title: Ki67 index changes, pathological response and clinical benefits in primary breast cancer patients treated with 24 weeks of aromatase inhibition.
abstract: Aromatase inhibitor shows efficacy for hormone receptor positive postmenopausal breast cancer. We evaluated the activity of 24 weeks of aromatase inhibition with exemestane for primary breast cancer in a neoadjuvant setting. Patients with stage II/IIIA invasive breast cancer with estrogen receptor (ER) and/or progesterone receptor (PgR)-positive status were eligible. Primary endpoints were objective response rate (ORR) and safety. A steroidal aromatase inhibitor exemestane of 25 mg/day was administered for 16 weeks with an 8-week extension. Secondary endpoints were rates of breast-conserving surgery (BCS), and change of Ki67 index and ER/PgR expression in central laboratory analyses. Between March 2006 and December 2007, 116 patients were enrolled. Among those, 102 patients completed 24 weeks of administration. The ORR was 47% (55/116) at Week 16 and 51% (59/116) at Week 24, respectively. No serious toxicity was seen. ORR was associated with ER Allred scores but not with PgR scores. The significant reduction in Ki67 index was confirmed. No progression was experienced in tumors with less than 15% Ki67 index. Pathological response was observed in 28 (30%) of 94 evaluated cases. No statistical correlation between pre-treatment Ki67 index and pathological response was detected; however, a trend of correlation was found between the post-treatment preoperative endocrine prognostic index (PEPI), a prognostic score and the pathological response. At diagnosis, 59 patients (51%) would have required mastectomy but 40 patients were converted to BCS, showing an increase in the rate of BCS (77%). The 24-week aromatase inhibition provided preferable clinical benefits with significant reduction in Ki67 index. More precise mechanisms of the response need to be investigated.
authors.affiliation: Department of Surgery (Breast Surgery), Kyoto University, Kyoto, Japan. toi@kuhp.kyoto-u.ac.jp
authors.forename: Masakazu
authors.initials: M
authors.lastname: Toi
authors.forename: Shigehira
authors.initials: S
authors.lastname: Saji
authors.forename: Norikazu
authors.initials: N
authors.lastname: Masuda
authors.forename: Katsumasa
authors.initials: K
authors.lastname: Kuroi
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Sato
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takei
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Shinji
authors.initials: S
authors.lastname: Ohno
authors.forename: Hiroko
authors.initials: H
authors.lastname: Yamashita
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Hisamatsu
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Aogi
authors.forename: Hiroji
authors.initials: H
authors.lastname: Iwata
authors.forename: Masahiro
authors.initials: M
authors.lastname: Takada
authors.forename: Takayuki
authors.initials: T
authors.lastname: Ueno
authors.forename: Shigetoyo
authors.initials: S
authors.lastname: Saji
authors.forename: Niramol
authors.initials: N
authors.lastname: Chanplakorn
authors.forename: Takashi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Hironobu
authors.initials: H
authors.lastname: Sasano
mesh_terms: D000368:Aged; D000730:Androstadienes / Q000627:therapeutic use*; D001141:Aromatase / Q000737:chemistry*; D047072:Aromatase Inhibitors / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism*; D008207:Lymphatic Metastasis; D015412:Mastectomy, Segmental; D008875:Middle Aged; D009367:Neoplasm Staging; D017698:Postmenopause; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000730:Androstadienes; D047072:Aromatase Inhibitors; D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D001141:Aromatase; C056516:exemestane