1 / 55

Neoadjuvante Therapy of Breast Cancer

Neoadjuvante Therapy of Breast Cancer. Cancer statistics Genesis of cancer Cancer in detail Treatment of cancer Prevention Follow-up NEWS Research. INCIDENCE OF CANCER. Colorectal cancer Breast cancer Lung Cancer Prostate cancer Cervix carcinoma Meaning of

jules
Download Presentation

Neoadjuvante Therapy of Breast Cancer

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Neoadjuvante Therapy of Breast Cancer

  2. Cancer statistics • Genesis of cancer • Cancer in detail • Treatment of cancer • Prevention • Follow-up • NEWS • Research

  3. INCIDENCE OF CANCER • Colorectal cancer • Breast cancer • Lung Cancer • Prostate cancer • Cervix carcinoma • Meaning of • Prevention and • risk - behavior

  4. Principles of treatment for malignant disease at an early stage • most possible radical removal of tumour with maximal protection of healthy structures and precise indication. • preventing the growth of possible metastasis depending on the availability of effective treatment and tumour characteristics

  5. Principles of treatment for malignant disease with distant metastases • Maintain organ function • Quality of life • Prolongation of life with consideration of QoL and tolerance of treatment • Psychological support, if wished for • Adequate pain management

  6. Treatment modalities for malignant diseases • Surgery • Radiation therapy • Chemotherapy • Anti-hormone therapy • Antibodies • Disturbance of the capillary supply • Gene manipulation

  7. Main feedback mechanisms of cell division and their down-regulation in the development of cancer. 1. Independence of cell replication from exogeneous growth factors. 2. Insensitivity to growth factors – inhibition signaling 3. Resistance to induction of apoptosis 4. Unlimited span of life5. Neoangiogenesis 6. Cellular mobility and cell growth in foreign tissue Hanahan & Weinberg, Cell 100: 57, 2000.

  8. Cancer treatment in breast cancer as an example • Treatment dependent from • Tumour characteristics • time of treatment • desired short- and middle term results • At a cleat long-term goal of a disease free survival

  9. Characteristics of breast cancer cells • Growth • hormone receptors • HER-2/neu-Protein overexpression • Differentiation • histopathological differentiation • Dissemination • lymph node infiltration

  10. Medical-oncologic form of treatment in malign diseases * NEOADJUVANT THERAPY* ADJUVANT THERAPY* PALLIATIV THERAPY

  11. NEOADJUVANT THERAPY Medical-oncologic treatment is administered pre-surgical

  12. CONCEPT OF NEOADJUVANT THERAPY IN BREAST CANCER Administration of substances that known to inhibit cell division (chemotherapy, anti-hormone therapy) pre-operatively with the goal to decrease tumour size and thereby decrease the extension of surgical intervention. Response to neoadjuvant therapy is a parameter for tumour cells and their treatment sensitivity (!)

  13. Open question conserning the concept of neoadjuvant therapy in breast cancer. 1. ZEITVERSÄUMNIS by surgery-delay (= potential danger for the patient?) 2.Quality of treatment result in comparison to post-surgery (adjuvant) therapy 3. Advantages?

  14. NEOADJUVANT THERAPY IN BREAST CANCER:NSABP B-27 STUDY STUDY DESIGN1.523 patients with breast cancer, who received747 pre-surgery (neoadjuvant) chemotherapy759 post-surgery (adjuvant) chemotherapyChemotherapy scheme: AC

  15. NEOADJUVANT THERAPY IN BREAST CANCER:NSABP B-27 STUDY TUMOR SIZE <2cm 2.1-5.0cm >5.1cmCOMPLETE REMISSION 57% 35% 17%PARTIAL REMISSION 22% 46% 58%STABLE DISEASE 15% 16% 22%PROGRESSION 5% 3% 3%

  16. NEOADJUVANT THERAPY IN BREAST CANCER: EINFLUSS AUF BRUSTERHALTENDE CHIRURGIE. TUMOR SIZE <2cm 2.1-5.0cm >5.1cmINITIAL PRESENTATION 79% 63% 8%AFTER CHEMOTHERAPY 81% 71% 22%

  17. NEOADJUVANT THERAPY IN BREAST CANCER : SURVIVAL DATA IN THE NSABP-B27 STUDY. NEOADJUVANT ADJUVANTDISEASE FREE 67% 67%5-YEAR-SURVIVAL 80% 80%

  18. NEOADJUVANT THERAPY IN BREAST CANCER : CONCLUSION FROM THE NSABP-B27 STUDY. 1. Neoadjuvant therapy is possible2. Neoadjuvant therapy reduces tumour size and allows reduced surgical intervention 3. Patients have no disadvantage with a delay of surgery

