1. Challenges for the treatment of breast cancer
Nick Thatcher
Christie Hospital NHS Trust Manchester, UK

2. Thursday 7 February 2008 Agenda
Opening and welcome Tuygan Goeker
Welcome and introduction from the Undersecretary for Health Affairs, Ministry of Health, Oman HE Ahmed Al-Ghassani
Welcome from the Head of the Department of Medical Oncology, Royal Hospital, Ministry of Health, Oman Bassim Al Bahrani
Medical oncology services in Oman Medhat Faris
10.15 Chair’s opening Nick Thatcher
10.20 A decade of success: trastuzumab in HER2-positive metastatic breast cancer Christian Jackisch
11.00 Innovation + strength = effective management for HER2-negative metastatic breast cancer David Miles
11.45 Treatment advances for early breast cancer: selecting patients for optimal outcome Marjorie Green
12.25 Discussion
12.40 Lunch

3. How are we addressing the challenges of MBC?
Molecular diagnostics
Effective cytotoxic agents
Managing side effects and pain
Improving outcomes
Rational combinations
Endocrine therapy
Overall survival
1975: 31 per 100,000 women died of breast cancer
2001: 26 per 100,000 women died of breast cancer
Screening: incidence of early breast cancer has increased, tumours being detected at earlier stages
Tumors: traditional risk assessments (nodal status) no longer primary consideration in treatment, tumors assessed by endocrine responsiveness
Chemotherapy: from CMF to anthracycline-containing regimens and newer agents (eg taxanes)
Aromatase inhibitors replacing tamoxifen as the endocrine treatment of choice
Elkin et al 2005; Goldhirsch et al 2005
Targeted therapy
Anti-angiogenic therapy
MBC = metastatic breast cancer

4. Patient and disease characteristics influence treatment choice in MBC
ER/PR
status
Disease-free interval
Anticipated side effects of treatment
Availability/ access to treatment
Choice of therapy
Patient
preferences
Previous
therapy
HER2
status
Visceral versus non-visceral
metastases
Patient
symptoms
ER = oestrogen receptor PR = progesterone receptor; HER2 = human epidermal growth factor receptor 2
Adapted from Beslija S, et al.
Ann Oncol 2007;18:215–25 4

5. Combination chemotherapy
Standard chemotherapy regimens for MBC have reached an efficacy plateau of around 9 months
Median PFS/TTP
9 months
Docetaxel Chan 1999
Doxorubicin Chan 1999
Monotherapy
Paclitaxel Seidman 2004
Vinorelbine Muñoz 2006
Doxorubicin + paclitaxel Jassem 2001
Capecitabine + docetaxel O’Shaughnessy 2002
Gemcitabine + paclitaxel Albain 2004
Combination chemotherapy
Fluorouracil + epirubicin Zielinski 2005
Gemcitabine + vinorelbine Muñoz 2006
Epirubicin + taxane Pacilio 2006
Months
PFS = progression-free survival; TTP = time to progression

6. How are we addressing the challenges of early breast cancer?
Earlier diagnosis
Better surgery
Revised risk classification
Improving outcomes
Better radiotherapy
New treatment modalities
Overall survival
1975: 31 per 100,000 women died of breast cancer
2001: 26 per 100,000 women died of breast cancer
Screening: incidence of early breast cancer has increased, tumours being detected at earlier stages
Tumors: traditional risk assessments (nodal status) no longer primary consideration in treatment, tumors assessed by endocrine responsiveness
Chemotherapy: from CMF to anthracycline-containing regimens and newer agents (eg taxanes)
Aromatase inhibitors replacing tamoxifen as the endocrine treatment of choice
Elkin et al 2005; Goldhirsch et al 2005
Aromatase inhibitors
New chemotherapy regimens

7. Treatment choice in early breast cancer depends on numerous factors
Lymph node status
ER/PR
status
Availability/access
to treatment
Choice of therapy
Anticipated side effects of treatment
Tumour stage
Patient
preferences
Tumour grade
HER2
status 7

8. Breast cancer: what are the challenges that we face in the next decade?
How best to tailor treatment to the individual patient
identification of suitable biomarkers to select patients for therapy
Determine whether sequential or combination treatment approaches offer optimal management of breast cancer
Identify new therapeutic approaches or therapeutic combinations
to reduce recurrence in early disease
to further improve overall and PFS in the metastatic setting

9. Potential therapeutic targets increase as knowledge of cancer grows
Unlimited cell growth
Insensitivity to antigrowth signals
Reduced sensitivity to apoptosis
Limitless replicative potential
Development and maintenance of vasculature (angiogenesis)
Invasion and metastasis
Cancer
Most human tumours require
deregulation of all of these processes
Hanahan D, et al. Cell 2000;100:57–70