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Journal of General Internal Medicine
Published in: Journal of General Internal Medicine 2/2009

01-11-2009 | Review

The Expanding Use of Third-Generation Aromatase Inhibitors: What the General Internist Needs to Know

Authors: Susan Hong, MD, MPH, Aarati Didwania, MD, MS, Olufunmilayo Olopade, MD, Pamela Ganschow, MD

Published in: Journal of General Internal Medicine | Special Issue 2/2009

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ABSTRACT

BACKGROUND

Breast cancer patients represent the largest group of adult cancer survivors in the US. Most breast cancers in women 50 years of age and older are hormone receptor positive. Third generation aromatase inhibitors (AIs) are the newest class of drugs used in treating hormone responsive breast cancer. It is often during start of adjuvant hormone therapy that the breast cancer patient establishes (or reestablishes) close follow-up with their general internist.

OBJECTIVE

Given the large numbers of breast cancer patients in the US and the increasing use of third generation AI’s, general internists will need to have a clear understanding of these drugs including their benefits and potential harms. Currently there are three third generation aromatase inhibitors FDA approved for use in the US. All have been shown to be superior to tamoxifen in disease free survival (DFS) in the treatment of both metastatic and early breast cancers.

RESULTS

While the data on side effects is limited, AI (compared to tamoxifen) may result in higher rates of osteoporosis and fractures, more arthralgias, and increased vaginal dryness and dysparuenia. Limited information on their effects on the cardiovascular system and neuro-cognitive function are also available. Patient’s receiving adjuvant hormone therapy are generally considered disease free or disease stable and require less intensive monitoring by their breast cancer specialist.

