Breast Cancer

Breast cancer definition

Breast cancer is a malignant tumor (a collection of cancer cells) arising from the cells of the breast. Although breast cancer predominantly occurs in women, it can also affect men. This article deals with breast cancer in women. Breast cancer and its complications can affect nearly every part of the body.

There are many risk factors that increase the chance of developing breast cancer. Although we know some of these risk factors, we don't know the cause of breast cancer or how these factors cause the development of a cancer cell.

We know that normal breast cells become cancerous because of mutations in the DNA, and although some of these are inherited, most DNA changes related to breast cells are acquired during one's life.

Proto-oncogenes help cells grow. If these cells mutate, they can increase growth of cells without any control. Such mutations are referred to as oncogenes. Such uncontrolled cell growth can lead to cancer.

Some of the breast cancer risk factors can be modified (such as alcohol consumption) while others cannot be influenced (such as age). It is important to discuss these risks with a health care provider when starting new therapies (for example, postmenopausal hormone therapy).

Several risk factors are inconclusive (such as deodorants), while in other areas, the risk is being even more clearly defined (such as alcohol use).

The following are risk factors for breast cancer:

• Age: The chances of breast cancer increase as one gets older.
• Family history: The risk of breast cancer is higher among women who have relatives with the disease. Having a close relative with the disease (sister, mother, daughter) doubles a woman's risk.
• Personal history: Having a breast cancer diagnosis in one breast increases the risk of cancer in the other breast or the chance of an additional cancer in the original breast.
• Women diagnosed with certain benign (non-cancerous) breast conditions have an increased risk of breast cancer. These include atypical hyperplasia, a condition in which there is abnormal proliferation of breast cells but no cancer has developed.
• Menstruation: Women who started their menstrual cycle at a younger age (before 12) or went through menopause later (after 55) have a slightly increased risk.
• Breast tissue: Women with dense breast tissue (as documented by mammogram) have a higher risk of breast cancer.
• Race: White women have a higher risk of developing breast cancer, but African-American women tend to have more tumors that are aggressive when they do develop breast cancer.
• Exposure to previous chest radiation or use of diethylstilbestrol increases the risk of breast cancer.
• Having no children or the first child after age 30 increases the risk of breast cancer.
• Breastfeeding for one and a half to two years might slightly lower the risk of breast cancer.
• Being overweight or obese increases the risk of breast cancer both in pre- and postmenopausal women but at different rates.
• Use of oral contraceptives in the last 10 years increases the risk of breast cancer slightly.
• Using combined hormone therapy after menopause increases the risk of breast cancer.
• Alcohol consumption increases the risk of breast cancer, and this seems to be proportional to the amount of alcohol used. A recent meta-analysis reviewing the research on alcohol use and breast cancer concluded that all levels of alcohol use are associated with an increased risk for breast cancer. This includes even light drinking.
• Exercise seems to lower the risk of breast cancer.
• Genetic risk factors: The most common causes are mutations in the BRCA1 and BRCA2 genes (breast cancer and ovarian cancer genes). Inheriting a mutated gene from a parent means that one has a significantly higher risk of developing breast cancer.

Do antiperspirants or deodorants cause breast cancer? 

Earlier research has shown that parabens (a preservative used in deodorants) can build up in breast tissues. However, this study did not show that parabens cause breast cancer or find a link between parabens (which many other products contain) and deodorant use. There is currently no strong scientific evidence to support the claim that deodorants increase breast cancer risk.

A few small studies in which people with and without breast cancer have been asked about their deodorant/antiperspirant use have suggested an association, but the design of this type of study limits the interpretation of them.

