Montclair Breast Center

Breast Cancer; Study results from Israel, India and the United States update understanding of breast cancer

18 September 2007
Life Science Weekly
© Copyright 2007 Life Science Weekly via NewsRx.com
2007 SEP 18 - ( NewsRx.com) -- New breast cancer study findings have been published by scientists in Israel, India and the United States.

Study 1: "Rationale and Neoadjuvant systemic therapy (NST) is the standard treatment for locally advanced breast cancer and a common option for primary operable disease. It is important to develop standardized imaging techniques that can monitor and quantify response to NST enabling treatment tailored to each individual patient, and facilitating surgical planning," investigators in Rehovot, Israel report.

"Here we present a high spatial resolution, parametric method based on dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI), which evaluates breast cancer response to NST. DCE-MRI examinations were performed twice on 17 breast cancer patients, before and after treatment. Seven sets of axial breast images were sequentially recorded at 1.5 Tesla applying a three-dimensional, gradient echo at a spatial resolution similar to 2 x 1.2 x 0.6 mm(3) and temporal resolution similar to 2 minutes, using gadopentate dimeglumine (0.1 mmol/kg wt). Image analysis was based on a color-coded scheme related to physiologic perfusion parameters. A high Pearson correlation coefficient of 0.96 (P < .0001) was found between the histopathologic estimation of viable neoplastic tissue volume and the segmented volume of all the pixels demonstrating fast and steady state washout after NST (colored in light red and green). Segmentation of these pixels before and after NST indicated response in terms of reduced tumor volume and a parallel decrease in enhancement rate which reflects diminished transcapillary transfer of the contrast agent. The use of a parametric MRI technique provided a means to standardize segmentation and quantify changes in the perfusion of breast neoplastic tissue in response to NST," wrote C.P. Chou and colleagues.

The researchers concluded: "Whether this technique can serve to predict breast cancer recurrence and survival rates requires further clinical testing."

Chou and colleagues published their study in Academic Radiology (Research reports on breast cancer from C.P. Chou and colleagues provide new insights. Academic Radiology, 2007;14(5):561-573).

For additional information, contact C.P. Chou, Weizmann Institute Science, Dept. of Regulatory Biology, IL-76100 Rehovot, Israel.

Study 2: The therapeutic response of breast cancer patients could be monitored by in vivo proton (H-1) MR spectroscopy (MRS).

According to a recent article published in the Journal of Magnetic Resonance Imaging, scientists in India conducted a study "to evaluate the use of the water-to-fat (W-F) value obtained from in vivo proton (H-1) MR spectroscopy (MRS) as a response indicator of cytologically confirmed patients with locally advanced breast cancer (LABC), and to monitor the therapeutic response of such patients to neoadjuvant chemotherapy (NACT)."

"Serial H-1 MR spectra were recorded both before and after the completion of chemotherapy in 33 LABC patients (with infiltrating ductal carcinoma (IDC)) at 1.5 T," explained M. Kumar and colleagues, All India Institute of Medical Sciences. "In addition, spectra from normal breast tissues of 28 healthy volunteers were recorded. Malignant breast tissues showed elevated W-F values compared to normal breast tissues of controls. Statistically significant higher pretherapy W-F value (p<.01) was observed in patients compared to controls.

"In patients who received NACT resulting in the reduction of the primary tumor size, the W-F value showed a decrease that was statistically significant (p<.01). Analysis of the MR data further indicates that the W-F value had no correlation with the menstrual status of the patients. A comparison of pretherapy W-F value with pretherapy tumor volume showed a fair correlation (p=.05), while the posttherapy W-F value showed no such correlation with the posttherapy tumor volume."

The researchers concluded, "This study demonstrates that simple, conventional in vivo H-1 MRS is a useful technique for monitoring the therapeutic response of breast cancer patients. The observed trend in the reduction of W-F value provides a noninvasive response indicator to monitor the clinical outcome of locally advanced breast cancer patients to NACT."

Kumar and colleagues published their study in the Journal of Magnetic Resonance Imaging (Monitoring the therapeutic response of locally advanced breast cancer patients: Sequential in vivo proton MR spectroscopy study. J Magn Reson Imaging, 2006;24(2):325-332).

Additional information can be obtained by contacting N.R. Jagannathan, All India Institute of Medical Sciences, Dept. of NMR, New Delhi 110029, India.

Study 3: Breast cancer choline (Cho) metabolism correlates with angiogenesis activity.

