Patients with early stage invasive cancer with close or positive margins treated with conservative surgery and radiation have an increased risk of breast recurrence that is delayed by adjuvant systemic therapy
G. Freedman et al., Patients with early stage invasive cancer with close or positive margins treated with conservative surgery and radiation have an increased risk of breast recurrence that is delayed by adjuvant systemic therapy, INT J RAD O, 44(5), 1999, pp. 1005-1015
Citations number
54
Categorie Soggetti
Radiology ,Nuclear Medicine & Imaging","Onconogenesis & Cancer Research
Journal title
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
Purpose: The association between a positive resection margin and the risk o
f ipsilateral breast tumor recurrence (IBTR) after conservative surgery and
radiation is controversial. The width of the resection margin that minimiz
es the risk of IBTR is unknown. While adjuvant systemic therapy mag decreas
e the risk of an IBTR in all patients, its impact on patients with positive
or close margins is largely unknown. This study examines the interaction b
etween margin status, margin width, and adjuvant systemic therapy on the 5-
and 10-year risk of IBTR after conservative surgery and radiation.
Methods and Materials: A series of 1,262 patients with clinical Stage I or
II breast cancer were treated by breast-conserving surgery, axillary node d
issection, and radiation between March 1979 and December 1992. The median f
ollow-up was 6.3 years (range 0.1-15.6). The median age was 55 years (range
24-89). Clinical size was T1 in 66% and T2 in 34%. Seventy-three percent o
f patients were node-negative. Only 5% of patients had tumors that were EIC
-positive. Forty-one percent had a single excision, and 59% had a reexcisio
n. The final margins were negative in 77%, positive in 12%, and close (less
than or equal to 2 mm) in 11%. The median total dose to the tumor bed was
60 Gy with negative margins, 64 Gy with close margins, and 66 Gy with posit
ive margins. Chemotherapy +/- tamoxifen was used in 28%, tamoxifen alone in
20%, and no adjuvant systemic therapy in 52%.
Results: The 5-year cumulative incidence (CI) of IBTR was not significantly
different between patients with negative (4%), positive (5%), or close (7%
) margins. However, by 10 years, a significant difference in IBTR became ap
parent (negative 7%, positive 12%, close 14%,p = 0.04). There was no signif
icant difference in IBTR when a close or positive margin was involved by in
vasive tumor or DCIS. Reexcision diminished the IBTR rate to 7% at 10 years
if the final margin was negative; however, the highest risk was observed i
n patients with persistently positive (13%) or close (21%) (p = 0.02) margi
ns. The median interval to failure was 3.7 years after no adjuvant systemic
therapy, 5.0 years after chemotherapy +/- tamoxifen, and 6.7 gears after t
amoxifen alone. This delay to IBTR was observed in patients with close or p
ositive margins, with little impact on the time to failure in patients with
negative margins. The 5-year CI of IBTR in patients with close or positive
margins was 1% with adjuvant systemic therapy and 13% with no adjuvant the
rapy. However, by 10 years, the CI of IBTR was similar (18% vs. 14%) due to
more late failures in the patients who received adjuvant systemic therapy.
Conclusion: A negative margin (> 2 mm) identifies patients with a very low
risk of IBTR (7% at 10 Sears) after conservative surgery and radiation. Pat
ients with a close margin (less than or equal to 2 mm) are at an equal or g
reater risk of IBTR as with a positive margin, especially following a reexc
ision. A margin involved by DCIS or invasive tumor has the same increased r
isk of IBTR. A reexcision of an initially close or positive margin that res
ults in a negative final margin reduces the risk of IBTR to that of an init
ially negative margin. A close or positive margin is associated with an inc
reased risk of IBTR even in patients who are EIC-negative or receiving high
er boost doses of radiation. The median time to IBTR is delayed; however, t
he CI is not significantly decreased by adjuvant systemic therapy in patien
ts with close or positive margins-the 5 year results in these patients unde
restimate their ultimate risk of recurrence. (C) 1999 Elsevier Science Inc.