Breast cancer profiling

DUNCAN M, MERZ-DEMLOW E, XU X, PHIPPS w R and KURZER M s (2000) Premenopausal equol excretors show plasma hormone profiles associated with lowered risk of breast cancer. Cancer Epidemiol Biomarkers Prev 9, 581-6. 

Black cohosh has been one of the most studied herbal remedies for vasomotor symptoms, and it has not demonstrated a substantial benefit over placebo. The mechanism of action, safety profile, drug-drug interactions, and adverse effects of black cohosh remain unknown. In non-placebo-controlled trials conducted for 6 months or less, black cohosh demonstrated a small reduction in vasomotor symptoms. It has not been shown to be effective for vasomotor symptoms in women with breast cancer.33 There have been case reports of hepatotoxicity with the use of black cohosh.36 Caution should be exercised when considering the use of this product, especially in patients with liver dysfunction. 

Toremifene is a recently marketed antiestrogen whose primary advantage is a lower estrogenic antiestrogenic ratio than tamoxifen (based on laboratory data).41 Toremifene (60 mg orally daily) has been found to have efficacy similar to that of tamoxifen in metastatic disease and a generally similar side-effect profile.42 Currently, toremifene is indicated as an alternative to tamoxifen in patients with metastatic breast cancer, but studies are ongoing that evaluate its safety and efficacy in the adjuvant setting. 

Sandhu, C., Connor, M., Kislinger, T., Slingerland, J., Emili, A. (2005). Global protein shotgun expression profiling of proliferating mcf-7 breast cancer cells. J. Proteome Res. 4,674—689. 

Hedenfalk I et al. Gene expression profiles in hereditary breast cancer. N Engl J Med 2001 344 539-548. 

Sgroi DC et al. In vivo gene expression profile analysis of human breast cancer progression. Cancer Res 1999 59 5656-5661. 

In phase I clinical trials 47 patients, all of whom had previously failed standard treatments for solid tumors, received the drug in the UK, Italy, and Switzerland on three different schedules.123,124 Dose-limiting toxicities have been defined as bone marrow depression and diarrhea. The latter is treatable with loperamide. Signs of biological activity were seen. Notably one patient with metastatic pancreatic cancer showed a partial response (for 4 months) and two further patients, one with metastatic melanoma and one with bronchoalveolar carcinoma, also showed partial responses. In a phase I trial in combination with 5-FU, a partial response in breast cancer was observed.125 Furthermore, a reduction in tumor marker levels was observed in two patients, one with ovarian cancer, and one with colon cancer. Phase II studies have shown partial responses in cisplatin-resistant ovarian and nonsmall-cell lung cancer.126,127 The indications are that the profile of clinical activity is different and complementary to the mononuclear platinum agents. 

This type of modeling, as well as wide field FLIM [84-86] and endoscopy [72] have tremendous potential for clinical diagnosis. Although still at the preclinical stage, various groups have looked at the differences in fluorescence spectrum and decay profiles in breast cancer [87, 88], the gastrointestinal tract [89], and skin cancer [90, 91] (see also Chapter 4). 

Daigo Y, Chin S-F, Gorringe KL, et al. Degenerate oligonucleotide primed-polymerase chain reaction-based array comparative genomic hybridization for extensive Amplicon profiling of breast cancers. A new approach for the molecular analysis of paraffin-embedded cancer tissue. Am. J. Pathol. 2001 158 1623-1631. 

Hasemeier B, Christgen M, Kreipe H, et al. Reliable microRNA profiling in routinely processed formalin-fixed paraffin-embedded breast cancer specimens using fluorescence labelled bead technology. BMC Biotechnology 2008 8 90, doi 10.1186/1472-6750-8-90. 

Chong BE, Lubman DM, Miller FR, et al. Rapid screening of protein profiles of human breast cancer cell lines using non-porous reversed-phase high performance liquid chromatography separation with matrix-assisted laser desorption/ionization time-of-flight mass spectral analysis. Rapid Commun. Mass Spectrom. 1999 13 1808-1812. 

Trioxifene is an older SERM with low estrogenic properties and a higher affinity for ER than tamoxifen. It has shown an unfavorable safety profile in clinical studies of women with breast cancer (leukopenia in 41% of patients, nausea in 31%) (Witte et al. 1986), which is why, in addition to its response rates being no better than in tamoxifen (Lee et al. 1986), its clinical development has been cancelled. 

It is remarkable that most of the data collected from the available SERMs are unanimous in reproducing an estrogen agonistic profile in venous thrombogenesis. The vast clinical experience acquired with tamoxifen confirms an augmented risk for both deep venous thrombosis and pulmonary embolism. This increase, however, did not presuppose increased mortality in the overview of randomized trials of adjuvant tamoxifen for early breast cancer, where the one extra death per 5000 woman-years of tamoxifen attributed to pulmonary embolus was not statistically significant (Early Breast Cancer Trialists Collaborative Group 1998). 

Toremifen is a SERM considered a tamoxifen analog characterized by one chlorine atom and is approved for first-line treatment of metastasic breast cancer in postmenopausal women who have tumors that are either ER(+) or of unknown status. In a 3-year face-to-face study with tamoxifen, there were no significant differences between both drugs. The number and profile of adverse events are also similar. Experience with toremifen is limited and far from that accumulated with tamoxifen. 

Brough R, Frankiun JR, Sims D et al (2011) Fimctional viability profiles of breast cancer. Cancer Discov 1 260-273... 

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