Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Symptoms and General Pathology

Breast Neoplasms

Disease Susceptibility

Breast Diseases

Skin Diseases

Lothar Lilge, PhD

This study aims to evaluate if a light based technique, called Optical Breast Spectroscopy (OBS) formerly known as Transillumination Breast Spectroscopy (TiBS), can be used to detect differences in breast tissue between high- and low-risk populations and within the high-risk population between BrCa1 or 2 carriers and non-carriers. These differences may include differences in breast tissue composition and metabolism at time of enrollment into the study (possibly reflecting changes occurring in adolescence) and in the rate of breast tissue change over time (possibly reflecting rate of tissue transformation from normal to ultimately malignant state).

Preliminary data show Optical Breast Spectroscopy (OBS)has the ability to detect tissue differences with various pathologies and age-related changes in breast tissue over a two year period. In the present study, we want to determine whether OBS has the ability to detect optical differences between women who harbor a mutation in the breast cancer susceptibility gene, BrCa1 or BrCa2, and their age-matched controls (non-carriers). More specifically, possible differences in the breast tissue at time of enrollment into the study (reflecting changes potentially occurring in adolescence) and in the rate of breast tissue change over time (reflecting rate of tissue transformation from normal to ultimately malignant state). The overall goal is to develop a pre-screening technique to survey or monitor the risk of breast tissue and to advise the earliest point when imaging techniques (e.g. MRI) should be initiated or when more drastic primary prevention measures are recommended.

Breast Cancer Risk Assessment Using Optical Breast Spectroscopy (OBS)

the primary optical measurements are utilized to determine principal component scores in the analysis which in turn will be used as time dependent variable in a linear regression analysis to determine the rate of change.

Mount Sinai Hospital, Canada

Hamilton Health Sciences Corporation

University Health Network, Toronto

Women with confirmed unilateral breast carcinoma or ductal carcinoma in situ (DCIS)

Women without radiological suspicious lesions, matched to cases by age (± 2.5 years), date of screening mammogram, and screening center.

This study aims to evaluate if a light based technique, called Transillumination Breast Spectroscopy (TIBS), can be used to construct a non-invasive breast cancer risk predictor which provides a better odds ratio than mammographic parenchymal density.

In a previous cross sectional study in a group of women without breast cancer and with varying degrees of parenchymal density patterns, a strong association was demonstrated between Transillumination Breast Spectroscopy (TIBS) and x-ray derived mammographic density. From this, we expect that TIBS should also provide a comparable odds ratio (4-6) as mammographic density for breast cancer risk shown in other independent epidemiological studies. It is possible that TIBS may provide complementary information and a higher odds ratio if compared to the incidence of breast cancer. In contrast to mammography derived parenchymal density pattern, no historical TIBS data is available for a retrospective analysis and hence a cross sectional study within a group of screened women is proposed. We hypothesize that TIBS provides physical information about the breast tissue which can be used to construct a breast cancer risk predictor with an odd ratio \> 6.

Breast Study to Learn More About the Application of Optical Transillumination Measurements to Assess Breast Cancer Risk and to Potentially Detect the Presence of Breast Cancer.

Transillumination for Breast Cancer Risk Assessment

Dr. Lothar Lilge

Menopause

The purpose of this study is to learn more about the application of transillumination measurements in the determination of breast cancer risk. The goal is to demonstrate a correlation between non-invasive optical transillumination spectroscopy and parenchymal density pattern.

X-ray generated images, such as mammograms, rely on the density of tissue within the breast. Tissue density are believed to be associated with proliferation of stroma and/or epithelium, which result in an increase in water associated light absorption and a decrease in lipid associated light absorption. The amount of density of the breast tissue has been shown to be an indicator of cancer risk. Thus, assessing this breast tissue density is also an important tool in determining breast cancer risk.

Optical transillumination has been shown to give information about tissue composition and tissue density. Unlike x-ray mammography which uses ionizing radiation, optical transillumination uses normal white light and is deemed safe to be used frequently for women of all ages and therefore can be used for those situations where mammography is not an option.

Normal white light is shone into the tissue and the light that leaves the breast on the other side from the source is detected and analyzed. Since the same physiological conditions that contribute to dense breast tissue, as seen in mammography, also will have unique optical signatures.

We will compare the amount of this dense tissue from the mammogram, taken with 12 months, to the density measurements found through the optical procedure. The goal is to be able to duplicate the information from the mammogram using the transillumination technique. All measurements are non-invasive and no blood samples or biopsies are required.

Breast Study to Determine the Ability of Non-Invasive Optical Transillumination Spectroscopy to Predict Breast Density.

Optical Transillumination Spectroscopy of Breast Tissue in Pre- and Post-Menopausal Women.

United States Department of Defense

All Drugs and Chemicals

Antineoplastic Agents

Reproductive Control Agents

Estrogens, Conjugated (USP)

Hormones

Progesterone

Medroxyprogesterone Acetate

Medroxyprogesterone

Women receiving HRT treatment of Premarin.

Women receiving combination HRT treatment of Premarin + Provera.

Women receiving combination HRT treatment of Premarin + Prometrium.

Hormone Replacement Therapy (HRT) is a double edged sword: it can alleviate the effects of menopause for a significant proportion of the female population, however for a smaller proportion, it will induce a significant increase in their short-term and lifetime risk to develop breast cancer (BC). Fewer women are prescribed HRT compared to a decade ago due to concerns pertaining to BC by both physicians and patients. By developing a technology that could identify women at risk for the adverse effects of HRT, during the first few months of its use, physicians may offer HRT to a wider proportion of the female population during menopause. More importantly, as it relates to BC prevention, such a technology will identify women at risk and provide a useful decision making tool regarding their care during the menopausal years.

