ABSTRACT
A critical shortage of skilled healthcare workers is a primary cause of disparate global cancer outcomes. We report participant evaluation of a multidisciplinary preceptorship program. In collaboration with the city of Kumasi, Ghana, Mayo Clinic and the City Cancer Challenge hosted a preceptorship program for comprehensive multidisciplinary breast and cervix cancer training. A total of 14 healthcare workers from Kumasi received two weeks of training at Mayo Clinic in November and December 2021. Each participant and preceptor were requested to complete an anonymous post-participation survey. Of the 14 trainee participants, 10 (71%) completed the survey. All respondents found the program "valuable and applicable to their clinical practice." Ninety percent reported they were able to "review effective and critical elements in the development and expansion of the multidisciplinary team" and able to "solve practical clinical cases as a team". General themes of satisfaction included: (1) organization and administration, (2) clinical observations and demonstrations, (3) guidelines development, and (4) recognizing the central importance of cultivating a team-based approach. Of the 40 preceptors, 16 (40%) completed the survey. All respondents reported they felt the training would meaningfully "influence patient care in Ghana", that participation "added value or joy to their clinical practice," and all wished to "participate in future preceptorship programs". After a focused two-week program, trainees reported high satisfaction, usefulness from observing specialized cancer care, and value in closely observing a multidisciplinary oncology team. Preceptors reported the experience added joy and perspective to their clinical practice and wished to participate in future programs.
Subject(s)
Medical Oncology , Preceptorship , Humans , Ghana , Medical Oncology/education , Female , Health Personnel/education , Patient Care Team , Surveys and Questionnaires , Male , Program Evaluation , Adult , Breast NeoplasmsABSTRACT
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.
Subject(s)
Breast Neoplasms , Insect Repellents , Insecticides , Malaria , Animals , Humans , Female , Mosquito Control , Insecticides/adverse effects , Ghana/epidemiology , Breast Neoplasms/epidemiology , Breast Neoplasms/etiology , Breast Neoplasms/prevention & control , Malaria/prevention & control , Insect Repellents/adverse effectsABSTRACT
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.
Subject(s)
Breast Neoplasms , Postmenopause , Body Height , Body Mass Index , Breast Neoplasms/metabolism , Case-Control Studies , Cross-Sectional Studies , Estrogens/metabolism , Female , Ghana/epidemiology , Humans , Prospective Studies , Risk FactorsABSTRACT
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.
Subject(s)
Breast Neoplasms , Gastrointestinal Microbiome , Microbiota , Breast Neoplasms/epidemiology , Case-Control Studies , Feces/microbiology , Female , Gastrointestinal Microbiome/genetics , Ghana/epidemiology , Humans , Logistic Models , Phylogeny , RNA, Ribosomal, 16S/geneticsABSTRACT
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.
Subject(s)
Triple Negative Breast Neoplasms , Black or African American/genetics , Female , Ghana/epidemiology , Humans , Neoplasm Recurrence, Local , Triple Negative Breast Neoplasms/genetics , White PeopleABSTRACT
BACKGROUND: Data from population-based cancer registries (PBCRs) are a useful resource for estimating the incidence of cancers. PBCR data is useful in the planning and implementation of cancer prevention and control strategies. Ghana's plan for control of non-communicable diseases recognises the need for good quality data to facilitate the attainment of set goals. METHODS: We reviewed data from the Kumasi Cancer Registry for the year 2015. Data collected included clinical and demographic information, laboratory reports and source of case information. Data was entered into the Canreg-5 software. Data was initially analysed using Canreg-5 to estimate the incidence and age standardised rates (ASR) for various tumours. Data was also exported to Microsoft Excel for further analysis using Epi Info version 7.1.4. Microsoft Excel was used to generate charts and graphs. Aggregated data for the years 2013 and 2014 were also analysed for trends in cancer incidence and ASR. RESULTS: A total of 736 cancer cases were recorded among the residents of Kumasi for the year 2015. Females accounted for 62.4% of all cases. The overall incidence of cancer in Kumasi for 2015 was 46.1 per 100,000. The mean age of all cases was 51.3 years (with a range of 1 to 99 years). The incidence among female residents was estimated at 54.1 per 100,000 compared with 37.1 per 100,000 in males. Among females, breast and cervical cancers recorded the highest incidences of 16.1 per 100,000 and 13.7 per 100,000 respectively. Among males, prostate cancer had the highest incidence of 10.5 per 100,000. Breast, cervical and liver cancers were the commonest in both sexes accounting for 19.7, 14.7 and 11.4% of cases respectively. CONCLUSION: There has been significant improvement in data quality and coverage since the inception of our PBCR in 2012. PBCRs are feasible; therefore there is the need for more such registries to improve data on cancers in Ghana. Consistent with other evidence, we found breast cancer as the commonest female cancer in Ghana.
