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The influence of age on outcome in early state breast cancer
Proceedings
Conclusions:
of the 35th Annual ASTRO Meeting
149
The patients were furtherdivided on the basis of their pathologic nodal status. There were no statistically significant differences among the three age groups for axillary node positive patients for overall survival (75%vs. 80% vs. 74%). relapse-free survival (73%vs. 73%vs. 62%) cause spccitic sunivat (75% vs. 85%vs. 80%), distant metastasis (18%vs. IS%vs. 16%),or breast recurrence(0%vs. 9% vs. 6%). The findings were identical when the analysis was restrictedto node positive patients who received chemotherapy. Howler, for axillaty node negative women, young age was associated with a statistically sign&cant decmamd overal survival (7 1%vs. 83%vs. 92%), relapse free survival (5 1%vs. 65%vs. 76%), and cause specitic survival (71%vs. 86%vs. 94%)and a statistically increased risk of breast recurrence(40%vs. 16%vs. 13%).regional node recurrence(3 vs. 1%vs. C%),and distant metastasis (8% vs. 12%vs. 7%). Young women with early stage breast cancer do significantly worse when compared to older women in terms of relapse-freesurvival, cause specific sunival, distant metastasis,breast and regional node recurrence. However, in a subset analysis, the adverse effect of young age on outcome appears to be limited to the node negative patients. These findings suggest that node negative early stage breast cancer in young women is a more aggressive disease with au increased risk for all patternsof failure and a decreased smvivat.
37 LOCAL BREAST RECURRENCE (LBR) POST-LUMPECTOMY IS PREDICTIVE OF SUBSEQUENT MORTALITY: RESULTS FROM A RANDOMIZED TRIAL T. Whelan, R. Clark, R. Roberts, M. Levine, C. Foster Ontario Clinical Oncology Group, Ontario, Canada PURPOSE/OBJECTIVE:
Adjuvant radiation post-lumpectomy has been shown to reduce the risk of LBR with no significant impact on distant relapse (DR) and overall survival. More recently, it has been demonstrated that LBR post-lumpectomy is predictive for DR in women with early breast cancer (NSABP, Lancet 1991; 338:327). These apparently conflicting observations could be explained in part by the potential bias, whereby a LBR initiated a starch for metastatic disease or LBR post radiation conferred greater risk. The objective of our study was to determine if LBR post-lumpectomy was indcpcndcntly predictive of DR and mortality in patients with node negative breast cancer. MATERIALS & METHODS: A randomized trial was conducted in Ontario between 1984 and 1989, in which 837 women with node negative disease who had undergone lumpcctomy and axillary dissection were randomized to either post-operative radiation (4000 cGy in 16 fractions to the whole breast, followed by a boost of 1250 cGy in 5 fractions to the primary site), or no further treatment (JNCI 1992; &t:683). A Cox proportional hazards regression analysis was performed on the end points, mortality and DR for the fixed covariates. treatment, age, tumour size, and grade; and the time dependant variable LBR. RESULTS: The relative risk (RR) for mortality with radialion treatment was 0.84, (I’ = 0.36. (95% C.I. 0.59-1.21). Significant independent baseline predictors for mortality were tumour grade, high vs medium and low (RR = 2.28, p = 0.0001) and size, > 2 cm vs 5 2 cm (RR = 1.61, p = 0.01). In addition, LBR predicted increased mortality (RR = 2.18, p = 0.0007). Similar results were observed for DR. In a second analysis LBR after radiation was associated with a somewhat higher risk of subsequent mortality (RR = 2.91) than LBR after lumpectomy alone (RR = 1.92). but this was not statistically significant (p = 0.38). LBR within one year of surgery was associated with a higher risk of DR (RR = 3.26, p = 0.0001) then LBR after one year (RR=1.70. p=O.Ol). CONCLUSION: These results confirm the observation that LBR post-lumpectomy is a marker of more aggressive disease and do not necessarily indicate a cause effect relationship. LBR after adjuvant radiation or within the first year of surgery may confer extra risk. Whether patients with LBR post-hunpectomy am candidates for systemic therapy should be explored in future studies.
38 IS IPSILATERAL BREAST TUMOR RECURRENCE AN INDEPENDENT PREDICTOR OF DISTANT DISEASE? Bruce G. Haffty, M.D.‘, Diana Fischer, Ph.D.‘, Darryl Carter, M.D.2 Departments
of Therapeutic Radiology’ and Pathology’, Yale University School of Medicine
Pttrpoae: In a recent analysis of data from NSABP-B06 &at& 338;327-331, 1991), ipsilateral breast tumor recurrence (IBTR) following conservative surgery mm) proved to he a powerful independent marker for distant metastases. The purpose of this study was to determine if, in patients treated with CS+RT, IBTR proved to be an independent predictor of distant metastases and to determine what, if any, pathological markers predict for both local and distant relapse. Methods & Materi&: Between 1962 and 1989,958 patients with invasive breast cancer were treated with CS+RT at YNHH. Follow-up as of 3/92 was 6.8 years (range :!.l-30.7 years). In univariate analysis, prognostic factors tested as possible predictors for distant metastasea included primary tumor size, nodal status, receptor status, patient age, adjuvant therapy and whether or not a patient experienced IBTR. A multivariable model was then constructed with all pertinent clinical parameters to determine whether IBTR was an independent predictor of distant metastases. IBTRs were then divided into early (~5 years following original diagnosis) or late (r 5 years) to determine whether diictionofearly or late IBTR was an independent predictor of distant metastaaes. A pathological analysis was performed on the first 180casea treated prior to 1981(follow-up = 14 years) in which complete pathological data (i.e tumor grade, vascular invasion, necrosis, intraductal component, etc.) were available.
