- What is adjuvant therapy for breast cancer?
Adjuvant therapy for breast cancer is any treatment given after primary therapy
to increase the chance of long-term disease-free survival. Primary therapy
is the main treatment used to reduce or eliminate the cancer. Primary therapy
for breast cancer usually includes surgery—a mastectomy (removal of
the breast) or a lumpectomy (surgery to remove the tumor and a small amount
of normal tissue around it; a type of breast-conserving surgery). During either
type of surgery, one or more nearby lymph nodes are also removed to see if
cancer cells have spread to the lymphatic system. When a woman has breast-conserving
surgery, primary therapy almost always includes radiation therapy.
Even in early-stage breast cancer, cells may break away from the primary
tumor and spread to other parts of the body (metastasize). Therefore, doctors
give adjuvant therapy to kill any cancer cells that may have spread, even
if they cannot be detected by imaging or laboratory tests. Studies have shown
that adjuvant therapy for breast cancer may increase the chance of long-term
survival by preventing a recurrence (1).
- What types of adjuvant therapies are used for breast cancer?
Most adjuvant therapies are systemic: They use substances that travel through
the bloodstream, reaching and affecting cancer cells all over the body. Adjuvant
therapy for breast cancer can include chemotherapy, hormonal therapy, the
targeted drug trastuzumab (Herceptin®), radiation therapy, or a combination
of treatments.
- Adjuvant chemotherapy uses drugs to kill cancer cells. Research
has shown that adjuvant chemotherapy for early-stage breast cancer helps
to prevent the cancer from returning (1). Usually, more
than one drug is given during adjuvant chemotherapy (called combination
chemotherapy).
- Hormonal therapy deprives breast cancer cells of the hormone
estrogen, which many breast tumors need to grow. A commonly used hormonal
treatment is the drug tamoxifen, which blocks estrogen's activity in the
body. Studies have shown that tamoxifen helps prevent the original cancer
from returning and also helps to prevent the development of new cancers
in the other breast; however, many women develop resistance to the drug
over time (1, 2). Tamoxifen can be given
to both premenopausal and postmenopausal women.
Postmenopausal women may also receive hormonal therapy with a newer type
of drug called an aromatase inhibitor (AI), either after tamoxifen therapy
or instead of tamoxifen therapy. Rather than blocking estrogen's activity,
as tamoxifen does, AIs prevent the body from making estrogen. Clinical
trials suggest that AIs may be more effective than tamoxifen in preventing
breast cancer recurrence in some women (3–6).
Using AIs to block estrogen production in premenopausal women is not very
effective, in part because the ovary is stimulated to make more estrogen
when blood levels of estrogen fall below normal. This does not occur in
postmenopausal women, whose ovaries have stopped making estrogen.
Some premenopausal women may undergo ovarian ablation or suppression,
which greatly reduces the amount of estrogen produced by the body, either
permanently or temporarily. Premenopausal women who have BRCA1 or BRCA2
gene mutations are at very high risk of breast cancer recurrence as well
as of ovarian cancer and may decide to have their ovaries surgically removed
as part of adjuvant therapy. The surgical removal of the ovaries also
decreases the risk of ovarian cancer. Other premenopausal women who have
a lower risk of recurrence may be prescribed drugs that temporarily suppress
the function of the ovaries, in addition to tamoxifen.
- Trastuzumab is a monoclonal antibody that targets cancer cells
that make too much of, or overexpress, a protein called HER2. When cancer
cells overexpress HER2 protein, they are said to be HER2 positive. Approximately
20 percent of all breast cancers are HER2 positive. Clinical trials have
shown that targeted therapy with trastuzumab in addition to chemotherapy
decreases the risk of relapse for women with HER2-positive tumors (7–9).
- Radiation therapy is usually given after breast-conserving surgery
and may be given after a mastectomy. (When doctors give radiation therapy
after breast-conserving surgery, it is usually considered part of primary
therapy.) For women at high risk of recurrence, doctors may use radiation
therapy after mastectomy to kill cancer cells that may be left in tissues
next to the breast, such as the chest wall or nearby lymph nodes. Radiation
therapy is a type of local therapy, not systemic therapy.
