Breast cancer

Every 10th woman will develop breast cancer during her lifetime.

In Norway, there were 2,956 women who received this diagnosis in 2012.  In comparison, the disease affected 1,235 women in 1970. Breast cancer affects first and foremost women over the age of 50. Only 5.6% of new cases occurred in women under 40 years in 2004. The disease constitutes 40% of all cancer in women between the ages of 30 to 54 years. The average age at diagnosis is 59. The risk increases with age, but isolated cases occur in women under 30 years of age.

Breast malignancy Overview

Breast cancer is by far the most common form of cancer in women. The disease is characterized by a varied course, from rapidly growing tumors with early distant metastasis, to slow growing tumors which remain in the breasts without metastasizing. Twenty-five to 35% of breast tumors are aggressive. The majority of breast tumors are carcinomas. Sarcoma tumors are rare, but are important to be aware of as they are treated differently from other breast carcinomas.

Increased survival

Survival after diagnosis and treatment has continually improved over many decades. This is in part due to increased use of mammography screening, which provides early detection of the disease, and improved treatment. Approximately 2/3 of patients are cured of the disease. Five year survival without a sign of relapse, all stages considered, is more than 80%. In 2004, 694 women and 3 men died of breast cancer in Norway. Of these, 423 were over 65 years. Breast cancer is the most important cause of lost years of life in women under 65 years and ranks before both heart/vascular diseases and accidents. At the end of 2005, there were 31,548 women with the diagnosis.

Early diagnosis is, despite great differences in biology, the most important means of improving the prognosis. The prognosis is also strongly dependent on stage. Five year relative survival where the disease is limited to the breast is 94.1%, compared to 16.9%, if there is distant metastasis at the time of diagnosis.

Varieties

Seventy to 80% of invasive breast carcinomas are histologically of the infiltrating ductal type. Ten to 20% are of the infiltrating lobular type, while other types constitute the rest.

Premalignant lesions are recognized microscopically by abnormal proliferative activity (cell growth) in the ductal system or in the glands (lobular), but where there are no signs that the epithelial cells have penetrated the basal membrane. The lesions can be classified according to proliferation, cellular atypia and tissue architecture as shown below:

• Lobular and ductal epithelial hyperplasia without atypia
• Lobular and ductal epithelial hyperplasia with atypia
• Lobular carcinoma in situ (LCIS)
• Ductal carcinoma in situ (DCIS) grade 1-3 (van Nuys grading) (2)

DCIS, also known as intraductal carcinoma, should not be confused with invasive carcinoma of the ductal type. Previously, DCIS was considered a rare condition and constituted only between 1.4 and 5.3% of all newly diagnosed breast cancer cases. After the introduction of mammography screening, more women are diagnosed with DCIS (10-30%).

In areas with established mammography screening programs, DCIS constitutes 25-30% of new breast cancer cases in the first screening round. In later screening rounds, the number is 10-20%. The main problem with DCIS is that the risk for local recurrence in the breast after resection alone is much greater than with other pre-malignant lesions in breast tissue. In addition,a large majority of DCIS will not develop into invasive carcinoma if left untreated. For this reason, there is a great need for dependable prognostic markers.

Our breast cancer materials

• Normal breast – This material consists of 43 normal breast specimens which can be used as control material. We have previously measured DNA ploidy for all cases.

• Ductal carcinomas in situ – Ductal carcinoma in situ represents a special diagnostic challenge, since around 20% develop into invasive cancer and there is no clear maker for identification. We have a total of 121 patients separated into 75 patients from Nottingham (75 DCIS + 25 samples which later developed into invasive tumor) and 43 patients from Oslo University Hospital.

• Invasive cancer stage I/II - We have samples from a total of 480 patients with a clear prognosis (good prognosis: disease free > 10 years after treatment, poor prognosis: recurrence or death within 5 years from the disease). This is a pilot material used in the search for new prognostic marker for breast cancer.  We have previously made TMA blocks for the project. The material has been used for a collaboration project with CCB (Kirsten Sandvig) where the purpose is to investigate the clinical significance of Flotillin 1 and 2, and the connection between expression levels of Flotillins and the known clinical biomarker ErbB2.