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UNDERSTANDING INVASIVE LOBULAR BREAST CANCER

About the Project

Invasive lobular carcinoma (ILC) is the second most common type of breast cancer following invasive ductal carcinoma (IDC), accounting for 10-15% of all cases. Histologically IDC tumors form spheroid-like masses (lumps), while ILCs grow as small, dis-cohesive cells in a single-file pattern. This unique growth pattern, largely attributed to the loss of E-cadherin-mediated adherens junctions, makes mammographic detection and surgical removal of ILC difficult, complicating breast conservation. In addition, compared to IDCs, ILCs present more frequently as multi-centric and bilateral and with metastases to unique sites such as ovaries, peritoneum and gastrointestinal tract. Paradoxically, while patients with ILC display favorable prognostic and predictive factors (Estrogen Receptor [ER] positive, Progesterone Receptor [PR] positive, HER2 negative, low Ki67 index), their long-term response to endocrine therapy is worse than that of patients with IDC. However, despite such distinctive histological and clinical features, ILC has remained a gravely understudied subtype of breast cancer.

In the Oesterreich lab, we are taking several complementary approaches to understand the mechanisms of ILC endocrine resistance and the genetic drivers of ILC disease progression. By comparing and contrasting human ILC and IDC cell lines and studying endocrine resistant cultures, we are discovering key regulators of unique ILC biology and ER-dependent and independent mediators of endocrine resistance. Taking advantage of our access to a large collection of clinical ILC samples, and long-term clinical follow-up data, we are identifying novel genetic drivers of ILC disease progression. To further validate the significance of our findings, we are utilizing human ILC cell line and patient-derived xenografts grown in mice. Our multidisciplinary team of biologists, clinicians, biomedical engineers and bioinformaticians is creating both a highly collaborative environment and an excellent training opportunity for graduate students and postdoctoral fellows.