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. 2022 May 4:16:1382.
doi: 10.3332/ecancer.2022.1382. eCollection 2022.

A hierarchical approach to combine histological grade and immunohistochemical factors to identify high-risk luminal breast cancers

Felipe Andrés Cordero da Luz  1   2   3 , Eduarda da Costa Marinho  1   4 , Camila Piqui Nascimento  1   5 , Lara de Andrade Marques  1   6 , Patrícia Ferreira Ribeiro Delfino  1   7 , Rafael Mathias Antonioli  1   8 , Rogério Agenor de Araújo  1   9   10 , Marcelo José Barbosa Silva  2   11
Affiliations

A hierarchical approach to combine histological grade and immunohistochemical factors to identify high-risk luminal breast cancers

Felipe Andrés Cordero da Luz et al. Ecancermedicalscience. .

Abstract

Background: The luminal subtype accounts for ~70% of newly diagnosed breast cancer patients. Although it has a better prognosis, approximately 30% of them develop a late relapse. Identifying those patients is of interest to improve treatment decisions.

Methods: A retrospective observational, single-centre study based on data from medical records of 572 non-metastatic (I-III) invasive ductal breast carcinoma patients, 448 with luminal tumours and 124 with triple-negative tumours. Kaplan-Meier, Cox regression and time-dependent Cox regression were carried out to obtain the prognosis value of risk factors.

Results: During a median observation of 5.5 years, 105 distant metastasis events and 105 all-cause deaths were observed. In addition to known clinicopathological factors (i.e., age, tumour size and lymph node metastasis), the high semi-quantitative expression of both hormone receptors was associated with distant metastasis-free survival (DMFS) (adjusted hazard ratio (HaR): 0.524 (0.316-0.867), p = 0.012) and overall survival (OS) (adjusted HaR: 0.486 (0.286-0.827), p = 0.008). The stratified analysis made it possible to identify risk modification factors. Subsequent stratification by histological grade, Ki-67 and semi-quantitative PR expression or, mainly, the composite semi-quantitative expression of hormone receptors (cHR) enabled the identification of luminal breast cancer patients of adjuvant schema at higher risk for metastasis and death. However, initial analyses including patients of neoadjuvant therapy pointed to a path of subsequent stratification by cHR and histological grade, also enabling grouping of luminal breast cancer patients with similar prognosis for DMFS (cHR ≤ 4+ G2 or G3 versus triple-negative, adjusted HaR: 0.703 (0.415-1.189), p = 0.189) and OS (cHR ≤4+ G2 or G3 versus triple-negative, adjusted HaR: 0.662 (0.403-1.088), p = 0.104).

Conclusion: The semi-quantitative expression of both cHR, Ki-67 proliferation index and histological grade can identify luminal breast cancer patients at greater risk of developing metastasis and death when combined in a hierarchical fashion, and could be useful for a better prognosis stratification in services from low- and middle-income countries.

Keywords: Ki-67 antigen; breast neoplasms; neoplasm grading; oestrogen receptor alpha; progesterone receptors.

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Conflict of interest statement

The authors declared no conflicts of interest.

Figures

Figure 1.
Figure 1.. Cumulative survival curves by the KM estimator according to the Ki-67 expression level in luminal breast cancer patients (n = 448). (a): DMFS. (b): OS.
Figure 2.
Figure 2.. Cumulative survival curves by the KM estimator according to the semi-quantitative expression level of the PR in luminal breast cancer patients (n = 448). (a): DMFS. (b): OS. Legend: PR – Progesterone receptor.
Figure 3.
Figure 3.. Cumulative survival curves by the KM estimator according to the cHR in luminal breast cancer patients (n = 448). (a): DMFS. (b): OS. Legend: cHR – Composite semi-quantitative expression of hormone receptors.
Figure 4.
Figure 4.. Cumulative survival curves by the KM estimator according to the qualitative expression of hormone receptors in luminal breast cancer patients (n = 448). (a): DMFS. (b): OS.
Figure 5.
Figure 5.. Cumulative survival curves by the KM estimator according to the histological grade in luminal breast cancer patients (n = 448). (a): DMFS. (b): OS. Legend: G1 – Well differentiated; G2 – Moderately differentiated; G3 – Poorly differentiated.
Figure 6.
Figure 6.. Cumulative survival curves by the KM estimator according to the subsequent risk stratification by cHR and histological grade. (a): DMFS. (b): OS. A total of 572 patients were included. Legend: cHR – Composite semi-quantitative expression of hormone receptors; G1 – Well differentiated; G2 – Moderately differentiated; G3 – Poorly differentiated.
Figure 7.
Figure 7.. Cumulative survival curves by the KM estimator according to the subsequent risk stratification by Ki-67 and semi-quantitative expression of the progesterone receptor (PR). (a): DMFS. (b): OS. A total of 572 patients were included.
Figure 8.
Figure 8.. Cumulative survival curves by the KM estimator according to the subsequent risk stratification by Ki-67 and cHR. (a): DMFS. (b): OS. A total of 572 patients were included.
Figure 9.
Figure 9.. Cumulative survival curves by the KM estimator according to the subsequent risk stratification by grade, Ki-67 and semi-quantitative expression of the progesterone receptor (PR). (a) DMFS. (b): OS. A total of 431 patients of adjuvant schema were included.
Figure 10.
Figure 10.. Cumulative survival curves by the KM estimator according to the subsequent risk stratification by grade, Ki-67 and semi-quantitative expression of both hormone receptors (cHR). (a): DMFS. (b): OS. A total of 431 patients of adjuvant schema were included.
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