Survival benefits of radiation in late breast cancers – post mastectomy, post lumpectomy after neo-adjuvant chemotherapy, and hormonal therapy
Late or advanced stage breast cancers include stages IIIB, IIIC and IV. In stage IIIA, as discussed earlier, although the tumor could be >5 cm, it does not invade the chest wall, even though a spread of tumor to the axillary nodes is present.
Stage IIIA is considered as a stage that is amenable to good outcome after treatment. On the other hand, when the tumor has advanced to the breast skin, chest wall or both, the stage is IIIB. Axillary nodes (1-9) and deeper internal mammary nodes may be present. Further, in stage IIIC, more nodes in and around the clavicle (infraclavicular (below the clavicle bone) and supraclavicular (above the clavicle bone) nodes) will report cancer, including >10 lymph nodes being affected in the axillary region. Stage III is limited to the same side of the chest.
In far advanced cancer, stage IV, the cancer has spread to distant sites as well, including, liver, lungs, bones or other sites. Once, the cancer returns after any initial treatment it is known as recurrent/relapsed breast cancer.
The goal of treatment in breast cancer is to eradicate all evidence of cancer as detailed in the pathology report, including the clinical examination and radiological imaging. The recommendation for radiation therapy is based on the stage of breast cancer that has been identified.
In locally advanced breast cancer amongst the pre-menopausal women it is recommended to down stage the disease with neo-adjuvant chemotherapy (NACT). After 3-4 cycles once the tumour in the breast has shrunk the breast surgeon places an opaque marker in the residual tumour under radiological guidance. The patient then completes six cycles of chemotherapy and can undergo breast conserving surgery with lumpectomy and axillary dissection rather than complete removal of breast (mastectomy). If the disease is multi-centric at the beginning then a complete surgery is required.
After surgery either lumpectomy or mastectomy patient is given external beam radiotherapy to sterilize the whole breast or the chest wall and nodal basins to prevent a local recurrence. Radiation therapy can kill microscopic cancer cells that can persist after initial treatment, thereby playing a vital role in reducing the risk of a relapse and improve survival. The role of radiation after mastectomy has been an important area of oncological research. Analyses from long-term studies have indicated that women with lymph node-positive (stage II or III) breast cancer benefit from radiation therapy after mastectomy (breast cancer surgery). The risk of recurrence is lowered by 32%, as well as the risk of dying from breast cancer is considerably reduced (by 20%) in patients with breast cancer with one to three nodes.
Furthermore, for breast cancer with four or more lymph nodes, radiation after mastectomy reduced the risk of recurrence by 21% and improved survival rates by 13% compared to not getting radiation therapy after mastectomy. Similar benefits of adjuvant radiation therapy were observed even in patients receiving chemotherapy or hormonal therapy. Chemotherapy plus radiation results in a survival of 54% at 10 years as compared to 45% with chemotherapy alone. Addition of radiation to hormonal therapy resulted in 10 year survival of 45% compared to 36% with hormonal therapy alone . An overall survival benefit is also observed in women with 4 or more positive lymph nodes and cancer that had spread to the skin (IIIB).
Although adjuvant radiotherapy for breast cancer has been shown to improve local as well as regional control and overall survival, oncologists decide the benefits against possible radiation toxicity and quantify the dosage and delivery according to individual patient’s disease. Adverse effects that were observed with radiation therapy in the heart or lung have been minimized or made negligible with the advent of conformal and intensity modulated radiotherapy as well as cardiac sparing techniques. The risk of lymphedema after axillary dissection is 26% and addition of radiation made it close to 40%, however, since last 10-15 years axillary radiation has been stopped after a good axillary dissection and the incidence of lymphedema is decreasing now. The risk of second primary cancer after chemotherapy and radiation is 2.1 per hundred thousand and extends from 4.5 to 20 years post treatment.