Breast Cancer

BREAST CANCER: Symptoms, causes, types, genetic testing, and treatment

  • Breast Cancer is a type of cancer that originates from the breast ducts cells or tubes that carry milk to the nipple or lobules glands cells that make milk
  • A lump that is painless, hard, and has uneven borders or edges is more like likely to be cancer
  • In 2018, an estimated 266,120 new cases of invasive breast cancer are expected to be diagnosed in women in the U.S., along with 63,960 new cases of non-invasive (in situ) breast cancer. About 40,920 women in the U.S. are expected to die in 2018 from breast cancer
  • Targeted Therapy: Targeted therapies are drug treatments that help the body’s immune system fight cancer. Herceptin® is a type of biologic therapy that targets cells that produce too much of a protein called HER2

Breast Cancer is a type of cancer that originates from the breast ducts cells or tubes that carry milk to the nipple or lobules glands cells that make milk. Less commonly, breast cancer can begin in the stromal tissues, which include the fatty and fibrous connective tissues of the breast. It occurs in both women and men, although breast cancer in women is more frequent. There are several subtypes of breast cancer, but some of them are quite rare.

 

 

How frequent is Breast Cancer?

Breast cancer is the most common form of cancers in women and is second only to lung cancer as the leading cause of cancer deaths among women in the United States.  It is estimated that 1 in every 8 U.S. women (12.4%) will develop breast cancer at some point in her life.  Breast cancer occurs more frequently in the older woman, but 1 in 4 breast cancers is diagnosed in woman under the age of 50.  Less than 5% of all breast cancer diagnosed in women younger than 35.

In 2018, an estimated 266,120 new cases of invasive breast cancer are expected to be diagnosed in women in the U.S., along with 63,960 new cases of non-invasive (in situ) breast cancer. About 40,920 women in the U.S. are expected to die in 2018 from breast cancer.  Afro-American women under 45 are more affected by breast cancer than white women. Men also can develop breast cancer. About 2,550 new cases of invasive breast cancer are expected to be diagnosed in men in 2018. A man’s lifetime risk of breast cancer is about 1 in 1,000.

 

What causes Breast Cancer?

 

Today, it is not clear why breast cancer occurs. A generally accepted theory is that cancer occurs as a result of mutations, or abnormal changes, in the genes orchestrating or regulating the growth of cells and keeping them in order and within normal healthy limits. The genes are in each cell’s nucleus and dictate the normal growth pattern of cells. When mutations occur certain genes can “turn on” while some genes are “turn off”.  These changes set an abnormal pattern of cell division, characterized by an uncontrollable cell division, producing more cells with abnormal features referred to as malignant cells and as they aggregate and accumulate, a tumor is formed. A tumor can be benign (not dangerous to health) or malignant (has the potential to be dangerous). Benign tumors are not considered cancerous: their cells are close to normal in appearance, they grow slowly, and they do not invade nearby tissues or spread to other parts of the body. Malignant tumors are cancerous. Left unchecked, malignant cells eventually can spread beyond the original tumor to other parts of the body and this is referred to as metastases.  Over time, cancer cells acquired the ability to evade the natural immune system and can invade nearby healthy breast tissue and make their way into the underarm lymph nodes, small organs that filter out foreign substances in the body. If cancer cells get into the lymph nodes, they then have a pathway into other parts of the body.

 

What are the risks of developing breast cancer?

As of today, numerous risk factors have been identified.  But these risks factors are neither necessary nor sufficient to cause cancer by itself.  The most significant factor for breast cancer is gender (being a woman) and age (growing older).  

Cancer-related genes

Gene mutations caused about 10% of breast cancers.  They can be inherited from the mother or the father.

