Breast tissue composition and its dependence on demographic risk factors for breast cancer: non-invasive assessment by time domain diffuse optical spectroscopy.

BACKGROUND: Breast tissue composition is recognized as a strong and independent risk factor for breast cancer. It is a heritable feature, but is also significantly affected by several other elements (e.g., age, menopause). Nowadays it is quantified by mammographic density, thus requiring the use of ionizing radiation. Optical techniques are absolutely non-invasive and have already proved effective in the investigation of biological tissues, as they are sensitive to tissue composition and structure. METHODS: Time domain diffuse optical spectroscopy was performed at 7 wavelengths (635-1060 nm) on 200 subjects to derive their breast tissue composition (in terms of water, lipid and collagen content), blood parameters (total hemoglobin content and oxygen saturation level), and information on the microscopic structure (scattering amplitude and power). The dependence of all optically-derived parameters on age, menopausal status, body mass index, and use of oral contraceptives, and the correlation with mammographic density were investigated. RESULTS: Younger age, premenopausal status, lower body mass index values, and use of oral contraceptives all correspond to significantly higher water, collagen and total hemoglobin content, and lower lipid content (always p < 0.05 and often p < 10-4), while oxygen saturation level and scattering parameters show significant dependence only on some conditions. Even when age-adjusted groups of subjects are compared, several optically derived parameters (and in particular always collagen and total hemoglobin content) remain significantly different. CONCLUSIONS: Time domain diffuse optical spectroscopy can probe non-invasively breast tissue composition and physiologic blood parameters, and provide information on tissue structure. The measurement is suitable for in vivo studies and monitoring of changes in breast tissue (e.g., with age, lifestyle, chemotherapy, etc.) and to gain insight into related processes, like the origin of cancer risk associated with breast density.

Estimate of tissue composition in malignant and benign breast lesions by time-domain optical mammography.

The optical characterization of malignant and benign breast lesions is presented. Time-resolved transmittance measurements were performed in the 630-1060 nm range by means of a 7-wavelength optical mammograph, providing both imaging and spectroscopy information. A total of 62 lesions were analyzed, including 33 malignant and 29 benign lesions. The characterization of breast lesions was performed applying a perturbation model based on the high-order calculation of the pathlength of photons inside the lesion, which led to the assessment of oxy- and deoxy-hemoglobin, lipids, water and collagen concentrations. Significant variations between tumor and healthy tissue were observed in terms of both absorption properties and constituents concentration. In particular, benign lesions and tumors show a statistically significant discrimination in terms of absorption at several wavelengths and also in terms of oxy-hemoglobin and collagen content.

Underestimation rate of lobular intraepithelial neoplasia in vacuum-assisted breast biopsy.

OBJECTIVES: To evaluate the underestimation rate and clinical relevance of lobular neoplasia in vacuum-assisted breast biopsy (VABB). METHODS: A total of 161 cases of LN were retrieved from 6,435 VABB. The histological diagnosis was ALH (atypical lobular hyperplasia) in 80 patients, LCIS (lobular carcinoma in situ) in 69 patients and PLCIS (pleomorphic lobular carcinoma in situ) in 12 patients. Seventy-six patients were operated on within 2 years after VABB and 85 were clinically and radiologically monitored. The mean follow-up was 5.2 years, and the prevalence of malignancy was evaluated in the group of 85 patients. RESULTS: The clinico-pathological characteristics significantly favouring surgery were larger lesions, occurrence of a residual lesion following VABB and histological LCIS and PLCIS subtypes. The VABB underestimation rate as compared to surgery was 7.1% for ALH, 12% for LCIS and 50% for PLCIS. Overall, 11 of the 148 patients included in this survival analysis developed an ipsilateral tumour. CONCLUSION: Although obtained retrospectively in a relatively small series of patients, our data suggest that only patients with a diagnosis of PLCIS in VABB should be treated with surgery, whereas patients with ALH and LCIS could be monitored by clinical and radiological examinations. KEY POINTS: • The treatment of ALH and LCIS in VABB is still debated • Some authors favour radical treatment and others a more conservative approach • Only patients with PLCIS in VABB should be treated by surgery.

Optical identification of subjects at high risk for developing breast cancer.

