Stage II Breast Cancer

Overview

Patients diagnosed with Stage II breast cancer have a primary cancer that either involves axillary lymph nodes and is less than five centimeters (two inches) in size, or is greater than two centimeters (3/4 inch) in size and does not involve any axillary lymph nodes.

Effective treatment of Stage II breast cancer generally requires both local and systemic therapy. Local therapy consists of surgery and/or radiation and is directed at destroying cancer cells in or near the breast. Systemic therapy is directed at destroying cancer cells throughout the body, and may include chemotherapy, targeted therapy, and/or hormonal therapy. Systemic therapy is often administered as adjuvant therapy, which means treatment after surgery.

The following is a general overview of treatment for Stage II breast cancer. Multi-modality treatment, which utilizes two or more treatment techniques, is increasingly recognized as an important approach for improving a patient’s chance of cure or prolonging survival. In some cases, participation in a clinical trial utilizing new, innovative therapies may provide the most promising treatment. Circumstances unique to each patient’s situation may influence how these general treatment principles are applied. The potential benefits of multi-modality care, participation in a clinical trial, or standard treatment must be carefully balanced with the potential risks. The information on this website is intended to help educate patients about their treatment options and to facilitate a mutual or shared decision-making process with their cancer physician.

Local Therapy: Surgery and Radiation

Systemic Therapy

• Chemotherapy
• Targeted Therapy
• Hormonal Ttherapy

The Era of Personalized Medicine

• Who Benefits from Chemotherapy?

Strategies to Improve Treatment

Local Therapy

Surgery and radiation are considered local therapies because they can treat the cancer in the breast and prevent cancer recurrence in the affected breast and surrounding area, but cannot treat cancer that has already spread to other locations in the body.

Surgery: Surgery for Stage II breast cancers may consist of mastectomy or lumpectomy. A mastectomy involves removal of the entire breast, whereas a lumpectomy involves removal of the cancer and a portion of surrounding tissue. Because a lumpectomy alone is associated with a higher rate of cancer recurrence than mastectomy, patients who elect to have a lumpectomy are also treated with radiation therapy. This combination of lumpectomy and radiation therapy is called breast-conserving therapy. Clinical studies have shown that breast conserving therapy is associated with a lower risk of local cancer recurrence compared with lumpectomy alone.

Mastectomy and breast-conserving therapy are the current standards of care for the local treatment of Stage II breast cancers and both are considered acceptable options. Furthermore, breast conserving therapy and mastectomy have been shown to produce similar long-term survival.

Surgery for early-stage breast cancer may also involve the evaluation of axillary (underarm) lymph nodes in order to determine whether cancer has spread outside the breast and establish the stage of the cancer. This is important to determine whether additional treatments beyond local therapies, such as chemotherapy, are required. For over 30 years, the standard of practice for breast cancer staging has included the removal of approximately 10-25 axillary lymph nodes to help determine whether the cancer has spread. This procedure, called an axillary lymph node dissection, can be associated with chronic side effects, including pain, limited shoulder motion, numbness, and swelling.

A newer approach for evaluating whether cancer has spread to the lymph nodes is a sentinel lymph node biopsy. The advantage to this procedure is that it involves the removal of a single lymph node (or a small number of nodes), called the sentinel node, which is the first lymph node to collect excess fluid surrounding the cancer. Prior to surgery, blue dye is injected near the cancer. The dye drains from the area containing the cancer into the nearby lymph nodes, through the sentinel node. The node containing the dye is removed during surgery and evaluated under a microscope to determine whether cancer has spread. Sentinel lymph node biopsy is becoming the standard approach for determining whether cancer has spread to the axillary lymph nodes.

Researcher now indicates that sentinel node biopsy appears to be just as effective in determining cancer spread to axillary lymph nodes as an axillary lymph node dissection and results in fewer side effects in patients with early-stage breast cancer.

For more detailed information, go to Surgery for Breast Cancer.

Radiation therapy: Radiation therapy is usually administered to patients who undergo a lumpectomy, and may also be administered to selected patients who undergo a mastectomy. Radiation therapy is often administered using a machine that delivers a beam of radiation deep into the body where the cancer resides, a technique called external beam radiation therapy (EBRT). These treatments are typically administered five days per week for five to six weeks.

