K is for Karla Kerlikowske

Karla Kerlikowske has taken a second and third look at X-ray screening mammography. And what she has found, detailed most prominently in a series of articles that have appeared in the Journal of the American Medical Association (JAMA) over the past decade, is that the screening has both benefits and drawbacks.

Such a balanced assessment may seem an unlikely lightning rod, but being at odds with "accepted" wisdom — namely that mammography benefits women beginning at age 40 — it has thrust this physician and member of the UCSF Comprehensive Cancer Center into the front lines of a health policy debate.

For the moment, US health agencies continue to recommend mammography for women beginning at age 40. At the other end of the spectrum, over the past year, an independent advisory panel to the National Institutes of Health, as well as a study published by Dutch researchers in the prominent British medical journal, The Lancet, have concluded that the benchmark mammography studies were flawed and that there is no good evidence that screening mammography generally benefits any age group of women. The Canadian Task Force on Preventive Health Care and the International Union Against Cancer, an organization that makes recommendations for European countries, recently reviewed the randomized controlled trial data on screening mammography. Both bodies concluded that there is little benefit to undergoing screening mammography for women under age 50, but that women aged 50 to 69 do benefit.

In a seminal 1996 JAMA article, Kerlikowske and department of epidemiology colleagues Virginia Ernster and Deborah Grady reported results from their own meta-analysis of previous studies, in which they concluded that evidence did not yet warrant routine mammography for women under 50.

Kerlikowske and her colleagues also warned against the tendency for regular screening mammography to produce false positive results. Most abnormal mammograms are not due to cancer, but a positive test provokes anxiety, additional imaging studies, and oftentimes, biopsies, before cancer can be ruled out. The incidence of false positive mammogram results is greater still among pre-menopausal women, who as a group have a lower risk for breast cancer and denser breasts that make detection of lesions more difficult.

Another issue illuminated by the UCSF epidemiologists is the skyrocketing rate of diagnosis — in large part due to mammography — of a type of breast cancer called ductal carcinoma in situ (DCIS). DCIS is a lesion confined to milk ducts within the breast. Researchers believe that not all DCIS tumors are destined to become potentially life-threatening, invasive breast cancers: The risk of developing invasive cancer is thought to be roughly 15 percent over 10 years following a DCIS diagnosis, and the risk of dying of invasive cancer is estimated in the 1 percent to 2 percent range. However, there is no way to know which DCIS tumors will progress to invasive cancer, so surgical treatment for DCIS now is the standard of care.

Regardless of the size of the apparently modest mortality reduction for women aged 50 to 69 who undergo screening mammography and the smaller benefit for women aged 40 to 49, Kerlikowske advocates informing all women about both the harm and benefit associated with screening mammography.

"If women start at age 50 and undergo ten mammograms, one every two years from age 50 to 69, they will maximize their chances of benefiting from mammography and minimize their chances of being exposed to the potential harm of screening."

by Jeffrey Norris