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High Ki-67 Expression and Low Progesterone Receptor Expression Could Independently Lead to a Worse Prognosis for Postmenopausal Patients With Estrogen Receptor-Positive and HER2-Negative Breast Cancer.
Clin Breast Cancer. 2015 Jun; 15(3):204-11.CB

Abstract

We examined the prognostic significance of progesterone receptor (PgR) expression in immunohistochemical-based luminal subtypes defined by Ki-67 expression, taking menopausal status into consideration. The study included 327 surgically removed estrogen receptor-positive and human epidermal growth factor receptor 2-negative breast cancers. High Ki-67 expression (> 15%) and low PgR expression (£ 20%) were significant independent factors resulting in worse distant relapse-free survival. This association was observed in postmenopausalwomen but not in premenopausal women.

BACKGROUND

Accurate classification of luminal A and luminal B characteristics of estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer is considered clinically important for determining effective adjuvant treatment. Although Ki-67 expression has been identified as an essential constituent for this classification, the role of progesterone receptor (PgR) expression has yet to be fully elucidated. Because PgR expression is influenced by the estrogen milieu, we examined the prognostic significance of PgR expression in immunohistochemical (IHC)-based luminal subtypes defined by Ki-67 expression, taking menopausal status into consideration.

MATERIALS AND METHODS

We examined 327 surgically removed ER(+) and HER2(-) breast cancer specimens. ER, PgR, and Ki67 expression was determined IHC for semiquantitative measurement. We used 1%, 20%, and 15% as the cutoff value for ER, PgR, and Ki-67, respectively.

RESULTS

Breast cancer with low PgR (≤ 20%) expression was significantly associated with postmenopausal status, a large tumor size, and low ER expression. The low PgR expression subset had significantly worse distant relapse-free survival (DRFS) than the high PgR expression subset (P = .0067). This association was observed consistently in postmenopausal women but not in the premenopausal women. Multivariate analysis demonstrated that high Ki-67 expression (hazard ratio [HR], 3.80; 95% confidence interval [CI], 1.57-10.58; P = .003) and low PgR expression (HR, 2.54; 95% CI, 1.08-6.40; P = .038) were significant independent factors affecting DRFS.

CONCLUSION

Low PgR expression was independently associated with a poorer prognosis for ER(+) and HER2(-) breast cancer. Determination of PgR expression combined with that of Ki-67 could thus improve the accuracy of IHC-based classification of luminal A and luminal B breast cancer, especially for postmenopausal women.

Authors+Show Affiliations

Division of Breast and Endocrine, Department of Surgery, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.Division of Breast and Endocrine, Department of Surgery, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.Division of Breast and Endocrine, Department of Surgery, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.Division of Breast and Endocrine, Department of Surgery, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.Division of Breast and Endocrine, Department of Surgery, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.Division of Breast and Endocrine, Department of Surgery, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.Division of Breast and Endocrine, Department of Surgery, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.Division of Breast and Endocrine, Department of Surgery, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.Sakita Clinic, Nishinomiya, Hyogo, Japan.Uminosato Clinic, Minamiawaji, Hyogo, Japan.Division of Breast and Endocrine, Department of Surgery, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan. Electronic address: ymiyoshi@hyo-med.ac.jp.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25600243

