March 23, 2011 — Long-term results from 2 large trials of ductal carcinoma in situ (DCIS) have shown that these women have an excellent prognosis and are more likely to die from other causes than from breast cancer.
Overall, the 15-year overall survival exceeded 85% and the incidence of death from breast cancer was less than 5%.
The results also show that combination treatment with lumpectomy followed by radiation and tamoxifen is the most effective approach for reducing the risk for invasive breast cancer.
This triple therapy approach halved the risk, compared with lumpectomy alone; lumpectomy plus radiation was also significantly better than lumpectomy alone.
These results, published in the March 16 issue of the Journal of the National Cancer Institute, come from a long-term follow-up of women involved in 2 large trials, both conducted by the National Surgical Adjuvant Breast and Bowel Project.
The B-24 trial followed 1799 women for a median of 207 months; the B-17 trial followed 813 women for a median of 163 months.
"These are landmark trials with mature data," said lead author Irene Wapnir, MD, chief of breast surgery at Stanford Cancer Center, California.
"Now we can see the natural history of this disease in a large patient population over a period of up to 2 decades," she noted in a statement.
DCIS Incidence Increasing Dramatically
"It is increasingly important to advance our understanding of the biological behavior of this disease" Dr. Wapnir and colleagues write, because the incidence of DCIS has risen dramatically over the past 2 decades, and it might be continuing to rise.
The increase in prevalence is largely the result of the increased use of mammographic screening, they explain, noting that DCIS now accounts for about 25% of all new diagnoses of breast cancer.
Risk for Invasive Breast Cancer
These 2 studies, the largest to date investigating women with DCIS, show that the most common first failure event is an ipsilateral breast tumor recurrence (IBTR). The most worrying of these is an invasive IBTR, which carries an increased mortality risk; a recurrence of DCIS does not.
The long-term results show that over the course of 15 years, there were 490 IBTR events, 263 (53.7%) of which were invasive.
Combination treatment with lumpectomy plus radiation plus tamoxifen (triple therapy) halved the risk of developing invasive breast cancer (hazard ratio [HR], 0.48; P < .001). Over the 15 years of follow-up, invasive IBTR occurred in 19.4% of women treated with lumpectomy and in 8.5% of women treated with triple therapy — a 52% reduction in risk.
Results on women who were treated with lumpectomy plus radiation but no tamoxifen come from slightly different groups in the 2 trials.
In the B-17 trial, invasive IBTR occurred in 8.9% of women treated with lumpectomy plus radiation, which is similar to the 8.5% seen in women treated with triple therapy.
However, in the larger of the 2 trials — B-24 — there was a significant difference. In that trial, invasive IBTR occurred in 10% of women treated with lumpectomy and radiation plus placebo, and in 8.5% of those treated with triple therapy (HR, 0.68; P = .0025). These results show the benefit of adding tamoxifen to the combination treatment, say the researchers.
Invasive Cancer Alters the Prognosis
Developing invasive breast cancer alters the subsequent prognosis, the researchers note. The mortality risk increased approximately 2-fold in women who developed invasive IBTR, compared with those who did not.
Developing invasive IBTR is the dominant, but not the sole, pathway by which a breast-cancer-related death occurs in women with DCIS, they add.
The exact incidence of breast cancer death varied with the treatment received; the 15-year cumulative incidence of breast cancer death was 3.1% for those treated with lumpectomy alone, and 2.3% for those treated with triple therapy.
For treatment with lumpectomy and radiation, the equivalent figures were 4.7% for those in the B-17 trial (lumpectomy and radiation) and 2.7% for those in the in the B-24 trial (lumpectomy, radiation, and placebo).
"We speculate that an invasive IBTR after radiation therapy may be biologically more aggressive, and that many of the invasive IBTRs in the lumpectomy-alone group are biologically indolent," the researchers note.
Concerns Over Overtreatment
There has been concern within the oncology community about the overtreatment of DCIS; there have even been suggestions that it should not be treated automatically, but followed with an active surveillance approach. There have also been proposals that radiation be omitted in cases where the initial DCIS lesion is small or low grade.
Dr. Wapnir herself acknowledged "that critics will point out that the majority of women who were treated with lumpectomy alone didn't have a recurrence."
However, she noted that these 2 trials show a significant benefit from adding radiation to lumpectomy, and that most of the DCIS lesions were small — the great majority were 1 cm or less.
