Reviewers: John Han-Chih Chang, MD and Kenneth Blank, MD
Source: Journal of Clinical Oncology 1998; volume 16 (number 2): pages 441 - 452
With the use of screening studies such as mammograms and ultrasounds along with self breast exams, there has been a trend towards an increased incidence of finding breast cancers that are not invasive at the time of diagnosis (intraductal carcinoma or ductal carcinoma in situ - DCIS). These patients usually have a very good outcome. Standard of care in the past has been a mastectomy. In the recent decades, many have advocated a localized removal of the lump with a margin of normal breast tissue instead of mastectomy. This seemed to be fairly successful form of breast conservation surgery. The question remained as to whether adding radiation would increase the local control rates after breast conservation surgery and improve the outcome in such patients. The National Surgical Adjuvant Breast and Bowel Project (NSABP) B-17 trial attempted to address this very issue.
Eight hundred and eighteen women were enrolled from 1985 to 1990. This article updated the results through a mean follow-up of 8.5 years. Women were eligible if there was a "sufficient" amount of histologically normal tissue around the tumor with the lumpectomy. This was a subject of criticism, because there was not a specified amount that was considered "sufficient." The recurrence rate in lumpectomy alone patients could be correlated to an inadequate margin. Randomization was after lumpectomy was performed. Patients either received no further therapy or ipsilateral (lumpectomy side) radiation therapy to a dose of 5000 centi-Gray or rads. Four hundred and five patients received no further treatment, while 413 were scheduled to receive radiation post-operatively. In this report, 4 patients were lost to follow-up and were not included.
Nearly 85% of all patients in this trial had non-palpable disease and only 5% were clinically greater than 2 cm. In the pathological specimen, over 50% of the cases had no gross tumor (able to be visualized with the naked eye). Another one-third had gross tumors equal to or less than 1 cm. Ninety percent of all the patients in the trial had their mammograms reviewed centrally by the NSABP B-17 group. Tumor masses were only seen in 15% of the cases with 45% of those being less than 1 cm.
Event-free survival at 8 years was improved with radiation post-operatively over lumpectomy alone, 75% versus 62%, respectively (p = 0.00003). The percent incidence of ipsilateral breast tumor (treated same breast) as the site of first failure was higher with lumpectomy alone patients versus the lumpectomy and radiation therapy group. Of those that had an ipsilateral breast tumor after treatment, nearly 85% had recurrence in very close proximity of their prior lesion. The cumulative incidence of an ipsilateral DCIS recurrence in the radiation therapy arm at 8 years was 8.2% versus 13.4% for lumpectomy alone. The cumulative incidence of an ipsilateral invasive tumor recurrence was decreased from 13.4% to 4% with radiation added after lumpectomy for DCIS.
Most patients that recurred locally had either another lumpectomy or a mastectomy. Only 3 deaths were noted in those that recurred in the ipsilateral breast. A total of 9 lumpectomy and radiation therapy patients and 6 lumpectomy alone had distant failures as first or subsequent sites of recurrence. No significant difference were seen in distant failures, local regional failures (other than ipsilateral breast tumors), or contralateral breast tumors between the two arms of treatment. Contralateral breast tumors were seen in 3.3% in the lumpectomy alone arm, while found in nearly 6% of the lumpectomy plus radiation patients. Second primary tumors (exclusive of a contralateral breast tumor) were seen in approximately 3% in both groups.
Overall survival was excellent for both groups. Ninety-four percent overall survival at 8 years for the lumpectomy alone group, while the combined modality arm had a 95% 8 year overall survival.
As the 5 year follow-up data revealed in the 1993 New England Journal of Medicine article, this 8 year follow-up continues to tout the effectiveness of post-lumpectomy radiation therapy in the setting of local control for DCIS. There is no significant survival advantage as expected, since the salvage of local recurrences is successful in a majority of cases. These data are consistent with the extensive retrospective experience published by Solin L et al in a 1996 Journal of Clinical Oncology article. This was a 15 year follow-up on over 250 patients with DCIS treated with breast conservation surgery (lumpectomy) and post operative definitive radiation therapy. Less than 20% had a local failure with the time to local failure being 5 years. The 15 year cause-specific survival was 96%, while overall survival was 87% at 15 years.
Radiation boost after was not discussed in this article, but was noted to be done in approximately 9% of those patients. The nearly 85% local failure rate at the same location of the initial primary in those that had an ipsilateral breast tumor recurrence lends some credence in utilizing a boost to the tumor bed.
A significant criticism of this trial is that it failed to include an arm of patients that were to be treated with mastectomy alone, which is the standard of care at certain institutions and a good curative option. Survival and local control data from retrospective reviews on the subject demonstrate near equivalence between mastectomy alone and breast conservation surgery and radiation therapy, but a substantial randomized trial has not been done concerning that subject.
New avenues of pursuit in the war against DCIS are underway. One such study is the NSABP B-24 trial focusing on the issues of large DCIS and utility of adding Tamoxifen to lumpectomy and radiation therapy.
DCIS is a very curable entity. Despite the limited shortcomings, NSABP B-17 has demonstrated that lumpectomy with the addition of post-operative definitive radiation therapy is more efficacious than lumpectomy alone for local control. Overall, though, the patient's prognosis in overcoming this disease is greater than 90% - 95%.