Stuart J. Schnitt

Background: Breast phyllodes tumours (PTs) are rare biphasic fibroepithelial neoplasms, classified into benign, borderline and malignant categories. Stromal mitotic activity is a key criterion in grading PT, but the methodology for mitotic assessment has not been clearly articulated. Materials and methods: We discuss the approach to determining stromal mitotic activity in PTs. Whether the most mitotically active area (hotspot) or an average count across several tumour regions should be adopted is reviewed. We also outline the operational protocol for mitotic hotspot evaluation, accounting for different microscope models with varying field diameters. Results: A standardized method of determining stromal mitoses in PTs is recommended in order to improve interobserver reproducibility and accuracy in grading PTs. The application of digital tools in stromal mitotic counting is also addressed. Conclusion: We advocate using the hotspot method of obtaining the highest stromal mitotic count, together with other histological parameters, to classify PTs.

Representativeness of Study Participants

Purpose:Cyclin-dependent kinase 4/6 inhibitors can significantly extend survival when given in combination with endocrine therapy in patients with hormone receptor–positive metastatic breast cancer. However, their activity has been relatively underexplored in patients with metastatic triple-negative breast cancer (mTNBC).Patients and Methods:We conducted a single-arm phase II study of abemaciclib monotherapy in patients with Rb-positive mTNBC. Patients were treated with abemaciclib 200 mg orally twice daily until disease progression, unacceptable toxicity, or withdrawal of consent. The primary endpoint was the objective response rate; secondary endpoints included progression-free survival (PFS), overall survival (OS), clinical benefit rate, disease control rate, and safety and tolerability.Results:A total of 27 patients were enrolled before the trial was closed early because of slow accrual. Patients had received a median of two lines of systemic therapy in the metastatic setting prior to enrollment. After a median follow-up of 28.5 months, the objective response rate was 0%, the clinical benefit rate was 14.8%, and the disease control rate was 22.2%. The median PFS was 1.94 months (95% confidence interval, 1.84–11.47), and the median OS was 8.44 months (95% confidence interval, 4.57–15.57). Median PFS and OS did not differ significantly based on androgen receptor and PD-L1 status. Pretreatment gene expression profiling of tumor tissue provided some hypothesis-generating insights into biological features associated with clinical benefit in this study. The most common treatment-related adverse events of grade 2 or higher were diarrhea (40.7%), neutropenia (40.7%), anemia (29.6%), and nausea (29.6%).Conclusions:Abemaciclib monotherapy did not show clinical activity in patients with pretreated Rb-positive mTNBC.

The 6th edition of the WHO Classification of Breast Tumours introduces both major and minor changes based on recent advances in our understanding of breast biology, developments in diagnostic modalities, identification of specific molecular targets and new treatment regimens necessitating modifications to pathology reporting and tumour biomarker categorisation. This review summarises the main changes that strive towards a classification of global relevance. In invasive carcinoma, predictive factors increasingly inform modern breast cancer treatment. The 6th edition provides an update on HER2 reporting categories following the DESTINY‐Breast 04 and 06 trials. Terminologies used to classify invasive tumours are clarified, with the term ‘variant’ now reserved for molecular/genetic alterations. Invasive lobular carcinoma (ILC) with extracellular mucin is recognised as a new diagnostic entity with prognostic implications. The diagnosis of mucinous carcinoma (MC) is reserved for mucin secreting carcinomas with grade 1 or 2 morphology and a favourable biomarker profile. The diagnosis of malignant phyllodes tumours requires only four of the original five adverse histological criteria. Classification of neuroendocrine tumours (NETs) is revised, recognising that the unified model, promoted in the 5th edition, is difficult to apply to the breast. New approaches to the classification of adenomyoepithelioma are discussed but the 5th edition system is broadly retained. A new section on ‘Small Diagnostic Samples’ outlines the merits of non‐operative biopsy diagnosis, the B coding system and the importance of multidisciplinary review. Changes to diagnostic practice and the emerging role of artificial intelligence, with advantages and challenges, are discussed in a new section on ‘Digital Pathology’.

Representativeness of Study Participants

Phyllodes tumours (PTs) of the breast present diagnostic challenges due to their complex histological features and potential for malignant behaviour. The World Health Organisation (WHO) classification requires the presence of five adverse histological criteria to categorise PTs as malignant, aiming to avoid overdiagnosis and improve diagnostic consistency. However, emerging evidence suggests that these strict criteria may underdiagnose tumours with metastatic potential and histological features that would otherwise be considered malignant in soft tissue tumours, leading to significant implications for prognosis and treatment. Recent studies have highlighted cases where tumours classified as borderline PT by WHO criteria exhibited metastatic behaviour, emphasising the need to refine the diagnostic framework. Microscopic criteria used to classify PT also vary among reporting pathologists, resulting in suboptimal reproducibility. This review examines the histological parameters utilised in the classification of malignant PT, highlights existing evidence gaps and analyses international breast pathologist survey data to propose a pragmatic diagnostic approach. We recommend redefining malignant PTs to include cases meeting four of the five WHO criteria, supplemented by comprehensive sampling and clinical context. This approach balances the risk of underdiagnosis with the need for standardised, reproducible diagnostic practices. Future collaborative efforts should focus upon developing evidence‐based, biologically relevant classification systems and leveraging technological advancements to enhance diagnostic precision. These efforts aim to refine classification, improve prognostic accuracy and optimise patient management strategies.

Purpose: Cyclin-dependent kinase 4/6 inhibitors can significantly extend survival when given in combination with endocrine therapy in patients with hormone receptor–positive metastatic breast cancer. However, their activity has been relatively underexplored in patients with metastatic triple-negative breast cancer (mTNBC). Patients and Methods: We conducted a single-arm phase II study of abemaciclib monotherapy in patients with Rb-positive mTNBC. Patients were treated with abemaciclib 200 mg orally twice daily until disease progression, unacceptable toxicity, or withdrawal of consent. The primary endpoint was the objective response rate; secondary endpoints included progression-free survival (PFS), overall survival (OS), clinical benefit rate, disease control rate, and safety and tolerability. Results: A total of 27 patients were enrolled before the trial was closed early because of slow accrual. Patients had received a median of two lines of systemic therapy in the metastatic setting prior to enrollment. After a median follow-up of 28.5 months, the objective response rate was 0%, the clinical benefit rate was 14.8%, and the disease control rate was 22.2%. The median PFS was 1.94 months (95% confidence interval, 1.84–11.47), and the median OS was 8.44 months (95% confidence interval, 4.57–15.57). Median PFS and OS did not differ significantly based on androgen receptor and PD-L1 status. Pretreatment gene expression profiling of tumor tissue provided some hypothesis-generating insights into biological features associated with clinical benefit in this study. The most common treatment-related adverse events of grade 2 or higher were diarrhea (40.7%), neutropenia (40.7%), anemia (29.6%), and nausea (29.6%). Conclusions: Abemaciclib monotherapy did not show clinical activity in patients with pretreated Rb-positive mTNBC.