Breast cancer is a global health problem and the most common malignancy affecting women worldwide. Women have a 1 in 8 lifetime risk of breast cancer. Breast cancer is the second leading cause of cancer related death in American women. In 2011 approximately 230,480 new cases were diagnosed in the United States, with an expected 39,520 deaths. It is a heterogeneous, phenol-typically diverse disease composed of several biologic subtypes that have distinct behavior and response to therapy. -The use of adjuvant therapy is responsible for at least in part the reduction in cause-specific mortality from breast cancer seen in almost every western nation. Whether the tumors are estrogen (ER) or progesterone receptor (PR) positive or negative, the choice of agents used as adjuvant chemotherapy is the same.  The new era for breast cancer has shown that management and treatment can be totally individualized based on tumor characteristics. Genetic profiling and molecular measurements have refined our ability to predict outcomes and response to treatment assessment of stage, grade, ER/PR and HER-2 markers provide useful prognosis information; and have lead us to a specific and challenging new frontier in breast cancer known as targeted therapy. The new assay, Oncotype- Dx, measures the expression of 16 related genes normalized to 5 reference genes on molecular level ,  quantifies the likelihood of breast cancer of breast cancer recurrence in women ER positive/ node negative, predicts the magnitude of chemotherapy benefit, and strongly suggest that not all women with breast cancer benefit equally from chemotherapy.

Mapping the genetic landscape of a tumor allows for identification of biomarkers which can be used to predict response to treatment or a patient with high risk for recurrence. For example, the research team at Dana –Farber Institute has identified a marker of DNA damage in patient with triple negative that may be able to predict whether a patient has a potential to respond to platinum –base chemotherapy agents such as carboplatin and cisplatin. New targeted therapies are emerging on a regular basis and the result of clinical trials and studies of these new medications are encouraging. For example, endocrine therapy as a neoadjuvant for patients with hormone receptor positive breast cancer has been proven to reduce mortality. Furthermore, HER-2 targeted therapy in early breast has been shown to reduce the risk of relapse by 50% and the risk of mortality by 1/3 over chemotherapy alone. Although it was a great advance that led to the improvement in survival of patients with an aggressive form of breast cancer, trastuzumab is not a “magic bullet”, significant problems of resistance to the therapy and relapse require new drug development of next generation HER-2 therapy.  Although, anti-HER2 therapy with trastuzumab and chemotherapy is the standard first line treatment, the best therapeutic regimen has yet to be defined and new strategies are evolving.

Between 2000 and 2050, the number of new cancer patients diagnosed annually is expected to double with an accompanying increase in treatment cost of more than 80 billion over the next decade. Efficacious strategies for cancer prevention will therefore be vital for improving patient’s quality of life and reducing healthcare cost. Evidence from placebo controlled, randomized clinical trials supports the use of chemoprevention in women at high risk for developing breast cancer, and two agents Tamoxifen and Raloxifene are FDA-approved for the indication.  (ASCO 2012).

Dr. Gardith Joseph, MD
Hematology/Oncology

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