  19. EXTREMITY CONSERVING SURGERY IN TUMOURS OF THE BONE : 30-YEAR-RESULTS OF THE DEPARTMENT OF ORTHOPEDIC, UNIVERSITY HOSPITAL Period 1Period 2Period 3 (1965-1974) (1975-1984) (1985-1994) Died 116 (71.6%) 104 (53.3%) 152 (37.3%) Alive 46 (28.4%) 91 (46.7%) 256 (62.7%) 3-year-survival 76 (46.9%) 120 (61.5%) 295 (72.3%) R. Kotz et al., 2000

  20. ADJUVANT THERAPY * Is administered after surgery in patients who have no clinical manifestation of distant-metastases, however the probability of disease relapse. * Goal: prolongation of disease-free interval and survival time

  21. DECISION CRITERIA FOR ADJUVANT THERAPY * Probability of relapse (= metastases)* Probability of treatment efficacy * Therapy-associated toxicity in relation to treatment result * Only statistical consulting, not individual

  22. ADJUVANT THERAPY: PROGNOSTIC DISEASE VARIABLES * Affected local lymph nodes * Tumour size * Radical surgery concerning the removal of tumour cells * Tumour characteristics that can be influenced biologically and therapeutically * Biologic characteristics of the tumours that make a relapse probable

  23. RATIONALE OF ADJUVANT THERAPY * Small tumour cell clusters (<3mm) are not visible even with the best radiological methods. Their presence can only be assumed using the known risk factors. * Disseminated tumour cells “awaken” from their „dormant state“, growth and form undetectable metastases.* small tumour cell cluster are treatable more effectively than large, radiological detectable metastases

  24. ADJUVANT THERAPY IN BREAST CANCER:RISK FACTORS FOR LATER FORMATION OF METASTASES * Involvement of axillar lymph nodes (none, 1-3, 4-10, >10)* estrogen receptor status (POSITIV / NEGATIV)* histological grading (G1-4)* tumour size

  25. ADJUVANT THERAPY IN BREAST CANCER: THERAPY OPTIONEN * Radiation therapy* Anti-hormone therapy* Chemotherapy

  26. FUNCTION OF ESTROGEN RECEPTOR 1. Localisation within the tumour cell 2. Interaction with estrogen causes activation of cell growth 3. Blockade inhibits growth of malignant cells

  27. ADJUVANT THERAPY IN BREAST CANCER: THERAPY OPTIONEN TAMOXIFEN * Breast cancer cells of about 50% of all patients develops and growth under the influence of estrogen.* Tamoxifen blocks the estrogen receptor competitively.

  28. TAMOXIFEN AS ADJUVANT THERAPY IN BREAST CANCER Patients37.000 women from 55 worldwide, randomized studies (<1990 - 1995); = 87% of worldwide data. Estrogen receptor (ER)- positive18.000 patients with ER-positive tumours 12.000 patients with unknownMedian Follow-up10 YearsStatistical methodsIntention-to-treat, metaanalysis EBCTCG, LANCET 351: 1451, 1998

  29. REDUCTION OF RELAPSE AND MORTALITY USING TAMOXIFEN IN DEPENDENCY OF TREATMENT DURATION % Reduction of Relapse Mortality 2p 1 Year 18  3 10  3 <.00001/.0006 2 Years 25  2 15  2 <.00001/.00001 5 Years 42  3 22  4 <.00001/.00001Total 27  2 15  2 <.00001/.00001 EBCTCG, LANCET 351: 1451, 1998

  30. REDUCTION OF RELAPSE AND MORTALITY USING TAMOXIFEN IN DEPENDENCY OF ESTROGEN RECEPTOR. % REDUCTION OF Relapse Mortality 2p 1 Year 20 mg/day 18  4 12  5 30 - 40 mg/day 22  5 11  5 >.1/.1 5 Years 20 mg/day 45  4 21  6 30 - 40 mg/day 49  5 32  6 >.1/.1 EBCTCG, LANCET 351: 1451, 1998

  31. REDUCTION OF RELAPSE AND MORTALITY USING TAMOXIFEN IN DEPENDENCY OF ESTROGEN RECEPTOR % REDUCTION OF Relapse Mortality 2p ER low 6  11 3  11 ER unknown 37  8 21  9 ER positive 50  4 28  5 Subtotal 43  3 23  4 <.00001/.00001 ER+ vs. ER- <.00001/.005 EBCTCG, LANCET 351: 1451, 1998

  32. SECONDARY DISEASES AFTER 5-YEARS OF TAMOXIFEN-TREATMENT IN PATIENTS WITH BREAST CANCER. EVENTS/1000 YEAR 10-YEAR-RISK/1000TAM. KONTR. 2p TAM. KONTR. DIFFERENZ KONTRALATERALE MAMMACARCINOM-INZIDENZ93/23.6 159/21.0 <.00001 26 47 -21  5GEBÄRMUTTERKREBS-INZIDENZ43/26.9 9/23.6 <.0001 11 3 +9  2GEBÄRMUTTERKREBS-MORTALITÄT7/26.4 0/23.2 .02 2 0 +2  0.8 EBCTCG, LANCET 351: 1451, 1998

