Evaluation of total choline from in-vivo volume localized proton MR spectroscopy and its response to neoadjuvant chemotherapy in locally advanced breast cancer

Abstract

Breast cancer is the commonest cancer among women the world over. In India, the reported age adjusted incidence of breast cancer in women is about 26.7/1 00 000 population (NCRP, 1992). Unlike the West, in India, majority of the patients (about 60%) present with locally advanced breast cancer (LABC) or disseminated disease (Goel et al, 1995). In LABC, the treatment policy followed at most centres, is neoadjuvant chemotherapy (NACT) followed by surgery and local or locoregional radiotherapy. The response to NACT is assessed by clinical evaluation and supplemented by radiological measurement of reduction in tumour volume by mammography and/or ultra sonography. None of the currently available indicators of response (clinical and radiological) correlate well with the actual response as assessed on histopathological examination of the tumour.MR imaging (MRI) is a valuable new tool for diagnostic mammography (Orel et al, 1996;Friedrich, 1998; Harms, 1998;Orel, 1998). Recently, dynamic contrast enhanced MRI techniques have also been developed for differentiation between benign and malignant tumours (Kaiser, 1991;Harms et al, 1993; Haywang-Kobrunner et al, 1997;Piccoli, 1997;Daniel et al, 1998). The above techniques, however, do not provide any metabolic/ biochemical information. On the contrary, magnetic resonance spectroscopy (MRS) permits non-invasive detection of metabolic (biochemical) differences between tumours and normal tissues, and can also be used to monitor response to different treatment regimens. Recently, we have shown that in LABC, the assessment of response to NACT can be made using water-to-fat ratio calculated from volume localized proton MRS (Jagannathan et al, 1998(Jagannathan et al, , 1999. In addition, we also reported the presence of choline in a majority of the breast cancer patients (Jagannathan et al, 1998).In this study, results of evaluation of choline in LABC and its response to NACT using in-vivo proton MRS are presented. The objectives are: (i) to evaluate the potential of proton MRS in the study of breast cancer, and (ii) to investigate further, the recent observation of choline containing compounds in malignant breast tissues and its response to NACT. To the best of our knowledge, this is the first report assessing the response of breast cancer to NACT in a large cohort of patients using in-vivo proton MRS. PATIENTS AND METHODS Patients67 women with cytologically confirmed infiltrating ductal carcinoma (IDC) were recruited. Necessary clearance from the Institute ethical committee and written informed consent were obtained prior to examination from patients and controls. Patients were evaluated clinically and tumour size was measured using Vernier calipers. Metastatic workup included liver function tests, chest

Neoadjuvant chemotherapy in breast cancer: early response prediction with quantitative MR imaging and spectroscopy

“…Such studies have recently been carried out in breast cancer (Jagannathan et al, 2001;Meisamy et al, 2004), lymphoma and germ cell tumours (Schwarz et al, 2002), and glioma (Preul et al, 2000), where positive treatment response has been associated with reduction in the levels of total choline. Similar studies using phosphorous spectroscopy to detect changes in phosphocholine or phosphomonoesters have also been carried out in lymphoma (Arias-Mendoza et al, 2004) and head and neck cancer (Shukla-Dave et al, 2002a, b).…”

“…Proton magnetic resonance spectroscopy (MRS) can be used to characterise breast lesions through differences in the ratio of fat and water signals (Chu et al, 1987;Sijens et al, 1988) or the intensity of signal from choline-containing compounds (Bradamante et al, 1988;Katz-Brull et al, 2002;Bolan et al, 2003;Jacobs et al, 2004;Jacobs et al, 2005). Both fat : water ratios (Jagannathan et al, 1998) and choline levels (Preul et al, 2000;Jagannathan et al, 2001;Schwarz et al, 2002;Meisamy et al, 2004) have also been used to monitor treatment-induced changes, and phosphorous MRS has been used to predict response using differences in the levels of phosphocholine or phosphomonoesters (Shukla-Dave et al, 2002a, b;Arias-Mendoza et al, 2004). Sodium MRI might also be useful in monitoring treatment response (Kline et al, 2000;Schepkin et al, 2005).…”

Monitoring the therapeutic response of locally advanced breast cancer patients: Sequential in vivo proton MR spectroscopy study

“…Elevated levels of choline-containing compounds (TCho) in water-suppressed spectra from neoplastic breast tissues have also been documented (23)(24)(25)(26). Changes in the levels of TCho can be used as a marker to assess the response of breast cancer patients to NACT (23).…”

“…Elevated levels of choline-containing compounds (TCho) in water-suppressed spectra from neoplastic breast tissues have also been documented (23)(24)(25)(26). Changes in the levels of TCho can be used as a marker to assess the response of breast cancer patients to NACT (23). A recent study conducted at 4 T with an improved water-and fat-suppression sequence showed that TCho resonance could be observed in all patients with invasive carcinoma and in some patients with benign breast lesions (27).…”

A high spatial resolution 1H magnetic resonance spectroscopic imaging technique for breast cancer with a short echo time

“…Analysis of early pooled clinical experience with in vivo 1 H MRS yielded a sensitivity and specificity for detection of breast cancer of 83% and 85%, respectively, with near 100% for both in a subgroup of young women [32]. A reduction or disappearance of the Cho signal has been associated with response to neoadjuvant chemotherapy of locally advanced breast cancer [33].…”