The EBC Council Manifesto on optimal breast pathology

Transcription

1 ECP 2017 Amsterdam Joint Symposium Breast Pathology / Pathology in favour of developing countries: Diagnostic management of breast cancer in low resource settings The EBC Council Manifesto on optimal breast pathology Tibor Tot Pathology & Cytology Dalarna Sweden

2 Conflict of interest/funding X None Company: Product royalties Paid consultant Research support

3 Surgery / radiology Radicality Extent Size Multifocality Lymph nodes mm numbers Oncology ER HER2 Ki67 Genetics Molecular % Reproducibility Pathology Histology Benign/malignant Invasive/in situ Tumor type/grade Immunohistochemistry description

4 Commission Working Group on Breast Screening Pathology: J.P. Sloane (Chair) I Amendoeira N. Apostolikas J.P. Bellocq, S. Bianchi W. Boecker G. Bussolati D. Coleman, C.E. Connolly V. Eusebi C. De Miguel P. Dervan, R. Drijkoningen C.W. Elston D. Faverly A. Gad, J. Jacquemier M. Lacerda J. Martinez-Penuela C. Munt J.L. Peterse F. Rank M. Sylvan, V. Tsakraklides B. Zafrani Consistency achieved by 23 European pathologists from 12 countries in diagnosing breast disease and reporting prognostic features of carcinomas Virchow s Arch 1999:434:3-10. Parameter Kappa value (overall, 4 rounds) Consistency in diagnosing ADH 0.27 Consistency in diagnosing LVI 0.38 Consistency in grading DCIS/3 grades 0.38 Consistency of grading DCIS/2 grades 0.46 Consistency in grading invasive ca Diagnosing DCIS 0.87 Diagnosing invasive carcinoma 0.94

5 Breast pathology WHO blue book TNM8 CAP guidelines EWGBCSP European guidelines Oncology guidelines (ASCO, St Gallen, San Antonio) National, regional, local guidelines Individual routine

6 Guidelines

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8 Candidates will be required to have knowledge of: Molecular biology of breast cancer: main pathways involved in the development and progression of breast cancer. Epidemiology and risk factors. Prevention of breast cancer and genetic counselling. Breast cancer screening. Clinical and instrumental diagnosis of breast cancer. Principles of differential diagnosis with other breast diseases. Natural history of breast cancer. TNM and disease staging. Multidisciplinary approach to management of breast disease. Principles of breast cancer treatment: surgery, radiotherapy and medical treatment. Principles of imaging of breast cancer. Translational research in breast cancer: principles and main applications. Protocol drafting and editing, writing a scientific manuscript, presenting results at scientific meetings. Knowledge of the European guidelines on clinical and translational research: Good Clinical Practice. Interpretation of results from scientific papers: reading a scientific report.

9 Candidates will need to be familiar with these practical aspects: Needle core biopsy interpretation and classification. Breast cytology interpretation and classification. X-ray-guided localisation biopsy examination. Use of specimen radiography. Examination of diagnostic surgical biopsies. Examination of cancer treatment surgical resectionspecimens. EU and WHO guidelines for pathological classification of breast disease (working knowledge of). Assessment of prognostic factors. Pathology of hereditary breast cancer. Pathology of breast sarcomas, lymphomas, and rare tumour types. Pathology of breast cancer in males. Methodology and interpretation of predictive tests, including hormone receptors and HER2 status.

10 At the end of the training candidates should: Have trained and worked in specialist units seeing a minimum of 150 breast cancer cases per year. Be responsible for diagnosis and classification of breast disease and breast cancer, including immuno-histochemistry and in situ hybridisation for predictive markers. Be conversant with techniques for breast pathology specimen evaluation. Operate in a multidisciplinary environment (i.e. in collaboration with other specialists in the breast cancer field within the same hospital or collaborative group). Have published in the field of breast cancer medicine, in peer-reviewed international journals having an impact factor greater than 1: a minimum of one original article as first author and/or; a minimum of five original articles as co-author. Take part in external quality assurance. Participate in an audit. Teach at symposia/training sessions on breast pathology. Participate in continuing professional development.

