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138 Pathologic margin involvement and the risk of recurrence inpatients treated with breast-conserving therapy
210
Radiation Oncology, Biology, Physics Volume 32, Supplement 1
138 P A T H O L O G I C MARGIN I N V O L V E M E N T AND T H E R I S K O F R E C U R R E N C E IN P A T I E N T S T R E A T E D W I T H BREAST-CONSERVING THERAPY I r e n e G a g e 1, Asa J. Nixon 1, Stuart J. Schnitt 2, A b r a m Recht 1, Rebecca G e l m a n L Barbara Silver 1, J a m e s L. ConnoLly~, Jay R. Harris 1 tjoint Center for Radiation Therapy; 2Department of Pathology, Beth Israel Hospital; H a r v a r d Medical School, Boston, M A PURPOSE: T o assess the relationship between microscopic margin status and recurrence after breast-conserving therapy for tumors with or without an extensive intraductal c o m p o n e n t (EIC). MATERIALS A N D M E T H O D S : During the years 1968 to 1986, 1865 w o m e n with unilateral clinical stage I or II breast cancer w e r e treated with radiation therapy for breast conservation. Of these, 340 received >-60 G y to the t u m o r bed and had margins that were evaluable on review of their pathologic slides; these constitute the study population. The m e d i a n follow-up was 109 months. All available slides were reviewed by one of the study pathologists (SS, JC). Final radial margins of excision were classified as negative > 1 m m (no invasive or ductal carcinoma in-situ within 1 m m of the inked margin), negative -<1 m m (any c a r c i n o m a _<1 m m of the inked m a r g i n but not at ink) or positive (any carcinoma at the inked margin). A focally positive margin was defined as any invasive or in-situ c a r c i n o m a at the marginin s 3 LPF. T h e extent of positivity was not evaluable in 2 patients and the distance of the tumor from the margin was not evaluable in 48 patients with a negative margin. Thirty-nine percent of EIC-negative and 46% of EIC-positive patients underwent a re-excision and, for these, the final margin analyzed was from the re-excised specimen. The m e d i a n dose to the t u m o r bed was 63 Gy for patients with positive margins and 62 Gy for patients with negative margins. Recurrent disease was classified as ipsilateral breast recurrence (IBR) or distant metastasis/regional nodal failure ( D M / R N F ) . RESULTS: Five year crude rates for the first site of recurrence were calculated separately for all patients, EIC-negative and EIC-positive. All p-values tested All Pnllents Final Margin IBR p-Value DM/RNF 1111t Positive, > Focally 28% (14/50) 30% (15/50) 19% (6/31) Positive, Focally + 9% (7/79) 19% (15/79) 9% (6/65) p- 0.002 Negative g l mm 2% (1/54) 15% (8/54) 2% (1/44) Negative > 1 mm 3% (3/107) 19% (20/107) 1% (1/93) p = 0.87 All Positive 16% (Z1/131) 23% (30/1_31) 12% (12/97) All Negative 2% (41209) t7% (281209) 1% (21137) p
for 340 patients evaluable at 5 years. Results w e r e tabulated for differences in the distribution of sites of first failure. ~|~ lrlC ÷ p-Value DM/RNF [IIR p- gltlue DM/RNF 39% (12/31) 42% (8/19) 16% O/19) 20% (13/65) 7% (1/14) 14% (2/14) p-0.03 p=O,06 18% (8/44) 0% (0/10) 0% (0/10) 20% (19/93) 14% (2/14) 7% (1/14) p =0.84 p= 0.49 26% (25,/97) 27% (9/34) 15% (5/34) 20% (27/t37) 8% (2124) 4% (t/24) p
C O N C L U S I O N S : T h e risk of ipsilateral breast recurrence is equally low for patients with close (<1 ram) or negative ( > 1 ram) margins for both EIC-negative and ElC-positive cancers. These d a t a suggest that some patients with focally positive margins may also be reasonably treated with breast-conserving therapy. Patients with greater than focally positive margins (with or without an EIC) are at a significantly higher risk of failure c o m p a r e d to those with focally positive or negative margins.
