Chest Wall Radiation Alone for Breast Cancer Patients With 1-3 Positive Lymph Nodes Treated by Mastectomy

Reviewer: Charles B. Simone, II, MD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: November 1, 2007

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Presenter: Shannon M. MacDonald, MD
Presenter's Affiliation: Massachusetts General Hospital
Type of Session: Scientific

Background

  • Numerous studies have demonstrated that the administration of adjuvant comprehensive postmastectomy radiation, which includes radiation to the chest wall and supraclavicular region, reduces locoregional recurrences and improves overall survival in patients with four or more positive lymph nodes or primary tumors larger than 5 cm. 
  • There currently is no consensus as to whether postmastectomy radiation is similarly beneficial for patients with T1 or T2 tumors with disease in one to three positive lymph nodes.
  • The chest wall is the most common site of locoregional recurrence following mastectomy. Prior studies have demonstrated low rates of axillary failure following adjuvant chest wall irradiation alone.
  • The study was designed to identify possible predictors of locoregional recurrence and to determine if chest wall radiation alone without a supraclavicular field would decrease the rate of locoregional recurrence when compared with patients who did not receive adjuvant radiation or who received comprehensive postmastectomy radiation.

Materials and Methods

  • 238 women were retrospectively analyzed in this study, which included all women with breast cancers less than 5 cm and with one to three involved lymph nodes who underwent mastectomy and axillary lymph node dissection at Massachusetts General Hospital between 1990 and 2004.
  • The median age of patients in the study was 54 (range 31 to 93 years). The median number of nodes excised was 14. Seventy-three patients were treated with adjuvant irradiation, while 165 did not receive postmastectomy radiotherapy.
  • Among those who received adjuvant irradiation, 46 patients received radiation to the chest wall only, of which 11 received irradiation to the internal mammary nodes and 35 did not. Additionally, 27 patients received comprehensive postmastectomy radiation to the chest wall and supraclavicular region, of which 15 also received irradiation to the axillary region and 12 did not. 
  • The chest wall was treated using tangential fields with or without a boost. The mean dose of radiation was 5283 cGy for patients receiving chest wall radiation alone and 5592 cGy for patients treated to the chest wall and peripheral nodes. The mean dose to the supraclavicular region was 4921 cGy, while the mean dose to the axillary region was 4831 cGy.
  • Over 93% (222 of 238) of patients received additional adjuvant therapy, with 35 receiving chemotherapy, 54 receiving hormonal therapy, and 133 undergoing combined systemic treatment.

Results

  • At a median follow-up of 80 months, locoregional recurrences among those not treated with irradiation were noted in 13 patients in 18 locations. Most recurrences occurred in the chest wall (ten), while five occurred in the axilla and three were diagnosed in the supraclavicular fossa. Locoregional recurrences were isolated in six patients and associated with synchronous distant metastasis in seven patients. 
  • No recurrences were noted among patients who received postmastectomy radiation. 
  • At 10 years, the rate of locoregional recurrence was 10.2% in the patients without irradiation, while no patients developed local recurrence in the treatment group (p = 0.02). Patients who received irradiation had improved disease-free survival at five years (96% vs. 85%, p=0.02) and at 10 years (96% vs. 75%, p = 0.02). The improvements in locoregional recurrence and disease-free survival became evident within two years following mastectomy and irradiation. 
  • There was no significant improvement in overall survival at ten years in patients who received irradiation (85.2% vs. 77.7%, p = 0.07).
  • Factors found to be associated with disease-free survival included adjuvant irradiation, lymphovascular invasion, the number of involved lymph nodes, tumor grade, and estrogen receptor status.
  • Among patients who did not receive irradiation, poor tumor grade was the only factor associated with an increased risk of locoregional recurrence (p < 0.001).
  • Since no patients who received postmastectomy radiation experienced a recurrence, subset analysis could not identify a benefit to regional lymphatics irradiation or show a correlation between recurrence and tumor grade. 
  • Patients with extracapsular extension were more likely to receive comprehensive postmastectomy radiation when compared to those who received chest wall irradiation alone (88% vs. 56%, p=0.04).-There was also a trending to administer nodal irradiation in patients with over 20% of lymph nodes positive on axillary dissection (37% vs. 17%, p=0.06). 

Author's Conclusions

  • Postmastectomy radiation to the ipsilateral chest wall was demonstrated to decrease locoregional recurrence in patients with T1 to T2 tumors and one to three involved lymph nodes.
  • Comprehensive postmastectomy radiation could be superior to adjuvant chest wall irradiation alone in preventing locoregional recurrence in patients with extranodal extension or other poor prognostic factors.

Clinical/Scientific Implications

There is a general consensus within the field of radiation oncology that high-risk breast cancer patients with tumors greater than 5 cm or at least four involved lymph nodes who undergo mastectomy should received adjuvant irradiation. Similarly, there is a general agreement that patients with smaller tumors and a negative lymph node evaluation do not need irradiation. However, uncertainty exists as to whether patients with larger tumors and one to three involved lymph nodes would benefit from irradiation, and the extent of adjuvant radiation therapy that is needed. This study is clearly important in showing that patients who receive postmastectomy radiation are less likely to experience a locoregional recurrence and have an improved disease-free survival. However, the question regarding the extent of radiation needed cannot be addressed due to the complete lack of events in the radiation group, thus limiting the ability to compare comprehensive postmastectomy radiation and chest wall only radiation. Additionally, this study was retrospective and nonrandomized, and the sample size for the number of patients receiving chest wall only irradiation was small. Future investigation with a larger patient population that is randomized will be needed to determine if chest wall irradiation alone is as effective as comprehensive irradiation in reducing locoregional recurrence and improving disease-free survival. If both treatment techniques prove to be equally as effective, the administration of chest wall only irradiation will allow patients to benefit from lower rates of brachial plexopathy, lymphedema, and other complications that are more often seen when irradiating the regional lymph nodes.

Partially funded by an unrestricted educational grant from Bristol-Myers Squibb.