The regrouping of Luminal B (<scp>HER2</scp> negative), a better discriminator of outcome and recurrence score

Yang, Zhengjun; Liu, Yu‐Xiao; Huang, Yue; Chen, Zu‐Jin; Zhang, Hao‐Zhi; Yu, Yue; Wang, Xin; Cao, Xuchen

doi:10.1002/cam4.5089

Cited by 13 publications

(7 citation statements)

References 37 publications

(82 reference statements)

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“…Further studies will be needed to investigate the prognostic value of mitotic density and of the other components of Nottingham grading for HER2+ tumors. Such tumors are often included within the category of luminal B, which has been di cult to de ne 31 . It is worth pointing out that the experimental setup of the current study, in which AI is used to evaluate a large number of cases with high accuracy and reproducibility, warrants such re-assessment of existing morphological tumor characteristics.…”

Section: Discussionmentioning

confidence: 99%

Prognostic value of deep learning based mitotic count in hormonal receptor- and HER2-positive breast cancer

Balkenhol

Mercan

Tessier

et al. 2023

Preprint

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The discovery of molecular subtypes has corroborated the heterogeneity of breast cancers. But in clinical routine, treatment selection relies on measuring the aggressiveness of the tumor via histopathology, which is routinely based on grading, a prognostic yet laborious, poorly reproducible, and subjective procedure defined more than 30 years ago, before molecular subtypes existed. In this paper, we present an interpretable deep learning-based computer-aided diagnosis method to automate mitotic count, one of the components of grading; the method complies with current guidelines and automates hot-spot finding on full digital whole-slide images of routinely prepared pathologic slides stained with hematoxylin and eosin. We use the computer model to query the current “one-size-fits-all” mitotic count procedure by investigating subtype-specific prognostic value of mitotic count using an external independent large-scale multicentric dataset of 1,709 breast cancers. We show that for human epidermal growth factor-2 (HER2) positive tumors, mitotic count was not prognostic. In hormone-receptor positive/HER2 negative cancers, an average mitotic count density different from clinically used cut offs predicted worse recurrence free survival in multivariable analysis, adjusted for known clinical prognosticators. We provided some first experimental evidence that the prognostic role of mitotic count should be reviewed.

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Section: Discussionmentioning

confidence: 99%

Prognostic value of deep learning based mitotic count in hormonal receptor- and HER2-positive breast cancer

Balkenhol

Mercan

Tessier

et al. 2023

Preprint

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“…Luminal B BC has several poor biological characteristics, such as a higher mutational load and a higher proliferation index (such as Ki-67), compared with luminal A BC. These features are prominent hallmarks in this group, thus making it more prone to ET resistance [8,[25][26][27]. In such conditions, resistant cancer cells could proliferate and develop new cells with more biological mutations, eventually causing clinical jeopardy in patients [28,29].…”

Section: Discussionmentioning

confidence: 99%

Positive p53 Expression Is Associated with Primary Endocrine Therapy Resistance in Locally Advanced Stage Luminal B HER2-Negative Breast Cancer Patients: A Cross-Sectional Study in Indonesia

et al. 2023

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Luminal B HER2-negative breast cancer (BC) is the most common type in Indonesian BC patients, and frequently manifests with locally advanced staging. Recurrence often occurs within two years of the endocrine therapy course (primary endocrine therapy (ET) resistance). p53 mutation often exists in luminal B HER2-negative BC, but its application as an ET resistance predictor in those populations is still limited. The primary purpose of this research is to evaluate p53 expression and its association with primary ET resistance in luminal B HER2-negative BC. This cross-sectional study compiled 67 luminal B HER2-negative patients’ clinical data during their pre-treatment period until they completed a two-year course of endocrine therapy. They were divided into two groups: 29 patients with primary ET resistance and 38 without primary ET resistance. Pre-treatment paraffin blocks from each patient were retrieved, and the p53 expression difference between the two groups was analyzed. Positive p53 expression was significantly higher in patients with primary ET resistance [odds ratio (OR) of 11.78 (95% CI: 3.72–37.37, p-value < 0.0001)]. We conclude that p53 expression could be a beneficial marker for primary ET resistance in locally advanced luminal B HER2-negative BC.

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“…Our result was in line with a study conducted in China which revealed a substantial association between various tumor subtypes and DFS. 22 Researchers and clinicians have not yet agreed on a standard for the proportion of stromal TIL in breast cancer. In this study, anatomical pathologists performed the stromal TIL examination using the recommendations of the International TIL Working Group for Breast Cancer.…”

Section: Discussionmentioning

confidence: 99%

“…The idea is that cancer cells can prevent these lymphocytes from entering tumors by overexpressing FasL (PDL-1) on their surface. 22,23 Additionally, it is thought that the production of FasL results in "exhausted" lymphocytes and is linked to the apoptosis of tumor-infiltrating lymphocytes in vivo. There is currently no information about the onset of PDL production by cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Stromal Tumor Infiltrating Lymphocytes (TIL) as a potential prognostic biomarker for recurrence in Locally Advanced Breast Cancer (LABC) patients

et al. 2022

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Background: Tumor-infiltrating lymphocytes (TIL) serves as the host adaptive immune response in breast cancer. TIL has the potential to be an independent prognostic factor in breast cancer patients. In this study, we aimed to examine the association between stromal TIL and recurrence in locally advanced breast cancer patients. Methods: A cohort retrospective study was conducted using medical records of female breast cancer patients with locally advanced breast cancer. We collected patients' data, including demographic data from the medical record. Stromal TIL was examined following the recommendations of the International TIL Working Group 2014. Results: 75 samples were included with an average age of 49.5±8.4. Ductal carcinoma was the most common type histologically (88.0%). Luminal B Her2-negative was the predominant breast cancer subtype (32.0%). There was a significant association between the breast cancer subtype and disease-free survival (P – 0.014). The optimal cut-off to determine the recurrence of breast cancer was 15%. The sensitivity, specificity, PPV, NPV, and accuracy of TIL to predict the 24-month disease-free survival (DFS) were 80.5%, 82.4%, 84.6%, 77.8%, and 81.3%, respectively. Every 10% increase in TIL percentage could raise the DFS by 5.45 months (p=0.001). Patients with high TIL values had higher survival than those with low TIL values. Conclusion: There was a significant correlation between the stromal TIL and the recurrence rate. The pre-therapy stromal TIL percentage can be employed as a potential biomarker to predict breast cancer recurrence, particularly in the first two years.

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The regrouping of Luminal B (HER2 negative), a better discriminator of outcome and recurrence score

Cited by 13 publications

References 37 publications

Prognostic value of deep learning based mitotic count in hormonal receptor- and HER2-positive breast cancer

Prognostic value of deep learning based mitotic count in hormonal receptor- and HER2-positive breast cancer

Positive p53 Expression Is Associated with Primary Endocrine Therapy Resistance in Locally Advanced Stage Luminal B HER2-Negative Breast Cancer Patients: A Cross-Sectional Study in Indonesia

Stromal Tumor Infiltrating Lymphocytes (TIL) as a potential prognostic biomarker for recurrence in Locally Advanced Breast Cancer (LABC) patients

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