Ten year results of conservative surgery and irradiation for stage I and II breast cancer

Inr J Rudiarion Oncolog?, Bwi Phyv Vol. 21, Pnnted I” the U.S.A All rights reserved.

0360-3016191 $3.00 + .oO Copyright C. I99 Pergamon Press plc

pp.269-277

I

l Original Contribution

TEN YEAR RESULTS OF CONSERVATIVE SURGERY AND IRRADIATION FOR STAGE I AND II BREAST CANCER BARBARA L. FOWBLE, M.D., * LAWRENCE J. SOLIN, M.D.,’ DELRAY J. SCHULTZ, AND ROBERT L. GOODMAN, M.D.’

M.A.*

‘Department of Radiation Oncology, University of Pennsylvania School of Medicine, and the Fox Chase Cancer Center: and ‘Department of Statistics, University of Pennsylvania Cancer Center, Philadelphia, PA Between 1977 and 1985,697 women with clinical Stage I or II invasive breast cancer underwent excisional biopsy, axillary dissection, and definitive irradiation. Reexcision of the primary was performed in 330 and residual tumor was identified in 57% of these patients. Margins of resection were assessed in 50% and 257 had final margins of resection that were negative. Four hundred eighty patients had negative axillary dissections and 217 had histologically positive axilhuy nodes. Median follow-up was 58 months. The IO-year actuarial survival for the entire group was 83% with an NED survival of 73%. The IO-year actuarial survival was 87% for clinical Stage I and 77% for clinical Stage II patients with an NED survival of 79% and 67%, respectively. Patients with histologically negative axillary nodes had a IO-year overall survival of 86% (NED 78%) compared to 74% (NED 66%) for patients with positive nodes. Sixty-one patients developed a recurrence in the treated breast and in seven of these it was associated with simultaneous distant metastases. The cumulative probability of an isolated breast recurrence was 6% at 5 years and 16% at 10 years. The overall breast recurrence rate (? distant metastasis) was 8% at 5 years and 18% at 10 years. Breast recurrence was unrelated to T size, clinical stage, or histologic nodal status. The addition of adjuvant chemotherapy significantly decreased the risk of an isolated breast recurrence both at 5 and 10 years; however, there was no significant impact on the overall risk of a breast recurrence. Complications of treatment included moderate arm edema (5%), symptomatic pneumonitis (less than 1%), rib fraction (l%), pericarditis (O%), and brachial plexopathy (less than 1%). Cosmesis was judged to be good to excellent in 93% of patients in 10 years. These results have been achieved in a series of patients who for the most part have been treated by contemporary standards, that is, pathologic assessment of the axilla in all patients, reexcision in 47%, and adjuvant chemotherapy in 77% of node positive patients. Assessment of resection margins, however, was not performed in all patients (50%) and further follow-up in the group of patients with margin assessment will provide long term information on breast recurrence rate in this group of patients. Breast recurrence, Radiation therapy.

that is, 110 years. Two prospective randomized trials have reported 10 year results (44, 52). However, in one (44) of these, adjuvant chemotherapy was not used for node positive patients. Veronesi (5 1) recently reported an update of the Milan trial with follow-up to 17 years. Several retrospective series (8, 10, 12, 2 1, 23, 26, 36, 37, 43,47, 48, 50, 54) have reported lo- and 15-year results; however, in the older series pathologic staging of the axilla was not routinely performed (8, 10, 21, 23, 36, 47) and adjuvant chemotherapy was either not given (12, 2 1, 47) or infrequently used in node positive patients (8,23). The purpose of this report is to present the lo-year results of conservative surgery and radiation for Stage I and II breast cancer in a relatively contemporary series in which all patients

INTRODU(X’ION

The results of six prospective randomized trials (4, 16, 20, 22, 44, 45, 49, 52) have established conservative surgery and radiation as an alternative equal to mastectomy in terms of local-regional recurrence and overall and disease-free survival for the treatment of early invasive breast cancer. In addition, the recent NIH Consensus Development Conference on early stage breast cancer concluded that breast preservation is preferable to mastectomy in appropriately selected patients since it provides equivalent survival and preserves the breast (34). Despite these findings, some physicians are reluctant to accept the conservative approach without data regarding long term results,

Presented at ASTRO October 1990.

