Validation trial

The 2,000 patient validation trial commenced in 2007 and was supported by major radiology and diagnostic groups. The trial involved Australian women who have been referred to radiologists by their GP for breast imaging. The results from the Fermiscan Test were compared to current screening methods of mammography and ultrasound (and any subsequent biopsy & pathology results). The trial has been completed.

The results of the validation trial have been released. The outcome confirms that the Fermiscan Test has the potential to offer an effective and non-invasive addition to current breast cancer screening options.

The key results were:

Overall accuracy level of the Fermiscan Test in the 2,020 patient trial was 77%. In general the trial showed that the test performed better in younger women (see Chart I below for the results by age groups).
The Fermiscan Test provided a correct negative diagnosis for 1,515 women, (a 99% negative predictive value) The test correctly identified as negative for breast cancer 85% of patients referred for a biopsy as a result of mammography. This highlights the potential value of the test in conjunction with current screening methods.
The test correctly identified 25 out of 39 patients as positive for breast cancer. The false positive rate was 23% (a 5% positive predictive value). Some false positives may turn out to be positive which were missed by imaging. This will become clearer with long term follow up.
14 patients found to be positive for breast cancer by a mammogram and biopsy were missed by the Fermiscan Test. This is believed to be due to damage to hair from treatments and/or biological variation.

Chart One Fer2k Trial results by age (2,009 patients)

Table One Comparision of the Fermiscan Test to current screening methods

Results	Fermiscan Test ⁽¹⁾ %	Mammography alone ⁽²⁾ %	Ultrasound alone ⁽²⁾ %	Mammography plus Ultrasound ⁽²⁾ %
Sensitivity	74	50	50	78
Specificity	77	96	92	89

Definitions:
Sensitivity - the ability to accurately detect cancer - refers to the proportion of people with disease who were correctly detected by the test
Specificity - the ability to accurately confirm the absence of cancer - refers to the proportion of people without disease who returned a negative test result

¹ Fermiscan 2,000 patient clinical trial, 2008, for patients aged less than 70 years.
² USA study 2,809 patients JAMA Vol 299 No 18, May 4, 2008 Combining screening with ultrasound and mammography vs mammography alone in women at elevated risk of breast cancer

Analysis of the results demonstrated that of the 2009 patients, 201 (10%) were sent for biopsy as a result of a suspicious mammogram or ultrasound examination. 39 (19%) were confirmed to have invasive breast cancer. The average age of these women was 55. Of these, 25 (64%) were positive by the Fermiscan Test.

1970 patients ( 1808 patients without breast cancer (negative by imaging) and 162 patients without breast cancer (negative by biopsy), recorded no detectable breast cancer. Fermiscan recorded an abnormal hair X-ray diffraction pattern for 455 (23%) of these patients.
Of the 162 (81%) patients with negative biopsy results, the Fermsican Test correctly called 137 (85%) negative.

Table Two Analysis of the Fer2K results

Results	Patients with breast cancer confirmed by biopsy	Patients without breast cancer (negative by biopsy)	Patients without breast cancer (negative by imaging)	Total
Fermiscan Positive (Ring)	25	25	430	480
Fermiscan Negative (No ring)	14	137	1378	1529
Total	39	162	1808	2009

The accuracy of the test in the market is expected to improve as women will prepare for the test by ensuring they have undamaged new growth of hair for testing, (approximately 4 weeks - 10.5mm in length is required). During the trial this could not take place as patients had no advance notice of the test and the requirements. The value of the test for women of all ages was confirmed with patients covering a wider age group than current screening recommendations.

Table Three Comparative studies on mammography

Country	False Positive	False negative
UK ¹	10%	28%
Singapore study ²	14%	46%
Australian Study ³	12%	25%
American Study ⁴	16%	34%
American Study ⁵	32%	16%
American Study ⁶	2%	59%
Japan Study ⁷	8%	39%
USA ⁸	4%, 8%	50%
Fermiscan Test ⁹	23%	36%

¹ Journal of the National Cancer Institute. Vol.94, No 5, March 6, 2002
² Annals of the Academy of Medicine, Singapore 2004
³ American Journal of Roentgenology (April 2003) Sydney Breast Imaging Accuracy Study
⁴ Results of a Multi-Center, Multi-Reader Trial. Presented RSNA Nov 25-30, 2007 conference
⁵ http://breast-cancer-research.com/content/3/1/55 12 April 2000
⁶ Etta D. Pisano et al, 2005, Diagnostic Performance of Digital versus Film Mammography for Breast-Cancer Screening. The New England Journal of Medicine 353:1773-1783
⁷ Jpn J Clin Oncol 2007; 37 (9) 715-720
⁸ JAMA Vol 299 No 18, May 4, 2008 Combining screening with ultrasound and mammography vs mammography alone in women at elevated risk of breast cancer
⁹ 2,000 Blinded patient trial, 2008 Fermiscan Test accuracy compared to mammography/ultrasound and biopsy

Small Study

In June 2008 the results from a small open study to detect breast cancer analysed hair from 35 women confirmed to have either early breast cancer or diagnosed with metastatic disease, (which involves the spread of cancer from the breast to other organs of the body) demonstrated a sensitivity of 84 per cent. In this small study, the indications for the test for metastatic disease are encouraging but larger numbers are required before firm conclusions can be drawn.