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Mohammad Ammad Ud Din, Hania Liaqat, Ayesha Tayyab

The incidence rate of breast cancer (BC) is the highest in Pakistan among all Asian countries.1 In 2018 alone, 2.1 million cases were diagnosed, although the exact number is likely much higher due to poor reporting in rural areas and the lack of a formal national cancer registry.1,2 Over the last decade, multiple non-governmental organizations and large […]

Aromatase Inhibitors as Neoadjuvant Treatment in Elderly Patients with Locally Advanced Breast Cancer

Lucia Borgato, Antonella Brunello, Vittorina Zagonel, Tania Saibene, Silvia Michieletto
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Published Online: May 15th 2012 European Oncology & Haematology, 2012;8(3):184-8 DOI: https://doi.org/10.17925/EOH.2012.08.3.184
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1

Abstract

Overview

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

2

Article

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 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

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2

References

  1. Ferlay J, Shin HR, Bray F, et al., Estimates of worldwide
    burden of cancer in 2008: GLOBOCAN 2008, Int J Cancer,
    2010;127:2893–2917.

  2. Sader C, Ingram D, Hastrich D, Management of breast
    cancer in the elderly by complete local excision and
    tamoxifen alone, Aust N Z J Surg, 1999;69:790–3.

  3. Wanebo HJ, Cole B, Chung M, et al., Is surgical
    management compromised in elderly patients with breast
    cancer?, Ann Surg, 1997;225:579–86, discussion 586–9.

  4. Hutchins LF, Unger JM, Crowley JJ, et al.,
    Underrepresentation of patients 65 years of age or older in
    cancer-treatment trials, N Engl J Med, 1999;341:2061–7.

  5. Lewis JH, Kilgore ML, Goldman DP, et al., Participation of
    patients 65 years of age or older in cancer clinical trials,
    J Clin Oncol, 2003;21:1383–9.

  6. Talarico L, Chen G, Pazdur R, Enrollment of elderly
    patients in clinical trials for cancer drug registration:
    a 7-year experience by the US food and drug
    administration, J Clin Oncol, 2004;22:4626–31.

  7. Carlson RW, Moench S, Hurria A, et al., NCCN task force
    report: Breast cancer in the older woman, J Natl Compr Canc
    Netw, 2008;6(Suppl. 4):S1–25, quiz S26–7.

  8. Newman LA, Epidemiology of locally advanced breast
    cancer, Semin Radiat Oncol, 2009;19:195–203.

  9. Becker N, Breast cancer epidemiology. In: Jatoi I, Kaufman
    M (eds), Management of Breast Diseases, New York: Springer,
    2010;121–30.

  10. Anderson WF, Chu KC, Chang S, Inflammatory breast
    carcinoma and noninflammatory locally advanced breast
    carcinoma: distinct clinicopathologic entities?, J Clin Oncol,
    2003;21:2254–9.

  11. Semiglazov VF, Semiglazov VV, Dashian GA, et al., [Phase II
    clinical trial of neoadjuvant hormone therapy in
    comparison with chemotherapy of patients with breast
    cancer], Vopr Onkol, 2007;53:400–8.

  12. Wyld L, Garg DK, Kumar ID, et al., Stage and treatment
    variation with age in postmenopausal women with breast
    cancer: compliance with guidelines, Br J Cancer,
    2004;90:1486–91.

  13. Bergman L, van Dongen JA, van Ooijen B, van Leeuwen FE,
    Should tamoxifen be a primary treatment choice for
    elderly breast cancer patients with locoregional disease?,
    Breast Cancer Res Treat, 1995;34:77–83.

  14. Gazet JC, Ford HT, Gray R, et al., Estrogen-receptordirected
    neoadjuvant therapy for breast cancer: Results of
    a randomised trial using formestane and methotrexate,
    mitozantrone and mitomycin C (MMM) chemotherapy,
    Ann Oncol, 2001;12:685–91.

  15. Willsher PC, Robertson JFR, Jackson L, et al., Investigation
    of primary tamoxifen therapy for elderly patients with
    operable breast cancer, Breast, 1997;6:150–4.