Accepted for publication

Reprint requests to: Barbara Fowble, M.D., Dept. Radiation Oncology, Hosp. Univ. of Pennsylvania, 3400 Spruce St., Phila., PA 19104. 269

25 January

199 1.

270

1. J. Radiation Oncology 0 Biology0 Physics

had an excisional biopsy and axillary node dissection and 77% of node positive patients received adjuvant multiagent chemotherapy. METHODS

AND MATERIALS

Between 1977 and 1985,697 women with AJC clinical Stage I and II (1) breast cancer underwent excisional biopsy, a level I-II axillary dissection, and definitive irradiation at the University of Pennsylvania and Fox Chase Cancer Center. Guidelines for patient selection, surgical and radiotherapeutic techniques, and 5-year results have been reported elsewhere (46). Patients characteristics are present in Table 1. The median age of the patient population was 51 years with a range of 22 to 85 years. Four hundred eleven patients had Table 1. Patient characteristics No. pts. Total no. pts. Menopausal status Pre-menopausal Peri-menopausal Post-menopausal Clinical tumor size Tl T2 Pathology Intraductal and invasive ductal Invasive ductal Lobular Medullary Ductal/lobular Colloid Other Surgery for primary tumor Excisional biopsy Re-excision Positive Negative Final margin assessment Unknown Negative Close Positive Estrogen receptor status Positive Negative Not done/unknown Progesterone receptor status Positive Negative Not done/unknown Axillary dissection Pathologic nodal status Negative Positive l-3 24 Adjuvant chemotherapy Node negative Node uositive

697 291 51 255 411 286 251 346 33 26 14 10 17 697 330 189 141 346 257 37 57 341 136 220 245 157 295

480 217 168 49 185 17 168

July 1991, Volume 21, Number 2

clinical Tl tumors and 286 had clinical T2 tumors. The median follow-up was 58 months with a range of 2 to 137 months. The number of patients at risk for 5, 8, and 10 year follow-up is 33 1, 77 and 14, respectively. All patients underwent an excisional biopsy. For the most part this represented a wide excision with removal of a rim of normal adjacent breast tissue. Three hundred thirty patients (47%) underwent reexcision and in 189 patients reexcision revealed residual tumor. The final status of the resection margin was unknown in 346 patients (50%). For 35 1 patients, inking of the surgical specimen was performed and the final margins were microscopically assessed. Two hundred fifty-seven patients had negative margins of resection, that is, >2 mm, 37 patients had close margins of resections, that is, 12 mm, and 57 patients had positive margins of resection with tumor at the resection margin. Histology of the primary tumor consisted of 25 1 patients with an intraductal and invasive ductal cancer, 346 patients with an invasive ductal carcinoma, 33 patients with an infiltrating lobular carcinoma, 14 patients with an infiltrating ductal and infiltrating lobular carcinoma, and 53 patients with miscellaneous histologic types including medullary, colloid, tubular, and papillary carcinomas. Estrogen receptor status was known in 477 patients of which 34 1 were positive and 136 were negative. Progesterone receptor was positive in 245 patients and negative in 157. It was unknown for 295 patients. All patients underwent a level I-II axillary node dissection. The median number of nodes removed was 15 with a range of 1 to 75. Four hundred eighty patients had histologically negative axillary nodes and 2 17 patients had positive axillary nodes. One hundred sixty-eight patients had 1 to 3 positive nodes and 49 patients had 4 or more positive nodes. In general, radiotherapy consisted of treatment to the entire breast with tangential fields to a total dose of 4600 to 5000 cGy delivered in 180 to 200 cGy fractions over a period of 41 to 5 weeks. The regional nodes received 4600 to 5000 cGy delivered over a period of 41 to 5 weeks. A 6 MV linear accelerator was used. The primary site was boosted with either electrons, external beam therapy, or an iridium 192 implant to an additional dose of 1400 to 2000 cGy. Of the 480 patients with histologically negative axillary nodes, treatment was directed to the breast only in 440 and to the breast and regional nodes in 40 patients. Three hundred thirty-seven of these patients had a boost with electrons, 123 a boost with an implant, and 11 had a boost treatment delivered with further external beam therapy. Nine patients had no boost. Of the 2 17 patients with positive axillary nodes, 19 1 received treatment to the breast and regional nodes and 26 received treatment to the breast only. One hundred fifty-three of these patients received boost treatment with electrons, 46 with an implant and 16 with external beam therapy. Two patients received no boost.

