Breast Cancer

Overview

Breast cancer is the most common cancer in women, other than skin cancer, and the second deadliest cancer in U.S. women; lung cancer is the deadliest. Approximately 231,840 cases of invasive breast cancer will be diagnosed in 2015, according to the American Cancer Society (ACS). Though an estimated 40,290 women will die from breast cancer, there are more than 2.8 million breast cancer survivors in the United States, according to the ACS.

Breast cancer rates increased for about two decades and then started decreasing in 2000, dropping 7 percent between 2002 and 2003. This drop was thought to be a result of the decline in hormone replacement therapy in post-menopausal women that occurred after results of the Women’s Health Initiative came out in 2002, which linked use of hormone therapy to increased risk of both breast cancer and heart disease.

Rates of breast cancer have been stable in recent years in white women and increased slightly in African American women. The rates among Asian American and Hispanic women are significantly lower than rates among white and African American women, though the rate among Asian Americans has risen in recent years.

Breast cancer is a disease in which malignant (cancerous) cells are found in breast tissue. Each breast has 15 to 20 sections called lobes, which have many smaller sections called lobules. The lobes and lobules are connected by thin tubes called ducts.

One of the most important factors when it comes to breast cancer is whether the cancer is invasive or noninvasive. Noninvasive (in situ) cancers are confined to the ducts or lobules and have not spread to surrounding tissues or other parts of the body. Noninvasive cancers can develop into more serious invasive tumors. Invasive breast cancer has spread outside the milk duct and into the normal tissue inside the breast. Whether a breast cancer is invasive or noninvasive determines treatment and prognosis.

The different kinds of breast cancer that involve the lobes, lobules and/or ducts are:

  • Ductal carcinoma in situ (DCIS). Also known as intraductal carcinoma or noninvasive breast cancer, DCIS is confined to the ducts and has not invaded surrounding tissue. As the use of screening mammography has increased in the United States, the frequency of DCIS diagnosis has increased significantly. It is the most common subgroup of noninvasive breast cancer; one out of five cases of breast cancer is DCIS.
  • Invasive ductal cancer. Also called infiltrating ductal carcinoma, this type of breast cancer is the most common of all breast cancers. It makes up about 80 percent of all newly diagnosed cases of invasive breast cancer. It is found in the cells of the ducts and is usually a hard lump.
  • Invasive lobular carcinoma. This form of breast cancer occurs at the ends of the ducts or in the lobules and accounts for 10 percent of invasive breast cancers.

Less common types of breast cancer:

  • Mucinous carcinoma (colloid carcinoma). A rare type of invasive breast cancer, mucinous carcinoma is formed by mucin-producing cancer cells. Prognosis for this type of invasive breast cancer is generally better than for other more common types.
  • Medullary carcinoma. This type of breast cancer accounts for 3 to 5 percent of all breast cancers and involves a distinct boundary between tumor tissue and normal tissue. These tumors are called “medullary” because they resemble the grayish soft tissue of the brainstem, called the medulla. Medullary tumors are usually small, but the cells are frequently high grade, which means they look very different from normal cells and/or they divide rapidly. Medullary tumors are also often “triple-negative,” which means they test negative for estrogen and progesterone receptors, as well as the HER2/neu protein. The prognosis for this type of cancer is generally better than for other invasive forms.
  • Tubular carcinoma. Tubular carcinoma is characterized by tubular structures ringed with a single layer of cells. Only 2 percent of all breast cancers fall into this category. The prognosis is usually good.
  • Paget’s disease. A rare breast cancer in the ducts beneath the nipple accounting for only 1 percent of cases, invasive Paget’s disease starts with an itchy, eczema-like rash around the nipple. Paget’s disease can be associated with a noninvasive or invasive underlying mass. For noninvasive cases, it is believed that the cells have migrated from the ducts of the nipple to the nipple’s epidermis, though this is still under study.
  • Inflammatory carcinoma. This aggressive type of breast cancer accounts for 1 to 3 percent of all cases. Skin over the breast appears acutely inflamed and swollen because skin lymph vessels are blocked by cancer. The skin resembles the peel of an orange.
  • Triple-negative breast cancer. This type of breast cancer, usually invasive ductal carcinoma, has cells that lack receptors for the hormones estrogen and progesterone, and it does not express a specific protein called HER2, which makes tumors grow quickly. Triple-negative breast cancers tend to occur in younger women and African-American women and spread more quickly than most other breast cancer types.
  • Metaplastic carcinoma. Also called carcinoma with metaplasia, this is a very rare type of invasive ductal breast cancer. These tumor cells make tissue not normally found in the breast such as bone and even cartilage and are treated like invasive ductal cancer.
  • Papillary carcinoma. This type of breast cancer, which can be separated into noninvasive and invasive types, includes cells arranged in small, fingerlike projections. These cancers are more common in older women and make up fewer than 1 percent of all breast cancers.
  • Mixed tumors. Mixed breast tumors contain a variety of cell types, such as invasive lobular breast cancer combined with invasive ductal cancer.
  • Adenoid cystic carcinoma (adenocystic carcinoma). These breast cancers have both cylinder-like (cystic) and glandular (adenoid) features and make up less than 1 percent of breast cancers. Because they rarely spread to the lymph nodes and distant areas, these tumors usually have a very good prognosis.
  • Phyllodes tumor. A very rare form of breast tumor, phyllodes tumor forms in the connective tissue of the breast, called the stroma. Phyllodes tumors are usually benign but may be malignant in rare cases, and the malignant form can spread (metastasize).
  • Angiosarcoma. This form of breast cancer begins in cells that line blood vessels or lymph vessels. It rarely forms in the breast, but a risk factor for this is prior radiation treatment.

