Swedish breast imagingpioneer scoops Britishmedical literary prize

December 1, 2008

An aggressive, stealthy small breast cancer sub-type accounts for 10 percent of all breast cancers but half of all lesion-related deaths.

A text about an insidious subtype of small breast cancers that causes death in stealth, running contrary to the good prognosis typical for small lesions found early, has earned mammography expert Dr. László Tabár first prize in the radiology section of the British Medical Association's 2008 medical book competition.

Potentially lethal casting type calcifications have been on Tabár's radar since the late 1970s, as part of his extensive research into mammographically detected lesions smaller than 14 mm. Part of a series about early detection of breast cancer with mammography, the book, Casting Type Calcifications: Sign of a subtype with deceptive features, was published by Thieme in 2007 and picked up the BMA award in September 2008.

The casting type accounts for just 10% of all breast cancers but causes half of deaths related to lesions under the size of 10 mm, a fatality rate Tabár calls unacceptably high, regardless of the tumor size. In cases of in situ breast cancer, between 2% and 3% of patients die from the disease, seemingly inexplicably.

"This book serves as a wakeup call for physicians not to lump together the many different subtypes of screen-detected, tiny breast cancers," Tabár said. "Most of them have a 25-year survival outcome well over 90%, while this subtype shows a behavior of an advanced tumor."

As shown in the book, mammographic images provide invaluable help to physicians in distinguishing small cancers.

"The mammogram helps in predicting the long-term outcome of the small screen-detected breast cancers (1 to 14 mm in size) better than conventional histology does; therefore, we recommend using the mammographic prognostic features together with the other well-known prognostic factors," he said.

For the best results, tumor features on the mammograms should be looked at side by side with results from large thin-section and subgross large thicksection (3D) histology, he said. Such newer pathology technology more clearly delineates important anatomical features such as ducts and the terminal ductal lobular units, complementing traditional mammography and other imaging methods.

In contrast, the gold standard conventional pathology results in undercalling of cancers in comparison with newer breast imaging modalities, notably MRI.

"This very delicate discrimination between good- and bad-acting cancers is considerably more difficult to achieve with conventional histology," Tabár said. "We simply have to introduce an entirely new way of thinking. One has to handle ‘baby cancers' differently from those large palpable cancers that physicians have treated for centuries."

Tabár has been documenting his own consecutive cases since 1977, working alongside Dr. Tibor Tot, an associate professor of pathology at Uppsala University and coauthor of the award-winning book. Prof. Peter B. Dean, professor of radiology at the University of Turku in Finland, is the other coauthor.

A study evaluating long-term outcomes in over 700 women with small invasive breast cancer showed that for women with tumors sized 10 to 14 mm, the 20-year survival rate was 52% if casting calcifications were present versus 86% to 100% for those with other mammographic features (Cancer 2004;101[8]:1745-1759).

Another volume in the Thieme series, focused on crushed stone-like calcifications-the most common malignant subtype-was published in March this year.

The authors are currently working on a new book about stellate/spiculated tumors with no associated calcifications. Stellate lesions are associated with an excellent long-term survival rate of about 95%.

In Tabár's view, research suggests that changes to the TNM classification system for malignant breast tumors may be necessary in order to more accurately reflect the more dangerous nature of the casting subtype.

Women with cancers marked by casting type calcifications are typically undertreated, based on an assumption that they have early-stage disease. Unfortunately, by the time calcifications are visible on the mammogram, the disease is usually very extensive and should be treated differently from other types of screen-detected cancers, he said.

"Today's therapy methods can hardly influence the outcome of this subtype. What we are doing is pointing out the unexpectedly aggressive nature of this breast cancer to researchers and to the pharmaceutical industry and saying we need to come up with a better way of controlling this disease," Tabár said.

It is possible that the casting type calcifications result from gene damage and that new targeted therapeutic regimens could be developed by pharmaceutical companies, he said.

-By Emily Hayes