Subject(s)
Neoplasms/classification , Neoplasms/epidemiology , Adolescent , Adult , Age Distribution , Aged , Child , Child, Preschool , Female , Ghana/epidemiology , Humans , Incidence , Infant , Infant, Newborn , Male , Middle Aged , Registries , Sex Distribution , Young AdultABSTRACT
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.
Subject(s)
Breast Neoplasms/diagnosis , Breast Neoplasms/epidemiology , Population Surveillance/methods , Risk Assessment/statistics & numerical data , Adolescent , Adult , Case-Control Studies , Female , Ghana/epidemiology , Humans , Logistic Models , Middle Aged , Odds Ratio , Parity , Prevalence , Research Design , Risk Assessment/methods , Risk Factors , Socioeconomic Factors , Young AdultABSTRACT
Objective: The goal of this study was to elucidate the attitudes, beliefs, and barriers interfering with cancer pain management, the degree of barrier interference with trainees' care of patients, and the relationships among prohibitive factors to pain management for physicians in a lowmiddle-income countries (LMICs) vs high-income countries (HICs). Design and Setting: A multi-institutional cross-sectional survey of physicians in specialties with a focus in pain management training was performed. All surveys were completed anonymously from July 1, 2015, to November 30, 2015. Subjects: One hundred and twenty physicians participated in the survey. Methods: Surveys were based on prior questionnaires published in the literature. Descriptive statistics were calculated, and chi-square (âµ2) analysis, Fisher's exact test, and Spearman rank correlation analyses were performed. Results: Compared with their peers in HICs, physicians in LMICs reported less experience with cancer pain management despite seeing more cancer patients with advanced disease (41% vs 15.2%, p < 0.05). Some barriers were common to both environments, but a few were unique to each setting. Organized by percentage of severity of interference, cultural values/beliefs about pain (84% vs 76%) and lack of training and expertise (87% vs 78%) were significantly more prohibitive for physicians in LMICs than those in HICs; p < 0.05. Conclusion: There are significant differences in perceived barriers and degree of prohibitive factors to cancer pain management among trainee physicians in low- vs high-resource environments. Understanding these differences may spur further collaboration in the design of contextually relevant solutions, which could potentially help improve the adequacy of cancer pain management
Subject(s)
Cancer Pain/therapy , Health Knowledge, Attitudes, Practice , Pain Management , Physicians , Adult , Cross-Sectional Studies , Female , Humans , Internship and Residency , Male , Practice Patterns, Physicians'/statistics & numerical data , Surveys and QuestionnairesABSTRACT
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.
Subject(s)
Carcinoma, Ductal, Breast/chemistry , Carcinoma, Lobular/chemistry , Isoenzymes/analysis , Receptors, Androgen/analysis , Retinal Dehydrogenase/analysis , Triple Negative Breast Neoplasms/chemistry , Adult , Aldehyde Dehydrogenase 1 Family , Carcinoma, Ductal, Breast/epidemiology , Carcinoma, Lobular/epidemiology , Female , Ghana/epidemiology , Humans , Middle Aged , Prevalence , Receptor, ErbB-2/analysis , Receptors, Estrogen/analysis , Receptors, Progesterone/analysis , Triple Negative Breast Neoplasms/epidemiologyABSTRACT
PURPOSE: There is limited information on preferences for place of care and death among patients with cancer in low- and middle-income countries (LMICs). The aim was to report the prevalence and determinants of preferences for end-of-life place of care and death among patients with cancer in LMICs and identify concordance between the preferred and actual place of death. METHODS: Systematic review and meta-analysis guided by Preferred Reporting Items for Systematic Reviews and Meta-Analyses was conducted. Four electronic databases were searched to identify studies of any design that reported on the preferred and actual place of care and death of patients with cancer in LMICs. A random-effects meta-analysis estimated pooled prevalences, with 95% CI, with subgroup analyses for region and risk of bias. RESULTS: Thirteen studies were included. Of 3,837 patients with cancer, 62% (95% CI, 49 to 75) preferred to die at home; however, the prevalence of actual home death was 37% (95% CI, 13 to 60). Subgroup analyses found that preferences for home as place of death varied from 55% (95% CI, 41 to 69) for Asia to 64% (95% CI, 57 to 71) for South America and 72% (95% CI, 48 to 97) for Africa. The concordance between the preferred and actual place of death was 48% (95% CI, 41 to 55) for South Africa and 92% (95% CI, 88 to 95) for Malaysia. Factors associated with an increased likelihood of preferred home death included performance status and patients with breast cancer. CONCLUSION: There is very little literature from LMICs on the preferences for end-of-life place of care and death among patients with cancer. Rigorous research is needed to help understand how preferences of patients with cancer change during their journey through cancer.
