Treatment of breast cancer depends on the stage of disease (as discussed above). Other factors that determine the treatment are type and grade to tumor, hormone receptor status, Her 2 neu status, menopausal status, performanace status of patient, etc. But the final treatment decision is taken by the oncologist after clinical evaluation of the patient.
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.
So, the treatment for Localised Breast Cancer may be summarized as follows-
- Localised disease includes cases upto T2N1M0 and T3N0M0. It may be treated with Breast Conservation Surgery (BCS) or Modified Radical Mastectomy (MRM).
- For early stage disease and small tumor size, if the patient fulfills the criterion and is willing for the same, BCS is a suitable option. In case of large tumors, when BCS is not possible upfront, neoadjuvant chemotherapy may be given and then tried for BCS.
- If the tumor size is large, or the patient doesn’t fulfill the criterion for BCS, or is unwilling for the same, then the suitable option is MRM. In this technique whole breast tissue and draining lymph nodes are removed.
- Decision to add chemotherapy in the neoadjuvant or adjuvant setting is taken on the basis of size of tumor, involvement of axillary lymph nodes, type of surgery (BCS or MRM), performance status, etc.
- Addition of hormonal therapy and/or targeted therapy is done on the basis of hormone receptor status (ER/PR positive or negative) and Her 2 neu status of the tumor, along with other factors.
- Adjuvant radiation is required in all patients after BCS, but only in selected cases after MRM.
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.
So, the treatment for Locally Advanced Breast Cancer may be summarized as follows-
- It is treated as localised breast cancer (as discussed above), with addition of radiation therapy in all cases.
T4, N2 or N3 disease
- These cases are upfront unresectable, so neoadjuvant therapy is required in all the cases. Thereafter, decision for BCS and MRM is taken depending on response to neoadjuvant treatment, patient’s preference and other factors.
- Then, adjuvant radiation is required for all patients.
- Decision to add adjuvant chemotherapy, targeted therapy and/or hormonal therapy is taken by the oncologist on individual patient basis.
Treatment of Metastatic Breast Cancer
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.
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),
- mTOR Inhibitors like everolimus
- PARP Inhibitors like Olaparib in BRCA positive breast cancers
Bone Directed therapies for Bone Metastasis
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.
As discussed above, chemotherapy for breast cancer may be given as neoadjuvant (before surgery), adjuvant (after surgery) and palliative (for metastatic disease). The chemotherapy regimens are different in these settings.
Some of the chemotherapy agents that have a role in breast cancer treatment are-
Adriamycin/Doxorubicin, Liposomal Doxorubicin