Diagnosis of Metastatic Breast Cancer— A Case Report Using Molecular Cancer Classification

Yogesh Gandhi, Sunil Gandhi
US Oncology & Hematology, 2011;7(2):116-8
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Abstract

An accurate cancer diagnosis is critical as it can direct the use of site-directed, and potentially more effective, treatment options for specific types of cancer. A differential or uncertain diagnosis could prevent cancer patients from receiving optimal treatment, thus affecting their overall prognosis. Advances in molecular technology have led to the development of molecular cancer classifiers that can direct or confirm the diagnosis of metastatic cancers which would otherwise be considered uncertain or unknown. This case report describes the role of molecular diagnostics in the evaluation of a patient with a large pancreatic mass and a history of breast cancer. Results from a 92-gene molecular profiling assay (CancerTYPE ID®) predicted that this new mass was breast cancer. This diagnosis allowed for effective treatment and complete response in this patient.
Keywords
Molecular cancer classification, CancerTYPE ID®, breast cancer
Disclosure The authors have no conflicts of interest to declare.
Received: May 25, 2011 Accepted August 17, 2011
Correspondence: Sunil Gandhi, MD, FACP, 521 North Lecanto Highway, Lecanto, FL 34461. E: sunilggandhi@gmail.com

Despite the increasing sophistication of methods for detecting and diagnosing cancer, these methods fail to reveal a primary site of origin for a subset of patients with metastatic disease. Histopathology, the traditional cornerstone of cancer diagnosis, relies on cell morphology and tissue architecture, but can be subjective. Immunohistochemical analysis of specific tumor markers, in addition to histology and clinical findings, also aids in a differential cancer diagnosis, but can be subjective or misinterpreted as well, since many metastatic tumors do not retain the morphologic or phenotypic characteristics of their organ of origin.1,2

Despite comprehensive work-up, the tissue of origin remains uncertain or unknown in approximately 10–15 % of metastatic cases, and the possibility of misclassification remains a challenge. Failure to identify the primary origin of cancer of a metastasis despite extensive clinical work-up can lead to a diagnosis of carcinoma of unknown primary origin (CUP), or occult primary malignancy, and highlights the importance of diagnosis of the primary site.1,3,4 CUP accounts for approximately 3–5 % of all malignancies.1,3,4 A tumor’s primary anatomic site of origin usually dictates the optimal treatment, expected outcome, and overall prognosis for a cancer patient. The overall prognosis for patients with CUP is usually poor, with a median survival of three to nine months, even with newer treatment regimens.5–10 Multiple empiric chemotherapy regimens have been used for CUP patients, but there are few randomized data to support a specific regimen.11 The median survival in randomized studies is approximately seven months, which is both poor and significantly less than the expected survival for patients with breast and bowel malignancy following standard therapy.12 Survival improvement has been demonstrated in the CUP subset of patients if the primary site is identified, allowing for specific therapy to be initiated.2,13–17 Unfortunately, primary tumor detection remains a challenge in CUP: currently, the accuracy rate of a diagnostic work-up for CUP by histopathology, immunohistochemistry, and radiologic or other clinical methods is only 20–30 %.12,18,19 Additionally, extensive CUP work-up is expensive and time-consuming.20 Therefore, there is a need for more sophisticated tools to aid in correct primary diagnosis, particularly with the development in the last decade of targeted biologic therapies for specific tumor types, such as trastuzumab in breast cancer,21 erlotinib in lung cancer,22 and bevacizumab in renal cell,23 breast,24 and colorectal cancers,25 to name a few.

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