2012 EDUCATIONAL BOOK - American Society of Clinical Oncology

east cancer incidence deserves further investigation and
may, ultimately, shed light on the biology of DCIS and
invasive breast cancer and the factors that control invasive
progression.
The use of breast MRI for patients with DCIS is not yet
established. MRI can influence treatment recommendations
for some patients by identifying occult disease not visualized
with mammography. Among patients with DCIS, three
studies found that the sensitivity of detecting multicentric
disease is higher with MRI compared with mammography.
11,12 Breast MRI can potentially influence treatment
decisions by providing more accurate information on the size
and extent of the known DCIS. Such findings may determine
the choice of breast-conserving surgery (BCS) compared
with mastectomy or the width of excision margins. Studies
have been mixed when comparing whether MRI overestimates
or underestimates tumor size relative to mammography.
The potential benefits of MRI include fewer re-excisions
after BCS and decreased local recurrence rates after excision.
However, no studies to date have reported that MRI
yields these improved patient outcomes. Breast MRI may
also have potential disadvantages such as increased patient
anxiety, costs, and unnecessary use of breast biopsy; for
example, one study of MRI for women with DCIS reported
that 47.6% of the biopsies stemming from a positive MRI
were negative. 13 If MRI leads to overestimation of the extent
and size of DCIS in some patients, it points to MRI use
resulting in more mastectomies and, for BCS, wider excisions
and their associated less favorable cosmetic outcomes.
SLNB is recommended for patients with invasive breast
cancer to determine prognosis and to guide adjuvant treatment
decisions. The risk of SLN metastasis is higher for
patients with a final diagnosis of DCIS with microinvasion
compared with pure DCIS (9.3% vs. 4.8%). 14 In addition,
approximately 15% of patients who are initially diagnosed
with DCIS on core needle biopsy have invasive breast cancer
identified in the excision or mastectomy specimen. 15 Thus,
some patients may require axillary lymph node staging
after definitive surgical treatment for presumed DCIS. Although
SLNB is feasible for most patients after excision,
it is not feasible after mastectomy. 16 Thus, some authors
recommend routine SLNB for women with high-risk DCIS
(palpable mass, comedo necrosis) and for those patients
undergoing mastectomy. 17
The 10-year breast cancer mortality rate from DCIS is less
46
KEY POINTS
● Most of the risk factors for DCIS and invasive breast
cancer are similar.
● Rates of DCIS have risen and are associated with
rising use of mammography.
● The value of breast MRI for women diagnosed with
DCIS is not clear.
● Sentinel lymph node biopsy is thought to be most
valuable for women with high-risk disease or undergoing
mastectomy.
● Treatment of DCIS includes surgery, radiation, and
endocrine therapy. Studies of the optimal treatment
are ongoing.
VIRNIG, WANG, AND TUTTLE
than 2%. 18 Therefore, the primary outcomes for DCIS are
ipsilateral and contralateral breast cancer recurrence. Many
of the prognostic factors are shared between DCIS and
invasive cancer. The local and recurrence rates for DCIS are
between 10% and 24% after 10 years. Younger age at
diagnosis is a consistent adverse prognostic factor. Women
older than 40 or 50 years consistently have reduced risk of
DCIS or invasive recurrence than younger women. This increased
risk may reflect the observation that DCIS in younger
women is more often symptomatic and more extensive.
Studies of racial differences in DCIS recurrence point to a
somewhat complex story. Studies of single treatments that
only adjust for demographic factors alone, 19,20 report that
black women with DCIS are more likely than white women
to die from breast cancer (response rate [RR] � 1.35) or
experience an invasive recurrence (RR � 1.4). However, the
studies that adjust for a more detailed set of tumor factors
find no difference between racial groups and risk of DCIS or
invasive recurrence (RR � 1.12). This suggests that there
may be differences in the tumor characteristics between
black and white women. There also may be systematic
differences in aggressiveness of DCIS treatment by race.
Positive surgical margins are consistently associated with
increased DCIS and invasive breast cancer recurrence, although
the magnitude of excess risk varies considerably. 21
There is considerable debate regarding whether width of a
negative margin (width of a margin negative for tumor cells)
is associated with a decreased risk of recurrence. In general,
larger tumors were associated with higher rates of local
DCIS and invasive recurrence than smaller tumors. 18,20
Although somewhat inconsistently labeled, a higher pathologic
or nuclear grade (grade 3) was consistently associated
with a higher probability of local DCIS or invasive recurrence
than an intermediate or low grade (grade 2 or 1).
Comedo necrosis, a factor unique to DCIS, is strongly and
consistently associated with poorer outcomes and increased
risk of DCIS or invasive recurrence. 20
Few of the important markers of tumor aggressiveness in
invasive breast cancer are well studied in DCIS. Rates of
estrogen receptor (ER) testing for women with DCIS are
rising but still lag behind testing for invasive cancer. However,
rates of ER positivity as a percentage of tumors tested
are similar for DCIS and invasive breast cancer with 81% to
85% positivity. ER positivity has been linked with a decreased
risk of recurrence in several small studies. DCIS
is rarely tested for HER2 positivity, but, nonetheless, several
small studies have linked it to increased risk of recurrence
(RR � 1.5–3.7) and reduced time to recurrence. 22 The
possibility of treating HER2-positive tumors is being studied
in ongoing trials. Ongoing research is also focusing on
developing genetic markers of DCIS that has more or less
favorable biology.
In randomized trials including NSABP-17 and the European
Organization for Research and Treatment of Cancer
(EORTC) randomized phase III trial 10853, whole-breast
radiation therapy (RT) following BCS was associated with
reduced local DCIS or invasive carcinoma recurrence. Although
statistically significant, the number of events prevented
per 1,000 treated women was less than 10%. Despite
the reduced recurrence, RT had no effect on either breast
cancer mortality or total mortality. 23-25 Neither randomized
nor observational studies pointed to compelling evidence
that BCS plus radiation has differing relative effectiveness