Treatment

The treatment you and your health care professional choose will depend upon many things. Treatment often includes surgical, radiation and medical therapy.

The most common surgical treatment for invasive cancer is lumpectomy (also called partial mastectomy or segmental mastectomy) with sentinel lymph node biopsy technique described below. Also known as excisional biopsy or wide excision, lumpectomy is a breast-conserving surgical procedure.

During lumpectomy, a surgeon removes just the tumor along with a margin of healthy tissue, leaving the remainder of the breast intact, followed by radiation. Regardless of whether you choose lumpectomy or mastectomy, a dissection or sampling of an axillary lymph node or nodes (a large group of lymph nodes located under the armpit or axilla) should be performed for invasive forms of the disease. A new technique called sentinel lymph node sampling takes one to three lymph nodes from under the arm. These lymph nodes are found by injecting a dye into the breast and looking for the first lymph node that picks up this dye. The surgeon can then remove the smallest number of lymph nodes possible. The idea is that if a lymph node is positive for cancer, it is most likely in the sentinel lymph node.

A mastectomy is another common surgical treatment for invasive cancer, and there are two primary types:

  • Simple or total mastectomy: The entire breast is removed, including breast tissue, skin, areola and nipple, but not the chest tissue underneath.
  • Modified radical mastectomy: The entire breast is removed along with underarm lymph nodes and sometimes the lining over the chest muscles and, more rarely, part of the chest wall muscle. This may be recommended if your tumor is large or if it is your preference.

Adjuvant Therapy

In addition to surgery, adjuvant therapy is used to kill any cancer cells that may have spread. In deciding whether adjuvant treatment is necessary, your doctor takes into account the extent (stage) and nature of your disease, general health and other prognostic factors.

The choice of the type of adjuvant therapy depends on many factors, such as: whether the cancer cells contain hormone receptors (estrogen and progesterone); whether there is a protein called HER2, which makes tumors grow more quickly; the grade of tumor; and the size of tumor and lymph nodes. Most women receive some form of adjuvant therapy.

Adjuvant therapy usually begins between two and 12 weeks after surgery. It may also start about 12 weeks before surgery to shrink the tumor and make it easier to surgically remove (called neoadjuvant therapy). It includes chemotherapy and/or hormone therapy.

  • Chemotherapy involves a combination of anticancer drugs. These drugs are powerful and can have many side effects. Anticancer drugs are given by mouth or by injection into a blood vessel. Either way, the drugs enter the bloodstream and travel throughout the body.Chemotherapy is given in cycles: a treatment period followed by a recovery period, then another treatment period, and so on. Most patients receive treatment in an outpatient part of the hospital or at the doctor’s office. Adjuvant chemotherapy usually lasts for three to six months.Hormone therapy deprives cancer cells of the female hormone estrogen, which some breast cancer cells need to grow. For many women, hormone therapy means treatment with the drug tamoxifenfulvestrant (Faslodex), a drug that works similarly to tamoxifen but eliminates the estrogen receptor instead of blocking it; toremifene (Fareston), a drug that is similar to tamoxifen but is only approved to treat metastatic breast cancer, or an aromatase inhibitor, such as anastrozole (Arimidex), letrozole (Femara) or exemestane (Aromasin). Aromatase inhibitors stop estrogen production in post-menopausal women.

