EARLY STAGE BREAST         CANCEROperable local-regional inv cancer     (Stage I, II, some IIIA)         Elshami M. Elamin...
TNM Staging Stage IA:        T1 (< 2 cm) Stage IB:        T0-1, N1mi Stage IIA:       T0-1, N1 or                   T2 ...
Work-up H/P CBC, LFT, Alk Mammo +/- US Path review Bone scan detects mets      Stage I = 5.1%      Stage II = 5.6% ...
PROGNOSTIC  FACTORS             5
Lymph Nodes Node +ve:   50-70% Risk of relapse     10 LN+ve: 80% Risk of relapse/mets Node –ve:   Up to 20-30% Risk o...
Axillary LN                          5 Yr Survival (%)                     N-        1-3 +      4+Moon et al           89 ...
Tumor size                                 5 Yr Survival (%)                            <2cm     2-5cm      >5cmCarter et ...
Estrogen Receptor                    DFS (%)*     OS (%)#                    ER+    ER-   ER+     ER-NSABP               7...
STEROID RECEPTORSThe best use of ER/PR is not in determination of    prognosis but in the selection of optimal           a...
Age Young age is a significant predictor of local  recurrence after breast conserving therapy                            ...
Histology Invasive ductal and lobular have similar prognosis Pure tubular, mucinous or colloid, and papillary:   usuall...
Pathologic Factors Histologic subtypes Histologic grade Nuclear grade Mitotic indix Vascular/lymphatic invasion Infl...
Biologic Factors S-phase Ki 67 Her-2/neu Tumor supressor genes P53                              14
Principle of Her-2 neu   IHC assay testing (Lab meets quality assurance standards for IHC methodology)        IHC 0, 1+ ...
Molecular Subtypes of Breast  Cancer1. Luminal A: ER+ and or PR+ Her2 -ve2. Luminal B: ER+ and or PR + Her2+3. Her2: Her2+...
BREAST CA SUBTYPES Hormone responsive;    ER/PR positive    Luminal A and B disease by microarray Her-2 neu overexpres...
Risk Categories               Low     Intermed High               (All)             (> 1) LN           -ve     -ve       ...
St Gallens risk categories     for Node negative Low risk:   ER/PR+ve and all of following:     pT < 2cm (inv component...
Surgical Options Breast conservation  Lumpectomy + ALN staging MRM + reconstruction                              22
Breast Conservation           CONTRAINDICATIONS     Absolute                      Relative Multicentricity              ...
Re-excision of Primary Indications:  Extensive Intraductal Component (EIC)   especially with close margins (<2cm)  Posi...
Margin status Breast conserving surgery is predicted on  achieving a negative margin What if margins remain positive?!  ...
ROLE OF LN DISSECTION Diagnostic and/or Therapeutic?   LN –ve:     70-90% 5YS     10% chance of death in 10Y   LN+ve:...
Sentinel L. Node           Dissection Candidates:   Clinically -ve nodes   Solitary T1 or T2   ?? High grade/extensive...
Breast conservation            (Lumpectomy + RT)             MRM: S%   Lump/RT: S%NSABP        60        62EORTC        73...
Lumpectompy + RT                     Local recurrence              Pts    L%         L+RT%NSABP         1262   35       10...
Post-MRM R.T. > 4 positive LN:      RT to chest wall + ICV LN + SCV LN +/- IM LN: 1-3 positive LN:      Strongly consi...
Is R.T. required for            elderly? Age > 70, Stage I, ER +ve treated with  lumpectomy +/- RT  Tam:   Median f/u o...
Why Neoadjuvant Therapy? Downstages the primary tumor in most women. Allows a higher rate of breast preservation. Provi...
Why pre-Chemo SLND? Pathologic LN CR following preop chemo  Guide local and systemic treatment                          ...
NSABP B-18 Preop AC:     Breast conservation is more likely     Improves DFS/OS in pt with Pathologic CR No disease sp...
NSABP B-27 Three arms:  1. Preop AC  local therapy  2. Preop AC/Doce  local therapy  3. Preop AC  local therapy  Doce...
NSABP B-27 ACx4  surg     40% clinical CR     14% partial CR ACx4  Taxotere100 x4  surg     65% cCR     26% pCR ...
