Dataset Information

Association of molecular subtypes with Ki-67 changes in untreated breast cancer patients undergoing pre-surgical trials.

ABSTRACT:

Background

Ki-67 is increasingly being used as a response biomarker in window of opportunity, pre-surgical trials for breast cancer patients. Since Ki-67 is often higher at surgery than at baseline core biopsy in subjects allocated to placebo, we investigated which factors affected this change.

Patients and methods

We retrieved data from 274 patients who received no active treatment in three consecutive pre-surgical trials from a single institution. We assessed the association between changes in Ki-67 from diagnostic biopsy to surgical specimen and the following factors: age, body mass index, tumor prognostic and predictive factors, including immunohistochemical molecular subtype, number and size of biopsy specimens, time from biopsy to surgery, circulating insulin-like growth factor-I, sex hormone-binding globulin and hsCRP.

Results

A total of 269 patients with paired measures of Ki-67 at biopsy and surgery were analyzed. Overall, the mean (±SD) change was 2.2 ± 9.2% after a median interval of 41 days (inter-quartile range 33-48). Molecular subtype was the only factor associated with a significant change of Ki-67 (P = 0.004), with a mean absolute increase of 5.3% [95% confidence interval (CI): 2.3-8.3, P = 0.0005] in estrogen receptor-negative HER2-positive tumors (n = 36) and 5.4% (95% CI: 2.9-7.9, P < 0.0001) in triple-negative tumors (n = 78). No significant change in luminal-A (n = 46), luminal-B (n = 85) and luminal-B HER2-positive (n = 24) tumors was observed.

Conclusions

A significant increase in Ki-67 from baseline biopsy to end point surgery in untreated subjects was ascertained in HER2-positive and triple-negative tumors. This biological association suggests a real increase in cancer proliferation, possibly as a result of a biopsy-driven wound healing effect, and should be considered in the design and interpretation of pre-surgical studies.

Registered clinical trial numbers

ISRCTN86894592; ISRCTN16493703.

SUBMITTER: Gandini S

PROVIDER: S-EPMC4433505 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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Publications

Association of molecular subtypes with Ki-67 changes in untreated breast cancer patients undergoing pre-surgical trials.

Gandini S S Guerrieri-Gonzaga A A Pruneri G G Serrano D D Cazzaniga M M Lazzeroni M M Veronesi P P Johansson H H Bonanni B B Viale G G DeCensi A A

Annals of oncology : official journal of the European Society for Medical Oncology 20131218 3

<h4>Background</h4>Ki-67 is increasingly being used as a response biomarker in window of opportunity, pre-surgical trials for breast cancer patients. Since Ki-67 is often higher at surgery than at baseline core biopsy in subjects allocated to placebo, we investigated which factors affected this change.<h4>Patients and methods</h4>We retrieved data from 274 patients who received no active treatment in three consecutive pre-surgical trials from a single institution. We assessed the association bet ...[more]

PMID: 24351403

Similar Datasets

Project description:IntroductionKi-67 labeling index assessed by immunohistochemical assays has been shown useful in assessing the risk of recurrence for estrogen receptor (ER)-positive HER2-negative breast cancers (BC) and distinguishing Luminal A-like from Luminal B-like tumors. We aimed to assess the performance of the Ventana CONFIRM anti-Ki-67 (30-9) Rabbit Monoclonal Primary Antibody.MethodsWe constructed a case-cohort design based on a random sample (n?=?679) of all patients operated on for a first primary, non-metastatic, ER-positive, HER2-negative BC at the European Institute of Oncology (IEO) Milan, Italy during 1998-2002 and all additional patients (n?=?303) operated during the same period, who developed an event (metastasis in distant organs or death due to BC as primary event) and were not included in the previous subset. Multivariable Cox proportional hazards regression with inverse subcohort sampling probability weighting was used to evaluate the risk of event according to Ki-67 (30-9) and derived intrinsic molecular subtype, using previously defined cutoff values, i.e., respectively 14% and 20%.ResultsKi-67 was?<?14% in 318 patients (32.4%), comprised between 14 and 19% in 245 patients (24.9%) and???20 in 419 patients (42.7%). At multivariable analysis, the risk of developing distant disease was 1.88 (95% CI 1.20-2.93; P?=?0.006) for those with Ki-67 comprised between 14 and 19%, and 3.06 (95% CI 1.93-4.84; P?<?0.0001) for those with Ki-67???20% compared to those with Ki-67?<?14%. Patients with Luminal B-like BC had an approximate twofold risk of developing distant disease (HR?=?1.91; 95% CI 1.35-2.71; P?=?0.0003) than patients with Luminal A-like BC defined using Ki-67 (30-9).ConclusionsKi-67 evaluation using the 30-9 rabbit monoclonal primary antibody was able to stratify patients with ER-positive HER2-negative BC into prognostically distinct groups. Ki-67 assessment, with strict adherence to the international recommendations, should be included among the clinically useful biological parameters for the best treatment of patients with BC.

Dataset Information

Association of molecular subtypes with Ki-67 changes in untreated breast cancer patients undergoing pre-surgical trials.

Background

Patients and methods

Results

Conclusions

Registered clinical trial numbers

Publications

Association of molecular subtypes with Ki-67 changes in untreated breast cancer patients undergoing pre-surgical trials.

Similar Datasets

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