Several studies have compared aromatase inhibitors with tamoxifen as adjuvant therapy in post-menopausal women with breast cancer and found that aromatase inhibitors better reduce the risk of cancer recurrence than using tamoxifen by itself for five years. The drug schedules that appear to be the most helpful include the following:

  • Tamoxifen for two to three years followed by an aromatase inhibitor to complete five years of total treatment
  • Tamoxifen for five years, followed by an aromatase inhibitor for five years
  • An aromatase inhibitor for five years

For post-menopausal women with hormone receptor-positive breast cancers, experts recommend using aromatase inhibitors as part of adjuvant therapy. Researchers are now investigating the best way to give these drugs, whether it’s before or after tamoxifen or using them for five years or longer.

Tamoxifen also carries some risks, however, including increased risk of stroke, pulmonary emboli and fatal uterine cancers. Patients should discuss these risks with their health care professionals. In most cases, the benefits of using tamoxifen as a treatment for breast cancer outweigh the risks.

Some premenopausal patients may have surgery to remove their ovaries, which are a woman’s main source of estrogen. Or they may be treated with a medication to reduce ovarian function.

  • Radiation therapy should be used in people having a lumpectomy. It also may be used after a mastectomy for women with large cancer tumors or with four or more positive lymph nodes, or when the margins of the surgical removal show some cancer cells. It also may be used in women with high-risk factors such as lymphovascular involvement. For all women—even those with high risk factors—radiation therapy is considered on an individual basis. Such treatment can help destroy breast cancer cells that may have been left behind in the area where the breast was.Radiation comes in two forms—external radiation, where radiation is delivered as external beams outside the body, and internal radiation, where radioactive seeds or pellets are placed into a device in the affected area of breast tissue.External radiation is the more popular choice. The standard course of external radiation treatment is five days a week for five to six weeks for women who’ve had a mastectomy.
    When radiation is used as part of breast conservation therapy, in conjunction with a lumpectomy, it is usually used for three weeks or six weeks.Some doctors use more accelerated schedules, including those that give slightly larger daily doses for only three weeks, the so-called Canadian fractionated schedule or hypofractionated radiation therapy. Other new techniques are 3-D conformal radiotherapy and intensity-modulated radiation therapy, both of which give radiation that better targets the area where the tumor was, sparing normal tissue such as the heart from residual effects.

    Internal radiation is also called brachytherapy. It can be used as part of breast conservation therapy, either as a boost before or after five weeks of external beam therapy or on its own through a brachytherapy catheter. The brachytherapy catheter delivers small radioactive pellets directly into the lumpectomy cavity. This treatment is called accelerated partial breast radiation. It is given twice a day for five days, with treatments separated by six hours. If the person is not a candidate for this type of brachytherapy, similar therapy can be done through small fields of external radiation, though less tissue will be spared. Again the treatments are twice a day for five days. At the last treatment, the catheter device is removed.

Choosing the Right Treatment

So how do you know which treatment to choose? Your health care professional will try to determine your prognosis—the likely outcome after treatment. One indicator most commonly used is lymph node involvement.

Cancer cells commonly spread from the breast to lymph nodes in underarm and chest areas. To determine if and how far breast cancer has spread, and which treatment option may be the best option, a number of lymph nodes are typically removed for biopsy to see if they contain cancer cells.

If cancer is found, the woman is said to be “node positive.” If the lymph nodes are free of cancer, the patient is said to be “node negative.” Women who have multiple positive nodes are more likely than those with negative nodes to have a systemic recurrence. Plus, the more lymph nodes that are involved, the more serious the cancer.

A procedure that is widely used is called sentinel lymph node biopsy. It is effective as a less invasive technique than conventional axillary lymph node dissection to determine if certain cancers have spread.

Sentinel nodes are a small cluster of lymph nodes to which cancer first spreads from the primary tumor. In a sentinel node biopsy, a surgeon removes only one or a few of the sentinel nodes instead of the larger number of nodes typically removed for biopsy. The surgeon identifies the sentinel nodes to remove by injecting a radioactive tracer substance or dye near the tumor. Then, using a scanner, he or she searches for the nodes containing the dye/tracer and removes them to check for cancer cells.

