Is Breast Radiation Therapy Necessary in the Elderly? Cancer and Leukemia Group B Radiation Therapy Oncology Group Eastern Cooperative Oncology Group
CALGB 9343 Submitted 1990 Opened July 15, 1994 Closed February 26, 1999 647 patients Eligible 631 Ineligible 5 Canceled/Never treated 11 Median follow-up 12 years
ELIGIBILITY Age 70 Clinically Node Negative Lumpectomy, Negative Margin Tumor size 2 cm ER Positive or Indeterminate STRATIFICATION Age < 75 75 Axillary Dissection Yes No R A N D O M I Z E CALGB 9343 Radiation Tamoxifen Tamoxifen
Patient characteristics RT+Tam Total treated 317 319 Tam Age >75 176 (56%) 172 (54%) ER Positive 308 (97%) 310 (97%) Size < 2cm 295 (93%) 296 (93%) No Ax dissection 200 (63%) 203 (64%)
IBTR (Ipsilateral Breast Tumor Recurrence) 98% 91%
Ultimate Outcome
Actuarial survival for given ages at entry D. Berry 8/28/11
The Radiation Oncologists Response
The Radiation Oncologists Response The in-breast recurrence rate is unacceptable 9343 might be true, but only for selected subgroups If we don t radiate, people will die I have retrospective data that negates your prospective randomized data
In breast recurrence rate is unacceptable approaches a threshold where some patients and doctors may make an informed decision [for added treatment] These rates of recurrence might seem unacceptable Psychological burden of patients with recurrence
In breast recurrence rate is unacceptable approaches a threshold where some patients and doctors may make an informed decision [for added treatment] These rates of recurrence might seem unacceptable Psychological burden of patients with recurrence J Clin Oncol 25:3259-3265. 2007
In breast recurrence rate is unacceptable approaches a threshold where some patients and doctors may make an informed decision [for added treatment] These rates of recurrence might seem unacceptable Psychological burden of patients with recurrence J Clin Oncol 25:3259-3265. 2007
9343 might be true, but only for selected subgroups Which patient is in need of RT, using the genomic and proteomic profiling so that RT be delivered on an individual basis They meant Older women with high risk cancers need RT The corollary Younger women with low risk cancers do not need RT
People will die Provided sufficient time is allowed, mortality will be increased. For every 4 local recurrences prevented, one mortality is spared 15 years later What the Lancet article actually says: if absolute differences of >10% in 5-year risk local recurrence IF little difference in 5-year local recurrence risk there was little difference in 15-year breast cancer mortality EBCTG, Lancet Vol 366: 2087 (2005)
People will die Provided sufficient time is allowed, mortality will be increased. For every 4 local recurrences prevented, one mortality is spared 15 years later J Clin Oncol 25:3259-3265. 2007
Is it time to decide what rate of IBTR is acceptable? Women 40 and younger Women 70 and older Women younger than 70 with luminal A DCIS
CONCLUSION: In older women, the benefits of radiation after lumpectomy are small Breast Recurrence Ultimate Mastectomy Second primary cancer Distant metastasis Death Death Other Causes Death from breast cancer Less Same Same Same Same Same Same 22 women
Greater compliance with tamoxifen inflates results If patients treated on CALGB 9343 had a greater degree of compliance [with tamoxifen] compared with that achieved in the general population, then the recurrence rates may underestimate the true recurrence risk.. Corollary 1 If patients treated on [Any prospective trial of adjuvant therapy] had a greater degree of compliance [with tamoxifen or chemotherapy or trastuzumab or radiation] compared with that achieved in the general population, then the recurrence rates may underestimate the true recurrence risk..
Greater compliance with tamoxifen negates results If patients treated on CALGB 9343 had a greater degree of compliance [with tamoxifen] compared with that achieved in the general population, then the recurrence rates may underestimate the true recurrence risk.. Corollary 1 Invalidates all prospective trials because ALL trials have better compliance by patient and physician
Greater compliance with tamoxifen negates results If patients treated on CALGB 9343 had a greater degree of compliance [with tamoxifen] compared with that achieved in the general population, then the recurrence rates may underestimate the true recurrence risk.. Corollary 2 Since patients treated on CALGB 9343 had suboptimal margins, the recurrence rates may overestimate the true recurrence risk Since patients treated on CALGB 9343 took tamoxifen instead of an AI, the recurrence rates may overestimate the true recurrence risk Since patients treated on CALGB 9343 had a longer life expectancy, the recurrence rates may overestimate the true recurrence risk
Managing the elderly If mastectomy needed Preop chemo or endocrine Mastectomy (With sentinel node) If breast preservation possible Clinically positive node Lumpectomy/Axillary dissection Tumor ER- or over 2 cm Lumpectomy/Sentinel node
Managing the elderly If mastectomy needed Preop chemo or endocrine Mastectomy (With sentinel node) If breast preservation possible Clinically positive node Lumpectomy/Axillary dissection Tumor ER- or over 2 cm Lumpectomy/Sentinel node If Clinical Stage I and ER+
CALGB 9343, 2004: Median 5 Year Breast Recurrence Ultimate Mastectomy Second primary cancer Distant metastasis Death Death Other Causes Death from breast cancer Less Same Same Same Same Same Same TamRT Tam Hughes et al, NEJM, 2004
Can we Vs should we? Can you treat? Slower growth increases the time needed to show benefit They may not live long enough to see benefit Tam/AI more effective
AS OF 2007, LITTLE CHANGE IN PRACTICE
1.9 cm, ER+, clinical N0 Cancer Lumpectomy Plus Radiation/Boost Tamoxifen Sentinel Node Chemotherapy BRCA testing
1.9 cm, ER+, clinical N0 Cancer Lumpectomy Plus Radiation/Boost Tamoxifen Sentinel Node Chemotherapy BRCA testing Lumpectomy Plus Radiation/Boost Tamoxifen/AI Sentinel Node Chemotherapy BRCA testing
Concerns regarding this study Patients randomized to no radiation would be inappropriately undertreated
Concerns regarding this study Patients randomized to receive no radiation would be inappropriately under-treated Patients randomized to radiation therapy would be inappropriately over-treated
Ipsilateral cancer risk
Radiation decreases local recurrence by ~7% Does it do anything else?
IBTR 6 4 RT Mastectomy 10 No RT IBTR 27 18 Lumpectomy
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, Jennifer Bellon, Constance Cirrincione, Donald Berry, Barbara L. Smith, Beryl McCormick, Hyman B. Muss, Clifford Hudis, Eric Winer, William Wood Cancer and Leukemia Group B Radiation Therapy Oncology Group Eastern Cooperative Oncology Group
Comparison of Lumpectomy Plus Tamoxifen With and Without Irradiation in Women 70 or Older with Clinical Stage I, ER+ Breast Carcinoma CALGB 9343 Kevin S. Hughes, Lauren A. Schnaper, Jennifer Bellon, Constance Cirrincione, Donald Berry, Barbara L. Smith, Beryl McCormick, Hyman B. Muss, Clifford Hudis, Eric Winer, Larry Norton, William Wood Cancer and Leukemia Group B Radiation Therapy Oncology Group Eastern Cooperative Oncology Group