Tumor size was not a significant prognostic factor, nor was it an indicator of which patients could forego radiotherapy.
"We were not able to identify a group that did not benefit from either radiation or radiation plus tamoxifen," Dr. Wapnir commented in a statement.
"I tell my patients when discussing treatment options that I don't know how to identify which patients will be in that category," she said.
Guiding Clinical Management
Elaborating to Medscape Medical News, Dr. Wapnir said: "We certainly hope that our results, and the hard work of hundreds of investigators and thousands of patients, will be viewed as medical evidence on which to guide the clinical management of patients."
Currently in the United States and Canada, about 60% of women with DCIS have a lumpectomy, the researchers write in their paper.
"We believe that these data support the continued safety and use of breast conservation, as only 0.84% of patients died as a result of invasive breast recurrence," Dr. Wapnir said.
When asked about the proposal to skip radiation after lumpectomy, Dr. Wapnir pointed out that in these trials, "65% of patients in the lumpectomy-alone arm did not have a recurrence in the ipsilateral breast," so if the patient wants to risk those odds, it is an option.
"But one would need to factor in age, as a younger patient has about double the risk of recurrence as a 65-year-old woman," she said. "In addition, there are other events, such as contralateral breast cancer, in which tamoxifen use is associated with fewer breast-cancer-related events."
Dr. Wapnir emphasized, however, that the results show that adding radiation and tamoxifen treatment to lumpectomy halved the number of recurrences, compared with lumpectomy alone.
What about the proposal to follow DCIS with active surveillance, because many of these lesions do not develop into invasive breast cancer?
These 2 studies were "not powered to answer the question you are asking," Dr. Wapnir told Medscape Medical News. "We simply don't have the molecular tools to state with any reliability which DCIS patients have nearly zero risk of developing invasive breast cancer."
There are other studies that might shed some light on the nonintervention perspective, she noted. Among them is the prospective nonrandomized ECOG 5194 trial, in which 7-year local recurrence rates after lumpectomy with radiation were 10% for low-grade DCIS and 18% for high-grade DCIS.
The authors have disclosed no relevant financial relationships.
J Natl Cancer Inst. 2011;103:478-488. Abstract
Overall, the 15-year overall survival exceeded 85% and the incidence of death from breast cancer was less than 5%.
The results also show that combination treatment with lumpectomy followed by radiation and tamoxifen is the most effective approach for reducing the risk for invasive breast cancer.
This triple therapy approach halved the risk, compared with lumpectomy alone; lumpectomy plus radiation was also significantly better than lumpectomy alone.
These results, published in the March 16 issue of the Journal of the National Cancer Institute, come from a long-term follow-up of women involved in 2 large trials, both conducted by the National Surgical Adjuvant Breast and Bowel Project.
The B-24 trial followed 1799 women for a median of 207 months; the B-17 trial followed 813 women for a median of 163 months.
"These are landmark trials with mature data," said lead author Irene Wapnir, MD, chief of breast surgery at Stanford Cancer Center, California.
"Now we can see the natural history of this disease in a large patient population over a period of up to 2 decades," she noted in a statement.
DCIS Incidence Increasing Dramatically
"It is increasingly important to advance our understanding of the biological behavior of this disease" Dr. Wapnir and colleagues write, because the incidence of DCIS has risen dramatically over the past 2 decades, and it might be continuing to rise.
The increase in prevalence is largely the result of the increased use of mammographic screening, they explain, noting that DCIS now accounts for about 25% of all new diagnoses of breast cancer.
Risk for Invasive Breast Cancer
These 2 studies, the largest to date investigating women with DCIS, show that the most common first failure event is an ipsilateral breast tumor recurrence (IBTR). The most worrying of these is an invasive IBTR, which carries an increased mortality risk; a recurrence of DCIS does not.
The long-term results show that over the course of 15 years, there were 490 IBTR events, 263 (53.7%) of which were invasive.
Combination treatment with lumpectomy plus radiation plus tamoxifen (triple therapy) halved the risk of developing invasive breast cancer (hazard ratio [HR], 0.48; P < .001). Over the 15 years of follow-up, invasive IBTR occurred in 19.4% of women treated with lumpectomy and in 8.5% of women treated with triple therapy — a 52% reduction in risk.
