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Estrogen receptor/progesterone receptor (ER/PR) positive breast cancers tend to grow more slowly than ER/PR negative cancers, and are more likely to respond to hormone therapy. Approximately two-thirds of breast cancers are ER and/or PR positive.
Estrogen receptors and progesterone receptors are proteins on the cell surface which stimulate cell growth and division in response to estrogen or progesterone, the two female hormones. Breast cancer is considered hormone receptor (HR) positive if either or both of these hormone receptors are present in the cancer cells.
In HR negative cancers, cancer growth is not stimulated by hormones and is less likely to respond to hormone therapy. Hormone therapy is usually given after breast cancer treatment to reduce the risk of recurrence. Hormone therapy reduces estrogen levels in the body or blocks the activity of estrogen receptors on the cancer cells.
Cancers are a group of diseases in which some types of cells turn abnormal and proliferate without control. Cancer that originates in the breast is known as breast cancer. Breast cancer is one of the most common cancers in women and the second leading cause of cancer deaths in women. Men can also develop breast cancer, but less than 1% of breast cancers are in men.
What is triple negative breast cancer?
In addition to being negative for estrogen and progesterone receptors, triple negative breast cancer cells also lack a protein known as HER2. Human epidermal growth factor receptor-2 (HER2) is a protein that promotes cell growth and HER2 positive breast cancers have a higher than normal presence of these proteins, because of mutations in HER2 gene.
Triple negative cancers account for approximately 15% of breast cancers. Triple negative breast cancer more often occurs in African-American women younger than 40, or women who have an inherited mutation in BRCA1 gene, which normally is a tumor suppressor gene, which suppresses cell growth.
What are the categories of breast cancer?
Breast cancers are categorized into the following groups based on the hormone receptor and HER2 status:
- Luminal A: ER and PR positive, and HER2 negative breast cancer
- Luminal B: ER positive, PR negative and HER2 positive breast cancer
- HER2 positive: HR negative and HER2 positive breast cancer
- Triple positive: ER, PR and HER2 positive breast cancer
- Triple negative (basal like): HR and HER2 negative breast cancer
What are the stages of breast cancer?
Breast cancer is staged by the size of the tumor and extent of spread. Breast cancers are also graded from one to three, based on how abnormal the cancer cells look and how fast they grow. One is low grade cancer and three is high grade cancer that grows and spreads rapidly.
The four stages of breast cancer are:
- Stage I: The tumor is relatively small and localized to the original site, with possible spread to the sentinel lymph nodes, which are the first lymph nodes the cancer is likely to spread to.
- Stage II: The tumor has grown and spread to a few nearby lymph nodes.
- Stage III: The tumor has grown into many lymph nodes and other tissue in the breast.
- Stage IV: The cancer has spread (metastatic cancer) to distant parts of the body.
Another highly detailed classification system is the TNM classification system based on tumor size, lymph node involvement and metastatic spread.
What are the symptoms of breast cancer?
The most common symptom of most breast cancers is a lump in the breast. A painless, hard mass with irregular edges is most likely cancer, but breast cancers can also have a lump that is soft and tender to the touch. Other possible symptoms in the first three stages of breast cancer include:
- Change in the size and shape of the breast
- Swelling of the breast
- Asymmetry in the breast compared to the other
- Skin dimpling or other abnormal changes in the breast’s skin
- Nipple inversion or other nipple abnormalities such as ulceration
- Nipple discharge, especially if bloodstained
- Swollen lymph nodes under the arm or near the collarbone
Symptoms of metastatic cancer depends on where the cancer has spread and can include:
How is breast cancer hormone receptor status diagnosed?
A test known as immunohistochemistry (IHC) test is performed to detect the presence of estrogen and/or progesterone receptors. A sample of breast tissue is taken during a biopsy or surgery and tested in the laboratory. Lab-manufactured antibodies are used to see if they are attracted to the cancer cells, which will indicate the presence of hormone receptors.
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What is the treatment for HR positive breast cancer?
Treatment for breast cancer is individualized depending on the type, grade, stage, gene mutations and HR and HER2 status. Treatment also depends on the age, overall health and whether the woman is menopausal or not. Treatment may be more complicated if the woman is pregnant. Patients also have the option of enrolling for clinical trials for new treatments.
The primary treatment for all types of breast cancers, including HR positive cancers typically include a combination of two or more of the following:
Most women have surgery as part of the treatment, and surgical procedures may include:
- Lumpectomy: Removal of the tumor with a healthy margin, in low grade early stage cancers.
- Mastectomy: Removal of the whole breast if the cancer has spread to other breast tissue.
- Lymphadenectomy: Removal of sentinel lymph nodes, where the cancer is likely to spread first, and/or the lymph nodes under the arm, to test for cancer.
Many women also undergo a breast reconstruction surgery after surgery for tumor removal. Surgery may also be useful in some situations in metastatic cancers as palliative care.
Radiotherapy is the use of high-energy rays or particles to destroy the cancer cells. Radiotherapy is typically used after surgical removal of breast cancer, to make sure any remaining cancer cells are destroyed, or if cancer has spread to other parts.
Chemotherapy is the use of medications that kill cancer cells. Chemotherapy is typically used after surgery to lower the risk of recurrence, or sometimes before surgery to shrink large localized tumors.