11 At the end of the training candidates should: Have trained and worked in specialist units seeing a minimum of 150 breast cancer cases per year. Be responsible for diagnosis and classification of breast disease and breast cancer, including immuno-histochemistry and in situ hybridisation for predictive markers. Be conversant with techniques for breast pathology specimen evaluation. Operate in a multidisciplinary environment (i.e. in collaboration with other specialists in the breast cancer field within the same hospital or collaborative group). Have published in the field of breast cancer medicine, in peer-reviewed international journals having an impact factor greater than 1: a minimum of one original article as first author and/or; a minimum of five original articles as co-author. Take part in external quality assurance. Participate in an audit. Teach at symposia/training sessions on breast pathology. Participate in continuing professional development.

12 The qualification of a potential candidate aspiring to the title of Specialist in Breast Pathology will be evaluated through a multiple choice test that will cover all the theoretical topics listed above, and will contain some clinical cases for which a pathological diagnosis is required. The candidate will also have to meet all the entry requirements listed above. Every 3 years both theoretical and practical contents will have to be re-assessed.

13 4.3. Breast pathology Breast pathologist: A board certified specialist in pathology with a special interest to breast disease.

14 4.3. Breast pathology The Breast Centre must have at least two dedicated breast pathologists (one of whom should be nominated as the breast pathology lead for the team). To be considered a breast specialist, the lead pathologist must spend 50% of his/her working time in breast disease and the other dedicated pathologists at least 25%. This 25% and 50% has to be calculated on the basis of the standard weekly full working time as defined in the national collective agreement on working times. The specialist breast pathologists should be responsible for all breast pathology and cytology dealt with by the Breast Centre. All specialist pathologists reporting breast cancer must report on at least 50 primary breast cancer resections per year. The dedicated breast pathologists should take part in regional, national or European breast cancer reporting quality assurance schemes.

15 Breast cancer pathology - a manifesto for optimal care This manifesto was prepared by a European Breast Cancer (EBC) Council working group and launched at the European Breast Cancer Conference in Glasgow on 20 March It sets out optimal technical and organizational requirements for a breast cancer pathology service, in the light of concerns about variability and lack of patient-centred focus. It is not a guideline about how pathology services should be performed. It is a call for all in the cancer community pathologists, oncologists, patient advocates, health administrators and policymakers to check that services are available that serve the needs of patients in a high quality, timely way.

16 Breast cancer pathology - a manifesto for optimal care The members of the working group are: Alberto Costa (scientific director, European School of Oncology, Milan, Italy) Emiel Rutgers (head of surgery, The Netherlands Cancer Institute) Elizabeth Bergsten Nordström, president, Europa Donna, Europe s breast cancer advocacy organisation Tibor Tot, associate professor of pathology, Uppsala University, and head of laboratory medicine at Central Hospital Falun, Dalarna, Sweden Giuseppe Viale (director, department of pathology, European Institute of Oncology, Milan, Italy)

17 Breast cancer pathology - a manifesto for optimal care Pathologists play a vital role in managing all types of cancer but their work can be compromised by lack of resources, lack of training and lack of multidisciplinary teamwork in hospitals

18 Breast cancer pathology - a manifesto for optimal care Part 1: Optimal breast cancer pathology essential diagnostic and prognostic services Accurate and detailed diagnosis of breast cancer from the examination of the specimen Prognostic parameters from this morphological examination Molecular parameters that determine therapeutic decision making and predict the patients response to the applied therapy Evaluation of the efficacy of surgical and oncological treatment.

19 Breast cancer pathology - a manifesto for optimal care The 10 essential / obligatory parameters Tumour type (according to the actual WHO classification) Tumour size / disease extent Tumour grade (Nottingham histology grade by Elston and Ellis) Lymph node status Operative margins Peritumoral vascular invasion Multifocality/centricity Hormone receptor status (ER/PR) HER2 status Ki67 labelling index In addition, these services are likely to be needed in future: Gene profiling Biobanking

20 Radiological pathological correlation is essential in diagnosing breast carcinoma The radiology images are courtesy of Prof Laszlo Tabár, DRs Nadja Lindhe and Mats Ingvarsson

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22 Mammographic ultrasound MRI large-section correlation: basal like cancer of the breast

23 Invasive breast carcinoma NST Invasive breast carcinoma NST

24 Early invasive breast carcinoma Advanced invasive breast carcinoma

25 Cumulative survival in early (in situ and <15 mm invasive) breast carcinomas, Falun, ,9 0,8 0,7 0,6 In situ and <15 mm invasive carcinoma (13/252) 94.3% 0,5 0,4 0,3 0,2 0,1 0 Up to 12 years follow-up, 8.34 at average, SD+/ years Kahán Z, Tot T. Breast Cancer, a Heterogeneous Disease Entity. The Very Early Stage, Springer 2011.

