How do doctors decide who needs adjuvant therapy?

Not all women with breast cancer need adjuvant therapy. Patients at higher risk of cancer recurrence are more likely to need adjuvant therapy. Doctors look at both prognostic and predictive factors to decide which patients might benefit from adjuvant treatments. Prognostic factors help doctors estimate how likely a tumor is to recur. Predictive factors help doctors estimate how likely cancer cells are to respond to a particular treatment.

In addition to a woman’s age and menopausal status, several other prognostic factors are used to determine the risk of recurrence (10).

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Stage of the cancer. Cancer stage refers to the size of the tumor and whether it is in the breast only or has spread to nearby lymph nodes or other places in the body. Larger tumors (especially those that are more than 5 centimeters—about 2 inches—in diameter) are more likely to recur than small tumors. Breast cancer often first spreads to the lymph nodes under the arm (axillary lymph nodes). During surgery, doctors usually remove some of these underarm lymph nodes to determine whether they contain cancer cells. Cancer that has spread to these lymph nodes is more likely to recur.

Tumor grade. This term refers to how closely the tumor cells resemble normal breast cells when viewed under a microscope. Tumors with cells that bear little or no resemblance to normal breast cells (called poorly differentiated tumors) are more likely to recur. Women with tumor cells that look like normal breast cells (called well-differentiated tumors) tend to have a better prognosis.

Proliferative capacity of the tumor. Proliferative capacity refers to how fast the tumor cells divide, or multiply, to form more cells. Women who have tumor cells that have a low proliferative capacity (that is, the cells divide less often and grow more slowly) tend to have a better prognosis.

Hormone receptor status. The cells of many breast tumors express receptors for the hormones estrogen and progesterone. Tumors with cells that do not express hormone receptors are more likely to recur. Doctors can determine whether a tumor expresses hormone receptors with laboratory tests.

HER2 status. Tumors that produce too much of a protein called HER2 are more likely to recur. Doctors can determine whether a tumor produces too much HER2 with a laboratory test.

Two major predictive factors are currently used to determine whether cancer cells might respond to particular treatments (11):

Hormone receptor status. As mentioned above, the cells of many breast tumors express receptors for the hormones estrogen and progesterone. These hormones bind to the receptors and help the cancer cells grow. Blocking the activity of these hormones with hormonal therapy stops the growth of the cancer cells. Hormonal therapy will not help patients whose tumors do not express hormone receptors.

HER2 status. Tumors that produce too much of the protein HER2 can be treated with trastuzumab, which can cut the risk of recurrence by up to about half (7). Women whose tumors do not produce too much HER2 do not benefit from treatment with trastuzumab.

Clinical trials are under way to see if genetic information collected from tumors can help predict which women will benefit from adjuvant chemotherapy. See Question 7 for more information about these tests.

Prognostic and predictive factors cannot determine exactly which patients may benefit from adjuvant therapy and which patients may benefit from primary therapy alone. Decisions about adjuvant therapy must be made on an individual basis. This complicated decision-making process is best carried out by consulting an oncologist, a doctor who specializes in cancer treatment. In addition to the factors described above, doctors will take into account a woman’s general health and her personal treatment preferences. 

What is neoadjuvant therapy?

Neoadjuvant therapy is treatment given before primary therapy. A woman may receive neoadjuvant chemotherapy for breast cancer to shrink a tumor that is inoperable in its current state, so it can be surgically removed. A woman whose tumor can be removed by mastectomy may instead receive neoadjuvant therapy to shrink the tumor enough to allow breast-conserving surgery (12–14).

Neoadjuvant chemotherapy is given in the same manner as adjuvant chemotherapy (see Question 3). If a tumor does not respond (shrink) or continues to grow during neoadjuvant chemotherapy, the doctor may stop treatment and try another type of chemotherapy or perform surgery instead, depending on the stage of the cancer.

Clinical trials are examining whether hormonal therapy or trastuzumab is effective when given before surgery. See Question 7 for more information about clinical trials of neoadjuvant therapies.

What are the side effects of adjuvant and neoadjuvant therapy?

Chemotherapy: The side effects of chemotherapy depend mainly on the drugs a woman receives. As with other types of treatment, side effects vary from person to person. In general, anticancer drugs affect rapidly dividing cells. These include blood cells, which fight infection, cause the blood to clot, and carry oxygen to all parts of the body. When blood cells are affected by anticancer drugs, patients are more likely to get infections and bruise or bleed easily, and may have less energy during treatment and for some time afterward. Cells in hair follicles and cells that line the digestive tract also divide rapidly. As a result of chemotherapy, patients may lose their hair and may have other side effects, such as loss of appetite, nausea, vomiting, diarrhea, or mouth sores.

Doctors can prescribe medications to help control nausea and vomiting caused by chemotherapy. They also monitor patients for any signs of other problems and may adjust the dose or schedule of treatment if problems arise. In addition, doctors advise women who have a lowered resistance to infection because of low blood cell counts to avoid crowds and people who are sick or have colds. The side effects of chemotherapy are generally short-term. They gradually go away during the recovery part of the chemotherapy cycle or after the treatment is over. However, some chemotherapy drugs, called anthracyclines, can increase the risk of heart problems. Women who receive an anthracycline as part of their treatment should be monitored closely by their doctors for heart problems for the rest of their lives.

Hormonal therapy: In general, the side effects of tamoxifen are similar to some of the symptoms of menopause. The most common side effects are hot flashes, vaginal discharge, and nausea. Tamoxifen also increases the risk of cataract development. Not all women who take tamoxifen have these symptoms. Most of these side effects do not require medical attention.

Doctors carefully monitor women taking tamoxifen for any signs of more serious side effects. Among women who have not had a hysterectomy (surgery to remove the uterus), the risk of developing uterine cancer is increased for those taking tamoxifen. Women who take tamoxifen should talk with their doctor about having regular pelvic exams, and should be examined promptly if they have pelvic pain or any abnormal vaginal bleeding. Women taking tamoxifen, particularly those who are receiving chemotherapy along with tamoxifen, have a greater risk of developing a blood clot.

Aromatase inhibitors also cause hot flashes, vaginal dryness, and other symptoms of menopause. Women taking an aromatase inhibitor may also experience joint pain (arthralgia) or muscle pain (myalgia) during treatment.

Women taking aromatase inhibitors may have a higher risk of heart problems than those taking tamoxifen. Aromatase inhibitors also reduce bone density and increase the risk of bone fractures. Doctors should carefully monitor women taking aromatase inhibitors for any signs of heart damage or changes in bone density. A type of drug called a bisphosphonate can help reduce bone loss caused by aromatase inhibitors for patients at high risk of fractures. 

Trastuzumab: Side effects from trastuzumab can include nausea, vomiting, hot flashes, and joint pain. Trastuzumab can also increase the risk of heart problems. Women receiving trastuzumab should be monitored closely by their doctors for any reduction in the heart’s ability to pump blood, both during and after treatment.

Radiation therapy: Skin in the area treated by radiation may become red, dry, tender, and itchy, and the breast may feel heavy and tight. These problems usually go away over time. Women receiving radiation therapy may become very tired, especially in the later weeks of treatment.

Careful studies have shown that the risks of adjuvant therapy for breast cancer are outweighed by the benefit of treatment—that is, increasing the chance of long-term survival. However, it is important for women to share any concerns they may have about their treatment or side effects with their doctor or other health care provider.