power oint

1. DISCUSS THE ROLE OF PRECISION
MEDICINE IN THE CONTEMPORARY
THERAPY OF BREAST CANCERS
PRESENTER- SANUSI A.A
SUPERVISOR- DR ENWELUONYE, CONSULTANT GENERAL SURGEON
DEPT OF SURGERY
UATH
6/21/2019 1

2. OUTLINE
• Introduction
• Pathology
• Management
• Patient assessment
• Aims of treatment
• Modalities of treatment
• Role of precision medicine
• Challenges of precision medicine
• Conclusions
• References
6/21/2019 2

3. INTRODUCTION
• The concept of precision medicine also known as personalized
medicine or individualized medicine
• It is a treatment tailored to unique characteristics of an individual
disease and/or patient
• In contrast to the “one size fits all” approach, it is an emerging
approach aims to optimize effectiveness of disease prevention and
treatment and minimize side effects, by considering an individual specific
make up of genetic, biomarker, phenotypic, and psycho-social
characteristics
6/21/2019 3

4. INTRODUCTION
• This approach will allow doctors and researchers to predict more
accurately which treatment and prevention strategies for a particular
disease will work in which groups of people
• Precision will be achieved at each phase of care from diagnosis to
follow up care
6/21/2019 4

5. INTRODUCTION
• Statement of surgical importance
• Breast cancer is highly complex, heterogenous, and multi-factorial
disease, hence the need to develop management strategies that will
individualized patients care, maximize benefits, reduce risk/side
effects, and save costs
6/21/2019 5

6. INTRODUCTION
• Epidemiology
• Breast cancer is the most common malignancy in women
• Leading cause of cancer related death in women aged 20-59 years
• Account for 25-30% of cancers in women
• Incidence: 96/100,000 in Western Europe; 38/100,000 in Africa
6/21/2019 6

7. INTRODUCTION
• Historical management models
• Halstedian model (radical approach)
• Fisher’s model (systemic approach)
• Current model (mixture, based on tumour biology,
individualized)
6/21/2019 7

8. PATHOLOGY- AETIOLOGY/RISK FACTORS
6/21/2019 8

9. PATHOLOGY
• Classifications
• Histologic
• Greater than 95% of breast
malignancies are
adenocarcinomas
• In situ vs. invasive
• Invasive cancers
• No special type (NST)
• Special types
• Lobular
• Tubular medullary
• Mucinous
• Papillary
• Inflammatory
6/21/2019 9

10. PATHOLOGY
• Classification
• Degree of differentiation
• Well differentiated
• Moderately differentiated
• Poorly differentiated
6/21/2019 10

11. PATHOLOGY-MOLECULAR SUBTYPES
6/21/2019 11

12. MANAGEMENT
• Patient assessment
• History
• Symptoms
• Risk factors
• Complications
• Physical examination
• General examination
• Breast examination
• Examination for metastasis; Chest, Abdomen, Spine
6/21/2019 12

13. MANAGEMENT
• Investigations
• Imaging; USS, Mammography, MRI/CT
• Pathological
• FNAC
• Core biopsy
• Open biopsy
• Incision (ulcerated lesion, Paget’s disease)
6/21/2019 13

14. MANAGEMENT
• Excision (mostly for benign lesions, small lesions that may be
missed by needle biopsy)
• Wide local excision
• Staging investigations
• CXR, abdominal USS, LFT, renal function test, skeletal survey
• Staging
• Aims of treatments
• Based on stage, grade, tumour characteristics and patient’s function
• Curative or palliative
6/21/2019 14

15. MANAGEMENT
• Modalities of treatment
• Two principles of treatment
• Reduce chances of local recurrence
• Reduce risk of metastatic spread
• Treatment decisions are best taken by a multidisciplinary team
• Current treatment modalities: - surgery, radiotherapy,
chemotherapy, hormonal therapy, targeted therapy
6/21/2019 15

