While mammograms reduce breast cancer mortality by 15-20%, the diagnosis in many cases—approximately 15% of all breast cancers—occurs after a patient has a negative mammogram and before her next recommended screening. These are “interval cancers,” and they carry big implications. Patients who receive a cancer diagnosis during the interim see poorer outcomes than those whose cancers show up in screening. Yet some practical gaps in the research have persisted, says Anne Marie McCarthy, assistant professor of epidemiology.

“Most of the literature on this topic has focused on patients who are diagnosed with cancer within one year of a negative mammogram, an approach that ignores current U.S. Preventive Services Task Force screening recommendations: a mammogram every two years, for women over 50,” she says. Most of the existing studies also don’t differentiate between early-stage and advanced-stage tumors. “A small early-stage cancer diagnosed within one year of a negative mammogram may be of less concern than an advanced-stage tumor diagnosed two years afterward,” she says.

A study she led, one of the largest of its kind to date, highlights several important factors that can help us pick out and possibly adjust the screening plan for women who are most likely to be diagnosed with advanced-stage cancers within that two-year timeframe. The findings are published in the journal Cancer.

Interval cancers include some that a patient’s most recent mammogram missed, and some that, given their rapid growth rates, developed during the interval since the last screening. Though breast density—a characteristic that can help tumors hide from mammography—has attracted a lot of attention from clinicians, McCarthy’s team found evidence that body mass index, or BMI, is also important, especially in the year between screenings. Obese women were almost twice as likely to be diagnosed with advanced stage cancer in the year after a negative mammogram compared to women with BMI in the normal range, and were also at elevated risk of advanced cancer in year two. Their analysis also showed that overweight and obese women had a 40% higher risk of early-stage cancer in year two.