Breast Cancer Treatment by Stage

Breast Cancer Treatments: Radiation Therapy

The stage of a cancer refers to the extent to which it has spread within the body at the time of diagnosis. Staging of cancers is typically done using a variety of tests and imaging studies to look for the extent of the cancer. To accurately determine the stage of a tumor, doctors look at the size of the tumor, the degree to which it has spread to nearby tissues, and the degree to which it has spread via the bloodstream to other organs or via the lymphatic vessels to the lymph nodes.

Breast cancer stages are divided into four broad groups: I, II, III, and IV. Within each of these four groups are several different subgroups. Ductal carcinoma in situ (DCIS) is a regarded as a very early form of breast cancer in which the abnormal cells have not begun to invade outside of the breast ducts; DCIS is sometimes referred to as stage 0 cancer. This article will focus on the treatment of invasive breast cancer in stages I-IV.

Stage I breast cancers are small and have not spread to the lymph nodes or have spread to the lymph nodes only in a tiny area. While this is an early stage of breast cancer, there is a risk of such cancers recurring if not treated effectively.

Surgery is the standard treatment for early-stage breast cancers. Both breast-conserving surgery (BCS; also referred to as lumpectomy or partial mastectomy) or mastectomy may be performed, depending upon many factors, including both location of the tumor and patient preference. The lymph nodes will also be evaluated to make certain there is no spread to these areas. This can be done by either a sentinel lymph node biopsy (looking at the lymph node most likely to be the site of tumor spread) or an axillary lymph node dissection. Breast reconstruction surgery can be done either at the same time as the cancer surgery or later on.

When BCS is performed, it is most commonly followed by radiation therapy to help reduce the risk of the cancer coming back (recurring). In women over 70 years of age who have small tumors that have not spread to the lymph nodes, radiation therapy may not always be given if the tumor has been shown to express hormone receptors and hormone therapy is given.

Any additional therapy intended to improve the likelihood that the cancer will never recur is called an adjuvant therapy. Such treatment depends upon the characteristics of the tumor. If the tumor expresses hormone receptors (estrogen, progesterone), it is said to be hormone-sensitive or hormone receptor-positive. This means that hormones stimulate growth of the cancer cells, and hormone therapy is recommended. The goal of hormone therapy is to block the body's ability to make hormones or to interfere with the activity of hormones.

Two different kinds of hormone therapy may be given. Tamoxifen (Nolvadex) is a commonly used drug of the selective estrogen receptor modulator (SERM) class. These drugs bind to estrogen receptors, preventing estrogen from binding. Tamoxifen is typically prescribed for premenopausal women (and men) who have estrogen receptor-positive breast cancer. Tamoxifen therapy is given for five to 10 years. Another drug class used for breast cancer hormone therapy is the aromatase inhibitors (AI). These further reduce levels of estrogen by blocking the conversion of adrenal hormones to estrogen through the process of aromatization in the fat. Women who are postmenopausal will usually receive adjuvant hormone therapy with an aromatase inhibitor, like anastrozole (Arimidex), letrozole (Femara), or exemestane (Aromasin). Women who become postmenopausal during tamoxifen treatment may be switched to an aromatase inhibitor. Because women may stop having periods on tamoxifen, blood tests to measure hormone levels are often needed to determine whether menopause has occurred. Another option for premenopausal women, instead of tamoxifen, is taking a medication to suppress activity of the ovaries along with an AI. Bisphosphonates are a drug class that can help reduce bone loss and fractures as well as improves survival in women taking AIs for breast cancer.

Hormone therapy is one type of adjuvant therapy. Chemotherapy is another type of adjuvant therapy. For early-stage breast cancers, including stage I tumors, chemotherapy is sometimes recommended. Chemotherapy is usually recommended if the tumor is hormone receptor-negative or is HER2-positive (see below). Chemotherapy may also be recommended for an estrogen-receptor-positive tumor if the tumor is large or has an unfavorable result on a genomic profiling assay such as the Oncotype DX Breast Cancer Assay. Chemotherapy is usually given for a period of three to six months depending upon the exact regimen selected.

