Background
Breast cancer is the most common malignancy in women, affecting over 1.5 million women every year, which accounts for the highest number of cancer-related deaths in women globally.
Hereditary breast cancer (HBC), an important subset of breast cancer, accounts for 5–10% of total cases. However, in Low Middle-Income Countries (LMICs), the population-specific risk of HBC in different ethnicities and the correlation with certain clinical characteristics remain unexplored.
Methods
Retrospective chart review of patients who visited the HBC clinic and proceeded with multi-gene panel testing from May 2017 to April 2020.
Descriptive and inferential statistics were used to analyze clinical characteristics of patients. Fisher’s exact, Pearson’s chi-squared tests and Logistic regression analysis were used for categorical variables and Wilcoxon rank-sum test were used for quantitative variables. For comparison between two independent groups, Mann-Whitney test was performed. Results were considered significant at a p value of < 0.05.
Results
Out of 273 patients, 22% tested positive, 37% had a VUS and 41% had a negative genetic test result. Fifty-five percent of the positive patients had pathogenic variants in either BRCA1 or BRCA2, while the remaining positive results were attributed to other genes. Patients with a positive result had a younger age at diagnosis compared to those having a VUS and a negative result; median age 37.5 years, IQR (Interquartile range) (31.5–48). Additionally, patients with triple negative breast cancer (TNBC) were almost 3 times more likely to have a positive result (OR = 2.79, CI = 1.42–5.48 p = 0.003). Of all patients with positive results, 25% of patients had a negative family history of breast and/or related cancers.
Conclusions
In our HBC clinic, we observed that our rate of positive results is comparable, yet at the higher end of the range which is reported in other populations. The importance of expanded, multi-gene panel testing is highlighted by the fact that almost half of the patients had pathogenic or likely pathogenic variants in genes other than BRCA1/2, and that our test positivity rate would have only been 12.8% if only BRCA1/2 testing was done. As the database expands and protocol-driven referrals are made across the country, our insight about the genetic architecture of HBC in our population will continue to increase.
Breast cancer is the most commonly diagnosed cancer worldwide with an estimated 2.3 million new cases (GLOBOCAN, 2021). The incidence of breast cancer is higher in high income countries (HICs; country with gross national income capita exceeding US dollars 12,056 per the World Bank) compared to low-middle income countries (LMICs; country with gross national income capita within the ranges of US dollars 906 to 3,595 per the World Bank), but it is unclear whether this is due to increased hormonal, reproductive and lifestyle risk factors or simply due to better detection rates because of organized and opportunistic mammographic screening in HICs (GLOBOCAN, 2021;Sung et al., 2021;Thun et al., 2017). The reported mortality is higher in LMICs when compared to HICs with Pakistan being the 7th highest among south-central Asia countries (GLOBOCAN, 2021;Sung et al., 2021). This may be explained by late diagnosis, as well as lack of access to multidisciplinary care required in the optimal management of breast cancer. Moreover, lack of screening and poor access to diagnostic centers in rural areas for early detection, along with sub-standards of healthcare facilities,
In the theory of fuzzy fixed point, many authors have been proved different contractive type fixed point results with different types of applications. In this paper, we establish some new fuzzy cone contractive type unique coupled fixed point theorems (FP-theorems) in fuzzy cone metric spaces (FCM-spaces) by using “the triangular property of fuzzy cone metric” and present illustrative examples to support our main work. In addition, we present a Lebesgue integral type mapping application to get the existence result of a unique coupled FP in FCM-spaces to validate our work.
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