SYSTEMIC MANAGEMENT OF BREAST CANCER

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SYSTEMIC MANAGEMENT OF BREAST CANCER

• Dr Alice Musibi
• Medical Oncologist
• KENYATTA NATIONAL HOSPITAL

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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

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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

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BREAST CANCER TREND IN NAIROBI
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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

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Out-come

• Poor overall results of survival
• Frequent local recurrence and distant metastases
• Treatment worse than disease
• Concept of quality life
• Womens insistence for breast preservation

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Treatment

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

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Systemic therapy

• 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

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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

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Adjuvant systemic therapy

• 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 1995332901)

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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

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Choice of treatment regime

• 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

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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)

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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

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Metastatic breast cancer (MBC)

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

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MBC -2

• 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.
• especially in patients with only bone metastases
• (JCO, Vol 24, No 18 (June 20), 2006 pp.
  2743-2749)

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Many of our women are presenting like this!!
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Language
Lack of medical insurance
Poverty
Fears
False beliefs
Fatalism
Lack of information
Knowledge
Attitude
Behavior
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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

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Risk factors

• 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)

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Recommendations
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Recommendations

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

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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

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