Radiation may also be delivered over a shorter time period using a procedure known as breast brachytherapy. Patients may wish to discuss with their doctor whether this is an appropriate approach for them.

For more detailed information, go to Radiation Therapy for Breast Cancer.

Systemic Therapy: Chemotherapy, Targeted Therapy, and Hormonal Therapy

Systemic therapy is treatment directed at destroying cancer cells throughout the body. Some patients with Stage II breast cancer already have small amounts of cancer that have spread outside the breast that the surgery or radiation does not treat. These cancer cells are referred to as micrometastases. The presence of micrometastases may cause breast cancer recurrence following local treatment with surgery and/or radiation therapy alone. An effective systemic treatment is needed to eliminate micrometastases in order to improve a patient’s duration of survival and potential for cure.

Chemotherapy

Chemotherapy is any treatment involving the use of drugs to kill cancer cells, and is a standard adjuvant (post-surgery) treatment for early-stage breast cancer. Cancer chemotherapy may consist of single drugs or combinations of drugs, and can be administered through a vein or delivered orally in the form of a pill.

Chemotherapy options: There are many different chemotherapy drugs and combinations of drugs (regimens). The regimen consisting of cyclophosphamide, methotrexate and fluorouracil (CMF) was the first standard combination used to treat individuals with early-stage breast cancer and has been in use for many years. CMF chemotherapy is typically administered for six cycles over a period of approximately four to six months.

Research shows that the inclusion of the chemotherapy drug doxorubicin in adjuvant chemotherapy increases the number of women that can expect to survive without evidence of cancer compared to combination chemotherapy without doxorubicin. CAF (cyclophosphamide, doxorubicin, and fluorouracil) and AC (doxorubicin and cyclophosphamide) are also considered standard chemotherapy regimens for the treatment of early-stage breast cancer. However, these regimens are typically associated with more side effects than CMF.

Taxanes: The taxanes are a class of chemotherapy drug that have been shown to improve cancer-free survival in women with Stage II-III breast cancer. Taxotere® (docetaxel) appears to be more effective than paclitaxel in the treatment of patients with advanced breast cancer. The taxanes are typically combined with AC chemotherapy.In 2004, the U.S. Food and Drug Administration (FDA) approved Taxotere for the treatment of early-stage breast cancer.

Dose-dense chemotherapy: AC, TAC, CMF, and other chemotherapy regimens are typically administered every three weeks. Dose-dense chemotherapy refers to chemotherapy treatment that is administered more frequently. Dose-dense treatment is given every two weeks rather than at the conventional three-week interval in order to increase the total amount of chemotherapy used to treat the cancer.

Researchers have reported that patients with node-positive breast cancer treated with dose-dense chemotherapy live longer without cancer recurrence than patients treated with conventional chemotherapy. The 2,005 patients involved in one study received chemotherapy treatment with doxorubicin, paclitaxel, and cyclophosphamide either every three weeks (conventional treatment) or every two weeks (dose-dense). Four years after treatment, 82% of patients treated with dose-dense therapy were disease-free, compared to 75% of those treated with conventional chemotherapy.

Targeted Therapy

Targeted therapies are anticancer drugs that interfere with specific pathways involved in cancer cell growth or survival. Some targeted therapies block growth signals from reaching cancer cells; others reduce the blood supply to cancer cells; and still others stimulate the immune system to recognize and attack the cancer cell. Depending on the specific “target,” targeted therapies may slow cancer cell growth or increase cancer cell death.

Herceptin® (trastuzumab): Herceptin is a targeted therapy that binds to a protein known as HER2. Twenty to thirty percent of breast cancers overexpress (make too much of) HER2, and could potentially respond to treatment with Herceptin. Results from an important clinical trial indicate that adding Herceptin to chemotherapy improves survival for patients with advanced HER2-positive breast cancer. Herceptin has also been shown to improve survival among women with early-stage HER2-positive breast cancer that is node-positive or high-risk node-negative. Among women with early-stage breast cancer, Herceptin is part of a treatment regimen that also includes chemotherapy.

Hormonal Therapy

Estrogen causes some cancers to grow. The breasts, uterus and other female organs are composed of cells that contain estrogen receptors. When cells that have estrogen receptors become cancerous, exposure to estrogen increases the cancer’s growth. Cancer cells that have estrogen receptors are referred to as estrogen receptor-positive (ER-positive) cancers.

