Pathology's Changing Role in Breast Cancer Diagnosis and Treatment

Abstract:

The pathological examination has been the gold standard for cancer diagnosis as well as the clarification of aetiology, pathophysiology, clinicopathological correlation, and prognosis. The introduction of modern technology, as well as the understanding that breast cancer is heterogeneous, has changed the focus to prognosis, with more emphasis placed on the identification of morphological and immunohistochemical markers of prognostic significance. Despite significant efforts, the majority of immunohistochemical biomarkers in breast cancer have not been shown to be useful in multivariate analysis, with only the oestrogen receptor, progesterone receptor, and Her2/neu expression remaining essential components of the pathological examination. These three markers were first used for prognosis, but their significance in treatment also made them predictive.

The relevance of proliferative gene expression in these subtypes has been proven, and surrogate immunohistochemistry markers for more expensive molecular testing include ER, PR, Her2/neu, and Ki67. Importantly, molecular technologies have not only revealed new insights into the heterogeneity of breast cancer but have also opened up new paths for treatment by identifying crucial signalling molecules in the proliferation and survival of neoplastic cells. Cancer treatment is thus shifting away from the traditional "one size fits all approach and toward individualised treatment suited to the specific characteristics of the tumour. Pathologists continue to play their traditional diagnostic role.

Introduction:

The biological examination is still the mainstay of diagnosis, especially in the case of malignant disorders. Pathologists examine gross and microscopic features to assess aetiology, anticipate behaviour, and give a diagnosis that correlates with the clinical presentation of the disease. Initially, this was done on excised specimens and was based on simple macroscopic findings including tumour size, amount of involvement, presence of necrosis, and presence of metastasis or vascular invasion. With the advent of less invasive techniques, smaller samples of diseased tissue became available for examination, and tumour behaviour prediction became increasingly centred on microscopic features such as cell type, the extent of differentiation, mitotic activity, microscopic lymphovascular invasion, lymphoplasmacytic reaction, metastasis, and tumour border nature.

The pathologist's job as a diagnostic oncologist thus encompasses the entire spectrum or continuum of cancer care, from prevention and screening to diagnosis, prognosis, prediction of therapeutic response, and disease monitoring. This role has recently been expanded to include molecular components that allow for a deeper understanding of cancer development and treatment.

This rising significance for pathology is demonstrated by the revelation that breast cancer is not a single disease and that subgroups of breast cancer with variable clinical outcomes may be detected visually.

The goal to provide individualised medicine in place of the old 'one size fits all strategy, as well as complementary and supplementary to conventional treatment modalities, has resulted in this paradigm change in breast cancer.

The Conventional Role of pathology:

The Scarff-Bloom-Richardson grading system for breast cancer was devised using microscopic observations based on tubule development, mitotic activity, and cellular pleomorphism. Following refining and introduction into the Nottingham Prognostic Index, a robust scoring system that predicted long-term survival for breast cancer patients was developed. This and other approaches have served as the foundation for the majority of clinical management choices involving adjuvant therapy. However, using traditional treatment methods like surgery, chemotherapy, and radiation, it became clear that many patients relapse after treatment and that many patients who qualify for recognised treatment regimens or regimes do not benefit from the treatment.

It is also worth noting that the relative importance of the prognostic variables used in the Nottingham Prognostic Index changes with time; a prognostic feature that is highly relevant for outcome in the first year following diagnosis may be of little consequence after 5 years. In a long-term study of 464 breast cancer patients, it was discovered that umor diameter, axillary lymph node status, glandular formation, and the proportion of intraductal growth had prognostic value for up to 5 years; the mitotic index was significant for the first 2 years, but the histological grade and morphometric nuclear factors had only short-term value.

The Role of Pathology in the Molecular Era:

Cancer is a disease of accumulating genetic abnormalities, and characterization of these variations is expected to help not only in understanding the genesis of various tumours, but also in diagnosis, prognosis, and treatment. The rapid development of high-throughput molecular technologies has made significant contributions to breast cancer research by providing insights into the disease's molecular complexity and a realisation that biological heterogeneity may have implications and opportunities for new forms of treatment.

Cancer Stem Cells:

According to the stem cell theory of cancer, tumours contain a small number of tumour-initiating cells or cancer stem cells that drive tumour growth, as well as populations of more differentiated nontumorigenic daughter cells that are analogous to transit-amplifying and differentiated cells in normal tissue. Indeed, several studies point to parallels between normal stem cells and tumorigenic cells. Both normal stem cells and tumorigenic cells have the ability to proliferate and give rise to new (normal or pathological) tissues. Tumours and normal tissues are both made up of many cell populations with varying phenotypic traits and proliferative potential.

because the majority of cancers have a clonal origin. Tumorigenic cancer cells must produce a phenotypically varied progeny that includes cancer cells with unlimited proliferative potential as well as cancer cells with limited or no proliferative potential. This shows that tumorigenic cancer cells go through mechanisms similar to normal stem cell self-renewal and differentiation. Although some tumour heterogeneity is caused by ongoing mutagenesis, it is also possible that heterogeneity is caused by cancer cells' abnormal differentiation.

Conclusions:

Pathology has traditionally focused on diagnosis, aetiology, prognosis, and clinicopathological connections.

Prognosis has been assisted by immunohistochemical examination of protein gene products, and three indicators, namely in breast cancer, ER, PR, and Her2/neu (and, more recently, Ki67), are frequently evaluated as prognostic and predictive markers.

The advancement of high-throughput technologies, as well as the advent of molecular tools such as CGH arrays, proteomic profiling, and sequencing technology, has opened up new areas of investigation into the genesis of breast cancer. More crucially, it has led to the recognition that there may be new and specially designed therapeutic options. Such advancements have defined a new role for pathology,

which encompasses breast cancer prognosis and treatment.

Thank you….

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https://medium.com/@elizaedwards2021/10th-world-breast-pathology-and-breast-cancer-conference-6db6e4fc81c2

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https://www.quora.com/profile/BreastCancerUCGConferences/10th-World-Breast-Pathology-and-Breast-Cancer-Conference-Dear-colleagues-and-guests-welcome-to-the-10th-World-Breast-Pa

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https://www.reddit.com/user/breastcancerucg1/comments/taq1kt/10th_world_breast_pathology_and_breast_cancer/

https://www.blogger.com/blog/post/edit/3238443600245550728/7246086302346767315 10th World Breast Pathology and Breast Cancer Conference | LinkedIn

https://medium.com/@elizaedwards2021/10th-world-breast-pathology-and-breast-cancer-conference-6886c15ccb37

https://wordpress.com/post/breastpath2022.wordpress.com/6

https://medium.com/@elizaedwards2021/breast-cancer-disease-f0324f19b8a2

https://www.blogger.com/blog/posts/3238443600245550728

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