Many early breast cancers do not produce symptoms and are found on screening procedures. For those cancers that do produce symptoms, the most common sign of breast cancer is a new lump or mass in the breast. In addition, the following are possible signs of breast cancer:

• Thickening or lump in the breast that feels different from the surrounding area
• Inverting of the nipple (as a change from previous appearance)
• Nipple discharge or redness (especially any bloody discharge)
• Breast or nipple pain
• Swelling of part of the breast
• Redness
• Changes in the skin of the breast
• Skin dimpling (peau d’orange)
• Lymph node changes

There are many types of breast cancer. Some are more common than others, and there are also combinations of cancers. Some of the most common types of cancer are as follows:

1. Ductal carcinoma in situ: The most common type of non-invasive breast cancer is ductal carcinoma in situ (DCIS). This early-stage breast cancer has not spread and therefore usually has a very high cure rate.
2. Invasive ductal carcinoma: This cancer starts in the milk ducts of the breast and grows into other parts of the surrounding tissue. It is the most common form of breast cancer. About 80% of invasive breast cancers are invasive ductal carcinoma.
3. Invasive lobular carcinoma: This breast cancer starts in the milk-producing glands of the breast. Approximately 10% of invasive breast cancers are invasive lobular carcinoma.
4. The remainder of breast cancers are much less common and include the following:
5. Mucinous carcinoma is formed from mucus-producing cancer cells. Mixed tumors contain a variety of cell types.
6. Medullary carcinoma is infiltrating breast cancer that presents with well-defined boundaries between the cancerous and noncancerous tissue.
7. Inflammatory breast cancer: This cancer makes the skin of the breast appear red and feel warm (giving it the appearance of an infection). These changes are due to the blockage of lymph vessels by cancer cells.
8. Paget's disease of the nipple: This cancer starts in the ducts of the breast and spreads to the nipple and the area surrounding the nipple. It usually presents with crusting and redness around the nipple.
9. Adenoid cystic carcinoma: These cancers have both glandular and cystic features. They tend not to spread aggressively and have a good prognosis.
10. Lobular carcinoma in situ: This is not cancer but an area of abnormal cell growth. This pre-cancer can increase the risk of invasive breast cancer later in life.

The following are other uncommon types of breast cancer:

1. Papillary carcinoma
2. Phyllodes tumor
3. Angiosarcoma
4. Tubular carcinoma

Male breast cancer 

Breast cancer is rare in men but makes up about 1% of all breast cancers. It typically has a significantly worse outcome. This is partially related to the often late diagnosis of male breast cancer, when the cancer has already spread.

Symptoms are similar to the symptoms in women, with the most common symptom being a lump or change in skin of the breast tissue or nipple discharge. Although it can occur at any age, male breast cancer usually occurs in men over 60 years of age.

Diagnosis, staging, and treatments for male breast cancer are the same as those for women.

Although the above signs and symptoms can diagnose breast cancer, the use of screening mammography has made it possible to detect many of the cancers early before they cause any symptoms.

The American Cancer Society (ACS) has the following recommendations for breast cancer screenings:

Women should have the choice to begin annual screening between 40-44 years of age. Women age 45 and older should have a screening mammogram every year until age 54. Women 55 years of age and older can have mammograms for screening every other year but should have the opportunity to continue screening annually. Women should continue screening mammography as long as their overall health is good and they have a life expectancy of 10 years or longer.

Mammograms are a very good tool for breast cancer screening. As with any test, mammograms have limitations and will miss some cancers. Everyone should discuss their family history and mammogram and breast exam results with their health care provider.

The ACS does not recommend clinical screening exams in women of any age.

Women at high risk (greater than 20% lifetime risk) should get an MRI and a mammogram every year. Women at moderate risk (15%-20%) should talk to their doctor about the benefits and limitations of adding MRI screening to their yearly mammogram.

The BRCA gene test analyses DNA to look for harmful mutations in two breast cancer genes (BRCA1 or BRCA2). This test is performed as a routine blood test. The test should only be performed on patients who have specific types of breast cancers or have a family history suggesting the possibility of having an inherited mutation. These mutations are uncommon, and inherited BRCA gene mutations are responsible for about 10% of breast cancers.

Who is a candidate for BRCA gene testing?

