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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.

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.

Hair relaxers and skin lighteners have been commonly used by African women, with suggestions that they may have hormonal activity.To investigate the relationship of hair relaxer and skin lightener use to serum estrogen/estrogen metabolite levels.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.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.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.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.

Background: Breast cancer risk estimates for women carrying germline mutations in breast cancer susceptibility genes are mainly based on studies of European ancestry women, with limited data for women in West African. Methods: We investigated associations between pathogenic variants in 34 putative susceptibility 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 a population-based study in Ghana, and estimated lifetime risk for mutation carriers in the general population. We compared results to those for European, Asian and African-American women. Findings: The frequency of pathogenic mutations in nine breast cancer genes (BRCA1, BRCA2, PALB2, TP53, ATM, BARD1, CHEK2, RAD51C, RAD52D) was 8·38% in cases and 1·22% in controls from GBHS. Mutations in BRCA1, BRCA2, PALB2, and TP53 were significantly associated with breast cancer risk at P

Circulating tumor DNA (ctDNA) sequencing studies could provide novel insights into the molecular pathology of cancer in sub-Saharan Africa. ctDNA was readily detected in 15 blood samples collected in Ghana at the time of suspected breast cancer. Genomic alterations previously associated with unfavorable prognostic outcomes were observed in the majority of patients. This supports the use of liquid biopsies for diagnosis, surveillance and clinical management of breast cancer in Ghana.

BackgroundHigher proportions of early-onset and estrogen receptor (ER) negative cancers are observed in women of African ancestry than in women of European ancestry. Differences in risk factor distributions and associations by age at diagnosis and ER status may explain this disparity.MethodsWe analyzed data from 1,126 women (aged 18–74 years) with invasive breast cancer and 2,106 population controls recruited from three hospitals in Ghana from 2013 to 2015. Odds ratios (OR) and 95% confidence intervals (CI) were estimated for menstrual and reproductive factors using polytomous logistic regression models adjusted for potential confounders.ResultsAmong controls, medians for age at menarche, parity, age at first birth, and breastfeeding/pregnancy were 15 years, 4 births, 20 years, and 18 months, respectively. For women ≥ 50 years, parity and extended breastfeeding were associated with decreased risks: >5 births vs. nulliparous, OR 0.40 (95% CI 0.20–0.83) and 0.71 (95% CI 0.51–0.98) for ≥19 vs. P-heterogeneity by ER = 0.02), which was offset by extended breastfeeding. Similar associations were observed by intrinsic-like subtypes. Less consistent relationships were observed with ages at menarche and first birth.ConclusionReproductive risk factor distributions are different from European populations but exhibited etiologic heterogeneity by age at diagnosis and ER status similar to other populations. Differences in reproductive patterns and subtype heterogeneity are consistent with racial disparities in subtype distributions.Key MessagesDistribution of intrinsic-like breast cancer subtypes among Ghanaian women are distinct compared to European ancestry populations, with a higher proportion of ER-negative subtypes at younger ages.Increasing number of births and extended breastfeeding were associated with reduced risk for both ER-positive and ER-negative subtypes among later-onset breast cancer cases (women age ≥50 years).Extended breastfeeding offset a direct association that we observed of multiparity with early-onset (women age Number of births and breastfeeding duration are much higher in Ghanaian women compared to women of European ancestry and African Americans, however the relationships with risk are consistent when assessed by molecular subtype.

Purpose: Analysis of cell free DNA could provide a rapid and non-invasive approach to detect cancer and provide new molecular insights in many African countries where expert pathology is lacking. Hence, we tested whether whole-genome sequencing of cfDNA (WGS-cfDNA) could identify somatic alterations that drive breast cancer. Methods: We conducted a pilot on 15 Ghanaian women (median age 49.5 years) recruited as part of the Ghana Breast Health Study. cfDNA was extracted and subjected to WGS at 30x and 0.1x. ichorCNA software was used to predict copy number alterations and ctDNA fractions. Results: We found extensive amplification and deletion of multiple chromosomal regions including those with oncogenes and tumor suppressor genes associated with breast cancer. Similar copy number alterations for selected breast cancer genes were observed with 0.1x and 30x cfDNA-WGS with increasing concordance between the two instruments as the ctDNA fraction increases. We observed a high frequency (>50%) of copy number gain in 3/5 regions and potential target genes for the amplification (chr8p11-12 [ZNF703] n=8, 53.3%; chr8q24.2 [MYC] n=9, 60%; chr19q12 [CCNE1] n=9, 60%), which were in agreement to previous observations among African-American (AA) ancestry compared to European-American (EA) ancestry in TCGA datasets. Conclusion: Our data provided evidence that ctDNA-based genomic studies are possible and ctDNA analysis could be a tool for future molecular oncology studies in Africa for cancer etiology, surveillance and clinical trials. Citation Format: Samuel Ahuno, Anna-Lisa Doebley, Thomas Ahearn, Joel Yarney, Nicholas Titiloye, Nancy Hamel, Ernest Adjei, Joe-Nat Clegg-Lamptey, Lawrence Edusei, Baffour Awuah, Xiaoyu Song, Verne Vanderpuye, Mustapha Abubakar, Maire Duggan, Daniel Stover, Kofi Nyarko, John Bartlet, Francis Aitpillah, Daniel Ansong, Kevin Gardner, Anne Bowcock, Carlos Caldas, William Foulkes, Seth Wiafe, Wiafe-Addai, Montserrat Garcia-Closas, Alexander Kwarteng, Gavin Ha, Jonine Figueroa, Paz Polak, On Behalf Of Ghana Breast Health Study Team. Studying Ghanian Cancer Genomes Using Cell-free DNA [abstract]. In: Proceedings of the 9th Annual Symposium on Global Cancer Research; Global Cancer Research and Control: Looking Back and Charting a Path Forward; 2021 Mar 10-11. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2021;30(7 Suppl):Abstract nr 81.

