1. Treatement of Metastatic Breast Cancer: A Long and Winding Road Slovenian Experience
Simona Borštnar, MD, PhD
Division of Medical Oncology
Head of breast cancer multidisciplinary board
President of Slovenian Senologic Society
Skopje, 24.October 2017

2. Breast cancer statistic
WORLD
~522,000
BC deaths annually
25.1%
All cancers in women
14.7%
Cancer deaths
in women
~1.67m new BC cases annually
Includes:
458,718 women in Europe (28.6%)2
232,714 women in the US (29.9%)2
Includes:
131,347 deaths in Europe (16.9%)2
43,909 deaths in the US (15.0%)2
SLOVENIA ~
BC deaths annually
new BC cases annually
20.5%*
All cancers in women
14.6%*
Cancer deaths
in women
Data 2014: N=1288
Data 2014: N= 379

3. Age standardised incidence and mortality rates for breast cancer in Slovenia

4. Incidence of early, primary and secondary metastatic Breast cancer in Slovenia
All BC patients
Incidence ≈1250
Prevalence ≈16000
Primary metastatic (6%)
N ≈90 (per year)
Secondary Metastatic BC (25%-30%)
N ≈300

5. Adjuvant systemic therapy
Why is adjuvant systemic treatment important?
Adjuvant systemic therapy
surgery
, Fisher “demonstrated that the regional lymph nodes were not a barrier to the dissemination of tumor cells, as postulated earlier, but were routes traversed by tumor cells to gain access to the circulating bloodstream and lymphatic system. Out of this basic work on cancer metastasis came a new model for the management of breast cancer based on the premise that the disease is systemic from its inception.
Adapted fromAdjuvant!online.com

6. Common Breast Cancer Metastasis Sites
When cancer cells break away from a tumor, they can travel to other areas of the body through the bloodstream or the lymphatic system.

7. Facts About Metastatic Breast Cancer
20% to 30% of people initially diagnosed with early stage disease will develop metastatic breast cancer.
Early detection does not guarantee a cure.
Metastatic breast cancer can occur 5, 10 or 15 years after primary diagnosis and successful treatment checkups and annual mammograms.

8. Clinical Breast Cancer Subsets Defined by IHC in metastatic disease

9. Treatment options
Chemotherapy
Hormonal therapy
Anti-HER2 therapy

10. The Goals of Treatment of Metastatic Breast Cancer
Maximizing the quality of life
Prevention and palliation of symptoms
Prolongation of survival

11. Treatment of Breast Cancer
Treatment for metastatic breast cancer is lifelong, characterized by remissions and relapses.
ST 1
ST 5
ST 2
ST 3
ST 4 PT
ST= systemic treatment , PT= palliative treatment

12. Hormonal therapy Most important treatment in HR positive BC
Estrogen receptor positive breast cancer need hormones to grow
Hormone therapies can work by either
Stopping hormones being made
Preventing the hormone reaching the cancer cell
Estradiol
Hormonal therapy is a treatment that adds, blocks, or removes hormones. For certain conditions (such as diabetes, hypothirosis or menopause), hormones are given to adjust low hormone levels. The principe of hormonal therapy in cancer is actualy opposite.
Cancers that are hormone sensitive or hormone dependent need hormones to grow. So stopping the hormone reaching the cancer cells may either slow down or stop the growth of the cancer. Hormone therapies can work by either stopping hormones being made or preventing the hormone reaching the cancer cell.
Hormone-sensitive breast cancer cells contain proteins known as hormone receptors that become activated when hormones bind to them. The activated receptors cause changes in the expression of specific genes, which can lead to the stimulation of cell growth.
Gene transcription
Estrogene receptor
Proliferation

13. Types of hormonal therapies
Drug
Route of administration, dose
Aromatase inhibitors
Anastrozole (Arimidex)
P.O.(1x1 mg)
Letrozole (Femara)
P.O.(1x 2,5 mg)
Exemestane (Aromasin)
P.O. (1x 25 mg)
Antiestrogenes
Tamoxifen (Nolvadex)
P.O.(2 x 10 mg)
Fulvestrant (Faslodex)
500 mg I.M. on Days 1 and 15 of Cycle 1 and Day 1 of each cycle thereafter)
Gonadotropin-reeasing hormon agonist
Goserelin (Zoladex)
S.C.(3,6 mg every 4 weeks)
Progestin
Megestrol acetate (Megace)
P.O.(1 x 160 mg)

14. HR+ HER2- mBC: Response to endocrine therapy
Sequential endocrine therapy provides high-quality survival for many of HR+ HER2- mBC patients
Eventually, tumors become endocrine-resistant R E S I T A N C
40-50%
30%
25%
15%
Unfortunately, the majority of patients with HR+ advanced breast cancer will ultimately progress despite endocrine therapy thus, resistance is a major clinical problem.
1. line
2. line
3. line
4. line

15. Targeted treatments in HR+ mBC
m-TOR INHIBITOR (everolimus)
CDK 4/6 INHIBITORS
(palbociclib, ribociclib, abemaciclib)

16. Chemotherapy
Cytotoxic chemotherapy works primarily through the inhibition of cell division.
In addition to cancer cells, other rapidly dividing cells (e.g., hair, gastrointestinal epithelium, bone marrow) are affected by these drugs. 

17. Chemotherapy for metastatic breast cancer
Mono- or poli-chemotherapy
anthracylines
docetaxel
paclitaxel
nab-paclitaxel
capecitabine
cyclophosphamide
cisplatin
carboplatin
gemcitabine
vinorelbine
eribulin
methotrexate
5-FU
liposoma doxorubicine

18. Forms and routes of chemotherapy administration
Peripheral vein
Port-a-cath

19. HER2 positive breast cancer
HER2 overexpression ~ % of breast cancers
normal ~ 25,000-50,000 HER2 receptors
Overexpression of HER2 receptors (10-100x)
do ~ 2,000,000 receptors HER2
Pegram MD, et al. Cancer Treat Res. 2000;103:57-75.
Ross JS, et al. Am J Clin Pathol. 1999;112(suppl 1):S53-S71.
Slamon DJ, et al. Science. 1987;235:
excessive cell division ad proliferation

20. Dr. Dennis Slamon

21. Anti-HER 2 Therapies trastuzumab pertuzumab T-DM1 lapatinib HER3 HER2

22. Availability of anti- HER2 drugs
FDA
EMA
Slovenija
Herceptin mBC
September 1998
August 2000
2001
Herceptin eBC
November 2006
May 2006
July 2005
Perjeta mBC
June 2012
March 2013
October 2014
Kadcyla mBC
February 2013
November 2013
May 2016
eBC=early breast cancer ; mBC=metastatic breast cancer

23. New Treatments (not registered yet)
PARP INHIBITOR (olaparib)
BRCA 1/2 MUTATION PRESENT
CHECKPOINT INHIBITORS
TNBC

24. Publications for Patients

25. Colaboration with patients associations

26. CONCLUSIONS
Approximately 20% to 30% of woman initially diagnosed with early stage disease will develop metastatic breast cancer.
The goals of treatment are: maximizing the quality of life, prevention and palliation of symptoms, and prolongation of survival.
Treatment is lifelong, characterized by remissions and relapses.
The trust and collaboration between oncologist and patient is crucial for successful treatment.

27. THANK YOU!