This should be discussed with your health care provider or treatment team as this information is frequently updated. Guidelines for testing may include

• a personal history of breast cancer diagnosis at a young age, bilateral breast cancer, breast and ovarian cancer diagnosis, or a personal history of ovarian cancer;
• family history of breast cancer at a young age (under 50) or ovarian cancer and a personal history of breast cancer;
• family member with bilateral breast cancer, ovarian cancer, or both breast and ovarian cancer;
• relative with a known BRCA1 or BRCA2 mutation; and
• a male relative with breast cancer.

For about 20% of women with breast cancer, the cancer cells test positive for HER2. HER2 is a growth-promoting protein located on the surface of some cancer cells. HER2-positive breast cancers tend to grow more rapidly and spread more aggressively.

All patients with invasive breast cancer should have their tumor cells tested for HER2. This is usually done in the lab after a sample of the breast cancer tissue has been removed (by surgery to remove the tumor or a biopsy to diagnose the cancer).

Discuss the interpretation of the tests with your health care team. Health care professionals may use either immunohistochemistry (IHC) to identify the HER2 protein or in-situ hybridization (ISH) testing to look for the gene.

The signs and symptoms for HER2-positive breast cancers are the same as for HER2-negative breast cancers, except for the fact that HER2-positive cancers grow faster and are more likely to spread.

Staging is the process of determining the extent of the cancer and its spread in the body. Together with the type of cancer, staging is used to determine the appropriate therapy and to predict chances for survival.

To determine if the cancer has spread, several different imaging techniques can be used.

• Chest X-ray: It looks for spread of the cancer to the lung.
• Mammograms: More detailed and additional mammograms provide more images of the breast and may locate other abnormalities.
• MRI: Health care professionals use an MRI to further evaluate the breast or examine other parts of the body.
• Computerized tomography (CT scan): These specialized X-rays look at different parts of your body to determine if the breast cancer has spread. It could include a CT of the brain, lungs, or any other area of concern.
• Bone scan: A bone scan determines if the cancer has spread (metastasized) to the bones. Low-level radioactive material is injected into the bloodstream, and over a few hours, images are taken to determine if there is uptake in certain bone areas, indicating metastasis.
• Positron emission tomography (PET scan): Medical professionals inject a radioactive material that rapidly growing cells (such as cancer cells) absorb preferentially. The PET scanner then locates these areas in your body.

Staging system

A health care team uses this system to summarize in a standard way the extent and spread of the cancer. They use this staging to determine the treatment most appropriate for the type of cancer.

The most widely used system in the U.S. is the American Joint Committee on Cancer TNM system. Medical professionals developed a new eighth edition of this staging system in 2018 that includes results of testing for certain biomarkers, including the HER2 protein and the results of gene expression assays, in addition to the factors (TNM) described below.

Besides the information gained from the imaging tests, this system also uses the results from surgical procedures. After surgery, a pathologist looks at the cells from the breast cancer as well as from the lymph nodes. This information gained is incorporated into the staging, as it tends to be more accurate than the physical exam and X-ray findings alone.

TNM staging uses letters and numbers to describe certain tumor characteristics in a uniform manner. This allows health care providers to stage the cancer (which helps determine the most appropriate therapy) and aids communication among health care providers.

T: This describes the size of the tumor. A number from 0 to 4 follows. Higher numbers indicate a larger tumor or greater spread:

• TX: Primary tumor cannot be assessed
• T0: No evidence of primary tumor
• Tis: Carcinoma in situ
• T1: Tumor is 2 cm or less across
• T2: Tumor is 2 cm-5 cm
• T3: Tumor is more than 5 cm
• T4: Tumor of any size growing into the chest wall or skin

N: This describes the spread to lymph node near the breast. A number from 0 to 3 follows.

