454
Journal of the Royal Society of Medicine Volume 85 August 1992
Loco-regional recurrence and survival, after wide local excision, radiotherapy and axillary clearance for early breast cancer
C Hamilton FRCR R Carpenter MS FRCS G T Royle MS FRCS M Cross R Buchanan FRCR FRCP I Taylor MD FRCS Untversity Surgical Unit and Department of Radiotherapy, Royal South Hants Hospital; Graham Road; Southampton Keywords: breast cancer; conservation surgery; local recurrence; axillary clearance
Summary After breast conservation for early breast cancer which comprised wide local excision, axillary clearance and radiotherapy to the breast, 145 women have been followed prospectively for a median of 42 months. Local recurrence occurred in 11 (7%) and axillary recurrence in three (2%). Distant recurrence has occurred in 32 and accounted for 80% of all first recurrences. Local treatment failure has occurred in three women and would not have been prevented by mastectomy. Loco-regional recurrence in the absence of preceding or synchronous distant disease was unusual and did not pose a significant clinical problem. Introduction Breast conservation does not prejudice survival of women with early breast cancer'. However, controversy persists regarding 'what constitutes adequate loco-regional disease control and most recently this has centred on the surgical treatment of the axilla2. Loco-regional recurrence rates after conservation surgery vary from 8% in prospective studies"3 to 21% in a recent retrospective review4. These studies differ in that in the former the axilla was surgically cleared, in the latter, node sampling was undertaken. Since 1983 the policy in Southampton has been to offer women with early breast cancer conservation surgery which consists of wide local excision and axillary clearance together with radiother,apy to the breast. Selection is based on simple clinical and mammographic criteria and we report the results of a prospective follow-up -of patients over the years 1983-1990. Patients and methods Indications for conservation surgery were a tumour less than 5 cm in maximum clinical dimension which was freely mobile in the breast and unifocal on mammography. Single mobile axillary nodes were not a contraindication to conservation surgery; however, central lesions or those which involved the nipple were considered unsuitable. All patients were assessed clinically by mammography and by aspiration cytology and a diagnosis made by a combination of all three modalities. After diagnosis, women were
offered a choice of treatment by conservation surgery or mastectomy. One hundred and forty-five women have been followed-up between 1983 and 1990. Conservation treatment consisted of macroscopic clearance aiming to provide at least a centimetre of non involved breast tissue around the tumour. The excision was routinely taken to include the pectoral fascia although it did not constitute a segmental excision. Either by the same or more commonly a separate incision the axillary contents -were cleared below the level of the axillary vein 'and included the apical lymph node. Pectoralis minor was not routinely divided. Subsequently the women underwent radiotherapy to the breast to a total dose of 5000 rads delivered over a 5-week period. Women older than 50 were commenced on adjuvant tamoxifen 20 mg daily, women younger than 50 with positive nodes were offered adjuvant chemotherapy. All women were reviewed at 3 monthly intervals for the first 2 years, 6 monthly intervals for the -next 2 years and subsequently -annually. Data was recorded prospectively. At first recurrence screening inve*tigations of bone scan, liver scan and chest Xrays were undertaken.
