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Screening Recommendations for Men with BRCA Gene Mutations

Dharamvir Jain, MD Assistant Professor of Medicine James Graham Brown Cancer Center University of Louisville Health Sciences Center. Screening Recommendations for Men with BRCA Gene Mutations • Easily challenged because efficacy data is lacking • Annual mammography and clinical exam

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Screening Recommendations for Men with BRCA Gene Mutations

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  1. Dharamvir Jain, MDAssistant Professor of MedicineJames Graham Brown Cancer CenterUniversity of Louisville Health Sciences Center

  2. Screening Recommendations for Men with BRCA Gene Mutations • Easily challenged because efficacy data is lacking • Annual mammography and clinical exam beginning at age 30. • Annual prostate screening (DRE, PSA) beginning at age 40. • Colonoscopy per usual guidelines.

  3. Immunohistochemical Characterization of Subtypes of Male Breast Carcinoma • Luminal A and luminal B are the major subtypes of male breast carcinoma. • The immunophenotypical features of male breast cancer differ from those of its female counterpart. • Luminal B tumors tend to have high nuclear grade and more frequent expression of EGFR and NF-κB. luminal A (ER+ and/or progesterone receptor (PR)+, HER2-) luminal B (ER+ and/or PR+, HER2+) HER2+/ER- (ER-, PR-, HER2+) basal-like (ER-, PR-, HER2-, CK5/6+) unclassified (negative for all five markers) Yimin Ge et al. Breast Cancer Research. 09/2009

  4. Aromatase Inhibitors in Males *Turner KJ et al. J Endoc 2000;164(2):225-38. ** Roselli CE. J Steroid Biochem Mol Biol 1997;61:365-74 • Have not been adequately studied in men with breast cancer • In male rats exposed to anastrozole*: • Significant increase in FSH • Significant increase in testosterone • No detectable change in estradiol • Possible explanations:** • Increased substrate for aromatization(testosterone) • Increased expression of aromatase • Associated with increase in testosterone concentrations in humans, non-human primates, ex.dogs..

  5. ….6-OXO - The First Effective All-Natural Aromatase Inhibitor ….The hypothalamus is the primary sensor in this system, and it responds to both androgens (i.e. testosterone, DHT) and estrogens (derived from aromatization of androgens). The hypothalamus is so sensitive to estrogens in fact that administration of an estrogen blocker can often result in a very substantial surge in testosterone production. This is why steroid using bodybuilders take products such as Clomiphene (an estrogen receptor antagonist) and Anastrazole (an aromatase inhibitor) after cycles to jump-start their suppressed testicular testosterone production. Now, with the introduction of 6-OXO™, there is a natural - over the counter alternative available to these prescription only drugs…

  6. Men with breast Ca S0511: Goserelin +Anastrozole for Advanced Male Breast Cancer -Design Treatment for 8 cycles or until disease progression N = 56 Phase II, One Stage Design REGISTRATION Anastrozole 1mg PO daily + Goserelin acetate 3.6 mg SubQ monthly Endpoint PFS OS Markers Toxicity Serum and tissue repository • Recurrent or metastatic • ER • PR positive • > 18 yr. old Imaging Core biopsy Pharmacogenomics Plasma hormonal levels(E1, E1s E2, E3, PSA, Testosterone, FSH, LH, DHEA)

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