• NX: Nearby lymph nodes cannot be assessed (for example if they have previously been removed).
• N0: There has been no spread to nearby lymph nodes. In addition to the numbers, this part of the staging is modified by the designation "i+" if the cancer cells are only seen by immunohistochemistry (a special stain) and "mol+" if the cancer could only be found using PCR (special detection technique to detect cancer at the molecular level).
• N1: Cancer spreads to one to three axillary lymph nodes (underarm lymph nodes) or medical professionals find tiny amounts of cancer in internal mammary lymph nodes (lymph nodes near breastbone).
• N2: Cancer has spread to four to nine axillary lymph nodes or the cancer has enlarged the internal mammary lymph nodes.
• N3: Any of the conditions below
  • Cancer has spread to 10 or more axillary lymph nodes with at least one cancer spread larger than 2 mm.
  • Cancer has spread to lymph nodes under the clavicle with at least area of cancer spread greater than 2 mm.

M: This letter is followed by a 0 or 1, indicating whether the cancer has spread to other organs.

• MX: Medical professionals cannot assess metastasis.
• M0: Health care providers find no distant spread on imaging procedures or by physical exam.
• M1: Spread to other organs is present.

Once the T, N, and M categories have been determined, physicians combine them into staging groups. There are five major staging groups, stage 0 to stage IV, which are subdivided into A and B, or A and B and C, depending on the underlying cancer and the T, N, and M scale.

Cancers with similar stages often require similar treatments.

Patients with breast cancer have many treatment options. Doctors adjust most treatments specifically to the type of cancer and the staging group. Treatment options undergo frequent adjustments, and your health care provider will have the information on the current standard of care available. Discuss treatment options with a health care team. The following are the basic treatment modalities used in the treatment of breast cancer.

Surgery

Many people with breast cancer will require surgery. Broadly, the surgical therapies for breast cancer include breast-conserving surgery and mastectomy.

Breast-conserving surgery

This surgery will only remove part of the breast (sometimes referred to as partial mastectomy). The size and location of the tumor determine the extent of the surgery.

In a lumpectomy, surgeons only remove the breast lump and some surrounding tissue. Medical professionals inspect the surrounding tissue (surgical margins) for cancer cells. If no cancer cells are found, doctors call this "negative" or "clear margins." Frequently, patients receive radiation therapy after lumpectomies.

Mastectomy

During a mastectomy (sometimes also referred to as a simple mastectomy), all the breast tissue is removed. If immediate reconstruction is considered, surgeons sometimes perform a skin-sparing mastectomy. In this surgery, surgeons remove all the breast tissue, as well, but preserve the overlying skin. A nipple-sparing mastectomy keeps the skin of the breast, as well as the areola and nipple.

Radical mastectomy

During this surgery, the surgeon removes the axillary lymph nodes as well as the chest wall muscle in addition to the breast. Physicians perform this procedure very rarely, as in most cases, a modified radical mastectomy is as effective.

Modified radical mastectomy

This surgery removes the axillary lymph nodes in addition to the breast tissue. Depending on the stage of the cancer, a health care team might give someone a choice between a lumpectomy and a mastectomy. Lumpectomy allows sparing of the breast but usually requires radiation therapy afterward. If lumpectomy is indicated, long-term follow-up shows no advantage of a mastectomy over the lumpectomy.

Preventive surgery

For a small group of patients who have a very high risk of breast cancer, surgery to remove the breasts may be an option. Although this reduces the risk significantly, a small chance of developing cancer remains.

Double mastectomy is a surgical option to prevent breast cancer. This prophylactic (preventive) surgery can decrease the risk of breast cancer by about 90% for women at moderate to high risk for breast cancer.

Discuss such an approach with a health care team.

The discussion about whether to undergo any preventive surgery should include

• genetic testing for BRCA1 or BRCA2 gene mutations,
• full review of risk factors,
• family history of cancer and specifically breast cancer, and
• other preventive options such as medications.

Radiation therapy

Radiation therapy destroys cancer cells with high-energy rays. There are two ways to administer radiation therapy.

External beam radiation

This is the usual way health care providers administer radiation therapy for breast cancer. An external machine beam of radiation focuses onto the affected area. A health care team determines the extent of the treatment and is based on the surgical procedure performed and whether lymph nodes were affected or not.

