Is it Time to Retire the Term of Low-Grade Ductal Carcinoma in Situ and Replace it With Ductal Neoplasia?

As the leading cause of cancer morbidity and the second leading cause of cancer mortality among women, breast cancer continues to remain a major global public health problem. Consequently, significant attention has been directed toward early breast cancer detection and prevention. As a result, the number of image-detected biopsies has increased, and minimally invasive diagnostic procedures have almost replaced open surgical biopsies. Therefore, pathologists are expected to provide more information with less tissue and diagnose increasing numbers of atypical proliferative breast lesions, in situ lesions, and small breast carcinomas. This is a difficult task, as reflected by continuous reports highlighting the challenges associated with morphologic distinction between atypical ductal hyperplasia and low-grade ductal carcinoma in situ. The current interobserver variability among pathologists to accurately define these two entities often leads to silent overdiagnosis and overtreatment. Up to now, there are no reproducible morphologic features and/or any reliable biomarkers that can accurately separate the above-mentioned entities. Despite these reports, patients diagnosed with low-grade ductal carcinoma in situ are subject to cancer therapy regardless of the fact that low-grade ductal carcinoma in situ is known to be an indolent lesion. Studies have shown that low and high-grade ductal carcinoma in situ are genetically different forms of breast cancer precursors; however, the term ductal carcinoma in situ is followed by cancer therapy regardless of the grade and biology of the tumor. In contrast, patients with the diagnoses of atypical ductal hyperplasia do not undergo cancer therapy. In the current article, attempts are made to highlight the continuous dilemma in distinction between atypical ductal hyperplasia and low-grade ductal carcinoma in situ. Going forward, we suggest that low-grade ductal carcinoma in situ be referred to as ductal neoplasia. This alternative terminology allows for different management and follow-up strategies by eliminating the word carcinoma.

The Breast Health Global Initiative 2018 Global Summit on Improving Breast Healthcare Through Resource-Stratified Phased Implementation: Methods and overview.

BACKGROUND: The Breast Health Global Initiative (BHGI) established a series of resource-stratified, evidence-based guidelines to address breast cancer control in the context of available resources. Here, the authors describe methodologies and health system prerequisites to support the translation and implementation of these guidelines into practice. METHODS: In October 2018, the BHGI convened the Sixth Global Summit on Improving Breast Healthcare Through Resource-Stratified Phased Implementation. The purpose of the summit was to define a stepwise methodology (phased implementation) for guiding the translation of resource-appropriate breast cancer control guidelines into real-world practice. Three expert consensus panels developed stepwise, resource-appropriate recommendations for implementing these guidelines in low-income and middle-income countries as well as underserved communities in high-income countries. Each panel focused on 1 of 3 specific aspects of breast cancer care: 1) early detection, 2) treatment, and 3) health system strengthening. RESULTS: Key findings from the summit and subsequent article preparation included the identification of phased-implementation prerequisites that were explored during consensus debates. These core issues and concepts are key components for implementing breast health care that consider real-world resource constraints. Communication and engagement across all levels of care is vital to any effectively operating health care system, including effective communication with ministries of health and of finance, to demonstrate needs, outcomes, and cost benefits. CONCLUSIONS: Underserved communities at all economic levels require effective strategies to deploy scarce resources to ensure access to timely, effective, and affordable health care. Systematically strategic approaches translating guidelines into practice are needed to build health system capacity to meet the current and anticipated global breast cancer burden.

Breast cancer treatment: A phased approach to implementation.

Optimal treatment outcomes for breast cancer are dependent on a timely diagnosis followed by an organized, multidisciplinary approach to care. However, in many low- and middle-income countries, effective care management pathways can be difficult to follow because of financial constraints, a lack of resources, an insufficiently trained workforce, and/or poor infrastructure. On the basis of prior work by the Breast Health Global Initiative, this article proposes a phased implementation strategy for developing sustainable approaches to enhancing patient care in limited-resource settings by creating roadmaps that are individualized and adapted to the baseline environment. This strategy proposes that, after a situational analysis, implementation phases begin with bolstering palliative care capacity, especially in settings where a late-stage diagnosis is common. This is followed by strengthening the patient pathway, with consideration given to a dynamic balance between centralization of services into centers of excellence to achieve better quality and decentralization of services to increase patient access. The use of resource checklists ensures that comprehensive therapy or palliative care can be delivered safely and effectively. Episodic or continuous monitoring with established process and quality metrics facilitates ongoing assessment, which should drive continual process improvements. A series of case studies provides a snapshot of country experiences with enhancing patient care, including the implementation of national cancer control plans in Kenya, palliative care in Romania, the introduction of a 1-stop clinic for diagnosis in Brazil, the surgical management of breast cancer in India, and the establishment of a women's cancer center in Ghana.

