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.
Watch this video to better understand the treatment of Localised Breast Cancer
If we see the localised disease in detail, it includes cases till T3, that is tumor more than 5 cm but not infiltrating the skin or chest wall, or N1, that is presence of mobile axillary lymph nodes.
In early stage disease, the decision to move ahead with BCS depends on patient as well as oncologist. The patient has to be willing for it and give consent for the same, and oncologist has to look for any contraindications for the procedure. If everything is in favor, and the tumor size is small, breast conservation surgery maybe done directly.
Whereas if the tumor is large, we first have to give neo-adjuvant chemotherapy to shrink the tumor, and then reassess for breast conservation surgery, depending upon the response to chemotherapy.
So, the decision to add chemotherapy in the neoadjuvant or adjuvant setting is taken on an individual patient basis, after discuss in a tumor board. Also the decision to add hormonal therapy and targeted therapy is taken depending upon the ER, PR and her-2 receptor status and along with other factors.
After Breast Conservation Surgery, radiation therapy is given in all the cases. Where as after modified radical mastectomy, the decision to add radiation therapy is taken by the radio oncologist depending upon the T-status, N-status, margins of resection along with other factors.
Watch this video to better understand the treatment of locally advanced breast cancer
Locally advanced breast cancer includes cases with a T4 disease, that is infiltration of the chest wall or skin or N2 or N3 disease, that is, fixed or matted axillary lymph nodes. This figure shows T4 disease, with infiltration into the chest wall or skin, and N2 or N3 disease, with a presence of matted or fixed axillary lymph nodes.
These cases are not upfront resectable. That is why, neoadjuvant chemotherapy, that is, chemotherapy before surgery, is required in almost all the cases of locally advanced breast cancer.
One exception is T3N1 disease, that may be upfront resectable, but neo adjuvant chemotherapy may be required in these cases if planning for breast conservation surgery, in these cases.
In locally advanced disease also, the decision to do BCS or MRM is taken after neoadjuvant chemotherapy, depending upon the response to chemotherapy, as we have discussed previously for localized disease.
So the decision to add neoadjuvant or adjuvant chemotherapy is taken in an individual basis, after discussion in the tumor board. The decision to add hormonal therapy or targeted therapy depends upon the ER, PR and HER-2 status, as we discussed previously for localized disease.
Radiation therapy is required in almost all cases of locally advanced diseases but the final decision is taken by the radiation oncologist by completely assessing the patient.
This brings us to the end of treatment for locally advanced breast cancer.
Watch this video to better understand Metastatic Breast Cancer Treatment
Metastatic disease constitutes for 5-10% of the cases of breast cancer.
The treatment options for metastatic breast cancer are chemotherapy, hormonal therapy for ER PR positive disease, and anti Her-2 therapy for Her-2 positive disease. Radiotherapy or surgery may be added for palliation, i.e., reduction of symptoms, and bone redirected therapy may be given in presence of bone metastasis.
Remember cure is not the intent for giving treatment in metastatic disease. It is mainly given to prolong the life, reduction of symptoms, and improvement of quality of life. Treatment for metastatic disease is decided based on the site of metastasis, previous treatments taken, ER, PR, HER-2 status, performance status of the patient and the comorbidities in the patient.
Types of Breast Cancer Surgery
First of all, we will discuss the types of surgery done for breast cancer.
Breast cancer Surgery can either be a breast conservation surgery or modified radical mastectomy.
First we come to breast conservation surgery.
In early stage disease, when the tumor size is small and it can be removed with adequate margins, without removing the whole breast, it is called breast conservative surgery.
Its advantage is that, it helps preserve breast tissue and results in better cosmesis.
For advanced stage disease with larger tumor size, breast conservation surgery may be tried.
In this, we first have to shrink the tumor size by giving neoadjuvant chemotherapy, and later reassess the tumor for breast conservation surgery, depending upon the response to chemotherapy.
If after neoadjuvant chemotherapy, there is shrinkage of tumor to a size when it can be removed with adequate margins without removing the whole breast, breast conservation surgery may be done.
Where as when the tumor size is very large and breast conservation surgery is not possible, we do the modified radical mastectomy or MRM.
As you can see, the complete breast tissue is removed in MRM, along with the axillary lymph nodes.
In early-stage disease also, MRM may be done in place of BCS in certain cases, such as when the patient is apprehensive and does not give consent for BCS or when there are contraindications against BCS
But the final decision is taken after discussing with the patient and discussion in the tumor board on an individual patient basis.
Chemotherapy, Targeted and Hormonal Therapy
Chemotherapy may be required for localized or locally advanced disease, or for metastatic disease.
For localized or locally advanced disease, it can be either neoadjuvant, that is, given before surgery, or adjuvant, that is given after the surgery.
For metastatic disease, it is called palliative chemotherapy.
Next comes the hormonal therapy. As we have discussed previously ER and PR testing is done on biopsy samples of breast tissue. If it is positive, hormonal therapy may be added.
Similarly, if the biopsy shows her-2 positivity, anti-her2 therapy is added.
Breast cancer treatment methods Details
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:
2. 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.
3. 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.
4. 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.
5. 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.
6. 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.
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.
- 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.
- 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.
- 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.
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:
- Reduction of symptoms
- Prolongation of life
- Improvement of overall quality of life
Join our BREAST CANCER COMMUNITY to connect with fighters and survivors across the globe.