Symposium on Cancer - September 2010
Tex Med . 2010;106(9):56-58.
By Robert Ruxer, MD; Janice Tomberlin, MD; and Anita Chow, MD
The treatment for breast cancer requires the expertise of multiple specialties. Diagnostic radiologists, surgeons, and medical and radiation oncologists form a multidisciplinary team that works closely together to develop treatment plans that will be most beneficial for patients.
Overall, the surgical treatment of breast disease has become less invasive and therefore causes less discomfort for patients without compromising the clinical outcome. We also recognize that the psychological impact of the surgical treatment has significant influence on the quality of life of cancer patients.
The method of diagnosing breast disease has changed over the last 15 years. When a patient presents with a palpable breast mass or an imaging abnormality, the current standard of care is to obtain tissue diagnosis via image-guided core needle biopsy. This is less invasive than a surgical biopsy. The diagnosis of the disease gives an opportunity for the physician to discuss the treatment options with the patient. Furthermore, it allows the physician to begin assessing the extensiveness of the disease, thus determining the clinical stage before surgery.
To evaluate the local extensiveness of the disease, recent advancements in breast magnetic resonance imaging (MRI) technology has added another dimension to the workup. Because breast MRI is more sensitive in detecting invasive malignancy compared with mammogram and breast sonogram, it can be a helpful adjunct in evaluating those patients with dense breast tissue. In addition to assessing the local extensiveness of the disease, the surgeon also recognizes the possibility of the patient having metastatic disease at the time of diagnosis. Body computed tomography (CT) scan, bone scan, and positron emission tomography (PET)-CT scan are important tools in the systemic disease evaluation process. This clinical staging information will allow the multidisciplinary team to devise treatment options and treatment sequences that suit the particular patient.
Mastectomy and breast conservation therapy are the two main surgical approaches for local disease control. The NSABP B-6 trial demonstrated that patient survival is comparable between mastectomy and breast conservation therapy. That breast conservation therapy requires obtaining clear surgical margins around the tumor and the patient being offered postsurgical breast radiation therapy should be emphasized.
The techniques of mastectomy have continued to evolve. Skin-sparing mastectomy has been used more frequently now because of its superior cosmetic outcome when it is done with immediate reconstructive surgery.
The 1998 Women's Health and Cancer Rights Act guarantees reconstructive procedures associated with mastectomy as a part of breast cancer treatment. It can be done as an immediate (at the time of mastectomy) or as a delayed (after completing cancer treatments) procedure.
For those patients who present with clinically early-stage disease and who desire reconstruction, immediate reconstructive surgery offers better cosmetic result and potentially few surgical procedures. Reconstruction uses either saline or silicone implants or autologous tissue flap transfer techniques.
On the other hand, for those patients who have tumor greater than 5 centimeters or who have more than four metastatic lymph nodes, delayed reconstruction is advised because of the need for postmastectomy radiation therapy, which can compromise the reconstructive process.
Aside from managing disease in the breast, surgeons also play an active role in lymph node staging and treatment. Lymph node disease management is an important aspect of locoregional control of the disease. Sentinel lymph node biopsy (SLNB) has replaced axillary lymph node dissection (ALND) as the initial evaluation method of the lymph node basin for patients who present with clinically negative lymph node. The principle of SLNB is that if the first draining lymph node is histologically negative for malignancy, then the remaining lymph node basin should be free of the disease. However, if the sentinel lymph node contains metastatic focus, then ALND is carried out to further evaluate the lymph node basin. Patients undergoing ALND often experience lymph edema and significant paresthesia of the arm; SLNB can minimize the patients' exposure to those side effects. Furthermore, the histologic evaluation method of a sentinel lymph node is more sensitive in detecting small focus of metastatic disease.
SLNB has shown to increase the accuracy of lymph node evaluation and sometimes can upstage patients' disease. This has a significant impact on the decision of adjuvant treatment planning. Better locoregional control can translate into better survival for the patients. The American College of Surgeons has ongoing prospective clinical trials in assessing the clinical impact of sentinel lymph node containing micrometastatic focus of disease (> 0.2 mm, < 2.0 mm), and lymph node with isolated tumor cells (< 0.2 mm). These results will further modify our surgical management of locoregional disease.
Once the definitive surgery and clinical staging are complete, the next step for the patient is to visit with the medical oncologist. Factors such as whether the cancer cells were influenced by estrogen or whether they expressed the HER2 protein on their surfaces can help predict the prognosis of each individual patient. New tests like the Oncotype Dx, which is a 21-gene assay that provides an individualized prediction of chemotherapy benefit and 10-year distant recurrence rate, help oncologists and patients make treatment decisions in early-stage node-negative cases.
