Impact of factors affecting the residual tumor size diagnosed by MRI following neoadjuvant chemotherapy in comparison to pathology.

BACKGROUND AND OBJECTIVES: To investigate accuracy of magnetic resonance imaging (MRI) for measuring residual tumor size in breast cancer patients receiving neoadjuvant chemotherapy (NAC). METHODS: Ninety-eight patients were studied. Several MRI were performed during NAC for response monitoring, and the residual tumor size was measured on last MRI after completing NAC. Covariates, including age, tumor characteristics, biomarkers, NAC regimens, MRI scanners, and time from last MRI to operation, were analyzed. Univariate and Multivariate linear regression models were used to determine the predictive value of these covariates for MRI-pathology size discrepancy as the outcome measure. RESULTS: The mean (±SD) of the absolute difference between MRI and pathological residual tumor size was 1.0 ± 2.0 cm (range, 0-14 cm). Univariate regression analysis showed tumor type, morphology, HR status, HER2 status, and MRI scanner (1.5 T or 3.0 T) were significantly associated with MRI-pathology size discrepancy (all P < 0.05). Multivariate regression analyses demonstrated that only tumor type, tumor morphology, and biomarker status considering both HR and HER-2 were independent predictors (P = 0.0014, 0.0032, and 0.0286, respectively). CONCLUSION: The accuracy of MRI in evaluating residual tumor size depends on tumor type, morphology, and biomarker status. The information may be considered in surgical planning for NAC patients.

Optical imaging of breast cancer oxyhemoglobin flare correlates with neoadjuvant chemotherapy response one day after starting treatment.

Approximately 8-20% of breast cancer patients receiving neoadjuvant chemotherapy fail to achieve a measurable response and endure toxic side effects without benefit. Most clinical and imaging measures of response are obtained several weeks after the start of therapy. Here, we report that functional hemodynamic and metabolic information acquired using a noninvasive optical imaging method on the first day after neoadjuvant chemotherapy treatment can discriminate nonresponding from responding patients. Diffuse optical spectroscopic imaging was used to measure absolute concentrations of oxyhemoglobin, deoxyhemoglobin, water, and lipid in tumor and normal breast tissue of 24 tumors in 23 patients with untreated primary breast cancer. Measurements were made before chemotherapy, on day 1 after the first infusion, and frequently during the first week of therapy. Various multidrug, multicycle regimens were used to treat patients. Diffuse optical spectroscopic imaging measurements were compared with final postsurgical pathologic response. A statistically significant increase, or flare, in oxyhemoglobin was observed in partial responding (n = 11) and pathologic complete responding tumors (n = 8) on day 1, whereas nonresponders (n = 5) showed no flare and a subsequent decrease in oxyhemoglobin on day 1. Oxyhemoglobin flare on day 1 was adequate to discriminate nonresponding tumors from responding tumors. Very early measures of chemotherapy response are clinically convenient and offer the potential to alter treatment strategies, resulting in improved patient outcomes.

Breast cancer: evaluation of response to neoadjuvant chemotherapy with 3.0-T MR imaging.

PURPOSE: To assess how the molecular biomarker status of a breast cancer, including human epidermal growth factor receptor 2 (HER2), hormone receptors, and the proliferation marker Ki-67 status, affects the diagnosis at 3.0-T magnetic resonance (MR) imaging. MATERIALS AND METHODS: This study was approved by the institutional review board and was HIPAA compliant. Fifty patients (age range, 28-82 years; mean age, 49 years) receiving neoadjuvant chemotherapy were monitored with 3.0-T MR imaging. The longest dimension of the residual cancer was measured at MR imaging and correlated with pathologic findings. Patients were further divided into subgroups on the basis of HER2, hormone receptor, and Ki-67 status. Pathologic complete response (pCR) was defined as when there were no residual invasive cancer cells. The Pearson correlation was used to correlate MR imaging-determined and pathologic tumor size, and the unpaired t test was used to compare MR imaging-pathologic size discrepancies. RESULTS: Of the 50 women, 14 achieved pCR. There were seven false-negative diagnoses at MR imaging. The overall sensitivity, specificity, and accuracy for diagnosing invasive residual disease at MR imaging were 81%, 93%, and 84%, respectively. The mean MR imaging-pathologic size discrepancy was 0.5 cm ± 0.9 (standard deviation) for HER2-positive cancer and 2.3 cm ± 3.5 for HER2-negative cancer (P = .009). In the HER2-negative group, the size discrepancy was smaller for hormone receptor-negative than for hormone receptor-positive cancers (1.0 cm ± 1.1 vs 3.0 cm ± 4.0, P = .04). The size discrepancy was smaller in patients with 40% or greater Ki-67 expression (0.8 cm ± 1.1) than in patients with 10% or less Ki-67 expression (3.9 cm ± 5.1, P = .06). CONCLUSION: The diagnostic accuracy of breast MR imaging is better in more aggressive than in less aggressive cancers. When MR imaging is used for surgical planning, caution should be taken with HER2-negative hormone receptor-positive cancers.