MD Anderson regimen            (Her2-neu +ve) NeoAdj: Taxol X4 + Trastuzumzb  CEF x4 + Trastuzumab (Total of 24 wks)   ...
Significantly Higher Pathologic Complete RemissionRate After Neoadjuvant Therapy With Trastuzumab,Paclitaxel, and Epirubic...
Ongoing Anti-Her2   NeoALTTO – Neoajuvant               BIG 01-06 (phase III):     Adj Lap/Traz/Taxol vs LT vs H/T      ...
Stage II-IIIA (T3N1)               (Pt desires breast                  preservation)1- Core biopsy of breast tumor + mark ...
Stage II-IIIA (T3N1)           (Pt desires breast4- According topreservation)               preop chemo response:     Lum...
Who is a candidate for adj.     Systemic therapy? Healthy Positive LN T >1 cm     (IDC or ILC) T >3 cm     (tubular,...
46
Chemotherapy Chemo reduce mortality by 25%    N+ =8% benefit    N-ve.=2% benefit Chemo reduce risk of recurrence by:  ...
Anthracyclines Anthracycline vs non-Anthracycline:     12% proportional odd risk reduction of      recurrence     11% o...
CEF vs CMF CEF-120 vs CMF:    DFS; 62% vs 53%    OS; 77% vs 70% CEF:    29% risk reduction in recurrence    19% risk...
Intergroup (CALGB 93-44)  3170 pts, node positive (18 m median F/U)          AC                   AC ⇒ T                  ...
NSABP B-28 AC  Taxol:   >3,000 N+ve pts)     Initial analysis: Benefits Receptors -ve pts     Updates: Improves DFS &...
DOSE-DENSE CALGB 9741  AC T (q2wk vs q3wk)    G-CSF support     Dose-dense improves DFS      4Y DFS 82% vs 75%     ...
Docetaxel + AC   (High risk patients) NSABP B-27 ECOG 2197 NSABP B-30                          55
AC+Taxotere TAX316 (Adj TAC vs FAC )    LN +ve    TAC     improves DFS; sig     improves OS                          ...
BCIRG 006 AC-Tere+/-Herceptin:   Herceptin arm reduces risk of relapse by 51% Taxotere/Carbo + Herceptin (TCH):   redu...
Adjuvant Herceptin    (Over-expression of Her2-neu) NSABP B-31  AC/Taxol AC/T q3wkx4 + Hx52 HERA  standard adj chemo ...
Adj. Herceptin     (NSABP_B31,NCCTG-N9831, HERA studies) Joint analysis (NSABP_B31, NCCTG-N9831):    Reduce overall risk...
Short course of Herceptin FinHer trial:   Doce or Nav +/- Herc X 9wks  CEF     9 wk adj Herceptin + taxotere or navelb...
Randomized Trials of Adj.             HDCT Negative          ? Positive   Netherlands       S. African   MD Anderson ...
ONCOTYPE DX Assay Done on Formalin-fixed,Paraffin-  embadded tumor tissue: Gene panel (total of 21 genes)   Proliferati...
ONCOTYPE IN CLINICAL PRACTICE Node negative ER positive:   Scores out 100:     <18 = low risk (4-10% risk of distant re...
Hormonal Therapy Tamoxifen reduce risk of recurrence by 50% and risk of death by 30% Do not give Hormonal therapy during...
Aromatase Inhibitors Non-steroidal AI:     Letrozole (Femara)     Anastrazole (Arimidex) Steroidal AI:     Exemestane...
ATAC Adj study Arimidex is superior to Tam in efficacy  and tolerability.       17% improvement in DFS       60% vs 50%...
MA 17 Tam x 5yrs  Letrozole x 5yrs    reduce recurr in both N - & +ve    reduce contralateral cancer    Improve OS in...
Tam  AI IES study;-    Tam x2-3yr  Exemestine vs Tam x5yr ABCSG/ARNO;    Tamx2y ->AIx3                              ...
SYSTEMIC THERAPY                 Summary Hormonal therapy improves survival irrespective of    age and menopausal status...
Risk Categories               Low     Intermed High               (All)             (> 1) LN           -ve     -ve       ...