The role of pathologists in recognition of morphologic and biologic features of genetically mutated breast cancer.

The recent introduction of genomic medicine and emphasis on optimizing breast cancer risk reduction mortalities has provided opportunities for pathologists to partner with clinicians in advancing the diagnosis and management of breast cancer patients. The discovery of breast cancer genes BRCA1, BRCA2, and other breast cancer genes is considered a major breakthrough in the understanding of hereditary breast cancer. These discoveries have contributed to investigate the nature of tumorigenesis and the genetic and molecular pathology in multistep tumor development, as well as their relationship to endocrine and environmental factors. The recognition of unique morphologic and biological features associated with genetically mutated breast cancer by pathologists may have an impact on appropriate follow-up management of breast cancer patients.

Is it ductal carcinoma in situ with microinvasion or "Ductogenesis"? The role of myoepithelial cell markers.

Mammary myoepithelial cells have been under-recognized for many years since they were considered less important in breast cancer tumorigenesis compared to luminal epithelial cells. However, in recent years with advances in genomics, cell biology, and research in breast cancer microenvironment, more emphasis has been placed on better understanding of the role that myoepithelial cells play in breast cancer progression. As the result, it has been recognized that the presence or absence of myoepithelial cells play a critical role in the assessment of tumor invasion in diagnostic breast pathology. In addition, advances in screening mammography and breast imaging has resulted in increased detection of ductal carcinoma in situ and consequently more diagnosis of ductal carcinoma in situ with microinvasion. In the present review, we discuss the characteristics of myoepithelial cells, their genomic markers and their role in the accurate diagnosis of ductal carcinoma in situ with microinvasion. We also share our experience with reporting of various morphologic features of ductal carcinoma in situ that may mimic microinvasion and introduce the term of ductogenesis.

The changing role of pathologists from morphologists to molecular pathologists in the era of precision medicine.

Pathology is the study of human illness. Throughout centuries of scientific discoveries, pathologic examination of tissue samples has been the gold standard for diagnosis and pathologists have been involved in the elucidation of aetiology, assessment of the biology, clinicopathologic correlation and prediction of prognosis. The advances in science and technology and focused interest in breast cancer research have provided ample opportunities for pathologists to participate in better understanding of the basic fundamental cascade of events leading to tumorigenesis in breast cancer. They also partnered with their clinical colleagues and scientists to find more effective therapeutic options. This change has been possible with recognition of the fact that morphology alone may not be sufficient to tell the entire story of clinical behaviour of all breast cancer patients. In addition, the realization of heterogeneity of breast cancer and the differences in the expression of various biomarkers and the observed differences in response to therapy have resulted in extensive efforts to better define the characters of each breast cancer subtype. It is now generally agreed that breast cancer is not a single disease and not all patients with breast cancer can benefit from the same therapy. These changes have brought new challenges for pathologists. Pathologist are now required to not only provide diagnosis, but also study the precise molecular characterization of each individual breast cancer case and play a significant role in the treatment planning of breast cancer patients. This remarkable change in the role of the pathologist require his/her involvement in the modern taxonomy of this disease and to rise to the challenge of genomic medicine and molecular diagnostics, which are the fastest growing areas of medicine. Emphasis should also been placed to create a new morphomolecular pathology and train our young pathologist to expand beyond morphology and to embrace the power of molecular diagnostics, in order to be able to effectively practise in the era of precision medicine.

Development of a novel approach for breast cancer prediction and early detection using minimally invasive procedures and molecular analysis: how cytomorphology became a breast cancer risk predictor.

With enhanced public awareness, advances in breast imaging, and emphasis on early breast cancer detection and prevention, more women are seeking consultation to assess the status of their breast health. Risk assessment has become an integral part of established multi-disciplinary breast care, and breast cancer risk reduction interventions have received a great deal of attention. Similarly, interest in identification of high-risk individuals has increased significantly. Atypical proliferative changes in breast epithelial cells are ranked high among various known breast cancer risk factors and, in recent years, have been the subject of several investigations. Breast tissue and fluid in the ductal system provide a rich source of cells and biomarkers that have the potential to aid in the assessment of short-term risk of breast cancer development, and assess responses to interventional prevention efforts. There are three minimally invasive procedures currently being utilized to sample breast tissue in asymptomatic high-risk individuals. These procedures are: fine-needle aspiration biopsy, nipple aspiration fluid, and ductal lavage. In this review article, the merits and limitations of each procedure are presented, and the contribution of cytomorphology and molecular analysis in breast cancer prediction is highlighted. In addition, the role of Masood Cytology Index as a surrogate endpoint biomarker in chemopreventative trials is discussed.