Comparison of breast density measured on MR images acquired using fat-suppressed versus nonfat-suppressed sequences.

PURPOSE: To investigate the difference of MR percent breast density measured from fat-suppressed versus nonfat-suppressed imaging sequences. METHODS: Breast magnetic resonance imaging (MRI) with and without fat suppression was acquired from 38 subjects. Breasts were divided into subgroups of different morphological patterns ("central" and "intermingled" types). Breast volume, fibroglandular tissue volume, and percent density were measured. The results were compared using nonparametric statistical tests and regarded as significant at p < 0.05. RESULTS: Breast volume, fibroglandular volume, and percent density between fat-suppressed and nonfat-suppressed sequences were highly correlated. Breast volumes measured on these two sequences were almost identical. Fibroglandular tissue volume and percent density, however, had small (<5%) yet significant differences between the two sequences-they were both higher on the fat-suppressed sequence. Intraobserver variability was within 4% for both sequences and different morphological types. The fibroglandular tissue volume measured on downsampled images showed a small (<5%) yet significant difference. CONCLUSIONS: The measurement of breast density made on MRI acquired using fat-suppressed and nonfat-suppressed T1W images was about 5% difference, only slightly higher than the intraobserver variability of 3%-4%. When the density data from multiple centers were to be combined, evaluating the degree of difference is needed to take this difference into account.

Characterization of metabolic differences between benign and malignant tumors: high-spectral-resolution diffuse optical spectroscopy.

PURPOSE: To develop a near-infrared spectroscopic method to identify breast cancer biomarkers and to retrospectively determine if benign and malignant breast lesions could be distinguished by using this method. MATERIALS AND METHODS: The study was HIPAA compliant and was approved by the university institutional review board. Written informed consent was obtained. By using self-referencing differential spectroscopy (SRDS) analysis, the existence of specific spectroscopic signatures of breast lesions on images acquired by using diffuse optical spectroscopy imaging in the wavelength range (650-1000 nm) was established. The SRDS method was tested in 60 subjects (mean age, 38 years; age range, 22-74 years). There were 17 patients with benign breast tumors and 22 patients with malignant breast tumors. There were 21 control subjects. RESULTS: Discrimination analysis helped separate malignant from benign tumors. A total of 40 lesions (22 malignant and 18 benign) were analyzed. Twenty were true-positive lesions, 17 were true-negative lesions, one was a false-positive lesion, and two were false-negative lesions (sensitivity, 91% [20 of 22]; specificity, 94% [17 of 18]; positive predictive value, 95% [20 of 21]; and negative predictive value, 89% [17 of 19]). CONCLUSION: The SRDS method revealed localized tumor biomarkers specific to pathologic state.

Impact of MRI-evaluated neoadjuvant chemotherapy response on change of surgical recommendation in breast cancer.

