evidence for adjuvant radiation therapy benefiting breast cancer patients with 1 to 3 positive lymph...

Evidence for adjuvant radiation therapy benefiting breast cancer patients with 1 to 3 positive lymph nodes treated with a modified

radical mastectomy and systemic therapyShaheenah 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 CenterDepartments of Breast Medical Oncology, Surgical Oncology and Radiation Oncology

Dubai Hospital, U.A.E, Department of Medical OncologyDepartments of Breast Medical Oncology, and Quantitative Sciences

(Abstract number :507

Disclosure

• I have no relevant relationships to disclose.

Postmastectomy RadiationOxford: Mastectomy +/- XRT

Trials

LN - Disease

LN + Disease

Breast Recurrence Breast Ca Deaths

8% vs. 3%

29% vs. 8%

28% vs. 31%

60%vs. 55%

Local Recurrence

• 2/3 reduction

Breast Ca Survival

• none in LN-

• 5% for LN+

• 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 IIBreast Cancer Stage I and II

Breast Cancer

Mastectomy + no Radiation

Mastectomy + no Radiation

Segmental Resection + 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 follow-up.

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)

P value

N

1585 (42.37%)

2155 (57.63%)

Range of year

Of diagnosis

2001 2003

Median Age 48 50

SubgroupsT1N0T2N0T1N2T1N2

434 (27.38%)

469 (29.59%)

383 (24.16%)

299 (18.86%)

757 (35.13%)

528 (24.50%)

493 (22.88%)

377 (17.49%) <.0001Median nodes

removed 13(1-58) 10(1-57)

Mastectomy

(No Radiation)

Segmental

(Radiation)

P value

Neoadjvuant chemotherapy

No

Yes1239 (78.17%)

346 (21.83%)1627 (75.5%)

528 (24.5%) 0.0564Anthracycline

No

Yes141 (9.02%)

1423 (90.98%)155 (7.29%)

1972 (92.71%) 0.0561Taxane No

Yes716 (45.78%)

848 (54.22%)919 (43.21%)

1208 (56.79%) 0.1198

ResultsNumber

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 HRLower 95% CI

Upper 95% CI 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

LRDFS Among LN Negative Groups

T1N0 (N=1191) T2N0 (N=997)

5- Year EstimatesSegmental : 92%Mastectomy: 91%P=0.93


LRDFS Among LN Positive Groups

T1N1 (N=876) T1N2 (N=676)



Adjusted Hazard Ratios for LRDFS among various subgroups

T1N0

T2N0

T1N1

T2N1

Whole Cohort

T1N0

T2N0

T1N1

T2N1

Forrest Plot For Sub-Groups

Hazard Ratios LDFS

No Neoadjuvant group (HR = 2.62 , 95% CI 1.26-5.46, P =0.00099

Favors SegmentalFavors Mastectomy

Multivariate Analysis for DDFS

DDFS

Whole Cohort HRLower 95% CI

Upper 95% CI 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

DDFS Among LN Negative Groups

T1N0 (N=1191) T2N0 (N=997)



DDFS Among LN Positive Groups

T1N1(N=876) T2N1(N=676)



Adjusted Hazard Ratios for DDFS among various subgroups

T1N0

T2N0

T1N1

T2N1 HR = 1.71 , 95% CI 1.15-2.52, P =0.007

No Neoadjuvant group (HR = 1.54, 95% CI 0.98-2.23, P =0.061)

Favors SegmentalFavors Mastectomy

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. BuchholzDr. Ana M. Gonzalez-AnguloDr. Mona Al RhukhaimiDr. Farid Khalifa

Thank You

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