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Lumpectomy With and Without Radiation for Early-Stage Breast Cancer and DCIS

Lumpectomy With and Without Radiation for Early-Stage Breast Cancer and DCIS

ABSTRACT: Breast-conserving therapy with lumpectomy and breast irradiation is an accepted standard treatment for patients with early-stage invasive breast cancer or ductal carcinoma in situ (DCIS). For both diseases, investigators have tried to identify subgroups of patients who can be "safely" treated with lumpectomy without radiation. Some data suggest that it may be reasonable to omit radiation therapy in patients with small, low-grade invasive or noninvasive tumors and/or in "elderly" patients. Additional studies are needed to better identify criteria to prospectively select appropriate patients for treatment with lumpectomy alone. [ONCOLOGY 11(9):1361-1374, 1997]

Introduction

Breast-conservation therapy with lumpectomy and breast irradiation is
a widely accepted, pre
ferred[1] treatment option for both patients with early-stage invasive
breast cancer and those with ductal carcinoma in situ (DCIS). Numerous
randomized trials demonstrate that, in women with invasive cancer, such
breast-conserving therapy provides survival outcomes equivalent to those
achievable with masectomy.[2-6] The same appears to be true for DCIS,[7-9]
although no randomized comparative data are available. Due to the cost,
inconvenience, and potential toxicity of breast irradiation, there is continued
interest in identifying subsets of patients who may be "adequately"
treated with lumpectomy alone. This article reviews the results of clinical
studies assessing lumpectomy without radiation therapy for early-stage
invasive cancer and DCIS. The studies reviewed have varying follow-up periods.
Thus, to facilitate comparisons between the studies, the annual
breast failure rate will be the primary outcome reported. If not reported
in the study, the annual failure rate was estimated by dividing the overall
failure rate by the average duration of follow-up.

Ductal Carcinoma In Situ

Randomized Data

One randomized study comparing lumpectomy alone to lumpectomy plus radiation
therapy—the National Surgical Adjuvant Project for Breast Cancer (NSABP)
B-17 trial[10-12]—has been published (Table
1
). Overall, in this trial, the addition of radiation reduced the annual
breast failure rate from approximately 5% to 2%.

In a retrospective subset analysis, the addition of radiation decreased
the annual breast recurrence rate in all subgroups, regardless of margin
status and the presence or absence of moderate/marked comedo necrosis.
In the subgroup of patients with the most favorable risk profile, ie, those
with clear margins and absent/minimal comedo necrosis, the absolute reduction
in the annual breast failure rate was less than 1%. In the "highest-risk"
group, ie, those with positive margins and prominent necrosis, the addition
of radiation reduced the absolute annual breast failure rate by 7% (from
10% to 3%).[11]

Additional randomized data are available from NSABP B-06.[7,8] This
study was intended to include only patients with invasive cancer. However,
on histologic review, a small subset of patients were judged to have DCIS.
In NSABP B-06, as in the larger NSABP B-17 study, the addition of radiation
reduced the breast failure rate from approximately 6% to 1%.

Following breast-conserving therapy for DCIS, recurrent lesions may
be either invasive or noninvasive. In the NSABP B-17 trial, the addition
of breast irradiation reduced the fraction of recurrences that were
invasive. Among the group treated with local incision alone, 50% of the
recurrences were invasive, whereas in the irradiated group, only 29% of
the recurrences were invasive. Thus, the addition of radiation reduced
both the incidence of a breast recurrence and the fraction of recurrences
that were invasive.

Looking at the data another way, the annual rate of an invasive
breast cancer recurrence was reduced from approximately 2.6% to 0.6% (a
76% relative risk reduction [P < .001]). Since patients with
DCIS who develop an invasive recurrence are likely to be at a higher risk
of death from distant metastases than those who have a recurrence of DCIS,
this is an interesting observation.

No differences in overall survival were reported in the NSABP B-17 trial.

Nonrandomized Data

The data from multiple nonrandomized series using lumpectomy without
radiation therapy are summarized in Table
2
.[13-26] The annual breast failure rate ranges from 2% to 6%, with
a weighted mean of ~4%.