  33. RESULTS OF BREAST CANCER PROPHYLAXIS IN WOMEN WITH GENETIC DISPOSITION USING TAMOXIFEN. Study design 13.388 women with genetic disposition (high risk) 20 mg tamoxifen/day for 5 years Placebo-controlled

  34. DEFINITION OF INCREASED GENETIC DISPOSITION FOR BREAST CANCER DEVELOPMENT • Age > 60 Years • 2. 35-59 years with an anamnesis of lobular carcinoma in situ or a 5-year-risk of >1.66% including • * one first degree relatives or • * two aunts with breast cancer with breast cancer • * preceding breast biopsy to verify radiological suspect areas • * pathologic diagnose of a atypical hyperplasia

  35. RESULTS OF BREAST CANCER PROPHYLAXIS IN WOMEN WITH GENETIC DISPOSITION USING TAMOXIFEN. Tamoxifen Placebo invasive breast cancer 85 154 non-invasive carcinomas 31 59 Bone fractures 47 71 Endometrial carcinoma 33 14 Thromboembolis 99 70

  36. ADJUVANT CHEMOTHERAPY IN BREAST CANCER Reduction of yearly risk using chemotherapy Relapse -23.5  2.1% <.00001Death -15.3  2.4% <.00001 Lancet 352: 930, 1998.

  37. REDUCTION OF RELAPSE AND MORTALITY USING TAMOXIFEN AND CHEMOTHERAPY IN BREAST CANCER % Reduction of Relapse Mortality 2p 5 year tamoxifen vs. 0 -46  4 -22  5 5 year tamoxifen + chemotherapy vs. chemotherapy -52  8 -47  9 >.1 />.1 EBCTCG, LANCET 351: 1451, 1998

  38. ADJUVANT THERAPY IN BREAST CANCERCONCLUSION Adjuvant therapy with tamoxifen and/or chemotherapy leads to a significant reduction of incidence of metastases and mortality. Choice of treatment modality depends on tumour characteristicsImprove of criteria's for selection is necessary to identify patients with a principally good prognosis. Patients with breast cancer and their existing data patientinnen mit mammacarcinom sollte auf grund vorliegender daten adjuvante therapie empfohlen werden

  39. PALLIATIV THERAPY * Is administered after clinical manifestation of distant metastasis into organs and bone * Aims: introduce a remission, increase of survival time and palliation of symptoms

  40. PALLIATIV THERAPY MODALITIES * Anti-hormone therapy* Chemotherapy* Antibody* Radiation therapy* Palliativ and supportiv therapy

  41. PROGNOSTIC ORIENTATED TREATMENT IN METASTATIC BREAST CANCER Good prognosis defined by:* Hormone-receptor positively * formation of metastasis into skin, bone, lymph node, connective tissue         * Interval between primary diagnosis and relapse >2 years    Anti-hormone therapy (estrogen withdrawal)

  42. PROGNOSTIC ORIENTATED TREATMENT IN METASTATIC BREAST CANCER Poor prognosis defined by:* hormone receptor-negativity         * formation of metastasis into organs (liver, lung).        * interval between primary diagnosis and relapse <2 years    cytostatic chemotherapy

  43. TREATMENT OF GENERALIZED BREAST CANCER Treatment in dependency of * Estrogen receptor status        * Her-2/neu – positively         * Criteria for prognosis

  44. ANTI-HORMONE THERAPY OF METASTASISED CARCINOMA Hormone withdrawal* surgical * pharmacological

  45. ANTI-HORMONE THERAPY OF METASTASISED CARCINOMA Competitive hormone receptor blockade* Estrogene * Testosterone

  46. ANTI-HORMONE THERAPY IN METASTASISED BREAST CANCER Pre-menopausal* Ovariectomy * LH-RH-agonist * TamoxifenPost-menopausal* Aromataseinhibitors (letrozol, anastrozol) * Tamoxifen

  47. OLD AND NEW CHEMOTHERAPEUTICS:A SELECTION • Old New • Fluorouracil Carboplatin • Methotrexat Capecitabine • Epirubicin • Vinca Alkaloide Gemcitabine • Cyclophosphamid Irinotecan • Ifosfamid Lipos. • Etoposid Doxorubicin • Cisplatin Topotecan • Vinorelbine

  48. POSITIVE RESULTS OF NEW CHEMOTHERAPEUTICS IN MALIGN DISEASE • Testicular carcinoma • Breast cancer • Lung cancer • Colon carcinoma • Ovarian carcinoma • Bladder carcinoma • Pancreatic cancer

  49. ADVANCES OF CHEMOTHERAPY 5-year survival rate for different malignant diseases 1960-1993 (USA) 1960 1993

  50. Antibody inhibit growth Receptor Growth factor Tumorprogression No growth Influence of growth factors on tumour growth

More Related