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

2. Disclosure
I have no relevant relationships to disclose.

3. Postmastectomy Radiation Oxford: Mastectomy +/- XRT Trials
Breast Recurrence Breast Ca Deaths
LN - Disease
Local Recurrence
2/3 reduction
Breast Ca Survival
none in LN-
5% for LN+
8% vs. 3%
28% vs. 31%
LN + Disease
29% vs. 8%
60%vs. 55%

4. 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.

5. 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

6. Methodology Stage I and II Breast Cancer
Mastectomy + no Radiation
Segmental Resection + Radiation

7. 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

8. Outcome Measures Follow-up cut-off was 30th December 2008.
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 follow-up.

9. 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.

10. Patient and Tumor Characteristics
Mastectomy
(No Radiation)
Segmental
(Radiation)
P value N
1585
(42.37%)
2155
(57.63%)
Range of year
Of diagnosis
2001
2003
Median Age 48 50
Subgroups
T1N0
T2N0
T1N2
434 (27.38%)
469 (29.59%)
383 (24.16%)
299 (18.86%)
757 (35.13%)
528 (24.50%)
493 (22.88%)
377 (17.49%)
<.0001
Median nodes removed
13(1-58)
10(1-57)

11. Neoadjvuant chemotherapy No Yes
Mastectomy
(No Radiation)
Segmental
(Radiation)
P value
Neoadjvuant chemotherapy No Yes
1239 (78.17%)
346 (21.83%)
1627 (75.5%)
528 (24.5%)
0.0564
Anthracycline No Yes
141 (9.02%)
1423 (90.98%)
155 (7.29%)
1972 (92.71%)
0.0561
Taxane No Yes
716 (45.78%)
848 (54.22%)
919 (43.21%)
1208 (56.79%)
0.1198

12. Results Number Total no. analyzed 3740 Deaths 767 (18.1%)
Median follow-up
54 months ( months)
Median OS
161 months
(95% CI months)
5-year DDFS
78%
(95% CI 76%-79%)
5-year LRDFS
88%
(95% CI 87%-90%)

13. Multivariate Analysis of LRDFS
Whole Cohort HR
Lower
95% CI
Upper
P-Value
Mastectomy vs. Segmental
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

14. 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

15. LRDFS Among LN Positive Groups
T1N1 (N=876)
T1N2 (N=676)
5- Year Estimates
Segmental : 91%
Mastectomy: 90%
P=0.65
5- Year Estimates
Segmental : 91%
Mastectomy: 87%
P=0.009

16. Adjusted Hazard Ratios for LRDFS among various subgroups
Favors Mastectomy
Forrest Plot For Sub-Groups
Favors Segmental
Whole Cohort
T1N0
T1N0
T2N0
T2N0
T1N1
T1N1
T2N1
T2N1
No Neoadjuvant group (HR = 2.62 , 95% CI , P =
Hazard Ratios LDFS

17. Multivariate Analysis for DDFS
Whole Cohort HR
Lower
95% CI
Upper
P-Value
Mastectomy vs. Segmental
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

18. DDFS Among LN Negative Groups
T1N0 (N=1191)
T2N0 (N=997)
5- Year Estimates
Segmental : 87%
Mastectomy: 86%
P=0.11
5- Year Estimates
Segmental : 85%
Mastectomy: 80%
P=0.38

19. DDFS Among LN Positive Groups
T1N1(N=876)
T2N1(N=676)
5- Year Estimates
Segmental : 90%
Mastectomy: 85%
P=0.004
5- Year Estimates
Segmental : 77%
Mastectomy: 68%
P=0.0177

20. Adjusted Hazard Ratios for DDFS among various subgroups
Favors Mastectomy
Favors Segmental
T1N0
T2N0
T1N1
T2N1
HR = 1.71 , 95% CI , P =0.007
No Neoadjuvant group (HR = 1.54, 95% CI , P =0.061)

21. 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.

22. 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.

23. Acknowledgement Mentors Dr. Thomas A. Buchholz
Dr. Ana M. Gonzalez-Angulo
Dr. Mona Al Rhukhaimi
Dr. Farid Khalifa

24. Thank You