IO year results of conservative surgery and radiation 0 B. L.

Chemotherapy consisted of cyclophosphamide 100 mg/ m2 po, days 1 through 14, methotrexate 40 mg/m2 IV days 1 and 8, Huorouracil 600 mg/m’ IV days 1 and 8 (CMF) with or without prednisone 40 mg/m* days 1 through 14 of a 28-day cycle for a total of 6 to 8 cycles. One hundred eighty-five patients received adjuvant systemic chemotherapy, and in 178 it consisted of CMF with or without prednisone. Seven patients received cyclophosphamide 100 mg/m2 po days l-l 4, Adriamycin 30 mg/m2 IV days 1 and 8, and 5-fluorouracil 500 mg/m’ IV days 1 and 8 (CAF). Chemotherapy was given concurrently with radiation in 162 patients. During irradiation methotrexate and Adriamycin were omitted and 2 cycles of cyclophosphamide and 5-fluorouracil were given. Twenty-three patients received sequential treatment with chemotherapy given first. Twenty patients received adjuvant Tamoxifen alone (10 mg pobid). Seventeen of the 480 patients (4%) with histologically negative axillary nodes received adjuvant chemotherapy. This included 14 of 198 premenopausal patients, none of 33 perimenopausal, and 2 of 249 postmenopausal patients. One hundred sixty-eight of the 217 patients (77%) with histologically positive axillary nodes received adjuvant chemotherapy. This included 86 of 93 premenopausal patients, 15 of 18 perimenopausal patients, and 67 of 106 postmenopausal patients. Results are presented in terms of breast recurrence, overall, no evidence of disease (NED), and relapse-free (RFS) survival, complications, and cosmesis. An isolated breast recurrence was defined as first site of recurrence in the treated breast without associated simultaneous clinically apparent regional node involvement or distant metastases. The overall breast recurrence rate was defined as first site of recurrence within the treated breast with or without simultaneous regional node involvement or distant metastasis. For analysis of NED survival, patients were required to be alive and without evidence of disease at the time of last follow-up. For analysis of relapse-free survival, patients were required to be alive and continuously without evidence of disease. Patients who relapsed and subsequently underwent salvage therapy and were alive without evidence of disease were considered a failure for relapse-free survival but not NED survival. Survival curves and actuarial rates of breast recurrence were calculated using the Kaplan Meyer method (28) for a time period beginning at the onset of definitive radiotherapy. Statistical comparisons between curves were performed using the Mantle-Cox test (33). Statistically significant differences were conferred by p values of 10.05. RESULTS

Sixty-one of the 697 patients developed a breast recurrence as the first site of failure. In 48 patients this was confined to the breast only; in 6 patients there was also clinical evidence of regional node involvement (i.e., axillary or supraclavicular nodes), and in 7 patients the breast

211

FOWBLE el al.