Systemic therapy is designed to kill cancer cells that may have spread elsewhere in the body. Systemic therapy given after the definitive surgery to treat microscopic cancer cells is called adjuvant therapy. Three options for adjuvant systemic therapy include chemotherapy, hormonal therapy, and targeted therapy. These are combined in various regimens, dependent on the prognostic factors of the individual's cancer cells. Treatment regimens are evaluated constantly and changed on the basis of evidence learned through clinical trials. Recently, the combination of a cancer cell being estrogen and progesterone receptor negative along with HER2neu negative has been identified as a particularly aggressive behaving breast cancer. These cancers are called basal like malignancies; research trials are ongoing to address the best combination of drugs for this particular breast cancer.
The most common chemotherapy drugs used in breast cancer include cyclophosphamide, methotrexate, fluorouracil (5-FU), adriamycin, and the taxane drugs taxol and taxotere. Chemotherapy usually starts several weeks after surgery and is given in cycles that repeat every 3 weeks for 4 to 8 cycles over several months. Recently, interest has grown in giving chemotherapy in a dose-dense fashion, which gives the same number of cycles over a shorter period of time. This requires the use of blood-stimulating drugs to allow the bone marrow to recover quicker; this regimen is usually used in patients with a poorer prognosis. Sometimes, for patients with locally advanced breast cancer, the chemotherapy is given before surgery in what is called a neoadjuvant fashion. Success rates have been shown to be similar for chemotherapy given before and after surgery. This is part of what the multidisciplinary team individualizes for each patient.
Targeted therapy with herceptin is used in combination with chemotherapy in cases where the cancer cells overexpress the protein HER2/neu on their cell surfaces. HER2/neu overexpression is present in about 25% of breast cancer patients and generally indicates a more aggressively behaving cancer cell. Herceptin binds to the receptor and tells the body's defense system to target the cancer cell. It may also stop the HER2 cancer cell from telling itself to grow and divide. Poly (ADP-ribose) polymerase (PARP) inhibitors are a new class of targeted therapy in development. The PARP enzyme repairs damage done to DNA. It is postulated that drug resistance may be due to cancer cells using PARP to repair DNA damage. PARP inhibitors interfere with the PARP enzyme.
Hormonal therapy takes advantage of the estrogen receptor that is expressed on the surface of some, usually less-aggressive breast cancer cells. Tamoxifen and the more recently developed aromatase inhibitors affect estrogen's ability to bind to the surface of the cancer cell and stimulate cell division. Oral antiestrogen medications can be given in an adjuvant fashion after or during chemotherapy in selected cases and are usually continued for 5 years. In some cases, switching from one antihormonal agent to another midway through the 5 years to further affect the cancer cells is beneficial.
Radiation is almost always used after a lumpectomy or partial mastectomy to complete the breast conservation process. In the original NSABP B-6 trial, the group of patients treated with lumpectomy alone without breast irradiation had about a 40% recurrence rate in the breast. The fact that most of the time these recurrences were in the same location as the original tumor has led some researchers to investigate whether partial breast irradiation is an option for some patients. An ongoing randomized NSABP B-30 trial is investigating a partial breast irradiation compared with whole breast irradiation in selected patients. In this treatment, a catheter device is inserted into the lumpectomy cavity shortly after the lumpectomy, and high-dose-rate brachytherapy irradiation is given to a 1 cm surface from the applicator. Treatment is given to this smaller volume of tissue twice daily for 10 fractions over 5 days.
Radiation is sometimes used as an adjunctive therapy after a mastectomy, usually when the tumor is bigger than 5 cm or involve four or more lymph nodes. This requires coordination with the medical oncologist, breast surgeon, and plastic surgeon. Radiation usually follows chemotherapy and in the cases that are treated in a neoadjuvant fashion, decisions about radiation are made on the stage at presentation rather than the pathologic stage following chemotherapy.
After the initial treatment course is complete, most patients are followed long term and for at least 5 years by the oncologist. If a patient develops a recurrence, additional systemic therapies with chemotherapy, hormonal therapy, or targeted therapies are considered. Radiation is very useful in the treatment of metastatic breast cancer, specifically when the bones or brain are involved. Quadrimet, a targeted radiotherapy for bone metastases, attaches a Samarium-153 radioactive molecule and a tetraphosphonate chelator (EDTMP) and targets areas in the bone where breast cancer cells are active.
In recent years, surgeons have also played an increasingly important role in the care of patients with metastatic disease. With the advancements in systemic therapy, the ability to control systemic disease has improved. Emerging data suggest that if the systemic disease is controlled, surgical intervention such as mastectomy not only serves as a local palliative procedure, but also can improve the patient's survival.
Undoubtedly, the surgical, medical, and radiologic treatment of breast disease will continue to evolve. The ongoing research and clinical trials will continue to change the practice of breast cancer management and ultimately to better serve our patients.
Robert Ruxer, MD, of Fort Worth, specializes in medical oncology. Janice Tomberlin, MD, of Bedford, specializes in breast cancer. Anita Chow, MD, has practiced with Texas Health Care in Fort Worth since 2006.
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