The breast cancer treatment depends on patient’s menopausal status, the hormonal receptor and HER2 status, the type of breast cancer, stage and grade of the tumor, and patient’s performance status, along with other factors. Following are the preferred treatment approaches for different stages of breast cancer, but the final decision is taken after clinical assessment of the patient by an oncologist.
Stage I breast cancer is generally treated with modified radical mastectomy (MRM) or breast conservation surgery (BCS). Radiation therapy is given after BCS in all cases. Chemotherapy and/or hormonal therapy and/or HER2 targeted therapy may be given in selected cases as per oncologist’s discretion.
Stage II breast cancer is generally treated with MRM or BCS. Radiation therapy is given in all cases after BCS and in some cases after MRM. Chemotherapy and/or hormonal therapy and/or HER2 targeted therapy may be given in selected cases as per oncologist’s discretion.
|III (Locally advanced)||
Stage III breast cancer is mostly upfront unresectable (except T3N1) and is generally treated with chemotherapy and/or hormonal therapy and/or HER2 targeted therapy to shrink the tumor size. This is followed by MRM or BCS. Radiation therapy has to be given in all cases after surgery.
T3N1 disease is generally treated with modified radical mastectomy (MRM) or breast conservation surgery (BCS). Radiation therapy is given in all cases. Chemotherapy and/or hormonal therapy and/or HER2 targeted therapy may be given as per oncologist’s discretion.
Stage IV breast cancer is generally treated with chemotherapy and/or hormonal therapy and/or HER2 targeted therapy.
Other treatment options like surgery, radiation therapy or bone-directed therapy may be considered for palliation or relief of symptoms.
Following is the brief description of various treatment types commonly used for breast cancer:
1.Surgery: Surgery is the treatment for most localized and locally advanced tumors that have not spread to distant body parts and can be completely removed by a surgical procedure. Following are some commonly employed surgical procedures for the treatment of breast cancer:
-Breast Conservation Surgery: In this surgical procedure, only a part of the affected breast is removed, along with the axillary lymph nodes. This surgery is sometimes referred to as lumpectomy, quadrantectomy, partial mastectomy, or segmental mastectomy. The advantage of this technique is that the patient can retain most of her breast. In most of the cases, breast-conversion surgery is followed by radiation therapy to prevent disease recurrence. If the patient is willing for the same, it may be done upfront in the early stage and after neoadjuvant chemotherapy in the advanced stage if the patient is the suitable candidate for the same as assessed by the oncologist.
-Modified Radical Mastectomy: In this surgical procedure, the entire breast containing the tumor is removed, along with axillary lymph nodes. Radiation therapy is not required in all the cases after mastectomy, hence the procedure can be employed in patients who are not good candidates for the same (e.g., pregnant women, prior radiation to the chest wall). Also, it may be preferred in patients with certain genetic mutations (eg, BRCA) when there are high chances of tumor recurrence.
-Sentinel Lymph Node Biopsy (SLNB): In this surgical procedure, sentinel lymph nodes (the first draining lymph node station from the tumor) are removed and checked for the presence of cancer cells. The advantage of SLNB is that it allows removal of relatively less number of lymph nodes. An absence of cancer in the sentinel lymph nodes indicates cancer has not spread to other lymph nodes. To find the sentinel lymph node, a surgeon first injects a radioactive substance and/or a dye into the cancer tissue. The sentinel lymph node is then determined as the first node detected to have radioactivity and/or the dye color.
-Axillary Lymph Node Dissection (ALND): In this surgical procedure, axillary lymph nodes are removed and checked for the presence of cancer cells. It is mostly performed along with mastectomy or breast-conservation surgery as the same procedure.
-Breast Reconstruction Surgery: Some patients may wish to restore their breast’s appearance after deformation of breasts due to breast cancer surgery. This can be achieved by a breast reconstruction surgery that can be performed at the same time as breast cancer surgery or at a later time as a separate procedure. Artificial graft or patient’s own tissue may be used for breast reconstruction.
2.Radiation Therapy: Radiation therapy (or radiotherapy) uses high-energy radiation directed to the affected area to kill cancerous cells. It can be employed either by using an external radiation source (external beam radiation therapy) or by directly placing the source of radiation near the cancer tissue (brachytherapy). It is used in all cases after BCS and in selected cases after MRM. It may sometimes be used for palliation of symptoms such as pain, bleeding, etc.
3.Hormonal Therapy: This treatment approach is based on the fact that ER or PR positive breast cancer cells grow under the influence of estrogen and progesterone, respectively. Estrogen is predominately produced by the ovaries and a small amount is also produced by the fat tissue in the females. Depriving the breast cancer cells of the estrogen or by lowering the estrogen level in the blood might reduce their rate of growth. The hormonal therapy is considered as the standard treatment for hormone receptor-positive disease. Following are the types of hormonal therapy used for the treatment of breast cancer:
-Selective Estrogen Receptor Modulator, SERM (Tamoxifen): Tamoxifen blocks the estrogen receptors in breast cancer cells (ER-positive) and acts as a weak estrogen in other body tissues like the uterus and bones. It is generally used for the treatment of ER and/or PR positive breast cancer. Common side effects of tamoxifen include hot flushes, venous thromboembolism, increased risk of uterine cancer, etc.