139 R E L A T I O N S H I P OF T U M O R G R A D E T O O T H E R P A T H O L O G I C F E A T U R E S AND T O T R E A T M E N T O U T C O M E FOR PATIENTS WITH EARLY-STAGE BREAST CANCER TREATED WITH BREAST-CONSERVING THERAPY Asa J. Nixon 1, Irene Gage I , James L. Connolly 2. Stuart Schnill 2, Barbara Silver I , Stella Hetelekidis I , Abram Recht 1, and Jay R. Harris I l Joint Center for Radiation Therapy; 2 Department of Pathology. Beth Israel Hospital; Harvard Medical School, Boston MA P'urpo,~: To study the relationship of tumor grade to the distribution o! pathologic features and to the risk of local and distant recurrence following breast-conserving therapy in patients with pure infiltrating ductal carcinoma, and Io explore the differences between this type and tubular carcinoma. M a t e r i a l s and Methods: Between 1968 and 1986, 1624 patients were treated for clinical Stage I or II invasive breast cancer with a complete gross excision and _>60Gy to the tumor bed. The original slides were reviewed in 1337 cases (82%). Of these, 1081 were pure infiltrating ductal carcinoma and 28 were tubular carcinoma and these constitute the study population. Fifty-five patients (5%) have been tost to followup after 7-181 months. Median followup for 742 survivors is 134 months (7-278 mos.) We evaluated the following features: histologic grade (modified Bloom Richardson system), the presence of nodal metastases (in 891 pts. (80%) undergoing axillary dissection [pLN+]), an extensive intraductal component (EIC), lymphatic vessel invasion (LV1), mononuclear cellular response (MCR). and necrosis. We analyzed the incidence of clinical and pathologic characteristics as a function of histology and histologic grade (Table 1). We also examined the I 0-year crude rates of first failure for evaluable patients (Table 2) and calculated actuarial curves for regional nodal failure or distant metastasis (RNF/DM) at any time during followup (Figure 1). Results:
T A B L E l.
GRADE #Pts. med. age %EIC+ tubular 28 51 yr,, 32 1 219 5t 22 ll 482 52 25 III 380 47 25 p-value for gr 1,I1,111: <.(I01 .68
T A B L E 2: 1 0 - y e a r c r u d e r a t e s o f first f a i l u r e (%) # evaluable fzlg2kD_~ oadems %TR/MM %E %RNF/DM %NED tubular Ig 6 6 0 89 I 145 10 4 15 71 11 353 10 5 25 60 lIl 278 9 3 28 59 p-value= 0.03 for gr 1 vs. gr ll,IIl abbreviallong:TR/MM true recurrence/marginalmiss; E: elsewherein breast: RNF/DM: regional node failure/distantmetaslasis: NED no evidenceol disease
%LVI+ 4 ~2 38 40 .15
%Nec 0 2 13 49 <.001
%MCR+ 0 4 10 37 <.001
F I G U R E 1: A c t u a r i a l
%TI 93 72 58 43 <.001
%_<1 cm 70 34 24 II <.001
r a t e s o f a n y RNF/DM
: I _
%pLN+ 17 4I 37 39 .61
i ~
i g YEARS
: tubular fo
fs
C o n c l u s i o n s : 1) The proportion of tumors with LVI. EIC, or lymph node involvement did not vary significantly by histologic grade. Low grade tumors tended to be smaller and exhibit less MCR and necrosis; 2) Grade did not predict for local recurrence, Distant recurrence rates were significantly higher in patients with grade II or lIl as cumpared with grade I tumors, although recurrence rates continued to rise for grade 1 tumors through 10 years of followup; 3) Although patient numbers are small, tubt]lar breast carcinomas appear to have an excellent prognosis with little risk of distant recurrence up to 10 years after treatment.
