Should Older Women Receive Radiation Therapy?
Editor's Note:
The management of breast cancer in older women is not straightforward, partly because definitions of "older" differ across trials (eg, 50 and older, 65 and older, 70 and older) and partly because older women are seldom the focus of randomized controlled trials. Furthermore, reluctance to treat older women with standard therapy is related to concerns about their ability to tolerate the stresses of radiation therapy and chemotherapy. Some large, randomized trials of breast cancer therapies have included older women, and the results of these trials in that subpopulation provide information to guide management decisions.
Medscape Oncology spoke with Timothy Whelan, BM, BCh, MSc, FRCPC, a radiation oncologist at McMaster University, about local management of older women with estrogen receptor (ER)-positive breast cancer, including the role of radiation and axillary node dissection.
Medscape: How would you define local management?
Dr. Whelan: Local management includes radiation and surgery (mastectomy, lumpectomy, sentinel node biopsy, and axillary node dissection). Systemic therapy includes chemotherapy, oophorectomy (in younger patients), and hormonal therapies. For the purposes of this interview, let's confine our discussion to local breast cancer, meaning stage I (no nodal involvement) or II (tumors > 2 cm and < 5 cm and/or nodal involvement).
Medscape: What is standard local therapy for younger women with ER-positive breast cancer?
Dr. Whelan: Younger women undergo mastectomy or lumpectomy and whole breast irradiation as well as sentinel node biopsy, axillary dissection, or both. Two studies published in 2004 suggested that older women with early breast cancer may be able to forego whole breast irradiation after lumpectomy. One study randomly assigned 636 women with node-negative, ER-positive breast cancer treated with lumpectomy to receive tamoxifen plus whole breast irradiation (n = 317) or tamoxifen alone (n = 319). At 5 years, the rate of local or regional recurrence was 1% in the group treated with radiation vs 4% in women given tamoxifen alone (P < .001). Although the rate of locoregional failure was slightly higher in women who did not have radiation, overall survival was the same in both treatment arms: 87% vs 86%, respectively. This study was recently updated. At 10 years, the rate of local or regional recurrence was 2% in the group treated with radiation vs 10% in women given tamoxifen alone (P < .015), but no differences in survival were observed between the 2 treatment groups.
This study suggested that it may be safe to withhold radiation therapy in older women with smaller tumors who are node-negative because this strategy has no negative impact on survival.
Medscape: You mentioned 2 important studies in older women. What was the second study and what did it show?
Dr. Whelan: The second study had a somewhat different population. It included approximately 150 women with ER-negative tumors. The study randomly assigned 769 women with early breast cancer (tumor diameter of ≤ 5 cm) to receive tamoxifen plus whole breast irradiation (n = 386) vs tamoxifen alone (n = 383). At 5 years, the relapse rate was 0.6% with tamoxifen plus radiation vs 7.7% with the tamoxifen alone (P < .001). Disease-free survival rates were 91% vs 84%, respectively (P = .004). A preplanned subgroup analysis of 611 women with node-negative, receptor-positive tumors indicated a significant benefit for radiation therapy; the 5-year rate of local relapse was 0.4% for tamoxifen plus radiation vs 5.9% for tamoxifen alone (P < .001). However, there was no significant difference between treatment arms in rates of distant relapse or overall survival.
Medscape: Both studies were conducted in 2004 using older radiation techniques. What are some of the newer strategies, and wouldn't those have an impact on the decision about whether to treat with radiation?
Dr. Whelan: We are now seeing increased use of hypofractionated radiation given over 3 weeks and accelerated partial breast irradiation given over 1 week.
Medscape: What happens in clinical practice? Do most physicians treat older women with ER-positive early breast cancer with radiation?
Dr. Whelan: That depends on the oncologist and patient preference. Some oncologists feel that with the newer techniques given over much shorter time periods, there is no reason to avoid radiation because it provides a benefit in preventing recurrence. Some women may opt for radiation because they don't want to have to have a subsequent mastectomy if they have a recurrence, although the study by Hughes and colleagues found that the rate of mastectomy for recurrence was not increased in the tamoxifen-alone group.
