1. CALGB 9343 Comparison of Lumpectomy Plus Tamoxifen With and Without Irradiation in Women 70 or Older with Clinical Stage I, ER+ Breast Carcinoma
Kevin S. Hughes, Lauren A. Schnaper, Constance Cirrincione, Donald Berry, Beryl McCormick, Hyman B. Muss, Clifford Hudis, Eric Winer, Barbara L. Smith
Cancer and Leukemia Group B
Radiation Therapy Oncology Group
Eastern Cooperative Oncology Group 1

2. CALGB 9343 R A N D O M I Z E Radiation Tamoxifen Tamoxifen
ELIGIBILITY Age ³ 70
Clinically
Node Negative Lumpectomy, Negative Margin Tumor size £ 2 cm
ER Positive or Indeterminate
R A N D O M I Z E
Radiation
Tamoxifen
Tamoxifen 2

3. Objections to this study
Patients randomized to receive no radiation would be inappropriately under-treated
Patients randomized to receive radiation therapy would be inappropriately over-treated

4. CALGB 9343 Opened July 15, 1994 Closed February 26, 1999 647 patients
Eligible
Ineligible
Canceled/Never treated 11
Median follow-up 12 years

5. Patient characteristics
RT+Tam Tam
Total treated
Age > (56%) 172 (54%)
ER Positive (97%) 310 (97%)
Size < 2cm (93%) 296 (93%)
No Ax dissection (63%) 203 (64%)

6. IBTR (Ipsilateral Breast Tumor Recurrence)
21 women
TamRT
Tam
(N=317)
(N=319)
Events
6 (2%)
27 (9%)
p=0.0001

7. Ultimate mastectomy TamRT Tam Events (N=317) (N=319) 4 (2%) 10 (4%)
p=0.1779

8. IBTR 6 4 RT
Mastectomy 10
IBTR 27 17
Lumpectomy
No RT

9. Axillary recurrence TamRT Tam 317 319 No ax dissection 200 203
Ax Recurrence
6 (3%)

10. Free of Second Primary Cancer
TamRT
Tam
(N=317)
(N=319)
Events
36 (12%)
33 (9%)
p=0.7268

11. Overall Survival TamRT Tam Events (N=317) (N=319) 157 (33%) 166 (33%)
P=0.8045

12. Free from distant metastasis
TamRT
Tam
(N=317)
(N=319)
Events
21(5%)
16 (5%)
P=0.461

13. Breast cancer specific survival
TamRT
Tam
(N=317)
(N=319)
Events
12 (3%)
8 (2%)
P=0.4115

14. Ultimate Outcome

15. Benefits of RT are small
21 women
TamRT
Tam
N=317
N=319
N (10 years)
Breast Recurrence
6 (2%)
27 (9%)
p=0.0001
Ultimate Mastectomy
4 (2%)
10 (4%) NS
Second primary cancer
36 (12%)
33 (9%)
Distant metastasis
21(5%)
16 (5%)
Death
157 (33%)
166 (33%)
Death Other Causes
145
148
Death from breast cancer 12 8
N (% at 10 yeas) N (% at 10 years)

16. Ultimate breast preservation NS Second primary cancer NS
CONCLUSION: In older women, the benefits of radiation after lumpectomy are small
21 women
Breast recurrence ~7%
Radiate 319 women to avoid 21 in breast recurrences
Ultimate breast preservation NS
Second primary cancer NS
Distant metastases NS
Death breast cancer NS
Death from any cause NS

17. Ultimate breast preservation NS Second primary cancer NS
CONCLUSION: In older women, the benefits of radiation after lumpectomy are small
21 women
Breast recurrence ~7%
Radiate 319 women to avoid 21 in breast recurrences
Ultimate breast preservation NS
Second primary cancer NS
Distant metastases NS
Death breast cancer NS
Death from any cause NS
Study is mature: 12 years Median, Half of patients dead
With modern margins and AI’s, RT will likely have even less benefit

18. Ultimate breast preservation NS Second primary cancer NS
CONCLUSION: In older women, the benefits of radiation after lumpectomy are small
21 women
Breast recurrence ~7%
Radiate 319 women to avoid 21 in breast recurrences
Ultimate breast preservation NS
Second primary cancer NS
Distant metastases NS
Death breast cancer NS
Death from any cause NS
Omitting Radiation in women 70 and above with Clinical Stage I breast cancer is a reasonable alternative for our patients