Treatment: Node -ve                Low risk    Intermed risk      High risk Premenop      Tamoxifen   Chemo + Tam        ...
Treatment:       Node +ve Premenop, ER/PR +ve    Chemo + Tam                         ? Ov ablation Premenop, ER/PR -ve  ...
Anthracycline benefits only;  -Her2-neu +ve                                                             ER/PR +, Her2 +  -...
Herceptin in pts with small  tumors (T1a-b), N-, Her2+ No enough data available Before use herceptin remember:    Toxic...
Adj Therapy of Favorable              Histology    (Tubular, Mucinous/Colloid) Usually ER +ve, Her2-neu –ve Medullary ca...
THANKS         84
Early Breast Cancer
Early Breast Cancer
Early Breast Cancer
Early Breast Cancer
Early Breast Cancer
Early Breast Cancer
Early Breast Cancer
Early Breast Cancer
Early Breast Cancer
Early Breast Cancer
Early Breast Cancer
Early Breast Cancer
Early Breast Cancer
Early Breast Cancer
Early Breast Cancer
Early Breast Cancer
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Early Breast Cancer

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by Elshami Elamin, Consultant Oncologist, Wichita, KS

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Early Breast Cancer

  1. 1. EARLY STAGE BREAST CANCEROperable local-regional inv cancer (Stage I, II, some IIIA) Elshami M. Elamin, MD Medical Oncologist Central care Cancer Center www.cccancer.com Wichita, KS - USA 2
  2. 2. TNM Staging Stage IA: T1 (< 2 cm) Stage IB: T0-1, N1mi Stage IIA: T0-1, N1 or T2 (>2 - 5cm) Stage IIB: T2 + N1 T3 (>5cm) Stage IIIA: T0-2 + N2 T3 +N1-2 (N2 = adv IIIA) 3
  3. 3. Work-up H/P CBC, LFT, Alk Mammo +/- US Path review Bone scan detects mets  Stage I = 5.1%  Stage II = 5.6%  T3N1 = 14% Liver US, C-x-ray detect mets:  Stage I,II = None CT abd+/-pelvis, Chest imaging, Bone scan;  Should be considered for T3N1 Staging PET not recommended 01/03/13 4
  4. 4. PROGNOSTIC FACTORS 5
  5. 5. Lymph Nodes Node +ve:  50-70% Risk of relapse  10 LN+ve: 80% Risk of relapse/mets Node –ve:  Up to 20-30% Risk of relapse Negativity is reliable only if 6-10 LN were removed and examined 6
  6. 6. Axillary LN 5 Yr Survival (%) N- 1-3 + 4+Moon et al 89 68 48Carter et al 92 81 57Valagussa et al 88 69 42Ariel et al 81 66 48Fisher et al 78 62 32 7
  7. 7. Tumor size 5 Yr Survival (%) <2cm 2-5cm >5cmCarter et al (24,740 pts) 91 80 63Schottenfeld (304 pts) 92 71 55Nemoto et al (13,384 pts) 62 49 34 8
  8. 8. Estrogen Receptor DFS (%)* OS (%)# ER+ ER- ER+ ER-NSABP 74 66 92 82San Antonio 76 67 84 75* P value <0.001# P value <0.0001 9
  9. 9. STEROID RECEPTORSThe best use of ER/PR is not in determination of prognosis but in the selection of optimal adjuvant systemic therapy 10
  10. 10. Age Young age is a significant predictor of local recurrence after breast conserving therapy 01/03/13 11
  11. 11. Histology Invasive ductal and lobular have similar prognosis Pure tubular, mucinous or colloid, and papillary:  usually small, N-ve  favorable prognosis (ER+, Her2 –ve)  treat with breast conservation  May omit systemic adj therapy (if T <3cm) Pure or typical medullary has better prognosis than ductal but favorable as tubular or colloid.  However, because pure/typical medullary is uncommon and difficult to diagnose pathologically it is recommended to treat medullary same as inv ductal carcinoma. 12
  12. 12. Pathologic Factors Histologic subtypes Histologic grade Nuclear grade Mitotic indix Vascular/lymphatic invasion Inflammatory response Tumor necrosis Mononuclear cell infiltration 13
  13. 13. Biologic Factors S-phase Ki 67 Her-2/neu Tumor supressor genes P53 14
  14. 14. Principle of Her-2 neu IHC assay testing (Lab meets quality assurance standards for IHC methodology)  IHC 0, 1+ (negative)  IHC 2+ (borderline)  FISH  IHC 3+ (positive) FISH assay (Lab meets quality assurance standards for Her-2 neu methodology  FISH non-amplified (negative)  FISH borderline  IHC or Retest or Count additional cells  FISH amplified (positive) HERmark (quantitative test)  Her-2 Dual ISH assay detect both Her2 and chromos. 17 15
