Breast Cancer

Breast Cancer - Mestatatic

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Overview

Breast cancer is a malignant tumor in which the abnormal cells in the breast divide and multiply uncontrollably. The cells can invade nearby tissue and can spread through the bloodstream and lymphatic system to other parts of the body

There are 3 major sub-types of breast cancer in women. It can be determined by specific tests on the tissue sample.

Subtypes
HR+ve (Hormone receptor-positive)
  • Approx 60-75% of tumors express proteins in and on the cell surface. Tumors that have estrogen receptors are called “ER-positive.” Tumors that have progesterone receptors are called “PR-positive.”
HER2+ve (HER2-positive)
  • About 20% to 25% of breast cancers depend on the gene called human epidermal growth factor receptor 2 (HER2) to grow. These cancers are called “HER2-positive” and have excessive numbers of HER2 receptors or copies of the HER2 gene. The HER2 gene makes a protein that is found on the cancer cell and is important for tumor cell growth.
  • Cancers that do not express the HER2 protein are called as HER2-ve (HER2 negative)
Triple Negative Breast Cancer
  • If a tumor does not express ER, PR, and/or HER2, the tumor is called “triple-negative.” Triple-negative breast cancer makes up about 15% of invasive breast cancers.
  • Triple-negative cancer is also more common in women with a mutation in the breast cancer genes 1 and 2, commonly called BRCA1 and BRCA2 genes. Experts recommend that all people with triple-negative breast cancer be tested for BRCA gene mutations

Ductal/Lobular classification

Most breast cancers start in the ducts or lobes and are called ductal carcinoma or lobular carcinoma. Breast cancer can be invasive or noninvasive. Invasive breast cancer is cancer that spreads into surrounding tissues. Noninvasive breast cancer does not go beyond the milk ducts or lobules in the breast.

Classification Description
Ductal carcinoma These cancers starts in the cells lining the milk ducts and make up the majority of breast cancers.
Ductal carcinoma in situ (DCIS) This is cancer that is located only in the duct. When a cancer spreads outside the ducts, it is called as invasive or infiltrating ductal carcinoma.
Lobular carcinoma. This is cancer that starts in the lobules. Lobular carcinoma in situ (LCIS). LCIS is located only in the lobules. LCIS is not considered cancer. However, LCIS is a risk factor for developing invasive breast cancer in both breasts

Risk Factors

Both exposure (environmental or occupational) to particular agents & an individual’s susceptibility to these agents are thought to contribute to one’s risk of developing breast cancer

Risk Factors
Gender Breast cancer is ~100 times more common among women than men
Family History Risk is higher among women whose close blood relatives have this disease
Age Only 12 % of invasive breast cancers are found in women < 45, while 66% of invasive breast cancers are found in women > 55
Race Caucasian women are slightly more likely to develop breast cancer than are African-American women
Density of Breast Tissue Women with denser breast tissue (as seen on a mammogram), which have more glandular tissue and less fatty tissue, have a higher risk of breast cancer (not due to the density, but due to the fact that the density makes imaging difficult)

Symptoms

The following are the common symptoms of breast cancer

Symptoms
Lump in a breast
Pain in the armpits or breast that does not seem to be related to the woman's menstrual period
Pitting or redness of the skin of the breast; like the skin of an orange
Rash around (or on) one of the nipples
Swelling (lump) in one of the armpits
An area of thickened tissue in a breast
One of the nipples has a discharge; sometimes it may contain blood
The nipple changes in appearance; it may become sunken or inverted
Changes in the size and shape of the breast
Peeling of, scaly or flaky skin on breasts and nipples
Bone pain and symptoms of hypercalcemia
Abdominal distention and jaundice

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Diagnosis

Both Imaging and clinical tests are done for diagnosis of breast cancer. The most common test is a Mammogram. However, a mammogram is not sufficient to confirm cancer and hence patients usually undergo additional tests like biopsy and other pathological tests to confirm cancer.

Test
X Ray
PET-CT Scan
Mammogram
MRI & Bone Scan
Biopsy

Symptoms

Presently there is no cure for metastatic breast cancer. The primary goals of the metastatic breast cancer are to ensure

  • Longest survival with the disease
  • Fewest possible side effects
  • Best and longest quality of life possible

Systemic therapy and radition therapy are often used to treat metastatic breast cancer.

