CONCLUSIONES Y RECOMENDACIONES

MRI.

Metabolic imaging, predominantly MRS, is another path for exploration. It is well established that total choline, in particular phosphocholine, is elevated in breast can- cer58,68–71,94_{. As spectroscopic techniques improve, quantification of in-vivo spec-}

tra can be done more reliably. This replaces the criterion of seeing or not seeing the choline peak with more sophisticated quantitative criteria for judging whether a breast lesion might be malignant58_{. However, for future screening application, mul-}

tivoxel techniques (2D, or better, 3D) are needed. Moreover, the SNR is so low that voxels are in the size order of cubic centimeters, thus, still not suitable for screening. Nevertheless, novel approaches to metabolic imaging, such as phosphorous spec- troscopy and chemical saturation transfer imaging (CEST) may enable much higher resolution levels in the near future that might give them access to a new platform for screening research95_.

2.10

Conclusion

Breast MRI is solidly established as the most accurate screening technique for breast cancer available, even though currently mainly applied to women at increased risk of breast cancer. Current state-of-the-art protocols are multiparametric in nature and focus on achieving both a high sensitivity and a high specificity. As the added value of additional sequences on top of simple T1-weighted acquisitions in a screening set- ting appears questionable and is, likely, not cost-effective, current research focuses on shortening of MRI protocols. Both abbreviated and ultrafast approaches to breast MRI allow acquisition within minutes without losing in accuracy.

Future research focuses on the use of non-contrast techniques for screening. DWI currently seems most suitable. However, so far this technique cannot deliver the quality of screening obtained with contrast-enhanced techniques.

Screening performance of breast MRI

and mammography

3

Suzan Vreemann, Albert Gubern-Merida, Margrethe S. Schlooz-Vries, Peter Bult, Carla H. van Gils, Nicoline Hoogerbrugge, Nico Karssemeijer, Ritse M. Mann

Adapted from: Influence of risk category and screening round on the performance of an MR imaging and mammography screening program in carriers of theBRCA

mutation and other women at increased risk

Abstract

PurposeTo evaluate the real-life performance of a breast cancer screening program for women with different categories of increased breast cancer risk with multiple follow-up rounds in an academic hospital with a large screening population.

Materials and MethodsScreening examinations (magnetic resonance [MR] imaging and mammography) for women at increased breast cancer risk (January 1, 2003, to January 1, 2014) were evaluated. Risk category, age, recall for workup of screening- detected abnormalities, biopsy, and histopathologic diagnosis were recorded. Re- call rate, biopsy rate, positive predictive value of recall, positive predictive value of biopsy, cancer detection rate, sensitivity, and specificity were calculated for first and follow-up rounds.

ResultsThere were 8818 MR and 6245 mammographic examinations performed in 2463 women. Documented were 170 cancers; of these, there were 129 screening- detected cancers, 16 interval cancers, and 25 cancers discovered at prophylactic mas- tectomy. Overall sensitivity was 75.9% including the cancers discovered at pro- phylactic mastectomy (95% confidence interval: 69.5%, 82.4%) and 90.0% excluding those cancers (95% confidence interval: 83.3%, 93.7%). Sensitivity was lowest for carriers of theBRCA1mutation (66.1% and 81.3% when including and not including cancers in prophylactic mastectomy specimens, respectively). Specificity was higher at follow-up (96.5%; 95% confidence interval: 96.0%, 96.9%) than in first rounds (85.1%; 95% confidence interval: 83.4%, 86.5%) and was high for both MR imag- ing (97.1%; 95% confidence interval: 96.7%, 97.5%) and mammography (98.7%; 95% confidence interval: 98.3%, 99.0%). Positive predictive value of recall and positive predictive value of biopsy were lowest in women who had only a family history of breast cancer.

ConclusionScreening performance was dependent on risk category. Sensitivity was lowest in carriers of theBRCA1mutation. The specificity of high-risk breast screen- ing improved at follow-up rounds.

3.1 Introduction 39

3.1

Introduction

Breast magnetic resonance imaging (MRI) is considered to be the most sensitive imaging modality for early breast cancer detection and is recommended as a supple- mental screening technique for women with a lifetime risk for the development of breast cancer of 20 - 25% or higher11,12_{. This includes women with aBRCAgermline}

mutation, for whom the lifetime risk is as high as 56 - 84%, and women who under- went radiation therapy to the chest wall at young age11,12,37,96_{. Furthermore, women}

with a strong family history for breast cancer, women with a personal history of breast cancer, and women with high-risk lesions such as atypical ductal hyperplasia and lobular carcinoma in situ are at increased risk, though for the latter risk cate- gories the indication for additional screening with MRI is less clear11,12,97. Nonethe- less, supplemental screening may be indicated for all these women because the rate of interval cancers is relatively high98–100_.

Whereas the sensitivity of breast MR imaging has been reported101 _{to be as high as}

95% in women with known breast cancer, the sensitivity of breast MRI in screening is lower. Initially, the sensitivity was reported to be around 77% in the screening set- ting, but more recent studies document a higher sensitivity of around 90%15,41,75,102_.

Studies15,41,75_{show a nearly doubled cancer detection of combined MR imaging and}

mammography screening compared with mammography screening alone. Conse- quently, high-risk screening programs with MR imaging and mammography have been implemented in clinical practices worldwide, although there are national, re- gional, and local differences regarding whom to screen with supplemental MR imag- ing11,12,103_{. This is likely also because it is so far unknown whether the diagnostic}

value of breast MR imaging screening is different for groups with a different under- lying risk and whether the added value of MR imaging persists in follow-up evalu- ations for all groups.

A major criticism regarding breast MR imaging screening, beyond availability and cost, is that the specificity appears lower than generally accepted for mammogra- phy screening. Reported specificities range from 81% to 95% and compare poorly to a specificity of 99% for mammography screening14,15,37,38,75,102,104. However, to our knowledge, hardly any data exist on the effect of routine use of breast MR imaging and the availability of prior examinations on the diagnostic accuracy of breast MR imaging. Only a few recent studies of breast MR imaging screening programs docu- ment recall rates, false-positive findings, and interval cancers15,41_.

The purpose of this study is to evaluate the real-life performance of a breast cancer screening program for women with different categories of increased breast cancer risk with multiple follow-up rounds in an academic hospital with a large screening population.