Adding ultrasound to mammography screening tests could improve rates of breast cancer detection in Japanese women, according to a new study.
Findings showed that combining ultrasound with mammography resulted in correctly detecting cancer in more than 9 of 10 cases (91% sensitivity), whereas for women given mammography alone, just more than three quarters of tests correctly identified breast cancer (77% sensitivity).
These data are important because mammography screening alone may not be sufficient for screening Asian women, owing to the fact that they characteristically have higher-density breasts than women of other ethnicities and because breast cancer tends to present at an earlier age in Japan than in Europe or the United States. The accuracy of mammography is reduced both in women with high-density breast tissue and in young women.
Therefore, the use of adjunctive ultrasonography could offer a low-cost way to increase sensitivity and detection rates of early cancers in women with dense breast tissue, note the authors, led by Noriaki Ohuchi, MD, PhD, of Tohoku University Graduate School of Medicine, Miyagi, Japan.
"Our results suggest that adding ultrasound to mammography results in more accurate screening results for women in Japan, which could ultimately lead to improved treatment and reduced deaths from the disease," said Dr Ohuchi in a statement. "Further work will now be needed to see if these results can be extended to other countries in Asia. In addition, long-term follow-up of these results will determine whether including ultrasound tests in breast cancer screening ultimately affects the likelihood of successful treatment and survival, as we would expect."
The study was published online November 5 in the Lancet.
The incidence of breast cancer has been increasing substantially in Japan and other Asian countries over the past 3 decades. The age-specific incidence of female breast cancer in Asia peaks at age 40 to 49 years, note the authors, whereas in western countries, the peak is at age 60 to 70 years. But regardless of ethnic origin, it is estimated that about 60% of women in their 40s have dense breasts.
Higher Detection of Invasive Cancers
In the Japan Strategic Anti-cancer Randomized Trial (J-START), Dr Ohuchi and colleagues assessed the efficacy of adjunctive ultrasonography in breast cancer screening for Japanese women aged 40 to 49 years.
They enrolled 72,998 women between 2007 and 2011; 36,859 were assigned to ultrasound testing plus mammography (the intervention group), and 36,139 were assigned to the control group of mammography alone. Screening was conducted twice during a 2-year period.
The mean age of participants was 44 years; 3344 (4.6%) participants reported a history of breast cancer in first-degree female relatives, and 917 (1.3%) reported having had one or more benign breast conditions.
The authors found that sensitivity was significantly higher in the intervention group than among the control patients (91.1% vs 77.0; P = .0004), but specificity was significantly lower (87.7 vs 91.4; P < .0001), so the downside is substantially more false-positive findings.
A higher number of cancers were detected in the intervention group than in the control group (184 [0.50%] vs 117 [0.32%]; P = .0003). Of 184 cancers detected in the intervention group, 128 (70%) were invasive, as compared with 86 (74%) of 117 in the control group.
Cancers were more frequently of clinical stage 0 and I in the intervention group compared with the control group (144 [71.3%] vs 79 [52.0%]; P= .0194). The frequency of breast cancers that were of clinical stage II or higher did not differ significantly between the two groups.
A total of 18 interval cancers (0.05%) were diagnosed in the intervention group, compared with 35 (0.10%) in the control group, so the use of ultrasound was associated with a decrease of 0.05% in interval cancers. Sixteen (89%) of the 18 cancers and 27 (77%) of 35 interval cancers were invasive.
Further assessment was recommended for 4647 women in the intervention group, compared with 3153 in the control group. The number of biopsies performed after the first round of screening was also higher in the intervention group than in the control group.
Challenges to Ultrasound Use
In an accompanying editorial, Martin Yaffe, PhD, and Roberta Jong, MD, both from Sunnybrook Research Institute and Department of Medical Biophysics, University of Toronto, Canada, note that this trial is important for several reasons. It is the first randomized trial of population screening with ultrasonography conducted in asymptomatic women at average risk, and it was done in relatively young women.
"Despite evidence of mammography screening effectively reducing mortality in women in their 40s, this method is seldom recommended or provided for women younger than 50 years," they write. "Definitive evidence of whether ultrasonography screening of women from age 40 years can further reduce breast cancer mortality could be an important step."
These results are also likely to be generalizable to other populations, both Asian and non-Asian, at least for women with small, dense breasts, Dr Yaffe and Dr Jong write.
But there are challenges to using ultrasound for high-volume screening, they point out. More time is needed per examination than for mammography, and it is likely to result in more recalls, follow-up after shorter intervals, and lower positive predictive value for biopsy results than for mammography.
"Automated breast ultrasonography systems would greatly facilitate the screening process, but outcomes must be at least equal to those of the handheld systems that at present are the mainstay of practice," the editorialist add.
The study was funded by the Ministry of Health, Labour and Welfare of Japan. The authors and editorialists have disclosed no relevant financial relationships.