Subject(s)
Developing Countries , Neoplasms , Patient Preference , Terminal Care , Humans , Terminal Care/psychology , Neoplasms/mortality , Neoplasms/therapy , Neoplasms/psychology , Developing Countries/statistics & numerical data , Patient Preference/psychology , Patient Preference/statistics & numerical data , PrevalenceABSTRACT
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.
Subject(s)
Antineoplastic Agents , Breast Neoplasms , Lung Neoplasms , Female , Humans , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , BRCA1 Protein/genetics , BRCA1 Protein/metabolism , BRCA2 Protein/genetics , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Cell Line, Tumor , DNA , Genes, p53 , Lung Neoplasms/genetics , Mutation , Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use , Poly(ADP-ribose) Polymerases/metabolism , Temozolomide/pharmacology , Temozolomide/therapeutic use , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolismABSTRACT
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.
Subject(s)
Breast Neoplasms/genetics , Carcinoma/genetics , Isoenzymes/genetics , Mammary Glands, Human/metabolism , Neoplastic Stem Cells/metabolism , Retinal Dehydrogenase/genetics , Adolescent , Adult , Aldehyde Dehydrogenase 1 Family , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Breast Neoplasms/diagnosis , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Carcinoma/diagnosis , Carcinoma/ethnology , Carcinoma/pathology , Cohort Studies , Female , Gene Expression Regulation, Enzymologic , Gene Expression Regulation, Neoplastic , Ghana , Humans , Isoenzymes/metabolism , Mammary Glands, Human/pathology , Middle Aged , Neoplastic Stem Cells/pathology , Precancerous Conditions/diagnosis , Precancerous Conditions/ethnology , Precancerous Conditions/genetics , Precancerous Conditions/pathology , Retinal Dehydrogenase/metabolism , Young AdultABSTRACT
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.
Subject(s)
Estrogens , Lye , Female , Humans , Estrogens/metabolism , Ghana/epidemiology , Postmenopause , Estriol , HairABSTRACT
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.
ABSTRACT
The human fecal and oral microbiome may play a role in the etiology of breast cancer through modulation of endogenous estrogen metabolism. This study aimed to investigate associations of circulating estrogens and estrogen metabolites with the fecal and oral microbiome in postmenopausal African women. A total of 117 women with fecal (N = 110) and oral (N = 114) microbiome data measured by 16S rRNA gene sequencing, and estrogens and estrogen metabolites data measured by liquid chromatography tandem mass spectrometry were included. The outcomes were measures of the microbiome and the independent variables were the estrogens and estrogen metabolites. Estrogens and estrogen metabolites were associated with the fecal microbial Shannon index (global P < 0.01). In particular, higher levels of estrone (ß = 0.36, P = 0.03), 2-hydroxyestradiol (ß = 0.30, P = 0.02), 4-methoxyestrone (ß = 0.51, P = 0.01), and estriol (ß = 0.36, P = 0.04) were associated with higher levels of the Shannon index, while 16alpha-hydroxyestrone (ß = -0.57, P < 0.01) was inversely associated with the Shannon index as indicated by linear regression. Conjugated 2-methoxyestrone was associated with oral microbial unweighted UniFrac as indicated by MiRKAT (P < 0.01) and PERMANOVA, where conjugated 2-methoxyestrone explained 2.67% of the oral microbial variability, but no other estrogens or estrogen metabolites were associated with any other beta diversity measures. The presence and abundance of multiple fecal and oral genera, such as fecal genera from families Lachnospiraceae and Ruminococcaceae, were associated with several estrogens and estrogen metabolites as indicated by zero-inflated negative binomial regression. Overall, we found several associations of specific estrogens and estrogen metabolites and the fecal and oral microbiome. IMPORTANCE Several epidemiologic studies have found associations of urinary estrogens and estrogen metabolites with the fecal microbiome. However, urinary estrogen concentrations are not strongly correlated with serum estrogens, a known risk factor for breast cancer. To better understand whether the human fecal and oral microbiome were associated with breast cancer risk via the regulation of estrogen metabolism, we conducted this study to investigate the associations of circulating estrogens and estrogen metabolites with the fecal and oral microbiome in postmenopausal African women. We found several associations of parent estrogens and several estrogen metabolites with the microbial communities, and multiple individual associations of estrogens and estrogen metabolites with the presence and abundance of multiple fecal and oral genera, such as fecal genera from families Lachnospiraceae and Ruminococcaceae, which have estrogen metabolizing properties. Future large, longitudinal studies to investigate the dynamic changes of the fecal and oral microbiome and estrogen relationship are needed.