  • Family history of breast cancer: Having a first-degree relative (mother, sister, daughter, brother, and father) who had breast cancer increases her risk of developing breast cancer, and it is more profound if this relative was under 45 years of age at the time of diagnosis.  Cancer at a young age of family members, especially breasts and/or ovarian cancer is a red flag for a genetic predisposition. BRCA1 and BRCA2 are the 2 main genes involved in familial forms of breast cancer. The lifetime risk of breast cancer in a BRCA1 mutation carrier is 80–85%, with a 60% chance that cancer will be bilateral. The risk of both subsequent breast cancer occurrence and mortality is reduced by prophylactic surgery. For women with a BRCA2 mutation, the risk is 45%. Breast cancer that is positive for the BRCA1 or BRCA2 mutations tends to develop more often in younger women. An increased ovarian cancer risk is also associated with these genetic mutations. In men, BRCA2 mutations are associated with a lifetime breast cancer risk of about 6.8%; BRCA1 mutations are a less frequent cause of breast cancer in men.  Another gene implicated in cancer is p53
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  • Breas cancer Risk factors

 

  • History of breast cancer: A history of having had breast cancer increases the risk of having breast cancer in a different part of the breasts or in the other breasts.

-Exposure to estrogens and progesterone: Menstrual periods before the age of 12 and ended after the age of 55 are at an increased risk of developing breast cancer.  Having no children or having then after age 30 out also at an increased risk. Additionally, the use of medication containing estrogens and progesterone-like oral contraceptive pills increases the risk of breast cancer.  This association has also been noticed with hormone replacement therapy after menopause

    • Benign breast conditions: Certain benign breast tumors, called atypical lobular hyperplasia and atypical ductal hyperplasia increases the risk of breast cancer.
    • Social factors: Women with a higher level of education are at an  increased risk of developing breast cancer
    • Radiotherapy exposure of the breasts:  seen in children or adolescents have received radiotherapy treatment for lymphomas.
    • Obesity and overweight: Estrogens production in fat tissue play an important role and being obese and overweight increases the risk of developing breast cancer.
    • Smoking and alcohol consumption: Multiple studies have confirmed the increased risk of breast cancer with alcohol consumption and smoking.
  • Diet high in saturated fat
  • Not getting enough exercise

 

What are the symptoms of breast cancer?

Because breast cancer symptoms vary from person to person, the best thing to do is to familiarize with your breasts so you know how “normal” feels and looks.  If you notice any changes, tell your doctor. Initially, breast cancer may not give you any symptoms or a lump may be too small for you to feel or to cause any usual changes that you can notice on your own.  Many breast cancers are found by mammograms before any symptoms appear. A lump that is painless, hard, and has uneven borders or edges is more like likely to be cancer.

But, almost 90% of all breast masses are caused by benign lesions (non-cancerous) and not due to malignancy.
According to the American Cancer Society breast cancer symptoms might include:

  • Lump or mass in your breast
  • Enlarged lymph nodes in the armpit
  • Lump in the underarm area
  • Changes in breast size, shape, skin texture or color
  • Dimpling or puckering
  • Nipple pain, changes or discharge other than breast milk
  • redness, scaliness, or thickening of the nipple or breast skin
  • Nipple pulling to one side or a change in direction

These symptoms do not always mean you have breast cancer. However, it is important to discuss any symptoms with your doctor, since they may also signal other health problems such as an infection or a cyst. It’s important to get any breast changes checked out promptly by a doctor.

 

Which are the most common types of breast cancer?

There are multiple types of breast cancer.  Breast cancer may have a single type, combination, or a mixture of invasive and noninvasive (in situ) cancer:

Here we provide a brief mention of the most common histological types and molecular types:

Ductal carcinoma

Ductal carcinoma is the most common form of breast cancer. Tumors form in the cells of the milk ducts, which carry milk to the nipples. Ductal carcinoma can be invasive with the potential to spread or non-invasive (also called ductal carcinoma in situ or DCIS). About one in five new breast cancer cases are DCIS. The chance for successful treatment of DCIS usually is very high.

Lobular carcinoma

Lobular carcinoma is the second most common type of breast cancer. This disease occurs in the lobules, which are the milk-producing glands. Lobular breast cancer can be non-invasive (in situ or LCIS, also called lobular neoplasia) or invasive (have a tendency to spread). About one in 10 breast cancer cases are invasive lobular cancer.

Inflammatory breast cancer

Inflammatory breast cancer or IBC, is a rare, aggressive form of breast cancer that affects the dermal lymphatic system. Rather than forming a lump, IBC tumors grow in flat sheets that cannot be felt in a breast exam.

