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Molecular Genetics of Lobular Breast Cancer in a South African cohort and effect of HIV infection.

UK - Department for Business, Energy and Industrial Strategy

Invasive lobular breast cancer (ILC) has distinct etiological, clinical and biological characteristics compared with the more common invasive ductal/no special type carcinoma (IDC). ILCs are characterized by E-cadherin loss, show stronger associations with the use of hormone replacement therapy (HRT) than IDC and have a different pattern of metastatic spread to IDCs, tending to infiltrate the peritoneum, ovary and gastrointestinal system. There is some evidence that they are less chemo-sensitive than IDC and that the 10-year survival rate of women with ILC is lower than that of ER+ IDCs. ILC accounts for 10-15% of all invasive breast cancer in Western countries and is less frequent in lower and middle income countries presumably due to lifestyle factors and lack of HRT use. However, there is evidence from the USA that African Americans have more aggressive invasive lobular carcinoma subtypes and inferior early outcomes. It is also likely that with changes in reproductive behaviors and westernized lifestyle factors there will be an increase in lobular breast cancer in sub-Saharan Africa. The objectives of this study are to: 1. Characterize clinico-pathological features and molecular genetics of ILC in African women to assess whether they have a more aggressive phenotype than a UK cohort of ILC 2. Assess whether HIV infection has any impact on the above and if anti-retrovirals can affect the metabolism of tamoxifen, a drug frequently used in the treatment of ILC. 3. Assess whether circulating tumor DNA can be used to detect metastatic ILC in HIV- and HIV + patients. 4. Develop a collaboration between the teams at Kings College London and University of Witwatersrand so that the above can be expanded to other subtypes of breast cancer

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