26 Life expectancy of screen-detected invasive breast cancer Age matched invited women with and without screen detected cancer (858) 6 year shorter survival in those with s.d.c. No difference in survival for those <15 mm comprising 40% of s.d.c. >=15 mm: 6 12 year shorter survival, depending on tumor size Otten JDM, Broeders MJM, Den Heeten GJ et al. Life expectancy of screen-detected invasive breast cancer patients compared with women invited to the Nijmegen Screening Program. Cancer 2010:

27 Molecular characteristics of early vs more advanced invasive breast carcinomas Early BC Advanced BC Total P-value < 15 mm >= 15 mm Basal-like 5.9% (12/203) 15.1% (48/317) 11.5% (60/520) = ER negative* 12.3% (42/342) 18.2% (93/510) 15.8% (135/852) = Tripple negative 6.4% (22/341) 10.5% (53/507) 8.8% (75/848) = Her-2 positive 8.9% (31/347) 13.3% (68/511) 11.5% (99/858) = Grade % (46/355) 29.5% (151/511) 22.0% (197/866) < Total 41.5% (362/873) 58,5% (511/873) 100% (873/873) Kahán Zs., Tot T., eds. Breast Cancer, a Heterogeneous Disease Entity: The Very Early Stage. Springer 2011

28 ER pos breast carcinoma NST ER pos breast carcinoma NST

29 Unifocal invasive breast carcinoma Multifocal invasive breast carcinoma

30 P < Tot T. The Sick Lobe Concept. In Francescatti DS, Silverstein MJ eds. Breast Cancer. A New Era in Management, Springer 2014, pp 79-94

31 Alice P Chung, Kelly Huynh, Travis Kidner, Parisa Mirzadehgan, Myung-Shin Sim, Armando E Giuliano. Comparison of Outcomes of Breast Conserving Therapy in Multifocal and Unifocal Invasive Breast Cancer ( J Am Coll Surg 2012;215: by the American College of Surgeons) 164 MF tumors ( 2 or more distinct tumors in a single incision or segmentectomy ) Only breast conserving surgery. Median follow-up 112 months. Results: patients in the MF group had higher 10-year LR (0.6% vs 6.1%, p<0.001) and lower 10-year DFS (97.7% vs 89.3%, p<0.001) and OS (98.4% vs 85.8%, p<0.001). On multivariable analysis, multifocality was independently significantly associated with local recurrence-free survival (LRFS), DFS, and OS.

32 Mutifocality appears to be associated with a worse prognosis, however, substantial inter-study heterogeneity limits the precise determination of increased risk. Francisco E et al. Effect of multifocality and multicentricity on outcome in early stage breast cancer: a systematic review and meta-analysis. Breast Cancer Res treat 2014

33 Invasive tumor focality by St Gallen 2013 molecular phenotypes, Dalarna County, LA LB HER2 TN Total U 64.5% (267) 56.6% (294) 43.8% (14) 63.4% (59) 59.9% (634) MF 30.4% (126) 36.3% (189) 56.2% (18) 35.5% (33) 34.6% (366) D 5.1% (21) 7.1% (37) 0 1.1% (1) 5.5% (59) Total 100% (414) 100% (520) 100% (32) 100% (93) 100% (1059) U 56.6% (249/440) MF 35.9% (158/440) D 7.5% (33/440) Total 100% (440/440) LB HER2 - LB HER2+ HER2 56.2% (45/80) 38.9% (31/80) 5.0% (4/80) 100% (80/80) 43.8% (14/32) 56.2% (18/32) 0 100% (32/32) Tot T: Breast cancer: The relation of some radiological and morphological parameters to molecular phenotypes and prognosis. Journal of OncoPathology 2(4), (2014)

34 Cumulative survival in 499 invasive breast carcinoma cases by distribution of the invasive component, Falun, ,9 0,8 0,7 0,6 0,5 0,4 0,3 89.6% 76.0% P < % Unifocal (30/311) Multifocal (28/122) Diffuse (8/26) 0,2 0, Time since diagnosis (years) Distribution unknown in 40 cases Tot et al. Breast cancer multifocality, disease extent, and survival. Hum Path 2011

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36 HER2 Tot T, Int J Breast Cancer, 2012

37 Breast cancer pathology - a manifesto for optimal care Part 2: Optimal breast cancer pathology organisation Individuals professional expertise and development requirements A high level of competency in all aspects of breast pathology, including both classical morphological and modern molecular/genetic aspects, according to current guidelines Continuous education and improvement of diagnostic skills Understanding of the clinical consequences of every detail in the pathology report Networking with experts for discussing professional views