The growth of ER-positive breast cancer cells can be prevented or slowed by reducing the exposure to estrogen. This is the goal of hormonal therapy for breast cancer. Hormonal therapy drugs include tamoxifen as well as a newer of drugs known as aromatase inhibitors. Aromastase inhibitors include Femara® (letrozole), Arimidex® (anastrazole), and Aromasin® (exemestane). In premenopausal women, surgical removal of the ovaries or suppression of ovarian activity may also be used to reduce estrogen exposure.

For more information, go to Hormonal Therapy for Breast Cancer.

The Era of Personalized Medicine

An important advance in the treatment of cancer is the development of more individualized cancer therapy. Information provided by genomic tests or from analysis of other characteristics of cancer cells can often help guide the selection of treatments that have the best chance of success for a particular patient.

In the case of node-negative breast cancer, adjuvant chemotherapy has been shown to benefit many, but the extent of the benefit varies by the likelihood of cancer recurrence. Women with very small node-negative breast cancers, for example, have a low risk of recurrence and may not require adjuvant therapy to further reduce recurrence risk. In contrast, women with larger tumors – or other poor prognostic factors, such as high tumor grade -  are more likely to benefit from adjuvant therapy.

Although factors such as tumor size can help guide decisions about the need for adjuvant therapy in women with node-negative breast cancer, researchers have been interested in developing more accurate approaches to the assessment of recurrence risk. One such approach involves genomic testing of tumor tissue. The expression, or activity, of certain genes has been linked with the likelihood of cancer recurrence; testing tumor tissue for the expression of these genes may provide important information about prognosis and likely response to treatment.

Oncotype DX is a test that measures the expression of 21 genes in a sample of early-stage breast cancer cells. The test is used to calculate a Recurrence Score, which indicates the likelihood of cancer recurrence. Studies have reported that among women with node-negative, estrogen receptor-positive breast cancer treated with tamoxifen, the Recurrence Score is a better predictor of recurrence than standard measures such as patient age, tumor size, and tumor grade. The Recurrence Score was also linked with the response to chemotherapy among women with node-negative, hormone receptor-positive breast cancer, and can help guide decisions about the need for chemotherapy.

Strategies to Improve Treatment

The development of more effective cancer treatments requires that new and innovative therapies be evaluated with cancer patients. Clinical trials are studies that evaluate the effectiveness of new drugs or treatment strategies. Future progress in the treatment of Stage II breast cancer will result from the continued evaluation of new treatments in clinical trials. Participation in a clinical trial may offer patients access to better treatments and advance the existing knowledge about treatment of this cancer. Patients who are interested in participating in a clinical trial should discuss the risks and benefits of clinical trials with their physician. Areas of active investigation aimed at improving the treatment of Stage II breast cancer include the following:

Additional Approaches to Personalized Medicine

• Who Benefits from Tamoxifen?

Neoadjuvant Chemotherapy

Newer Approaches to Radiation Therapy

Adjuvant Bisphosphonate Therapy

Additional Approaches to Personalized Medicine

Who benefits from tamoxifen? Pharmacogenomics refers to the study of how inherited genetic variation influences drug response. As this field progresses, it is likely to lead to more individualized cancer therapy. For example, a gene known as CYP2D6 plays a role in tamoxifen metabolism (the processing of tamoxifen by the body). Most people have two functional versions of this gene and are able to effectively process tamoxifen. Some people, however, have versions of this gene that are less effective at processing tamoxifen. Testing patients for these gene variants could eventually help doctors identify patients who are less likely to respond to tamoxifen.

Neoadjuvant Chemotherapy

Neoadjuvant therapy is treatment administered before surgery. The purpose of neoadjuvant therapy is to immediately treat and shrink the cancer in order to increase the likelihood that it may be completely removed with surgery. A committee of physicians, called The Consensus Conference Committee, has published treatment guidelines stating that neoadjuvant chemotherapy is “the treatment of choice” for patients with Stage III breast cancer and is “worthy of consideration” in patients with Stage IIA and IIB breast cancer. The committee’s guidelines are determined by an extensive review of clinical studies that evaluated neoadjuvant chemotherapy in different stages of breast cancer.

