SYSTEMIC MANAGEMENT OF BREAST CANCER

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 • 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 • 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 • Breast cancer was leading with 22.9% followed by cervical cancer with 19.3% • The mean age of diagnosis was 45 years

5. BREAST CANCER TREND IN NAIROBI

9. Treatment • 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 • Frequent local recurrence and distant metastases • Treatment worse than disease • Concept of quality life • Women’s insistence for breast preservation

11. Treatment • Multidisciplinary • Surgery • Chemotherapy, hormonal therapy, immunotherapy • Radiation therapy • Palliative therapy • Occupational/physiotherapy • Lymph edema therapy • etc

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

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. For patients at risk of disease recurrence after treatment of primary tumior Known tumor or maximum bulk should be removed Chemotherapy started as soon as possible post op Effective chemotherapy must be used at maximally tolerated doses Usually for a period (6-8 cycles) 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) Adjuvant systemic therapy

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

16. 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] Choice of treatment regime

18. Prognosis • Five year relative survival is dependent on the stage of breast cancer at diagnosis Stage Survival rate 0 100% I 98% IIA 88% IIB 76% IIIA 56% IIIB 49% IV 16% *(Overview American Cancer Society –2003)*

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

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

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

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

23. Language Lack of medical insurance Poverty Fears False beliefs Fatalism Lack of information Knowledge Attitude Behavior

24. Risk factors • 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 • Most women with breast cancer do not have any identifiable risk factors

25. Age Ethnicity – more cancer in white women but more mortality in blacks Family history of breast cancer Previous history of personal breast cancer gives 1-2% risk of contralateral breast cancer/year Previous history of ovarian or endometrial cancers 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 BRCA1 (85%) BRCA2 p53 gene – 1% in women with cancer of breast below 40 years Lifestyle factors Dietary factors – particularly increased fat consumption Obesity Lack of exercise Alcohol consumption Smoking (???) Prior Radiation therapy Atypical epithelial hyperplasia of the breast Fibrocystic disease with proliferative changes Lobular carcinoma in situ (LCIS) Risk factors

26. Recommendations

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

28. Recommendations • 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