Citation

Nishimukai, Arisa, et al. "High Ki-67 Expression and Low Progesterone Receptor Expression Could Independently Lead to a Worse Prognosis for Postmenopausal Patients With Estrogen Receptor-Positive and HER2-Negative Breast Cancer." Clinical Breast Cancer, vol. 15, no. 3, 2015, pp. 204-11.
Nishimukai A, Yagi T, Yanai A, et al. High Ki-67 Expression and Low Progesterone Receptor Expression Could Independently Lead to a Worse Prognosis for Postmenopausal Patients With Estrogen Receptor-Positive and HER2-Negative Breast Cancer. Clin Breast Cancer. 2015;15(3):204-11.
Nishimukai, A., Yagi, T., Yanai, A., Miyagawa, Y., Enomoto, Y., Murase, K., Imamura, M., Takatsuka, Y., Sakita, I., Hatada, T., & Miyoshi, Y. (2015). High Ki-67 Expression and Low Progesterone Receptor Expression Could Independently Lead to a Worse Prognosis for Postmenopausal Patients With Estrogen Receptor-Positive and HER2-Negative Breast Cancer. Clinical Breast Cancer, 15(3), 204-11. https://doi.org/10.1016/j.clbc.2014.12.007
Nishimukai A, et al. High Ki-67 Expression and Low Progesterone Receptor Expression Could Independently Lead to a Worse Prognosis for Postmenopausal Patients With Estrogen Receptor-Positive and HER2-Negative Breast Cancer. Clin Breast Cancer. 2015;15(3):204-11. PubMed PMID: 25600243.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - High Ki-67 Expression and Low Progesterone Receptor Expression Could Independently Lead to a Worse Prognosis for Postmenopausal Patients With Estrogen Receptor-Positive and HER2-Negative Breast Cancer. AU - Nishimukai,Arisa, AU - Yagi,Tomoko, AU - Yanai,Ayako, AU - Miyagawa,Yoshimasa, AU - Enomoto,Yukie, AU - Murase,Keiko, AU - Imamura,Michiko, AU - Takatsuka,Yuichi, AU - Sakita,Isao, AU - Hatada,Takuya, AU - Miyoshi,Yasuo, Y1 - 2014/12/24/ PY - 2014/09/26/received PY - 2014/12/16/accepted PY - 2015/1/21/entrez PY - 2015/1/21/pubmed PY - 2016/1/16/medline KW - Breast cancer KW - Ki-67 KW - Postmenopausal KW - Progesterone receptor KW - Prognostic factor SP - 204 EP - 11 JF - Clinical breast cancer JO - Clin Breast Cancer VL - 15 IS - 3 N2 - UNLABELLED: We examined the prognostic significance of progesterone receptor (PgR) expression in immunohistochemical-based luminal subtypes defined by Ki-67 expression, taking menopausal status into consideration. The study included 327 surgically removed estrogen receptor-positive and human epidermal growth factor receptor 2-negative breast cancers. High Ki-67 expression (> 15%) and low PgR expression (£ 20%) were significant independent factors resulting in worse distant relapse-free survival. This association was observed in postmenopausalwomen but not in premenopausal women. BACKGROUND: Accurate classification of luminal A and luminal B characteristics of estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer is considered clinically important for determining effective adjuvant treatment. Although Ki-67 expression has been identified as an essential constituent for this classification, the role of progesterone receptor (PgR) expression has yet to be fully elucidated. Because PgR expression is influenced by the estrogen milieu, we examined the prognostic significance of PgR expression in immunohistochemical (IHC)-based luminal subtypes defined by Ki-67 expression, taking menopausal status into consideration. MATERIALS AND METHODS: We examined 327 surgically removed ER(+) and HER2(-) breast cancer specimens. ER, PgR, and Ki67 expression was determined IHC for semiquantitative measurement. We used 1%, 20%, and 15% as the cutoff value for ER, PgR, and Ki-67, respectively. RESULTS: Breast cancer with low PgR (≤ 20%) expression was significantly associated with postmenopausal status, a large tumor size, and low ER expression. The low PgR expression subset had significantly worse distant relapse-free survival (DRFS) than the high PgR expression subset (P = .0067). This association was observed consistently in postmenopausal women but not in the premenopausal women. Multivariate analysis demonstrated that high Ki-67 expression (hazard ratio [HR], 3.80; 95% confidence interval [CI], 1.57-10.58; P = .003) and low PgR expression (HR, 2.54; 95% CI, 1.08-6.40; P = .038) were significant independent factors affecting DRFS. CONCLUSION: Low PgR expression was independently associated with a poorer prognosis for ER(+) and HER2(-) breast cancer. Determination of PgR expression combined with that of Ki-67 could thus improve the accuracy of IHC-based classification of luminal A and luminal B breast cancer, especially for postmenopausal women. SN - 1938-0666 UR - https://www.unboundmedicine.com/medline/citation/25600243/High_Ki_67_Expression_and_Low_Progesterone_Receptor_Expression_Could_Independently_Lead_to_a_Worse_Prognosis_for_Postmenopausal_Patients_With_Estrogen_Receptor_Positive_and_HER2_Negative_Breast_Cancer_ DB - PRIME DP - Unbound Medicine ER -