Subject(s)
Breast Neoplasms , Lactobacillales , Microbiota , Female , Humans , Estrogens/urine , Postmenopause/physiology , RNA, Ribosomal, 16S/genetics , Ghana/epidemiology , Breast Neoplasms/epidemiology , Breast Neoplasms/urine , Lactobacillales/metabolismABSTRACT
Importance: Radiotherapy is critical for comprehensive cancer care, but there are large gaps in access. Within Ghana, data on radiotherapy availability and on the relationship between distance and access are unknown. Objectives: To estimate the gaps in radiotherapy machine availability in Ghana and to describe the association between distance and access to care. Design, Setting, and Participants: This is a cross-sectional, population-based study of radiotherapy delivery in Ghana in 2020 and model-based analysis of radiotherapy demand and the radiotherapy utilization rate (RUR) using the Global Task Force on Radiotherapy for Cancer Control investment framework. Exposures: Receipt of radiotherapy and the number of radiotherapy courses delivered. Main Outcomes and Measures: Geocoded location of patients receiving external beam radiotherapy (EBRT); median Euclidean distance from the district centroids to the nearest radiotherapy centers; proportion of population living within geographic buffer zones of 100, 150, and 200 km; additional capacity required for optimal utilization; and geographic accessibility after strategic location of a radiotherapy facility in an underserviced region. Results: A total of 2883 patients underwent EBRT courses in 2020, with an actual RUR of 11%. Based on an optimal RUR of 48%, 11â¯524 patients had an indication for radiotherapy, indicating that only 23% of patients received treatment. An investment of 23 additional EBRT machines would be required to meet demand. The median Euclidean distance from the district centroids to the nearest radiotherapy facility was 110.6 km (range, 0.62-513.2 km). The proportion of the total population living within a radius of 100, 150 and 200 km of a radiotherapy facility was 47%, 61% and 70%, respectively. A new radiotherapy facility in the northern regional capital would reduce the median of Euclidean distance by 10% to 99.4 km (range, 0.62-267.7 km) and increase proportion of the total population living within a radius of 100, 150 and 200 km to 53%, 69% and 84%, respectively. The greatest benefit was seen in regions in the northern half of Ghana. Conclusions and Relevance: In this cross-sectional study of geographic accessibility and availability of radiotherapy, Ghana had major national deficits of radiotherapy capacity, with significant geographic disparities among regions. Well-planned infrastructure scale-up that accounts for the population distribution could improve radiotherapy accessibility.
Subject(s)
Health Services Accessibility , Cross-Sectional Studies , Ghana/epidemiology , HumansABSTRACT
BACKGROUND: Risk estimates for women carrying germline mutations in breast cancer susceptibility genes are mainly based on studies of European ancestry women. METHODS: We investigated associations between pathogenic variants (PV) in 34 genes with breast cancer risk in 871 cases [307 estrogen receptor (ER)-positive, 321 ER-negative, and 243 ER-unknown] and 1,563 controls in the Ghana Breast Health Study (GBHS), and estimated lifetime risk for carriers. We compared results with those for European, Asian, and African American ancestry women. RESULTS: The frequency of PV in GBHS for nine breast cancer genes was 8.38% in cases and 1.22% in controls. Relative risk estimates for overall breast cancer were: (OR, 13.70; 95% confidence interval (CI), 4.03-46.51) for BRCA1, (OR, 7.02; 95% CI, 3.17-15.54) for BRCA2, (OR, 17.25; 95% CI, 2.15-138.13) for PALB2, 5 cases and no controls carried TP53 PVs, and 2.10, (0.72-6.14) for moderate-risk genes combined (ATM, BARD1, CHEK2, RAD51C, RAD52D). These estimates were similar to those previously reported in other populations and were modified by ER status. No other genes evaluated had mutations associated at P < 0.05 with overall risk. The estimated lifetime risks for mutation carriers in BRCA1, BRCA2, and PALB2 and moderate-risk genes were 18.4%, 9.8%, 22.4%, and 3.1%, respectively, markedly lower than in Western populations with higher baseline risks. CONCLUSIONS: We confirmed associations between PV and breast cancer risk in Ghanaian women and provide absolute risk estimates that could inform counseling in Ghana and other West African countries. IMPACT: These findings have direct relevance for breast cancer genetic counseling for women in West Africa.
