NEW ORLEANSIn women treated with a breast-conserving approach
for early-stage invasive breast cancer, adequate excision
of the primary tumor is necessary to obtain optimal local tumor
control. But what constitutes an adequate excision prior to radiation
therapy, and what are the risk factors for local recurrence? A
Harvard pathologist discussed this issue at the American Society of
Breast Disease annual meeting.
Surgical procedures less than a gross excision result in unacceptably
high local recurrence rates. However, the optimal extent of surgery
needed beyond a complete gross excision has not been established.
Ideally, the surgical procedure should be large enough to
ensure good local control but not so large that it compromises the
cosmetic result, said James L. Connolly, MD, director of
anatomic pathology, Beth Israel Deaconess Medical Center, and
associate professor of pathology, Harvard Medical School.
The established risk factors for local recurrence include an
incomplete excision and diffuse, malignant microcalci-fications on
mammography. Other relevant factors include patient age under 35;
treatment factors such as extent of surgery, radiotherapy protocol,
and addition of chemotherapy; and various tumor-related factors.
Presence of EIC
Many studies have investigated the relationship between the presence
of an extensive intraductal component (EIC) and the risk of local
recurrence after conservation. Despite differences in design,
these studies have generally shown that invasive tumors with an EIC
are associated with a significantly higher risk of local recurrence
than tumors lacking an EIC, at least when information regarding the
status of the microscopic margins is not available, Dr.
At Harvard, tumors with an EIC are defined as infiltrating ductal
carcinomas that show the simultaneous presence of prominent ductal
carcinoma in situ (DCIS) within the tumor (25% or more of tumor area
and any DCIS adjacent to the tumor). This includes tumors that are
predominantly DCIS with one or more microscopic foci of stromal
invasion. Tumors lacking one or more of these features are
categorized as EIC negative.
Harvard investigators have reported that EIC-positive tumors carry a
24% risk for local recurrence, compared with a 6% risk in
EIC-negative tumors when margins were not evaluated. The vast
majority of patients without EIC have low recurrence rates, Dr.
The Joint Center for Radiation Therapy, Boston, found that the
likelihood of residual cancer was significantly higher in EIC-positive
than in EIC-negative cancers, 88% vs 48% (P = .002). Moreover, in
EIC-positive patients, most residual tumors were composed mostly of
DCIS and were often widespread.
In EIC-negative patients, residual tumor typically consisted of only
scattered microscopic foci of infiltrating cancer and/or DCIS. Other
studies have made similar findings, he said, although the NSABP B-06
trial, which excluded patients with involved margins, found no
Dr. Connolly and his colleagues conducted a study in a mastectomy
database to determine the relationship between EIC and the findings
in the remainder of the breast. They found that 60% of EIC-positive
tumors had residual tumor, compared with 30% of EIC-negative tumors.
They also looked at the amount of prominent (about 3.6
cm) residual tumor and concluded that the vast majority of EIC-negative
tumors were adequately treated with radiotherapy, but about 30% of
EIC-positive cases contained too much residual tumor to treat in this
manner. If you adequately excise these lesions, you can still
treat them conservatively, he said. But some patients
with EIC-positive tumors have too much breast involved for a good
cosmetic result, and need a mastectomy.
In EIC-positive tumors, the associated intraductal involvement is
often more extensive than can be appreciated clinically or at the
time of surgery, Dr. Connolly said. Therefore, EIC-positive patients
who undergo a limited resection of the clinically evident tumor
frequently have considerable residual DCIS in the vicinity of the
tumor site. EIC-negative patients, however, do not have high
recurrence rates, so doing a large excision is a disservice to
them, he commented.
Recent studies from Harvard and Stanford indicate that the presence
of an EIC is not an independent predictor of local recurrence when
the microscopic margin status is taken into consideration. Therefore,
he added, EIC has evolved into more of a patient selection factor
than a prognostic factor for local recurrence, helping to determine
the extent of the surgical excision prior to radiotherapy.
Perhaps the most important information from the pathologic exam is
the status of the microscopic margins; however, margin status is
always subject to sampling error. At our institution, we
consider a margin positive when cancer cells (either invasive cancer
or DCIS) abut the inked surface. If the tumor is not present at the
inked surface, we report the smallest distance between the edge of
the tumor and the inked tissue edge. This is done for both the
invasive component and the associated DCIS, he said.
Very wide excisions are probably not necessary in patients with
negative margins, since they have a much lower recurrence rate. Dr.
Connollys most recent follow-up showed that local recurrence
was only 7% in patients with negative margins or close margins.
The risk for recurrence in patients with
greater-than-focally-positive margins appears to be three times
higher than in patients with focally positive margins. When
greater-than-focally-positive margins is combined with EIC status,
the risk is 19% in EIC-negative patients and 42% in EIC-positive patients.
Dr. Connolly added that the presence of margin involvement is not
necessarily a contraindication to conservative surgery and radiation
therapy. In many patients, negative margins can be obtained after
re-excision. If prominent margin involvement persists in the
re-excision specimen, however, mastectomy may be the most prudent
approach, he said.
You should consider the location of the positive margins. If
either the superficial margin or the deep margin abutting the
pectoral fascia is involved, additional surgery is not necessary,
since most of the breast tissue has been removed.
Additional factors that may affect local recurrence include lymphatic
invasion, which is a factor in both EIC-negative and EIC-positive
patients. Infiltrating lobular histology does not carry increased
risk, and lobular carcinoma in situ appears not to be a risk factor
for recurrence after breast conservation. Age less than 35 is also
associated with an increased risk of local recurrence as well as