38 Breast cancer pathology - a manifesto for optimal care Departmental requirements Access to all relevant clinical information for each patient Full attention to breast specimens and a team of technicians that provides high quality breast preparations Day-to-day multidisciplinary teamworking, such as with detailed correlation between radiology and pathology, and with molecular biology and pathology Understanding of the capabilities and limitations of imaging methods, biopsy modalities and histopathology techniques Pathologists should be part of the patient-facing team and available to explain reports to patients At least, an informal system for obtaining or giving second opinions on selected cases, involving experts at external institutions

39 Breast cancer pathology - a manifesto for optimal care Hospital requirements High quality of work, checked with continuous internal monitoring to meet international standards Adherence to Good Laboratory Practice (GLP) guidelines and participation in external quality control schemes Monitoring of multidisciplinary teamwork among departments, not only in centres with oncology specialists but also in general hospitals External laboratories when used should also follow guidelines and be subject to quality control Services should be available in a timely way to every breast cancer patient: unnecessary wait times should be identified and eliminated Maintenance of a high-quality biobank for research

40 Breast cancer pathology - a manifesto for optimal care Health system requirements A commitment to a pathology service that is organised to meet the needs of multidisciplinary teams and their patients A national pathology quality standards organisation A monitoring system to audit key breast cancer pathology parameters across cancer centres and hospitals National and international auditing of laboratory testing A strategy for referring borderline cases to experts for second opinions An education and training strategy to ensure that sufficient pathologists and technicians are in post Incorporating patient-advocate viewpoints in service reviews

41 Highlights of the Manifesto This manifesto calls for high quality pathology services for all breast cancer patients in Europe. The pathology services must meet the needs of the patients and clinicians. The diagnostic and prognostic information for decision making must be timely delivered. Hospitals should ensure pathology integrated in multidisciplinary teamwork visible to patients. Pathology: vital discipline with substantial career potential for pathologists and technicians.

42 3.4. Staffing The core breast cancer services - radiology, surgery, medical oncology, radiotherapy, pathology, nursing - must have at least two professionals in each department, and all staff should comply with EUSOMA s guidelines on standards for training specialized health professionals who deal with breast cancer [20]. Note that in 2013, a manifesto adopted at the Ninth European Breast Cancer Conference identified breast cancer pathology services as needing particular attention [21].

43 European Commission Report on a European survey on the organization of breast cancer care services, 2014

44 The 4th edition of the European guidelines for quality assurance in breast cancer screening and diagnosis, issued in 2006, included a chapter providing indications for a model centralizing breast cancer care in the so-called breast units and requirements for those units. Ten years after issuing that model and following-up the European Parliament resolution of 2006 on breast cancer this report provides up-to-date information on how and where these requirements have been implemented across Europe.

45 The 2016 deadline for all patients in European Union countries to access specialist, multidisciplinary breast cancer units or centres, will be missed by most countries, despite numerous resolutions and declarations issued since the year 2000 that have called for universal specialist services. This means that many women, and some men, do not receive optimal breast cancer care in Europe.

46 Of 30 responsing countries, two different sources of information compared

47 The mandatory requirements defined in the 2006 European Guidelines, 1. A definition of the volume (critical mass) of cases necessary in order to set up breast units: more than 150 newly diagnosed cases of primary breast cancer each year. 2. A definition of the composition of the core team working in the breast unit: Clinical Director of Breast services, breast surgeons, breast radiologists, breast pathologists, breast oncologists, breast diagnostic radiographers, data managers, and patient support staff (such as breast care nurses) with a defined minimum experience. 3. Each member of the core team must have special training in breast cancer. 4. Each member of the breast unit core team must undertake continuing professional education (CME) on a regular basis.

48 Of 30 responsing countries, two different sources of information compared

49 Implementation of mandatory volume requirement of 150 new cases/year according to ECIBC National Contacts.

50 The Directorate General for Health and Food Safety (DG SANTE) asked the European Commission s Joint Centre (JRC) to coordinate the European Commission Initiative on Breast Cancer (ECIBC) to ensure and harmonize the quality of breast cancer services across European Countries via QA scheme supported by the Guidelines

51 Conclusion: The optimal breast cancer pathology report is Interdisciplinary product Combines morphological and molecular parameters Meets the requirements for the individual patients care Timely available