Results on women who were treated with lumpectomy plus radiation but no tamoxifen come from slightly different groups in the 2 trials.
In the B-17 trial, invasive IBTR occurred in 8.9% of women treated with lumpectomy plus radiation, which is similar to the 8.5% seen in women treated with triple therapy.
However, in the larger of the 2 trials — B-24 — there was a significant difference. In that trial, invasive IBTR occurred in 10% of women treated with lumpectomy and radiation plus placebo, and in 8.5% of those treated with triple therapy (HR, 0.68; P = .0025). These results show the benefit of adding tamoxifen to the combination treatment, say the researchers.
Invasive Cancer Alters the Prognosis
Developing invasive breast cancer alters the subsequent prognosis, the researchers note. The mortality risk increased approximately 2-fold in women who developed invasive IBTR, compared with those who did not.
Developing invasive IBTR is the dominant, but not the sole, pathway by which a breast-cancer-related death occurs in women with DCIS, they add.
The exact incidence of breast cancer death varied with the treatment received; the 15-year cumulative incidence of breast cancer death was 3.1% for those treated with lumpectomy alone, and 2.3% for those treated with triple therapy.
For treatment with lumpectomy and radiation, the equivalent figures were 4.7% for those in the B-17 trial (lumpectomy and radiation) and 2.7% for those in the in the B-24 trial (lumpectomy, radiation, and placebo).
"We speculate that an invasive IBTR after radiation therapy may be biologically more aggressive, and that many of the invasive IBTRs in the lumpectomy-alone group are biologically indolent," the researchers note.
Concerns Over Overtreatment
There has been concern within the oncology community about the overtreatment of DCIS; there have even been suggestions that it should not be treated automatically, but followed with an active surveillance approach. There have also been proposals that radiation be omitted in cases where the initial DCIS lesion is small or low grade.
Dr. Wapnir herself acknowledged "that critics will point out that the majority of women who were treated with lumpectomy alone didn't have a recurrence."
However, she noted that these 2 trials show a significant benefit from adding radiation to lumpectomy, and that most of the DCIS lesions were small — the great majority were 1 cm or less.
Tumor size was not a significant prognostic factor, nor was it an indicator of which patients could forego radiotherapy.
"We were not able to identify a group that did not benefit from either radiation or radiation plus tamoxifen," Dr. Wapnir commented in a statement.
"I tell my patients when discussing treatment options that I don't know how to identify which patients will be in that category," she said.
Guiding Clinical Management
Elaborating to Medscape Medical News, Dr. Wapnir said: "We certainly hope that our results, and the hard work of hundreds of investigators and thousands of patients, will be viewed as medical evidence on which to guide the clinical management of patients."
Currently in the United States and Canada, about 60% of women with DCIS have a lumpectomy, the researchers write in their paper.
"We believe that these data support the continued safety and use of breast conservation, as only 0.84% of patients died as a result of invasive breast recurrence," Dr. Wapnir said.
When asked about the proposal to skip radiation after lumpectomy, Dr. Wapnir pointed out that in these trials, "65% of patients in the lumpectomy-alone arm did not have a recurrence in the ipsilateral breast," so if the patient wants to risk those odds, it is an option.
"But one would need to factor in age, as a younger patient has about double the risk of recurrence as a 65-year-old woman," she said. "In addition, there are other events, such as contralateral breast cancer, in which tamoxifen use is associated with fewer breast-cancer-related events."
Dr. Wapnir emphasized, however, that the results show that adding radiation and tamoxifen treatment to lumpectomy halved the number of recurrences, compared with lumpectomy alone.
What about the proposal to follow DCIS with active surveillance, because many of these lesions do not develop into invasive breast cancer?
These 2 studies were "not powered to answer the question you are asking," Dr. Wapnir told Medscape Medical News. "We simply don't have the molecular tools to state with any reliability which DCIS patients have nearly zero risk of developing invasive breast cancer."
There are other studies that might shed some light on the nonintervention perspective, she noted. Among them is the prospective nonrandomized ECOG 5194 trial, in which 7-year local recurrence rates after lumpectomy with radiation were 10% for low-grade DCIS and 18% for high-grade DCIS.
The authors have disclosed no relevant financial relationships.
J Natl Cancer Inst. 2011;103:478-488. Abstract
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