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

Thursday 7 February 2008 Agenda 09.45 Opening and welcome Tuygan Goeker 09.50 Welcome and introduction from the Undersecretary for Health Affairs, Ministry of Health, Oman HE Ahmed Al-Ghassani 10.00 Welcome from the Head of the Department of Medical Oncology, Royal Hospital, Ministry of Health, Oman Bassim Al Bahrani 10.05 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

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

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

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 0 2 4 6 8 10 12 14 Months PFS = progression-free survival; TTP = time to progression

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

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

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

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