If you avoid radiation, the patient still has to take hormonal therapy for 5 years, but if you undergo radiation, then you may be able to forego hormonal therapy. Small tumors with no nodal involvement have a low rate of recurrence, so this is a decision that must be made by the oncologist and the patient.
Medscape: What about complete axillary dissection for older women with ER-positive breast cancer and minimal nodal involvement? Can these women be safely treated with sentinel node dissection alone?
Dr. Whelan: The ACOSOG Z0011 study, which tended to include older women, suggested that complete axillary dissection may not be necessary in selected patients with 1 or 2 positive sentinel lymph nodes.The study was conducted at 115 sites and had a targeted enrollment of 1900 patients, but accrual was slow. Results from 813 patients with clinical node-negative tumors and 1 or 2 positive sentinel lymph nodes have been published. All patients underwent lumpectomy and whole breast irradiation and were then randomly assigned to receive axillary lymph node dissection or no further axillary treatment. At a median follow-up of 6.3 years, 5-year overall survival was 91.8% for axillary lymph node dissection vs 92.5% with sentinel lymph node dissection alone; 5-year disease-free survival was 82.2% vs 83.9%, respectively.
Although this study showed that survival was not inferior using sentinel node dissection alone, this is still controversial because accrual was lower than expected. This strategy may be more useful in older women because younger women tend to have worse outcomes compared with older women.
Medscape: What are the take-home messages for our readers?
Dr. Whelan: Age alone should not be a barrier for standard therapy. Selected older patients with no serious comorbid conditions can be safely treated with standard therapy. Whole breast radiation may be withheld in selected older women with early-stage ER-positive breast cancer, provided they are prepared to accept a slightly higher recurrence rate and the caveat that newer techniques may make radiation more attractive for patients. It appears to be possible to eliminate axillary dissection in patients with 1 or 2 positive sentinel nodes without compromising survival.
Editor's Note:
The management of breast cancer in older women is not straightforward, partly because definitions of "older" differ across trials (eg, 50 and older, 65 and older, 70 and older) and partly because older women are seldom the focus of randomized controlled trials. Furthermore, reluctance to treat older women with standard therapy is related to concerns about their ability to tolerate the stresses of radiation therapy and chemotherapy. Some large, randomized trials of breast cancer therapies have included older women, and the results of these trials in that subpopulation provide information to guide management decisions.
Medscape Oncology spoke with Timothy Whelan, BM, BCh, MSc, FRCPC, a radiation oncologist at McMaster University, about local management of older women with estrogen receptor (ER)-positive breast cancer, including the role of radiation and axillary node dissection.
To Irradiate or Not to Irradiate?
Medscape: How would you define local management?
Dr. Whelan: Local management includes radiation and surgery (mastectomy, lumpectomy, sentinel node biopsy, and axillary node dissection). Systemic therapy includes chemotherapy, oophorectomy (in younger patients), and hormonal therapies. For the purposes of this interview, let's confine our discussion to local breast cancer, meaning stage I (no nodal involvement) or II (tumors > 2 cm and < 5 cm and/or nodal involvement).
Medscape: What is standard local therapy for younger women with ER-positive breast cancer?
Dr. Whelan: Younger women undergo mastectomy or lumpectomy and whole breast irradiation as well as sentinel node biopsy, axillary dissection, or both. Two studies published in 2004 suggested that older women with early breast cancer may be able to forego whole breast irradiation after lumpectomy. One study randomly assigned 636 women with node-negative, ER-positive breast cancer treated with lumpectomy to receive tamoxifen plus whole breast irradiation (n = 317) or tamoxifen alone (n = 319). At 5 years, the rate of local or regional recurrence was 1% in the group treated with radiation vs 4% in women given tamoxifen alone (P < .001). Although the rate of locoregional failure was slightly higher in women who did not have radiation, overall survival was the same in both treatment arms: 87% vs 86%, respectively. This study was recently updated. At 10 years, the rate of local or regional recurrence was 2% in the group treated with radiation vs 10% in women given tamoxifen alone (P < .015), but no differences in survival were observed between the 2 treatment groups.
