Younger women at increased risk for breast cancer may benefit from biennial mammography screening beginning at age 40, according to a pair of studies published May 1 in Annals of Internal Medicine.

Heidi D. Nelson, MD, MPH, from Oregon Evidence-Based Practice Center at Oregon Health & Science University in Portland, and colleagues sought to determine what factors increase risk for breast cancer in women aged 40 to 49 years and the magnitude of risk for each factor.

“Risk-based screening has been recommended for other health conditions in the U.S. and may provide a similar evidence-based approach for breast cancer," wrote Nelson and colleagues. "Although most women who develop breast cancer have no known risk factors, information about risk may be particularly useful when making decisions about screening.”

The researchers evaluated data from 66 published articles and from the Breast Cancer Surveillance Consortium and examined 13 possible risk factors. The data showed that having extremely dense breast tissue and a first-degree relative with breast cancer (parent, sibling or child) doubled a woman’s breast cancer risk, according to Nelson et al. “This level of risk corresponds to the risk thresholds of the Cancer Intervention and Surveillance Modeling Network (CISNET), which demonstrated similar benefits and harms for increased-risk women starting biennial screening at age 40 years and average-risk women starting at age 50 years.”

The risk was even higher for a woman with more than one first-degree relative with breast cancer or first-degree relatives with a diagnosis before age 50.

Having a prior breast biopsy, second-degree relatives with breast cancer or heterogeneously dense breasts increased a woman’s risk by 1.5- to two-fold; and current use of oral contraceptives, never giving birth to a child or giving birth to a first child after age 30 increased a woman’s risk by one- to 1.5-fold.

The researchers suggested that focusing on high breast density and first-degree family history might offer a feasible approach to personalized screening. However, they also acknowledged the challenges associated with applying breast density as a stratification tool and noted that clinical studies have not established its role in clinical practice. In addition, radiologists employ variability in reporting of breast density.

Nicolean T. van Ravesteyn, MSc, from Erasmus Medical Center in Rotterdam, the Netherlands, and colleagues aimed to determine the threshold relative risk (RR) which tipped the balance of benefits and harms to support screening mammography beginning at age 40.

van Ravesteyn and colleagues recognized the role of screening technology and wrote, “Technology that improves screening test performance might influence the balance of benefits and harms of screening mammography in younger women. … Digital has higher test sensitivity than film mammography in women younger than 50 years, detects more cases of ductal carcinoma in situ and leads to more false-positive results,” they wrote.

The researchers used four microsimulation models to determine RR for women aged 40 to 49. They compared mammography screening starting at age 40 versus age 50 using either digital or film mammography and also compared annual and biennial screening intervals to determine which approach yielded the most benefits (life-years gained, breast cancer deaths averted) and least harms (false-positives).

For women aged 40 to 49 with a two-fold increased risk for breast cancer, the harm-benefit ratio of biennial screening with film mammography was similar to that of biennial screening of average-risk women aged 50 to 74, according to van Ravesteyn et al.

They noted that annual screening is associated with a small additional benefit. In addition, digital mammography was linked with greater harm relative to benefit than film among women in their 40s. That’s because digital results in more false-positive studies.

van Ravesteyn and colleagues observed that the four models produced consistent results among outcome measures, “predicting considerably higher threshold RRs when breast cancer deaths averted are used instead of life-years gained, because there are more life-years to gain by averting a death in the 40- to 49-year age group than in older age groups.” This measure also takes into account the number of lives saved and the number of life-years gained per life saved.