recurrence was associated with simultaneous distant metastases with or without regional node involvement. The location of the breast recurrence was recorded in 58 patients. In 28 patients the recurrence was located in the vicinity of the original primary tumor (true recurrence), in 15 patients it was adjacent to the original primary tumor or in the same quadrant (marginal recurrence), and in 15 patients it was in the separate quadrant (elsewhere). Three patients had diffuse involvement of the breast. The 5- and 1O-year actuarial rates of breast recurrence are presented in Table 2. For all patients, the lo-year actuarial rate of an isolated breast recurrence was 16%. The overall loyear actuarial rate of a breast recurrence including patients who presented with simultaneous distant metastasis was 18%. Breast recurrence at 5 and 10 years was unrelated to tumor size; however, T 1 tumors tended to have a higher but not significantly increased risk of breast recurrence. Breast recurrence was also unrelated to histologic nodal status when comparing patients with negative versus positive nodes. The addition of adjuvant chemotherapy was associated with a significant decrease in the risk of an isolated breast recurrence; however. there was no impact on the overall risk of a breast recurrence. A separate analysis was then performed for the risk of a breast recurrence in patients with negative margins of resection and those with unknown margins of resection (Table 3). The division of patients into these two groups resulted in a smaller number of patients at risk at 10 years, and therefore, the actuarial analysis was limited to 8-year results. The S-year actuarial risk of an isolated breast recurrence was 13% in the 257 patients with negative margins of resection, and the overall risk of a breast recurrence was 14%. Breast recurrence in patients with negative margins of resection was unrelated to tumor size, pathologic nodal status, and the addition of adjuvant systemic chemotherapy. The 8-year actuarial risk of an isolated breast recurrence was 15% in the 346 patients with unknown margins of resection, and the overall risk of a breast re-

Table 2. Breast recurrence following conservative surgery and radiation for Stage I and II breast cancer Breast only

All pts. Tumor size TI T2 p value Path nodal status NO NI

p

5 yr

10 yr

5 yr

IO yr

6

16

8

18

6 6

18 12

8 8

20 14

.68 7 5

value

Chemotherapy No Yes p value

Breast f DM

.52 16 18

8 7

.33 7 1

.60 17 15

.028

18 21

9 5

19 19 .15

1. J. Radiation Oncology 0 Biology 0 Physics

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July 1991. Volume 21, Number 2

in patients with unknown or negative margins of resection

Table 3. Breast recurrence

8 yr. actuarial breast recurrence %

Negative margins Tumor size Tl T2 p value Path nodal status NO Nl p value Chemo Yes No p value Unknown margins Tumor size Tl T2 p value Path nodal status NO Nl p value Chemo Yes No p value

No. pts.

Breast

257

13

ALL

PATIENTS

‘Z\_________

b

Breast + DM 14

50 40

162 95

I5 8

17 8 .58

30

.25

20 10 i

185 72

13 12 .73

15 14 .74

60 197

10 13

346

15

17

201 145

I5 14

17 16

16 I1

.99 18 15

.43 101 245

5 18

.61 9 20

.02

FROM

TREATYENT

(VRS.)

.95

.96 233 113

TIME

Fig. 1. Overall (OS), no evidence of disease (NED), and relapsefree survival (RFS) for all patients.

12 15 .98

O!--T--Yo

.09

currence in this group was 17%. In patients with unknown margins of resection, breast recurrence was unrelated to tumor size or pathologic nodal status. The addition of adjuvant systemic chemotherapy resulted in a significant decrease in the incidence of isolated breast recurrence and a nonsignificant decrease in the risk of overall breast recurrence. The number of patients with close or positive margins of resection was small, and factors correlating with breast recurrence in these patients is the topic of a separate report. The pattern of breast recurrence was related to the interval to recurrence. Forty-five recurrences occurred within 5 years with 16 occurring beyond 5 years. For recurrences occurring within 5 years, 62% had initial Tl lesions (28 patients) and 74% were true or marginal (34 patients). For recurrences occurring after 5 years, 8 1% had an initial T 1 tumor size ( 13 patients) and 40% were true or marginal in location (4 patients). The location of the recurrence was unknown in 5 patients. Actuarial overall, NED, and relapse-free survival are presented in Figures 1 through 4. For all patients the loyear actuarial overall, NED, and relapse-free survival were 83%, 73%, and 61%, respectively. For patients with histologically negative axillary nodes the IO-year actuarial overall, NED, and relapse-free survival were 86%, 78%, and 65%, respectively. For patients with histologically positive axillary nodes the 1O-year actuarial overall, NED,