Triple-negative breast cancer

Triple-negative breast cancer (15% of all breast tumors) is usually an invasive ductal carcinoma with cells that lack estrogen and progesterone receptors and do not have an excess of HER2 protein on their surfaces. These types of breast cancers tend to spread more quickly and do not respond to hormone therapy or drugs that target HER2.

Recurrent breast cancer

This is cancer that has returned after being undetected for a time. It can occur in the remaining breast tissue or at other sites such as the lungs, liver, bones or brain. Even though these tumors are in new locations, they still are called breast cancer.

 

 

How is breast cancer diagnosed?

If you have any symptoms are noticed any lumps on your breasts, your doctor will examine you and ask you questions about your healthy lifestyle, including smoking and drinking habits and your family history.  Your doctor may recommend one or more of the following tests that can be used to find out if you have breast cancer and if he has a spread.

Biopsy: Small sample of the suspicious area of the breasts is removed for examination under the microscope.  These biopsies may be done in one of the following ways:

Fine needle aspiration (FNA): A thin, hollow needle is inserted into the breast. Fluid and cells are removed from the tumor and looked at with a microscope. While this test can help to determine if breast cancer is present, it cannot determine if the cancer is invasive. Additional biopsies may be needed if breast cancer is found.

Core biopsy: A thicker needle is used to remove one or more small cylinder-shaped tissue samples from the tumor.

Stereotactic needle biopsy: This procedure uses a mammogram-directed technique using computerized mammogram breast images which helps to map the exact location of the breast lump

Surgical biopsy: An incision (small cut) is made in the breast. Surgeons find the tumor by touch or with a CT (or CAT, computed axial tomography) scan, ultrasound or mammogram. In an excisional biopsy, the entire mass is removed. In an incisional biopsy, part of the tumor is removed

Sentinel lymph node biopsy: Lymph nodes are olive-sized glands that are part of the lymphatic system that circulates lymph fluid throughout the body. The lymphatic system also can carry cancer cells from the tumor site to other areas of the body. In breast cancer, the first nodes to be affected are under the arms. In a sentinel lymph node biopsy, a radioactive blue dye is injected into the area before surgery. The dye shows up in cancerous lymph nodes. The node with the highest amount of blue dye is the “sentinel” node. The surgeon removes all nodes with blue dye. Sentinel node biopsy can spare healthy lymph nodes, which results in fewer side effects such as lymphedema.

 

Imaging tests: which may include:

  • Mammograms: A low radiation X-ray called. Mammograms can often detect a breast lump before it can be felt. It also shows small deposits of calcium in the breast. Although most calcium deposits are benign, a cluster of very specks of calcium (called microcalcifications) may be an early sign of cancer
  • Ultrasonography: Using high-frequency sound waves, ultrasonography can often show whether a lump is a fluid-filled cyst (not cancer) or a solid mass (which may or may not be cancer)
  • Magnetic Resonance Imaging (MRI): MRI is used to define the size and extent of cancer within the breast tissue. It is mostly used in women whose dense breast tissue makes it more difficult to find tumors with a mammogram
  • Digital Mammography: Digital mammography is similar to standard mammography and it uses radiographs to image the breast. The advantage of digital mammography is that images are stored digitally and can be enhanced by modifying the brightness or contrast.

Blood tests: Biological protein markers levels are normally ordered, like carcinoembryonic antigen (CEA), CA 27.29, alkaline phosphatase and liver enzymes.  Additional tests are performed to assess the white blood cells, the red blood cells, and the platelets, and tests performed to exclude any problems in the kidneys and the bones.

 

What are the common results of the biopsy?

Once the tumor is obtained, it will be examined in the laboratory by a pathologist.  This is very important to confirm the results of the biopsy and to provide further information on cancer.  Some of the results of the biopsy, commonly, include the following:

Histological type: assignment of histological type is based on the type of cells that comprise the tumor. Breast cancers form in tissues of the breast, usually the ducts or the lobules. The main histological types of breast cancer are ductal carcinomas and lobular carcinomas. The histopathological examination will also classify cancer as invasive or non-invasive. Non-invasive cancers are also called cancer in situ

Grade: Assignment of the grade is based on the heterogeneity of tumor cells, the architectural structure of the tissue they form and the frequency of mitosis (cell division) of tumor cells. A well-differentiated tumor (grade 1) has low heterogeneity of cells, preserved architectural structure, and few mitoses. An undifferentiated tumor (grade 3) has high heterogeneity, loss of architecture and many mitoses. A moderately differentiated tumor (grade 2) is in between grade 1 and grade 3. The lower the grade, the better the prognosis.

