Monitoring of Breast Tissue Change Due to Hormone Replacement Therapy in Post-menopausal Women Using OBS
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Study type: Observational

Summary: 
      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.
    

Detailed description: 
      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.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Post-menopausal women attending the Endocrinology Clinic at St. Michael's Hospital
        (Toronto, Ontario, Canada) who have elected to undergo a 1-year HRT regiment 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. Controls will be recruited among women at the
        University Health Network or attending the Endocrinology Clinic at St. Michael's Hospital
        (Toronto, Ontario, Canada).
      
Biospecimen description: 
      Whole blood
    
Keywords: Breast Cancer Risk; Hormone Replacement Therapy; Optical Transillumination Spectroscopy; Optical Breast Spectroscopy; Transillumination Breast Spectroscopy