1. SYSTEMIC MANAGEMENT OF BREAST CANCER Dr Alice Musibi Medical Oncologist KENYATTA NATIONAL HOSPITAL

2. BREAST CANCER INTRODUCTION Is one of the deadliest and most common cancers ailing women all over the world Is one of the deadliest and most common cancers ailing women all over the world In Australia 1 in 13 women will develop ca breast at sometime in her life In Australia 1 in 13 women will develop ca breast at sometime in her life In USA 215,990 women will be found to have invasive ca breast in 2004 In USA 215,990 women will be found to have invasive ca breast in 2004 More common in older than younger women with average age of diagnosis of 64 years More common in older than younger women with average age of diagnosis of 64 years

3. CANCER IN NAIROBI (KENYA) A total of 2,716 cases were registered, comprising of 1246 men and 1470 women between 2000-2003 A total of 2,716 cases were registered, comprising of 1246 men and 1470 women between 2000-2003 Breast cancer was leading with 22.9% followed by cervical cancer with 19.3% Breast cancer was leading with 22.9% followed by cervical cancer with 19.3% The mean age of diagnosis was 45 years The mean age of diagnosis was 45 years

5. BREAST CANCER TREND IN NAIROBI

9. Treatment Local management Local management –18th century – Louis Petit of France - total mastectomy and excision of axillary's lymph nodes –1895 - William Halstead - popularized radical mastectomy –Harvey Cushing - extended radical - internal mammary chain excised after splitting the mediastinum –1923-1937 - local excision and radium needles. –Conventional radiotherapy

10. Out-come Poor overall results of survival Poor overall results of survival Frequent local recurrence and distant metastases Frequent local recurrence and distant metastases Treatment worse than disease Treatment worse than disease Concept of quality life Concept of quality life Women’s insistence for breast preservation Women’s insistence for breast preservation

11. Treatment Multidisciplinary Multidisciplinary –Surgery –Chemotherapy, hormonal therapy, immunotherapy –Radiation therapy –Palliative therapy –Occupational/physioth erapy Lymph edema therapy –etc

12. Systemic therapy Types Types –Primary induction therapy –Neo-adjuvant chemotherapy –Adjuvant chemotherapy –Palliative Associated with Associated with – a decrease in the death rate –prolonged relapse- free survivals Acute and chronic side effects Acute and chronic side effects

13. Systemic therapy- combination –Maximum cell kill –Tolerable range of toxicity for each drug –Broader range of interaction between drugs and tumor cells –Less chance of developing cellular drug resistance

14. Adjuvant systemic therapy For patients at risk of disease recurrence after treatment of primary tumior For patients at risk of disease recurrence after treatment of primary tumior Known tumor or maximum bulk should be removed Known tumor or maximum bulk should be removed Chemotherapy started as soon as possible post op Chemotherapy started as soon as possible post op Effective chemotherapy must be used at maximally tolerated doses Effective chemotherapy must be used at maximally tolerated doses Usually for a period (6-8 cycles) Usually for a period (6-8 cycles) Milan CMF trial (overview)- Milan CMF trial (overview)- –CMF vs. surgery alone Relapse free survival- median 19.4 –benefits in pre-menopausal patients (Bonnadona G et al N Engl. J Med 1995;332;901)

15. Neo-adjuvant chemotherapy Systemic therapy given preoperatively Systemic therapy given preoperatively –Advantage Early exposure to micro- metastasis Early exposure to micro- metastasis Tumor response measurable Tumor response measurable Reduce tumor bulk so less extensive surgery Reduce tumor bulk so less extensive surgery –Disadvantage May delay surgery in tumors which may turn out to be chemo-resistant May delay surgery in tumors which may turn out to be chemo-resistant May obscure real extent of disease May obscure real extent of disease

16. Choice of treatment regime Depends on prognostic factors for recurrence/survival Depends on prognostic factors for recurrence/survival –Age –tumour size, –nodal status –histologic grade, –hormone receptors, –??Her-2/neu over- expression (about 40% of breast cancers) –?Lymphatic/vascular invasion) –Estimated benefit of therapy in terms of absolute risk reduction of relapse and death. –Estimation of the toxicity associated with therapy –[COST]