There are 3 types of systemic therapy:

Treatment Approach
Hormonal Therapy

Hormonal therapy, also called endocrine therapy, is an effective treatment for many tumors that test positive for either ER or PR.The goal of this type of therapy is to lower the levels of estrogen and progesterone in the body or to block these hormones from getting to cancer cells.If the hormones cannot get to the cancer cells, the cancer cannot use them to grow.

The choice of hormonal therapy depends if the woman in menstruating or has gone through menopause as well as prior treatment history and the patient's immediate health.

Examples of drug given for hormonal therapy are

  • Tamoxifen
    • Tamoxifen is a drug that blocks estrogen from binding to breast cancer cells. It is a pill taken daily by mouth The treatment is an option for both premenopausal and postmenopausal women.
  • Aromatase inhibitors (AIs)
    • These inhibitors block the aromatase enzyme and block production of estrogen in the body.
    • This enzyme changes hormones called androgens into estrogen when the ovaries have stopped making estrogen after menopause. These drugs include anastrozole (Arimidex), exemestane (Aromasin), and letrozole (Femara). All of the AIs are pills taken daily by mouth.
    • Women who have not gone through menopause should not take AI's
  • Fulvestrant (Faslodex)
    • Fulvestrant blocks the ability of estrogen to attach to these receptors
    • Typically, 2 injections are given every 2 weeks for 3 doses and continued monthly.
Chemotherapy

Common ways to give chemotherapy include an intravenous (IV) tube placed into a vein using a needle or in a pill or capsule that is swallowed (orally).

Common chemotherapies include (common brand names in brackets)

  • Capecitabine (Xeloda)
  • Carboplatin (Paraplatin)
  • Cisplatin
  • Cyclophosphamide
  • Docetaxel
  • Doxorubicin
  • Pegylated liposomal doxorubicin (Doxil)
  • Epirubicin
  • Eribulin
  • Fluorouracil (5-FU)
  • Gemcitabine (Gemzar)
  • Irinotecan
  • Ixabepilone
  • Methotrexate (also used for Rheumatoid Arithritis)
  • Paclitaxel
  • Protein-bound paclitaxel (Abraxane)
  • Vinorelbine (Navelbine)
Targeted Therapies

These treatments are very focused and work differently than chemotherapy or hormonal therapy. This type of treatment blocks the growth and spread of cancer cells while limiting damage to healthy cells.

There are different types of targeted therapies that vary in how they target the cancer cells:

  • Monoclonal antibodies
    • It is a type of targeted therapy that recognizes and attaches to a specific protein in the cancer cells, and renders them ineffective. These therapies do not affect cells that don’t have that protein.
  • Small molecule inhibitors
    • These are drugs designed to specifically target parts of a cancer cell that contribute to its growth and survival. The parts of a cancer cell that these drugs target may be receptors on the outside of the cell, enzymes on the inside of a cell, or a protein important for cell growth

Therapies for Different Subtype of Cancer

Approach Treatment
HER2+ve metastatic breast cancer
  • Herceptin
    • For metastatic breast cancer, trastuzumab can be given in combination with different types of chemotherapy or with endocrine therapy. Trastuzumab can be given as a weekly infusion, or once every 3 weeks.
  • Perjeta
    • . Research shows that adding pertuzumab to trastuzumab and chemotherapy as part of first-line therapy for HER2-positive metastatic breast cancer lengthens lives with few additional side effects.
  • Ado-trastuzumab emtansine or T-DM1 (Kadcyla).
    • This is approved for the treatment of metastatic breast cancer for patients who have previously received trastuzumab and chemotherapy with either paclitaxel or docetaxel. T-DM1 is a combination of trastuzumab linked to very small amount of a strong chemotherapy.
  • Lapatinib (Tykerb)
    • Women with HER2-positive metastatic breast cancer may benefit from lapatinib when trastuzumab and pertuzumab in combination with docetaxel are no longer effective at controlling the cancer’s growth.
    Hormone receptor-positive/HER2-negative breast cancer
    • Palbociclib (Ibrance) and Ribociclib (Kisqali)
      • These drug targets a protein in breast cancer cells called CDK4/6, which is believed to stimulate cancer cell growth.
    • Everolimus (Afinitor, Zortress)
      • Everolimus is used with the AI exemestane for ER-positive, HER2-negative metastatic breast cancer that has grown despite treatment with another AI.

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