  16. Macaskill EJ, Renshaw L, Dixon JM, Neoadjuvant use of
    hormonal therapy in elderly patients with early or locally
    advanced hormone receptor-positive breast cancer,
    Oncologist, 2006;11:1081–8.

  17. Chia YH, Ellis MJ, Ma CX, Neoadjuvant endocrine therapy
    in primary breast cancer: Indications and use as a
    research tool, Br J Cancer, 2010;103:759–64.

  18. Miller WR, Dixon JM, Endocrine and clinical endpoints of
    exemestane as neoadjuvant therapy, Cancer Control,
    2002;9:9–15.

  19. Coombes RC, Hall E, Gibson LJ, et al., A randomized trial of
    exemestane after two to three years of tamoxifen therapy
    in postmenopausal women with primary breast cancer,
    N Engl J Med, 2004;350:1081–92.

  20. Ellis MJ, Suman VJ, Hoog J, et al., Randomized phase II
    neoadjuvant comparison between letrozole, anastrozole,
    and exemestane for postmenopausal women with
    estrogen receptor-rich stage 2 to 3 breast cancer: Clinical
    and biomarker outcomes and predictive value of the
    baseline PAM50-based intrinsic subtype – ACOSOG Z1031,
    J Clin Oncol, 2011;29:2342–9.

  21. Thürlimann B, Keshaviah A, Mouridsen H, BIG 1-98:
    Randomized double-blind phase III study to evaluate
    letrozole (L) vs tamoxifen (T) as adjuvant endocrine
    therapy for postmenopausal women with receptorpositive
    breast cancer, Amer Soc Clin Oncol, 2005;511.

  22. Howell A, Cuzick J, Baum M, et al., Results of the ATAC
    (arimidex, tamoxifen, alone or in combination) trial after
    completion of 5 years’ adjuvant treatment for breast
    cancer, Lancet, 2005;365:60–2.

  23. Smith IE, Dowsett M, Ebbs SR, et al., Neoadjuvant
    treatment of postmenopausal breast cancer with
    anastrozole, tamoxifen, or both in combination: the
    immediate preoperative anastrozole, tamoxifen, or
    combined with tamoxifen (IMPACT) multicenter doubleblind
    randomized trial, J Clin Oncol, 2005;23:5108–16.

  24. Ellis MJ, Ma C, Letrozole in the neoadjuvant setting: the
    P024 trial, Breast Cancer Res Treat, 2007;105(Suppl. 1): 33–43.

  25. Eiermann W, Paepke S, Appfelstaedt J, et al., Preoperative
    treatment of postmenopausal breast cancer patients with
    letrozole: a randomized double-blind multicenter study,
    Ann Oncol, 2001;12:1527–32.

  26. Gibson L, Lawrence D, Dawson C, Bliss J, Aromatase
    inhibitors for treatment of advanced breast cancer in
    postmenopausal women, Cochrane Database Syst Rev,
    2009;(4):CD003370.

  27. Seo JH, Kim YH, Kim JS, Meta-analysis of pre-operative
    aromatase inhibitor versus tamoxifen in postmenopausal
    woman with hormone receptor-positive breast cancer,
    Cancer Chemother Pharmacol, 2009;63:261–6.

  28. Hind D, Wyld L, Beverley CB, Reed MW, Surgery versus
    primary endocrine therapy for operable primary breast
    cancer in elderly women (70 years plus), Cochrane Database
    Syst Rev, 2006;(1):CD004272.

  29. Mouridsen H, Gershanovich M, Sun Y, et al., Superior
    efficacy of letrozole versus tamoxifen as first-line therapy
    for postmenopausal women with advanced breast cancer:
    results of a phase III study of the international letrozole
    breast cancer group, J Clin Oncol, 2001;19:2596–606.

  30. Mouridsen H, Gershanovich M, Sun Y, et al., Phase III
    study of letrozole versus tamoxifen as first-line therapy of
    advanced breast cancer in postmenopausal women:
    Analysis of survival and update of efficacy from the
    international letrozole breast cancer group, J Clin Oncol,
    2003;21:2101–9.