22. CALGB 9343 enrolled 647 patients
CALGB 9343 enrolled 647 patients. Eleven patients never began protocol therapy; findings are based upon the 636 patients who began protocol treatment. As of May 2010, the median follow-up for treated patients was 12 years with a maximum of 16 years. Three hundred nine (309) patients are alive and in active follow-up. Two hundred thirty-nine (239, 77%) of them have survived at least 10 years from enrollment. Only four patients (<1%) have been lost to follow-up, and only 10 patients (1.5%) withdrew consent to be followed.
Table 1. Patient enrollment
Tam + RTTamTotalTotal enrolled323 (100%)324 (100%)647 (100%)Never began Rx6 (2%)5 (2%)11 (2%)Treated317 (98%)319 (98%)636 (98%)
Data as of May 2010
Median follow-up = 12 years (range = 1, 16)
Table 2. First event
The table below describes the first recurrence: local, distant or local and distant synchronously. Because the entries are for first recurrence, a patient may only be counted once.
StatusArmTotalTam + RTTamTreated317 (100%)319 (100%)636 (100%)Total recurrences234164Type of recurrencea. Local only In breast only ( 4) (22) (26) Axillary only ( 0) ( 5) ( 5) In-breast + axillary ( 0) ( 1) ( 1)b. Distant only171128c. Local + distant *224
* All local recurrences were IBTR only.
Table year incidence of each study endpoint by treatment arm
This table considers the occurrence of each event at any time in follow-up. It is therefore unlike Table 2, which is restricted to site of first recurrence only. A patient may have an event for each of the five endpoints.
ArmEndpointFree from local recurrenceWithout subsequentmastectomyFree from distant metsOSBC-specific survivalTam + RT98%(96-99%)98%(96-99%)95%(92-97%)67% (61-72%)97%(94-99%)Tam90%(85-93%)96%(93-98%)95%(91-97%)67%(61-72%)98%(95-99%)
Table 4. Comparison by treatment arm of entire distribution of each endpoint
EndpointTime to local recurrenceTime to subsequent mastectomyTime to distant metsOSBC-specific survivalP-value from logrank test
Table 5. Second primaries
SiteArmTotalTam+RTTamBreast Invasive DCIS213 Lymph nodes101Blood AML112 CLL011 MDS011Lymphoma Lymphoma325 NHL112GI Abdomen011 Bowel101 Colon448 Epiglottis101 Peritoneum011 Rectum101 GI, NOS101GU Bladder Endometrium314Hepatic Liver Pancreas Spleen101Lung4711Melanoma202
Two patients had two new primaries.

23. Site
Arm
Total
Tam+RT
Tam
Breast
Invasive 9 18
DCIS 2 1 3
Lymph nodes
Blood
AML
CLL
MDS
Lymphoma 5
NHL GI
Abdomen
Bowel
Colon 4 8
Epiglottis
Peritoneum
Rectum
GI, NOS GU
Bladder
Endometrium
Hepatic
Liver
Pancreas
Spleen
Lung 7 11
Melanoma

24. Time to local recurrence Time to subsequent mastectomy
Endpoint
Time to local recurrence
Time to subsequent mastectomy
Time to distant mets OS
BC-specific survival
P-value from logrank test
0.0001
0.18
0.46
0.80
0.41

25. Free from local recurrence
Arm
Endpoint
Free from local recurrence
Without subsequent
mastectomy
Free from distant mets OS
BC-specific survival
Tam + RT
98%
(96-99%)
95%
(92-97%)
67%
(61-72%)
97%
(94-99%)
Tam
90%
(85-93%)
96%
(93-98%)
(91-97%)
(95-99%)

26. Status
Arm
Total
Tam + RT
Tam
Treated
317 (100%)
319 (100%)
636 (100%)
Total recurrences 23 41 64
Type of recurrence
a. Local only 4 28 32
In breast only
( 4)
(22)
(26)
Axillary only
( 0)
( 5)
In-breast + axillary
( 1)
b. Distant only 17 11
c. Local + distant * 2

27. Tam + RT
Tam
Total
Total enrolled
323 (100%)
324 (100%)
647 (100%)
Never began Rx
6 (2%)
5 (2%)
11 (2%)
Treated
317 (98%)
319 (98%)
636 (98%)

31. Can we? Should we? Patient factors are dependent on physiologic age
Tumor factors are dependent on chronologic age

32. Concerns regarding this study
Patients randomized to receive no radiation would be inappropriately under-treated

33. Concerns regarding this study
Patients randomized to receive no radiation would be inappropriately under-treated
Patients randomized to receive radiation therapy would be inappropriately over-treated

34. 2007: Median 8.2 Yr

35. Axillary recurrence

38. Time to IBTR TamRT Tam Free from In-Breast Recurrence (N=317) (N=319)
20 women
TamRT
Tam
(N=317)
(N=319)
Free from In-Breast Recurrence
6 (98%)
26 (92%)
p=0.0001

39. Concerns regarding this study
Patients randomized to receive no radiation would be inappropriately under-treated
Patients randomized to receive radiation therapy would be inappropriately over-treated

41. Second Primary Cancer TamRT Tam TOTAL 36 (12%) 33 (9%) Breast 12 10
Leukemia 1 2
MDS
Lymphoma 4 3
Colorectal 6 5
Epiglottis
Peritoneum
GI,NOS
Liver
Pancreas
Spleen
Bladder
Endometrium
Lung 7
Melanoma