When systemic treatment is planned before surgery, the biopsy results should include hormone receptor* status and HER2 status. When no systemic treatment is planned before surgery, these can be determined in the tumor (and/or the lymph nodes) after their removal by surgery.

Hormone receptor status for estrogen and progesterone: Tumor cells can present receptors to estrogen and receptors to progesterone on their surface or inside the cell. Cells of some tumors present a high level of receptors. This means that their growth and multiplication are stimulated by hormones. Tumors with a high level of estrogen receptors (ER+)* and/or progesterone receptors (PR+) have a better prognosis than tumors lacking estrogen receptors (ER-) and/or lacking progesterone receptors (PR-).

HER2 status:  HER2 is a cell surface protein present in about 20% of breast cancer cases. HER2 is involved in the growth and migration of cells.

Multigene expression profiles: the quantification of the expression of distinct sets of genes expressed by the tumor can also be performed on the biopsy. Such multigene signature analyses are not routinely performed but can help to predict the risk of recurrence and the likelihood of benefit from chemotherapy.

Ki-67 labeling index: Ki-67 is a protein found in the nucleus of cells when they are dividing but not when they rest. Ki-67 labeling index indicates the percentage of cells in which Ki-67 can be found. Analysing the proportion of dividing cells is a method to determine the level of proliferation of the tumor. Highly proliferating tumors grow faster and have a worse prognosis than slowly proliferating tumors, but at the same time, highly proliferating tumors are more sensitive to chemotherapy.

Oncotype DX is a 21-tumor gene expression assay designed to predict the need for chemotherapy based on patient scores from 0 to 100. Those with a score of 26 to 100 are found to benefit from the addition of chemotherapy to endocrine therapy. However, patients with a score of 0 to 10, defined as a low risk of recurrence, derive minimal to no benefit from added chemotherapy. The benefit of added chemotherapy has been uncertain for patients with intermediate risk (11-25)

Oncotype testing

 

Breast cancer staging

Doctors use staging to assess the risks and prognosis associated with specific characteristics of the patient and the type of cancer involved.  Staging is a way of the determining how much disease is in the body and where he has a spread. This information is essential because it helps your doctor decide the best time for treatment for you and the outlook for your recovery and prognosis. The TNM staging* system is commonly used. The combination of the size of the tumor (T) and invasion of nearby tissue, the involvement of lymph nodes (N), and metastasis* or spread of cancer (M) to other organs of the body, will classify cancer into one of the following stages.

The stage of cancer is fundamental for decisions regarding treatment. The less advanced the stage, the better the prognosis is. Staging is usually performed twice: after clinical and radiological examination as well as after surgery. If surgery is performed, staging may also be influenced by the laboratory examination of the removed tumor and lymph nodes.

Breast Cancer Stages

(source: National Cancer Institute)

Stage 0 (carcinoma in situ): Cancer has not spread from the site of origin. There are two types of breast carcinoma in situ:

Ductal carcinoma in situ (DCIS) is a noninvasive condition in which abnormal cells are found in the lining of a breast duct. The abnormal cells have not spread outside the duct to other tissues in the breast. In some cases, DCIS may become invasive breast cancer and spread to other tissues.

Lobular carcinoma in situ (LCIS) is a condition in which abnormal cells are found in the lobules of the breast (where milk is made). This condition seldom becomes invasive cancer. However, having LCIS in one breast increases the risk of developing breast cancer in either breast.

Stage IA: The breast tumor is no more than 2 centimeters (no more than 3/4 of an inch) across. Cancer has not spread to the lymph nodes.

Stage IB: The tumor is no more than 2 centimeters across. Cancer cells are found in lymph nodes.

Stage IIA: The tumor is no more than 2 centimeters across, and the cancer has spread to underarm lymph nodes, or The tumor is between 2 and 5 centimeters across, but the cancer hasn’t spread to underarm lymph nodes

Stage IIB: The breast cancer tumor is larger than 2 centimeters but not larger than 5 centimeters and has spread to the axillary lymph nodes, or The tumor is larger than 5 centimeters but has not spread to the axillary lymph nodes.