  31. Eiermann W, Paepke S, Appfelstaedt J, et al., Preoperative
    treatment of postmenopausal breast cancer patients with
    letrozole: a randomized double-blind multicenter study,
    Ann Oncol, 2001;12:1527–32.

  32. Dixon JM, Love CD, Bellamy CO, et al., Letrozole as
    primary medical therapy for locally advanced and large
    operable breast cancer, Breast Cancer Res Treat,
    2001;66:191–9.

  33. De Laurentiis M, Arpino G, Massarelli E, et al., A metaanalysis
    on the interaction between HER-2 expression and
    response to endocrine treatment in advanced breast
    cancer, Clin Cancer Res, 2005;11:4741–8.

  34. Carlomagno C, Perrone F, Gallo C, et al., c-erb B2
    overexpression decreases the benefit of adjuvant
    tamoxifen in early-stage breast cancer without axillary
    lymph node metastases, J Clin Oncol, 1996;14:2702–8.

  35. Newby JC, Johnston SR, Smith IE, Dowsett M, Expression
    of epidermal growth factor receptor and c-erbB2 during
    the development of tamoxifen resistance in human breast
    cancer, Clin Cancer Res, 1997;3:1643–51.

  36. Ellis MJ, Coop A, Singh B, et al., Letrozole is more effective
    neoadjuvant endocrine therapy than tamoxifen for ErbB-1-
    and/or ErbB-2-positive, estrogen receptor-positive primary
    breast cancer: Evidence from a phase III randomized trial,
    J Clin Oncol, 2001;19:3808–16.

  37. Milla-Santos A, Milla L, Calvo N, et al., Anastrozole as
    neoadjuvant therapy for patients with hormonedependent,
    locally-advanced breast cancer, Anticancer Res,
    2004;24:1315–8.

  38. Dixon JM, Renshaw L, Bellamy C, et al., The effects of
    neoadjuvant anastrozole (arimidex) on tumor volume in
    postmenopausal women with breast cancer:
    a randomized, double-blind, single-center study,
    Clin Cancer Res, 2000;6:2229–35.

  39. Cataliotti L, Buzdar AU, Noguchi S, et al., Comparison of
    anastrozole versus tamoxifen as preoperative therapy in
    postmenopausal women with hormone receptor-positive
    breast cancer: the Pre-Operative “Arimidex” Compared to
    Tamoxifen (PROACT) trial, Cancer, 2006;106:2095–2103.

  40. Mustacchi G, Mansutti M, Sacco C, et al., Neo-adjuvant
    exemestane in elderly patients with breast cancer:
    a phase II, multicentre, open-label, Italian study, Ann Oncol,
    2009;20:655–9.

  41. Mlineritsch B, Tausch C, Singer C, et al., Exemestane as
    primary systemic treatment for hormone receptor positive
    post-menopausal breast cancer patients: A phase II trial of
    the Austrian breast and colorectal cancer study group
    (ABCSG-17), Breast Cancer Res Treat, 2008;112:203–13.

  42. Takei H, Suemasu K, Inoue K, et al., Multicenter phase II
    trial of neoadjuvant exemestane for postmenopausal
    patients with hormone receptor-positive, operable breast
    cancer: Saitama breast cancer clinical study group
    (SBCCSG-03), Breast Cancer Res Treat, 2008;107:87–94.

  43. Toi M, Saji S, Masuda N, et al., Ki67 index changes,
    pathological response and clinical benefits in primary
    breast cancer patients treated with 24 weeks of
    aromatase inhibition, Cancer Sci, 2011;102:858–65.

  44. Krainick U, Astner A, Jonat W, Wallwiener D, Phase II study
    to define safety and efficacy of exemestane as
    preoperative therapy for postmenopausal patients with
    primary breast cancer – final results of the German
    neoadjuvant aromasin initiative (GENARI), Breast Cancer Res
    Treat, 2003;82(Suppl. 1):S55.

