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Elshami M. Elamin, MD     Medical Oncologist  Central Care Cancer Center     www.cccancer.com      Wichita, KS - USA
192,370 New Cases                                      40,170 Deaths            4% Melanoma of skin                       ...
 CBC, Ca+, LFTs CEA, CA 27-29, CA 15-3 C-x-rays Bone scan Chest/Abd/Pelvis CT PET                           4
 Age, Menopausal status (at time of mets) ER/PR, Her2 status Prior therapy and response Number/Sites of mets (<3, soft...
   Palliation:        R.T.        Hormonal therapy        Chemotherapy        Anti-her2 therapy        Surgery   Pr...
 Routine        surgerical removal of the primary tumor usually is not recommended !!   Only for local control and compl...
Elisabetta Rapiti, Helena M. Verkooijen, Georges Vlastos,   Gerald Fioretta, Isabelle Neyroud-Caspar, André   Pascal Sappi...
   Geneva Cancer Registry (1977-1996)   Breast ca: Any T, any N, M1 = 317 pts (300 pts    included in the study)   Comp...
Local surgery   No. of pts   %No surgery      173          58Surg: -ve       61           20marginsSurg; +ve       33     ...
   Surgical removal of breast tumor improves    prognosis of women with met breast cancer.       40% reduction in breast...
13
   224 pts studied: 82 (37%) underwent    mastectomy and 142 (63%) were treated    without surgery. The median follow-up ...
 Retrospective study of 16,023 patients. Surgery of the primary tumor was associated  with a 39% reduction in the risk o...
   Women with metastatic breast cancer at diagnosis,    primary tumor removal with negative margins    significantly impr...
 New chemotherapy agents (Taxanes). Biologic agents.       Ant-Her2 (Herceptin, Tykerb)       ? Avastin Surgical comp...
Response   Time to     Duration of                  Rate %     Response    Response   Endocrine     30-40      2-3 mth   ...
 ER/PR Age Her-2 neu Sites of mets     Visceral/Bones                       21
   Tamoxifen (Novadex, Soltamox, Valodex,    Istubal)     Its metabolite hydoxytamoxifen acts as estrogen      antogonis...
   Premenopausal:     Cause polycystic ovary (contraindicated)   Postmenopausal:     Aromatization of adrenal androgen...
   Ovarian Ablation (Oophorectomy):     Surgical (immediate)     RT (2-3 months)     LH-RH analogues                  ...
   ER and/or PR +ve, Postmenopausal :     Within one yr of antiestrogen:      A.Is. are preferred     Antiestrogen naï...
   ER and/or PR +ve, Premenopausal:     Within one yr of antiestrogen:      Ovarian ablation is preferred + endocrine t...
   ER and/or PR +ve, Her2-neu +ve,    Postmenopausal:     Adding Trastuzumab or Lapatinib to A.Is.          Improves PF...
 ER/PR negative Symptomatic visceral mets Receptor +ve refractory to endocrine  therapy    01/04/13                    ...
   Paclitaxel (Taxol)       T+Adria interfere with Adria metabolism         Cardiac toxicity       High antitumor acti...
   Predictive response     Prior adjuvant chemo > 12 months     Her-2 neu     Topoisomerase IIa     ? In vitro study...
   Combination chemotherapy      Higher ORR      Longer TTP      Increased toxicity      Little survival benefit     ...
   Single-Agents (Adriamycin, Taxane, Xeloda, etc)     Inferior to combination in RR and “survival”     Recent studies ...
   First-line (CMF, CAF, AC):     RR                           40-65%     CR                           10-15%     Medi...
   What is the optimal Duration of Chemo?     ?6 cycles     To maximum response or Stable dz     2-3 cycles beyond CR ...
   Conventional chemo vs High-dose chemo + ASCT       No improvement in survival        Stadtmauer NEJM:2000     It is ...
Med OS mth               CHF   AC                       25                       7%   AC + Herceptin           33       ...
   ER/PR –ve:     Trastuzumab alone or with Taxol +/- Carbo or Doce      or Vinorelbine or Capecitabine   ER/PR +ve:   ...