  15. 15. Molecular Subtypes of Breast Cancer1. Luminal A: ER+ and or PR+ Her2 -ve2. Luminal B: ER+ and or PR + Her2+3. Her2: Her2+ ER-ve PR-ve4. Basal-like: ER-ve PR-ve Her2-ve, cytokeratin 5/6+, and or Her1+5. Normal-like: negative for all markers
  16. 16. BREAST CA SUBTYPES Hormone responsive;  ER/PR positive  Luminal A and B disease by microarray Her-2 neu overexpression;  Herceptin responsive  Her-2 neu overexpression by microarray Non hormone responsive, non-Her-2 neu overexpressive;  poor prognosis TRIPLE NEGATIVE  basal-like by microarray 17
  17. 17. Risk Categories Low Intermed High (All) (> 1) LN -ve -ve +ve Tumor size < 1cm > 1-2cm > 2cm ER/PR +ve +ve -ve Grade 1 1-2 2-3 Age > 35 <35 18
  18. 18. St Gallens risk categories for Node negative Low risk:  ER/PR+ve and all of following:  pT < 2cm (inv component)  G1  > 35Y High risk:  ER/PR -ve or  ER/PR +ve + one of following:  pT> 2cm (inv component)  G 2-3  <35Y 19
  19. 19. Surgical Options Breast conservation  Lumpectomy + ALN staging MRM + reconstruction 22
  20. 20. Breast Conservation CONTRAINDICATIONS Absolute Relative Multicentricity  Tumor size vs breast size Diffuse microcalcifications  Tumor location, or >5 cm Early pregnancy  Collagen vascular disease Previous RT (excluding RA) Positive margins  Focally positive margin 23
  21. 21. Re-excision of Primary Indications:  Extensive Intraductal Component (EIC) especially with close margins (<2cm)  Positive/uncertain margins  Residual microcalcifications 24
  22. 22. Margin status Breast conserving surgery is predicted on achieving a negative margin What if margins remain positive?!  Mastectomy  In selected cases may accept microscopically focally positive margin, but with conditions:  Absence of extensive intraductal component  Use of higher R.T. boost to tumor bed 25
  23. 23. ROLE OF LN DISSECTION Diagnostic and/or Therapeutic?  LN –ve:  70-90% 5YS  10% chance of death in 10Y  LN+ve:  50-70% risk of relapse  35% chance of death in 10Y  1-3 LN+ve: 60-80% 5YS  >4 LN+ve: 30-50% 5YS 26
  24. 24. Sentinel L. Node Dissection Candidates:  Clinically -ve nodes  Solitary T1 or T2  ?? High grade/extensive DCIS  No large hematoma or seroma  No neoadjuvant chemo SLN can’t be identified or +ve:  Formal axillary dissection 27
  25. 25. Breast conservation (Lumpectomy + RT) MRM: S% Lump/RT: S%NSABP 60 62EORTC 73 71Danish 82 79NCI 75 77 29
  26. 26. Lumpectompy + RT Local recurrence Pts L% L+RT%NSABP 1262 35 10Milan 567 12 2Ontario 837 35 11Sweden 381 18 2Scottish 585 25 6British 418 35 13 30
  27. 27. Post-MRM R.T. > 4 positive LN:  RT to chest wall + ICV LN + SCV LN +/- IM LN: 1-3 positive LN:  Strongly consider RT to chest wall + ICV LN + SCV LN +/- IM LN: T > 5 cm or positive margins:  Consider RT to chest wall +/- ICV LN/SCV LN/IM LN T < 5 cm and margin <1mm:  RT to chest wall T < 5 cm, N negative, margins > 1mm:  No RT 31
  28. 28. Is R.T. required for elderly? Age > 70, Stage I, ER +ve treated with lumpectomy +/- RT  Tam:  Median f/u of 8.2Y  Local-regional recurrence rate: 1% vs 4%  No diff in OS, DFS or need for mastectomy 01/03/13 32
  29. 29. Why Neoadjuvant Therapy? Downstages the primary tumor in most women. Allows a higher rate of breast preservation. Provides an in vivo assessment of tumor response to the particular drug regimen and, hence, an opportunity to optimize therapy. Pathologic complete response (pCR) after preoperative therapy is a powerful surrogate of long-term disease free survival. It is hypothesized that a regimen that produces higher rates of pCR in the neoadjuvant treatment setting will also result in higher rates of long-term cure.
