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Breast Cancer
A Practical Clinical Approach to Adjuvant Therapy in Breast Cancer—An Update
Stephanie L Hines, MD,
1
Winston Tan, MD, FACP,
1
Alvaro Moreno-Aspitia, MD, FAAP, FACP,
1
Vivek Roy, MD, FACP,
2
Laura A Vallow, MD,
3
Sarah A McLaughlin, MD
4
and Edith A Perez, MD
5
1. Assistant Professor of Medicine; 2. Associate Professor of Medicine; 3. Assistant Professor of Radiation Oncology;
4. Assistant Professor of Surgery; 5. Professor of Medicine, Mayo Clinic, Jacksonville
Abstract
Adjuvant therapy for breast cancer has evolved to reflect the heterogeneous nature of the disease. Specific subtypes such as luminal, HER2-
positive, and basal subtypes express different molecular markers that can be targeted by a variety of novel agents; therapy is tailored to the
individual profile of each tumor. New risk-stratification models, including models based on a tumor’s genetic expression, enhance assessments
of recurrence risk so that the potential toxicities of a particular regimen can be weighed against the potential benefit. More precise tailoring of
adjuvant therapy may be possible in the future with advances in pharmaco-genetics, which will help to predict an individual’s response to
various agents. Optimal adjuvant treatment of breast cancer involves tailoring therapy to the individual patient and tumor.
Keywords
Breast cancer, adjuvant therapy, HER2, estrogen receptor, chemotherapy, trastuzumab, aromatase inhibitors, tamoxifen
Disclosure: Stephanie L Hines, MD, has received research grants from Novartis and sanofi-aventis. Alvaro Moreno-Aspitia, MD, FAAP, FACP, has received research funding from
BMS and Genentech. Winston Tan, MD, FACP, has received research grants from Genentech, sanofi-aventis, Novartis, and Roche. The remaining authors have no conflicts of
interests to declare.
Received: February 16, 2009 Accepted: April 20, 2009
Correspondence: Stephanie L Hines, MD, Mayo Clinic, 4500 San Pablo Rd, Jacksonville, FL 32224. E: hines.stephanie@mayo.edu
Advances in gene expression and molecular profiling have clarified Personalized Medicine in
that breast cancer is not a single disease entity, but a heterogeneous Breast Cancer in 2009
disease with multiple subtypes. Breast cancers can now be This individualized approach utilizes the presence of hormone
categorized into the luminal subtypes, which express estrogen receptors in breast cancer to provide specific anti-estrogen therapy,
receptors (ERs), the human epidermal growth factor receptor 2 with or without systemic chemotherapy. The presence of HER2 over-
(HER2)-positive subtypes, which express ERBB2, and the basal expression is targeted by a chemotherapeutic regimen that includes
subtypes, which tend to be negative for ERs and ERBB2 expression;
1–3
trastuzumab. Patients with basal subtype breast cancers who lack
each subtype is associated with a different prognosis. As a result, the specific targets for anti-estrogen or anti-HER2 therapy are candidates
adjuvant treatment of breast cancer has also evolved to reflect for chemotherapy only.
the heterogeneous nature of the disease. This evolution of treatment
options illustrates the complexity of adjuvant therapy selection A subset of breast cancers exist that may be overtreated by systemic
for patients with newly diagnosed breast cancer. This article will chemotherapy, and includes patients with node-negative, ER-positive
highlight the evolution of treatments and risk stratification models disease. A 21-gene assay (Oncotype Dx) was developed to predict the
over time and introduce possible developments for the future of risk for recurrence in this subset of patients.
4
Protein expression in 16
breast cancer therapy. cancer-related genes and five reference genes were used to develop a
recurrence score (RS) that would determine an individual cancer’s risk
Selection of Adjuvant Therapy for recurrence and predict overall survival (OS). Higher RS implied a
The goals of systemic adjuvant therapy are to reduce the risk for greater risk for recurrence and, thus, a greater benefit from adjuvant
recurrence and improve survival while causing minimal additional chemotherapy. Those individuals with low RS would be expected to
toxicity. The discovery of specific breast cancer subtypes that express have a lower risk for recurrence and thus have limited benefit from
different molecular markers has allowed the selection of breast cancer adjuvant chemotherapy. The Program for the Assessment of Clinical
therapies to be tailored to the individual profile of a patient’s tumor Cancer Tests in Breast Cancer Patients with ER-Positive and/or
(including tumor size and lymph-node status), risk for recurrence, Progesterone-Positive Axillary Node-Negative Candidate for Adjuvant
patient comorbidities, patient menopausal status, and patient desires. Cytotoxic Therapy in Addition to Hormone Therapy (PACCT-1/TAILORx)
© TOUCH BRIEFINGS 2009 49
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