   Met, advanced BC overexp Her2 s/p anthra,    taxane, herceptin:     Xeloda (2000mg/m qd)+/-Tykerb 1250mg (5tab) qd:  ...
   First-line Taxol +/- Avastin      PFS 11.8 vs 5.9 m (P<0.001)      No sig diff in OS   FDA revoked its indication  ...
 Locoregional Systemic                 43
   Depends on:     Type and extent of local/regional failure   Includes:     RT     Excision     Endocrine therapy  ...
   Initial treatment; Mastectomy or breast    conservation:     EORTC 10801 and Danish BCG 82TM trials (stage      I-II)...
    After Mastectomy:      Resection + IFRT if possible    After Breast conservation:      Mastectomy and ALND if leve...
   Axilla      Resection if possible + RT   SCV      RT   IM Node      RT                                    47
   After local treatment:     Consider limited duration chemo or endocrine      therapy similar to adj therapy.     BIG...
   Consider addition of hyperthermia to    irradiation for local recurrence      No survival benefit     01/04/13       ...
 Treat   as metastatic                          50
 Bisphosphonates (Pamidronate, Zoledronic  acid) Denosumab (XGEVA)     Expected survival >3 months     Adequate renal ...
52
Brca mets
Brca mets
Brca mets
Brca mets
Brca mets
Brca mets
Brca mets
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  • Almost 200,000 new cases of breast cancer are diagnosed in the United States each year—breast cancer is the most common cancer diagnosed in women. In addition, despite the advances made to date, breast cancer remains the second-leading cause of cancer-related death for women, accounting for more than 40,000 deaths per year.
  • Transcript of "Brca mets"

    1. 1. Elshami M. Elamin, MD Medical Oncologist Central Care Cancer Center www.cccancer.com Wichita, KS - USA
    2. 2. 192,370 New Cases 40,170 Deaths 4% Melanoma of skin 2% Brain 4% Thyroid 26% Lung & bronchus 27% Breast 15% Breast 15% Lung & bronchus 6% Pancreas 3% Kidney & renal pelvis 9% Colon & rectum 10% Colon & rectum 5% Ovary 3% Ovary 3% Uterus 6% Uterus 4% Non-Hodgkin’s lymphoma 4% Non-Hodgkin’s lymphoma 3% Leukemia 3% Leukemia 2% Liver & intrahepatic bile duct 23% All other sites 25% All other sitesAmerican Cancer Society. Cancer Facts & Figures 2009. Atlanta, GA: American Cancer Society; 2009.
    3. 3.  CBC, Ca+, LFTs CEA, CA 27-29, CA 15-3 C-x-rays Bone scan Chest/Abd/Pelvis CT PET 4
    4. 4.  Age, Menopausal status (at time of mets) ER/PR, Her2 status Prior therapy and response Number/Sites of mets (<3, soft tissue/bone vs visceral) PS Co-morbidity Psychosocial 5
    5. 5.  Palliation:  R.T.  Hormonal therapy  Chemotherapy  Anti-her2 therapy  Surgery Prolong survival ? Cure 6
    6. 6.  Routine surgerical removal of the primary tumor usually is not recommended !! Only for local control and complications bleeding, ulceration, and infection at the primary tumor site, "toilette" mastectomy Survival is determined by distant mets, not by local disease ? No survival benefit ? May stimulate growth of mets 8
    7. 7. Elisabetta Rapiti, Helena M. Verkooijen, Georges Vlastos, Gerald Fioretta, Isabelle Neyroud-Caspar, André Pascal Sappino, Pierre O. Chappuis, Christine Bouchardy J Clin Oncol 24:2743-2749, 2006 9
    8. 8.  Geneva Cancer Registry (1977-1996) Breast ca: Any T, any N, M1 = 317 pts (300 pts included in the study) Compare mortality risks from breast ca between pts who had surgery of primary breast tumor to those had not. population-based observational study Not a randomized study 10
    9. 9. Local surgery No. of pts %No surgery 173 58Surg: -ve 61 20marginsSurg; +ve 33 11marginsSurg: margins 33 11unknownTotal 300 100 11