Stage IIIA: Breast cancer is found in axillary lymph nodes that are attached to each other or to other structures. Cancer may be found in lymph nodes near the breastbone, or The tumor is 2 centimeters or smaller. Breast cancer has spread to axillary lymph nodes that are attached to each other or to other structures. Cancer may have spread to lymph nodes near the breastbone, or The tumor is larger than 2 centimeters but not larger than 5 centimeters. Breast cancer has spread to axillary lymph nodes that are attached to each other or to other structures. Cancer may have spread to lymph nodes near the breastbone, or The tumor is larger than 5 centimeters. Breast cancer has spread to axillary lymph nodes that may be attached to each other or to other structures. Cancer may have spread to lymph nodes behind the breastbone.

Stage IIIB: The tumor may be any size and breast cancer: Has spread to the chest wall and/or the skin of the breast. May have spread to axillary lymph nodes that may be attached to each other or to nearby tissue. May have spread to lymph nodes near the breastbone

Stage IIIC: The breast cancer can be any size, and:  Cancer has spread to lymph nodes behind the breastbone and under the arm, or; Cancer has spread to lymph nodes above or below the collarbone

Stage IV: The tumor can be any size, and cancer has spread to other organs of the body, most often to the bones, lungs, liver or brain.

 

WHAT ARE THE TREATMENT OPTIONS?

 

At HEMATOLOGY & ONCOLOGY CARE we customize your breast cancer care so you can receive the most advanced, least invasive treatment with a few with side effects. Planning of the treatment involves an interdisciplinary team of medical professionals. This usually implies a meeting of different specialists, called a multidisciplinary opinion. In this meeting, the planning of treatment will be discussed based on the relevant information summarized above.

The treatment will usually combine intervention methods that:

Effective on cancer locally, such as surgery or radiotherapy

Effective on cancer cells all over the body with systemic therapy such as chemotherapy, hormone therapy and/or HER2-directed therapy.

 

The extent of the treatment will depend on the characteristics of the tumor cells, molecular markets, and on the stage of the cancer, as well as on the age, the menopausal status and the co-morbidity of the patient. It is recommended to ask an oncologist about the expected benefits and risks of every treatment in order to be informed of the consequences of the treatment. For some treatments, several options are available. The choice should be discussed according to the balance between benefits and risks.

Some of the treatment approaches include but are not limited to:

Neoadjuvant therapy: is therapy given before surgery or radiotherapy for breast cancer.  Contrary, to adjuvant therapy that he is given after surgery or radiotherapy.  Neoadjuvant chemotherapy for breast cancer is a new multidisciplinary strategy that was introduced with the aim of reducing tumor size before surgery. The main rationale behind this type of treatment is to reduce the tumor size, make an inoperable tumor operable and of course, which is a new tendency allowing more conservative surgery and is now widely used, particularly for large tumors.  One of the advantages seen with neoadjuvant chemotherapy is the opportunity to observe tumors diminished in size or shrink both palpably and on imaging, and having a clinical oncologist can have a rapid assessment of clinical response.  This could help tests the progressive responses in vivo of the tumor to new drugs regimens, which could then could be used as adjuvant therapies. Neoadjuvant chemotherapy can shrink a larger tumor enough so that lumpectomy plus radiation therapy becomes an option to mastectomy

Adjuvant therapy: is a therapy given in addition to surgery. For patients with stage I to III breast cancer, possible adjuvant therapies are radiotherapy, chemotherapy, hormone therapy and targeted therapy. In this setting, radiotherapy is a local treatment whereas chemotherapy, hormone therapy, and targeted therapy can reach cancer cells that may have spread to other parts of the body.

Hormone therapy: This therapy consists of one or possibly a combination of two of the following treatments:

A drug called tamoxifen which counteracts the action of estrogens on the breast and is active in both premenopausal and in postmenopausal patients

A drug from the aromatase inhibitor family like anastrozole, exemestane or letrozole which inhibit the production of estrogens in post-menopausal women

A drug from the gonadotropin-releasing hormone analogs family that lower the level of estrogens in pre-menopausal women

Ovariectomy – the removal of the ovaries in premenopausal women The choice of hormone therapy is based on the menopausal status of the patient.