-Selective Estrogen Receptor Degrader, SERD (Fulvestrant): Fulvestrant selectively and permanently blocks and degrades the estrogen receptors in breast cancer cells. It is generally used for the treatment of ER and/or PR positive metastatic breast cancer. Common side effects of fulvestrant include hot flushes, headache, nausea, bone pain, etc.
-Aromatase Inhibitors (AIs): Aromatase is an enzyme that helps in the production of estrogen from fatty tissue. In post-menopausal women, fatty tissue is the main source of estrogen. Thus, AIs (e.g. letrozole, anastrozole, and exemestane) help in lowering estrogen level in post-menopausal women and used for the treatment of breast cancer in these patients. AIs can also be used in pre-menopausal women in combination with surgical or medical oophorectomy (with GnRH/LHRH analogs). Side-effects of AIs include hot flushes, muscle pain, joint stiffness, arthralgia, osteoporosis, etc.
-Oophorectomy: Since the ovaries are the chief source of estrogen before menopause, their surgical removal reduces the blood estrogen level significantly, which leads to shrinkage of ER-positive breast cancers. It may be used in premenopausal women, or in combination with AIs in postmenopausal women
-Luteinizing Hormone-Releasing Hormone (LHRH) analogs: These drugs (e.g., leuprolide and goserelin) acts on the pituitary gland which in turn signals to stop the production of estrogen from the ovaries. It may be used in premenopausal women, or in combination with AIs in postmenopausal women, in patients who wish to retain their ovaries.
4. Chemotherapy: Chemotherapy means treatment with anti-cancer drugs that kill or decrease the growth of rapidly growing cancer cells. It is considered to be the mainstay of treatment for advanced stage disease that has spread to distant body parts. Depending on the physician’s preference and patient’s condition, it may also be combined with other treatment options to accelerate the benefit achievement. Chemotherapy may be used in the neoadjuvant (prior to surgry), adjuvant (after surgery) and palliative (metastatic disease) settings. It may be associated with side effects due to its effect on normal body cells apart from cancerous cells. Common side effects of chemotherapy include nausea, vomiting, hair-loss, diarrhea, mouth ulcers, increased chances of infection, fatigue, decrease in the number of blood cells, etc.
5. Targeted Therapy: Targeted drugs are designed to target a specific gene or protein characteristic of the breast cancer cells. With the advancement in diagnostic techniques, a number of genetic abnormalities for breast cancer have been identified that can be targeted with the help of targeted drugs. Molecular testing to confirm the genetic abnormality is the pre-requisite for starting a targeted therapy. Examples of targeted drugs for breast cancer include anti Her2 therapy (eg, trastuzumab, pertuzumab, etc) for Her2/Neu receptor-positive disease, CDK4/6 inhibitors (e.g. Palbociclib, ribociclib, abemaciclib, etc) that target cyclin-dependent kinases (CDKs, particularly CDK4 and CDK6), everolimus that targets mTOR protein (a protein that helps cells to grow and divide), Olaparib that target BRCA gene mutation, etc.
6. Bone Directed Therapy: Spread of breast cancer to bones may lead to various symptoms like pain in bones, fractures, hypercacemia, etc. To relieve symptoms of bone metastasis, and to prevent further complications, following bone directed therapies are generally employed :
-Bisphosphonates (e.g. Zoledronic acid, Pamidronic acid, etc) Normally, bones are constantly remodeled by two types of bone cells: osteoblasts (they increase bone density) and osteoclasts (they decrease bone density). Bisphosphonates decrease the activity of osteoclasts by inducing apoptosis (natural cell death) in them, and thus, help in maintaining bone density and to relieve symptoms of bone metastasis. Bisphosphonates may cause side effects such as flu-like symptoms, renal dysfunction, hypocalcemia and rarely, osteonecrosis of the jaw (ONJ).
-Denosumab: Denosumab is a monoclonal antibody that binds to RANKL and blocks osteoclast maturation, thus reducing bone resorption and helps in maintaining bone density and relieve symptoms of bone metastasis. It can cause side effects like hypocalcemia, osteonecrosis of the jaw, etc.
It is very important to assess the benefits of each treatment option versus the possible risks and side effects before making a treatment decision. Patient’s choice and health condition are also important to make a treatment choice.
Following are the goals of treating advanced-stage breast cancer:
-Prolongation of life
-Reduction of symptoms
-Improvement of overall quality of life
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