This prospective randomized controlled trial showed that undergoing A-MRI had no demonstrable impact on psychological well-being in women with a history of breast cancer. Our primary outcome trait anxiety was moderately high in all patients at baseline and did not change significantly over time; the average score of trait anxiety at the 6-month follow-up was 50.99+/-4.6 with MG vs 51.73+/-2.56 with A-MRI, p>0.05. Similarly, self-report worry, including worry of breast cancer recurrence, did not change over time for both conditions. Although there was some benefit of A-MRI over MG alone in reducing state anxiety when participants received their results (T2), which may reflect a higher confidence in women undergoing A-MRI, the difference was not considered clinically meaningful. Despite higher rates of biopsies and abnormal interpretations with A-MRI, it is notable that breast A-MRI was not associated with an increase in psychological distress. Considering the sustained elevated levels of anxiety and worsening in quality of health in these patients, ongoing consideration and monitoring of mental health issues is recommended. PHBC patients may benefit from psychologist counselling and ongoing support.
Our results support other studies on the impact of breast MRI on anxiety. The Dutch MRI screening (MRISC) study of patients at high risk for breast cancer found that the addition of breast MRI did not affect quality of life or anxiety. In a more recent prospective non-randomized multicentre study, 1561 women at intermediate and high breast cancer risk were noted to have similar moderate distress levels, and there were no more harmful psychological effects observed between standard MG plus ultrasound as compared with the addition of MRI to standard imaging.
A significantly higher CDR was noted in the patients who underwent A-MRI as compared with MG only, despite similar baseline demographic and clinical characteristics. We expected a recurrence rate of 1-2% per year after breast cancer diagnosis[30, 31]. Eighty percent of patients were within 5 years of their breast cancer diagnosis, and 9 in-breast recurrences and 1 lung metastasis were observed, within the expected range. Our study demonstrated A-MRI had a sensitivity of 100% and CDR 48/1000 as compared to mammography’s sensitivity of 14.2% and CDR 5/1000. The low sensitivity of mammography of 14% may be attributed to an early stage of diagnosis of breast cancer in most patients with A-MRI as well as the fact that 49% of women had dense breast tissue, which lowers mammographic sensitivity, with four patients with invasive carcinomas found with A-MRI in women with dense breast tissue (Table 5). The abnormal interpretation and biopsy rates were significantly higher for A-MRI than MG, 25% and 18.3% for A-MRI and 4.5% and 3% for MG, respectively. PPV3 was higher with A-MRI than MG, 26.3% vs 16.7%, although this difference did not reach statistical significance. When extra-mammary findings were included, A-MRI offered the benefit of detecting an incidental lung metastasis.
There have been multiple studies of A-MRI since Dr. Kuhl published her landmark study[4, 14–18, 32–34]. In a similar study of 725 women with PHBC, Choi et al found 12 cancers using A-MRI, for a CDR 15 per 1000 , with comparable sensitivity of 100% and specificity of 89.2%. The results of A-MRI in our study are comparable to reported sensitivities (86-100%) and specificities (45-95.3%). However, our specificity of 76.5% was lower than the ACR benchmark for screening breast MRI 85-90%. PPV3 26.3% was in the reported range for A-MRI (9.2-70.2%) and met the ACR benchmark of 20-50%. In 2020, Park et al retrospectively compared abbreviated to full MRI in 1200 women with PHBC, 656 with A-MRI vs 656 patients with full protocol and found no significant differences in sensitivity (70% vs 100%) or specificity (98% vs 96.9%), Negative predictive values (99.5 and 100%) and PPV (35% vs 23%) (all p>0.05).
We recognize some limitations of our study. Patients were recruited by their oncologists or treating surgeons, which could have introduced a bias in patient selection. This may have partly explained the CDR in the MG plus A-MRI group. Nonetheless, the fact that randomization was blinded mitigated any potential bias of intervention arm selection and there were no clinical differences between the two surveillance groups. As well, in follow-up, similar numbers of cancers were detected in each surveillance group. This may indicate earlier detection of cancers with A-MRI than interval cancers in the MG group. Because of the CDRs and minimal effect on anxiety in the MRI group we stopped the clinical trial early. Additionally, some patients could have developed breast cancer after the follow up period, which might have been missed with mammography. Given that the majority patients were followed for over 24 months, this is less likely. Another limitation is that the radiologists were not blinded to the allocation arm, which could have influenced their reporting of the mammogram, if they knew that an MRI would be done. However, given similar recall rates for mammography within both groups, this is unlikely to have been present. The high biopsy rate in the MRI group may be perceived as a limitation, but this was related to the high CDR with an acceptable PPV3. However, more research is required to find ways to further reduce the rate of false positives. There is likely a learning curve with A-MRI and the addition of T2 sequences may help to improve PPV3 without significant time cost. We have subsequently adapted an abbreviated protocol to include T2 sequence and two more post contrast sequences to improve the specificity of MRI. Another limitation is that assessment of anxiety was based on self-report questionnaires and limited by the time points in which it is measured. There was also a loss of data of the primary outcome for participants over time, which could have led to underestimation of the effect of the surveillance group on levels of anxiety. A more objective measure would be to evaluate adherence to follow-up rounds of screening, which may address poor compliance with MRI screening. This is recommended for future study. Also, our study lacked the sample size and enough long-term follow-up to be able to say whether the earlier detection in the A-MRI group led to any difference in survival.
In conclusion, the addition of A- MRI to surveillance mammography did not impact patient anxiety in women with PHBC, regardless of the significantly higher recall and biopsy rates. A-MRI showed significantly higher cancer detection rate compared to mammography alone, which is consistent with recent recommendations. Although further study with larger cohorts is warranted, an abbreviated protocol may be considered for surveillance in this population.