  30. 30. Why pre-Chemo SLND? Pathologic LN CR following preop chemo  Guide local and systemic treatment 01/03/13 35
  31. 31. NSABP B-18 Preop AC:  Breast conservation is more likely  Improves DFS/OS in pt with Pathologic CR No disease specific survival advantage over adj chemo in stage II 01/03/13 36
  32. 32. NSABP B-27 Three arms: 1. Preop AC  local therapy 2. Preop AC/Doce  local therapy 3. Preop AC  local therapy  Doce 01/03/13 37
  33. 33. NSABP B-27 ACx4  surg  40% clinical CR  14% partial CR ACx4  Taxotere100 x4  surg  65% cCR  26% pCR AC-->surg-->Taxotere  No improvement in lumpectomy  Higher rate of pathologic CR with AC/Doce  No DFS and OS diff  DFS favors preop Doce vs postop Doce in subset of pts with partial response to AC 38
  34. 34. MD Anderson regimen (Her2-neu +ve) NeoAdj: Taxol X4 + Trastuzumzb  CEF x4 + Trastuzumab (Total of 24 wks)  Trastuzumab increases path CR from 26 to 65.2% 01/03/13 39
  35. 35. Significantly Higher Pathologic Complete RemissionRate After Neoadjuvant Therapy With Trastuzumab,Paclitaxel, and Epirubicin Chemotherapy:Results of a Randomized Trial in Human EpidermalGrowth Factor Receptor 2–Positive Operable BreastCancerAman U. Buzdar, Nuhad K. Ibrahim, Deborah Francis, Daniel J. Booser, Eva S. Thomas,Richard L. Theriault, Lajos Pusztai, Marjorie C. Green, Banu K. Arun, Sharon H. Giordano,Massimo Cristofanilli, Debra K. Frye, Terry L. Smith, Kelly K. Hunt, Sonja E. Singletary,Aysegul A. Sahin, Michael S. Ewer, Thomas A. Buchholz, Donald Berry, and Gabriel N. Hortobagyi MD Anderson protocol:  prospective randomized phase III study were the goal of the study was to demonstrate that the addition of trastuzumab to a complete 6-month preoperative chemotherapy regimen will increase pCR rate two-fold compared with chemotherapy alone.  The study was powered to detect a 20% improvement in the pCR rate (ie, from 21% to 41%)
  36. 36. Ongoing Anti-Her2 NeoALTTO – Neoajuvant BIG 01-06 (phase III):  Adj Lap/Traz/Taxol vs LT vs H/T  Then adj ECF and Anti-Her2  LHT: pCR 51.3% in Breast and 47% in breast and LN (higher in ER neg) GeparQuinto:  Neoad EC/Doce + Herc or Tykerb followed by adj Herc  50% pCR (more with Herceptin) NeoSphere:  Neoadj Doce +/- Pertuzumab +/- Traztuzumab  3 drugs is better with 46% pCR; sig 41
  37. 37. Stage II-IIIA (T3N1) (Pt desires breast preservation)1- Core biopsy of breast tumor + mark tumor bed2- Axillary LN:  Clinically –ve  Consider SLD  Clinically +ve  Consider core Bx or FNA; if -ve  Consider SLD3- Then preop chemo/hormone:  Any adj regimen or  A.I. for postpenopausal or  Trastuzumab-bsed therapy for her2-neu +ve 01/03/13 42
  38. 38. Stage II-IIIA (T3N1) (Pt desires breast4- According topreservation) preop chemo response:  Lumpectomy + LND (may omit if preop SLN –ve)  Mastectomy + LND (may omit if preop SLN –ve)5- Additional chemo in clinical trial6- Adj therapy may include:  RT  Trastuzumab  Hormonal therapy (could be given with herceptin)  Xeloda as radiosensitizer for high risk of local recurrence (may give with herceptin) 01/03/13 43