Radiation Oncology, Biology, Physics Volume 32, Supplement 1
138 P A T H O L O G I C MARGIN I N V O L V E M E N T AND T H E R I S K O F R E C U R R E N C E IN P A T I E N T S T R E A T E D W I T H BREAST-CONSERVING THERAPY I r e n e G a g e 1, Asa J. Nixon 1, Stuart J. Schnitt 2, A b r a m Recht 1, Rebecca G e l m a n L Barbara Silver 1, J a m e s L. ConnoLly~, Jay R. Harris 1 tjoint Center for Radiation Therapy; 2Department of Pathology, Beth Israel Hospital; H a r v a r d Medical School, Boston, M A PURPOSE: T o assess the relationship between microscopic margin status and recurrence after breast-conserving therapy for tumors with or without an extensive intraductal c o m p o n e n t (EIC). MATERIALS A N D M E T H O D S : During the years 1968 to 1986, 1865 w o m e n with unilateral clinical stage I or II breast cancer w e r e treated with radiation therapy for breast conservation. Of these, 340 received >-60 G y to the t u m o r bed and had margins that were evaluable on review of their pathologic slides; these constitute the study population. The m e d i a n follow-up was 109 months. All available slides were reviewed by one of the study pathologists (SS, JC). Final radial margins of excision were classified as negative > 1 m m (no invasive or ductal carcinoma in-situ within 1 m m of the inked margin), negative -<1 m m (any c a r c i n o m a _<1 m m of the inked m a r g i n but not at ink) or positive (any carcinoma at the inked margin). A focally positive margin was defined as any invasive or in-situ c a r c i n o m a at the marginin s 3 LPF. T h e extent of positivity was not evaluable in 2 patients and the distance of the tumor from the margin was not evaluable in 48 patients with a negative margin. Thirty-nine percent of EIC-negative and 46% of EIC-positive patients underwent a re-excision and, for these, the final margin analyzed was from the re-excised specimen. The m e d i a n dose to the t u m o r bed was 63 Gy for patients with positive margins and 62 Gy for patients with negative margins. Recurrent disease was classified as ipsilateral breast recurrence (IBR) or distant metastasis/regional nodal failure ( D M / R N F ) . RESULTS: Five year crude rates for the first site of recurrence were calculated separately for all patients, EIC-negative and EIC-positive. All p-values tested All Pnllents Final Margin IBR p-Value DM/RNF 1111t Positive, > Focally 28% (14/50) 30% (15/50) 19% (6/31) Positive, Focally + 9% (7/79) 19% (15/79) 9% (6/65) p- 0.002 Negative g l mm 2% (1/54) 15% (8/54) 2% (1/44) Negative > 1 mm 3% (3/107) 19% (20/107) 1% (1/93) p = 0.87 All Positive 16% (Z1/131) 23% (30/1_31) 12% (12/97) All Negative 2% (41209) t7% (281209) 1% (21137) p
for 340 patients evaluable at 5 years. Results w e r e tabulated for differences in the distribution of sites of first failure. ~|~ lrlC ÷ p-Value DM/RNF [IIR p- gltlue DM/RNF 39% (12/31) 42% (8/19) 16% O/19) 20% (13/65) 7% (1/14) 14% (2/14) p-0.03 p=O,06 18% (8/44) 0% (0/10) 0% (0/10) 20% (19/93) 14% (2/14) 7% (1/14) p =0.84 p= 0.49 26% (25,/97) 27% (9/34) 15% (5/34) 20% (27/t37) 8% (2124) 4% (t/24) p
C O N C L U S I O N S : T h e risk of ipsilateral breast recurrence is equally low for patients with close (<1 ram) or negative ( > 1 ram) margins for both EIC-negative and ElC-positive cancers. These d a t a suggest that some patients with focally positive margins may also be reasonably treated with breast-conserving therapy. Patients with greater than focally positive margins (with or without an EIC) are at a significantly higher risk of failure c o m p a r e d to those with focally positive or negative margins.