Researchers affiliated with the National Surgical Adjuvant Breast and Bowel Project have reported that neoadjuvant chemotherapy that includes the drug Taxotere produces more anti-cancer responses than neoadjuvant chemotherapy without Taxotere or neoadjuvant chemotherapy plus adjuvant Taxotere. This trial involved over 2,000 women who were randomly assigned to receive one of the following treatments:

• AC (doxorubicin plus cyclophosphamide) before surgery
• AC plus Taxotere before surgery
• AC before surgery plus Taxotere after surgery

Approximately 91% of the patients treated with Taxotere before surgery had an anti-cancer response, compared to 85% of patients in the other two groups.

Newer Approaches to Radiation Therapy

Brachytherapy:Advances in radiation therapy have led to the development of an alternative to external beam radiation therapy (EBRT) called brachytherapy. Brachytherapy is a technique for delivering radiation internally by implanting a radioactive material directly into or near the cancer. An advantage of brachytherapy is that the total delivery time is reduced to several days (as opposed to several weeks with whole-breast external beam radiation therapy).

Radiation “boost” therapy: Standard radiation therapy following a lumpectomy consists of a limited dose of radiation (50 Gy) to the entire affected breast. While this treatment leads to long-term outcomes similar to those from mastectomy, women under age 50 experience higher rates of local recurrences following this treatment regimen compared to their elder counterparts. Researchers have theorized that an additional boost of radiation aimed only at the area from which the cancer was removed could reduce the rates of local recurrences, especially in younger patients.

The European Organization for Research and Treatment of Cancer has reported that an additional dose of radiation to the site of the removed cancer reduces local recurrence by nearly 50% among women with Stage I or II breast cancer. The 5,318 women involved in this trial had undergone a lumpectomy followed by the standard dose of radiation. Approximately half of the patients were given an additional small dose of radiation to the area where the cancer had been located, while the other half received no additional treatment. The researchers followed the women for an average of 5.2 years. Women 40 years old and younger exhibited the largest benefit; in this group, local recurrences occurred in only 10.2% of patients receiving additional radiation, compared to 19.5% of those receiving standard treatment. Overall survival rates and the development of distant metastases were similar whether women received an additional boost of radiation or standard therapy. Side effects including cosmetic results and fibrosis (formation of scar tissue) were not affected by the additional radiation.

Shorter-course Radiation Therapy: The current approach to radiation therapy involves several consecutive weeks of daily treatment. For many women, particularly those who have to travel long distances to reach a radiation therapy facility, this can interfere greatly with work and other activities of daily life.

A possible alternative approach is hypofractionated radiation therapy. Hypofractionation involves fewer radiation treatments with a higher dose of radiation at each treatment. Hypofractionated radiation therapy was compared to conventional radiation therapy in two clinical trials conducted in the U.K. Women treated with hypofractionated radiation therapy received a total radiation dose of 39 to 41.6 Gy administered over 13 to 15 visits. Women treated with conventional radiation therapy received a total radiation dose of 50 Gy administered over 25 visits. Risk of cancer recurrence was low with both approaches, and there was a suggestion that hypofractionation may result in better breast appearance. The long-term effects of hypofractionation remain unknown, however.

Adjuvant Bisphosphonate Therapy

Bisphosphonates are a class of drugs that inhibit bone resorption. They are used to treat osteoporosis, as well as hypercalcemia (high levels of calcium in the blood) and bone metastases in patients with cancer.

Recent research suggests that the bisphosphonate drug Zometa® (zoledronic acid) may also have a role in improving outcomes among women with early-stage breast cancer. A phase III clinical trial by the Austrian Breast Cancer Study Group enrolled 1,803 premenopausal women with Stages I-II, hormone receptor-positive breast cancer. Following surgery, all patients were treated with hormonal therapy; this consisted of Zoladex® (goserelin) for ovarian suppression, plus tamoxifen or Arimidex® (anastrozole). In addition to hormonal therapy, some patients were also treated with Zometa.

Compared with hormonal therapy alone, the combination of hormonal therapy and Zometa reduced the risk of cancer recurrence by 35%. The researchers concluded that the addition of Zometa to hormone therapy among premenopausal women with hormone receptor-positive breast cancer may improve recurrence-free survival.

References

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