and relapse-free survival were 74%, 66%, and 5 l%, respectively. The IO-year actuarial overall, NED, and relapse-free survival for patients with clinical Stage I disease were 87%, 79%, and 63%, respectively. For patients with clinical stage II disease the IO-year actuarial overall, NED, and relapse-free survival were 77%, 67%, and 59%, respectively. The difference between survival curves for clinical Stage I patients when compared to clinical Stage II patients was statistically significant (p = .002 overall survival, p < .OOOl NED survival, p = .002 relapse-free survival). For patients with pathologic Stage I disease the lo-year actuarial overall, NED, and relapse-free survival were 88%, 82%, and 66%, respectively. For patients with pathologic Stage II disease, the IO-year actuarial overall, NED, and relapse-free survival were 77%, 65%, and 56%, respectively. Again, the differences between these survival curves were statistically significant (p = .007 overall survival, p < .OOO1 NED survival, and a = .003 relapse-free survival).

PATH No

0

5 TlYE

FROY

TREATMENT

10 (VW.)

Fig. 2. Overall (OS), no evidence of disease (NED), and relapsefree survival (RFS) for patients with histologically negative axillary nodes.

10 year results of conservative surgery and radiation 0

B.

L. FOWBLE

et al.

213

DISCUSSION

The results presented are those from a relatively contemporary series in which all patients underwent excisional biopsy and axillary dissection. Reexcision of the primary tumor site was performed in 47% of patients, and

o!

.

.

.

1

0

.

.

,

10

5 TIME

FROM

TREATMENT

(VRS.)

Fig. 3. Overall (OS), no evidence of disease (NED), and relapsefree survival (RFS) for patients with histologically positive axillaiy nodes.

The most common complication following treatment was moderate to severe arm edema, which occurred in 5% of patients. This was defined as arm edema 2 2.5 cm or permanent edema. Five patients developed symptomatic pneumonitis, eight patients had a rib fracture, two patients developed brachial plexopathy, and there were no instances of pericarditis. Cosmesis was assessed at 5 and 10 years. A physician assessment cosmetic score as initially suggested by Harris et al. (64) was used. The overall cosmetic score was deemed excellent if the treated breast was almost identical to the untreated. A score of good recognized differences between the treated breast and untreated breast that were slight. A fair cosmetic result indicated that there were obvious differences between the treated and untreated breast and a poor cosmetic result was associated with marked distortion of the treated breast. At 5 years 9 1% of the patients had a good to excellent cosmetic result and 9% had a fair to poor cosmetic result. At 10 years 93% of the patients had a good to excellent cosmetic result and 7% had a fair to poor cosmetic result.

CLINICAL

STAGE

4 ;I

I VS. STAGE II

, .

0

5 TIME

FROM

TREATYENT

, IO

(YRS.)

Fig. 4. Overall (OS), no evidence of disease (NED), and relapsefree survival (RFS) clinical Stage I and clinical Stage II patients.

