title: Body mass index and menopausal disorders during menopause affect vasomotor symptoms of postmenopausal Japanese breast cancer patients treated with anastrozole: a prospective multicenter cohort study of patient-reported outcomes.
abstract: BACKGROUND
  Adverse events related to endocrine therapies have a major impact not only on patients' quality of life but also on treatment discontinuation. Although vasomotor symptoms induced by aromatase inhibitors are frequently recognized, risk factors, especially for Japanese women, are not well reported. To identify risk factors for vasomotor symptoms of Japanese breast cancer patients treated with adjuvant anastrozole, we conducted a prospective cohort study based on patient-reported outcomes (PROs).
  
  
  METHODS
  For this prospective cohort study (SAVS-JP, UMIN000002455), 391 postmenopausal Japanese estrogen receptor-positive breast cancer patients who were treated with adjuvant anastrozole were recruited from 28 centers. The PRO assessment was obtained from a self-reported questionnaire at baseline, 3, 6, 9 and 12 months between August 2009 and April 2012. Vasomotor symptoms, comprising hot flashes, night sweats, and cold sweats, were categorized into four grades (none, Grade 1: mild, Grade 2: moderate, Grade 3: severe). Pre-existing symptoms were only included if they had become worse than at baseline.
  
  
  RESULTS
  Hot flashes, night sweats, and cold sweats at baseline were reported by 20.5, 15.1, and 8.2 % of the patients, respectively, and new appearance or worsening of symptoms in comparison with baseline by 38.4, 29.3, and 28.7 %, respectively. About 80 % of newly occurring symptoms were Grade 1, and less than 5 % were Grade 3. Vasomotor symptoms were reported by 201 out of 362 patients (55.5 %) during the first year and the mean time to onset was 5.6 months. Patients with vasomotor symptoms were significantly younger (mean 62.8 years, range 38-86 vs 64.7 years, range 37-84; p = 0.02), had higher body mass index (BMI) (23.4 kg/m2, range 15.8-39.9 vs 22.4 kg/m2, range 15.8-34.9; p = 0.01), had vasomotor symptoms sooner after menopause (12.4 years, range 0-51 vs 15.1 years, range 1-37; p = 0.002), and had more menopausal disorders during menopause (63.3 vs 36.7 %; p = 0.002). Multivariate analysis showed that BMI [odds ratio (OR) 1.09 per unit of increase, 95 % confidence interval (CI) 1.02-1.16; p = 0.009] and experiencing menopausal disorders (OR 2.11, 95 % CI 1.35-3.30; p = 0.001) were significantly associated with vasomotor symptoms.
  
