An in-depth report on the causes, diagnosis, treatment, and prevention of breast cancer.
12% of women will develop invasive breast cancer in their lifetime. Each year in the United States, about 233, 000 women are diagnosed with invasive breast cancer. Although breast cancer in men is rare, about 2,000 American men are diagnosed each year with invasive breast cancer.
There are many different risk factors for breast cancer.
Most cases of breast cancer occur in women older than age 60. According to the American Cancer Society, about 1 in 8 cases of invasive breast cancer are found in women younger than age 45, while 2 in 3 cases of invasive breast cancer are found in women ages 55 and older.
Race and Ethnicity
Breast cancer is slightly more common among white woman than African-American, Asian, Latina, or Native American women. However, African-American women tend to have more aggressive types of breast cancer tumors and are more likely to die from breast cancer than women of other races.
Breast cancer is also more prevalent among Jewish women of Eastern European (Ashkenazi) descent.
Family and Personal History
Women who have a family history of breast cancer are at increased risk for developing breast cancer themselves. Having a first-degree relative (mother, sister, or daughter) who has been diagnosed with breast cancer doubles the risk for developing breast cancer.
Women who have had ovarian cancer are at increased risk for developing breast cancer. A personal history of breast cancer increases the risk of developing a new cancer in the same or other breast.
5 to 10% of breast cancer cases are due to inherited genetic mutations.
BRCA Genes: Inherited mutations in genes known as BRCA1 or BRCA2 are responsible for most cases of hereditary breast cancers and ovarian cancers.
BRCA gene mutations are present in only about 0.5% of the overall population. Jewish women of Eastern European (Ashkenazi) descent have a higher prevalence (2.5%) of BRCA gene mutations. However, BRCA gene mutations can occur in women of all ethnic backgrounds.
Screening for BRCA Genes: The U.S. Preventive Services Task Force (USPSTF) recommends BRCA screening for women at high risk due to family history. The USPSTF does not recommend routine genetic screening or testing in women whose family history does not suggest BRCA mutations. Women who do not have a family history of breast cancer have a low probability of inheriting BRCA genetic mutations and do not need to be tested.
Having several first-degree (mother, sister) or second-degree (aunt, grandmother) relatives who have had breast or ovarian cancer is an indication of risk. Risk assessment is based on family history of breast and ovarian cancer on both the maternal and paternal sides, as well the age at which these cancers occurred..
Your health care provider can screen you using a questionnaire that evaluates your family and personal medical history, and other factors. If your provider decides you are at risk, you may be referred to a genetic counselor who can discuss whether you should be tested for the BRCA1 and BRCA2 mutations. If a woman tests positive for a BRCA mutation, it does not mean that she will definitely develop breast cancer.
Other Genetic Mutations: Other genes associated with increased hereditary breast cancer risk include:
Mutations in the PALB2 gene significantly increase risk. Researchers are continuing to make progress in discovering genetic variants of breast cancer.
Exposure to Estrogen
Because growth of breast tissue is highly sensitive to estrogens, the more estrogen a woman is exposed to over her lifetime, the higher her risk for breast cancer.
Duration of Estrogen Exposure: Early age at menarche (first menstrual period) or later age at menopause may slightly increase a woman's risk for breast cancer.
Pregnancy: Women who have never had children or who had their first child after age 30 may have a slightly increased breast cancer risk. Having children at an early age, and having multiple pregnancies, reduces breast cancer risk. Scientific evidence shows there is no association between abortion and increased breast cancer risk.
Breastfeeding: Studies have been mixed on whether breastfeeding decreases breast cancer risk. Breastfeeding reduces a woman's total number of menstrual cycles and thereby estrogen exposure, which may account for its possible protective effects. Some studies suggest that the longer a woman breast-feeds, the lower her risk, and that breastfeeding may be especially protective for women with a family history of breast cancer.
Birth Control Pills: Because most oral contraceptives contain estrogen, there have been questions on whether they can increase cancer risk. Evidence indicates that current or former oral contraceptive use does not significantly increase breast cancer risk. Women who have used oral contraceptives may have slightly more risk for breast cancer than women who have never used them, but this risk declines once a woman stops using birth control pills.
Hormone Therapy: Hormone therapy (HT) for menopausal symptoms uses either estrogen alone or estrogen and progestogen:
- Estrogen-progestogen therapy (EPT) is used by women who have a uterus, because estrogen alone can increase the risk of uterine cancer. EPT significantly increases the risk for developing and dying from breast cancer, especially when used for more than 5 years.
- Estrogen-only therapy (ET) is prescribed for women who have had a hysterectomy and do not have a uterus. ET does not appear to increase the risk for breast cancer. In fact, some studies indicate that ET may reduce breast cancer risk. However, prolonged used of ET can increase the risk for other health problems including blood clots, heart attack, stroke, and possibly ovarian cancer.