OBJECTIVE: To investigate how MRI imaging of neoadjuvant chemotherapy (NAC) tumor response affects the recommendation for optimal breast cancer surgery, both before and after NAC. SUMMARY BACKGROUND DATA: Understanding how imaging findings are incorporated into surgeons' decision-making processes will help establish appropriate imaging guidelines for recommending breast conservation surgery (BCS) after the NAC. METHODS: Seventy-six breast cancer patients undergoing NAC with MRI follow-up studies were analyzed. Two experienced breast surgeons reviewed all cases. An initial surgical recommendation was made based on the pre-NAC lesion presentation; a subsequent surgical recommendation was made based on the post-NAC tumor response. Finally, the pathology results were disclosed and the surgeons were asked to decide on the optimal definitive surgical procedure. MRI findings throughout the entire course of the NAC were analyzed to understand how they affected different recommendations. RESULTS: Before the NAC, a large tumor size or extent of disease were the primary determinant factors for mastectomy. In this study, the mean tumor size was 5.3 +/- 3.4 cm (RECIST) in the mastectomy group and 3.2 +/- 1.6 cm in the lumpectomy group (P = 0.0001). After the NAC, based on consensus recommendations, 21 mastectomy candidates remained for mastectomy, with tumor size decreasing from 7.4 +/- 4.5 to 1.5 +/- 2.5 cm, and 22 mastectomy candidates were changed to lumpectomy, with tumor size decreasing from 4.2 +/- 2.1 to 0.4 +/- 0.6 cm. When the final pathology revealed pCR or minimal residual disease, the surgeons agreed that BCS is the optimal procedure. On the other hand, for a large extent of residual disease, mastectomy should be performed. CONCLUSION: In patients who had more extensive pretreatment disease, despite an excellent response to NAC, the surgeons still tended to apply an aggressive approach and recommended mastectomy. Given that the confirmation of pCR or minimal residual disease would change surgeons' recommendations for less aggressive, conservation surgery, the maturity of MRI for NAC response prediction may provide reliable staging information to aid in the recommendation of the optimal surgical procedure.

Diffuse optical spectroscopy measurements of healing in breast tissue after core biopsy: case study.

Diffuse optical spectroscopy (DOS) has been used to monitor and predict the effects of neoadjuvant (i.e., presurgical) chemotherapy in breast cancer patients in several pilot studies. Because patients with suspected breast cancers undergo biopsy prior to treatment, it is important to understand how biopsy trauma influences DOS measurements in the breast. The goal of this study was to measure the effects of a standard core breast biopsy on DOS measurements of tissue deoxyhemoglobin, hemoglobin, water, and bulk lipid concentrations. We serially monitored postbiopsy effects in the breast tissue in a single subject (31-year-old premenopausal female) with a 37x18x20 mm fibroadenoma. A baseline measurement and eight weekly postbiopsy measurements were taken with a handheld DOS imaging instrument. Our instrument used frequency domain photon migration combined with broadband steady-state spectroscopy to characterize tissues via quantitative measurements of tissue absorption and reduced scattering coefficients from 650 to 1000 nm. The concentrations of significant near-infrared (NIR) absorbers were mapped within a 50 cm(2) area over the biopsied region. A 2-D image of a contrast function called the tissue optical index (TOI=deoxyhemoglobinxwaterbulk lipid) was generated and revealed that a minimum of 14 days postbiopsy was required to return TOI levels in the biopsied area to their prebiopsy levels. Changes in the TOI images of the fibroadenoma also reflected the progression of the patient's menstrual cycle. DOS could therefore be useful in evaluating both wound-healing response and the effects of hormone and hormonal therapies in vivo.

Effect of contact force on breast tissue optical property measurements using a broadband diffuse optical spectroscopy handheld probe.

We investigated the effects of operator-applied force on diffuse optical spectroscopy (DOS) by integrating a force transducer into the handheld probe. Over the typical range of contact forces measured in the breasts of eight patients, absorption and reduced scattering coefficients (650 to 1000 nm) variance was 3.1 +/- 1.0% and 1.0 +/- 0.4%. For trained operators, we observed <5% variation in hemoglobin and <2% variation in water and lipids. Contact force is not a significant source of variation, most likely because of a relatively wide probe surface area and the stability of the DOS method for calculating tissue optical properties.

Regional differences in the use of sentinel lymph node biopsy for melanoma: a potential quality measure.