50% had microscopic margin assessment of the biopsy specimen. Seventy-seven percent of all node positive patients received multiagent adjuvant systemic chemotherapy. There are only two other comparable series with loyear results reported in the literature, and both of these are limited to Tl tumors (52, 54). The first consists of the Milan prospective randomized trial comparing quadrantectomy, axillary dissection, and radiation to radical mastectomy (5 1,52, 53, 55). In this trial all patients underwent quadrantectomy and complete axillary node dissection. Seventy-six percent of node positive patients received adjuvant CMF chemotherapy for 12 cycles. In a separate report, Veronesi et al. (54) reported the long term results of 1232 patients with Tl NO- 1 MO carcinoma of the breast treated with quadrantectomy, axillary dissection, and radiotherapy. This series included the 352 patients who had been entered into the prospective randomized trial as well as 880 patients routinely treated in a similar manner outside the trial. All patients underwent quadrantectomy and axillary node dissection, and 78% of node positive patients received adjuvant systemic chemotherapy consisting of CMF for 6 or 12 cycles or CMF combined with Adriamycin in an alternating scheme. A single additional prospective randomized trial has reported loyear results of conservative surgery and irradiation (44) although none ofthese patients received adjuvant systemic chemotherapy. Multiple retrospective series have reported lo- and 15-year results of conservative surgery and irradiation; however, axillary node dissection has not been used in all patients (8, 2 1, 23, 26.43,47,48), or adjuvant chemotherapy has been omitted or infrequently used in histologically node positive patients ( 12, 2 1, 23, 37, 47). The IO-year actuarial risk of an isolated breast recurrence was 16% with an overall IO-year actuarial risk of breast recurrence of 18%. These results are compared to others in the literature in Table 4. Overall the IO-year actuarial risk of a breast recurrence ranges from 8 to 20%. Note that the IO-year actuarial risk of a breast recurrence for patients with T 1 lesions undergoing quadrantectomy was recently reported by Veronesi ef al. (54) as 12.5%. The lack of correlation between tumor size, that is, Tl versus T2 tumors, and breast recurrence in patients undergoing excisional biopsy and irradiation was noted in the present series and has also been reported by others (6, 7, 9, 20, 35, 47). In the present series Tl tumors tended to have a somewhat higher risk of breast recurrence, although it was not statistically significant. This finding has been reported by Eberlein et al. (15) and by Clark et al. (9). Eberlein et al. (15) reported the highest crude breast recurrence rate for tumors 5 1 cm. The authors suggested that this finding was partially related to the fact that 4 of

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I. J. Radiation Oncology 0 Biology 0 Physics

Table 4. 10 year actuarial breast recurrence following conservative surgery and radiation for Stage I and II breast cancer

Veronesi et al. (54) Haley et al. (23) Stotter et al. (48) Fourquet et al. (2 1) Sarrazin et al. (43) Recht et al. (39) Clark et al. (8) Kurtz et al. (29) Present series Q = quadrantectomy;

No. pts.

Tumor size

1232 278 490 518 592 607 1130 1593 697

Tl TI, T2 Tl, T2 Tl,T2 Tl, T2 Tl,T2 TI-T4 TI, T2 Tl,T2

Surgery for primary

Q LE. WE LE, WE WE LE, WE LE LE, WE LE, WE WE

10 yr act. breast recurrence % 12.5 20 19 11 8 16 14 14 18

LE = local excision; WE = wide excision.

these patients had an extensive intraductal component. There is no obvious explanation for the higher risk of breast recurrence for T 1 tumors in the present series. This finding persisted even in patients with negative margins of resection (Table 3). In the present series, breast recurrence was also unrelated to the pathologic status of the axillary nodes for all patients as well as those with negative margins of resection or unknown margins of resection. This finding has also been reported by others (3, 9, 13, 20, 39, 50). The addition of adjuvant systemic chemotherapy significantly decreased the risk of an isolated breast recurrence; however, there was no impact on the overall risk of a breast recurrence, that is, with or without simultaneous distant metastasis. For patients with negative margins of resection, the 8-year actuarial risk of an isolated breast recurrence was 13% in patients who did not receive chemotherapy compared to 10% in those who did (p = .98). In the NSABP B-06 prospective randomized trial, all patients had negative margins of resection, and the 8year actuarial risk of a breast recurrence was 12% in patients who did not receive chemotherapy and 6% in those who did (20). In the NSABP B- 13 trial evaluating systemic chemotherapy (sequential methotrexate and 5-fluorouracil) for histologically node negative, estrogen receptor negative patients ( 18), the breast recurrence rate in patients who underwent conservative surgery and irradiation with adjuvant chemotherapy was 1% compared to 4% in those who did not receive chemotherapy. Rose et al. (4 1) reported a 17% breast recurrence rate in premenopausal women undergoing conservative surgery and irradiation who did not receive adjuvant systemic chemotherapy compared to a 5% rate in patients who received adjuvant systemic chemotherapy. As presented in Table 4 the overall IO-year actuarial risk of a breast recurrence for Stage I and II breast cancer following conservative surgery and irradiation ranges from 8 to 20%. The question arises as to whether this is higher than the local recurrence rate for similarly staged patients undergoing mastectomy. Unfortunately mastectomy series infrequently present local recurrence rates at 10 years,