  39. 39. Who is a candidate for adj. Systemic therapy? Healthy Positive LN T >1 cm  (IDC or ILC) T >3 cm  (tubular, papillary, mucinous) Data is limited for chemo in elderly (>70 yrs) 45
  40. 40. 46
  41. 41. Chemotherapy Chemo reduce mortality by 25%  N+ =8% benefit  N-ve.=2% benefit Chemo reduce risk of recurrence by:  30% in pre menopausal  20% in post menopausal Chemo reduce risk of death by:  25% in pre menopausal  15% in post menopausal 47
  42. 42. Anthracyclines Anthracycline vs non-Anthracycline:  12% proportional odd risk reduction of recurrence  11% odd risk reduction of death  Absolute gain in survival;  4% in N+ve  1.7% in N-ve Anthracycline benefits the most:  Her2-neu +ve  Topoisomerase lla +ve 49
  43. 43. CEF vs CMF CEF-120 vs CMF:  DFS; 62% vs 53%  OS; 77% vs 70% CEF:  29% risk reduction in recurrence  19% risk reduction in mortality 50
  44. 44. Intergroup (CALGB 93-44) 3170 pts, node positive (18 m median F/U) AC AC ⇒ T P DFS 86% + 1.2% 90% + 1.0% 0.0077 OS 95% + 0.7% 97% + 0.6% 0.0390  Improved DFS/OS from T but not from escalation of A dose.  Taxol reduce recurrence rate by 22% and death rate by 26% Henderson et al ASCO 1998 # 390A 52
  45. 45. NSABP B-28 AC  Taxol:  >3,000 N+ve pts)  Initial analysis: Benefits Receptors -ve pts  Updates: Improves DFS & OS regardless of receptors, use of tamoxifen, age or number of LNs  Taxol reduce DFS by 17%  Validates the CALGB 93-44 53
  46. 46. DOSE-DENSE CALGB 9741  AC T (q2wk vs q3wk)  G-CSF support  Dose-dense improves DFS  4Y DFS 82% vs 75%  Benefit both ER status 54
  47. 47. Docetaxel + AC (High risk patients) NSABP B-27 ECOG 2197 NSABP B-30 55
  48. 48. AC+Taxotere TAX316 (Adj TAC vs FAC )  LN +ve  TAC  improves DFS; sig  improves OS 56
  49. 49. BCIRG 006 AC-Tere+/-Herceptin:  Herceptin arm reduces risk of relapse by 51% Taxotere/Carbo + Herceptin (TCH):  reduces risk of relapse by 39% compared to AC-T  Lowe cardiac toxicity No sig diff in risk of relapse between AC-TH and TCH 57
  50. 50. Adjuvant Herceptin (Over-expression of Her2-neu) NSABP B-31  AC/Taxol AC/T q3wkx4 + Hx52 HERA  standard adj chemo  +/- H q3wk x12-24m NCCTG 9831  AC/Taxol wkly x12  AC/Twkly x12 +concur Hx52  AC/Twkly x12 seq Hx40 58
  51. 51. Adj. Herceptin (NSABP_B31,NCCTG-N9831, HERA studies) Joint analysis (NSABP_B31, NCCTG-N9831):  Reduce overall risk of local recurr by 52% and distant recurr by 53% @ 3yr  CHF risk increased by 3-4% HERA:  Hercept sig improve DFS  46% reduction in recurrence MUGA after AC, @ 6,9,18 m 59
  52. 52. Short course of Herceptin FinHer trial:  Doce or Nav +/- Herc X 9wks  CEF  9 wk adj Herceptin + taxotere or navelbine is as effective as 52 wks Herceptin  No cardiac toxicity 60
  53. 53. Randomized Trials of Adj. HDCT Negative  ? Positive  Netherlands  S. African  MD Anderson  CALGB  Scandinavian 61
