title: Double-Blind, Randomized Trial of Alternative Letrozole Dosing Regimens in Postmenopausal Women with Increased Breast Cancer Risk.
abstract: Aromatase inhibitors (AI) profoundly suppress estrogen levels in postmenopausal women and are effective in breast cancer prevention among high-risk postmenopausal women. Unfortunately, AI treatment is associated with undesirable side effects that limit patient acceptance for primary prevention of breast cancer. A double-blind, randomized trial was conducted to determine whether low and intermittent doses of letrozole can achieve effective estrogen suppression with a more favorable side-effect profile. Overall, 112 postmenopausal women at increased risk for breast cancer were randomized to receive letrozole at 2.5 mg once daily (QD, standard dose arm), 2.5 mg every Monday, Wednesday, and Friday (Q-MWF), 1.0 mg Q-MWF, or 0.25 mg Q-MWF for 24 weeks. Primary endpoint was suppression in serum estradiol levels at the end of letrozole intervention. Secondary endpoints included changes in serum estrone, testosterone, C-telopeptide (marker of bone resorption), lipid profile, and quality-of-life measures (QoL) following treatment. Significant estrogen suppression was observed in all dose arms with an average of 75% to 78% and 86% to 93% reduction in serum estradiol and estrone levels, respectively. There were no differences among dose arms with respect to changes in C-telopeptide levels, lipid profile, adverse events (AE), or QoL measures. We conclude that low and intermittent doses of letrozole are not inferior to standard dose in estrogen suppression and resulted in a similar side-effect profile compared with standard dose. Further studies are needed to determine the feasibility of selecting an effective AI dosing schedule with better tolerability.
authors.affiliation: Department of Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah.
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: López
authors.affiliation: Department of Internal Medicine, Mayo Clinic Rochester, Rochester, Minnesota.
authors.forename: Sandhya
authors.initials: S
authors.lastname: Pruthi
authors.affiliation: Department of Surgery, Mayo Clinic Rochester, Rochester, Minnesota.
authors.forename: Judy C
authors.initials: JC
authors.lastname: Boughey
authors.affiliation: Division of Cancer Prevention, National Cancer Institute, Rockville, Maryland.
authors.forename: Marjorie
authors.initials: M
authors.lastname: Perloff
authors.affiliation: University of Arizona Cancer Center, University of Arizona, Tucson, Arizona.
authors.forename: Chiu-Hsieh
authors.initials: CH
authors.lastname: Hsu
authors.affiliation: Department of Surgery, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California.
authors.forename: Julie E
authors.initials: JE
authors.lastname: Lang
authors.affiliation: University of Arizona Cancer Center, University of Arizona, Tucson, Arizona.
authors.forename: Michele
authors.initials: M
authors.lastname: Ley
authors.affiliation: University of Arizona Cancer Center, University of Arizona, Tucson, Arizona.
authors.forename: Denise
authors.initials: D
authors.lastname: Frank
authors.affiliation: University of Arizona Cancer Center, University of Arizona, Tucson, Arizona.
authors.forename: Josephine A
authors.initials: JA
authors.lastname: Taverna
authors.affiliation: University of Arizona Cancer Center, University of Arizona, Tucson, Arizona. schow@email.arizona.edu.
authors.forename: H-H Sherry
authors.initials: HH
authors.lastname: Chow
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D002278:Carcinoma in Situ / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D018275:Carcinoma, Lobular / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000077289:Letrozole; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D009570:Nitriles / Q000627:therapeutic use*; D017698:Postmenopause; D011379:Prognosis; D014230:Triazoles / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D009570:Nitriles; D014230:Triazoles; D000077289:Letrozole