International studies look to modify traditional breast cancer screening

SAN ANTONIO-While the U.S. breast cancer community grapples with the nuts and bolts of mammography screening, its international counterparts are working on enhancements and modifications to the screening process, which they presented at SABCS 2009.

Researchers in Taiwan and China found that combining mammography and ultrasound led to a higher cancer detection rate in women aged 40-49. Meanwhile in the UK, the National Health Service will drop the age for baseline screening from 50 to 47 years by 2012, but a group from West Midlands Research Collaborative have made a case for starting screening at age 40 in certain ethnic groups.

Finally, researchers in Germany assessed the value of semi-annual ultrasound exams in high-risk women. A study coauthor told Oncology NEWS International that he believed semi-annual sonographic screening in these women was more valuable than yearly mammography.

Taiwan experience

Chiun-Sheng Huang, MD, and colleagues from the Breast Cancer Screening Group of Taiwan conducted a population-based, cross-over, randomized screening trial that alternated mammography with ultrasound.

Dr. Huang and colleagues invited 79,691 Taiwan residents, aged 40-49, from 19 centers in 13 counties to join the trial, which started in 2003. “Women enrolled in the trial were randomized into two study groups and one control group. In the first study group [n = 20,040], they started with ultrasound screening the first year and then mammographic screening in the second year,” he said. “In the second study group [n = 20,088], they started with mammographic screening in the first year and ultrasound in the second year. The control group [n = 39,563] did not receive any screening until the fifth year, and then they received both ultrasound and mammography. The screening interval was one year.”

There was no mammography-only control arm in this trial. Because of their younger age, most of the women had heterogeneously dense breasts, Dr. Huang said. The detection rate and annual incidence rate of interval cancer as a percentage of the control group were compared between the two imaging modalities (abstract 73).

Dr. Huang reported that for the first round of screening, the attendance rate was 59% for mammography and 56% for ultrasound. The repeat attendance rate for the mammography plus ultrasound was 85% for the second round and 91% for the third round.

Using BIRADS (Breast Imaging Reporting and Data System) criteria, about 10% of women in the ultrasound screening group were assigned to category 3 and had to return for follow-up imaging at six months. Based on mammography screening, about 15% of women were assigned to category 0 and required additional imaging.

For the first year of screening, the cancer detection rate was 2.2/1,000 for ultrasound and 3.66/1,000 for mammography. This difference was not statistically significant, Dr. Huang said (P < .05). However, for the second year of screening, the cancer detection rate was 1.69/1,000 for ultrasound and 3.56/1,000 for mammography, which was statistically significant. The program sensitivity was 58.2% for ultrasound screening and 90.1% for mammography screening.

“After one year, the combination of ultrasound and mammography detected three times more cancers compared to the baseline incidence rate in the control group,” he said. “We found eight interval cancers on ultrasound screening and two interval cancers on mammography.”

The author noted that mammography screening was able to detect more in situ and small, invasive cancers in comparison with ultrasound screening. Most of the cancers detected in the control group were large, invasive cancers. The sensitivity for ultrasound for invasive cancers was 75% vs 96% for mammography. The sensitivity for ultrasound for all cancers was 78% vs 97% for mammography.

“The present trial suggests that breast cancer screening with alternating mammography and ultrasound can detect breast cancer earlier, and detect more breast cancers, in younger women in Taiwan,” Dr. Huang said. A more definitive conclusion will be made after the results of the fourth round of screening, he said.

Earlier screening for minorities

Previous reports have shown that ethnic minorities present with more advanced disease at a younger age, according to Soni Soumain, MD, and colleagues. “The West Midlands has a significant population of ethnic minorities who could potentially benefit from earlier screening,” they wrote in their poster. “We wanted to test this hypothesis by assessing the age and route of presentation of breast cancer across these ethnic groups.”

The group collected data on patients treated for breast cancer from 2001 to 2007. They correlated patient age with mode of presentation (screening or symptoms) with ethnicity. Data were available for 528 women classified as Asian, 274 classified as African Caribbean, and 18,941 labeled as Caucasian (abstract 4008).

Dr. Soni’s group found that the peak age of breast cancer incidence for Asian women and black women was 10-20 years younger than for white women. Among Asian women, 37% had their cancer found through screening, while 26% of African Caribbean women had disease presentation on screening. In the symptomatic group, 26.5% of Asian women and 35% of African Caribbean women were younger than 47 when they presented with disease vs 13% of the Caucasian population.

The group stated that lowering the screening age from 50 to 47 should increase screen-detected cancers across the board, but they pointed out that based on their analysis, ethnic women present at a younger age. “We suggest the age of prevalent screening in these groups should be reduced further to 40 years,” they wrote. “This may increase detection of cancers at an earlier stage.”

Dr. Soni acknowledged that this research had several limitations. First, there were no data indicating that starting screening at a younger age in minority women had an effect on mortality. Also, there is the issue of exposing younger women to more radiation over time. Finally, screening compliance has historically been low among ethnic minorities.

However, Dr. Soni estimated that in his region, the compliance rate among ethnic women is already fairly high (between 70% and 75%).

BRCA and ultrasound

In another poster presentation, a group from the University of Cologne in Germany incorporated semi-annual, whole-breast ultrasound exams into routine screening of women who were BRCA1 and BRCA2 mutation carriers.

In the patient population for this observational study, 221 were deemed BRCA carriers after genetic testing. Starting at age 30, the women underwent mammography plus ultrasound and MRI. They then underwent a second ultrasound six months after the initial screening exam. Detected tumors were classified by histological subtype, grade, and hormone receptor status.

The authors reported that 13 primary tumors and 14 secondary contralateral tumors associated with BRCA were found in 25 patients (ages 25-66). Seventy-six percent of the tumors classified as BIRADS IV and V were found with sonography while 33.3% were detected with mammography. MRI found 100% of the tumors. Eleven percent of the tumors were found only on the semi-annual screening ultrasound; two patients had interval tumors palpated between screening appointments (abstract 4004).

The most common histological subtype was invasive ductal carcinoma (77.7%). The majority of tumors were grade 3 (55.6%). Most patients were estrogen receptor-negative (66.6%) and progesterone-receptor negative (66.6%). The mean tumor size was 11.1 mm.

While ultrasound did find tumors that mammography did not, as well as identify additional invasive cancers, the authors acknowledged that long-term follow up was needed to show a reduction in mortality from the additional sonographic screening.

Study coauthor Mathias Warm, MD, said that this imaging protocol is now the standard of care for women with BRCA mutations at his institution. His group does plan to follow up these patients to see whether ultrasound screening led to a reduction in mortality.

“We do mammography every year, but with ultrasound screening every six months, I think we could do mammography every two years instead,” he said. “I think semi-annual ultrasound is a better option in these women.”