The local area will usually be marked after the radiation team has determined the exact location for the treatments. Usually, the patient receives the treatment five days a week for five to six weeks.

Brachytherapy

This form of delivering radiation uses radioactive seeds or pellets. Instead of a beam from the outside delivering the radiation, these seeds are implanted into the breast next to the cancer.

Chemotherapy

Chemotherapy is treatment of cancers with medications that travel through the bloodstream to the cancer cells. These medications are given either by intravenous injection or by mouth.

Chemotherapy can have different indications and may be performed in different settings as follows:

• Adjuvant chemotherapy: If surgery has removed all the visible cancer, there is still the possibility that cancer cells have broken off or stay behind. If health care providers administer chemotherapy to assure that these small amounts of cells are killed as well, it is called adjunct chemotherapy. Medical professionals don't administer chemotherapy in all cases, since some women have a very low risk of recurrence even without chemotherapy, depending upon the tumor type and characteristics.
• Neoadjuvant chemotherapy: If health care professionals administer chemotherapy before surgery, it is referred to as neoadjuvant chemotherapy. Although there seems to be no advantage to long-term survival whether the therapy is given before or after surgery, there are advantages to see if the cancer responds to the therapy and by shrinking the cancer before surgical removal.
• Chemotherapy for advanced cancer: If the cancer has metastasized to distant sites in the body, chemotherapy can be used for treatment. With cases of metastatic breast cancer, the health care team will need to determine the most appropriate length of treatment.

There are many different chemotherapeutic agents that are either given alone or in combination. Usually, these drugs are given in cycles with certain treatment intervals followed by a rest period. The cycle length and rest intervals differ from drug to drug.

Hormone therapy

This therapy is often used to help reduce the risk of cancer reoccurrence after surgery in certain breast cancers, but it can also be used as adjunct treatment.

Estrogen (a hormone produced by the ovaries) promotes the growth of many few breast cancers, specifically those containing receptors for estrogen (ER positive) or progesterone (PR positive). Hormone therapy or endocrine therapy is the term for the drugs that are given to treat people whose breast cancers express hormone receptors (estrogen or progesterone receptors). The following drugs are examples of those health care providers use in hormone therapy:

• Tamoxifen (Nolvadex): This drug prevents estrogen from binding to estrogen receptors on breast cells.
• Fulvestrant (Faslodex): This drug eliminates the estrogen receptor and can be used even if tamoxifen is no longer useful.
• Aromatase inhibitors: They stop estrogen production in postmenopausal women. Examples are letrozole (Femara), anastrozole (Arimidex), and exemestane (Aromasin).
• Elacestrant (Orserdu) is a drug used to treat advanced breast cancer that expresses hormone receptors when the cancer cells have a mutation in the estrogen receptor (ESR1) gene and the cancer has grown after at least one other type of hormone therapy.

What are the therapies for HER-2-positive breast cancer?

Your health care team needs to evaluate all therapy and provide guidance in response to all test results available and the specific circumstances of your cancer.

There are targeted therapies for HER2-positive breast cancers; a number of drugs are available to target this protein. Examples include:

• Trastuzumab: a monoclonal antibody given by itself or with chemotherapy to treat HER2-positive breast cancers
• Pertuzumab: another monoclonal antibody that targets HER2-positive cancers
• Ado-trastuzumab emtansine or TDM-1: a monoclonal antibody that is attached to a chemotherapy drug

BRCA-mutated breast cancer therapy

Olaparib (Lynparza) is a drug that is approved for treatment of metastatic breast cancer for patients who carry the BRCA mutation. Olaparib has already been used in ovarian cancer. The drug acts as an inhibitor of the enzyme PARP (known as a PARP-inhibitor drug), which is involved in the repair of damaged DNA. Blocking this enzyme may make it less likely to repair cancerous cells, leading to a slowdown or even stoppage of tumor growth.

