Prognostic relevance of Ki-67 in the primary tumor for survival after a diagnosis of distant metastasis

Abstract

Prediction of the prognosis for metastatic breast cancer patients depends on molecular subtypes similar to those found in patients with primary breast cancer. Several studies have shown that estrogen receptor (ER) and progesterone receptor (PR) status determine the course of the disease and the prognosis. As Ki-67 helps to differentiate molecular subtypes in patients with primary breast cancer, the aim of this study was to assess the prognostic relevance of Ki-67 in the primary tumor in relation to its prognostic relevance for patients with metastatic breast cancer. A total of 467 patients with invasive breast cancer were identified in the database of a single breast cancer center, in whom Ki-67 had been assessed in tumor material from the breast at the time of the primary diagnosis and who had developed a metastasis at any time during the subsequent course. For these patients, tumor and patient characteristics were used to determine prognostic factors relative to overall survival after the diagnosis of distant metastases. Ki-67 was added to this model to investigate whether this might improve the prediction of overall survival. In the multivariate Cox model, age at diagnosis, body mass index, nodal status, tumor size, ER and PR status, and time from diagnosis to metastasis were identified as relevant prognostic factors. Adding Ki-67 to the model improved the prediction of overall survival. There was also a significant and relevant interaction with the PR status. In patients with a low-proliferation primary tumor, a high level of PR expression would indicate an extraordinarily good prognosis (HR 0.39; 95 % CI, 0.23-0.66). In patients with higher-proliferation primary tumors, PR status was not capable of differentiating prognostic groups. Ki-67 is useful in addition to known prognostic factors for breast cancer. It is able to indicate a group of women with a poorer prognosis, specifically in the group of patients with PR-positive breast cancer.

Ki-67 is a prognostic parameter in breast cancer patients: results of a large population-based cohort of a cancer registry

“…In former studies, Ki-67 has also been valued as a prognostic factor being associated with breast cancer outcomes [3, 30, 36, 45–49]. Ki-67 previously has been already considered as a biomarker for therapeutic decision [13, 50]. Colozza et al [51] reviewed the role of proliferation markers as prognostic and predictive tools in early breast cancer.…”

Prognostic utility of atypical mitoses in patients with breast cancer: A comparative study with Ki67 and phosphohistone H3

“…Ki67 is the most widely studied proliferation marker in breast cancer; however, the role of Ki67 in breast cancer management remains controversial due to the lack of specificity and reproducibility . For the last decade, PHH3 has attracted attention as a prognostic marker of breast cancer, and a recent study by Gerring et al revealed that PHH3 has a stronger prognostic value than Ki67 in breast cancers.…”

“…Ki67 is a DNA‐binding protein expressed in all active phases of the cell cycle except for G0 . Ki67 has been commonly used as a biomarker to predict outcomes of patients with breast cancer; however, its utility has long been under debate because of conflicting reports . Histone H3, one of the core histone proteins, is a major component of chromatin .…”

Association of molecular subtypes with breast cancer risk factors

“…One strength is the single-center, uniform assessment of ER, PR, Ki-67, and HER2. Clinical uses of these data have been described in several previous studies (Wiesner et al, 2009;Fasching et al, 2011;Heusinger et al, 2012b;Loehberg et al, 2013). All Ki-67 data, as well as all other immunohistochemical data, were assessed directly at the time of the diagnosis, ensuring direct assessment of molecular subtypes according to the relevant markers.…”