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Breast Cancer Aromatase Inhibitors as Neoadjuvant Treatment in Elderly Patients with Locally Advanced Breast Cancer Lucia Borgato, 1 Antonella Brunello, 1 Vittorina Zagonel, 2 Tania Saibene 3 and Silvia Michieletto 3 1. Oncologist, Medical Oncology Unit 1; 2. Director of Medical Oncology, Medical Oncology Unit 1; 3. Surgeon, Surgical Oncology Unit, Veneto Oncological Institute, IRCCS Padova, Italy Abstract Pre-operative volume reduction of locally advanced breast cancers (LABC) is an issue of great importance when approaching elderly women, who often present with extensive disease along with a burden of co-morbidity which increases the risk of complications and mortality from treatment. A comprehensive geriatric evaluation is a necessary requirement before recommending any treatment in older patients. Endocrine treatment in the neoadjuvant setting allows disease control and downstaging of tumours and is fairly well tolerated. Tamoxifen has been the mainstay of endocrine therapy for patients unable to undergo surgery, but resistance eventually develops. Aromatase inhibitors (AIs) are superior to tamoxifen in this setting, with greater downstaging of the tumour and disease control. AIs are now the treatment of choice in elderly patients with oestrogen receptor-positive breast cancer who are being considered for neoadjuvant endocrine therapy. There are some data that definitive treatment with an AI for LABC in unfit patients may guarantee long-term control of disease. Keywords Neoadjuvant therapy, endocrine treatment, breast cancer, elderly patients, aromatase inhibitors Disclosure: The authors have no conflicts of interest to declare. Received: 12 January 2012 Accepted: 24 January 2012 Citation: European Oncology & Haematology, 2012;8(3):184–8 Correspondence: Lucia Borgato, Medical Oncology 1, Veneto Oncological Institute, IRCCS, Via Gattamelata 64, 35128 Padova, Italy. E: lucia.borgato@gmail.com Breast cancer is the most common type of cancer in the female population worldwide, with an estimated incidence of more than 1.3 million new cases and 458,000 deaths in 2008. 1 Up to 30 % of breast cancers are reported to occur in women aged 70 years or over; 2,3 however, due to the under-representation of elderly patients in cancer clinical trials, 4,5 there are few data to help define the optimum treatment for these patients. A retrospective study of trials submitted to the US Food and Drug Administration (FDA) for drug approval in the years 1995–2002 showed that the percentage of women aged 65 years and over enrolled in clinical trials of hormonal therapy for breast cancer closely matched the proportion of breast cancer patients of the same age in the US, but inclusion rates in chemotherapy trials are much lower. 6 Although the elderly population is heterogeneous, 65 years does not seem to be the optimum threshold for defining an elderly patient, and most of the members of a National Comprehensive Cancer Network (NCCN) taskforce for breast cancer in the elderly agreed to set 70 years as a better cut-off point. 7 Locally advanced breast cancer (LABC) refers to patients diagnosed with large primary cancers and/or regional adenopathy. Its frequency has diminished greatly thanks to screening mammography and early detection. However, there are some populations, such as women in low-income countries or elderly women in industrialised countries, who continue to experience disproportionately high breast cancer mortality rates, as they are at an increased risk of having locally advanced disease at diagnosis. Data show that the frequency of 184 LABC is indeed higher in elderly women, with 10 % of cases occurring in patients younger than 40 years but 30 % occurring in patients aged 70 years or over. 8–10 In oestrogen receptor-positive (OR+) tumours, hormonal therapy has been shown to have only minor toxicity and similar activity compared to chemotherapy, 11 which makes it a very attractive option for elderly patients with locally advanced or extensive disease not amenable to breast-conserving surgery (BCS). Wyld et al. reported that 40 % of women with breast cancer aged 70 years or over were receiving pre-operative endocrine therapy in the UK in 2002. 12 Tamoxifen has been the mainstay of endocrine therapy for OR+ breast cancer for more than 30 years, beyond being the first drug to be used in the neoadjuvant setting for elderly or frail patients unable to undergo surgery or more toxic therapies. 13–15 It has been demonstrated that, for post-menopausal and elderly women with large breast tumours (more than 3 cm) and expression of oestrogen receptors, the administration of a third-generation aromatase inhibitor (AI) for some months results in a more consistent tumour volume reduction than is obtained with tamoxifen, 16–18 allowing BCS to be performed in most cases. 19 There are three approved and currently available hormonal agents: the non-steroidal AIs letrozole and anastrozole and the steroidal AI exemestane. So far, all AIs have been demonstrated to be more effective than tamoxifen and, in a recently published randomised © TOUCH BRIEFINGS 2012