Other factors that help determine treatment and prognosis include the following:

  • Tumor size. In general, patients with small tumors have a better prognosis than do patients with large tumors.
  • Breast cancer grade. This term refers to how much the tumor cells resemble normal cells when viewed under the microscope. The grading scale usually ranges from 1 to 3. Grade 1 tumors are composed of cells that closely resemble normal ones. Grade 3 tumors contain very abnormal-looking and rapidly growing cancer cells.
  • Hormone receptors. Cells in the breast contain receptors for the female hormones estrogen and progesterone. These receptors allow the breast tissue to grow or change in response to changing hormone levels. Research finds that about two-thirds of all breast cancers contain significant levels of estrogen receptors. These tumors are said to be estrogen receptor positive (ER+). Tumors that contain progesterone receptors are said to be progesterone receptor positive (PR+). About two-thirds of breast tumors contain at least one of these receptors. Tumors that are hormone receptor positive are more likely to respond to hormone therapy. These tumors also tend to grow less aggressively, resulting in a better prognosis.
  • Gene patterns. Looking at patterns of a number of different genes at the same time (called gene expression profiling) can help predict how likely an early stage breast cancer is to recur after initial treatment. There are two tests of gene patterns currently available: the Oncotype DX and the MammaPrint.

Other tests may be performed to check the growth rate of the cancer and to help determine appropriate therapy.

In addition, about one in five women with breast cancer have an excess of a protein called HER2/neu (or just HER2), which makes tumors grow quickly. A number of drugs are used to target the HER2 protein, including

  • Trastuzumab (Herceptin)
  • Pertuzumab (Perjeta)
  • Ado-trastuzumab emtansine (Kadcyla)
  • Lapatinib (Tykerb)

Pregnancy and Breast Cancer

Breast cancer can occur during pregnancy or within the first year after giving birth. Unfortunately, changes in the breast during pregnancy and lactation may make detection difficult. Pregnancy also limits the treatment options for breast cancer.

Surgery remains an option, however, with special care taken during anesthesia, but radiation must be delayed until after the pregnancy because of its dangerous effects on the developing fetus.

However, chemotherapy can be given in the second or third trimester. Or, for women who want to save their breasts, chemotherapy can be given before surgery and radiation delayed until after delivery.

Post-Mastectomy and Reconstruction

After a mastectomy, some women may choose to wear a prosthesis (an artificial breast form). Others may decide to have breast reconstruction.

There are several methods to rebuild the breast after mastectomy. The method must be tailored to the individual patient’s needs. The simplest operation is to place an implant behind the remaining muscle and create a mound that resembles a normal breast. In some cases, breast reconstruction may be performed immediately following a mastectomy.

If you had a great deal of tissue removed, more skin can be created with a tissue expander. This is a balloon-type device that is placed beneath the muscle and skin. Over several weeks this is made larger by almost painless injections of saline in the health care provider’s office. After several months, the expander is replaced by a permanent implant.

Another approach is flap surgery. It uses tissue from your back, thigh or abdomen to rebuild the breast. This tissue is moved into its new position, leaving a defect at the donor site. It is more major surgery. If you had radiation, which can cause significant scarring, a flap may be the best option.

The scar from breast reconstruction depends on the method used. With the flap, for example, you will have a scar at the site where the flap is removed (the donor site) and another around the flap on the breast.

Whichever method is used, additional surgery is needed if you want to have the nipple and areola rebuilt.

Regardless of whether you have a mastectomy alone or the added reconstructive surgery, there is a period of time after the surgeries when you can expect a certain amount of pain and limited movement. Recovery times vary depending on your surgery and overall health. Various programs are available to help you regain function; ask your health care professional for a referral to one of those programs.

Prevention

There is no known way to prevent breast cancer. But there are some things you can do to reduce your risk of breast cancer.

For women with a known increased risk for breast cancer, the drugs tamoxifen and raloxifene may help reduce that risk. Drugs called aromatase inhibitors may also reduce risk. The aromatase inhibitor exemestane (Aromasin) is recommended by the American Society of Clinical Oncology for primary risk reduction among postmenopausal women who are at increased risk for invasive breast cancer. However, aromatase inhibitors are still being studied and aren’t yet FDA approved for breast cancer prevention. Additional compounds, including some dietary supplements, are also currently being studied. So far, none of them show promise.