Hormone Replacement Therapy (HRT) provides many benefits to post-menopausal women, which have been overshadowed by an increase in breast cancer in women following HRT, resulting in a negative HRT cost-benefit ratio. Epidemiological studies show evidence of a direct association between HRT use and breast cancer incidence. This increase in incidence was also reflected in an increase of the mammographic breast density (MBD). Endogenous MBD is a well established risk factor for breast cancer which provides a high odds ratio (OR 4 - 6) towards breast cancer. Increases in MBD have been reported in women who initiate HRT, which is of concern as it potentially indicates a greater adverse effect of HRT on those individuals. In these cases, the majority of the incremental MBD increase manifests itself during the first year of use and decreases in the case of therapy cessation. The ability to detect changes in MBD in women commencing HRT treatment, without the ionizing radiation dose penalty imparted by mammography, thus permitting improved monitoring of MBD changes de to HRT, would certainly impact the debate on the applicability of HRT. Women identified as having increased MBD induced by HRT should discontinue its use or modify the prescription as increases in MBD potentially indicates an adverse ratio; women whose MBD has not been adversely affected by HRT can continue its use and reap the benefits of HRT (e.g. relief of climacteric symptoms, beneficial effects against osteoporosis and coronary heart disease).

Optical Breast Spectroscopy (OBS) is a safe and non-invasive optical technique that provides information on breast tissue composition and physiology state. Comparison of breast tissue status over time will provide information on changes in the MBD and breast cancer risk due to interventions such as HRT. To demonstrate that breast tissue status changes with HRT use, we will exploit existing algorithms correlating OBS with various biological outcomes. A completed study on a cohort of 300 healthy women (age 38 to 72) showed a high correlation between OBS optical parameters and Cumulus derived MBD. An ongoing study, to be completed Q3 2008 with an interim analysis available, suggests that OBS parameters can optically detect differences between the contralateral breasts of women with a unilateral carcinoma or ductal carcinoma in situ (DCIS) and healthy controls. Through these studies, two OBS algorithms ("density" and "risk") are available for application in the proposed study. The algorithms take OBS optical data as input and output OBS-derived percent breast density (PBD) and OBS-derived risk values. The aim of the study is to examine changes in OBS-derived PBD and OBS-derived risk values due to the initiation, use and cessation of HRT over a 1 year period. The case group will comprise a population of post-menopausal women who have elected to undergo a HRT regiment designed to last at least 1 year but had no prior HRT treatment. The comparison group (control) will comprise of post-menopausal women not on HRT and had no prior HRT treatment. OBS measurements will be assessed at intervals corresponding to: baseline (pre-HRT), 1 month, 3 months, 6 months, and 1 year after initiation of HRT use, and 3 months after cessation of treatment (in cases where HRT is discontinued within one year). Blood will be collected at baseline and at 3 months during treatment to examine changes in circulating hormones (estrogen, progesterone). Mammography will be performed at three months during treatment and compared to a screening mammogram (taken within a year prior to HRT treatment) to determine changes in breast density. A Papanicolaou test (or PAP smear) will be performed at baseline to assess endometrial changes. Changes in OBS derived PBD and MBD as well as other pertinent risk values will be examined as a function of time.

Four model groups will be monitored consisting of cases receiving treatments of Premarin, Premarin + Provera combination, or Premarin + Prometrium combination and controls not on HRT. A total of 20 women will be recruited into each group of the four groups. While the total number of women intended for recruitment is small, they are sufficient to enable us to demonstrate that OBS changes as function of MBD changes. Of further interest, we want to determine whether OBS can detect changes prior to changes to MBD in standard clinical setting. In particular, we aim to determine the magnitude of the effect size and the variance within the study groups for later initiation of a larger definitive clinical monitoring trail of HRT effects by OBS.

The long term clinical goal is the identification of women adversely affected by HRT by OBS as they can be advised of alternative methods with possible lower risk to benefit ratio to relieve climacteric symptoms. An overall effect will be a reduction in the population-based incidence of breast cancer while not withholding the beneficial effects of HRT to the majority of women during menopause.

Study title	NCT ID	Conditions	Eligibility	Organization
Breast Cancer Risk Assessment Using Optical Breast Spectroscopy (OBS)	NCT00500383	Breast Cancer	25 Years - 60 Years	University Health Network, Toronto
Breast Study to Learn More About the Application of Optical Transillumination Measurements to Assess Breast Cancer Risk and to Potentially Detect the Presence of Breast Cancer.	NCT00188721	Breast Cancer	30 Years - 70 Years	University Health Network, Toronto
Breast Cancer Risk Assessment Using Optical Breast Spectroscopy (OBS)	NCT00500383	Breast Cancer	25 Years - 60 Years	University Health Network, Toronto
Breast Study to Determine the Ability of Non-Invasive Optical Transillumination Spectroscopy to Predict Breast Density.	NCT00188682	Breast Cancer	35 Years - 75 Years	University Health Network, Toronto
Monitoring of Breast Tissue Change Due to Hormone Replacement Therapy in Post-menopausal Women Using OBS	NCT00797199	Breast Cancer	30 Years - 65 Years	University Health Network, Toronto

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