Developments in Breast Cancer Treatment

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Developments in Breast Cancer Treatment
Professor Brian LeylandJones McGill University,
Canada
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Breast cancer the facts

• Second leading cause of cancer deaths in women
• More than a million cases of breast cancer are
• diagnosed each year
• Causes of breast cancer
• Exact causes not known
• Risk factors include
• Family history of breast cancer
• Early puberty
• Late childbearing
• Obesity
• Lifestyle factors e.g. smoking
• Age (over 60 years)

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Metastatic breast cancer
1975
1980
1985
1990
1995
'00
Future
Pre 1970
Surgery, Radiotherapy Chemotherapy
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Lumpectomy
Mastectomy
Radiotherapy
Chemotherapy
Breast Cancer Treatments
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Why are treatments combined?

• Cancer usually treated with several therapies
  because
• Disease is fought on two or more levels as one
• treatment may be more effective at a certain
  stage
• of cancer than another
• One treatment may enhance the
• effectiveness of another

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Improved chemotherapy

• Oral form of chemotherapy e.g. Xeloda
  (capecitabine)
• A smart tumor-activated tablet, targeting
• the tumor
• Increases survival
• Does not cause complete hair loss
• More convenient than injections

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Targeted action of Xeloda
Intestine
Liver
Tumour
Xeloda swallowed by patient
Enzyme action on Xeloda
Special Enzyme
Cancer killing 5-FU
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Addition of Xeloda to Taxotere extends survival
1.0 0.8 0.6 0.4 0.2 0.0
Xeloda Taxotere Taxotere
Estimated probability
11.5
14.5
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28
Months
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Can the benefits of Xeloda Taxotere be seen
earlier?
RANDO MIS ATION
Taxotere alone
Chemotherapy (AC)
Chemotherapy (AC)
Xeloda plus Taxotere
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Improvements in chemotherapy continue

• Trials are ongoing to investigate Xeloda both
  as
• a single treatment and in combination with
  other
• drugs
• As first line treatment in metatastatic breast
  cancer
• In early breast cancer, following surgery and
  chemotherapy
• In early breast cancer before surgery

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1st generation targeted therapies
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Hormonal therapy

• Tamoxifen
• Most commonly prescribed hormone therapy for
  breast cancer, used for the last 30 years
• Blocks oestrogen receptors which stimulate cancer
  cell growth
• Aromatase inhibitors
• Lowers amount of oestrogen produced by the body
  therefore less available for cancer cell growth
• Used in postmenopausal women
• Preliminary trial results suggest aromatase
  inhibitors may displace tamoxifen for adjuvant
  therapy of breast cancer

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Anastrozole more effective than tamoxifen (ATAC
Trial)
50
40
Number of cases where cancer spread to other
breast
30
20
10
0
tamoxifen
anastrozole
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Hormonal therapy

• Post-Menopausal
• Three aromatase inhibitors have shown promising
  results in post-menopausal women
• Arimidex (anastrozole)
• Femara (letrozole)
• Aromasin (exemestane)

• Pre-Menopausal
• In pre-menopausal women, GnRH analogues

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2nd generation targeted therapies
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Herceptin (trastuzumab)

• Biological treatment for aggressive
  (HER2-positive) breast cancer
• Blocks activity of HER2 gene, which is involved
  in cell growth control
• Targets cancerous cells, without harming healthy
  cells
• Knowledge of HER2 status is essential to
  determine whether treatment with Herceptin is
  appropriate

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Herceptin in advanced breast cancer

• In combination with standard chemotherapy
  (taxanes)
• As a single agent when chemotherapy is not
  appropriate
• Improved and lasting responses
• Increased survival rates
• Maintained quality of life

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Benefits of treatment with Herceptin
0 5 10 15 20 25 30 35 40 45 50
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Herceptin in early breast cancer

• Goal of treatment in early (adjuvant) breast
  cancer is to increase the number of cured
  patients
• Drugs that work in the advanced setting are
  usually effective in the early setting as well
• HER2-positivity defines aggressive disease in
  both early and advanced setting
• Four large phase III trials (gt13,000 patients)
• Excluding HERA (HERceptin Adjuvant)

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Fighting complications from breast cancer and
its treatment
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Fighting complications from breast cancer

• Bone Metastases
• Cancerous cells from the original tumour can
  spread through the body, preferably to the bone
• This is called Metastatic Bone Disease (MBD). MBD
  is a common complication of advanced cancer
• In breast cancer approximately 80 patients
  develop bone metastases

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Fighting complications from breast cancer

• Bisphosphonates
• Bisphosphonates are commonly used to treat MBD.
• Bondronat (ibandronate), a bisphosphonate,
• Provides sustained reduction in bone pain
• Limits bone fractures and breaks
• Has a potential survival benefit
• Renal safety is comparable to placebo

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BondronatPain reduction from day 3 on
Day 3
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Bondronat

• In 2003 Bondronat has received European approval
  for the prevention of skeletal events in patients
  with breast cancer and bone metastases
• Most European countries have launched Bondronat
  to date. New countries worldwide will continue to
  launch as soon as local regulatory processes are
  satisfied

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Anaemia is under-recognised and under-treated

• 60 of patients with cancer suffer from anaemia
• Only 40 of these anaemic patients receive
  treatment
• Fatigue is the most common symptom
• associated with cancer related anaemia
• Fatigue can be relieved so patients should
  discuss this with their doctor!

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Fatigue affects the lives of cancer patients
more than pain
Proportion of patients and oncologists reporting
that fatigue and/or pain affects the patients
daily life
Patients
Fatigue
Oncologists
Pain
Both
0
10
20
30
40
50
60
70
Respondents ()
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Anaemia can be conquered

• NeoRecormon (epoetin beta) effectively corrects
• and prevents anaemia, which leads to
  significant
• improvements in patients quality of life

1.5
NeoRecormon
Control
1.0
Mean change in quality of life
0.5
0.0
0.5
Weeks 34
Weeks 68
Week 12
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Anaemia can be conquered

• NeoRecormon is approved for convenient Once
  -Weekly use in haematologic tumours
  (non-Hodgkins lymphoma, multiple myeloma,
  chronic lymphocytic leukaemia)
• Roche is investigating Once-Weekly dosing and its
  impact on survival with NeoRecormon in patients
  with metastatic breast cancer (BRAVE study)

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CERA Continuous Erythropoietin Receptor Activator

• An innovative erythropoiesis-stimulating agent
• The first continuous erythropoietin receptor
  activator developed for the treatment of anaemia
• Currently in phase II development to provide
  rapid, sustained and stable correction of anaemia
  at extended dosing intervals in oncology

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Fighting complicationsfrom cancer treatments

• Nausea and Neutropenia
• Nausea and vomiting (emesis) affect about 70 of
  patients
• Can combat this with anti-emetic drugs e.g.
  Kytril (granisetron)
• Neutropenia (reduced white blood
• cell count which may increase risk of
• infection) is a common chemotherapy
• induced effect
• Medication e.g. Neupogen (filgrastim)
• means treatment can proceed as
• scheduled and the risk of potentially
• life-threatening infections is reduced

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Conclusion a promising future

• Molecular targets
• An evolving understanding of the biological basis
  of breast cancer is likely to help identify
  molecular targets for which to develop novel
  treatments
• Targeted therapies
• Have shown exciting results and are likely to
  play an increasing role in the systemic
  management of breast cancer, at an earlier stage
  of disease