Subject(s)
Breast Neoplasms , Germ-Line Mutation , Breast Neoplasms/epidemiology , Breast Neoplasms/genetics , Female , Genetic Predisposition to Disease , Ghana/epidemiology , Humans , RiskABSTRACT
Women of sub-Saharan African descent have disproportionately higher incidence of triple-negative breast cancer (TNBC) and TNBC-specific mortality across all populations. Population studies show racial differences in TNBC biology, including higher prevalence of basal-like and quadruple-negative subtypes in African Americans (AA). However, previous investigations relied on self-reported race (SRR) of primarily U.S. populations. Due to heterogeneous genetic admixture and biological consequences of social determinants, the true association of African ancestry with TNBC biology is unclear. To address this, we conducted RNA sequencing on an international cohort of AAs, as well as West and East Africans with TNBC. Using comprehensive genetic ancestry estimation in this African-enriched cohort, we found expression of 613 genes associated with African ancestry and 2,000+ associated with regional African ancestry. A subset of African-associated genes also showed differences in normal breast tissue. Pathway enrichment and deconvolution of tumor cellular composition revealed that tumor-associated immunologic profiles are distinct in patients of African descent. SIGNIFICANCE: Our comprehensive ancestry quantification process revealed that ancestry-associated gene expression profiles in TNBC include population-level distinctions in immunologic landscapes. These differences may explain some differences in race-group clinical outcomes. This study shows the first definitive link between African ancestry and the TNBC immunologic landscape, from an African-enriched international multiethnic cohort. See related commentary by Hamilton et al., p. 2496. This article is highlighted in the In This Issue feature, p. 2483.
Subject(s)
Triple Negative Breast Neoplasms , Humans , Female , Triple Negative Breast Neoplasms/genetics , Transcriptome , Black or African American/genetics , BiologyABSTRACT
Background: Breast cancer is the leading cause of cancer death among Ghanaian women and most women are identified once they develop symptoms. Women then must navigate a complex health care system to get diagnosed and receive orthodox medicine. We describe Ghanaian women's pathways of care from breast cancer-related symptom detection to treatment receipt. Methods: We conducted a qualitative study using an empirical phenomenological approach. We used a purposive sampling technique to recruit 31 women with breast cancer who were receiving treatment at Komfo Anokye Teaching Hospital in Kumasi, Ghana. They participated in semistructured in-depth interviews between November 2019 and March 2020. All interviews were transcribed verbatim and analyzed using a deductive coding approach. Results: Women navigate approximately nine steps from symptom detection to receiving orthodox breast cancer treatment. The breast cancer care pathway is not linear and women frequently move among different management approaches, including alternative therapy (faith healing and traditional herbal healing). All the women detected the symptoms themselves. Some of the women sought orthodox medicine due to information from the media. Conclusions: Alternative therapy providers play a critical role in the breast cancer diagnosis and care pathways in Ghana underscoring the need to formally integrate them into the health care system. Breast cancer awareness programs through the media and educational programs aimed at alternative therapy providers may reduce the time from symptom detection to receipt of orthodox medicine.
ABSTRACT
The effective implementation of locally adapted cancer care solutions in low- and middle-income countries continues to be a challenge in the face of fragmented and inadequately resourced health systems. Consequently, the translation of global cancer care targets to local action for patients has been severely constrained. City Cancer Challenge (C/Can) is leveraging the unique value of cities as enablers in a health systems response to cancer that prioritizes the needs of end users (patients, their caregivers and families, and health care providers). C/Can's City Engagement Process is an implementation framework whereby local stakeholders lead a staged city-wide process over a 2- to 3-year period to assess, plan, and execute locally adapted cancer care solutions. Herein, the development and implementation of the City Engagement Process Framework (CEPF) is presented, specifying the activities, outputs, processes, and indicators across the process life cycle. Lessons learned on the application of the framework in the first so-called Key Learning cities are shared, focusing on the early outputs from Cali, Colombia, the first city to join C/Can in 2017. Creating lasting change requires the creation of a high-trust environment to engage the right stakeholders as well as adapting to local context, leveraging local expertise, and fostering a sustainability mindset from the outset. In the short term, these early learnings inform the refinement of the approach in new cities. Over time, the implementation of this framework is expected to validate the proof-of-concept and contribute to a global evidence base for effective complex interventions to improve cancer care in low- and middle-income countries.