Breast cancer Peter Grell, Miloš Holánek Masaryk Memorial Cancer Institute Faculty of Medicine, Masaryk University Brno The 10 Most Common Causes of Cancer Death: 2012 Estimates Total Number and Percentage of Deaths from Cancer per Year, Worldwide Bowel including anus, ICD 10 C18-C21 Please include the citation provided in our Frequently Asked Questions when reproducing this chart: http://info.cancerresearchuk.org/cancerstats/faqs/#How Prepared by Cancer Research UK Original data sources: Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray, F.GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; 2013. Available from: http://globocan.iarc.fr, accessed on 16/01/2014. Cancer rates in Czech republic An individual woman in Czech Republic has a 1-in-10 chance of developing breast cancer over an 80-year lifespan Incidence nad mortality in Czech Republic Source: cruk.org/cancerstats You are welcome to reuse this Cancer Research UK statistics content for your own work. Credit us as authors by referencing Cancer Research UK as the primary source. Suggested style: Cancer Research UK, full URL of the page, Accessed [month] [year]. Breast Cancer (C50): 2011-2013 Average Number of New Cases Per Year and Age-Specific Incidence Rates per 100,000 Population, Females, UK Age-specific incidence of breast cancer Clinical signs what does a patient show up with ?? • Resistance in breast – most often in upper lateral quadrant • Skin edema • Erythematic skin • Skin retraction, ulceration • Inverted nipple • Usually painless • General symptoms: asthenia, weight loss, dyspnea Clinical signs Lump Large resistance Skin retraction Skin edema and erythema Orange peel skin inflammatory breast cancer Inverted nipple Risk factors or Can I do something to prevent cancer? Risk factors • Positive family history: breast cancer in 1st grade relatives – One relative 1.5 to 2.0 times risk – Two relatives 5.0 times • Early onset of menarche: earlier than 12 years • Late onset of menopause: after age of 55 • Nulliparity • Combined hormonal substitution (after menopause) • Smoking, lack of physical activity, alcohol (shift work?) • Benign breast afections: Atypical ductal hyperplasia • Genetic factors, responsible for 5-10 % of breast cancers Genetic risk factors • BRCA1 a BRCA2 genes – responsible for DNA reparation - Homologous recombination • Risk of breast cancer in woman with BRCA1 mutation is 80%, ovarian canrer 60%, with BRCA2 mutation 80%, and 25% respectively • Only prevention is bilateral mastectomy + salpingo- oophorectomy Diagnostics how do WE find out ?? ?? Initial diagnosis • Case 1: • 62 year old women • New resistance in left breast (upper top quadrant) • Overall in good shape • What studies to perform?? • TNM staging Mammography • Screening and diagnostic tool for breast cancer • Very sensitive a specific for breast cancer • Cheap • Measuring of primary tumor (in mm) – T stage • Diagnosis of local lymphatic nodes – N stage • Sometimes accompanied by ultrasound or breast MRI Breast cancer staging T classification Tumor size, characteristic T0 No evidence of primary tumor. T1 Tumor ≤20 mm in greatest dimension. T1a Tumor >1 mm but ≤5 mm in greatest dimension. T1b Tumor >5 mm but ≤10 mm in greatest dimension. T1c Tumor >10 mm but ≤20 mm in greatest dimension. T2 Tumor >20 mm but ≤50 mm in greatest dimension. T3 Tumor >50 mm in greatest dimension. T4 Tumor of any size with direct extension to the chest wall and/or to the skin (ulceration or skin nodules) T4a Extension to the chest wall, not including only pectoralis muscle adherence/invasion. T4b Ulceration and/or edema (including peau d'orange) of the skin, which do not meet the criteria for inflammatory carcinoma. T4c Both T4a and T4b. T4d Inflammatory carcinoma. Looking for distant metastases • M stage • Performing studies for: – Chest: X-ray, CT scan – Abdomen and pelvis: ultrasound, CT scans – Whole body – PET or PET/CT, wb CT – Bones – scintigraphy – Brain – MRI or CT Stage T N M I T1 N0 M0 IIA T0 N1 M0 T1 N1 M0 T2 N0 M0 IIB T2 N1 M0 T3 N0 M0 IIIA T1-3 N2 M0 T3 N1 M0 IIIB T4 Any N M0 IIIC Any T N3 M0 IV Any T Any N M1 Stage 5-year Survival Rate I 95% IIA 85% IIB 80% IIIA 67% IIIB 41% IIIC 49% IV 15% Breast cancer staging Case 1 • 62 years old • Left breast cancer 22mm - T2 • 2 pathologic lymphatic nodes in left axila – N1 • No distant metastases – M0 • TNM: T2 N1 M0 • Stage IIB • What is next? Histology what are we dealing with?? Histology • Morphology: – Ductal (85%), lobular, medullar, mixed • Grade of differentiation – G1(good)-G3(bad) • Molecular diagnostics: – Expression of receptors: • Estrogen receptor - ER • Progesterone receptor - PR • HER2 receptor – Ki-67 – marker of proliferation Subtypes of breast cancer Luminal A – less aggressive ER+, PR+, HER2-, Ki67 low Triple negative (10%) most aggressive ER-, PR-, HER2 negative Luminal B ER+, PR – or HER2+ or Ki67 high HER2 overexpressed (amplified) 15% Treatment how to cure patient? If not possible, how to prolong the life Principles of cancer treatment • In localized tumor – we can cure patients – Resection of tumor – only curative modality – Sometimes neoadjuvant therapy – treatment before surgery – chemotherapy and/or radiotherapy • To shrinking the tumor and allow less extensive surgery – Adjuvant treatment – treatment after surgery • To lower the risk of