CONCLUSIONS

In situations where patients experience significant negative side effects from AI therapy, discussions to discontinue treatment (and switch to an alternative endocrine therapy) should involve the cancer specialist and take into consideration the patient’s risk for breast cancer recurrence and the impact of therapy on their quality of life. In some cases, patients may choose to never initiate AI treatment. In other cases, patients may choose to prematurely discontinue therapy even if therapy is well tolerated. In both settings increased knowledge by the general internists will likely facilitate discussions of risks versus benefits of therapy and possibly improve compliance to adjuvant hormone therapy.
Literature
1.
Li CI, Daling JR, Malone KE. Incidence of invasive breast cancer by hormone receptor status from 1992 to 1998. J Clin Oncol. 2003;21(1):28–34.CrossRefPubMed
2.
Rugo HS. The breast cancer continuum in hormone-receptor positive breast cancer in postmenopausal women: evolving management options focusing on aromatase inhibitors. Ann Oncol. 2008;19(1):16–27.CrossRefPubMed
3.
Riggins RB, Schrecengost RS, Guerrero MS, Bouton AH. Pathways to tamoxifen resistance. Cancer Letters. 2007;256(1):1–24.CrossRefPubMed
4.
5.
Fabian CJ. The what, why and how of aromatase inhibitors:hormonal agents for treatment and prevention of breast cancer. Int J Clin Pract. 2007;61(12):2051–63.CrossRefPubMed
6.
Baum M, Buzdar A, Cuzick J, et al. Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early- stage breast cancer: results of the ATAC (Arimidex, Tamoxifen Alone or in Combination) trial efficacy and safety update analyses. Cancer. 2003;98(9):1802–10.CrossRefPubMed
7.
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(11):1081–92.CrossRefPubMed
8.
Goss PE, Ingle JN, Martino S, et al. Randomized trial of letrozole following tamoxifen as extended adjuvant therapy in receptor-positive breast cancer: updated findings from NCIC CTG MA.17. J Natl Cancer Inst. 2005;97(17):1262–71.PubMed
9.
Goss PE. Breast cancer prevention–clinical trials strategies involving aromatase inhibitors. J Steroid Biochem Mol Biol. 2003;86(3–5):487–93.CrossRefPubMed
10.
Janicke F. Are all aromatase inhibitors the same? A review of the current evidence. Breast. 2004;13(Suppl 1):S10–8.CrossRefPubMed
11.
Gibson L, Dawson CK, Lawrence DH, Bliss JM. Aromatase inhibitors for treatment of advanced breast cancer in postmenopausal women. Cochrane Database of Syst Rev. 2007;24(1):CD003370.
12.
Jonat W, Gnant M, Boccardo F, et al. Effectiveness of switching from adjuvant tamoxifen to anastrozole in postmenopausal women with hormone-sensitive early-stage breast cancer: a meta-analysis. The Lancet Oncol. 2006;7(12):991–6.CrossRef
13.
Coates AS, Keshaviah A, Thurlimann B, et al. Five years of letrozole compared with tamoxifen as initial adjuvant therapy for postmenopausal women with endocrine-responsive early breast cancer: update of study BIG 1–98. J Clin Oncol. 2007;25:486–92.CrossRefPubMed
14.
Goss PE. Letrozole in the extended adjuvant setting: MA.17. Breast Cancer Res Treat. 2007;105:45–53.CrossRefPubMed
15.
Mamounas E, Jeong J-H, Wickerman L, et al. Benefit from exemestane as extended adjuvant therapy after 5 years of adjuvant tamoxifen: intention-to-treat analysis of the National Surgical Adjuvant Breast and Bowel Project B-33 trial. J Clin Oncol. 2008;26:1965–71.CrossRefPubMed
16.
Goss PE. Extending the benefits of adjuvant therapy in early HR + breast cancer. Breast Cancer Res Treat. 2008;112:45–52.CrossRefPubMed
17.
Chen Z, Maricic M, Bassford TL, et al. Fracture Risk Among Breast Cancer Survivors: Results From the Women’s Health Initiative Observational Study. Arch Intern Med. 2005;165(5):552–8.CrossRefPubMed
18.
Chen Z, Maricic M, Pettinger M, et al. Osteoporosis and rate of bone loss among postmenopausal survivors of breast cancer. Cancer. 2005;104(7):1520–30.CrossRefPubMed
19.
Kanis JA, McCloskey EV, Powles T, Paterson AHG, Ashley S, Spector T. A high incidence of vertebral fracture in women with breast cancer. Br J Cancer. 1999;79:1179–81.CrossRefPubMed
20.
Ward RL, Morgan G, Dalley D, et al. Tamoxifen reduces bone turnover and prevents lumbar spine and proximal femoral bone loss in early postmenopausal women Effects of exemestane administered for 2 years versus placebo on bone mineral density, bone biomarkers, and plasma lipids in patients with surgically resected early breast cancer. Bone Miner. 1993;22(2):87–94.CrossRefPubMed
