Transcript Slide 1

Evidence for adjuvant radiation therapy
benefiting breast cancer patients with 1 to 3
positive lymph nodes treated with a modified
radical mastectomy and systemic therapy
Shaheenah Dawood, Ana M. Gonzalez-Angulo, Wendy
Woodward, Funda Meric-Bernstam, Kelly Hunt, Aman U.
Buzdar,Gabriel N. Hortobagyi, Thomas A. Buchholz
The University of Texas M. D. Anderson Cancer Center
Departments of Breast Medical Oncology, Surgical Oncology and Radiation Oncology
Dubai Hospital, U.A.E, Department of Medical Oncology
Departments of Breast Medical Oncology, and Quantitative Sciences
(Abstract number :507
Disclosure
• I have no relevant relationships to disclose.
Postmastectomy Radiation
Oxford: Mastectomy +/- XRT Trials
Breast Recurrence
Breast Ca Deaths
LN - Disease
8% vs. 3%
28% vs. 31%
Breast Ca Survival
• none in LN• 5% for LN+
LN + Disease
29% vs. 8%
Local Recurrence
• 2/3 reduction
60%vs. 55%
• There is current consensus that postmastectomy
radiation therapy is indicated for patients whose
tumors are either > 5cm and/or >= 4 positive
lymph nodes.
• Whether adjuvant radiation therapy should be
used for patients with early stage breast cancer
with tumors < 5cm and up to 3 positive axillary
lymph nodes treated with mastectomy and
systemic therapy is controversial.
Aim
• Thus the purpose of this retrospective
study was to determine if adjuvant radiation
therapy had an impact on survival for
patients with early stage breast cancer with
up to 3 positive axillary lymph nodes
treated with surgery and systemic therapy
Methodology
Stage I and II
Breast Cancer
Mastectomy + no
Radiation
Segmental
Resection +
Radiation
Methodology
•
•
•
Database : M.D Anderson Breast Cancer Management Systems Database
Inclusion criteria :
• Female patients
• Diagnosed between 1980 and 2007
• Surgery
• T1/T2 N0 or T1/T2/N1
• Tumors <5 cm
• Nodes <4
Exclusion criteria :
• Male patients
• More than one primary
• Hormone receptor positive who did not receive hormone treatment
• Mastectomy and radiation therapy
• Segmental resection and no radiation
Outcome Measures
• Follow-up cut-off was 30th December 2008.
• Outcome measures:
– Local-Regional Disease Free Survival (LRDFS):
Calculated from the date of diagnosis to the
date of first locoregional metastases or last
follow-up.
– Distant Disease Free Survival (DDFS):
Calculated from the date of diagnosis to the
date of first distant metastases or last followup.
Statistical Analysis
• Kaplan-Meier method used to calculate outcome and
segmental resection with radiation patients were compared
to those with mastectomy without radiation using two-sided
log rank tests.
• Cox proportional hazards was used adjusting for
differences in patient and tumor characteristics between
the two groups.
