Utility of Ki67 labeling index, cyclin D1 expression, and ER-activity level in postmenopausal ER-positive and HER2-negative breast cancer with neoadjuvant chemo-endocrine therapy

Abstract

In this study, we investigated the relationships of pathological response after neoadjuvant chemo-endocrine therapy with alterations in the Ki67 labeling index (LI), expression of cyclin D1 (CCND1) and progesterone receptor (PgR), and estrogen receptor (ER) activity in breast cancer. A total of 43 Japanese post-menopausal ER-positive and human epidermal growth factor receptor 2-negative invasive breast cancer patients with tumors >2 cm or positive lymph nodes were enrolled. Exemestane alone was administered for 2 months. Neoadjuvant chemo-endocrine therapy included four cycles of doxorubicin plus paclitaxel followed by weekly paclitaxel. The immunohistochemical expression of Ki67 LI, CCND1, and PgR, and ER activity were evaluated using core needle biopsy samples at the pretreatment and post-exemestane alone stages. ER activity was evaluated through transfection of an adenovirus vector carrying an estrogen-response element-green fluorescent protein gene. In current study, marked pathological responses (including 4.7% with pathological complete response) were obtained in 34.9% of patients. Ki67 LI and PgR expression were significantly decreased after treatment. High Ki67 LI at pretreatment was a significant predictive factor of marked pathological response. At the stage of post-exemestane alone, Ki67 LI was not significantly associated with pathological response; however, high CCND1 expression was significantly correlated with high Ki67 LI. Moreover, low-level ER activity at the post-exemestane alone stage was significantly associated with marked pathological response. In conclusions, pretreatment Ki67 LI was a predictor of response to neoadjuvant chemo-endocrine therapy. CCND1 expression and ER activity at the post-endocrine therapy alone stage may be useful in determining further treatments.

Prognostic value of tumor‑infiltrating lymphocytes in estrogen receptor‑positive and human epidermal growth factor receptor 2‑negative breast cancer

“…In the present study, none of the patients with luminal B-like breast cancer and intermediate or high-grade str-TIL count developed recurrence during follow-up. Luminal B-like tumors generally have a worse outcome compared with luminal A-like-subtype tumors, even with the administration of hormonal therapy (24). The biological differences between these subtypes may be caused by the intracellular signaling pathways associated with estrogen among ER-positive breast cancer cells (25,26).…”

DNAJC12 as a Mediator Between ESR1 and ERBB4 in Breast Carcinoma Cells

“…Breast cancer, for the majority of patients, is treated with upfront surgery followed by other adjuvant (post-operative) modalities including radiotherapy, chemotherapy, endocrine therapy, immunotherapy, and adjuvant therapy of traditional Chinese medicine ( 4 – 9 ). Estrogen receptor (ER)-positive and/or progesterone receptor (PR)-positive breast cancer accounts for approximately 70% of all breast cancers, and 85% of those in women over 70 years of age ( 10 – 12 ). ER-positive tumors often respond poorly to neoadjuvant chemotherapy and therefore require robust alternatives ( 13 – 16 ).…”

Neoadjuvant endocrine therapy in locally advanced estrogen or progesterone receptor-positive breast cancer: determining the optimal endocrine agent and treatment duration in postmenopausal women—a literature review and proposed guidelines

“…Each year, approximately two million women are diagnosed with breast cancer worldwide [ 2 , 3 ]. Estrogen receptor (ER)-positive and/or progesterone receptor (PgR)-positive breast cancer accounts for approximately 70% of all breast cancers, and 85% of those in women over 70 years of age [ 4 – 6 ]. At the time of diagnosis, 7 to 20% of women will present with locally advanced breast cancer (LABC) [ 7 – 9 ].…”