Monitoring Response to Treatment and Assessing Residual Disease

It is now well established that wide local excision of breast cancer followed by adjuvant breast irradiation gives the same outcome in terms of survival as mastectomy and, as such, breast conservation is the treatment of choice for many women with breast cancer (Fisher et al. 2002). For some women, however, breast conservation is not possible due to the size, position or multifocal/multicentric disease. Neoadjuvant chemotherapy (NAC), also termed primary systemic therapy, is chemotherapy delivered prior to definitive surgery and aims to both down stage the primary tumour and treat potential micro-metastatic disease. It also has the added advantage of allowing an assessment of tumour chemo-respon-siveness as the tumour remains in situ during therapy. For inoperable breast cancers (locally advanced or inflammatory) a high tumour regression rate (approximately 70%) has established NAC as the standard treatment option for this patient group (Kaufmann et al. 2003). A number studies have now demonstrated that NAC can also be used in patients with operable breast cancers to downstage the primary tumour and thereby increase the breast-conserving surgery rate while providing an equivalent outcome to adjuvant chemotherapy in terms of disease-free survival and overall survival (Fisher et al. 1998a; Makris et al. 1998; van der Hage et al. 2001). The largest of these randomised studies, the National Surgical Adjuvant Breast and Bowel Project (NSABP) B18 trial demonstrated that pathological response to NAC was a predictor of relapse free survival with a significant increase in 5-year relapse free survival from 77% to 86% in patients achieving a pathological complete response compared to patients achieving a clinical CR but not a pathological CR (Fisher et al. 1998a).

A proportion (2%-30%) of patients receiving NAC will fail to response to treatment and will have a worse outcome (Bonadonna et al. 1998; Fisher et al. 1998a; Makris et al. 1998). The ability to identify non-responders early during treatment would enable the use of alternative therapies which may be more beneficial (Smith et al. 2002). Many studies evaluating NAC in patients with breast cancer have shown that clinical examination, X-ray mammography and ultrasonography are imperfect techniques especially as change in tumour size often only becomes apparent after several cycles of chemotherapy. Assessment of women undergoing NAC has been identified as an area of clinical practice where an immediate impact of breast MRI can be realised (Harms 2001). MRI has two main roles to play in the assessment of patients receiving NAC. Firstly, MRI may help in the early identification of non-responding patients thus allowing treatment intervention that may be more beneficial. Secondly, MRI may provide a more accurate assessment of residual tumour at the end of NAC and thus aid in decisions regarding surgery.

Fig. 10.11. Monitoring chemotherapy response of breast cancer with DCE-MRI. 44-year old post-menopausal woman with a 4 cm, grade 3 invasive ductal cancer of the right breast with palpable ipsilateral axillary nodal enlargement. Rows depict T2-weighted anatomical images, early (100 seconds) subtraction images, transfer constant, relative blood volume (rBV) parametric images and relative signal intensity time curves (ROIs in whole tumour-green, normal tissue-red and fat-blue) at identical slice positions before and after two cycles of FEC (5-Fluorouracil, Epiru-bicin, Cyclophosphamide) chemotherapy. Transfer constant map (colour range 0-1 min-1) and relative blood volume (colour range 0-500 AU). With treatment, a reduction in the size of individual lesions is seen with a reduction in relative blood volume and transfer constant. This patient had a complete clinical and radiological response to treatment after 6 cycles of chemotherapy with pathology showing microscopic residual disease only.

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