Gene expression tests which evaluate the risk of recurrence are often performed to assess the possible benefit of chemotherapy and individualize the treatment plan based on the patient’s needs. Chemotherapy is also used to treat metastatic breast cancers.
HR positive treatments
In addition to the primary cancer treatments, HR positive breast cancer patients may benefit from one or more of the following treatments:
Removal of ovaries (oophorectomy) may be an option for some women with HR positive breast cancer who are premenopausal. Oophorectomy permanently stops estrogen production by the ovaries and can reduce the risk of cancer recurrence.
Certain chemotherapy drugs may be used to damage the ovaries in HR positive premenopausal women to stop estrogen production. The ovaries may regain their function after several years or become permanent in some women.
Hormone therapy is used as an adjuvant therapy after surgery, to reduce risk of cancer recurrence and to stop or slow down cancer growth in metastatic cancer. Hormone therapy is used only for breast cancers that are HR positive. The types of medications used in hormone therapy include:
- Selective estrogen receptor modulators (SERMs): SERMs block estrogen receptors on the cancer cells and prevent estrogen from attaching to them. SERMs are prescribed for both pre- and post-menopausal women. Examples of SERMs are:
- Selective estrogen receptor degraders (SERDs): SERDs damage the estrogen receptors. The FDA-approved SERD to treat post-menopausal women is:
- Fulvestrant (Faslodex)
- Aromatase inhibitors: Aromatase inhibitors block the activity of aromatase, an enzyme found in fat cells which produces estrogen. Aromatase inhibitors are prescribed as adjuvant therapy for most post-menopausal women, and for select pre-menopausal women in combination with medication that stops ovarian production of estrogen. Examples of aromatase inhibitors include:
- Luteinizing hormone-releasing hormone (LHRH) analogs: LHRH analogs block the signals that stimulate the ovaries to produce estrogen. These medications are used in pre-menopausal women in combination with other hormone therapy medications. LHRH analogs include:
Targeted therapy medications do not kill cancer cells, but slow down their growth by blocking the activity of specific proteins that help each particular type of tumor grow.
Targeted therapy drugs used to treat HR positive breast cancers are medications that inhibit the following types of proteins all of which promote cancer cell growth and division in different ways:
- CDK4/6 inhibitors:
- Palbociclib (Ibrance)
- Ribociclib succinate (Kisqali)
- Abemaciclib (Verzenio)
- mTOR inhibitors:
- Everolimus (Afinitor)
- PI3K inhibitor:
- Alpelisib (Piqray)
What is the treatment for triple negative breast cancer?
The primary treatments for triple negative breast cancers are surgery, radiation and chemotherapy in the first three stages of cancer. In addition, treatment for stage IV cancer include:
Targeted therapy used to treat triple negative cancer include:
- PARP inhibitors: PARP inhibitors are used to treat triple negative, as well as HR positive and HER2 negative breast cancers which have BRCA mutations. Poly ADP ribose polymerase (PARP) is an enzyme that helps DNA repair, and PARP inhibitors block the cancer cells from repairing their DNA so they die. PARP inhibitors include:
- Olaparib (Lynparza)
- Talazoparib tosylate (Talzenna)
- Antibody-drug conjugates (ADC): Antibody-drug conjugates are antibodies that specifically attach to a protein in cancer cells and also deliver a chemotherapy drug to kill the cancer cell. ADC used to treat triple negative cancer which has the protein Trop-2 is:
- Sacituzumab govitecan-hziy (Trodelvy)
Immunotherapy drugs enhance the ability of immune cells to identify and kill the cancer cells. Immunotherapy is used to treat triple negative cancers that have a protein known as PD-L1 in them.
- PD-1 inhibitors: PD-1 protein in immune cells (T-cell) prevents them from attacking the body’s cells, including cancer cells. Blocking PD-1 activity improves T-cell’s ability to kill cancer cells. PD-1 inhibitors used to treat triple negative cancers that have PD-1 in them include:
- Pembrolizumab (Keytruda)
- PD-L1 inhibitors: Some cancers produce PD-L1 proteins which bind to PD-1 in T-cells and stimulate their activity to escape death. PD-L1 inhibitors block PD-L1. PD-L1 inhibitor used to treat PD-L1 positive triple negative cancer is:
- Atezolizumab (Tecentriq)
What is the survival rate for HR positive breast cancers?
The survival rate for breast cancers are excellent if the cancer is detected early, and in general HR positive cancers grow slower and have a better prognosis. Overall, breast cancers that are both HR positive and HER2 negative have the best outcomes.
According to recent National Cancer Institute data, the four-year survival rate for combined stages of cancer, based on HR and HER2 status are:
- HR positive/HER2 negative: 92.5%
- HR positive/HER2 positive: 90.3%
- HR negative/HER2 positive: 82.7%
- HR negative/HER2 negative: 77%
What is the survival rate for triple negative breast cancer?
Triple negative cancers are more aggressive than other cancers, more likely to recur, and are usually diagnosed in more advanced stages than other breast cancers, and hence have the poorest prognosis. The five-year survival rate for triple negative breast cancers are:
- Localized cancer: 91%
- Regional spread: 65%
- Distant metastasis: 12%
- All stages combined: 77%
Note that each patient is unique; survival rates are an average of a group of patients with similar problems.
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