Background: Women of African ancestry have a higher proportion of early-onset and oestrogen receptor (ER) negative cancers compared to women of European ancestry. Differences in risk factor distributions and associations by age at diagnosis and ER status might explain this disparity. Methods: We analysed data from 1,126 women with invasive breast cancer and 2,106 population controls aged 18-74 years recruited from three hospitals in Ghana from 2013-2015. Odds ratios (OR) and 95% confidence intervals (CI) were estimated for menstrual and reproductive factors using polytomous logistic regression models adjusted for potential confounders. Findings: Among controls, the medians for age at menarche, parity, age at first birth and breastfeeding/pregnancy were 15 years, 4 births, 20 years, and 18 months, respectively. For women >50 years, parity and extended breastfeeding were associated with decreased risks: >5 births vs. nulliparous, OR 0·40 (95% CI 0·20-0·83), and 0·71 (95% CI 0·51-0·98) for >19 vs.

Skin lighteners and hair relaxers, both common among women of African descent, have been suggested as possibly affecting breast cancer risk. In Accra and Kumasi, Ghana, we collected detailed information on usage patterns of both exposures among 1,131 invasive breast cancer cases and 2,106 population-controls. Multivariate analyses estimated odds ratios (OR) and 95% confidence intervals (CIs) after adjustment for breast cancer risk factors. Control usage was 25.8% for ever use of skin lighteners and 90.0% for use of hair relaxers for >1 year. The OR for skin lighteners was 1.10 (95% CI 0.93-1.32), with higher risks for former (1.21, 0.98-1.50) than current (0.96, 0.74-1.24) users. No significant dose-response relations were seen by duration, age at first or frequency of use. In contrast, an OR of 1.58 (95% CI 1.15-2.18) was associated with hair relaxers, with higher risks for former (2.22, 1.56-3.16) than current (1.39, 1.00-1.93) users. Although numbers of burns were inconsistently related to risk, associations increased with duration of use, restricted to women who predominately used non-lye products (p for trend

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.

Background: Breast cancer is a heterogeneous disease with clinically, molecularly and pathologically defined subtypes that have different etiologies, clinical presentations and outcomes. African women reportedly have especially high rates of breast cancers that are estrogen receptor (ER) or progesterone receptor (PR) negative, or triple negative [ER, PR and human epidermal growth factor receptor-2 (HER-2) negative], with the proportion reported for triple negative breast cancers ranging from 28-82%, compared to 11-20% among Caucasian populations. However, it is unclear to what extent pathology and specimen handling affect receptor measurements in Africa. Here we sought to determine pathology specimen quality of breast tumor tissues from three hospitals in Ghana where we are conducting a molecular epidemiologic study of breast cancer. Methods: We acquired 15 formalin-fixed paraffin-embedded (FFPE) archived breast cancer tissue blocks with specimens obtained at biopsy (N=5) or surgery (N=10) from three hospitals in Ghana. Blocks were re-embedded and four 0.5um whole sections were cut for hematoxylin and eosin stains, and immunohistochemistry (IHC) using previously validated protocols for ER (clone 1D5), PR (clone PgR1294) and HER2 (polyclonal), all obtained from Dako (Carpinteria CA). Specimens were considered ER or PR positive if 10% or more cells stained positive, while HER2 was considered positive if intensity of staining was 3+. Results: Specimens were noted to be embedded in high-melting temperature paraffin. To perform ER, PR, and HER2 IHC staining, deparaffinization procedures were optimized for hard paraffin. Zonal and gradient staining patterns were noted in surgical specimens, features that are likely due to delayed/prolonged fixation. Zonal/gradient staining issues were not identified in the needle biopsies, which were smaller compared to specimens collected at surgery and generally placed in buffered formalin immediately after collection. IHC assays of the tumor specimens revealed that 67% were ER-positive, 20% PR-positive, and 66% HER2 positive. The proportion negative for all three markers was 13%. Conclusion: In contrast to previous reports for African breast cancer patients, within our sample of FFPE breast cancers from Ghana we found a higher prevalence of ER positive tumors and a lower prevalence of tumors negative for all three markers. These results suggest that the high rates of hormone receptor negativity previously reported in African populations may be inaccurate due to various sources of error, particularly fixation time and IHC staining protocols. Future studies focusing on proper documentation of sample collection procedures and optimization of IHC methods are required to determine the true prevalence of molecular subtypes of breast cancer among African women. Such efforts are essential for breast cancer surveillance, identifying etiologic factors for prevention efforts and developing more effective treatment programs. Citation Format: Jonine D. Figueroa, Lawrence Edusei, Ernest Adjei, Nicholas Titiloye, Kris Ylaya, Beatrice Addai, Joe Nat Clegg-Lamptey, Baffour Awuah, Kofi Nyarko, Daniel Ansong, Seth Wiafe, Louise A. Brinton, Stephen Hewitt. Impact of pathologic specimen quality on classifying molecular subtypes of breast cancer: A pilot study from three hospitals in Ghana, Africa. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr C11. doi:10.1158/1538-7755.DISP13-C11

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.