According to a study from the United States, "Although an magnetic resonance imaging (MRI) scanner is a single stand-alone modality, different acquisition techniques may be applied to collect structural and functional information, including vascular or angiogenic properties measured by dynamic contrast enhanced MRI (DCE-MRI) and Cho metabolism measured by proton MR spectroscopy imaging (MRSI). They may provide complementary information for a better characterization of neoplasm."

"In this study, we investigated the correlation between choline measured by MRSI and vascular parameters measured by DCE-MRI in breast cancer. Fourteen patients with histologically proven invasive breast cancer were included. MRSI from a grid of 8 x 8 voxels within a selected slab from each lesion was performed. Each voxel was 1.0 x 1.0 x 1.2 cm3. Choline signal-to-noise ratio (SNR) was measured from each voxel showing an identifiable choline peak," said M.Y. Su and colleagues, University of California.

They wrote, "Corresponding DCE kinetics was measured from each voxel, and analyzed with a 2-compartmental model to obtain pharmacokinetic parameters K-trans and kep. All parameters showed a wide variation within each lesion, and there were no consistent correlations between regional Cho and DCE parameters within the lesion of each individual patient. This finding might be attributed to the heterogeneous nature of breast cancer. The characteristic Cho and DCE-MRI parameters were obtained for each patient by averaging over all Cho-positive voxels.

"In these 14 patients there was a significant linear correlation between Cho with percent enhancement at 2 min after injection, SE%-2min (r=0.75, p=0.002), and pharmacokinetic parameters K-trans (r=0.74, p=0.003), and kep (r=0.76, p=0.002). The results suggested that overall there is a correlation between choline metabolism and angiogenesis activity."

"Since choline is associated with cell replication and angiogenesis is required to support tumor growth, this might explain the correlation between these two sets of measures among different lesions," researchers suggested.

Su and colleagues published the results of their research in Technology in Cancer Research & Treatment (Comparison of choline and pharmacokinetic parameters in breast cancer measured by MR spectroscopic imaging and dynamic contrast enhanced MRI. Technol Cancer Res Treat, 2006;5(4):401-410).

For additional information, contact M.Y. Su, University of California, John Tu & Thomas Yuen Center Functioning Oncoimaging, Irvine, CA 92697, USA.

Breast Cancer; Research data from the United States update breast cancer knowledge

22 May 2007
Life Science Weekly
© Copyright 2007 Life Science Weekly via NewsRx.com

2007 MAY 22 - ( NewsRx.com) -- Investigators in the United States have published new breast cancer data.

Study 1: Scientists discuss in "Case study of the morphologic variation of circulating tumor cells" new findings in breast cancer. "We report a detailed cytomorphologic evaluation of the circulating component of widely metastatic breast carcinoma. A previously healthy 38-year-old woman was diagnosed with breast cancer," scientists in the United States report.

"Wide local excision revealed a 1.7-cm infiltrating ductal adenocarcinoma, BSR score 7/9 with angiolymphatic invasion, and 4/20 lymph nodes positive for carcinoma. Five years later, a bone marrow biopsy revealed involvement of bone marrow by metastatic breast carcinoma, and shortly thereafter, metastases were identified in the liver and lung hilum. She enrolled in a clinical investigation for the detection of circulating tumor cells (CTCs) in breast carcinoma. A total of 659 CTCs were identified in a 10-mL blood sample using an immunofluorescent protocol targeting cytokeratins and detected using fiber-optic array scanning technology. The detected CTCs were subsequently stained with a Wright-Giemsa stain, and representative cells were evaluated in detail by light microscopy for morphologic evaluation. We find that the patient's CTCs exhibit a high degree of pleomorphism including CTCs with high and low nuclear-to-cytoplasmic ratios along with CTCs exhibiting early and late apoptotic changes," wrote D. Marrinucci and colleagues, Scripps Research Institute, Department of Cell Biology.

The researchers concluded: "In addition, in comparison with her tumor cells in other sites, the full morphologic spectrum of cancer cells present in primary and metastatic tumor is also present in peripheral blood circulation."

Marrinucci and colleagues published their study in Human Pathology (Case study of the morphologic variation of circulating tumor cells. Human Pathology, 2007;38(3):514-9).

For additional information, contact D. Marrinucci, The Scripps-PARC Institute for Advanced Biomedical Science, Dept. of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037 USA.

Study 2: A breast cancer nomogram for predicting nonsentinel lymph node (non-SLN) metastases after a positive sentinel node biopsy was validated.