16. MANAGEMENT
• Surgery
• Diagnosis, prophylaxis, curative or palliative
• Options
• Breast conservation surgery
• Wide local excision, lumpectomy, quadrantectomy
• Total mastectomy
• Simple, modified radical, radical
6/21/2019 16

17. MANAGEMENT
• Radiotherapy
• For local control, metastasis
• After breast conservation surgery
• Patient with high risk of loco-regional recurrence
• Locally advanced cancers
• Advanced metastatic cancer
• Dosage: 50Gy in 25 daily fractions over 5weeks
• Recently: 40-42Gy in 15-16 fractions over 3 weeks
6/21/2019 17

18. MANAGEMENT
• Chemotherapy
• Systemic control
• Adjuvant or neo-adjuvant
• Based on tumour biology
• Reduces mortality by 20%
• Given in cyclical combination
• However, not all patients respond equally to cancer therapeutic
compounds
6/21/2019 18

19. MANAGEMENT
• Hormonal therapy
• Indicated in hormones receptors positive patients
• Either to reduce oestrogen level or interfere with receptor activation
• About 80% of cancers that are both ER+ and PR+ respond to
hormone manipulations
• Resistance still occurs
• Also, being recommended for prophylaxis in high risk patients
6/21/2019 19

20. MANAGEMENT
• Targeted therapy
• For HER2 positive cancers (13% of primary and 25% of metastatic
disease)
• e.g. Trastuzumab, Pertuzumab
6/21/2019 20

21. ROLE OF PRECISION MEDICINE
• Not only about personalized medicine
• It is all about accuracy and certainty
• Determination of individual genome
• To furnish proper treatment to the right person at the right time
6/21/2019 21

22. ROLE OF PRECISION MEDICINE
• To correct the ineffectiveness of the traditional “one-dose-fits-all”
system
• Risk of drug toxicity
• Treatment failure
• Unnecessary costs
• Encompasses breast cancer detection, prevention, diagnosis, and
treatment
6/21/2019 22

23. ROLE OF PRECISION MEDICINE
6/21/2019 23

24. ROLE OF PRECISION MEDICINE
• Screening diagnostic
• Traditionally, population based (age, mammographic appearance, biopsy
finding, genetic predisposition)
• Over-screening or under-screening
• Precision medicine approach
• Gene sequencing for profiling genetic risk, determination of screening
method and frequency
• Advantages; Less frequent use of unnecessary test, Lessen
underscreening
6/21/2019 24

25. ROLE OF PRECISION MEDICINE
• Diagnosis
• Biopsy
• Image guided (fluoroscopy, USS)
• Stereotactic localization
• Proper labelling of biopsy tissues
• Histology (immunohistochemistry, genetic mutation screening)
6/21/2019 25

26. ROLE OF PRECISION MEDICINE
• Surgical treatment
• Shifting from more radical approach
• Current innovations are designed to lessen impact of surgical
treatment
• Refining surgical techniques
• Omission of surgery in selected cases
• Breast conserving surgery is more favorable in luminal A
• Sentinel lymph node concept
• Axillary reverse mapping
6/21/2019 26

27. ROLE OF PRECISION MEDICINE
• Radiation therapy
• Traditionally, radiation was applied uniformly
• Conventional fractionation schemes that took 5 to 7 weeks
• Recently, hypofractionated regimens have been validated in several
randomized trial
• Accelerated partial breast irradiation and intraoperative
radiotherapy techniques have also been validated
• Brachytherapy is also advantageous
6/21/2019 27

28. ROLE OF PRECISION MEDICINE
• Intensity Modulated Radiation Therapy (IMRT)
• Use of gene assays of radioresponsiveness to predict which cancers
are more or less resistant to radiation.
• In over all;
• Increase access to breast conservation treatment
• Reduce omission of treatment
• Also reduce acute and late toxicity
6/21/2019 28