In the first six studies listed in Table
2
, most or all of the patients had small mammographically detected
lesions and negative resection margins. In this subgroup of studies, the
breast failure rate ranged from 2% to 4.6%, with a weighted mean of 3.2%.
In all of these studies, the observed annual breast failure rate exceeds
that generally reported following lumpectomy plus radiation therapy.[9,10]

Prognostic Factors—In several of the studies listed in Table
2
, various prognostic factors were identified that are related to the
breast failure rate. Although the particular factors identified in the
individual studies vary, alow-grade, noncomedo subtype appears to have
the most favorable prognosis (Table 3).[14-20,
25, 26] The annual breast recurrence rate among patients with these "favorable"
factors ranged from 0% to 3.8%.

Dr. Silverstein and colleagues at the Breast Center in Van Nuys, California,
recently described a prognostic index based on tumor size, margin width,
and histologic appearance.[20] In their retrospective analysis, patients with the most favorable prognosis,
ie, those with the lowest index score (small tumor, wide excision margin,
and less aggressive pathology), appeared to have a very low breast recurrence
rate following lumpectomy without radiation therapy. These patients did
not benefit from breast irradiation.

In contrast, patients with a moderate index score (5 to 7) had a higher
relapse rate following lumpectomy alone and did derive benefit from breast
irradiation. Patients with the least favorable tumors (index score 8 or
9) also derived a modest benefit from radiation therapy, although the breast
relapse rate in these patients was unacceptably high with or without radiation.[20]
These results conflict with those of the randomized NSABP B-17 trial.[11]
The number of patients in these nonrandomized reports is small. Also, duration
of follow-up in both the randomized and nonrandomized studies is short.
Additional follow-up data from all of these studies will be interesting.

Invasive Cancer

Randomized Data

The data from five randomized studies comparing outcomes after lumpectomy
alone to those after lumpectomy plus radiation therapy are summarized in
Table 4.[2-5,27-33] Only patients with
negative resection margins and relatively small (£2
to 4 cm) tumors were included in these studies. In each study, the addition
of radiation reduced the annual breast recurrence rate from approximately
5% to 1%. No survival differences were reported (discussed below).

Nonrandomized Data

Table 5 outlines the results from
several nonrandomized series in which radiation therapy was omitted following
lumpectomy.[29, 30, 34-42] It is likely that patients in these series were
selected for treatment without irradiation because they were perceived
to have more "favorable" characteristics (eg, most of the studies
included only patients with small tumors). Despite this, the observed annual
breast failure rate was generally greater than the 1% typically seen with
lumpectomy plus radiation therapy.

The study by Schnitt et al represents the "cleanest" group
of women prospectively selected for lumpectomy without irradiation.[35]
This study enrolled 86 patients with a solitary T1 infiltrating cancer,
without lymphatic vascular invasion or an extensive intraductal component,
who had microscopically negative margins by at least 1 cm (all but two
of the patients had negative reexcisions). All 87 patients had pathologically
negative axillary nodes. Approximately 75% of the lesions were detected
mammographically, and the median age of the patients was 67 years (range,
27 to 84 years).

With a median follow-up of 56 months, the annual breast failure
rate was 3.6%. This is a remarkably high breast recurrence rate, in light
of the favorable nature of the tumors treated.

In a subset analysis, no recurrences were seen in 42 of the patients
with the "most favorable" histologic findings (26 grade 1 infiltrating,
9 mucinous, and 7 tubular tumors). It is difficult to know how to interpret
this type of retrospective identification of a most-favorable subgroup,
since all of the enrolled patients were initially considered to have a
favorable prognosis. Indeed, if all 14 recurrences are assigned to the
remaining 45 "less-favorable" patients, the annual recurrence
rate in this group is 6.6%.

Results in Elderly Patients—Some investigators have selected
women for treatment without irradiation based on their age. Table
6
outlines the results reported in "elderly" women treated
with lumpectomy without radiation therapy.[41-49] As there is no uniform
definition of "elderly" in these studies, the range of patient
age is included.

The lowest failure rates (0% to 2.75%) were noted in the study populations
of Nemoto et al and von Rueden et al, in whom margins were usually negative
and tumor sizes were less than 2 to 5 cm.[42,43] However, the studies by
Lee et al and Reed and Morrison reported an ~5% annual failure rate in
similarly selected patients.[47,49] Higher recurrence rates were generally
reported in series that did not specify margin status.[46] The average
follow-up in most of these studies was short (less than 4 years), and the
patient numbers were small.

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