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BRCA Risk factors

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BRCA Risk factors

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    1. BRCA Risk factors White Age FH (M, S, D) BRCA1&2 Endometrial Ca, fibrocystic disease, BRCA Early menarche (<12), late menopause (>50) Nulliparous or late first pregnancy

    2. Breast lesions

    3. Major trials on tamoxifen in DCIS NSABP B-24 UK/ANZ NSABP B-35 (tamoxifen and anastrozole) NSAPB P-1: 50% decrease in invasive breast cancer for LCIS and 86% decrease for ADH

    4. First events in NSABP B-24 trial (Lancet. 1999; 353)

    5. B-24 trial Tamoxifen decreases the cumulative incidence of breast-cancer events in women with DCIS Most pronounced effect in younger patients (<50 yo) Among the ER (+) DCIS lesions, tamoxifen reduced the incidence of all breast cancer events by 50% (Breast Cancer Res. Treat. 2002; 76)

    6. Events in UK/ANZ trial (Lancet. 2003; 362)

    7. UK/ANZ Tamoxifen did not produce additional benefit over and above that provided by radiotherapy (in a group of 316 patients, data not shown)

    8. B-24 vs UK/ANZ trial

    9. B-24: there is evidence that tamoxifen has some positive benefit in addition to surgery and radiotherapy UK/ANZ: it is indeterminate that tamoxifen does not have benefit in addition to surgery and radiotherapy

    10. Is it worth waiting? B-24 all event rate (per 100 per year): Placebo Tamoxifen All BRCA 2.9 1.8 Invasive 1.6 0.9 There is a 1% risk of a new event per year of observation NNT=19 to avoid an event, not to save a life

    11. HER2/neu Human epidermal GFR2 TK activity Transforms cells in vitro HER2+ BRCAs have worse prognosis 15-20% invasive tumors HER2 positive

    13. Primary end-point: disease-free survival. Events: Recurrence of BRCA at any site Ipsi- or contralateral BRCA (DCIS but not LCIS) Non-breast Ca (not Ba/Sq skin, not cervix) Death from any cause.

    14. Exclusion criteria Distant Mts Previous Invasive BRCA Other neoplasms (excluding the above) T4 tumors, inflammatory, supraclavicular LNs, suspicious int mamm nodes, prior mediastinal irradiation Cardiac (CHF, Q wave, angina, uHTN, unstable arrhythmias, valvular disease, EF<55%)

    19. Limitations Length of follow-up: risks Length of follow-up: brain mets (1/3) Length of follow-up: hormone status ? Correlation with HER2 expression ? Resistance to Herceptin

    20. Was the assignment of patients to treatments randomized? Were pts properly accounted for? Follow up complete? ‘Intention to treat’? Primary guides

    21. Secondary guides Pts, healthcare workers, personnel ‘blind’? Groups similar? Were groups treated equally? Statistics appropriate?

    22. Results Null hypothesis accepted/rejected? How large was the treatment effect? How precise was the estimate of effect?

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