  45. Tubiana-Hulin M, Becette V, Bieche I, et al., Exemestane as
    neoadjuvant hormonotherapy for locally advanced breast
    cancer: Results of a phase II trial, Anticancer Res,
    2007;27:2689–96.

  46. Semiglazov VF, Semiglazov VV, Ivanov VG, et al.,
    Exemestane (E) vs tamoxifen (T) as neoadjuvant endocrine
    therapy for postmenopausal women with ER+ breast
    cancer (T2N1-2, T3N0-1, T4N0M0), J Clin Oncol,
    2005;23(Suppl. 16):11S, Abstract 530.

  47. Barnadas A, Gil M, González S, et al., Exemestane as
    primary treatment of oestrogen receptor-positive breast
    cancer in postmenopausal women: a phase II trial,
    Br J Cancer, 2009;100:442–9.

  48. Krainick-Strobel UE, Lichtenegger W, Wallwiener D, et al.,
    Neoadjuvant letrozole in postmenopausal estrogen and/or
    progesterone receptor positive breast cancer: A phase
    IIb/III trial to investigate optimal duration of preoperative
    endocrine therapy, BMC Cancer, 2008;8:62.

  49. Brunello A, Monfardini S, Falci C, et al., Aromatase
    inhibitors as neoadjuvant treatment in elderly patients
    (>70 years) with locally advanced breast cancer:
    a monoinstitutional experience, Eur J Cancer,
    2011;47:S278–S279.

  50. Dixon JMJ, Renshaw L, Keys J, et al., Outcome of frail
    elderly patients treated with letrozole alone, Cancer Res,
    2010;70(24 Suppl.):175s, Abstract P1-12-06.

  51. Pal SK, Katheria V, Hurria A, Evaluating the older patient
    with cancer: understanding frailty and the geriatric
    assessment, CA Cancer J Clin, 2010;60:120–32.

  52. Albrand G, Terret C, Early breast cancer in the elderly:
    assessment and management considerations, Drugs Aging,
    2008;25:35–45.

  53. Balducci L, Yates J, General guidelines for the
    management of older patients with cancer, Oncology
    (Williston Park), 2000;14:221–7.

  54. Basso U, Falci C, Brunello A, et al., Prognostic value of
    multidimensional geriatric assessment (MGA) on survival
    of a prospective cohort of 880 elderly cancer patients,
    J Clin Oncol, 2011;29(Suppl.):Abstract 9065.

  55. Freyer G, Geay JF, Touzet S, et al., Comprehensive
    geriatric assessment predicts tolerance to chemotherapy
    and survival in elderly patients with advanced ovarian
    carcinoma: a GINECO study, Ann Oncol, 2005;16:1795–1800.

  56. Klepin H, Mohile S, Hurria A, Geriatric assessment in older
    patients with breast cancer, J Natl Compr Canc Netw,
    2009;7:226–36.

  57. Goldhirsch A, Wood WC, Coates AS, et al., Strategies for
    subtypesm – dealing with the diversity of breast cancer:
    highlights of the St. Gallen international expert consensus
    on the primary therapy of early breast cancer 2011,
    Ann Oncol, 2011;22:1736–47.

  58. Mustacchi G, Ceccherini R, Milani S, et al., Tamoxifen
    alone versus adjuvant tamoxifen for operable breast
    cancer of the elderly: long-term results of the phase III
    randomized controlled multicenter GRETA trial, Ann Oncol,
    2003;14:414–20.

  59. Olson JA Jr, Budd GT, Carey LA, et al., Improved surgical
    outcomes for breast cancer patients receiving
    neoadjuvant aromatase inhibitor therapy: Results from a
    multicenter phase II trial, J Am Coll Surg, 2009;208:906–14;
    discussion 915–6.

3

Article Information

Disclosure

The authors have no conflicts of interest to declare.

Correspondence

Lucia Borgato, Medical Oncology 1, Veneto Oncological Institute, IRCCS, Via Gattamelata 64, 35128 Padova, Italy. E: lucia.borgato@gmail.com

Received

2012-01-12T00:00:00

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