21.
Chien AJ, Goss PE. Aromatase inhibitors and bone health in women with breast cancer. J Clin Oncol. 2006;24(33):5305–12.CrossRefPubMed
22.
McCloskey EV, Hannon RA, Lakner G, et al. Effects of third generation aromatase inhibitors on bone health and other safety parameters: Results of an open, randomised, multi-centre study of letrozole, exemestane and anastrozole in healthy postmenopausal women. European Journal of Cancer. 2007;43(17):2523–31.CrossRefPubMed
23.
Hadji P. Reducing the risk of bone loss associated with breast cancer treatment. The Breast. 2007;16:10–5.CrossRef
24.
Hillner BE, Ingle JN, Chlebowski RT, et al. American Society of Clinical Oncology 2003 Update on the Role of Bisphosphonates and Bone Health Issues in Women With Breast Cancer. J Clin Oncol. 2003;21(21):4042–57.CrossRefPubMed
25.
Siris ES, Chen Y-T, Abbott TA, et al. Bone Mineral Density Thresholds for Pharmacological Intervention to Prevent Fractures. Arch Intern Med. 2004;164(10):1108–12.CrossRefPubMed
26.
27.
28.
Brufsky A, Harker WG, Beck JT, et al. Zoledronic acid inhibits adjuvant letrozole- induced bone loss in postmenopausal women with early breast cancer. J Clin Oncol. 2007;25(7):829–36. Epub 2006 Dec 11.CrossRefPubMed
29.
Camacho PM, Dayal AS, Diaz JL, et al. Prevalence of Secondary Causes of Bone Loss Among Breast Cancer Patients With Osteopenia and Osteoporosis. J Clin Oncol. 2008;26(33):5380–5.CrossRefPubMed
30.
Donnellan PP, Douglas SL, Cameron DA, Leonard RC. Aromatase inhibitors and arthralgia. J Clin Oncol. 2001;19(10):2767.PubMed
31.
Thorne C. Management of arthralgias associated with aromatase inhibitor therapy. Curr Oncol. 2007;14:S11–S9.CrossRefPubMed
32.
Crew KD, Greenlee H, Capodice J, et al. Prevalence of joint symptoms in postmenopausal women taking aromatase inhibitors for early-stage breast cancer. J Clin Oncol. 2007;25(25):3877–83.CrossRefPubMed
33.
Geisler J, Lonning PE, Krag LE, et al. Changes in bone and lipid metabolism in postmenopausal women with early breast cancer after terminating 2-year treatment with exemestane: a randomised, placebo-controlled study. Eur J Cancer. 2006;42(17):2968–75. Epub 006 Sep 11.CrossRefPubMed
34.
Taylor M, Rastelli A, Civitelli R, Ellis M. Incidence of 25-OH vitamin D deficiency in patients with a history of breast cancer who have musculoskeletal symptomatology. Breast Cancer Res Treat. 2004;88:S137.
35.
36.
Derzko C, Elliott S, Lam W. Management of sexual dysfunction in postmenopausal breast cancer patients taking adjuvant aromatase inhibitor therapy. Curr Oncol. 2007;14(Suppl 1):S20–40.PubMed
37.
Fallowfield L, Cella D, Cuzick J, Francis S, Locker G, Howell A. Quality of life of postmenopausal women in the Arimidex, Tamoxifen, Alone or in Combination (ATAC) Adjuvant Breast Cancer Trial. J Clin Oncol. 2004;22(21):4261–71.CrossRefPubMed
38.
Whelan TJ, Goss PE, Ingle JN, et al. Assessment of quality of life in MA.17: a randomized, placebo-controlled trial of letrozole after 5 years of tamoxifen in postmenopausal women. J Clin Oncol. 2005;23(28):6931–40. Epub 2005 Sep 12.CrossRefPubMed
39.
Krychman ML, Carter J, Aghajanian CA, Dizon DS, Castiel M. Chemotherapy-induced dyspareunia: a case study of vaginal mucositis and pegylated liposomal doxorubicin injection in advanced stage ovarian carcinoma. Gynecol Oncol. 2004;93(2):561–3.CrossRefPubMed
40.
Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women’s Health Initiative randomized controlled trial. JAMA. 2002;288(3):321–33.CrossRefPubMed
41.
Manson JE, Allison MA, Rossouw JE, et al. Estrogen therapy and coronary-artery calcification. N Engl J Med. 2007;356(25):2591–602.CrossRefPubMed
42.
Mouridsen H, Keshaviah A, Coates AS, et al. Cardiovascular Adverse Events During Adjuvant Endocrine Therapy for Early Breast Cancer Using Letrozole or Tamoxifen: Safety Analysis of BIG 1–98 Trial. J Clin Oncol. 2007;25(36):5715–22.CrossRefPubMed
43.
Crivellari D, Sun Z, Coates AS, et al. Letrozole Compared With Tamoxifen for Elderly Patients With Endocrine-Responsive Early Breast Cancer: The BIG 1–98 Trial. J Clin Oncol. 2008;26(12):1972–9.CrossRefPubMed
44.
Ewer M, Gluck S. A women’s heart: the impact of adjuvant endocrine therapy on cardiovascular health. Cancer. 2009;115:1813–26.CrossRefPubMed
45.
