Breast cancer: Treatment advances

Years ago, the standard treatment for any kind of localized invasive breast cancer was often a radical mastectomy, which involved the total removal of the whole breast, many lymph nodes and sometimes, skin and muscle of the chest wall.

In the decades since, advancement in the understanding of breast cancer — how it grows, where it occurs and when it might recur — has led to the development of an array of treatments for the breast and the entire body that are used to target particular cancer types. This individualization of treatment is a common theme among recent advances in breast cancer care. Although it has led to better treatment results, it has also made the treatment decision process more complex.

Classifying The Cancer

When a suspicious lump is discovered in your breast, a diagnostic process begins to determine if the lump is benign or malignant (refer to last week’s article). If it is proven cancerous, your doctor then proceeds to find out more about the characteristics of the cancer. These tests are the first steps taken toward individualizing your treatment, with the goal of determining:

• Your cancer type. The main distinction here is whether the cancer is noninvasive (in situ), meaning the cells are abnormal, but they haven’t developed the potential to invade or spread; or invasive, meaning the cells have developed the ability to spread. In addition, a grade may be assigned to your cancer based on the appearance of the aggressiveness of the cancer cells.

• The stage of your cancer. Staging tests help determine the size and location of the cancer and whether it has spread to lymph nodes or other organs.

• Additional indicators. Two female hormones — estrogen and progesterone — affect the growth of many breast cancers. A standard diagnostic test looks for the presence or absence of hormonal receptors on cancer cells that allow estrogen or progesterone to bind to them, which can fuel their growth and are important targets for hormonal or endocrine therapy to kill cancer cells.

Other tests look for an excess of the human epidermal growth factor receptor 2 (HER-2) protein. Normally, substances that attach to this receptor stimulate cell growth. When too many of these receptors are present, they can increase the likelihood of cancer cells spreading.

Keeping Cancer Away

One of the treatment decisions you may have to make involves additional therapies before (neoadjuvant) and/or after (adjuvant) breast cancer is removed. For those found to have hormone receptors on their breast cancer cells, drugs may be used before and/or after surgery to either block estrogen production or interfere with hormone receptors on the cells. The goal is to reduce the size of the cancer mass or to kill any remaining cancer cells. There are four main options for women with hormone-sensitive cancers. These are:

• Tamoxifen alone for five years. Tamoxifen has been the mainstay of adjuvant therapy treatment for decades, reducing risk of cancer recurrence by about 50 percent for most women. For premenopausal women, this is the only hormone-related adjuvant therapy drug of choice.

• The aromatase inhibitor anastrozole (Arimidex) or letrozole (Femara) alone for five years. For postmenopausal women, this option reduces the risk of cancer returning by about one to two percent over tamoxifen. Long-term survival is the same as with tamoxifen so far, though further studies are needed.

• Tamoxifen for two to three years, followed by the aromatase inhibitor exemestane (Aromasin) or anastrozole (Arimidex), for two to three years. Studies have shown that compared with taking tamoxifen for five years, this sequence of drugs significantly prolongs survival.

• Tamoxifen for five years, followed by the aromatase inhibitor letrozole (Femara) for five years. This course is less likely to be recommended if you’re just starting with adjuvant therapy. However, if you’ve already taken tamoxifen for five years, taking letrozole for an additional five years reduces the risk of cancer returning by an additional 43 percent and prolongs survival.

No one adjuvant drug or combination is right for all women. Often, there’s more than one option and the choice of which drug course to take, if any, may be determined by individual characteristics. For instance, researchers recently discovered that about 10 percent of Caucasian women inherit a variation of the CYP2D6 gene that prevents them from properly processing tamoxifen. In these women, tamoxifen doesn’t appear to be nearly as effective in preventing cancer recurrence. It’s also been found that antidepressant drugs, including selective serotonin uptake (SSRIs) and drugs in related cases, may blunt tamoxifen’s effect. These include drugs like fluoxetine (Prozac) and venlafaxine (Effexor).

For women who test positive for excess HER-2 protein — which is the case for about 20 to 25 percent of breast cancers — standard chemotherapy isn’t as effective at keeping cancer from returning. For these women, the drug trastuzumab (Herceptin) was developed to inhibit this abnormal protein. Recent studies have found that trastuzumab can reduce cancer recurrence by as much as 50 percent and significantly prolong survival in women with HER-2 positive cancer.

Late last year, the US FDA approved a drug that may offer new hope for women with advanced breast cancer that’s positive for an excess of HER-2 protein. The drug, lapatinib (Tykerb), is similar to trastuzumab (Herceptin) because it can block the effects of HER-2. Tykkerb, used in combination with chemotherapy, may help some women who are no longer benefiting from Herceptin or other standard treatments. Tykerb’s approval was based on a randomized study of about 400 women with this type of cancer. In this study, half the women received a combination of Tykerb and the chemotherapy drug capecitabine (Xeloda), while the other half were just given Xeloda. In the combination treatment group, tumors took longer to start growing again. Nevertheless, experts caution that more research is needed before it’s known if Tykerb will help women with advanced HER-2 positive breast cancer live longer. 

Advances In Radiation Treatment

For women who have had a lumpectomy (see diagram), radiation therapy is usually recommended to kill any cancer cells that may have been left behind. It reduces the risk of cancer recurrence from between 25 and 35 percent, to under 10 percent. The traditional form of radiation therapy — which typically causes fairly mild side effects — is whole breast external beam irradiation (see figure). The procedure is similar to getting an X-ray, but the radiation is much more intense. A typical therapy session, including setup, takes about 20 to 30 minutes and is usually done five days a week for about six weeks. A newer kind of therapy — partial breast irradiation — exposes only a portion of the breast to radiation. A course of this therapy lasts only a week. Partial breast irradiation consists of either brachytherapy, which involves surgically implanting radioactive substances to temporarily deliver radiation to an area inside your breast, or 3-D irradiation which involves focusing three to five external radiation beams on an area of your breast.

Although each of these techniques has been studied in smaller, short-term trials, it’s not known how they compare to each other in terms of survival, cancer recurrence, or side effects, or how partial breast irradiation compares to traditional whole breast external beam irradiation. A large study has recently been launched to try to answer these questions but even early results are likely still a couple of years away.

Latest Thinking

One of the first places breast cancer spreads is the lymph nodes under the arm. Until recently, the standard was an extensive surgical procedure — with potential complications — involving the removal of multiple lymph nodes. This may include postmastectomy lymphedema, wherein the arm swells due to blockage in the flow of lymph. Now, a procedure called sentinel node biopsy (see figure), involves removing only the sentinel nodes, the first nodes to receive lymph drainage. These are the most likely to contain cancer if the cancer has spread.

Surgeons are also increasingly offering added benefits to their breast cancer patients. The newest is removing the tumor and cosmetically repairing the breast at the same time. This emerging field of “oncoplastic surgery” could allow a patient to minimize the number of times she must go under the knife.

Advances in breast cancer treatment occur on a frequent basis. Keep in touch with your doctors to get the best care possible.