- Hormone therapy (EPT or ET) should not be used by women at high risk for breast cancer.
In general, most doctors recommend that women use HT only for short-term (1 to 2 years) relief of menopausal symptoms. Current guidelines advise initiating hormone therapy around the time of menopause when women are in their 40s or 50s. Starting HT past age 59 may increase the risk for breast cancer and other health problems.
Women who take HT should be aware that they need regular mammogram screenings, because HT increases breast cancer density, making mammograms more difficult to read.
Certain breast conditions may increase the risk for breast cancer, such as:
- Dense breast tissue. Dense breasts make mammograms more difficult to read, which increases the likelihood of missing early signs of cancer.
- Benign proliferative breast disease, or unusual cell growth known as atypical hyperplasia.
Common benign breast abnormalities pose little or no risk for breast cancer. These conditions include:
- Temporary breast pain
Still, check with your provider if you notice any changes in your breasts.
Click the icon to see an image of cysts in the breast.
Obesity is a risk factor for estrogen receptor-positive types of breast cancer. High amounts of fatty tissue increase estrogen levels in the body.
Estrogen is also involved in building bone mass. Therefore, women with heavy, dense bones are likely to have higher estrogen levels and to be at greater risk for breast cancer.
Exposure to Estrogen-like Industrial Chemicals: Chemicals with estrogen-like effects, called xenoestrogens, have been under suspicion for years. At this time, evidence of any causal association is very weak.
Exposure to Diethylstilbestrol: Women who took diethylstilbestrol (DES) to prevent miscarriage have a slightly increased risk for breast cancer. There may also be a slightly increased risk for their daughters (commonly called "DES daughters"), who were exposed to the drug when their mothers took it during pregnancy.
Radiation Exposure: Heavy exposure to radiation is a significant risk factor for breast cancer. Girls who receive high-dose radiation therapy for cancer face an increased risk for breast cancer in adulthood. Low-dose radiation exposure before age 20 may increase the risk for women with BRCA genetic mutations. Women should avoid unnecessary and excessive exposure to medical radiation, including x-rays and CT scans.
Alcohol consumption is a risk factor for breast cancer, especially for women who have 2 or more drinks a day.
Disproven Risk Factors
Antiperspirants or use of deodorants after shaving have not been linked with any higher risk for breast cancer. There is also no evidence that bras increase breast cancer risk. Stress has been ruled out as a risk factor for breast cancer development or recurrence.
The three main treatments of breast cancer are:
- Drug therapy
Most times, a combination of treatments is given. Treatment decision is determined by many factors, including:
- The age of the woman
- Menopausal status
- Cancer stage
- HER2 status
- Whether or not the tumor contains hormone receptors
Some women may be candidates for clinical trials exploring new types or combinations of treatments.
Breast cancer treatments are defined as local or systemic:
Local Treatment: Surgery and radiation are considered local therapies because they directly treat the tumor, breast, lymph nodes, or other specific regions. Surgery is usually the standard initial treatment.
Systemic Treatment: Drug treatment is called systemic therapy, because it affects the whole body. Drugs may include chemotherapy, hormone therapy, and targeted therapy (biologic drugs).
Radiation and drug therapy are often given after surgery. This is called adjuvant therapy. The purpose of adjuvant therapy is to kill any cancer cells that remain after surgery. In some cases, drug therapy may be given before surgery (neoadjuvant therapy) to shrink the tumor and make it easier to surgically remove.
Cancer Stage and Treatment Options
Treatment strategies depend in part on the stage of the cancer. Breast cancer is staged based on:
- The size and location of the primary Tumor (T)
- If the tumor has spread to the lymph Nodes (N)
- If the cancer has spread (Metastasized) to other parts of the body (M)
The TNM system is used to classify cancer in stages I to IV. Each stage is further divided into substages.
Stage 0 (Carcinoma in Situ): Stage 0 breast cancer is considered non-invasive ("in situ"), meaning that the cancer is still confined within breast ducts or lobules and has not yet spread to surrounding tissues. Stage 0 cancer is classified as either:
- Ductal carcinoma in situ (DCIS). These are cancer cells in the lining of a duct that have not invaded the surrounding breast tissue.
- Lobular carcinoma in situ (LCIS). These are cancer cells in the lobules of the breast. LCIS rarely develops into invasive breast cancer, but having it in one breast increases the risk of developing cancer in the other breast.
Treatment options for DCIS include:
- Breast-conserving surgery and radiation therapy (sometimes followed by hormone-blocking therapy for women with hormone-sensitive cancer). Many doctors recommend this approach.
- Total mastectomy
- Breast-conserving surgery without radiation therapy
Treatment options for LCIS include:
- Regular exams and mammograms to monitor any potential changes (observation treatment).
- Hormone-blocking therapy to prevent development of breast cancer (for women with hormone-sensitive cancer).