29. ROLE OF PRECISION MEDICINE
• Molecular subtypes and systemic therapy
• Various molecular subtypes have been identified through
immunohistochemistry
• Precision medicine in breast cancer was a product of these sub
groups
• However, further refinement of these classifications is the focus of
current basic science and clinical research
6/21/2019 29

30. ROLE OF PRECISION MEDICINE
• A variety of multigene assays are in clinical use or under
investigation, which further define the molecular characteristics of
the cancers’ dominant biologic pathways
• Clinically the gene assay is being used to guide recommendations on
the efficacy of systemic chemotherapy in addition to hormonal
therapy
6/21/2019 30

31. ROLE OF PRECISION MEDICINE
• All luminal cancers should be treated by endocrine therapy
• The majority of luminal A tumors, except those with high risk of
relapse, require no chemotherapy, while luminal B HER−
tumors need endocrine therapy and chemotherapy for the
majority of cases
6/21/2019 31

32. CHALLENGES OF PRECISION MEDICINE
• Genetic diagnostic facilities not readily available
• Tumour heterogeneity
• Availability of targeted therapy
• Reluctance in adopting the practice of precision medicine
6/21/2019 32

33. CONCLUSIONS
• Precision medicine is the current standard of care in oncology
• The ultimate aim of precision medicine in the contemporary therapy
of breast cancers is to enable clinicians to accurately and efficiently
identify the most effective preventive or therapeutic intervention for
a specific patient
• Several challenges must be overcome before this flood of profile data
is successfully translated into clinical utilities for patients with breast
cancer
6/21/2019 33

34. CONCLUSIONS
• Medical educational institutions should prepare the next
generation of physicians to use and interpret personal genetic
information appropriately and responsibly
• Finally, public and private insurers need to evaluate the clinical and
economic utility of personalized drugs and devices to facilitate
accessibility
6/21/2019 34

35. REFERENCES
• Alastair M. Thompson, et al.; Disorders of the Breast, in Essential
Surgical Practice, 5th ed. 2015; 17:384-411
• Ali Bettaieb, et al; Precision Medicine in Breast Cancers: Reality or
Utopia? in Journal of Translational Medicine (2017) 15:139
• Carmen W. H. Chan, et al; Novel Strategies on Personalized Medicine
for Breast Cancer Treatment: An Update, in International Journal of
Molecular Science, 2017 November, 18, 2423
6/21/2019 35

36. REFERENCES
• Catherine C. Parker, et al; the Breast, in Schwartz’s Principles of
Surgery, 11th ed. 2019; 17:555-612
• Eleanor E. R. Harris; Precision Medicine for Breast Cancer: The Path to
Truly Individualized Diagnosis and Treatment, in International Journal
of Breast Cancer, 2018 May
• J. N. Clegg-Lamptey, et al; The Breast, in BAJA’s Principles and Practice of
Surgery including Pathology in the Tropics, 5th ed. Vol 1, 2015; 28:514-537
6/21/2019 36

37. REFERENCES
• Jane Lowe Meisel MD, et al; Evolution of Targeted Therapy in Breast
Cancer: Where Precision Medicine Began, in Journal of American
Society of Clinical Oncology 2018
• Nicolas Carels, et al; Toward Precision Medicine of Breast Cancer, in
Journal of Theoretical Biology and Medical Modelling (2016) 13:7
• Richard C. Sanisbury; The Breast, in Bailey and Love’s Short Practice of
Surgery, 27th ed. Vol 2, 2018; 53:871-882
6/21/2019 37

38. REFERENCES
• Sang-Hoon Cho, et al; Personalized Medicine in Breast Cancer: A
Systemic Review, in Journal of Breast Cancer, 2012
September;15(3):265-272
• Vahit Özmen; Pardigm Shift From Halstedian Radical Mastectomy to
Personalized Medicine, in Journal of Breast Health 2017; 13: 50-53
• Yoichi Naito, Tetsuya Urasaki; Precision Medicine in Breast Cancer, in
Journal of Chinese Clinical Oncology 2018;7(3):29
6/21/2019 38