HER2/neu overexpression is associated with a poorer prognosis and is seen in 20% to 30% of all breast cancers.2 The treatment for an overexpressed HER2-neu is IV trastuzumab given every three weeks for one year. Trastuzumab has remained the mainstay of therapy in this population of patients since the American Society of Clinical Oncology’s 2007 update of recommendations for the use of tumor markers in breast cancer.6 Trastuzumab is a humanized monoclonal antibody that binds to HER2/neu, rendering the protein inactive. The antibody has been demonstrated in prospective randomized clinical trials to improve response rates, time to progression, and overall survival in patients with breast cancer.6
Surgery
Treatment for breast cancer starts with the surgical excision of the cancerous tumor. Once the diagnosis of breast cancer has been determined from the CNB, the patient is referred to a surgeon. The consultation involves discussion of what surgical procedure would provide the best outcome for the patient. Lumpectomy vs. mastectomy will be discussed. Lumpectomy (also referred to as breast conservation therapy, or BCT) is the excision of a tumor measuring <2 cm with clear margins >1 cm.7 Factors that indicate BCT over mastectomy include tumor size, location, number, and patient preference.
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BCT followed by radiation was shown to be as effective as mastectomy in early-stage breast cancer in terms of decreasing risk recurrence and improving overall survival.8 The patient needs to understand that BCT will be followed by radiation therapy (or if chemotherapy is indicated, radiation therapy will follow chemotherapy) to gain the full benefits of this treatment modality vs. mastectomy (which does not require radiation therapy). The rate of recurrence was shown to be higher in patients who underwent BCT without radiation (39.2%) compared with those who underwent BCT followed by radiation (14.3%). Thus, BCT followed by radiation therapy has become the standard of care.8
Radiation therapy is indicated to reduce risk of recurrence at the site of the excised tumor, as the likelihood of recurrence is highest at the primary site.2 Taking this one step further, the long-term results of a randomized trial comparing BCT/radiation with mastectomy at 10 years revealed no difference between the two groups in terms of overall survival rates (65% and 66%, respectively).7
Lymph nodes
Either sentinel-node biopsy or axillary-lymph-node dissection will take place along with the breast surgery. Because of the risk of long-term lymphedema of the arm, a sentinel-node biopsy is preferable whenever possible. The sentinel lymph node is the one most likely to be positive in metastatic disease, as it is the first node that would receive drainage from the breast tumor.2 The sentinel node is identified by injecting the tumor site with a radioactive tracer prior to surgery. During surgery, a gamma probe is used to detect the sentinel node.2 A section of tissue is excised and examined by the pathologist in surgery. If the sentinel node is positive, a complete axillary dissection will be necessary. This procedure requires removing 15 to 20 lymph nodes from the affected side.2
A randomized clinical trial was conducted to determine the effects of complete axillary-lymph-node dissection (ALND) on survival of patients with sentinel-lymph-node (SLN) metastasis of breast cancer. Among patients with limited SLN metastatic breast cancer treated with breast conservation and systemic therapy, the use of SLN biopsy alone did not result in inferior survival.9 Thus, SNL biopsy is rapidly becoming the perferred treatment in this population.
Oncology
After surgery, the patient will be referred to an oncologist to discuss secondary treatment options in the adjuvant setting. Adjuvant treatment includes radiation therapy, chemotherapy, and/or endocrine (hormone-blocking) therapy. For the purpose of this discussion, only treatment of Stage I (a tumor measuring <2 cm and lymph-node-negative), ER-positive breast cancer will be covered (as this is likely the most confusing diagnosis to treat). Treatment at this stage is not straightforward and is dependent on size of the tumor, histologic grade, hormone receptor status, and HER2-neu status.
Determining which patients will benefit from chemotherapy can be tricky. In early-stage breast cancer, a recommendation of chemotherapy is made based on the size and histologic grade of the tumor.2 A tumor measuring 0.6 to 1.0 cm with grade 2 (moderately differentiated) or grade 3 (poorly differentiated) features (or any tumor >1.0 cm) is considered appropriate for chemotherapy, according to guidelines from the National Comprehensive Cancer Network (NCCN).10 However, not all patients will benefit from adjuvant chemotherapy in early-stage breast cancer, despite the presence of such unfavorable features as tumor size or histologic grade.
Two tools can help determine whether adjuvant chemotherapy will reduce recurrence risk for these patients:
Adjuvant! Online, a Web-based program, allows clinicians to predict of the overall benefit of chemotherapy for all cancer patients based on age, overall health status, and pathology characteristics (histologic grade, tumor size, hormone receptor status, and node involvement). The goal is to help health-care professionals make estimates of the risk of negative outcomes (cancer-related mortality or relapse) without systemic adjuvant therapy, estimates of the reduction of these risks afforded by therapy, and risks of side effects of therapy.
A second tool that is used to gauge the potential benefit of chemotherapy is the Oncotype DX breast cancer assay. This 21-gene assay utilizes an algorithm to calculate a recurrence score (RS). A patient with a low RS who takes tamoxifen will have a <10% chance of experiencing disease recurrence during the subsequent 10 years.6 Patients who have a high-risk score benefit from the addition of chemotherapy, emphasizing the predictive value of this assay. A patient with a low RS would likely not benefit from adjuvant chemotherapy.11
When considering adjuvant systemic therapy for breast cancer patients, the following are essential steps in developing a treatment plan: (1) estimate risk for recurrence; (2) estimate likelihood of benefit from adjuvant treatment; (3) determine potential risks; and (4) identify patient preferences.