  
  CONCLUSIONS
  High BMI and experiencing menopausal disorders at menopause were found to be significantly associated with the occurrence of vasomotor symptoms. These findings are expected to prove useful for the management of postmenopausal Japanese women treated with aromatase inhibitors.
authors.affiliation: Department of Breast Surgery, Hyogo Cancer Center, 13-70 Kitaoji-cho, Akashi, Hyogo, 673-8558, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Tane
authors.affiliation: Department of Surgery, Kansai Rosai Hospital, 3-1-69 Inaba-so, Amagasaki, Hyogo, 660-8511, Japan.
authors.forename: Chiyomi
authors.initials: C
authors.lastname: Egawa
authors.affiliation: Department of Breast Surgery, Hyogo Cancer Center, 13-70 Kitaoji-cho, Akashi, Hyogo, 673-8558, Japan.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Takao
authors.affiliation: Department of Breast Surgery, Shinko Hospital, 1-4-47 Wakinohama-cho, Chuo-ku, Kobe, Hyogo, 651-0072, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yamagami
authors.affiliation: Department of Surgery, Kohnan Hospital, 1-5-16 Kamokogahara, Higashinada-ku, Kobe, Hyogo, 658-0064, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Miyashita
authors.affiliation: Department of Surgery, Itami City Hospital, 1-100 Koyaike, Itami, Hyogo, 664-8540, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Baba
authors.affiliation: Rokko Island Hospital, 2-11 Koyochonaka, Higashinada-ku, Kobe, Hyogo, 658-0032, Japan.
authors.forename: Shigetoshi
authors.initials: S
authors.lastname: Ichii
authors.affiliation: Department of Surgery, Hyogo Prefectural Nishinomiya Hospital, 13-9 Rokutanji-cho, Nishinomiya, Hyogo, 662-0918, Japan.
authors.forename: Muneharu
authors.initials: M
authors.lastname: Konishi
authors.affiliation: Department of Surgery, Kobe City Hospital Organization Kobe City Medical Center West Hospital, 2-4 Ichiban-cho, Nagata-ku, Kobe, Hyogo, 653-0013, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Kikawa
authors.affiliation: Department of Surgery, Kobe Kyodo Hospital, 2-4-7 Kubo-cho, Nagata-ku, Kobe, Hyogo, 653-0041, Japan.
authors.forename: Junya
authors.initials: J
authors.lastname: Minohata
authors.affiliation: Nishi-kobe Medical Center, 5-7-1 Kojidai, Nishi-ku, Kobe, Hyogo, 651-2273, Japan.
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Okuno
authors.affiliation: Miyauchi Clinic, 4-10-5 Mukonoso, Amagasaki, Hyogo, 661-0035, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Miyauchi
authors.affiliation: Chayamachi Breast Clinic, 3-1 Chayamachi, Kita-ku, Osaka, Osaka, 530-0013, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Wakita
authors.affiliation: Hyogo Prefectural Tsukaguchi Hospital, 6-8-17 Minamitsukaguchi-cho, Amagasaki, Hyogo, 661-0012, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Suwa
authors.affiliation: Hashimoto Clinic, 1-7-2 Sumiyoshihommachi, Higashinada-ku, Kobe, Hyogo, 658-0051, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Hashimoto
authors.affiliation: Department of Surgery, Takarazuka Municipal Hospital, 4-5-1 Kohama, Takarazuka, Hyogo, 665-0827, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Nishino
authors.affiliation: Department of Surgery, Kinki Central Hospital, 3-1 Kurumazuka, Itami, Hyogo, 664-8533, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Matsumoto
authors.affiliation: Kobe Century Memorial Hospital, 1-9-1 Misaki-cho, Hyogo-ku, Kobe, Hyogo, 652-0855, Japan.
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Hidaka
authors.affiliation: Kobe Urban Breast Clinic, 4-1-6 Kumoidori, Chuo-ku, Kobe, Hyogo, 651-0096, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Konishi
authors.affiliation: Department of Breast Surgery, Hyogo Prefectural Kakogawa Medical Center, 203 Kanno, Kanno-cho, Kakogawa, Hyogo, 675-8555, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Sakoda
authors.affiliation: Department of Surgery, Kuma Hospital, 8-2-35 Shimoyamatedori, Chuo-ku, Kobe, Hyogo, 650-0011, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Miya
authors.affiliation: Department of Breast and Endocrine Surgery, Meiwa Hospital, 4-31 Agenaruo-cho, Nishinomiya, Hyogo, 663-8186, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kishimoto
authors.affiliation: Nishikawa Clinic, 12-41 Nishidaimotsu-cho, Amagasaki, Hyogo, 660-0827, Japan.
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Nishikawa
authors.affiliation: Department of Breast and Endocrine Surgery, Kobe University School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan.
authors.forename: Seishi
authors.initials: S
authors.lastname: Kono
authors.affiliation: Kokufu Breast Clinic, 1-10-6 Takarazuka, Hyogo, 665-0861, Japan.
authors.forename: Ikuo
authors.initials: I
authors.lastname: Kokufu
authors.affiliation: Sakita Clinic, 2-35-101 Wajo-cho, Nishinomiya, Hyogo, 662-0971, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Sakita
authors.affiliation: Kitatsuji Clinic, 3-1-1 Nishitachibana-cho, Amagasaki, Hyogo, 660-0054, Japan.
authors.forename: Koushiro
authors.initials: K
authors.lastname: Kitatsuji
authors.affiliation: Kobe Adventist Hospital, 8-4-1 Arinodai, Kita-ku, Kobe, Hyogo, 651-1321, Japan.
authors.forename: Koushi
authors.initials: K
authors.lastname: Oh
authors.affiliation: Department of Medical Informatics, Niigata University Medical and Dental Hospital, Asahimachidori 1-754, Chuo-ku, Niigata, 951-8520, Japan.
authors.forename: Kouhei
authors.initials: K
authors.lastname: Akazawa
authors.affiliation: Division of Breast and Endocrine Surgery, Department of Surgery, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan. ymiyoshi@hyo-med.ac.jp.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Miyoshi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077384:Anastrozole; D047072:Aromatase Inhibitors / Q000009:adverse effects; D014408:Biomarkers, Tumor / Q000378:metabolism; D015992:Body Mass Index; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D019584:Hot Flashes / Q000503:physiopathology*; D006801:Humans; D007592:Joint Diseases / Q000139:chemically induced / Q000473:pathology*; D008593:Menopause; D008875:Middle Aged; D009570:Nitriles / Q000009:adverse effects*; D000071066:Patient Reported Outcome Measures; D011379:Prognosis; D011446:Prospective Studies; D011788:Quality of Life; D011960:Receptors, Estrogen / Q000378:metabolism; D013546:Sweating / Q000502:physiology; D014230:Triazoles / Q000009:adverse effects*; D014666:Vasomotor System / Q000187:drug effects / Q000473:pathology*
chemical_list: D047072:Aromatase Inhibitors; D014408:Biomarkers, Tumor; D009570:Nitriles; D011960:Receptors, Estrogen; D014230:Triazoles; D000077384:Anastrozole
keywords: Aromatase inhibitor; Breast cancer; Patient-reported outcomes; Vasomotor symptoms