Inflammatory Breast Cancer (IBC) Epidemiology and Prognostic factors

Transcription

1 Inflammatory Breast Cancer (IBC) Epidemiology and Prognostic factors Y.Bensouda, I.Ouziane, H.Errihani National Institute of Oncology (NIO) Rabat-Morocco

2 Inflammatory breast cancer 1. Agressive form of breast cancer High metastatic diffusion at initial diagnosis [35%] High rate of lymphatic involvment [55-85%] 2. Rare disease Incidence range from 2 to 7% Heterogeneous distribution North africa : high incidence Less frequency in Europe and America

3 Inflammatory breast cancer 3. Specific entity Particular evolution Specific biological markers Specific gene expression 4. Poor Outcome Before neoadjuvant chemotherapy Survival (5 years) 5-10% Multimodal therapy Optimal neoadjuvant chemotherapy + Surgery + Adjuvant Radiotherapy. +/- Adjuvant chemotherapy Hormonal therapy Trastuzuamb if HER2+ Survival (5 years) : 30 50%

4 Moroccan data (Rabat) Restrospective data 4 years: [January 2005 to December 2008]. All cases of inflammatory cancer Data: clinical, histological and therapeutic.

5 Inclusion criteria Female sex Histological confirmation of breast cancer Clinical diagnosis +++ Erythema taking more than a third of the breast «Peau d orange» Onset of symptoms: maximum delay 6 months Delay of symptoms N Pa6ents % < 3 months 76 45% 3< < 6 months 96 55%

6 IBC = clinical aspect Erythema Volume Diffuse Induration «Peau d Orange» Mammary retraction Thickening derm

7 Results : Epidemiology Frequency: 3400 cases of breast cancer treated during 4 years at the Institute 172 cases of IBC Incidence of 5%

8 IBC Incidence Heterogeneous distribu8on [1-7%] Rare disease in USA + Europe countries High rate in North Africa, Middle east region 5-7 % Vs 1-4% D Wrong data ini8ally reported by tunisian team Confusion T4B «Locally advanced breast cancer» and T4D

9 Tunisian Incidence - IBC Tabbane.F (1977) Mourali 1980 Maalej M B.Cancer 2000 Boussen S.Oncol 2008 N 283 / / / 2130 T4d «PEV3» 48.7% 10-15% 6.2% 5.7%

10 Incidence North africa vs Europe USA Tunisie (Boussen) Maroc (INO) Turquie (Gunhan) Espagne USA (SEER data Base) Période 6 years 4 years 12 years 12 years [ ] [ ] [ ] ( ) N / / % 5.7% 5% 5.1% 3% 2.5%

11 Epidemiological Study: AGE Median age : 46 years 68% < 50 ans

12 Epidemiological Study: Menopausal Status Status Frequency % No menopausal patients Menopausal patients ,7% 71 41,3%

13 Clinical Nodal status N+ = 73%

14 Histological Study : Type

15 Histological Study : SBR Grade High grade SBR II + III = 94%

16 Histological Study Hormonal Receptors Status ER- 57%

17 Histological Study HER2 Status Her2+ 59%

18 LiKerature DATA - IBC Histological Type Ductal carcinoma as others breast disease High index prolifera8on : SBR and mito8c index Hormonal receptors [Parton M, Breast 2004] Nega8vity of ER = 50-60% (MD ANDERSON Data) > 80% ER was reported Prognos8c is beaer whith ER+ > ER- Median survival 4 # 2 years (SEER database) HER2 neu [Sawaki M, Breast Cancer 2006] Surexpression and/or amplifica8on HER2 Hugh rate 40-50% compared to LABC and others

19 Molecular characteris6cs Epidermal Growth Factor Receptor EGFR [Le MG, Breast 2006] Surexpression of EGFR up to 58% Bad prognosis : Co- expression HER2neu/EGFR P53 [Yang CH, Future Oncol 2006] Gene8c Muta8on or protein surexpression Bad prognosis : high risk of dead if muta8on x8.6 Less response to primary chemotherapy

20 Molecular characteris6cs Surexpression of adhesion cellular molecules E- cadhérine and MUC- 1 Metas6c diffusion +++ Angio- lympha6que invasion ++ Angiogenesis Microvascular density Surexpression of proangiogenic factors : VEGF, Angiopoie8ne [ANG]- 1, FGF, IL- 8 et IL- 6 Lymphangiogenesis VEGF- C, VEGF- D, Flt- 4, prox- 1 et LYVE- 1

21 Specific Biomarkers IBC RhoC Guanosine Triphosphatase (GTPase) Oncogene surexpression in 90% cases of IBC versus only 38% in No inflammatory breast carcinoma. Angiogenic factor and metasta6c diffusion WISP3 ( lost in inflammatory breast cancer or LIBC) Suppressor gene Lack of expression in 80% cases IBC versus only 21% in NO IBC. Tumoral prolifera6on, angiogenesis, and local invasion Van Golen KL Clin Cancer Res 1995

22 «Specific gene6c expression» 80 IBC # 522 no IBC Mul8variate analysis: MIB1>20 (Ki67), HER2++/+++, ER- Surexpression E- cadherine>300, MUC1 5 factors >> 90.5 % probability of IBC++ 4 factors >> 75% de probability 2 ore more >> 50% de probability

23 Molecular Classifica6on Adapted to IBC Similar breast cancer molecular class Different distribu8on : High Frequency of BASAL = 26% HER2- posi6ve = 42% Van Laere S, Br J Cancer 2007

24 Local data Stage at ini6al diagnosis Localized IBC % Metastatic IBC 46 27%

25 Local data Metasta6c site : 46 cases

26 Modality of Treatment 172 patients 46 metastatics 126 non metastatics Pallia6ve chemotherapy +/- Neoadjuvante chemotherapy +surgery+/- RTH+/- Hormone therapy

27 Neoadjuvant Chemotherapy 124 pa6ents of 126 localized disease

28 Surgery Patey was done in 96/124 patients Rate of 77% Patients without surgery performed due to : Clincial progression or persistance of inflammatory symptoms

29 Pathologic Response Histological Evalua8on By Chevalier grading pcr «pathological complete response» pcr (Gr1) = 5.6% (7pts) pcr (Gr 1+2) = 8% (10 pts)

30 Adjuvant Chemotherapy Given to 66 patients of 96 with surgery performed Chemo therapy Anthracylines Taxanes Others Total N

31 Adjuvant Radiotherapy Given to 65 patients of 96 with surgery performed

32 Median survival = 22.3 months Estimated OS at 5years = 17.5%

33 Prognostics Factors Metastasis p< 0,0001

34 Tunisian data IBC Boussen, Semin Oncol 2008

35 Prognostics Factors Hormone Receptors Status v p<0,002

36 RH and IBC survival

37 Prognostics Factors HER2 Status p = 0,08

38 Conclusion One of the most agressive breast cancer. Poor survival in our sudy (17% at 5y) Non-optimal chemo regimen Lack of taxanes at this period Confirmation of literature data Specific characteristics of IBC More negativity of ER More HER2 expression

39 Conclusion Our data are limited to the retrospective methodology : Missing data Missing patients Necessity of Prospective study To identify biomarkers correlated with chemotherapy response