This study suggested that it may be safe to withhold radiation therapy in older women with smaller tumors who are node-negative because this strategy has no negative impact on survival.
Medscape: You mentioned 2 important studies in older women. What was the second study and what did it show?
Dr. Whelan: The second study had a somewhat different population. It included approximately 150 women with ER-negative tumors. The study randomly assigned 769 women with early breast cancer (tumor diameter of ≤ 5 cm) to receive tamoxifen plus whole breast irradiation (n = 386) vs tamoxifen alone (n = 383). At 5 years, the relapse rate was 0.6% with tamoxifen plus radiation vs 7.7% with the tamoxifen alone (P < .001). Disease-free survival rates were 91% vs 84%, respectively (P = .004). A preplanned subgroup analysis of 611 women with node-negative, receptor-positive tumors indicated a significant benefit for radiation therapy; the 5-year rate of local relapse was 0.4% for tamoxifen plus radiation vs 5.9% for tamoxifen alone (P < .001). However, there was no significant difference between treatment arms in rates of distant relapse or overall survival.
Medscape: Both studies were conducted in 2004 using older radiation techniques. What are some of the newer strategies, and wouldn't those have an impact on the decision about whether to treat with radiation?
Dr. Whelan: We are now seeing increased use of hypofractionated radiation given over 3 weeks and accelerated partial breast irradiation given over 1 week.
Medscape: What happens in clinical practice? Do most physicians treat older women with ER-positive early breast cancer with radiation?
Dr. Whelan: That depends on the oncologist and patient preference. Some oncologists feel that with the newer techniques given over much shorter time periods, there is no reason to avoid radiation because it provides a benefit in preventing recurrence. Some women may opt for radiation because they don't want to have to have a subsequent mastectomy if they have a recurrence, although the study by Hughes and colleagues found that the rate of mastectomy for recurrence was not increased in the tamoxifen-alone group.
If you avoid radiation, the patient still has to take hormonal therapy for 5 years, but if you undergo radiation, then you may be able to forego hormonal therapy. Small tumors with no nodal involvement have a low rate of recurrence, so this is a decision that must be made by the oncologist and the patient.
Yea or Nay to Axillary Dissection?
Medscape: What about complete axillary dissection for older women with ER-positive breast cancer and minimal nodal involvement? Can these women be safely treated with sentinel node dissection alone?
Dr. Whelan: The ACOSOG Z0011 study, which tended to include older women, suggested that complete axillary dissection may not be necessary in selected patients with 1 or 2 positive sentinel lymph nodes.The study was conducted at 115 sites and had a targeted enrollment of 1900 patients, but accrual was slow. Results from 813 patients with clinical node-negative tumors and 1 or 2 positive sentinel lymph nodes have been published. All patients underwent lumpectomy and whole breast irradiation and were then randomly assigned to receive axillary lymph node dissection or no further axillary treatment. At a median follow-up of 6.3 years, 5-year overall survival was 91.8% for axillary lymph node dissection vs 92.5% with sentinel lymph node dissection alone; 5-year disease-free survival was 82.2% vs 83.9%, respectively.
Although this study showed that survival was not inferior using sentinel node dissection alone, this is still controversial because accrual was lower than expected. This strategy may be more useful in older women because younger women tend to have worse outcomes compared with older women.
Medscape: What are the take-home messages for our readers?
Dr. Whelan: Age alone should not be a barrier for standard therapy. Selected older patients with no serious comorbid conditions can be safely treated with standard therapy. Whole breast radiation may be withheld in selected older women with early-stage ER-positive breast cancer, provided they are prepared to accept a slightly higher recurrence rate and the caveat that newer techniques may make radiation more attractive for patients. It appears to be possible to eliminate axillary dissection in patients with 1 or 2 positive sentinel nodes without compromising survival.
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