Ewer M, Gluck S. Evaluation of lipid profiles and cardiovascular (CV) safety data of aromatase inhibitors (AI). In: American Society of Clinical Oncology; 2008; Washington DC; 2008.
46.
Nabholtz J-M, Gligorov J. Cardiovascular Safety Profiles of Aromatase Inhibitors: A Comparative Review. Drug Safety. 2006;29(9):785.CrossRefPubMed
47.
Wasan KM, Goss PE, Pritchard PH, et al. The influence of letrozole on serum lipid concentrations in postmenopausal women with primary breast cancer who have completed 5 years of adjuvant tamoxifen (NCIC CTG MA.17L). Ann Oncol. 2005;16(5):707–15.CrossRefPubMed
48.
Engan T, Krane J, Johannessen DC, Lonning PE, Kvinnsland S. Plasma changes in breast cancer patients during endocrine therapy–lipid measurements and nuclear magnetic resonance (NMR) spectroscopy. Breast Cancer Res Treat. 1995;36(3):287–97.CrossRefPubMed
49.
Atalay G, Dirix L, Biganzoli L, et al. The effect of exemestane on serum lipid profile in postmenopausal women with metastatic breast cancer: a companion study to EORTC Trial 10951, ‘Randomized phase II study in first line hormonal treatment for metastatic breast cancer with exemestane or tamoxifen in postmenopausal patients’. Ann Oncol. 2004;15(2):211–7.CrossRefPubMed
50.
51.
Rock CL, Flatt SW, Newman V, et al. Factors associated with weight gain in women after diagnosis of breast cancer. Women’s healthy eating and living study group. Am Diet Assoc. 1999;99:1212–21.CrossRef
52.
Irwin ML, Crumley D, McTiernan A, et al. Physical activity levels before and after a diagnosis of breast carcinoma: the Health, Eating, Activity, and Lifestyle (HEAL) study. Cancer. 2003;97:1746–57.CrossRefPubMed
53.
Cauley JA, McTiernan A, Rodabough RJ, et al. Statin Use and Breast Cancer: Prospective Results From the Women’s Health Initiative. J Natl Cancer Inst. 2006;98(10):700–7.PubMedCrossRef
54.
Norman SA, Potashnik SL, Galantino MG, De Michele AM, House L, Localio AR. Modifiable risk factors for breast cancer recurrence: what can we tell survivors? Journal of Womens Health. 2007;16(2):117–90.CrossRef
55.
56.
Yaffe K, Sawaya G, Lieberburg I, Grady D. Estrogen Therapy in Postmenopausal Women: Effects on Cognitive Function and Dementia. JAMA. 1998;279(9):688–95.CrossRefPubMed
57.
Rapp SR, Espeland MA, Shumaker SA, et al. Effect of estrogen plus progestin on global cognitive function in postmenopausal women: the Women’s Health Initiative Memory Study: a randomized controlled trial. JAMA. 2003;289(20):2663–72.CrossRefPubMed
58.
Shumaker SA, Legault C, Kuller L, et al. Conjugated equine estrogens and incidence of probable dementia and mild cognitive impairment in postmenopausal women: Women’s Health Initiative Memory Study. JAMA. 2004;291(24):2947–58.CrossRefPubMed
59.
Reid-Arndt SA. Breast cancer and chemobrain: the consequences of cognitive difficulties following chemotherapy and the potential for recovery. Mo Med. 2009;106(2):127–31.PubMed
60.
Rugo HS, Ahles T. The impact of adjuvant therapy for breast cancer on cognitive function: current evidence and directions for research. Seminars in Oncology. 2003;30(6):749–62.CrossRefPubMed
61.
Bender CM, Sereika SM, Brufsky AM, et al. Memory impairments with adjuvant anastrozole versus tamoxifen in women with early-stage breast cancer. Menopause. 2007;14(6):995–8.CrossRefPubMed
62.
Hadji P. Menopausal symptoms and adjuvant therapy-associated adverse events. Endocr Relat Cancer. 2008;15(1):73–90.CrossRefPubMed
63.
Bundred NJ. The effects of aromatase inhibitors on lipids and thrombosis. Br J Cancer. 2005; 93S1: S23–7.CrossRefPubMed
64.
The Arimidex, Tamoxifen, Alone or in Combination (ATAC) Trialists’ Group. Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 100-month analysis of the ATAC trial. The Lancet Oncol. 2008;9(1):45–53.CrossRef
65.
Coombes R, Kilburn L, Snowdon C, et al. Survival and safety of exemestane versus tamoxifen after 2–3 years’ tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial. The Lancet. 2007;(369):559–70.
Metadata
Title
The Expanding Use of Third-Generation Aromatase Inhibitors: What the General Internist Needs to Know
Authors
Susan Hong, MD, MPH
Aarati Didwania, MD, MS
Olufunmilayo Olopade, MD
Pamela Ganschow, MD
Publication date
01-11-2009
Publisher
Springer-Verlag
Published in
Journal of General Internal Medicine / Issue Special Issue 2/2009
Print ISSN: 0884-8734
Electronic ISSN: 1525-1497
DOI
https://doi.org/10.1007/s11606-009-1037-2

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