If you have a high risk for breast cancer, talk to your health care professional about drugs that may prevent breast cancer.

Although prevention is difficult, you have a much better prognosis if you can find and treat breast cancer early. To do that, follow this advice:

  • At age 40 for women at an average risk of breast cancer, begin having screening mammograms every year.
  • For women at high risk of breast cancer, starting at an age determined by your health care professional, begin having annual screening mammograms together with magnetic resonance imaging (MRI).
  • To make sure you get the best possible mammogram, look for the FDA certificate, which should be prominently displayed at the facility. Facilities not meeting FDA requirements may not lawfully perform mammography. To find an FDA certified mammography facility in your area, go to: www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfMQSA/mqsa.cfm.
  • If you’re in your 20s and 30s and at an average risk, have your health care professional examine your breasts at least once every three years.
  • Become familiar with how your breasts feel and what is “normal” for you; examine your breasts periodically and see a health care professional if you feel or see any changes that don’t go away after one menstrual cycle.
  • Eat a healthy diet rich in fruits and vegetables, maintain your ideal body weight, exercise regularly and drink in moderation, if at all. A University of Washington (Seattle) study found that exercise and lack of obesity in adolescence significantly delayed the onset of breast cancer, including onset in high-risk women who carried genetic mutations for the disease.
  • Engage in frequent and regular physical exercise. Some studies suggest it may reduce your breast cancer risk.
  • If you’re at very high risk for breast cancer because of a strong family history of breast and ovarian cancer, an inherited breast cancer gene abnormality or previous breast cancer, talk to your health care professional about a prophylactic mastectomy.

Prophylactic mastectomy is an aggressive preventive surgery that removes both breasts before any cancer is detected. It can reduce the risk of breast cancer by approximately 90 percent, but doesn’t eliminate the risk entirely. Removing the ovaries (prophylactic oophorectomy) may also be a preventive choice for women with an inherited breast cancer gene abnormality, since the risk for ovarian cancer is also greater for these women.

Facts to Know

  1. An estimated 231,840 new cases of invasive breast cancer will be diagnosed in 2015. Approximately 40,290women will die from breast cancer in 2015. Breast cancer is the most common type of cancer in women (besides skin cancer) and the second-leading cause of cancer death in women.
  2. The five-year relative survival rate for localized breast cancer has increased from 72 percent in the 1940s to about 100 percent for stage 0 and 1, 93 percent for stage II,, 72 percent for III, and 22 percent for stage IV.
  3. Survival after a diagnosis of breast cancer continues to decline beyond five years. Ten-year survival and beyond is also stage-dependent, with the best survival observed in women with early stage disease.
  4. Well-known estrogen-related risks for developing breast cancer include early menstruation (at age 12 or younger); late menopause (after age 55); and no full-term pregnancy or first child until after age 30.
  5. Approximately 80 percent of biopsied breast abnormalities are noncancerous, but any breast lump must be evaluated by a physician. New, less invasive biopsy procedures permit removal of breast tissue in a physician or radiologist’s office.
  6. Sometimes more than one mammogram may be necessary to evaluate an abnormality. Common reasons for additional mammograms include film views that are unclear or different views requested by the radiologist.
  7. Some mammography centers provide immediate interpretation of your mammogram. This service can help prevent anxiety caused by waiting days to hear your results. Any additional films required also can be taken during the same visit.
  8. Many women panic when they see the “one in eight women will be diagnosed with breast cancer in her lifetime” statistic, but when the numbers are broken down, it means that one in 227 women will be diagnosed with breast cancer at age 30; one in 68 at age 40; one in 42 at age 50; one in 28 at age 60; and one in 26 at age 70.
  9. Some breast cancer cases are the result of a mutation in the BRCA 1 or 2 genes, which can be inherited. Hereditary breast cancer makes up approximately 5 to 10 percent of all breast cancer. Women who have an altered gene related to breast cancer and who have had breast cancer in one breast have an increased risk of developing breast cancer in the other breast. These women also have an increased risk of developing ovarian cancer and may have an increased risk of developing other cancers.
  10. Different types of treatment are available for patients with breast cancer. Some treatments are standard, and some are being tested in clinical trials. The four types of standard treatment currently used are surgery, radiation therapy, chemotherapy and hormone therapy.