DCIS and Clotting

Breast Cancer Prevention Drugs - Prevent Breast Cancer

Your blood contains proteins known as clotting factors. When a blood vessel is cut, the clotting factors help form a solid clot that acts as a plug to stop the wound bleeding.

Normally, blood clotting occurs when a blood vessel is damaged and bleeds. If the blood clots when a vessel is not damaged, a clot can form within a vein or artery (thrombosis) and restrict the blood flow.

There is an increased risk of DVT (Deep Vein Thrombosis) in people with cancer as their blood appears to clot easier. Analysis of a group of patients with cancer and DVT show they have a worse prognosis – they appear to have more aggressive cancer than patients with cancer and no thrombosis.

Therefore, it appears that there may be a link between cancer and clotting.

DCIS (ductal carcinoma in situ) is very early cancer which occurs in the milk ducts of the breasts. These cells are all contained inside the ducts and have not started to spread into the surrounding breast tissue.

Many clinicians describe DCIS as pre-cancer, because as it is contained, has not spread and so is not causing harm. However, if not treated DCIS can spread into the surrounding breast tissue and become invasive breast cancer. DCIS is being found more often than in the past. It is often picked up by mammograms when women are screened for breast cancer. DICS accounts for around 25% of all mammographic diagnoses.

Currently doctors advise treatment for all ladies diagnosed with DCIS. The only treatment at the moment though is surgery. This is often the removal of an area of the breast, that can leave scarring and deformity or it can sometimes mean removal of the whole breast (mastectomy).

We have seen signs of increased clotting in the breast tissue (fibroblasts) that surrounds DCIS. This has led us to wonder whether clotting may help cancer escape from the milk ducts and progress from pre-cancer (DCIS) into invasive cancer.

Our project aims to find an alternative method for preventing the spread of  this early or ‘pre-‘cancer into the rest of the breast, and becoming true ‘invasive’ cancer.  We shall do this by looking at the effects of anticlotting drugs on DCIS cells and other breast cells (fibroblasts) in the laboratory.

The Method

We will be investigating the effects of different types of fibroblasts on DCIS cells. We shall compare the effects of normal fibroblasts to the effects of fibroblasts that have been manufactured to cause clotting on DCIS. We will then study the effects of various anti-clotting drugs.  This shall be done using two laboratory techniques:

  • Boyden Chamber – The Boyden chamber is a useful tool to study cell migration and cell invasion (characteristics of cancer cells). It consists of a cylindrical insert that contains the cells to be studied (DCIS and fibroblasts). This is placed on top of a well that contains collagen-like cells. The insert and well are separated by a polycarbonate membrane with tiny pores in it. Cells that are able to migrate will move through the pores toward the collagen below and can be stained and counted. To study cell invasion, a protein layer can be put on top of the membrane and only invasive cells will get through this to the collagen, to be counted.
  • 3D Matrigel Model – Matrigel is a gelatinous protein mixture that resembles the supporting scaffold of proteins that surround cells in human tissue. It is used by cell biologists to grow and study cells. This can be used to see if cells can be changed from normal to DCIS by growing them under different conditions.

Outcomes

  • We hope to determine if the cells that cause clotting make DCIS cells behave like invasive breast cancer cells, and make normal cells act like DCIS cells.
  • We hope to determine if anti-clotting drugs slows or stops the progression of normal cells into DCIS cells, and DCIS cells into invasive cancer cells .

We hope that if the results from this study and further studies are promising, this will  lead to patient trials of drugs that may halt the progression of DCIS.