Breast Cancer Blog | 14 March 2022, Monday
Radiation Therapy in Breast Cancer – What, When, and Why?
Radiotherapy or Radiation therapy is a treatment modality used in breast cancer treatment as an adjuvant, to reduce the risk of recurrence of the disease.
The basic principle of radiotherapy is the use of high-energy rays to destroy the cancer cells, that may sometimes remain in the breast even after an optimal surgery for the cancer. Radiation therapy has a role in all stages of breast cancer.
In fact, recent evidence has also suggested the possible role of Radiation as prophylaxis against breast cancer in some selected cases. Let us understand the intricacies.
Treatment of breast cancer has evolved over more than a century. The Edwin Smith Surgical Papyrus, a medical text dating back to 3,000 – 2,500 BC, mentions breast cancer.
Even Hippocrates had described the stages of breast cancer in 400 BC. William Halstead in 1882 had performed the first radical mastectomy in which not only the breast but underlying pectoralis muscle was surgically removed and axillary lymph nodal clearance was done.
X-Ray was first discovered in the late 1890s and within a year of discovery, it was used in the treatment of breast cancer.
Presently, when it comes to surgery for breast cancer, we have come to a point where less is more. We have graduated from disfiguring radical mastectomies to breast conservation surgeries with aesthetic reconstructions.
This transformation from extensive tissue resection surgeries to aesthetic conservative procedures with minimal tissue loss has been possible only due to advances in adjuvant therapy, which includes radiation therapy, chemotherapy and hormonal therapy, which drastically reduces the risk of disease recurrence after an optimal surgery.
Radiation therapy uses high-energy X-rays, Gamma rays, protons or electrons to treat the affected breast and is indicated in almost all patients with early breast cancer undergoing breast conservation surgery.
In some selected patients, like older ladies with estrogen and progesterone receptor-strongly positive breast cancers, and those with small tumours and no nodal spread, after careful consideration, radiation may be avoided.
All patients who receive pre-surgery chemotherapy, due to the size of the tumour or due to nodal involvement, need to undergo adjuvant (treatment after surgery) radiotherapy.
All tumours more than five cm in size, or those causing skin ulceration over the breast tissue and those undergoing mastectomy will require adjuvant Radiation. The EBCTCG Meta-analysis of 2011, which included over 10,000 patients, showed a 50 % reduction in local recurrence of disease over ten years and also a 4% reduction in death due to breast cancer in those who received adjuvant Radiation (1).
Radiotherapy works by damaging the DNA of the cancer cells, thus killing them. The damage is either by direct ionisation or indirect ionisation of the DNA material of the cancer cells. Charged particles like protons can cause direct damage to the DNA material.
Photons like X-rays usually cause indirect ionisation due to the formation of free radicals which in turn damage the DNA structure beyond repair and hence cause cell death. The unit of Radiation is Grays(Gy).
Depending upon the intent of treatment and the site of treatment, the dosage varies. The dosage for breast cancer is 45 to 55 grams, administered in small daily fractions. Conventional Breast Radiotherapy includes 1.8 to 2 Gy per fraction for five days a week, over five weeks to complete a 50 Gy dose for breast cancer.
This Fractionation of radiotherapy over so many days is crucial as it gives time for the normal healthy cells, which also get affected, to recover from the harmful effects of the radiation.
Tumour cells are unable to recover. Fractionation also allows the tumour cells that have been in a relatively resistant phase of the cell cycle into a radiation-sensitive G2- M phase before the next dose of Radiation.
Fractionation also gives time for the tumour cells to reoxygenate, which makes them more vulnerable to the damaging effects of radiation, as oxygen is the primary source of free radicals which damage the tumour cell DNA. As Fractionation is such an important component, any modification can impact the outcome. With this basic understanding, trials have targeted this dose and duration of Radiation to come up with the most effective combination.
In this day and age of instant food and instant cricket, there has been a constant attempt towards reducing the duration of Radiation. What if we could adequately radiate the tumour bed, intra-operatively, when it is most accessible? This form of radiotherapy too has been tried.
After the excision of the tumour, a special kind of portable radiotherapy machine is brought into the surgical field in the operation theatre to precisely radiate the tumour bed and surrounding areas. This form of Radiation, where only a part of the breast is irradiated over a short period, is called Accelerated Partial breast radiation(ABPI).