18. Prognosis Five year relative survival is dependent on the stage of breast cancer at diagnosis Five year relative survival is dependent on the stage of breast cancer at diagnosis StageSurvival rate 0100% I 98% IIA 88% IIB 76% IIIA 56% IIIA 56% IIIB 49% IIIB 49% IV 16% *(Overview American Cancer Society –2003)*

19. Post-surgical Mx of breast cancer (KNH) [1989-2000] Surgery-374 patients Surgery-374 patients Chemotherapy Chemotherapy –Adjuvant -22 (5.8%) –Metastatic-21 Radiotherapy Radiotherapy –Adjuvant-46 (12.4%) –Palliation-53 Hormone therapy (tamoxifen)-126 (33.7%) Hormone therapy (tamoxifen)-126 (33.7%) East African Medical Journal: 2002 79(3): 156-162 East African Medical Journal: 2002 79(3): 156-162

20. Metastatic breast cancer (MBC) MBC is considered an incurable disease. MBC is considered an incurable disease. majority of patients with MBC do not survive beyond 5 years after diagnosis. majority of patients with MBC do not survive beyond 5 years after diagnosis. Treatment usually is palliative with systemic therapy including Treatment usually is palliative with systemic therapy including – chemotherapy –hormonal treatment –biologic therapy (e.g. Trastuzumab) Pain control Pain control

21. MBC -2 The surgery of breast tumors with distant metastases has been indicated to The surgery of breast tumors with distant metastases has been indicated to –prevent local complications (toilet surgery) –Removal of the metastatic lesions in selected patients (single brain, liver, bone or pulmonary lesions). Surgery of the primary tumor can actually improve survival of metastatic breast cancer. Surgery of the primary tumor can actually improve survival of metastatic breast cancer. – especially in patients with only bone metastases (JCO, Vol 24, No 18 (June 20), 2006: pp. 2743-2749) (JCO, Vol 24, No 18 (June 20), 2006: pp. 2743-2749)

22. Many of our women are presenting like this!!

23. Lack of information Poverty Fears Fatalism Lack of medical insurance False beliefs Language KnowledgeAttitudeBehavior

24. Risk factors Normal lifetime risk of developing breast cancer in white women is 1 in 8 or 9 Normal lifetime risk of developing breast cancer in white women is 1 in 8 or 9 There is no family history in over 75% of patients There is no family history in over 75% of patients Most women with breast cancer do not have any identifiable risk factors Most women with breast cancer do not have any identifiable risk factors

25. Risk factors Age Age Ethnicity – more cancer in white women but more mortality in blacks Ethnicity – more cancer in white women but more mortality in blacks Family history of breast cancer Family history of breast cancer Previous history of personal breast cancer gives 1-2% risk of contralateral breast cancer/year Previous history of personal breast cancer gives 1-2% risk of contralateral breast cancer/year Previous history of ovarian or endometrial cancers Previous history of ovarian or endometrial cancers Prolonged estrogen exposure Prolonged estrogen exposure –Early menarche (under age 12)/late menopause (after age 50) –Late first pregnancy/nulliparous/no full- term pregnancy (1.5 times higher incidence) –Hormone replacement therapy especially high estrogen based pills but more so the combined pills Genetic predisposition Genetic predisposition BRCA1 (85%) BRCA2 p53 gene – 1% in women with cancer of breast below 40 years Lifestyle factors Lifestyle factors –Dietary factors – particularly increased fat consumption –Obesity –Lack of exercise –Alcohol consumption –Smoking (???) Prior Radiation therapy Prior Radiation therapy Atypical epithelial hyperplasia of the breast Atypical epithelial hyperplasia of the breast Fibrocystic disease with proliferative changes Fibrocystic disease with proliferative changes Lobular carcinoma in situ (LCIS) Lobular carcinoma in situ (LCIS)

26. Recommendations Government- Acknowledge the volcano in cancer PolicyNational guidelines Clinical practice guidelines

27. Recommendations Clinical breast examination Clinical breast examination U/S U/S Mammography Mammography MRI scans of breast MRI scans of breast Genetic mapping Genetic mapping

28. Recommendations Facilities Facilities –Cancer centres – 1 (KNH) –Laboratories ordinary histopathology immunohistochemical studies –KEMRI mainly research purposes –Private hosp (Nbi, AKUH) – all send the specimens to SA or Italy –Radiotherapy units – 2

29. MEDICAL ONCOLOGY RADIOTHERAPY PATHOLOGY RADIOLOGY SURGEONS AND ORGAN SPECIALISTS