We employ Raman spectroscopy to diagnose benign and malignant lesions in human breast tissue based on chemical composition. In this study, 130 Raman spectra are acquired from ex vivo samples of human breast tissue (normal, fibrocystic change, fibroadenoma, and infiltrating carcinoma) from 58 patients. Data are fit by using a linear combination model in which nine basis spectra represent the morphologic and chemical features of breast tissue. The resulting fit coefficients provide insight into the chemical͞morpho-logical makeup of the tissue and are used to develop diagnostic algorithms. The fit coefficients for fat and collagen are the key parameters in the resulting diagnostic algorithm, which classifies samples according to their specific pathological diagnoses, attaining 94% sensitivity and 96% specificity for distinguishing cancerous tissues from normal and benign tissues. The excellent results demonstrate that Raman spectroscopy has the potential to be applied in vivo to accurately classify breast lesions, thereby reducing the number of excisional breast biopsies that are performed.spectral diagnosis ͉ optical vibrational disease

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We present the first demonstration of in vivo collection of Raman spectra of breast tissue. Raman spectroscopy, which analyzes molecular vibrations, is a promising new technique for the diagnosis of breast cancer. We have collected 31 Raman spectra from nine patients undergoing partial mastectomy procedures to show the feasibility of in vivo Raman spectroscopy for intraoperative margin assessment. The data was fit with an established model, resulting in spectral-based tissue characterization in only 1 second. Application of our previously developed diagnostic algorithm resulted in perfect sensitivity and specificity for distinguishing cancerous from normal and benign tissues in our small data set. Significantly, we have detected a grossly invisible cancer that, upon pathologic review, required the patient to undergo a second surgical procedure. Had Raman spectroscopy been used in a real-time fashion to guide tissue excision during the procedure, the additional reexcision surgery might have been avoided. These preliminary findings suggest that Raman spectroscopy has the potential to lessen the need for reexcision surgeries resulting from positive margins and thereby reduce the recurrence rate of breast cancer following partial mastectomy surgeries. (Cancer Res 2006; 66(6): 3317-22)

Our pooled analysis demonstrated that African American ethnicity is a significant and independent predictor of poor outcome from breast cancer, even after accounting for socioeconomic status by conventional measures. These findings support the need for further investigation of the biologic, genetic, and sociocultural factors that may influence survival in African American patients with breast cancer.

Raman spectroscopy has the potential to provide real-time, in situ diagnosis of breast cancer during needle biopsy or surgery via an optical fiber probe. Understanding the chemical/morphological basis of the Raman spectrum of breast tissue is a necessary step in developing Raman spectroscopy as a tool for in situ breast cancer diagnosis. To understand the relationship between the Raman spectrum of a sample of breast tissue and its disease state, near-infrared Raman spectroscopic images of human breast tissue were acquired using a confocal microscope. These images were then compared with phase contrast and hematoxylinand eosin-stained images to develop a chemical/morphological model of breast tissue Raman spectra. This model fits macroscopic tissue spectra with a linear combination of basis spectra derived from spectra of the cell cytoplasm, cell nucleus, fat, b-carotene, collagen, calcium hydroxyapatite, calcium oxalate dihydrate, cholesterol-like lipid deposits and water. Each basis spectrum represents data acquired from multiple patients and, when appropriate, from a variety of normal and diseased states. The model explains the spectral features of a range of normal and diseased breast tissue samples, including breast cancer. It can be used to relate the Raman spectrum of a breast tissue sample to diagnostic parameters used by pathologists.

Brain metastases (BM) from breast cancer are associated with significant morbidity and mortality. In the current study, we have examined a cohort of breast cancer patients who went on to develop BM for clinical-pathologic features and predictive markers that identify this high-risk subgroup of patients at the time of diagnosis. The primary tumors from 55 patients who developed BM were used to construct a tissue microarray. The clinical and pathologic features were recorded and the tissue microarray was stained for estrogen receptor, human epidermal growth factor receptor 2, cytokeratin 5/6, and epidermal growth factor receptor by immunohistochemistry. This cohort of patients was compared against a group of 254 patients who remain free of metastases (67 mo mean follow-up), and another cohort of 40 patients who developed mixed visceral and bone metastatic disease without brain recurrence over a similar period of time. Breast cancer patients who went on to develop BM were more likely to be <50 years old (P<0.001), and the primary tumors were more likely to be estrogen receptor negative (P<0.001) and high grade (P=0.002). The primary tumors were also more likely to express cytokeratin 5/6 (P<0.001) and epidermal growth factor receptor (P=0.001), and to overexpress human epidermal growth factor receptor 2 (P=0.001). The data presented above suggest a profile for breast cancer patients at increased risk for developing BM. Predictive factors to help identify patients with metastatic breast cancer who are at an increased risk for developing central nervous system recurrence might allow for screening of this population for early detection and treatment or for the development of targeted strategies for prevention.

Twenty-eight patients with a total of 35 suspect breast masses underwent positron emission tomography (PET) with [fluorine-18] 2-deoxy-2-fluoro-D-glucose (FDG) in order to study the utility of this technique in the evaluation of breast cancer. FDG PET allowed discrimination between eight benign and 27 malignant breast masses, with a sensitivity of 96% and specificity of 100%. Among the malignancies, there was a significant correlation between normalized FDG uptake and nuclear grade (P = .006). In addition, the results of PET imaging were compared with results of axillary node dissection in 20 cases of breast cancer. PET allowed correct categorization of 10 of 10 axillae as negative (specificity = 100%). PET results were equivocal in one axilla and positive in the remaining nine of 10 axillae with positive dissection results (sensitivity = 90%). The authors conclude that FDG PET may give useful information on breast masses and axillary node status prior to surgery.

The relation of breast cancer recurrence and overall survival to age, level of estrogen receptors, number of positive lymph nodes, obesity, race, socioeconomic status, and tumor size at the time of diagnosis was considered for 1,392 breast cancer patients (253 black, 1,132 white, and 7 of other races) entered into two multi-institutional prospective clinical trials. Baseline for the first trial was 1974-1979, and that for the second was 1980-1985; follow-up for this report ended in August 1990. Univariately, all factors except age and obesity were significantly related to disease-free survival, and all except age were significantly related to overall survival. A multivariate analysis using Cox's proportional hazards model indicated that a greater number of positive lymph nodes, a larger tumor diameter, lower socioeconomic status, and negative estrogen receptors were significantly related to shorter disease-free survival. After adjustment for socioeconomic status, race ceased to be a significant indicator of either disease-free survival or overall survival. Patients of either race who are of a lower socioeconomic status are more likely to have a recurrence and to die of breast cancer.