A time-domain multiwavelength (635 to 1060 nm) optical mammography was performed on 147 subjects with recent x-ray mammograms available, and average breast tissue composition (water, lipid, collagen, oxy- and deoxyhemoglobin) and scattering parameters (amplitude a and slope b) were estimated. Correlation was observed between optically derived parameters and mammographic density [Breast Imaging and Reporting Data System (BI-RADS) categories], which is a strong risk factor for breast cancer. A regression logistic model was obtained to best identify high-risk (BI-RADS 4) subjects, based on collagen content and scattering parameters. The model presents a total misclassification error of 12.3%, sensitivity of 69%, specificity of 94%, and simple kappa of 0.84, which compares favorably even with intraradiologist assignments of BI-RADS categories.

Effects of tissue heterogeneity on the optical estimate of breast density.

Breast density is a recognized strong and independent risk factor for developing breast cancer. At present, breast density is assessed based on the radiological appearance of breast tissue, thus relying on the use of ionizing radiation. We have previously obtained encouraging preliminary results with our portable instrument for time domain optical mammography performed at 7 wavelengths (635-1060 nm). In that case, information was averaged over four images (cranio-caudal and oblique views of both breasts) available for each subject. In the present work, we tested the effectiveness of just one or few point measurements, to investigate if tissue heterogeneity significantly affects the correlation between optically derived parameters and mammographic density. Data show that parameters estimated through a single optical measurement correlate strongly with mammographic density estimated by using BIRADS categories. A central position is optimal for the measurement, but its exact location is not critical.

Predictors of invasive breast cancer and lymph node involvement in ductal carcinoma in situ initially diagnosed by vacuum-assisted breast biopsy: experience of 733 cases.

OBJECTIVE: To predict presence of invasive component and nodal involvement in women diagnosed preoperatively with ductal carcinoma in situ (DCIS) by vacuum-assisted breast biopsy (VABB). MATERIALS AND METHODS: We retrospectively analyzed 733 patients with preoperatively diagnosed DCIS, investigating the association of clinical-radiological variables with invasive component and nodal involvement. RESULTS: Mammographic size >20 mm and residual lesion on post-VABB mammogram were related to invasive component (both p < 0.0001) and nodal involvement (p = 0.001, p = 0.03). Age <40 years was associated with presence of invasive component (p = 0.003). By multivariate analysis residual disease was associated with invasive component, and mammographic tumor size >20 mm with nodal involvement, both highly significant. CONCLUSIONS: Older age, lesion <20 mm, and no residual lesion predict absence of invasion and no nodal involvement in VABB-diagnosed DCIS. However it would be imprudent to routinely forego sentinel node biopsy in such patients as non-negligible proportions of them have invasive disease.

Stereotactic vacuum-assisted breast biopsy is not a therapeutic procedure even when all mammographically found calcifications are removed: analysis of 4,086 procedures.

OBJECTIVE: The purpose of our study was to assess whether in case of total removal of microcalcifications there is still residual tumor on the surgical specimen and, secondarily, to assess whether complete rather than partial excision of the imaging target with microcalcifications may result in increased diagnostic accuracy. MATERIALS AND METHODS: We retrospectively reviewed 4,086 stereotactic vacuum-assisted breast biopsy (VABB) procedures for microcalcifications and histologic findings to determine the frequency of malignancy, histologic underestimation, and complete removal of cancer. RESULTS: No residual microcalcifications on postbiopsy mammograms were seen in 1,594 of 4,047 (39.4%) procedures successfully completed: 351 of 1,594 lesions were malignant, 1,109 benign and 134 atypical. After partial removal of microcalcifications at VABB, the postsurgical specimen had infiltrating carcinoma in 130 of 566 cases (23%), whereas in case of total removal of microcalcifications, the underestimation occurred in 13 of 234 (5.5%) cases. The atypical ductal hyperplasia underestimation rate was 6.6% when the mammography target was completely removed and 38.7% when the target was only sampled. The percentage of lobular carcinoma in situ underestimation was the same for the two groups with partial and total removal of microcalcifications (21.2%). Among 1,016 VABB procedures with pathologic result of malignancy, 882 (86.6%) had residual cancer at surgery. In the group with complete removal of microcalcifications at VABB, residual cancer was found in 70% of cases. CONCLUSION: VABB may not be considered a therapeutic procedure, even in the case of complete removal of microcalcifications. However, a complete removal of microcalcifications may result in low rates of underestimation of malignancy and may consequently increase the diagnostic accuracy of the diagnostic procedure.

Noninvasive assessment of breast cancer risk using time-resolved diffuse optical spectroscopy.