    10. 10.  Surgical removal of breast tumor improves prognosis of women with met breast cancer.  40% reduction in breast cancer mortality  Only in pts with –ve margins  Sites of mets do not affect outcome.  Pts with bone mets benefit the most No significant survival benefit for axillary dissection 12
    11. 11. 13
    12. 12.  224 pts studied: 82 (37%) underwent mastectomy and 142 (63%) were treated without surgery. The median follow-up time was 32.1 months.  Surgery was associated with a trend toward improvement in overall survival (P=.12) and a significant improvement in metastatic progression- free survival (P=.0007) 14
    13. 13.  Retrospective study of 16,023 patients. Surgery of the primary tumor was associated with a 39% reduction in the risk of death  3 Yr Survival:  35% for patients excised to negative margins  26% for those with positive margins  17.3% for those not having surgery  (P < .0001).  No sig survival benefit for axillary dissection 15
    14. 14.  Women with metastatic breast cancer at diagnosis, primary tumor removal with negative margins significantly improves survival, especially in patients with only bone metastases. Well-designed prospective studies are needed to re-evaluate the treatment paradigm "no surgery of the primary tumor" in breast cancer with metastases at diagnosis and to determine the impact of breast surgery on outcome of these patients. 16
    15. 15.  New chemotherapy agents (Taxanes). Biologic agents.  Ant-Her2 (Herceptin, Tykerb)  ? Avastin Surgical complications are infrequent. In a multivariate analysis:  Each more recent year of recurrence was associated with a 1% per year reduction in the risk of death. 17
    16. 16. Response Time to Duration of Rate % Response Response Endocrine 30-40 2-3 mth 12-16 mth Combination 50-70 1.5-2 mth 8-12 mth Chemo 19
    17. 17.  ER/PR Age Her-2 neu Sites of mets  Visceral/Bones 21
    18. 18.  Tamoxifen (Novadex, Soltamox, Valodex, Istubal)  Its metabolite hydoxytamoxifen acts as estrogen antogonist in the breast  It acts an estrogen agonist in the endometrium Fulvestrant (Faslodex)  Pure anti-estrogen (downregulates ER in breast cancer cells) 22
    19. 19.  Premenopausal:  Cause polycystic ovary (contraindicated) Postmenopausal:  Aromatization of adrenal androgens → Estrogens ……  Aminoglutethemide  Anastrozole (Arimidex)  Letrozole (Femara)  Exemestane (Aromasin) 23
    20. 20.  Ovarian Ablation (Oophorectomy):  Surgical (immediate)  RT (2-3 months)  LH-RH analogues 24
    21. 21.  ER and/or PR +ve, Postmenopausal :  Within one yr of antiestrogen:  A.Is. are preferred  Antiestrogen naïve or more than 1 yr from antiestrogen  A.Is. appear superior compared to Tam  Recent Cochrane Review suggested small survival benefits 01/04/13 25
    22. 22.  ER and/or PR +ve, Premenopausal:  Within one yr of antiestrogen:  Ovarian ablation is preferred + endocrine therapy as postmenopaual  Antiestrogen naïve:  Antiestrogen alone  LHRH ovarian ablation + endocrine therapy as postmenopaual  LHRH ovarian ablation + A.I. is not recommended 01/04/13 26
    23. 23.  ER and/or PR +ve, Her2-neu +ve, Postmenopausal:  Adding Trastuzumab or Lapatinib to A.Is.  Improves PFS Anti-estrogen Fulvestrant is an option for:  Postmenopausal after Tamoxifen or A.Is. 01/04/13 27
    24. 24.  ER/PR negative Symptomatic visceral mets Receptor +ve refractory to endocrine therapy 01/04/13 29
    25. 25.  Paclitaxel (Taxol)  T+Adria interfere with Adria metabolism  Cardiac toxicity  High antitumor activity ABRAXANE (Alb-bound Paclitaxel) (Cremophor-free) Docetaxel (Taxotere/Adria)  Improvement in RR/OS  Febrile neutropenia Navelbine, Capecitabine, Gemcitabine IXEMPRA (ixabepilone) Halaven (Eribulin):  anti-microtubules extracted from sea sponge 30
