in 74% of cases with clinical and other investigations accounting for 17% and 9% respectively. The estimated cancer incidence Age Adjusted Standardised Rate for males was 10.9/100,000 and 22.4/100, 000 for females. CONCLUSION: This first attempt at population-based cancer registration in Ghana indicates that such registries are feasible in resource limited settings as ours. Strengthening Public Health Surveillance and establishing more Population-based Cancer Registries will help improve data quality and national efforts at cancer prevention and control in Ghana.

Trypanosoma Cruzi antibody screening in North Texas client owned dogs.

Despite multiple screening efforts to identify exposures to Trypanosoma cruzi, in dogs across southern USA, no published studies could be found involving client owned dogs in the North Texas Metroplex area. Therefore, a limited screen was conducted for client owned dogs, seeking routine or preventative care, from participating veterinary practices in the greater Dallas-Fort Worth (DFW) Metroplex from 2019 to 2021. Participants, with owner consent, ranged in age, breed, and length of time at recorded residence. Ninety-nine samples were acquired from participating veterinary practices, initially assessed with the Chagas StatPak, and positive samples were confirmed with IFA (indirect fluorescent antibody test) at the Texas Veterinary Medical Diagnostic Lab (TVMDL), College Station, Texas. Six samples were positive with the StatPak and only two were confirmed positive with IFA. Both animals were senior (10 and 8 years) with no owner reports of previous cardiac issues. The results appear reasonable within the context of previous studies and the seropositivity rate of 2% (n = 99) for client owned dogs included in this study are lower than previously reported rates for shelter dogs from the North Texas area.

An assessment of the direct and indirect costs of breast cancer treatment in leading cancer hospitals in Ghana.

BACKGROUND: In Ghana, breast cancer remains the most common cancer and the leading cause of cancer deaths among women. The cost of treating cancer is huge and poses a great challenge for patients, their families, and health care systems. While comprehensive studies have been conducted on the economic burden of cancers in developed economies such as the EU and the US, there are limited studies in Africa, and Ghana, in particular. This study quantitatively assessed Ghana's direct and indirect costs of breast cancer treatment. METHODS: Primary data were collected using a questionnaire administered to 217 breast cancer patients at the Korle-Bu and Komfo Anokye Teaching Hospitals, Ghana's two leading hospitals, and Sweden Ghana Medical Centre. Direct and indirect costs were computed using the Cost-of-Illness Approach. Quantitative analysis was done using multivariate linear regression. RESULTS: The findings showed that the breast cancer patients studied paid a median amount of Ghana cedis (GHC) 31,021.0 (IQR; 25,262.5-42,147.0), approximating USD 5,500.2 (IQR: 4,477.0-7,469.2 USD) for their treatment within one year of active treatment in 2019. About 61.9% (95% CI: 61.8-62.0%) of this cost was direct cost, while the remaining 38.1% (95% CI: 38.0-38.1%) was indirect cost. Patients who sought care from public facilities for breast cancer paid a median amount of GHC 29,606.3 (USD 5,249.3), while those who sought care from private facilities paid GHC 55,071.2 (USD 9,744.4). Findings from the multivariate linear regression indicate that being married/cohabiting, divorced/separated and having tertiary level education predicted higher cost of breast cancer treatment while patients on retirement and patients in the middle stage (Stage II) of breast cancer diagnoses were associated with lower cost of breast cancer treatment. CONCLUSIONS: The cost of breast cancer treatment poses a significant burden on patients and their families. There is a need for increased public funding for breast cancer treatment to reduce the huge economic burden its treatment poses for patients and their families.

Patient-derived tumor organoids with p53 mutations, and not wild-type p53, are sensitive to synergistic combination PARP inhibitor treatment.