Patient and Tumor Characteristics
Mastectomy
(No Radiation)
Segmental
(Radiation)
1585
(42.37%)
2155
(57.63%)
Range of year
Of diagnosis
2001
2003
Median Age
48
50
N
Subgroups
T1N0
T2N0
T1N2
T1N2
Median nodes
removed
434 (27.38%)
469 (29.59%)
383 (24.16%)
299 (18.86%)
757 (35.13%)
528 (24.50%)
493 (22.88%)
377 (17.49%)
13(1-58)
10(1-57)
P value
<.0001
Neoadjvuant
chemotherapy
No
Yes
Anthracycline
No
Yes
Taxane
No
Yes
Mastectomy
(No Radiation)
Segmental
(Radiation)
P value
1239 (78.17%)
346 (21.83%)
1627 (75.5%)
528 (24.5%)
0.0564
141 (9.02%)
1423 (90.98%)
155 (7.29%)
1972 (92.71%)
0.0561
716 (45.78%)
848 (54.22%)
919 (43.21%)
1208 (56.79%)
0.1198
Results
Number
Total no. analyzed
3740
Deaths
767 (18.1%)
Median follow-up
54 months (1- 312 months)
Median OS
161 months
(95% CI 144-180 months)
5-year DDFS
78%
(95% CI 76%-79%)
5-year LRDFS
88%
(95% CI 87%-90%)
Multivariate Analysis of LRDFS
LRDFS
Whole Cohort
Mastectomy vs. Segmental
HR
Lower
95% CI
Upper
95% CI
P-Value
1.26
0.95
1.68
0.11
Models adjusted for age, grade, hormone receptor status, HER2 status,
menopausal status, race, neoadjuvant chemo, anthracycline use, taxane use,
and lymphovascular invasion
LRDFS Among LN Negative Groups
T1N0 (N=1191)
T2N0 (N=997)
5- Year Estimates
Segmental : 92%
Mastectomy: 91%
P=0.93
5- Year Estimates
Segmental : 91%
Mastectomy: 89%
P=0.99
LRDFS Among LN Positive Groups
T1N1 (N=876)
5- Year Estimates
Segmental : 91%
Mastectomy: 90%
P=0.65
T1N2 (N=676)
5- Year Estimates
Segmental : 91%
Mastectomy: 87%
P=0.009
Adjusted Hazard Ratios for LRDFS among
various subgroups
Favors Mastectomy
Forrest Plot For Sub-Groups
Favors Segmental
Whole Cohort
T1N0
T1N0
T2N0
T1N1
T2N1
T2N0
T1N1
HR = 3.0 , 95% CI 1.58-5.71, P =0.0008
T2N1
No Neoadjuvant group (HR = 2.62 , 95% CI 1.26-5.46, P =0.00099
0
1
2
3
Hazard Ratios LDFS
4
5
6
Multivariate Analysis for DDFS
DDFS
Whole Cohort
Mastectomy vs. Segmental
HR
Lower
95% CI
Upper
95% CI
P-Value
1.38
1.13
1.70
0.0018
Models adjusted for age, grade, hormone receptor status, HER2 status,
menopausal status, race, neoadjuvant chemo, anthracycline use, taxane use,
and lymphovascular invasion
DDFS Among LN Negative Groups
T1N0 (N=1191)
5- Year Estimates
Segmental : 87%
Mastectomy: 86%
P=0.11
T2N0 (N=997)
5- Year Estimates
Segmental : 85%
Mastectomy: 80%
P=0.38
DDFS Among LN Positive Groups
T1N1(N=876)
5- Year Estimates
Segmental : 90%
Mastectomy: 85%
P=0.004
T2N1(N=676)
5- Year Estimates
Segmental : 77%
Mastectomy: 68%
P=0.0177
Adjusted Hazard Ratios for DDFS among
various subgroups
Forest Plot For Subgroups
Favors Mastectomy
Favors Segmental
Whole Cohort
T1N0
T2N0
T1N1
HR = 1.71 , 95% CI 1.15-2.52, P =0.007
T2N1
No Neoadjuvant group (HR = 1.54, 95% CI 0.98-2.23, P =0.061)
0
0.5
1
1.5
2
Hazard Ratio (DDFS)
2.5
3
Conclusions
• Patients with tumors <5 cm and 1 to 3 positive lymph have
an increase risk of loco-regional and distant disease
recurrence when radiation is not used as a component of
their local-regional treatment.
• The benefit of radiation appears to be most pronounced for
patients with T2N1 disease with the benefit still unclear for
those with T1N1 disease.
Limitations
• We acknowledge the following limitations:
– Retrospective nature of the study
– Comparing women who underwent segmental resection with
radiation to a comparable cohort who underwent mastectomy to
assess the benefit of post mastectomy radiation may not be ideal.
• However the results of our study are hypothesis generating and will
need to be confirmed in prospective randomized clinical trials.
Acknowledgement
Mentors
Dr. Thomas A. Buchholz
Dr. Ana M. Gonzalez-Angulo
Dr. Mona Al Rhukhaimi
Dr. Farid Khalifa
Thank You