Sentinel lymph node biopsy (SLNB) provides accurate nodal staging in patients with melanoma. However, its prevalence across geographic regions is unknown. Our aim was to determine if SLNB for melanoma has been widely adopted throughout the United States. All patients in the Surveillance, Epidemiology and End Results (SEER) cancer registry for 2004 with melanoma were evaluated. Data were collected for demographics, depth of melanoma, and type of nodal evaluation (regional lymph node dissection vs SLNB). Registry sites were categorized into West, Midwest, Northeast, and Southeast. Chi2 analysis was performed to identify regional differences in receipt of SLNB. Overall, the West region (n = 2352) had a higher use of SLNB compared with the Midwest (n = 497), Northeast (n = 630), and Southeast (n = 268) regions (82.1% vs 77.9%, 65.4%, and 60.1%, respectively; P < 0.001). Intermediate-thickness (1 to 4 mm) melanomas had differences in SLNB use between the West and Midwest (83.6% and 81.4%) versus the Northeast and Southeast (66.3% and 60.2%) (P < 0.05). This population-based analysis shows low use of SLNB for melanoma in some U.S. regions. Further studies need to address the reasons for these differences and target ways to improve rates. Results suggest that SLNB may be considered as a potential quality measure.

Predicting nodal status using dynamic contrast-enhanced magnetic resonance imaging in patients with locally advanced breast cancer undergoing neoadjuvant chemotherapy with and without sequential trastuzumab.

HYPOTHESIS: Dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) is a reliable and accurate method for monitoring primary tumor response in the breast and can be used as a surrogate to predict final axillary nodal status. DESIGN: Retrospective study (October 1, 2004, through February 28, 2006) of 46 patients with clinically staged locally advanced breast cancer. SETTING: Comprehensive cancer center. PATIENTS: Forty-six patients with locally advanced breast cancer. INTERVENTIONS: Neoadjuvant chemotherapy (NAC), DCE-MRI, mastectomy and lumpectomy, and axillary lymph node dissection. MAIN OUTCOME MEASURES: The DCE-MRI results and pathologic response of the breast and axillary lymph nodes. RESULTS: Forty-six patients underwent NAC with doxorubicin hydrochloride and cyclophosphamide, followed by paclitaxel and carboplatin, with or without trastuzumab based on human epidermal growth factor receptor 2 (HER2/neu) status. Twenty-one patients (46%) had a complete pathologic response. For the HER2/neu-positive patients, the complete pathologic response rate was 70% (14/20). The accuracy, sensitivity, and specificity of the primary tumor response in predicting the axillary nodal status were 78%, 88%, and 72%, respectively. The accuracy, sensitivity, and specificity of the DCE-MRI-measured response in the primary tumor in predicting axillary nodal status were 74%, 62%, and 82%, respectively. For the HER2/neu-positive patients, the accuracy, sensitivity, and specificity improved to 80%, 75%, and 82%, respectively. CONCLUSIONS: The results of DCE-MRI of the primary tumor can be predictive of axillary nodal status, especially in patients receiving trastuzumab who are HER2/neu positive. The HER2/neu-positive patients with a complete clinical response on DCE-MRI are highly unlikely to benefit from an axillary lymph node dissection. For HER2/neu-negative patients, sentinel lymph node sampling is warranted.

Diffuse optical monitoring of blood flow and oxygenation in human breast cancer during early stages of neoadjuvant chemotherapy.

We combine diffuse optical spectroscopy (DOS) and diffuse correlation spectroscopy (DCS) to noninvasively monitor early hemodynamic response to neoadjuvant chemotherapy in a breast cancer patient. The potential for early treatment monitoring is demonstrated. Within the first week of treatment (day 7) DOS revealed significant changes in tumor/normal contrast compared to pretreatment (day 0) tissue concentrations of deoxyhemoglobin (rctHHbT/N=69+/-21%), oxyhemoglobin (rctO2HbT/N=73+/-25%), total hemoglobin (rctTHbT/N=72+/-17%), and lipid concentration (rctLipidT/N=116+/-13%). Similarly, DCS found significant changes in tumor/normal blood flow contrast (rBFT/N=75+/-7% on day 7 with respect to day 0). Our observations suggest the combination of DCS and DOS enhances treatment monitoring compared to either technique alone. The hybrid approach also enables construction of indices reflecting tissue metabolic rate of oxygen, which may provide new insights about therapy mechanisms.