Targeted therapy

As we are learning more about gene changes and their involvement in causing cancer, drugs are being developed that specifically target the cancer cells. They tend to have fewer side effects than chemotherapy (as they target only the cancer cells) but usually are still used in adjunct with chemotherapy.

Immunotherapy

Immunotherapy makes use of drugs that enhance a person’s own immune system to destroy cancer cells more effectively. Pembrolizumab (Keytruda) is an example of an immunotherapy drug used to treat certain types of breast cancers.

Alternative treatments

Whenever a disease has the potential for much harm and death, physicians search for alternative treatments. As a patient or the loved one of a patient, there may be an inclination to try everything and leave no option unexplored. The danger in this approach is usually found in the fact that the patient might not avail themselves of existing, proven therapies. One should discuss any interest in alternative treatments with a health care team and together explore the different options.

Survival rates are a way for health care professionals to discuss the prognosis and outlook of a cancer diagnosis with their patients. The number most frequently discussed is 5-year survival. It is the percentage of patients who live at least 5 years after they are diagnosed with cancer. Many of these patients live much longer, and some patients die earlier from causes other than breast cancer. With a constant change in therapies, these numbers also change. The current 5-year survival statistic is based on patients who were diagnosed at least 5 years ago and may have received different therapies than are available today. As with all statistics, although the numbers define outcomes for the group, any individual's outcome has the potential for a wide range of variation.

All of this needs to be taken into consideration when interpreting these numbers for oneself.

The SEER database tracks 5-year relative survival rates for breast cancer in the United States, based on how far the cancer has spread. This database groups cancers into localized, regional, and distant stages:

• Localized: There is no sign that the cancer has spread outside of the breast.
• Regional: The cancer has spread outside the breast to nearby structures or lymph nodes.
• Distant: The cancer has spread to distant parts of the body such as the lungs, liver or bones.

Five-year survival rates are

• Localized: 99%
• Regional: 86%
• Distant: 31%
• All SEER stages combined: 91%

These statistics are for all patients diagnosed and reported. Several recent studies have looked at different racial survival statistics and have found a higher mortality (death rate) in African American women compared to white women in the same geographic area.

There is no guaranteed way to prevent breast cancer. Reviewing the risk factors and modifying the ones that can be altered (increase exercise, keep a good body weight, etc.) can help in decreasing the risk.

Following the American Cancer Society's guidelines for early detection can help early detection and treatment.

There are some subgroups of women that should consider additional preventive measures.

Women with a strong family history of breast cancer should be evaluated by genetic testing. This should be discussed with a health care provider and be preceded by a meeting with a genetic counselor who can explain what the testing can and cannot tell and then help interpret the results after testing.

Chemoprevention is the use of medications to reduce the risk of cancer. The two currently approved drugs for chemoprevention of breast cancer are tamoxifen (a medication that blocks estrogen effects on the breast tissue) and raloxifene (Evista), which also blocks the effect of estrogen on breast tissues. Their side effects and whether these medications are right for an individual need to be discussed with a health care provider.

Aromatase inhibitors are medications that block the production of small amounts of estrogen usually produced in postmenopausal women. They are being used to prevent reoccurrence of breast cancer but are not approved at this time for breast cancer chemoprevention.

For a small group of patients who have a very high risk of breast cancer, surgery to remove the breasts may be an option. Although this reduces the risk significantly, a small chance of developing cancer remains.

Without research and clinical trials, there would be no progress in our treatment of cancers.

Research can take many forms, including research directly on cancer cells or using animals.

Research that a patient can be involved in is referred to as a clinical trial. In clinical trials, different treatment regimens are compared for side effects and outcomes, including long-term survival. Clinical trials are designed to find out whether new approaches are safe and effective.

Whether one should participate in a clinical trial is a personal decision and should be based upon a full understanding of the advantages and disadvantages of the trial. One should discuss the trial with a health care team and ask how this trial might be different from the treatment one would usually receive.

Someone should never be forced to participate in a clinical trial or be involved in a trial without full understanding of the trial and a written and signed consent.