July 199 1, Volume 2 1, Number 2

and where data are available they are often crude, not actuarial, and frequently include T3 primary tumors. Table 5 presents lo-year local recurrence rates following radical and modified radical mastectomy for early breast cancer. Note that the crude and actuarial rates are similar to the IO-year actuarial risk of a breast recurrence for patients undergoing conservative surgery and irradiation. Also two prospective randomized trials comparing conservative surgery and irradiation to mastectomy have found no significant difference in local regional recurrence at 10 years (44, 53, 54, 55). The 8-year actuarial risk of an isolated breast recurrence in patients with negative margins of resection was 13% with an overall risk of 14%. Breast recurrence in patients with negative margins of resection was unrelated to the histologic nodal status, the addition of adjuvant systemic chemotherapy, and primary tumor size. Zafrani et al. (56) reported a IO-year actuarial risk of breast recurrence of 9% in patients with negative margins of resection. Kurtz et al. (30) reported an 8% breast recurrence rate in 283 patients with negative margins of resection with a median follow-up of 5.9 years. Fisher et al. (20) reported an 8year actuarial breast recurrence rate of 10% in 629 patients with negative margins of resection. These patients were entered in the NSABP B-06 prospective randomized trial and were randomized to conservative surgery and radiation. In this trial radiation was given to the breast only and a boost was not used. The 10% 8-year breast recurrence rate in this trial compares favorably to the 13% 8year actuarial risk in the present series. However, in the current series a boost dose of radiation was routinely used. This raises the question as to the value of the boost in patients with negative margins of resection. The European Organization for Research in Treatment of Cancer (EORTC) has initiated a prospective randomized trial for patients with primary tumors I 3 cm in diameter with either clinically positive or negative axillary nodes. Patients with negative margins of resection are randomized to boost with either electrons or iridium 192 versus no Table 5. 10 year local recurrence radical mastectomy

following radical or modified for early breast cancer 10 yr local recurrence %

Host et al. (27) Easson ( 14) Rutqvist et al. (42) Donegan (I 1) Maddox et al. (32) Fisher et al. ( 19) Fisher et al. ( 17) Bonadonna et al. (5)

No. pts.

Tumor size

264 527 321

Tl, T2 Tl-2 Tl-3, NO

362 175

TI-T3 TI-3

362 292 380

Tl-3, Tl-3, Tl-3, Lpam Tl-3, CMF

386

Crude

Actuarial

15 16 23 18 12

NO Nl Nl Nl

10 20 24 14 14 12

275

IO year results of conservative surgery and radiation 0 B. L. FOWBLE et al.