Do breast columnar cell lesions with atypia need to be excised?

Columnar cell lesion with atypia (CCLA) is a newly recognized pathologic entity seen in breast specimens. The breast cancer risk associated with this finding is unclear, although CCLA had been found adjacent to both in situ and invasive carcinomas, but the incidence is unknown. Breast specimens from patients with a columnar cell lesion were reviewed by a pathologist for atypia. Twenty-one specimens with CCLA were identified [core biopsy (8), excisional biopsy (11), and simple mastectomy (2)]. Six of eight specimens with CCLA on core had adjacent abnormal pathology: infiltrating ductal carcinoma (IDC)/lobular carcinoma in situ (LCIS) (1), ductal carcinoma in situ (DCIS)/LCIS (1), DCIS (1), LCIS (1), and papillomatosis (2). Five of 11 specimens with CCLA on excisional biopsy had adjacent abnormal pathology: IDC (3), DCIS/LCIS (1), and atypical ductal hyperplasia/papilloma (1). Two of two simple mastectomy specimens had CCLA associated with IDC (1) and DCIS (1). Overall, abnormal pathology was found adjacent to CCLA in 62 per cent of specimens (13/21). Breast pathologic specimens containing a columnar cell lesion should be carefully examined for atypia. Surgical excision is warranted for CCLA found on core biopsy. The future risk of breast cancer based on the finding of CCLA alone requires further investigation.

The predictive value of sentinel lymph node biopsy in locally advanced breast cancer patients who have undergone neoadjuvant chemotherapy.

With the increasing usage of neoadjuvant chemotherapy (NAC) in locally advanced breast cancer (LABC), there is the need to investigate the routine axillary node dissections performed in this group of patients. Controversy exists about the utility of sentinel node biopsy (SNB), either before or after NAC. With the addition of trastuzumab in the treatment of Her2/neu-positive LABC patients, the validity of SNB in this subset population needs to be investigated. A retrospective study of 20 patients who underwent NAC for LABC was undertaken. The pathology of the axillary nodes, sentinel nodes, and primary tumor after neoadjuvant chemotherapy were examined. Twenty patients underwent NAC with doxorubicin and cyclophosphamide, followed sequentially by paclitaxel and carboplatin, with or without trastuzumab based on Her2/neu status. Post chemotherapy, 20 patients underwent mastectomy or lumpectomy with SNB with axillary node dissections. The overall accuracy of SNB was 95 per cent with a false-negative rate of 14 per cent (1/7). In Her2/neu-positive patients, overall accuracy was 100 per cent (8/8) and a false-negative rate of zero per cent. Sentinel node biopsy is a viable option in patients who have undergone NAC. Her2/neu-positive patients who had undergone NAC with trastuzumab had comparable accuracy for sentinel node biopsy in predicting axillary node status.

In vivo absorption, scattering, and physiologic properties of 58 malignant breast tumors determined by broadband diffuse optical spectroscopy.

Diffuse optical imaging (DOI) may be a beneficial diagnostic method for women with mammographically dense breast tissue. In order to evaluate the utility of DOI, we are developing broadband diffuse optical spectroscopy (DOS) to characterize the functional origins of optical signals in breast cancer patients. Broadband DOS combines multifrequency intensity-modulated and continuous-wave near-infrared light to quantify tissue absorption and scattering spectra from 650 to 1000 nm. Values of intrinsic physiological properties (oxy- and deoxy-hemoglobin, water, lipid, and scatter power) derived from absorption and scattering spectra provide detailed information on breast physiology. We present the results of clinical studies of 58 stage II/III malignant breast tumors using a noninvasive, handheld, broadband DOS probe. On average, eight positions were scanned over tumor and contralateral normal breast for each subject. Intrinsic physiological properties were statistically significantly different for malignant vs. normal tissues for all subjects, without patient age or tumor size/type stratification. Breast tissues containing malignant tumors displayed reduced lipid content ( approximately 20%) and increased water, deoxy-, and oxy-hemoglobin (>50% each) compared to normal breast tissues. Functional perturbations by the tumor were significantly larger than functional variations in normal tissues. A tissue optical index (TOI) derived from intrinsic physiological properties yielded an average two-fold contrast difference between malignant tumors and intrinsic tissue properties. Our results demonstrate that intrinsic optical signals can be influenced by functional perturbations characteristic of malignant transformation; cellular metabolism, extracellular matrix composition, and angiogenesis. Our findings further underscore the importance of broadband measurements and patient age stratification in breast cancer DOI.