Conclusions:
of the 35th Annual ASTRO Meeting
149
The patients were furtherdivided on the basis of their pathologic nodal status. There were no statistically significant differences among the three age groups for axillary node positive patients for overall survival (75%vs. 80% vs. 74%). relapse-free survival (73%vs. 73%vs. 62%) cause spccitic sunivat (75% vs. 85%vs. 80%), distant metastasis (18%vs. IS%vs. 16%),or breast recurrence(0%vs. 9% vs. 6%). The findings were identical when the analysis was restrictedto node positive patients who received chemotherapy. Howler, for axillaty node negative women, young age was associated with a statistically sign&cant decmamd overal survival (7 1%vs. 83%vs. 92%), relapse free survival (5 1%vs. 65%vs. 76%), and cause specitic survival (71%vs. 86%vs. 94%)and a statistically increased risk of breast recurrence(40%vs. 16%vs. 13%).regional node recurrence(3 vs. 1%vs. C%),and distant metastasis (8% vs. 12%vs. 7%). Young women with early stage breast cancer do significantly worse when compared to older women in terms of relapse-freesurvival, cause specific sunival, distant metastasis,breast and regional node recurrence. However, in a subset analysis, the adverse effect of young age on outcome appears to be limited to the node negative patients. These findings suggest that node negative early stage breast cancer in young women is a more aggressive disease with au increased risk for all patternsof failure and a decreased smvivat.
37 LOCAL BREAST RECURRENCE (LBR) POST-LUMPECTOMY IS PREDICTIVE OF SUBSEQUENT MORTALITY: RESULTS FROM A RANDOMIZED TRIAL T. Whelan, R. Clark, R. Roberts, M. Levine, C. Foster Ontario Clinical Oncology Group, Ontario, Canada PURPOSE/OBJECTIVE:
Adjuvant radiation post-lumpectomy has been shown to reduce the risk of LBR with no significant impact on distant relapse (DR) and overall survival. More recently, it has been demonstrated that LBR post-lumpectomy is predictive for DR in women with early breast cancer (NSABP, Lancet 1991; 338:327). These apparently conflicting observations could be explained in part by the potential bias, whereby a LBR initiated a starch for metastatic disease or LBR post radiation conferred greater risk. The objective of our study was to determine if LBR post-lumpectomy was indcpcndcntly predictive of DR and mortality in patients with node negative breast cancer. MATERIALS & METHODS: A randomized trial was conducted in Ontario between 1984 and 1989, in which 837 women with node negative disease who had undergone lumpcctomy and axillary dissection were randomized to either post-operative radiation (4000 cGy in 16 fractions to the whole breast, followed by a boost of 1250 cGy in 5 fractions to the primary site), or no further treatment (JNCI 1992; &t:683). A Cox proportional hazards regression analysis was performed on the end points, mortality and DR for the fixed covariates. treatment, age, tumour size, and grade; and the time dependant variable LBR. RESULTS: The relative risk (RR) for mortality with radialion treatment was 0.84, (I’ = 0.36. (95% C.I. 0.59-1.21). Significant independent baseline predictors for mortality were tumour grade, high vs medium and low (RR = 2.28, p = 0.0001) and size, > 2 cm vs 5 2 cm (RR = 1.61, p = 0.01). In addition, LBR predicted increased mortality (RR = 2.18, p = 0.0007). Similar results were observed for DR. In a second analysis LBR after radiation was associated with a somewhat higher risk of subsequent mortality (RR = 2.91) than LBR after lumpectomy alone (RR = 1.92). but this was not statistically significant (p = 0.38). LBR within one year of surgery was associated with a higher risk of DR (RR = 3.26, p = 0.0001) then LBR after one year (RR=1.70. p=O.Ol). CONCLUSION: These results confirm the observation that LBR post-lumpectomy is a marker of more aggressive disease and do not necessarily indicate a cause effect relationship. LBR after adjuvant radiation or within the first year of surgery may confer extra risk. Whether patients with LBR post-hunpectomy am candidates for systemic therapy should be explored in future studies.
38 IS IPSILATERAL BREAST TUMOR RECURRENCE AN INDEPENDENT PREDICTOR OF DISTANT DISEASE? Bruce G. Haffty, M.D.‘, Diana Fischer, Ph.D.‘, Darryl Carter, M.D.2 Departments
of Therapeutic Radiology’ and Pathology’, Yale University School of Medicine
Pttrpoae: In a recent analysis of data from NSABP-B06 &at& 338;327-331, 1991), ipsilateral breast tumor recurrence (IBTR) following conservative surgery mm) proved to he a powerful independent marker for distant metastases. The purpose of this study was to determine if, in patients treated with CS+RT, IBTR proved to be an independent predictor of distant metastases and to determine what, if any, pathological markers predict for both local and distant relapse. Methods & Materi&: Between 1962 and 1989,958 patients with invasive breast cancer were treated with CS+RT at YNHH. Follow-up as of 3/92 was 6.8 years (range :!.l-30.7 years). In univariate analysis, prognostic factors tested as possible predictors for distant metastasea included primary tumor size, nodal status, receptor status, patient age, adjuvant therapy and whether or not a patient experienced IBTR. A multivariable model was then constructed with all pertinent clinical parameters to determine whether IBTR was an independent predictor of distant metastases. IBTRs were then divided into early (~5 years following original diagnosis) or late (r 5 years) to determine whether diictionofearly or late IBTR was an independent predictor of distant metastaaes. A pathological analysis was performed on the first 180casea treated prior to 1981(follow-up = 14 years) in which complete pathological data (i.e tumor grade, vascular invasion, necrosis, intraductal component, etc.) were available.