"Although completion lymph node dissection (CLND) is the standard of care for breast cancer patients with SLN metastases, the SLN is the only node with tumor in 40% to 60% of cases. To assist with decision-making regarding CLND, investigators at Memorial Sloan-Kettering Cancer Center devised and validated a nomogram for predicting the likelihood of non-SLN metastases," scientists in the United States reported.

"To assess the generalizable use of this nomogram, validation analysis was performed by using an external database," explained L.A. Lambert and colleagues, M.D. Anderson Cancer Center. "Eight clinicopathologic variables for 200 consecutive breast cancer patients at the University of Texas M.D. Anderson Cancer Center with SLN metastases and CLND were entered into the nomogram. The accuracy of the nomogram to predict non-SLN metastases was assessed by the receiver operating characteristic (ROC) curve and linear regression analysis. The accuracy of the nomogram with touch-imprint cytology (TIC) as a substitute variable for frozen section was also evaluated.

"The linear correlation coefficient of the nomogram-predicted probabilities correlated with the observed incidence of non-SLN metastases for all patients (.97). The accuracy of the nomogram as measured by the area under the ROC curve was .71. When applied solely to patients who had TIC assessment of the SLN, the area under the ROC curve was .74."

The researchers concluded, "This study validated the Memorial Sloan-Kettering Cancer Center breast cancer nomogram by using an external database. TIC seems to be an acceptable substitute for frozen section as a nomogram variable. The nomogram may help predict an individual's risk of non-SLN metastases and assist in patient decision making regarding the benefit of CLND."

Lambert and colleagues published their study in Annals of Surgical Oncology (Validation of a breast cancer nomogram for predicting nonsentinel lymph node metastases after a positive sentinel node biopsy. Ann Surg Oncol, 2006;13(3):310-320).

For additional information, contact L.A. Lambert, University of Texas, M.D. Anderson Cancer Center, Dept. Surgery Oncology, Unit 444, 1515 Holcombe Blvd., Houston, TX 77030, USA.

Study 3: Breast cancer outcome might improve after primary systemic chemotherapy in patients who achieved a pathologic complete response (pCR) from metastases.

According to recent research from the United States, "Breast carcinoma axillary lymph node (ALN) pCR after primary chemotherapy is associated with significantly higher recurrence-free survival (RFS) and overall survival (OS) rates. The purpose of the current study was to determine long-term outcome in patients achieving a pCR of cytologically proven inflammatory breast carcinoma ALN metastases after primary chemotherapy."

"Patients with cytologically documented ALN metastases from inflammatory breast carcinoma were treated in three prospective primary chemotherapy trials. After surgery, patients were subdivided into those patients with and those patients without residual ALN carcinoma. Survival was calculated using the Kaplan-Meier method," explained B.T. Hennessy and colleagues, M.D. Anderson Cancer Center.

"Of 175 patients treated, 61 had cytologically confirmed ALN metastases. Fourteen patients (23%) achieved a pCR of the ALNs after primary chemotherapy. The 5-year OS and RFS rates were found to be improved in those patients achieving a pCR of the ALNs (82.5% [95% confidence interval (95% CI), 62.8-100%] and 78.6% [95% CI, 59.8-100%], respectively, vs. 37.1% [95% CI, 25.4-54.2%] and 25.4% [95% CI, 15.5-41.5%], respectively) (p=.01 [for OS] and p=.001 [for RFS]).

"Combination anthracycline and taxane-based primary chemotherapy resulted in significantly more patients achieving an ALN pCR (45% vs. 16%; p=.01). pCR of ALN metastases is associated with an excellent prognosis in patients with inflammatory breast carcinoma," pronounced the investigative team.

The researchers concluded, "The rates of ALN pCR are nearly 50% in patients with inflammatory breast carcinoma who are treated with anthracyclines and weekly paclitaxel before surgery. However, those patients with residual ALN disease at the time of surgery greatly require the introduction of novel therapeutic strategies."

Hennessy and colleagues published their study in Cancer (Disease-free and overall survival after pathologic complete disease remission of cytologically proven inflammatory breast carcinoma axillary lymph node metastases after primary systemic chemotherapy. Cancer, 2006;106(5):1000-1006).

For additional information, contact B.T. Hennessy, University of Texas, M.D. Anderson Cancer Center, Dept. Breast Med Oncology, Unit 424, 1515 Holcombe Blvd., Houston, TX 77030, USA.

Keywords: Houston, Texas, United States, Breast Cancer, Breast Carcinoma, Chemotherapy, Diagnosis, Diagnostics, Inflammatory, Oncology, Paclitaxel, Pathologic Complete Response, Primary Tumor, Cancer Therapy, Women's Health, Metastases.