Imaging in breast cancer: diffuse optics in breast cancer: detecting tumors in pre-menopausal women and monitoring neoadjuvant chemotherapy.

Diffuse optical spectroscopy (DOS) and diffuse optical imaging (DOI) are non-invasive diagnostic techniques that employ near-infrared (NIR) light to quantitatively characterize the optical properties of centimeter-thick, multiple-scattering tissues. Although NIR was first applied to breast diaphanography more than 70 years ago, quantitative optical methods employing time- or frequency-domain 'photon migration' technologies have only recently been used for breast imaging. Because their performance is not limited by mammographic density, optical methods can provide new insight regarding tissue functional changes associated with the appearance, progression, and treatment of breast cancer, particularly for younger women and high-risk subjects who may not benefit from conventional imaging methods. This paper reviews the principles of diffuse optics and describes the development of broadband DOS for quantitatively measuring the optical and physiological properties of thick tissues. Clinical results are shown highlighting the sensitivity of diffuse optics to malignant breast tumors in 12 pre-menopausal subjects ranging in age from 30 to 39 years and a patient undergoing neoadjuvant chemotherapy for locally advanced breast cancer. Significant contrast was observed between normal and tumor regions of tissue for deoxy-hemoglobin (p = 0.005), oxy-hemoglobin (p = 0.002), water (p = 0.014), and lipids (p = 0.0003). Tissue hemoglobin saturation was not found to be a reliable parameter for distinguishing between tumor and normal tissues. Optical data were converted into a tissue optical index that decreased 50% within 1 week in response to neoadjuvant chemotherapy. These results suggest a potential role for diffuse optics as a bedside monitoring tool that could aid the development of new strategies for individualized patient care.

Coregistration of dynamic contrast enhanced MRI and broadband diffuse optical spectroscopy for characterizing breast cancer.

A hand-held scanning probe based on broadband Diffuse Optical Spectroscopy (DOS) was used in combination with dynamic contrast enhanced MRI (DCE-MRI) to quantitatively characterize locally-advanced breast cancers in six patients. Measurements were performed sequentially using external fiducial markers for co-registration. Tumor patterns were categorized according to MRI morphological data, and 3D DCE-MRI slices were converted into a volumetric matrix with isotropic voxels to generate views that coincided with the DOS scanning plane. Tumor volume and depth at each DOS measurement site were determined, and a tissue optical index (TOI) that reflects both angiogenic and stromal characteristics was derived from broadband DOS data. In all six cases, optical scans showed significant TOI contrast corresponding to MRI morphological information. Sharp TOI peaks were recovered for well-circumscribed masses. A reduction in TOI was found inside a tumor with a necrotic center. A broadened peak was observed for a diffuse tumor pattern, and an inflammatory septal case provided two TOI peaks that correlated qualitatively with MRI enhancement. These results provide qualitative confirmation of the common signal origin and complementary information content that can be achieved by combining optical and MR imaging for breast cancer detection and clinical management.

The role of diffuse optical spectroscopy in the clinical management of breast cancer.