Tumors that overexpress the HER2 (human epidermal growth factor receptor 2) receptor are generally treated with adjuvant HER2-targeted therapy. HER2 is a normal protein that helps normal breast cells grow and divide. However, in certain breast cancers, there are too many copies of the HER2 gene, leading to overexpression of the protein and uncontrolled cell growth. These are called HER2-positive cancers. Trastuzumab (Herceptin) is an example of an anti-HER2 drug that binds to the HER2 receptors and blocks their reception of growth signals.

Stage II breast cancer, but the risk that the cancer can recur is higher than in stage I. is also considered to be early stage breast cancer. Stage II cancers are larger than stage I tumors or have spread to a few nearby lymph nodes.

Surgery is also indicated to remove stage II breast cancers. Both breast-conserving surgery and mastectomy may be considered, depending on the size and location of the tumor and patient preferences. As with stage I tumors, lymph node status (whether or not the cancer has spread to lymph nodes) will be assessed. Women who received BCS or had larger tumor (over 5 cm) are typically then given radiation therapy as well.

Women with larger stage II tumors may be considered for neoadjuvant therapy. Unlike adjuvant therapies, which are given after surgery, neoadjuvant therapies are given before surgery. Hormone therapy, chemotherapy, and HER2-targeted therapies can all be given as neoadjuvant therapy. Typically, the reason that neoadjuvant therapy is given is to shrink the tumor prior to surgery so that less extensive surgery can be performed. Neoadjuvant therapies can shrink tumors, but they do not improve overall survival rates when compared to giving the therapies after surgery. Hormone therapy started as neoadjuvant therapy should be continued after surgery.

Types of adjuvant therapy for stage II breast cancer include hormone therapy, chemotherapy, and HER2-targeted therapy. The same considerations apply for choosing the appropriate adjuvant therapy as outlined above under stage I tumors. Sometimes more than one adjuvant therapy is recommended, such as a combination of hormone therapy and chemotherapy, or a combination of chemotherapy and HER2-targeted therapy. Other drugs that may be used for HER2-positive breast cancers include pertuzumab (Perjeta) and lapatinib (Tykerb).

Stage III breast cancers are larger (5 cm across or more), have spread into local tissues like the skin or muscle, or have spread to 10 or more nearby lymph nodes. The risk of recurrence of these cancers is high, but a cure remains possible.

Often, stage III breast cancers are treated with some kind of neoadjuvant therapy to shrink the tumors prior to surgery. If the tumor size can be significantly reduced, BCS may still be an option. If neoadjuvant therapy is not given or if the tumor has spread to nearby tissues, mastectomy is typically the procedure of choice. An axillary lymph node dissection is often performed to evaluate the lymph nodes, although for some patients a sentinel lymph node biopsy may be an option. Radiation therapy is recommended after surgery for patients with stage III tumors.

Adjuvant therapy is also given. The type of adjuvant therapy depends upon the characteristics of the tumor as described previously and can include hormone therapy, chemotherapy, HER2-targeted therapy, or a combination of these.

Stage IV breast cancers have spread to other sites in the body and are referred to as metastatic breast cancers. Today, save in anecdotal instances, these cancers are incurable.

Common sites to which tumors may have spread include the lungs, liver, and bones. Hormone therapy, chemotherapy, and HER2-targeted therapies (depending upon the characteristics of the tumor) are the mainstay of therapy. Surgery is generally not done except in special situations, such as relieving compression on the spinal cord, treating a small number of metastases in one area, or treating brain metastases in certain situations. Radiation therapy may also be used in certain situations for symptom relief or treating certain areas of metastatic tumor.

Hormone therapy is often the first treatment for stage IV cancers that are hormone receptor-positive, but since this may take some time to work, chemotherapy may be given first if there are severe symptoms. Switching to different types of hormone therapy or chemotherapy than originally received may be indicated. Likewise, additional HER2-targeted drugs may be given to patients with stage IV breast cancers that are HER2-positive.

Clinical trials to test new combinations of drugs or new drugs are another treatment option.