ABSTRACT: While radiation therapy for breast cancer can be omitted in some settings, in others it is now being recommended more often. Radiation is usually recommended for patients with invasive breast cancer who have undergone breast conserving surgery. Internationally, there is general agreement that regional nodal radiation is beneficial when four or more nodes are positive, and in BC adjuvant regional nodal radiation also tends to be offered to all patients with any number of positive nodes after both breast conserving surgery and mastectomy. Most patients who are found to be node-negative after mastectomy do not require adjuvant radiation therapy. However, patients at risk because of their young age or the size and biology of their tumors may be candidates for radiation therapy. Because adjuvant radiation therapy is based on pretreatment staging, it is important to accurately determine both the primary and nodal stage, especially in the setting of neoadjuvant chemotherapy. Typically, radiation therapy sessions last 15 to 20 minutes and can be given over 16 to 20 sessions. Patients are monitored regularly during treatment for management of side effects, which can include fatigue, dermatitis, and breast/chest wall tenderness. In the long term there can be permanent cosmetic changes, and rare risks of lung, rib, and heart damage, as well as second malignancies.
Easier access to radiation therapy in Northern BC appears to be why an increasing number of patients in one surgeon’s practice have opted for partial mastectomy and adjuvant radiation rather than mastectomy.
Adjuvant radiation therapy plays a significant role in the treatment of patients with breast cancer because it reduces the relative risk of recurrence by two-thirds and can improve survival. The decision to recommend adjuvant radiation is influenced by the type of surgery performed, whether breast conserving surgery (BCS) or mastectomy, and also by the stage of the cancer and a combination of histopathologic factors. With access to radiation therapy made easier with the opening of the BC Cancer Centre for the North in Prince George in 2012, patient choice of surgical procedures appears to have been affected.
In recent years, recommendations for managing breast cancer have evolved, and while radiation therapy can be omitted in some settings, in others it is being recommended more often.
Lobular carcinoma in situ requires no adjuvant radiation treatment. The local management of ductal carcinoma in situ (DCIS), however, is similar to that of invasive ductal cancer, despite the noninvasive nature of DCIS. The general approach to noninvasive malignancies is BCS followed by adjuvant whole-breast radiation. In select patients with small and widely excised tumors, radiation may be omitted. Consultation with a radiation oncologist is recommended after surgical removal of DCIS to discuss these cases individually. Adjuvant radiation is not necessary after mastectomy for DCIS.
Invasive node-negative breast cancer
In general, adjuvant whole-breast radiation is recommended for patients with node-negative disease who have undergone BCS as this approach reduces the risk of local recurrence by two-thirds and prevents one breast cancer death for every four local recurrences.
There is now evidence that older patients with small tumors and favorable receptor status (i.e., ER-positive, PR-positive, HER2-negative) may not gain any survival advantage from adjuvant radiation. Therefore, for patients older than 70 with ER-positive stage I breast cancer (T1 N0 M0), it is reasonable to omit radiation therapy and treat with a hormonal maneuver alone. BC Cancer has just completed participation in a trial to assess this treatment strategy in women older than 55 years of age with small (less than 2 cm) tumors and ER-positive, PR-positive, HER2-negative, node-negative disease. Partial-breast radiation, which can be delivered over shorter time periods, is not currently considered standard treatment in British Columbia but is under investigation.
Node-positive breast cancer
The general consensus internationally is that when four or more regional nodes are positive, adjuvant radiation therapy improves survival, with a reduction in breast cancer mortality of as much as 5%. While there is some controversy in the setting of fewer positive nodes (one to three), a recent trial has shown that the addition of regional nodal radiation not only improves locoregional control by a further 3% when compared to breast radiation alone, but also results in a reduction in breast cancer recurrence, with a 5% improvement in disease-free survival although not in overall survival. Similar benefit is also seen in the postmastectomy setting with one to three positive nodes. In British Columbia we tend to offer adjuvant regional nodal radiation to all patients with any number of positive nodes after both BCS and mastectomy.
High-risk node-negative breast cancer
Patients who have had a mastectomy and are node-negative do not usually require adjuvant radiation therapy. In a similar vein, patients who have had breast conserving surgery and are node-negative require only radiation to the breast, and not to the regional lymph nodes. However, high-risk patients may have radiation delivered to the chest wall and regional nodes or to the breast and regional nodes in order to improve locoregional control and breast cancer mortality.[7,8] Examples of factors that increase risk are patient age younger than 50, tumor larger than 2 cm, medial primary tumor location, lymphovascular space invasion, high-grade disease, and estrogen receptor negativity. Usually, a combination of these risk factors is required for an individual patient to be considered high-risk. For these patients, careful discussion with a radiation oncologist regarding the potential benefits and side effects of radiation therapy is important. Particular long-term side effects to be considered would be lymphedema, along with the rare occurrence of brachial plexopathy and radiation-induced second malignancy, which is of greater concern in younger patients.
