Evolution of HER2-Positive Breast Cancer: Yesterday, Today, and Tomorrow

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The fingerprint of breast cancer is understood in relation to its unique subtypes, each with its own molecular profile, biological behavior, and risk profile.
The fingerprint of breast cancer is understood in relation to its unique subtypes, each with its own molecular profile, biological behavior, and risk profile.

Breast cancer is the most common cancer diagnosed among women in the United States, accounting for nearly 1 in 3 cancer cases.1 It is second to lung cancer as a leading cause of cancer death in women. Women living in the United States have a 12.3%, or a 1-in-8 lifetime risk of developing breast cancer.1

Breast cancer is not an isolated uniform entity, but a complex group of diseases that is better understood as a result of greater knowledge of its biologic and genetic subtypes.2,3 The fingerprint of breast cancer is understood in relation to its unique subtypes, each with its own molecular profile, biological behavior, and risk profile.2 Evaluating biomarkers in breast cancer is crucial to diagnosis, prognosis, and treatment decisions. Prognostic and predictive markers are essential to therapeutic decision-making, especially as we aim to individualize treatment plans and outcomes.2 For the patient with breast cancer, a very important component of staging is to determine the status of estrogen, progesterone, and HER2. These are the biomarkers that guide decision-making and patient management, as well as characterize the nature of the breast cancer.

Tumor Biomarkers

Biomarkers provide clinicians with a more definitive and accurate diagnosis, identification of patients who may achieve a response to treatment and those with a greater likelihood of disease recurrence, and predictive measures for those patients most likely to experience toxicity.1 These markers are divided into subcategories: predictive and prognostic.

Predictive markers are associated with response or lack of response to a treatment. Prognostic markers — or indicators — provide baseline measurements that project a disease course.2 The role of biomarkers has exceeded that of just being a benchmark for the presence or absence of disease via measurements of serum-based proteins. The paradigm has shifted and the knowledge of biomarker monitoring and analysis has expanded to include assays of circulating factors in the peripheral blood, molecular and genetic assays of the tumor, and tumor/gene profiling via peripheral blood as well.

In relation to breast cancer, the American Society of Clinical Oncology (ASCO) guidelines were revised to include that tumor markers were acceptable in the prevention, screening, treatment and surveillance of breast cancer.2 Of these tumor biomarkers, identification of HER2 is recommended for all cases of newly diagnosed breast cancer to identify those patients who may benefit from HER2 monocolonal antibody treatments such as trastuzumab (Herceptin) and/or pertuzumab (Perjeta). 

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