Stage I and II (Early-Stage Invasive): In stage I cancer, the tumor is no more than 2 cm (about 3/4 of an inch) across and has not spread to axillary lymph nodes (in the armpit) or distant sites. In stage II cancer the tumor may be larger than 2 centimeters and may have spread to lymph nodes.
Stage I and stage II treatment options may include:
- Breast-conserving surgery (lumpectomy) followed by radiation therapy.
- Modified radical mastectomy with or without breast reconstruction.
- Post-surgical therapy (adjuvant therapy) with radiation, chemotherapy, hormone-blocking therapy.
- Targeted therapy with trastuzumab (Herceptin) given before surgery (neoadjuvant therapy) with pertuzumab (Perjeta), or after surgery (adjuvant therapy) with chemotherapy for women with HER2-positive cancer.
Stage III (Locally Advanced): In stage III, the cancer may have spread lymph nodes within the breast or under the arm. It may have also spread to tissues near the breast, including the skin or chest wall.
Stage III treatment options may include:
- Surgery followed by chemotherapy, radiation, hormone therapy, and targeted therapy. Targeted therapy may also be used before surgery for women with HER2-positive cancer (as discussed above).
- Chemotherapy, and possibly hormone therapy (sometimes in combination with chemotherapy).
- Chemotherapy (with or without targeted therapy) followed by surgery (breast-conserving surgery or total mastectomy) with lymph node dissection followed by radiation therapy and possibly more chemotherapy or hormone-blocking therapy.
Stage IV (Advanced Cancer): In stage IV, the cancer has spread (metastasized) from the breast to other parts of the body. In 75% of cases, the cancer has spread to the bone. The goals of treatment for stage IV cancer are to stabilize the disease and slow its progression, as well as to reduce pain and discomfort.
Stage IV treatment options may include:
- Chemotherapy, hormone therapy, or both.
- Targeted therapy in combination with chemotherapy or hormone therapy for women with HER2-positive cancer.
- Surgery or radiation to ease symptoms (palliative therapy).
- Drugs to prevent fractures if cancer has spread to the bone.
- Clinical trials of new drugs or combinations of treatments.
Recurrent Breast Cancer: Recurrent breast cancer is considered to be an advanced cancer. In such cases, the disease has come back in spite of the initial treatment. Most recurrences appear within the first 5 years after treatment, but breast cancer can recur many years later. Treatment options are based on:
- The stage at which the cancer reappears
- Whether or not the tumor is hormone responsive
- The age of the person
Women with recurrent breast cancer should discuss clinical trial options with their oncologists.
The American Society of Clinical Oncology (ASCO) recommends follow-up care for people who have been treated for breast cancer:
- Visit your doctor every 3 to 6 months for the first 3 years after your first cancer treatment, every 6 to 12 months during the fourth and fifth year, and once a year thereafter.
- Have a mammogram 1 year after the mammogram that diagnosed your cancer (but no earlier than 6 months after radiation therapy), and every 6 to 12 months thereafter.
- Perform a breast self-exam every month (however, this is no substitute for a mammogram).
- See your gynecologist regularly (women taking tamoxifen should be sure to report any vaginal bleeding).
- A year after diagnosis, you can either continue to see your oncologist or transfer your care to your primary care physician.
- If you are on hormone therapy, discuss with your oncologist how often to schedule follow-up visits for re-evaluation of your treatment.
- Genetic counseling may be helpful for some women including those with a family history of ovarian or breast cancer.
Breast cancer recurrences are often discovered by people in between doctor visits, it is important to notify your doctor if you experience any of the following symptoms in the years after treatment:
- New lumps in the breast
- Rash on breast
- Nipple discharge
- Swelling in lymph nodes under arm or collarbone
- Bone or chest pain
- Shortness of breath or difficulty breathing
- Persistent headaches or coughing
- Loss of appetite
Fertility and Pregnancy Treatment Considerations
There are no definite recommendations on how long a woman should wait to become pregnant after breast cancer treatment. Because of the connection between estrogen levels and breast cancer cell growth, some doctors recommend delaying pregnancy several months or years after treatment in order to reduce the risk of cancer recurrence and improve odds for survival. Discuss with your doctor your risk for recurrence, and when it may be safe to attempt pregnancy.
Women should discuss with their doctors any concerns and questions they may have about how cancer treatments could affect their fertility. They may also wish to have a consultation with a fertility specialist. Assisted reproductive technology such as embryo or oocyte (egg) cryopreservation ("freezing") may offer some women an option to later have children. ASCO recommends that you have these discussions with your health care team prior to starting cancer treatment.
The goal of hormone therapy is to prevent estrogen from stimulating breast cancer cells. It is recommended for women whose breast cancers are hormone-receptor positive (hormone sensitive). Like chemotherapy, hormone therapy works systemically. Hormone therapy is usually given after surgery (adjuvant) but may also be used in some cases before surgery (neoadjuvant).