Diffuse optical spectroscopy (DOS) of breast tissue provides quantitative, functional information based on optical absorption and scattering properties that cannot be obtained with other radiographic methods. DOS-measured absorption spectra are used to determine the tissue concentrations of deoxyhemoglobin (Hb-R), oxyhemoglobin (Hb-O2), lipid, and water (H2O), as well as to provide an index of tissue hemoglobin oxygen saturation (StO2). Tissue-scattering spectra provide insight into epithelial, collagen, and lipid contributions to breast density. Clinical studies of women with malignant tumors show that DOS is sensitive to processes such as increased tissue vascularization, hypoxia, and edema. In studies of healthy women, DOS detects variations in breast physiology associated with menopausal status, menstrual cycle changes, and hormone replacement. Current research involves using DOS to monitor tumor response to therapy and the co-registration of DOS with magnetic resonance imaging. By correlating DOS-derived parameters with lesion pathology and specific molecular markers, we anticipate that composite "tissue optical indices" can be developed that non-invasively characterize both tumor and normal breast-tissue function.

Spatial variations in optical and physiological properties of healthy breast tissue.

Near-infrared (NIR) diffuse optical spectroscopy (DOS) and diffuse optical imaging (DOI) show promise as noninvasive clinical techniques for breast cancer screening and diagnosis. Since NIR methods are based on optical contrast between healthy and diseased tissue, it is essential to characterize the sources of endogenous contrast in normal subjects. We report intra- and inter-subject variation and bilateral asymmetry of the optical and physiological parameters of 31 women using a seven-wavelength NIR frequency-domain photon migration (FDPM) instrument. Wavelength-dependent absorption and reduced scattering parameters (micro(a) and micro(s'), respectively) were measured in four major quadrants and the areolar regions of left and right breasts. These values were used to determine tissue concentrations of oxy-(HbO(2)) and deoxy-(Hb-R) hemoglobin, lipid content, water concentration, and tissue "scatter power." Mean total hemoglobin for premenopausal (PRE) women (20 to 30 microM) is approximately two-fold higher than for postmenopausal (POST) subjects at all positions. POST women have approximately 50% higher lipid content (50 to 60%) than PRE at all positions. Water concentration on average is 1.8-fold higher for PRE subjects (30 to 40%) than POST. These differences are most pronounced when comparing the areolar complex to the other regions of the breast. In premenopausal women, the areolar regions have 40 to 45% increased total hemoglobin concentration (THC), 20 to 25% lower lipid content, and 30 to 60% higher scatter power versus the quadrants. Small-scale (3 cm) changes in optical properties are negligible compared to large-scale variations over all quadrants, where the intrinsic spatial heterogeneity of healthy breast tissue is 20 to 40% for micro(a) and 5 to 12% for micro(s'). Although no consistent right-left differences are observed in the study population, relative differences between symmetric positions ranged from 18 to 30% for THC, 10 to 40% for adipose, 10 to 25% for water, and 4 to 9% for scattering (674 nm) within an individual.

Monitoring neoadjuvant chemotherapy in breast cancer using quantitative diffuse optical spectroscopy: a case study.

Presurgical chemotherapy is widely used in the treatment of locally advanced breast cancer. Monitoring the response to therapy can improve survival and reduce morbidity. We employ a noninvasive, near-infrared method based on diffuse optical spectroscopy (DOS) to quantitatively monitor tumor response to neoadjuvant chemotherapy. DOS was used to monitor tumor response in one patient with locally advanced breast cancer throughout the course of her therapy. Measurements were performed prior to doxorubicin-cyclophosphamide therapy and at several time points over the course of three treatment cycles (68 days). Our results show strong tumor to normal (T/N) tissue contrast in total hemoglobin concentration (T/N=2.4), water fraction (T/N=6.9), tissue hemoglobin oxygen saturation, S(t)O(2) (T/N=0.9), and lipid fraction (T/N=0.7) prior to treatment. Over a 10-week period, the peak total hemoglobin and water dropped 56 and 67%, respectively. Lipid content nearly returned to baseline (T/N =0.9) while S(t)O(2) exceeded pretreatment levels (T/N =1.5). Approximately half of the hemoglobin and water changes occurred within 5 days of treatment (26 and 37%, respectively). These data suggest that noninvasive, quantitative optical methods that characterize tumor physiology may be useful in assessing and optimizing individual response to neoadjuvant chemotherapy.