- How is adjuvant therapy given, and for how
long?
Adjuvant chemotherapy is given orally (by mouth) or by injection
into a blood vessel. It is given in cycles, consisting of a treatment period
followed by a recovery period. The number of cycles depends on the types of
drugs used. Most patients do not have to stay in the hospital for chemotherapy—they
can be treated as an outpatient or at the doctor’s office. Adjuvant
chemotherapy usually does not last for much more than 6 months.
Hormonal therapy is usually given orally, as a pill.
- Most women who undergo hormonal therapy take tamoxifen every day for 5
years.
- Some women may take an aromatase inhibitor every day for 5 years instead
of tamoxifen.
- Some women may receive additional treatment with an aromatase inhibitor
after 5 years of tamoxifen.
- Finally, some women may switch to taking an aromatase inhibitor after
2 or 3 years of tamoxifen, for a total of 5 or more years of hormonal therapy.
Trastuzumab is given by infusion into a blood vessel every 1 to
3 weeks for a year.
Radiation therapy given after mastectomy is divided into small doses
given once a day over the course of several weeks. Radiation therapy may not
be given at the same time as some types of chemotherapy or hormonal therapy.
- 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).
- 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.
- What are doctors and scientists doing to
learn more about adjuvant and neoadjuvant therapy for breast cancer?
Doctors and scientists are conducting research studies called clinical trials
to learn how to treat breast cancer more effectively. In these studies, researchers
compare two or more groups of patients who receive different treatments. Clinical
trials allow researchers to examine the effectiveness of new treatments in
comparison with standard ones, as well as to compare the side effects of the
treatments.
Researchers are also investigating whether molecular information obtained
from a woman’s tumor can be used to decide if the woman would benefit
from adjuvant therapy. Two large clinical trials sponsored by the National
Cancer Institute (NCI), a part of the National Institutes of Health, are currently
under way in this area of research.
The Trial Assigning Individualized Options for Treatment (TAILORx) is examining
whether molecular markers that are frequently associated with risk of recurrence
among women who have early-stage breast cancer can be used to assign patients
to the most appropriate and effective treatment. TAILORx is using a test called
Oncotype DX™, which calculates the risk of recurrence based on the levels
of expression of 21 genes in breast tumors, in over 10,000 women recruited
at 900 sites in the United States and Canada. Based on their risk of recurrence,
women will be assigned to one of three different treatment groups: Women with
a high risk of recurrence will receive chemotherapy plus hormonal therapy;
women with a low risk of recurrence will receive hormonal therapy alone; and
women with an intermediate risk of recurrence will be randomly assigned to
receive adjuvant hormonal therapy, with or without chemotherapy. Because the
degree of benefit of chemotherapy for women with an intermediate risk of recurrence
is unknown, TAILORx seeks to determine whether the Oncotype DX test will be
helpful in future treatment planning for this group.
In the Microarray In Node-negative Disease may Avoid Chemotherapy Trial (MINDACT),
investigators are studying genomic profiling compared with clinical assessment
to determine the need for chemotherapy in women with node-negative breast
cancer (cancer that has not spread to the axillary lymph nodes). The investigators
will use both a 70-gene signature test and clinical assessment to determine
the women’s risk of recurrence. Women eligible to receive chemotherapy
who have a high risk of recurrence according to the clinical criteria and
a low risk of recurrence according to the 70-gene signature, or have a low
risk of recurrence according to the clinical criteria and a high risk of recurrence
according to the 70-gene signature, will be randomly assigned to receive treatment
based on either the genetic or clinical criteria to determine which better
predicts the need for chemotherapy.
Women with breast cancer who are interested in taking part in a clinical
trial should talk with their doctor. Complete listings of current clinical
trials testing adjuvant and neoadjuvant therapies for female breast cancer
are available from NCI’s Web site:
Additional information about clinical trials can be found on NCI's Web site at http://www.cancer.gov/clinicaltrials on the Internet. NCI's Cancer Information Service (CIS) can also provide information about clinical trials and help with clinical trial searches. Call the CIS at 1–800–4–CANCER (1–800–422–6237).
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