The St. Gallen surrogate classification for breast cancer subtypes successfully predicts tumor presenting features, nodal involvement, recurrence patterns and disease free survival

doi:10.1016/j.breast.2016.07.016

The Breast

Volume 29, October 2016, Pages 181-185

https://doi.org/10.1016/j.breast.2016.07.016 Get rights and content

Highlights

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All the analyzed tumor features differed significantly among the breast cancer IHC surrogates (p < 0.0001).
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The surrogates remained predictive of nodal involvement after adjusting for age, tumor size, nodal involvement, EIC and MF/MC.
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HER2-neu positivity remained predictive of EIC and MF/MC, after adjusting for HR, age, tumor size, nuclear grade and LVI.
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The surrogates had specific patterns of first recurrence that were both time-dependent and site-specific.
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Luminal B showed bone as first recurrence site and basal-like showed a low occurrence of nodal metastasis. Higher rates of visceral recurrence occurred among basal-like and HER2-neu+, translating in shorter DFI.

Abstract

Aims

To evaluate how the St. Gallen intrinsic subtype classification for breast cancer surrogates predicts disease features, recurrence patterns and disease free survival.

Materials and methods

Subtypes were classified by immunohistochemical staining according to St. Gallen subtypes classification in a 5-tyre system: luminal A, luminal B HER2-neu negative, luminal B HER2-neu positive, HER2-neu non luminal or basal-like. Data were obtained from the records of patients with invasive breast cancer treated at our institution. Recurrence data and site of first recurrence were recorded. The chi(2) test, analysis of variance, and multivariate logistic regression analysis were used to determine associations between surrogates and clinicopathologic variables.

Results

A total of 2.984 tumors were classifiable into surrogate subtypes. Significant differences in age, tumor size, nodal involvement, nuclear grade, multicentric/multifocal disease (MF/MC), lymphovascular invasion, and extensive intraductal component (EIC) were observed among surrogates (p < 0.0001). After adjusting for confounding factors surrogates remained predictive of nodal involvement (luminal B HER2-neu pos. OR = 1.49 p = 0.009, non-luminal HER2-neu pos. OR = 1.61 p = 0.015 and basal-like OR = 0.60, p = 0.002) while HER2-neu positivity remained predictive of EIC (OR = 3.10, p < 0.0001) and MF/MC (OR = 1.45, p = 0.02). Recurrence rates differed among the surrogates and were time-dependent (p = 0.001) and site-specific (p < 0.0001).

Conclusion

The St. Gallen 5-tyre surrogate classification for breast cancer subtypes accurately predicts breast cancer presenting features (with emphasis on prediction of nodal involvement), recurrence patterns and disease free survival.

Introduction

Molecular breast cancer subtypes are defined by gene expression profiling. However, immunohistochemical (IHC) expression of hormonal receptors (HR), HER2-neu and Ki-67% can categorize breast cancer analogous to molecular profiling. The St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer defined a surrogate to distinguish luminal A–like breast cancer from luminal B–like, HER2-neu non-luminal and basal-like disease, based on a combination of estrogen receptor (ER), progesterone receptor (PR), Ki67% and HER2-neu status, without a requirement for molecular diagnostics. It was released for clinical purposes in order to guide treatment decision-making for adjuvant therapies. It was defined for predictive goals but not for prognostic purposes. Among hormone receptor positive tumors (luminal type), luminal B tumors may or not overexpress HER2-neu and, if HER2-neu negative, a cut-off Ki67% of 20% was defined. The subject of Ki-67 cut-off value remains a subject of intense debate, with the threshold for luminal A classification being extended to 20–29% in the latest (2015) St. Gallen Consensus [1]. The other major subtypes of HR negative tumors are the HER2-neu overexpressing subtype and the basal-like subtype. Previous studies have shown that tumor presentation varies among molecular subtypes using IHC surrogates. These studies have partly used outdated subtypes definition (according to St. Gallen Criteria) and the significance of this classification both in terms of presenting features and clinical outcome, disease free interval (DFI) and recurrence patterns, remains unclear. If it is confirmed that the St. Gallen surrogates based on IHC adequately represent the molecular subtypes, it is of great clinical importance because IHC is cost affordable, fast and does not require an ultra-specialized laboratory facility.

Approximately one third of patients with early breast cancer experience recurrence after initial diagnosis. Site-specific recurrence patterns are influenced by classic prognostic factors such as nodal status, but also by the intrinsic tumor biology. Most recurrences occur within the first 5 years of diagnosis, with a subset of HR positive tumors recurring even after 10 years. The capacity to determine disease course based on the surrogate IHC classification would further support the capacity to adequately reflect the intrinsic tumor biology determined by molecular subtype.

Section snippets

Patient population

Inclusion Criteria: Patients treated at the Breast Center Kurfurstendamm that had information about the ER, PR, HER2-neu and Ki67% status of their primary tumor and were classifiable into subtypes. All HER2+ patients had to have undergone chemotherapy and treatment with Trastuzumab, all basal-like tumor patients had to be treated with chemotherapy and all luminal tumors were treated with at least anti-hormonal therapy. The chemotherapy regimen consisted of the standard regimen at that given

Results

A total of 2.984 tumors were classifiable into surrogate subtypes. The mean patients age was 56.4 ± 12.8 (range 24–95) years. The follow-up was a mean of 65.9 ± 42.0 months (range 1–192). The distribution of subtypes was luminal A, 59.9%; luminal B HER-2 negative 7.6%, luminal B HER2 positive, 11.7%; HER2 positive non-luminal 7.4% and basal-like, 13.5%. The presenting characteristics of the population are presented in Table 1.

Table 2 displays the characteristics by subtype and p values. Among

Discussion

Gene expression profiling of breast cancers identifies distinct molecular subtypes that affect prognosis [2]. In this work, subtypes were classified by IHC surrogates as Luminal A, Luminal B HER2-neu negative, Luminal B HER2-neu positive, non-luminal HER2-neu positive and basal-like(1). We found a statistical significant difference among subtypes when comparing the pathological and clinical features at presentation. Tumor subtype was a predictor of tumor size, nuclear grade, nodal status, LVI,

Conflict of interest statement

None declared.

Acknowledgments

The authors have no financial disclosures.

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Original articleThe St. Gallen surrogate classification for breast cancer subtypes successfully predicts tumor presenting features, nodal involvement, recurrence patterns and disease free survival

Highlights

Abstract

Aims

Materials and methods

Results

Conclusion

Introduction

Section snippets

Patient population

Results

Discussion

Conflict of interest statement

Acknowledgments

Ann Oncol

Hum Pathol

Ann Oncol

Clin Breast Cancer

Clin Breast Cancer

Lancet

Ann Oncol

Presenting features of breast cancer differ by molecular subtype

Ann Surg Oncol

Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study

JAMA

Original article
The St. Gallen surrogate classification for breast cancer subtypes successfully predicts tumor presenting features, nodal involvement, recurrence patterns and disease free survival