tumor relapse – Toxicity is not the main concern (temporary) • In metastatic disease – we can prolong life – Systemic treatment – chemotherapy, hormonal therapy, targeted therapy – Toxicity matter, quality of life is very important Surgery until we can get rid of it!!! Mastectomy • Total mastectomy – removal of entire breast Partial mastectomy • Breast-conserving surgery - only removes the part of the breast that has cancer and surrounding tissue • The aim is to resect as little tissue as possible to keep the breast in its original shape Surgery of axilla • Axillary lymph node dissection - ALND – incision under the arm and removing 10–40 lymph nodes from level I and level II – Procedure in all patients with positive lymph nodes – Risk of lymphedema • Sentinel nodes biopsy – SNB – Sentinel nodes are the first few lymph nodes where cancer cells spread – Removal of 1-3 nodes is performed in all patients with negative nodes (on ultrasound or mammography) – If SNB is positive, conversion to ALND Adjuvant treatment go away and never come back!! Adjuvant treatment • Treatment after surgery • Reduce the risk of the cancer to relapse (coming back) • Multimodal therapy: – Chemotherapy – 4-5 months – Targeted therapy (in HER2 posit.) – 1 year – Radiotherapy – 3-5 weeks – Hormonal therapy (in ER/PR posit.)– 5 – 10 years Chemotherapy for breast cancer • In selected patients with high risk breast cancer (not all patients need chemo): – Large tumor – Positive lymph nodes – Biological aggressive cancer – triple negative, HER2 positive Chemotherapy for breast cancer • Most used cytostatics: – Antracyclines - Doxorubicin, Epirubicin – Taxanes - Paklitaxel, Docetaxel – Capecitabin – Vinorelbin • Combination in adjuvant tretament: – AC – doxorubicin+cyklofosfamid – AC a followed by paclitaxel – FAC – flurouracil+doxorubicin+cyklofosfamid – FEC – flurouracil+epirubicin+cyklofosfamid – TAC – docetaxel+doxorubicin+cyklofosfamid – CMF – cyklofosfamid+metotrexát+flurouracil • In palliative settintgs: – Mostly monotherapy – paclitaxel, epirubicin, vinorelbin, capecitabin Targeted therapy • In HER2 positive breast cancer, about 15% of breast cancer • HER2 – transmembrane receptor, HER family • Activation leads to cell survival, metastasis, and resistance to therapy HER2 positive breast cancer • Anti-HER2 treatment – monoclonal antibodies against the HER2 receptor • First used antibody was trastuzumab (Herceptine) • Next generation – pertuzumab, T-DM1 • Adding to chemotherapy boosts treatment efficacy Hormonal therapy • About 70% of breast cancer are hormonal receptor positive (Estrogen or Progesterone receptor) – i.e. hormonal sensitive disease • Low or moderately aggressive disease (Luminal A or B) • Sensitive to hormonal therapy: • Tamoxifen (Selective Estrogen Receptor Modulator - SERM) • Aromatase inhibitors • Non-steroidal AI (anastrozole, letrozole) • Steroidal (exemestan) • direct ER inhibitor (fulvestrant) Hormonal therapy • In adjuvant setting used for 5-10 years • Very effective in Luminal A breast cancer subtype • Many patients can omit chemotherapy and use only hormonal therapy • Very good toxicity profile (hot flashes, bone or joint pain, arteficial menopause, endometrial carcinoma in tamoxifen • After surgery and chemotherapy • Always after partial mastectomy, sometimes after total mastectomy (large tumor, positive lymph nodes) • Duration 3-5 weeks, dose 50 Gy • Reduce local recurrence of cancer but also prolongs survival • Adverse events: post radiation dermatitis, skin desquamation Radiotherapy • After surgery and chemotherapy • Always after partial mastectomy, sometimes after total mastectomy (large tumor, positive lymph nodes) • Duration 3-5 weeks, dose 50 Gy • Reduce local recurrence of cancer but also prolongs survival • Adverse events: post radiation dermatitis, skin desquamation Radiotherapy Oncological treatment of an advanced incurable disease prolong life and improve QoL Treatment in metastatic setting • In ER/PR positive breast cancer (Luminal A/B subtype) is hormonal therapy very effective – Tamoxifen → Aromatase Inhibitors → Fulvestrant • If hormonal therapy does not work anymore or in ER/PR negative disease – chemotherapy – Firts line, second line, third line…. • In HER2 positive disease combination with targeted therapy (trastuzumab, pertuzumab, T- DM1) Chemotherapy • Anthracyclines: – Doxorubicin – Epirubicin – liposomal doxorubicin • Taxanes – Paclitaxel – Docetaxel – Nab-paclitaxel • Vinca alkaloids – Vinorelbin • Antimetabolites – Capecitabine – Gemcitabine – Fluorouracil • Platin derivates – Carboplatin – Cisplatin • Other cytostatics – Cyclophosphamide – Metothrexate – Eribuline • Usually using in monotherapy • If one chemotherapy does not work, choose another (another line), etc. Specific treatment • In bone metastases – bone-modifying agents (BMA) – bisphosphonates, denosumabu • In painful bone metastases – radiotherapy • In central nervous system metastases - radiotherapy • In pleural effusion – drainage • Social, psychosocial, spiritual support Summary • Breast cancer is a common diagnosis • Heterogeneous diseases - various biological subtypes • Therapy is complex - multimodal - surgery, chemotherapy, hormonal therapy, targeted therapy, radiotherapy… • + supportive treatment !!! 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