The Role of NAF Cytology in the Identification of Atypical Ductal Hyperplasia

Atypical Ductal Hyperplasia. Atypical ductal hyperplasia (ADH) is a condition in which the cells lining the breast duct grow excessively and abnormally. Without other risk factors, it produces a five-fold increased risk of breast cancer. With a family history of breast cancer, a diagnosis of ADH increases the risk of breast cancer 11- to 22-fold and in one study fully one-third of women with a biopsy of ADH have an occult cancer growing nearby.

In fact, another study looked at changes in chromosome markers in ADH that are typical for invasive ductal cancer to determine if ADH was monoclonal for these changes, as expected of cancer, or polyclonal, as expected of hyperplasia. This study concluded that 40% of ADH was monoclonal and had the hallmarks of a cancerous growth. The analysis of NAF for these chromosomal changes could help determine the malignant or non-malignant properties of ADH in a particular patient and thus provide information allowing a Personalized Medicine therapeutic approach.

The incidence of ADH in otherwise normal women was determined in a study of women with normal mammograms who were undergoing breast reduction surgery and was found to be 4.4%. This would suggest that upwards of 4 million MM women have undiagnosed ADH.

ADH can only be diagnosed definitively by NAF analysis or a breast biopsy. In a study of 2.5 MM women having screening mammography, the incidence of biopsy-proven ADH was less than 0.1%, suggesting that mammography misses over 97% of patients with ADH. On the other hand, in a study of 1,134 women undergoing NAF sample collection, 6.3% had ductal hyperplasia or atypia, suggesting that this method is able to detect the true incidence of ADH. In addition, a Dutch study reported in December, 2009, that low dose radiation from mammograms can increase cancer incidence 1.5 to 2.5 fold in high risk women increasing the complexity of managing the high risk patient. The MASCT System involves no radiation and the Company believes this aspect will increase the acceptance of NAF testing with the MASCT System.

The most comprehensive study of the predictive value of NAF cytology for identifying high risk women for breast cancer was conducted at the University of California at San Francisco over a 21-year period. NAF was collected from 7673 women in two groups, the groups were stratified into women with acellular, normal, hyperplasia, or atypical NAF cytology and the incidence of breast cancer determined in the two groups over an average of 21- and 9-years follow-up, respectively. The incidence of hyperplasia by NAF cytology was 13.6% and the incidence of ADH was 1.6%. Breast cancer occurred in 3.7% of the women with acellular cytology and in 8.2% and 11.0% of the women with hyperplasia and atypia, respectively.