  54. 54. ONCOTYPE DX Assay Done on Formalin-fixed,Paraffin- embadded tumor tissue: Gene panel (total of 21 genes)  Proliferation set: ki67, etc  ER set: ER, PR, Bcl2, SCUBE2  Invasion set: stromelysin 3, cathepsin L2  Her2 set: Her2, GRB7  Other genes: BAG1, CD68 63
  55. 55. ONCOTYPE IN CLINICAL PRACTICE Node negative ER positive:  Scores out 100:  <18 = low risk (4-10% risk of distant recurrence)  Treat with Tamoxifen  18-31 = intermed risk (8-20% risk of distant recurrence)  31-50 = high risk (24-37% risk of dist recurrence)  Benefit from chemo Node positive ER positive: 64
  56. 56. Hormonal Therapy Tamoxifen reduce risk of recurrence by 50% and risk of death by 30% Do not give Hormonal therapy during Chemotherapy:  Risk of thromboembolism 65
  57. 57. Aromatase Inhibitors Non-steroidal AI:  Letrozole (Femara)  Anastrazole (Arimidex) Steroidal AI:  Exemestane (Aromasin) 66
  58. 58. ATAC Adj study Arimidex is superior to Tam in efficacy and tolerability.  17% improvement in DFS  60% vs 50% risk reduction in contral breast ca  Less vaginal bleed/discharge, hot flashes, VTE  Tam is better in fracture and musculoskeletal events 67
  59. 59. MA 17 Tam x 5yrs  Letrozole x 5yrs  reduce recurr in both N - & +ve  reduce contralateral cancer  Improve OS in N +ve pts only 68
  60. 60. Tam  AI IES study;-  Tam x2-3yr  Exemestine vs Tam x5yr ABCSG/ARNO;  Tamx2y ->AIx3 69
  61. 61. SYSTEMIC THERAPY Summary Hormonal therapy improves survival irrespective of age and menopausal status Polychemotherapy superior to monotherapy 12 months is not better than 6 months Additional benefit of chemo + HT in receptor +ve Anthracycline-regimen has better recurrence and survival rates than CMF Ovarian ablation is comparable to chemotherapy to reduce mortality in premenopausal 70
  62. 62. Risk Categories Low Intermed High (All) (> 1) LN -ve -ve +ve Tumor size < 1cm > 1-2cm > 2cm ER/PR +ve +ve -ve Grade 1 1-2 2-3 Age > 35 <35 72
  63. 63. Treatment: Node -ve Low risk Intermed risk High risk Premenop Tamoxifen Chemo + Tam Chemo + Tam ER/RP +ve ? Ov ablation ? Ov ablation Premenop Chemo ER/PR -ve Postmenop Hormone Hormone or Chemo Chemo or ER/PR +ve hormone Postmenop Chemo ER/PR -ve 73
  64. 64. Treatment: Node +ve Premenop, ER/PR +ve Chemo + Tam ? Ov ablation Premenop, ER/PR -ve Chemo Postmenop, ER/PR +ve Chemo or Hormones Postmenop, ER/PR -ve Chemo 74
  65. 65. Anthracycline benefits only; -Her2-neu +ve ER/PR +, Her2 + -topo ll +ve + Her2 P R+ Her2 - E R/ ER/PR +, Her2 - •Ductal •Lobular •Mixed •Metaplastic ER ER/PR -, Her2 + /PR Her2+ - Her2 ER/PR -, Her2 - (TN) - 76
  66. 66. Herceptin in pts with small tumors (T1a-b), N-, Her2+ No enough data available Before use herceptin remember:  Toxicities (cardiac)  Uncertain benefit in cohort 81
  67. 67. Adj Therapy of Favorable Histology (Tubular, Mucinous/Colloid) Usually ER +ve, Her2-neu –ve Medullary carcinoma should be treated as other invasive ductal carcinoma Prospective data regarding systemic adj therapy of favorable histology tumors are lacking 01/03/13 82
  68. 68. THANKS 84

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