Radiation following neoadjuvant chemotherapy
Patients who have undergone neoadjuvant chemotherapy can have dramatic responses with significant downstaging of their tumors. Currently, adjuvant radiation treatment recommendations are based on pretreatment staging. Therefore, the accurate determination of both primary and nodal stage prior to initiating chemotherapy is important. Ideally, this would mean either image-guided biopsy of suspicious nodes or axillary ultrasound in clinically node-negative patients. This practice may evolve as we continue to gain long-term experience with neoadjuvant chemotherapy and associated outcomes.
Radiation delivery and side effects
Radiation delivered for breast cancer is most commonly external beam radiation, namely X-rays. Prior to radiation treatment, patients must have a CT simulation scan to plan for treatment. The patient undergoes a noncontrast CT scan in the treatment position (typically, supine with arms up above the head), and tattoos are placed on the skin for accurate positioning on the treatment table. Radiation is delivered daily, with patients in the treatment room for 10 to 15 minutes for each session. Typically, radiation therapy is delivered in an accelerated fashion over 16 to 20 sessions. Depending on patient factors such as large breast size, potential cosmetic concerns, and plans for reconstructive surgery, 25 to 28 sessions may be recommended. Patients are advised about skin care and monitored regularly during treatment for management of side effects. The acute side effects of radiation therapy are fatigue, dermatitis, and breast/chest wall tenderness. Radiation-induced dermatitis can range from moderate to severe erythema, along with dry to moist desquamation. There is also a subacute risk of pneumonitis, which can develop anywhere from 4 to 12 weeks after radiation. This condition presents with nonproductive cough, dyspnea, low-grade fever, chest pain, malaise, and/or weight loss, and the diagnosis can be confirmed on radiographic imaging. For patients with more than minimal symptoms, prednisone is recommended for 2 weeks, followed by dose tapering for 3 to 12 weeks.10 Consultation with the treating oncologist is recommended in such cases. In the long term, inferior cosmesis resulting from telangiectasia and fibrosis is common. There is also a risk of pulmonary fibrosis and rib osteoporosis, as well as lymphedema if nodal radiation is given. There are rare risks of cardiotoxicity in left-sided breast cancers, brachial plexopathy if nodal radiation is given, and radiation-induced second malignancy.
Impact of Centre for the North opening on breast cancer treatment
Breast surgery for cancer has become less extensive over the years, moving from the Halsted (radical) mastectomy to the simple mastectomy to the partial mastectomy known commonly as lumpectomy. In 1973 a randomized controlled trial was started to compare survival in patients undergoing either simple mastectomy or partial mastectomy. Results after follow-up at 5, 8, 12, and 20 years showed no difference in overall survival or disease-free survival between the two groups. Despite this, patients in rural centres may choose mastectomy over BCS in order to avoid traveling for the radiation therapy recommended following BCS.
On 1 November 2012 the BC Cancer Centre for the North opened in Prince George. Before this date, any patient choosing to have BCS would have to travel to a regional cancer centre in Southern BC for adjuvant radiation therapy. Data from the University Hospital of Northern BC (UHNBC) suggest that access to a radiation centre close to where patients live can affect surgical choice. In 2011, before the Centre for the North opened, one of the authors of this article (FMS) performed 49 procedures for breast cancer (excluding cases where patients had neoadjuvant chemotherapy) at UHNBC. Of the patients treated, 86% (42/49) had mastectomies and 14% (7/49) had partial mastectomies (and presumably subsequent radiation therapy, although information on this was not collected). In contrast, 60 breast cancer procedures were performed by the same surgeon in 2016 (again excluding cases where patients had neoadjuvant chemotherapy). Of the patients treated, only 35% (21/60) had mastectomies and 65% (39/60) had partial mastectomies (P < .01, Fisher Exact test). This 51% decrease in the mastectomy rate represents a dramatic change in surgical care in the 5-year period after the opening of the Centre for the North, which was able to provide patients in Northern BC with closer-to-home access to radiation.
From the opening of the centre on 1 November 2012 to 31 January 2017, a total of 633 breast cancer consultations were completed by three full-time-equivalent radiation oncologists, and the number of consultations per year rose annually. One possible explanation for this is that the number of referrals has increased as physicians and patients have become more aware of the availability of radiation treatment. During this time, 317 courses of breast or chest wall plus or minus regional nodal adjuvant radiation were delivered to breast cancer patients from Northern BC.
Adjuvant radiation therapy is a critical component in the care of women who have had breast conserving surgery and may also be recommended for some women who have had a mastectomy. The indications for radiation therapy are evolving. Access to adjuvant radiation therapy is an important factor in surgical decision making, with the availability of a local treatment centre allowing more women to choose breast conserving surgery rather than mastectomy.
This article has been peer reviewed.
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Dr Sutter is a general surgeon in Prince George, BC, a clinical assistant professor in the Department of Surgery at UBC, and a member of the Breast Tumour Group of the BC Cancer Surgical Oncology Network. Dr Ye is a radiation oncologist at the BC Cancer Centre for the North, and a clinical instructor in the Department of Surgery at UBC.
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