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: Masakazu Toi, Shigehira Saji, Norikazu Masuda, Katsumasa Kuroi, Nobuaki Sato, Hiroyuki Takei, Yutaka Yamamoto, Shinji Ohno, Hiroko Yamashita, Kazufumi Hisamatsu, Kenjiro Aogi, Hiroji Iwata, Masahiro Takada, Takayuki Ueno, Shigetoyo Saji, Niramol Chanplakorn, Takashi Suzuki, Hironobu Sasano
• Journal: Cancer science (Cancer Sci) Vol. 102 Issue 4 Pg. 858-65 (Apr 2011) ISSN: 1349-7006 [Electronic] England
• PMID: 21231986 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2011 Japanese Cancer Association.

Chemical References

• Androstadienes
• Aromatase Inhibitors
• Biomarkers, Tumor
• Ki-67 Antigen
• Receptors, Estrogen
• Receptors, Progesterone
• Aromatase
• exemestane

Topics

• Aged
• Androstadienes (therapeutic use)
• Aromatase (chemistry)
• Aromatase Inhibitors (therapeutic use)
• Biomarkers, Tumor (analysis, metabolism)
• Breast Neoplasms (drug therapy, metabolism, pathology)
• Female
• Humans
• Ki-67 Antigen (metabolism)
• Lymphatic Metastasis
• Mastectomy, Segmental
• Middle Aged
• Neoplasm Staging
• Postmenopause
• Receptors, Estrogen (metabolism)
• Receptors, Progesterone (metabolism)
• Survival Rate
• Treatment Outcome