    26. 26.  Predictive response  Prior adjuvant chemo > 12 months  Her-2 neu  Topoisomerase IIa  ? In vitro study Prolong survival by ~ 20%  MS : 20 – 30 months 31
    27. 27.  Combination chemotherapy  Higher ORR  Longer TTP  Increased toxicity  Little survival benefit 01/04/13 32
    28. 28.  Single-Agents (Adriamycin, Taxane, Xeloda, etc)  Inferior to combination in RR and “survival”  Recent studies  Similar survival  Better QL  Less toxicity JCO 16:3720,1998 33
    29. 29.  First-line (CMF, CAF, AC):  RR 40-65%  CR 10-15%  Median Duration 10 months 2nd-line :  RR < 30%  CR < 10%  Duration of response < 6 months Adriamycin-Regimen:  Statistically significant RR, Time to treatment failure, Survival  More toxic (Alopecia, Myelosupression, Cardiotoxicity) 34
    30. 30.  What is the optimal Duration of Chemo?  ?6 cycles  To maximum response or Stable dz  2-3 cycles beyond CR  Chemo holiday 35
    31. 31.  Conventional chemo vs High-dose chemo + ASCT  No improvement in survival Stadtmauer NEJM:2000  It is not a practice anymore 36
    32. 32. Med OS mth CHF AC 25 7% AC + Herceptin 33 27% T 18 1% T + Herceptin 22 12%  Chemo + Herceptin significantly better Siamon ASCO 1998 #377, Norton ASCO 1999 # 483 38
    33. 33.  ER/PR –ve:  Trastuzumab alone or with Taxol +/- Carbo or Doce or Vinorelbine or Capecitabine ER/PR +ve:  Trastuzumab with endocrine therapy Progression on Trastuzumzab:  Continue Trastuzumab  Lapatinib +/- Capecitabine  Lapatinib +/- Trastuzumab Pertuzumab Trastuzumab-DM1 01/04/13 39
    34. 34.  Met, advanced BC overexp Her2 s/p anthra, taxane, herceptin:  Xeloda (2000mg/m qd)+/-Tykerb 1250mg (5tab) qd:  TTP 8.4 vs 4.4 m  Toxiciy;  diarhea  PPE  cardiac 1.6%  prolong QT  Dose reduce for;  low LVEF  hepatic 40
    35. 35.  First-line Taxol +/- Avastin  PFS 11.8 vs 5.9 m (P<0.001)  No sig diff in OS FDA revoked its indication 01/04/13 41
    36. 36.  Locoregional Systemic 43
    37. 37.  Depends on:  Type and extent of local/regional failure Includes:  RT  Excision  Endocrine therapy  Chemotherapy  Combinations 44
    38. 38.  Initial treatment; Mastectomy or breast conservation:  EORTC 10801 and Danish BCG 82TM trials (stage I-II):  No diff in initial events of local recurrences  No diff in survival after salvage treatment  50% of both groups were alive at 10 yrs Common sites of recurrence:  If MRM and adj chemo without RT:  Chest wall and supraclavicular LN 01/04/13 45
    39. 39.  After Mastectomy:  Resection + IFRT if possible After Breast conservation:  Mastectomy and ALND if level I/II not previously done  Limited data suggest that repeat SLND may be possible  Accuracy of repeat SLND is unproven Small isolated in scar/skin flap  Excision with 2-3 cm margin NCCN: After lumpectomy/SLN: •Mastectomy + level I/II ALND (preferred) •Consider SLN if prior axill staging done by SLN biopsy only 01/04/13 46
    40. 40.  Axilla  Resection if possible + RT SCV  RT IM Node  RT 47
    41. 41.  After local treatment:  Consider limited duration chemo or endocrine therapy similar to adj therapy.  BIG 101/IBCSG 27-02/NSABP B-37 [chemo for isolated local and/or regional ipsil recurrence in early stage breast cancer] 01/04/13 48
    42. 42.  Consider addition of hyperthermia to irradiation for local recurrence  No survival benefit 01/04/13 49
    43. 43.  Treat as metastatic 50
    44. 44.  Bisphosphonates (Pamidronate, Zoledronic acid) Denosumab (XGEVA)  Expected survival >3 months  Adequate renal function  Optimal duration not established  Dental exam  Calcium + Vit-D 51
    45. 45. 52
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