Poly (ADP-ribose) polymerase inhibitors (PARPi) are used for patients with BRCA1/2 mutations, but patients with other mutations may benefit from PARPi treatment. Another mutation that is present in more cancers than BRCA1/2 is mutation to the TP53 gene. In 2D breast cancer cell lines, mutant p53 (mtp53) proteins tightly associate with replicating DNA and Poly (ADP-ribose) polymerase (PARP) protein. Combination drug treatment with the alkylating agent temozolomide and the PARPi talazoparib kills mtp53 expressing 2D grown breast cancer cell lines. We evaluated the sensitivity to the combination of temozolomide plus PARPi talazoparib treatment to breast and lung cancer patient-derived tumor organoids (PDTOs). The combination of the two drugs was synergistic for a cytotoxic response in PDTOs with mtp53 but not for PDTOs with wtp53. The combination of talazoparib and temozolomide induced more DNA double-strand breaks in mtp53 expressing organoids than in wild-type p53 expressing organoids as shown by increased γ-H2AX protein expression. Moreover, breast cancer tissue microarrays (TMAs) showed a positive correlation between stable p53 and high PARP1 expression in sub-groups of breast cancers, which may indicate sub-classes of breast cancers sensitive to PARPi therapy. These results suggest that mtp53 could be a biomarker to predict response to the combination of PARPi talazoparib-temozolomide treatment.

Expression of aldehyde dehydrogenase 1 as a marker of mammary stem cells in benign and malignant breast lesions of Ghanaian women.

BACKGROUND: Breast cancers that are negative for the estrogen receptor (ER), the progesterone receptor (PR), and the HER2 (human epidermal growth factor receptor 2) marker are more prevalent among African women, and the biologically aggressive nature of these triple-negative breast cancers (TNBCs) may be attributed to their mammary stem cell features. Little is known about expression of the mammary stem cell marker aldehyde dehydrogenase 1 (ALDH1) in African women. Novel data are reported regarding ALDH1 expression in benign and cancerous breast tissue of Ghanaian women. METHODS: Formalin-fixed, paraffin-embedded specimens were transported from the Komfo Anoyke Teaching Hospital in Kumasi, Ghana to the University of Michigan for centralized histopathology study. Expression of ER, PR, HER2, and ALDH1 was assessed by immunohistochemistry. ALDH1 staining was further characterized by its presence in stromal versus epithelial and/or tumor components of tissue. RESULTS: A total of 173 women contributed to this study: 69 with benign breast conditions, mean age 24 years, and 104 with breast cancer, mean age 49 years. The proportion of benign breast conditions expressing stromal ALDH1 (n = 40, 58%) was significantly higher than those with cancer (n = 44, 42.3%) (P = .043). Among the cancers, TNBC had the highest prevalence of ALDH1 expression, either in stroma or in epithelial cells. More than 2-fold higher likelihood of ALDH1 expression was observed in TNBC cases compared with other breast cancer subtypes (odds ratio = 2.38, 95% confidence interval 1.03-5.52, P = .042). CONCLUSIONS: ALDH1 expression was higher in stromal components of benign compared with cancerous lesions. Of the ER-, PR-, and HER2-defined subtypes of breast cancer, expression of ALDH1 was highest in TNBC.

Mapping Health Fragility and Vulnerability in Air Pollution-Monitoring Networks in Dallas-Fort Worth.

Environmental air pollution remains a major contributor to negative health outcomes and mortality, but the relationship between socially vulnerable populations and air pollution is not well understood. Although air pollution potentially affects everyone, the combination of underlying health, socioeconomic, and demographic factors exacerbate the impact for socially vulnerable population groups, and the United States Clean Air Act (CAA) describes an obligation to protect these populations. This paper seeks to understand how air pollution monitor placement strategies and policy may neglect social vulnerabilities and therefore potentially underestimate exposure burdens in vulnerable populations. Multivariate logistic regression models were used to assess the association between being in an ozone-monitored area or not on 15 vulnerability indicators. It was found that the odds of not being in an ozone-monitored area (not covered, outside) increased for the predictor mobile homes (OR = 4.831, 95% CI [2.500-9.338] and OR = 8.066, 95% CI [4.390-14.820] for the 10 and 20 km spatial units, respectively) and decreased for the predictor multiunit structures (OR = 0.281, 95% CI [0.281-0.548] and OR = 0.130, 95% CI [0.037, 0.457] for the 10 and 20 km spatial units, respectively) and the predictor speaks English "less than well" (OR = 0.521, 95% CI [0.292-0.931] for 10 km). These results indicate that existing pollution sensor coverage may neglect areas with concentrations of highly vulnerable populations in mobile homes, and future monitoring placement policy decisions must work to address this imbalance.