Table 6. 10 year overall survival in patients undergoing conservative surgery and radiation for early breast cancer 10 yr act. survival % No. pts. Hamy et al. (23) Clark et al. (8) Stotter ef al. (48) Harris et al. (26) Veronesi et al. (54) Van Limbergen et al. (50) Dubois et al. ( 12) Sarrazin et al. (43) Fourquet et al. (2 1) Delouche et al. (10) Pierquin et al. (36, 37) Spitalier et al. (47) Present series

I

I & II

II

278

73

58

456 490

71 78

62 65

525 1232 235 292 592 518 410 1200 1133 697

85 78

57 61

87

:: 86 62 67 80 83

77

boost. Preliminary results from this trial (40) show no difference in terms of breast recurrence. Further analysis and long term follow-up of these results will help to resolve this question. Breast recurrences occurring after 5 years in the present series were more likely to have had an initial Tl clinical tumor size. Kurtz et al. (3 1) reported that 58% of recurrences after 5 years had an initial Tl tumor size. In the present series, 50% of recurrences after 5 years were elsewhere in location. Kurtz et ul. (31) reported that 32% of recurrences after 5 years were elsewhere, and Recht et ul. (39) reported that 27% of recurrences at 10 years were elsewhere. In the present series, the IO-year actuarial overall survival was 83% for all patients and 87% for clinical Stage 1 and 77% for clinical Stage II. These results are compared to others in the literature in Table 6. The overall survival is quite comparable to that reported by other series (12, 2 1, 43, 47). However, the survival for Stage II patients appears improved compared to those that reported by Harris et al. (26), Stotter et al. (48), Clark et al. (8), and HafTty et al. (23). This may reflect the use of adjuvant systemic chemotherapy in 77% of node positive patients, the majority of whom had 1 to 3 positive nodes. The lo-

Table 7. Complications Univ of PA Total no. pts. Complications Arm edema Symptomatic pneumonitis Rib fracture Pericarditis Brachial plexopathy

697 5*
year actuarial NED and relapse-free survival were 73% and 63%, respectively, in the present series. The difference between these two primarily reflects the salvagibility of an isolated breast recurrence. For patients with histologically negative axillary nodes, the 1O-year overall and NED survivals were 86% and 78% compared to 74% and 66% for patients with positive axillary nodes. The Milan trial reported a IO-year actuarial overall survival of 73% for patients with T 1 tumors and histologically positive axillary nodes who underwent quadrantectomy and axillary dissection with 12 cycles of CMF (52). For patients with negative axillary nodes the lo-year actuarial overall survival was 82% (52). Both the Milan trial (52) and the Institut Gustave-Roussy trial (44) have demonstrated no difference in 1O-year overall or disease-free survival when comparing conservative surgery and irradiation to mastectomy. The most common complication following conservative surgery and irradiation for early breast cancer in the present series was arm edema. Moderate to severe arm edema occurred in 5% of patients who underwent a level I-II axillary node dissection. Complications in the present series are compared with those reported from other series in Table 7. As can be seen, the most common complication is arm edema with the incidence of symptomatic pneumonitis, rib fracture, pericarditis, and brachial plexopathy being overall less than 2 to 3%. Cosmesis was judged to be good to excellent in 9 1% of patients at 5 years and 93% at 10 years. Two additional series have reported excellent cosmetic results of 84% (3) and 86% (2). In older series, a 70% good to excellent cosmetic result has been reported (7, 36, 38, 47) and this may reflect the radiotherapy technique used. In summary, in this relatively contemporary series conservative surgery and irradiation have achieved excellent cosmesis and IO-year overall and NED survivals with minimal complications. The 1O-year actuarial overall breast recurrence rate of 18% is comparable to that reported by others and partially reflects the results in patients treated early in the study in whom reexcision was not performed and margins were not routinely assessed. Further follow-up in the group of patients with margin assessment will provide long term information on breast recurrence rates in this group of patients.

following conservative surgery and radiation for early breast cancer

JCRT (25)

MDA (48)

Yale (38)

IGR & Hem? Mondor (37)

735

536

179

330

13* 1 3
* Arm edema in patients undergoing axillary dissection.

8 5 3 -

-

Centre Charlesbourg (10) 494

5 2


-

9 -

0

0
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I. J. Radiation Oncology 0 Biology0 Physics

July 1991, Volume 21, Number 2

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