Different types of hormone therapy work in different ways by:
- Blocking estrogen receptors in cancer cells (tamoxifen)
- Suppressing estrogen production in the body (aromatase inhibitors)
- Suppressing the ovaries, which produce estrogen (ovarian ablation)
Tamoxifen and Selective Estrogen Receptor Modulators (SERMs)
Tamoxifen (Nolvadex, generic) has been the standard hormonal drug used for breast cancer. It belongs to a class of compounds called selective estrogen receptor modulators (SERMs). SERMs chemically resemble estrogen and trick the breast cancer cells into accepting it in place of estrogen. Unlike estrogen, however, they do not stimulate breast cancer cell growth. Because SERMs block estrogen's effects on cancer cells, they are sometimes referred to as "anti-estrogen" drugs.
Tamoxifen is used for all cancer stages in (mainly premenopausal) women with hormone receptor-positive cancers. In addition, it is used to prevent breast cancer in high-risk women. Another SERM drug, fulvestrant (Faslodex), works in a similar anti-estrogen way to tamoxifen but belongs to a different drug class. Fulvestrant is approved only for postmenopausal women with hormone-sensitive advanced breast cancer in whom tamoxifen or aromatase inhibitors no longer work.
To prevent cancer recurrence, women should take tamoxifen for a total of 10 years following surgery. The American Society of Clinical Oncology (ASCO) recommends that women who are premenopausal or perimenopausal should start with tamoxifen for 5 years. If at that point they have still not reached menopause, they can continue with tamoxifen. If they have become postmenopausal, they can choose between tamoxifen and an aromatase inhibitor.
Tamoxifen is an effective cancer treatment, but it can cause unpleasant side effects and has small (less than 1%) but serious risks for blood clots and uterine (endometrial) cancer. Immediately report any signs of vaginal bleeding to your doctor, as this may be a symptom of uterine cancer. Tamoxifen risks for blood clots may be higher for women who are obese.
Less serious, but discomforting, side effects include hot flashes and mood swings. Some women want to stop treatment because of these side effects. However, stopping tamoxifen treatment prematurely can increase the risk for cancer recurrence and death. Talk with your cancer care team about therapies that may help you cope with side effects.
Aromatase inhibitors are recommended for postmenopausal women with hormone-sensitive breast cancer. Aromatase inhibitors are taken for up to 5 years. They can be used either before or after tamoxifen treatment.
Aromatase inhibitors block aromatase, an enzyme that is a major source of estrogen in many major body tissues, including:
- The breast
Aromatase inhibitors work differently than tamoxifen. Tamoxifen interferes with a tumors' ability to use estrogen by blocking their estrogen receptors. Aromatase inhibitors reduce the overall amount of estrogen in the body.
Because these drugs cannot stop the ovaries of premenopausal women from producing estrogen, they are recommended only for postmenopausal women.
Three aromatase inhibitors are approved for treating early-stage, hormone receptor-positive breast cancer in postmenopausal women:
- Anastrazole (Armidex and generic)
- Exemestane (Aromasin and generic)
- Letrozole (Femara and generic)
There are no significant differences between these three drugs. Women who cannot tolerate one type of aromatase inhibitor can switch to a different one. Studies indicate that the introduction of aromatase inhibitors has helped greatly in prolonging survival for women with advanced cancer.
Like tamoxifen, aromatase inhibitors can cause hot flashes. These drugs can also cause joint pain. Compared to tamoxifen, aromatase inhibitors are less likely to cause serious problems like blood clots and uterine cancer. However, they are more likely to cause osteoporosis, which can lead to fractures. Women should have their bone mineral density monitored during aromatase inhibitor treatment.
Ovarian ablation is a treatment that stops estrogen production from the ovaries. Medications can accomplish ovarian ablation. Destroying the ovaries with surgery or radiation can also shut down estrogen production. (Osteoporosis is one serious side effect of this approach, but can be treated with drug therapies.)
Chemical Ovarian Ablation: Drug treatment to block ovarian production of estrogen is called chemical ovarian ablation. It is often reversible. The primary drugs used are luteinizing hormone-releasing hormone (LHRH) agonists, such as goserelin (Zoladex). (They are also sometimes called GnRH agonists). These drugs block the release of the reproductive hormones LH-RH, therefore stopping ovulation and estrogen production.
Bilateral Oophorectomy: Bilateral oophorectomy, the surgical removal of both ovaries, is a surgical method of ovarian ablation. It may modestly improve breast cancer survival rates in some premenopausal women whose tumors are hormone receptor-positive. In these women, combining this procedure with tamoxifen may improve results beyond those of standard chemotherapies. Oophorectomy does not benefit women after menopause. The procedure causes sterility.
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