139 R E L A T I O N S H I P OF T U M O R G R A D E T O O T H E R P A T H O L O G I C F E A T U R E S AND T O T R E A T M E N T O U T C O M E FOR PATIENTS WITH EARLY-STAGE BREAST CANCER TREATED WITH BREAST-CONSERVING THERAPY Asa J. Nixon 1, Irene Gage I , James L. Connolly 2. Stuart Schnill 2, Barbara Silver I , Stella Hetelekidis I , Abram Recht 1, and Jay R. Harris I l Joint Center for Radiation Therapy; 2 Department of Pathology. Beth Israel Hospital; Harvard Medical School, Boston MA P'urpo,~: To study the relationship of tumor grade to the distribution o! pathologic features and to the risk of local and distant recurrence following breast-conserving therapy in patients with pure infiltrating ductal carcinoma, and Io explore the differences between this type and tubular carcinoma. M a t e r i a l s and Methods: Between 1968 and 1986, 1624 patients were treated for clinical Stage I or II invasive breast cancer with a complete gross excision and _>60Gy to the tumor bed. The original slides were reviewed in 1337 cases (82%). Of these, 1081 were pure infiltrating ductal carcinoma and 28 were tubular carcinoma and these constitute the study population. Fifty-five patients (5%) have been tost to followup after 7-181 months. Median followup for 742 survivors is 134 months (7-278 mos.) We evaluated the following features: histologic grade (modified Bloom Richardson system), the presence of nodal metastases (in 891 pts. (80%) undergoing axillary dissection [pLN+]), an extensive intraductal component (EIC), lymphatic vessel invasion (LV1), mononuclear cellular response (MCR). and necrosis. We analyzed the incidence of clinical and pathologic characteristics as a function of histology and histologic grade (Table 1). We also examined the I 0-year crude rates of first failure for evaluable patients (Table 2) and calculated actuarial curves for regional nodal failure or distant metastasis (RNF/DM) at any time during followup (Figure 1). Results:
T A B L E l.
GRADE #Pts. med. age %EIC+ tubular 28 51 yr,, 32 1 219 5t 22 ll 482 52 25 III 380 47 25 p-value for gr 1,I1,111: <.(I01 .68
T A B L E 2: 1 0 - y e a r c r u d e r a t e s o f first f a i l u r e (%) # evaluable fzlg2kD_~ oadems %TR/MM %E %RNF/DM %NED tubular Ig 6 6 0 89 I 145 10 4 15 71 11 353 10 5 25 60 lIl 278 9 3 28 59 p-value= 0.03 for gr 1 vs. gr ll,IIl abbreviallong:TR/MM true recurrence/marginalmiss; E: elsewherein breast: RNF/DM: regional node failure/distantmetaslasis: NED no evidenceol disease
%LVI+ 4 ~2 38 40 .15
%Nec 0 2 13 49 <.001
%MCR+ 0 4 10 37 <.001
F I G U R E 1: A c t u a r i a l
%TI 93 72 58 43 <.001
%_<1 cm 70 34 24 II <.001
r a t e s o f a n y RNF/DM
: I _
%pLN+ 17 4I 37 39 .61
i ~
i g YEARS
: tubular fo
fs
C o n c l u s i o n s : 1) The proportion of tumors with LVI. EIC, or lymph node involvement did not vary significantly by histologic grade. Low grade tumors tended to be smaller and exhibit less MCR and necrosis; 2) Grade did not predict for local recurrence, Distant recurrence rates were significantly higher in patients with grade II or lIl as cumpared with grade I tumors, although recurrence rates continued to rise for grade 1 tumors through 10 years of followup; 3) Although patient numbers are small, tubt]lar breast carcinomas appear to have an excellent prognosis with little risk of distant recurrence up to 10 years after treatment.