The Target A (Targeted intraoperative radiation therapy- A) trial with 3451 patients and the ELIOT (External versus Intraoperative radiation therapy) trial with 1305 patients concluded that this form of one-time radiation therapy during the surgery is associated with higher local recurrence rates(2,3).
Fig. 1 – Intraoperative radiation therapy
The tumour recurrences are even more with high-grade tumours and triple-negative breast cancers. Hence presently this type of intraoperative radiation therapy is not recommended outside trial settings. Another application of ABPI is Brachytherapy.
Fig. 2 – Brachytherapy cathetors in place
Brachytherapy is suitable for patients of breast cancer who are more than 50 years of age with a tumour size of 3 cms or less, grade 1 or 2, estrogen and progesterone receptor- strongly positive, Her 2 neu receptor-negative and node-negative.
At the time of surgery, multiple hollow catheters are placed in the surgical field / tumor bed after the tumor resection. Through a special radiotherapy machine, Radiation is delivered to the tumor bed through these hollow tubes.
With this method, radiotherapy is over in five days instead of the five weeks that is needed with conventional radiotherapy(4). five-day schedule has been a blessing.
Fig 3. External beam radiation therapy machine
his schedule has reduced the number of trips a patient has to make to the hospital. Also, the radiation facilities can now cater to more patients in a shorter period.
Fig. 4 – Radiation therapy planning
Radiation is associated with acute toxicities that involve the treated area skin, muscle and internal organs. These complications are relatively uncommon. Long term complications include lung injury, cardiotoxicity and secondary malignancy. With the improvements in radiotherapy planning and techniques, these long term side effects have been significantly reduced.
The fundamental principle of using radiation therapy in the adjuvant (after surgery for breast cancer) setting is that it reduces the risk of local recurrence. So, extending this logic, it could be assumed that radiation can prevent cancer in patients at high risk of developing breast cancer.
This hypothesis was put to the test by radiation oncologists in Israel. All BRCA mutation patients undergoing treatment for breast cancer were offered prophylactic radiotherapy to the opposite healthy breast. 81 patients opted for Radiation, whereas the other 81 patients opted for just surveillance and hence were enlisted as controls.
At a median follow-up of 58 months, 10 patients from the control group had developed cancer on the contralateral normal breast, while only 2 patients who had received prophylactic Radiation developed cancer.
These results are encouraging; however, a longer follow-up is required to include this treatment in practising guidelines. At present, for a patient with BRCA gene mutation, who are at higher risk of developing breast cancer in the opposite healthy breast, a prophylactic mastectomy with breast reconstruction is recommended.
Radiation is also a beneficial palliative modality. In patients with stage IV breast cancer, having bone metastases, single-dose radiation of up to 10 Gy can reduce the bone pain, which is otherwise often unresponsive to any analgesics.
Recently in very specialised centres, radiotherapy treatment using a proton beam is available. This modality allows for precise targeting of tumour beds with minimal collateral damage. For breast cancer, this treatment is still in the investigative stage and available only in a trial setting.
Thus, modern cancer treatment is a very sophisticated and advanced science offering the cutting edge of technology from different fields of medicine to help all those who are battling this Emperor of maladies.
Radiotherapy, along with Chemotherapy and Surgery is one of the three major pillars of modern cancer care. Radiotherapy has made a huge positive impact on the outcome and extent of surgery for breast cancer.
Gone are the days when breast cancer universally meant a disfiguring and life-changing mastectomy.
Today, with huge advances in the science of radiotherapy, breast-conserving surgery has become the new normal. Things have never looked so bright for breast cancer patients, as it is now.
Author Dr. Jay Anam: The author is a specialist breast surgical oncologist doing breast cancer surgeries with oncoplastic reconstructions.
Attachments: Saifee Hospital, H.N. Reliance Hospital, Jupiter Hospital, K.J Somaiya Medical College.
Acknowledgments: To Dr. Bhavin Visaria and Dr. Manish Chandra, Radiation oncologist par excellence for their inputs.
To my team at Specialty Surgical Oncology: Dr. Sanket Mehta, Dr. Praveen Kammar, and Dr. Chetan Anchan towards their valuable criticisms & inputs towards this blog.