The psychosocial burden of women seeking treatment for breast and cervical cancers in Ghana's major cancer hospitals.

BACKGROUND: Breast and cervical cancers remain the most common cancers and the leading cause of cancer deaths in Ghana. Non-communicable diseases such as cancers, have been associated with psychological burdens such as anxiety and depression disorders as well as severe mental disorders such as bipolar disorder. As such the World Health Organisation has noted that mental health and well-being are crucial in reducing the NCD burden. METHODS: A convergent mixed method approach was used to ascertain the psychosocial burden of breast and cervical cancer patients who sought treatment in three major cancer hospitals in Ghana. Primary data were collected using a questionnaire and an interview guide from 298 breast and cervical cancer patients seeking treatment at the Korle-Bu and Komfo Anokye Teaching Hospitals as well as the Sweden Ghana Medical Centre. Qualitative analysis was done using thematic content analysis while quantitative analysis was done using logistic regression. RESULTS: The findings of the study showed that patients not only battled with psychological burdens such as anxiety, depression, pain, stigma, fear of death and loss of spouses but also struggled with physical, social, and dietary restrictions. Patients with low educational levels and income status, retired or unemployed, and/or had larger household sizes suffered more psychosocial burdens. CONCLUSION: There is a need for liaison psychiatrists and health psychologists to assist oncologists to provide psychological support such as free and routine counselling services for cancer patients and their caregivers. Educational campaigns on mainstream and social media need to be intensified to demystify the stigma surrounding cancers in Ghana.

Relation of circulating estrogens with hair relaxer and skin lightener use among postmenopausal women in Ghana.

BACKGROUND: Hair relaxers and skin lighteners have been commonly used by African women, with suggestions that they may have hormonal activity. OBJECTIVES: To investigate the relationship of hair relaxer and skin lightener use to serum estrogen/estrogen metabolite levels. METHODS: We utilized the postmenopausal population-based controls of the Ghana Breast Health Study to estimate adjusted geometric means (GM) and 95% confidence intervals of individual circulating estrogen levels by hair relaxer/skin lightener exposure categories. RESULTS: Of the 585 postmenopausal women included in our analysis, 80.2% reported hair relaxer use and 29.4% skin lightener use. Ever hair relaxer use was positively associated with estriol (adjusted GM 95.4 pmol/L vs. never 74.5, p value = 0.02) and 16-epiestriol (20.4 vs. 16.8, p value = 0.05) particularly among users of lye-based hair relaxers. Positive associations between scalp burns and unconjugated estrogens were observed (e.g., unconjugated estrone: 5+ scalp burns 76.9 [59.6-99.2] vs. no burns 64.0 [53.7-76.3], p-trend = 0.03). No association was observed between use of skin lighteners and circulating estrogens. SIGNIFICANCE: This study presents evidence that circulating 16-pathway estrogens (i.e., estriol and 16-epiestriol) may be increased in users of lye-based hair relaxer products. Among hair relaxer users, unconjugated estrogen levels were elevated in women with a greater number of scalp burns. IMPACT STATEMENT: In this population-based study of hair relaxer and skin lightener use among postmenopausal women in Ghana, altered estrogen metabolism was observed with hair relaxer use, particularly among women using lye-based products or with a greater number of scalp burns. In contrast, skin lightener use was not associated with differences in estrogen metabolism in this population. Continued investigation of the potential biological impact on breast cancer risk of hair relaxer use is warranted.