Breast density is a recognized strong and independent risk factor for breast cancer. We propose the use of time-resolved transmittance spectroscopy to estimate breast tissue density and potentially provide even more direct information on breast cancer risk. Time-resolved optical mammography at seven wavelengths (635 to 1060 nm) is performed on 49 subjects. Average information on breast tissue of each subject is obtained on oxy- and deoxyhemoglobin, water, lipids, and collagen content, as well as scattering amplitude and power. All parameters, except for blood volume and oxygenation, correlate with mammographic breast density, even if not to the same extent. A synthetic optical index proves to be quite effective in separating different breast density categories. Finally, the estimate of collagen content as a more direct means for the assessment of breast cancer risk is discussed.

Ultrasound-guided vacuum assisted breast biopsy in the assessment of C3 breast lesions by ultrasound-guided fine needle aspiration cytology: results and costs in comparison with surgery.

Breast lesions defined C3 at ultrasound (US)-guided fine needle aspiration cytology (FNAC) are probably benign, but exhibit atypias. We evaluate the results of US-guided vacuum assisted breast biopsy (VABB) of these lesions. Patients diagnosed C3 by US-FNAC, submitted to US-VABB and with a minimum follow-up of 36 months or surgery were enrolled. Cost outcome of this diagnostic protocol was evaluated. We evaluated 138 patients with non-palpable C3 lesions. In 2/138 (1.4%) cases VABB results were inadequate. VABB diagnosed: 17/138 (12.3%) malignant and 119/138 (86.2%) benign lesions. In 28/138 cases (20.3%) surgery retrieved 18/28 (64.3%) malignant lesions. One false negative result of VABB was observed. Sensitivity and specificity of VABB resulted 94.4% and 100%. Our diagnostic algorithm estimated a 45% mean decrease of costs using VABB when compared with surgical biopsy of all C3 lesions.

Sensitivity of imaging for multifocal-multicentric breast carcinoma.

BACKGROUND: This retrospective study aims to determine: 1) the sensitivity of preoperative mammography (Mx) and ultrasound (US), and re-reviewed Mx to detect multifocal multicentric breast carcinoma (MMBC), defined by pathology on surgical specimens, and 2) to analyze the characteristics of both detected and undetected foci on Mx and US. METHODS: Three experienced breast radiologists re-reviewed, independently, digital mammography of 97 women with MMBC pathologically diagnosed on surgical specimens. The radiologists were informed of all neoplastic foci, and blinded to the original mammograms and US reports. With regards to Mx, they considered the breast density, number of foci, the Mx characteristics of the lesions and their BI-RADS classification. For US, they considered size of the lesions, BI-RADS classification and US pattern and lesion characteristics. According to the histological size, the lesions were classified as: index cancer, 2nd lesion, 3rd lesion, and 4th lesion. Any pathologically identified malignant foci not previously described in the original imaging reports, were defined as undetected or missed lesions. Sensitivity was calculated for Mx, US and re-reviewed Mx for detecting the presence of the index cancer as well as additional satellite lesions. RESULTS: Pathological examination revealed 13 multifocal and 84 multicentric cancers with a total of 303 malignant foci (282 invasive and 21 non invasive). Original Mx and US reports had an overall sensitivity of 45.5% and 52.9%, respectively. Mx detected 83/97 index cancers with a sensitivity of 85.6%. The number of lesions undetected by original Mx was 165/303. The Mx pattern of breasts with undetected lesions were: fatty in 3 (1.8%); scattered fibroglandular density in 40 (24.3%), heterogeneously dense in 91 (55.1%) and dense in 31 (18.8%) cases. In breasts with an almost entirely fatty pattern, Mx sensitivity was 100%, while in fibroglandular or dense pattern it was reduced to 45.5%. Re-reviewed Mx detected only 3 additional lesions. The sensitivity of Mx was affected by the presence of dense breast tissue which obscured lesions or by an incorrect interpretation of suspicious findings.US detected 73/80 index cancers (sensitivity of 91.2%), US missed 117 malignant foci with a mean tumor diameter of 6.5 mm; the sensitivity was 52.9%Undetected lesions by US were those smallest in size and present in fatty breast or in the presence of microcalcifications without a visible mass.US sensitivity was affected by the presence of fatty tissue or by the extent of calcification. CONCLUSION: Mx missed MMBC malignant foci more often in dense or fibroglandular breasts. US missed small lesions in mainly fatty breasts or when there were only microcalcifications. The combined sensitivity of both techniques to assess MMBC was 58%. We suggest larger studies on multimodality imaging.