Detection and minimally invasive treatment of small breast cancers
Breast cancer is the most common cancer diagnosed and leading cause of cancer death in women worldwide. Early detection of breast cancer in women is key as it allows for less aggressive treatment and reduces the risks of death from breast cancer. It is estimated that about one in eight women in Europe who lives to be 80 years old will develop invasive breast cancer over the course of their lifetime.
Part I | Minimally invasive treatment of breast cancer
Over the past decades several devices and treatment options have been developed and adopted to improve breast cancer treatment. One of the future aims is to increase the use of minimally invasive or even non-invasive treatment options. In Chapter 2 the strengths and weaknesses of the different diagnostic and therapeutic minimally invasive techniques was described in detail. So far, many diagnostic biopsy techniques have been developed and are in use. However, the development and application of minimally invasive treatment techniques lags behind, due to one huge limitation when ablation techniques are used: the lack of reliable margin evaluation or verification of therapeutic success. To date, most prospective studies performed for the assessment of minimally invasive treatment with ablation techniques are treat and resect studies, because there are no reliable imaging tools for real-time treatment planning and assessment of response to treatment. This is one advantage that minimally invasive excision techniques have over ablation techniques; theoretically, with the former, it is possible to evaluate the tumor margin and evaluate the success of therapy.
The breast lesion excision system (BLES) is an automated, image-guided, single-pass biopsy system, developed to overcome this issue. As opposed to other breast biopsy devices, the aim of BLES is to excise and retrieve an intact breast tissue specimen, which may not only facilitate easier diagnosis but also might allow for minimally invasive resections. In Chapter 3 the diagnostic and therapeutic potential of the device was determined in a systematic review. Overall, the BLES is an efficient and safe breast biopsy system with acceptable complication rates. Underestimation rates of biopsies are commonly used to determine the accuracy of percutaneous biopsy techniques. As described in Chapter 2 and 3, according to literature, the atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS) underestimation rates for BLES are in the range of 0% to 14% and 0% to 22%, respectively. This is a similar performance as that reported for vacuum-assisted biopsy (VAB) (21% and 11%, respectively). Even though most studies did not aim to remove lesions entirely, complete excision occurs regularly, depending on the type of lesion. Different studies reported a median complete excision of 60%, 50%, and 43% for ADH, DCIS, and invasive ductal carcinoma (IDC), respectively. Overall, these results point to the need for a trial to test the suitability of the BLES as a therapeutic device for the excision of small breast lesions.
Due to the shift towards minimally invasive treatment, accurate tumor size estimation is essential for the appropriate selection of small breast cancers that are eligible for limited Chapter 10 196 resection. In Chapter 4 the reliability of magnetic resonance imaging (MRI) based tumor size measurements was determined. Furthermore clinical, histological, and radiomics characteristics were examined to determine which are predictive for underestimation. In this Chapter we saw that the overall correlation of MRI measurements with pathology was moderately strong in small (<20 mm) breast cancers. Nevertheless, in 12.2% of the cases MRI underestimated the size of the lesion by more than 5 mm. Especially in highergrade tumors and DCIS lesions, this underestimation occurred more often, but none of the patient, imaging, or biopsy characteristics were predictive. Therefore, patients with high grade tumors or DCIS in the tumor should be selected with caution for minimally invasive treatment.
In Chapter 5 we investigated whether it is feasible to excise small breast cancers completely using the BLES under ultrasound (US) guidance. Specifically, 22 patients diagnosed with an invasive carcinoma ≤ 15 mm on US and mammography were enrolled in this prospective, multi-center study. To verify that the exact lesion size met the inclusion criteria, all patients underwent breast MRI. Eleven patients were eligible for BLES-based excision and surgical excision during the same procedure. Histopathological results were identical for the needle biopsy, BLES, and surgical specimens for all lesions. Unfortunately, none of the BLES excisions were adequate. Nevertheless, margin assessment was good for all BLES specimens and only one complication occurred during the procedure (no retrieval of a specimen). Overall, we could conclude based on Chapter 3 and 5 that the BLES allows accurate diagnosis of small invasive carcinomas but that it cannot be considered a therapeutic device.
As described in Chapter 2, the VAB has been proven as a reliable biopsy tool for diagnostic assessment of breast lesions, which removes multiple larger tissue samples. Also, as a therapeutic device vacuum-assisted excision (VAE) is approved as a minimally invasive alternative for surgical excision of benign lesions and lesions of uncertain malignant potential. Nevertheless, little evidence exists on the complete excision rate of malignant breast lesions and the use of VAE as a possible treatment modality for malignant lesions. Therefore, we designed a multi-center, translational clinical phase II trial to analyze whether it is feasible to remove small breast cancers completely using VAE under US guidance. The outline and methods of this study were discussed in Chapter 6.
Part II | Innovative MRI sequences for early detection of breast cancer
For the implementation of minimally invasive treatment methods, it is important that breast cancer lesions are small and are found at an early stage. Breast cancer screening programs play a major role in this. Nevertheless, current screening methods use radiation and/or contrast agents, which may harm the patient. Therefore, a new fast screening method without radiation and/or contrast agent would be an improvement. This improved screening method should approximate the same specificity as mammography and MRI, and the same sensitivity as MRI screening, to detect breast tumors at an early and Summary 197 10 small stage. The current evidence regarding such MRI screening sequences is extensively reviewed in Chapters 7 and 8.
In Chapter 7, we investigated the performance of a new diffusion-weighted imaging (DWI) sequence for breast MRI (simultaneous multi-slice single-shot echo-planar imaging (SMSss-EPI)). This sequence is intended to reduce acquisition time and enable higher spatial resolution scans within a clinically acceptable timeframe. Using this new sequence, we were able to obtain a DWI scan in less than 3 minutes at a spatial resolution of 0.9x0.9x4.0 mm. In this prospective patient study, we compared this sequence at 3T to our clinical standard readout-segmented (rs)-EPI-DWI sequence, in terms of image quality, lesion visibility and diagnosis, and description according to the breast imaging reporting and data system (BI-RADS) lexicon. Our results suggest an increased visibility of malignant lesions using the SMS-ss-EPI compared to rs-EPI, although the overall image quality is much better in the conventional sequence. Further development of the SMS-ss-EPI sequence is needed to improve image quality, decrease the presence of artifacts, and further increase lesion visibility.
In Chapter 8 we compared a prototype ss-EPI with modified Inversion Recovery Background Suppression (ss-EPI-mIRBS) sequence using a high b-value to the clinical standard rs-EPI sequence. The sequences were evaluated and compared in terms of image quality, lesion visibility, apparent diffusion coefficient (ADC) values, and reading time. The ss-EPImIRBS has a higher signal-to-noise ratio (SNR) in comparison to the rs-EPI, which allows the use of higher b-values without severe signal loss with a comparable scan time. Our results demonstrated that ss-EPI-mIRBS has at least equivalent image quality and lesion visibility. However, this prototype sequence resulted in a shorter reading time, which might eventually improve the clinical value of DWI for screening either as standalone technique or in addition to dynamic contrast-enhanced (DCE) MRI.
In summary, this thesis shows the current status of and explores possible future directions for minimally invasive treatment of small breast cancers and the mechanisms to identify these small breast cancers, which may be candidates for minimally invasive treatment. Several weaknesses have been identified and potential points for improvements have been discussed. Moreover, potential characteristics for MRI tumor size estimation is investigated and criticized. Lastly, this thesis takes a quick glance at improving the screening program with new MRI sequences.