Journal Article
. 2012 Sep; 52(1):91-101.
doi: 10.3109/0284186X.2012.713508.

Combined analysis of vascular invasion, grade, HER2 and Ki67 expression identifies early breast cancer patients with questionable benefit of systemic adjuvant therapy

Marit Synnestvedt 1 Elin Borgen  Hege G Russnes  Neena T Kumar  Ellen Schlichting  Karl-Erik Giercksky  Rolf Kåresen  Jahn M Nesland  Bjørn Naume  
  • PMID: 22934555
  •     9 citations


Introduction: Over-treatment of low-risk early breast cancer patients with adjuvant systemic therapies is an important clinical challenge. Better techniques are required which can be used to distinguish between the large group of patients with no residual disease after surgery and consequently no benefit of adjuvant treatment, from the smaller group with high relapse risk. A better integration of available prognostic factors might contribute to improved prediction of clinical outcome.

Material And Methods: The current study included 346 unselected pT1pN0 patients who did not receive adjuvant systemic treatment. In Norway, no patients with this stage were recommended systemic treatment at the time of the study (1995-1998). Histological type, tumour size, grade, vascular invasion (VI), hormone receptor (HR) status, HER2 and Ki67 (cut-off 10%) were analysed. Median follow-up was 86 months for relapse and 101 months for death.

Results: Thirty-eight patients experienced relapse, 31 with distant metastasis. Twenty-one patients died of breast cancer. In univariate analysis grade, HER2, HR, VI and Ki67 had impact on clinical outcome (p < 0.005, log rank). In multivariate analysis, only grade 1-2 vs. grade 3, HER2, VI, and Ki67 status were significant for disease free survival, distant disease free survival, and/or breast cancer specific survival. These factors were used in combination, to separate patients into groups based on the number of unfavourable factors present [combined prognostic score (CPS) 0-4]. Close to 2/3 of the patients (61.4%) had no unfavourable factor (CPS0), whilst 18.4% had CPS ≥ 2. Only 3.6% of those with CPS0 developed metastasis (p < 0.001). The outcome was clearly worse for patients with CPS ≥ 2 (p < 0.001), systemic relapse was detected in approximately 40%.

Conclusions: This study indicates that the combined use of grade, VI, HER2 and Ki67 identifies a subgroup of breast cancer patients with a relapse risk that may question the benefit of adjuvant systemic therapy.

High-throughput screens identify microRNAs essential for HER2 positive breast cancer cell growth.
Suvi-Katri Leivonen, Kristine Kleivi Sahlberg, +4 authors, Merja Perälä.
Mol Oncol, 2013 Oct 24; 8(1). PMID: 24148764    Free PMC article.
Highly Cited.
A three-long noncoding RNA signature as a diagnostic biomarker for differentiating between triple-negative and non-triple-negative breast cancers.
Man Liu, Lu-Qi Xing, Yi-Jing Liu.
Medicine (Baltimore), 2017 Mar 02; 96(9). PMID: 28248879    Free PMC article.
Assessment of Ki67 and uPA/PAI-1 expression in intermediate-risk early stage breast cancers.
Elise Deluche, Laurence Venat-Bouvet, +6 authors, Nicole Tubiana-Mathieu.
BMC Cancer, 2017 Sep 29; 17(1). PMID: 28954632    Free PMC article.
Persistent homology index as a robust quantitative measure of immunohistochemical scoring.
Akihiro Takiyama, Takashi Teramoto, +2 authors, Shinya Tanaka.
Sci Rep, 2017 Oct 27; 7(1). PMID: 29070862    Free PMC article.
Prognostic value of PAM50 and risk of recurrence score in patients with early-stage breast cancer with long-term follow-up.
Hege O Ohnstad, Elin Borgen, +11 authors, Bjørn Naume.
Breast Cancer Res, 2017 Nov 16; 19(1). PMID: 29137653    Free PMC article.
Clinical decision making in postmastectomy radiotherapy in node negative breast cancer.
Rodrigo Barrientos, Suraj Samtani, +3 authors, Mauricio Burotto.
Ecancermedicalscience, 2018 Nov 30; 12. PMID: 30483354    Free PMC article.
Changes in the Ki-67 labeling index between primary breast cancer and metachronous metastatic axillary lymph node: A retrospective observational study.
Naoya Ishibashi, Haruna Nishimaki, +5 authors, Masahiro Okada.
Thorac Cancer, 2018 Oct 31; 10(1). PMID: 30375185    Free PMC article.
Determining Whether High Nodal Burden in Early Breast Cancer Patients Can Be Predicted Preoperatively to Avoid Sentinel Lymph Node Biopsy.
Geok Hoon Lim, Sze Yiun Teo, +2 authors, Lester Chee Hao Leong.
J Breast Cancer, 2019 Apr 04; 22(1). PMID: 30941234    Free PMC article.
Ecotropic virus integration-1 and calreticulin as novel prognostic markers in triple-negative breast cancer: A retrospective cohort study.
Dongning He, Lei Wu, +3 authors, Youhong Juang.
Oncol Lett, 2019 Aug 20; 18(2). PMID: 31423253    Free PMC article.