 

Chemotherapy:

Chemotherapy for early-stage breast cancer consists of combining two or three anti-cancer drugs, which are given according to a precise protocol. For breast cancer, the treatment is generally given for 4 to 8 cycles, a cycle being a time period of 2 to 4 weeks with a precise dosage, duration, and sequence of drugs including a resting period before a new cycle is started. It is not clear which combination of drugs is best, but it is recommended that it contains doxorubicin or epirubicin, which are anti-cancer drugs from the anthracycline family. Assessment of heart function is important before therapy with anthracyclines. However, regimens without any anthracycline have been shown to be as effective, for instance, the combination of docetaxel and cyclophosphamide. Treatments are often named with acronyms using the initial letter of each drug name (e.g. FEC, stands for the combination of Fluorouracil, Epirubicin, and Cyclophosphamide). For frail or elderly patients the CMF (Cyclophosphamide, Methotrexate, and Fluorouracil) regimen may still be appropriate. Another option, especially for women in whom tumor cells have spread to the lymph nodes, is to combine an anthracycline (doxorubicin* or epirubicin) with a taxane drug (paclitaxel), preferably given in sequence rather than in combined fashion.

Targeted Therapy: Targeted therapies for breast cancer are drug treatments that help the body’s immune system fight cancer. Herceptin® is a type of biologic therapy that targets cells that produce too much of a protein called HER2. This protein is present in some breast cancer patients. Herceptin binds to the cells, shutting off HER2 production.

HER2-directed therapy is used for HER2 positive breast  cancers. Trastuzumab is a drug effective in patients with HER2 positive tumors, regardless of the size of the tumor and of its hormonal status. In the studies performed to evaluate its efficacy as an adjuvant therapy, trastuzumab was always given in combination with chemotherapy. It is not clear, whether the adjuvant use of trastuzumab without chemotherapy has a positive effect. The standard recommended the duration of adjuvant treatment with trastuzumab is 1 year. Results from studies comparing this standard duration to shorter or to longer durations are pending. Trastuzumab can be given together with paclitaxel or carboplatin but should not be given together with doxorubicin* or epirubicin. The latter two drugs and trastuzumab are both toxic to the heart. Trastuzumab cannot be given to patients whose heart function is abnormal. If there is doubt about the heart function, it should be assessed before trastuzumab treatment.

Surgery: Like all surgeries, breast cancer surgery is most successful when performed by a specialist with a great deal of experience in the particular procedure. 

Surgery is the most common treatment for breast cancer. Procedures may include:

Mastectomy: This surgery removes one or both breasts. The entire breast is removed, along with any affected lymph nodes. In about 80% of mastectomies, breast reconstruction or implant surgery is done during the same procedure, after the breast is removed.

Breast-sparing surgery is an attempt to save as much healthy breast tissue as possible. These procedures are best for treating early stage (I and II) breast cancer. Breast-sparing techniques include:

Lumpectomy: The tumor and a small margin of healthy breast tissue are removed.

Partial mastectomy: The breast cancer tumor is removed, along with a margin of healthy breast tissue. The lining of the chest muscles and any affected lymph nodes under the arm are removed also.

Breasts reconstruction: Using either breast implants or tissue from your abdomen or other parts of your body, the surgeon can recreate a breast either during the cancer surgery (immediate reconstruction) or after surgery (delayed reconstruction). Learn more about our guide to breast reconstruction.

Radiation Therapy: Radiation Therapy uses high-energy beams to destroy cancer cells. New radiation therapy techniques and remarkable skill allow doctors to target tumors more precisely, delivering the maximum amount of radiation with the least damage to healthy cells. Radiation therapy treatments available are Intensity-modulated radiation therapy (IMRT and Accelerated partial breast irradiation an internal (APBI)

 

The information in this document does not replace a medical consultation. It is for personal guidance use only. We recommend that patients ask their doctors about what tests or types of treatments are needed for their type and stage of the disease.

Sources:

American Cancer Society

The National Cancer Institute

National Comprehensive Cancer Network

American Academy of Gastroenterology

National Institute of Health

MD Anderson Cancer Center

Memorial Sloan Kettering Cancer Center

 

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