Results One hundred and forty-five women underwent conservation surgery between 1983 and 1989. The median follow-up for the group is 42 months (12-72). The median age was 54 years (19-77) and the median tumour size was 2 cm (0.5-5) Thirty-six per cent of the group were premenopausal; 34% were node positive.9-; Overall survival by life table analysis at6years was 47% 52% and disease free survivalfor the sami6-rod -(Figures 1 and 2). Of all fils recurrenc2 (80%) were at distant sites. Loco-regional recurrence occurred in 16 (11%). Isolated loco-regional recurrence 100 I-
III
n
N- 145
I
40
d 20
0141-0768/92
080454-03/$02.00/0 Correspondence to: Mr R Carpenter, 1st Floor Surgical, St Bartholomew's Hospital, West Smithfield, London EClA 7BE
2
4
TIME (YEARS)
Figure 1. Survival
a
a
1
1992
i) Royal EThe
Society of Medicine
Journal of the Royal Society of Medicine Volume 85 August 1992 Table 2. Pattern of recurrence, local and distant disease (n=10)
JooI
Ls
Z
1st distant
1st local/regional
Synchronous
2
2
6
m m
a v
Bo
J.-
a
2
N- 14S
o 40
" 40
w I.-
n x :3
u
20
2
10
4
J°e
TIM E ( YEARS )
Figure 2. Recurrence free survival
occurred in six (4%), five withir i the breast, and one in the ipselateral axilla (Table 1L). In 10 further cases of loco-regional recurrence tblere was associated distant disease. In those with b oth loco-regional and distant recurrence, local recurr ence occurred first in only two; in the remainder dist;ant disease occurred first or was synchronous wilth local recurrence (Table 2). Loco-regional treatment fail ure or uncontrolled disease occurred in three cases. In two this involved both supra clavicular fossae aind in one there was synchronous recurrence of diseEase in the ipsilateral and contralateral breast. In allI three cases distant disease occurred rapidly and miedian survival after loco-regional recurrence in this group was 9 months. Of those with loco-regional recgurrence, six women underwent mastectomy and t;he remainder were treated by local excision irncluding the three recurrences within the ipsilate ral axilla. Outcome after recurrence is se(en in Table 3. Median time to death after distant recur rence was 10 months (0-30) and 14 months (3-45) in the group with both local and distant recurrence. Seventeen premenopausal node positive women received adjuvant chemotherapy and 96 postnnenopausal women received tamoxifen. The median hospital stay for tthe group was 5 days (4-8) 24 seromas required aspirattion as an outpatient procedure. There have been nLo cases of clinically disabling lymphoedema. Discussion The most recent controversy surrounding breast conservation surgery has cent red on the need for axillary clearance2. Opinions vw ary but impressed by low regional recurrence rates of 3% following axillary clearance in prospective studies in both America and Italy'4 this form of regional co: ntrol was adopted in Southampton in 1983. Findings of low regional reci arrence rates in this series support this choice. Ther e have been no cases of treatment failure in the axilla and all three axillary recurrences were amenable to E simple local surgery. Comparison between series is toebe used with caution however, loco-regional recurre nce rates of 22% in Table 1. Recurrence after breast Distant
Local
24 (16.6%) 5 (3.4%)
co
Regional 1!oco-regional & distant 1 (0.7%)
1L0 (6.9%)
specialist centres where node sampling only has been employed would seem to indicate that prevention of ,recurrence is both possible and desirable3. While hospital stay is longer for conservation surgery involving axillary clearance than lumpectomy and node samnpling the vast majority of our patients were managed on a 5-day surgical ward. The argument that axillary clearance has significant morbidity was not borne out by the study and objective assessment of arm swelling has shown no significant lymphoedema5. This compares favourably with other studies where objective assessments of lymphoedema have been undertaken6. As a result of our policy to clear the axilla surgically, radiotherapy planning has been simplified since only the breast is irradiated. We have also gained accurate data on nodal status and in 17 premenopausal women with positive nodes we have been able to offer adjuvant chemotherapy. None of those with histologically-proven lymph node metastases had clinically involved lymph nodes. Since axillary node sampling has been shown to be unreliable7-9 and current techniques to image nodal metastatic disease are insufficiently sensitive01ll, these women might not have been offered adjuvant chemotherapy if they had not undergone axillary clearance. We would therefore support recent advocates of axillary clearance on the basis that currently only axillary clearance gives sufficient information to allow selection of adjuvant chemo-
therapy
2
.
Local recurrence in the breast occurred in 11 (7.6%) cases. In five of these cases, however, there was preceding or synchronous distant disease and those with such combination of disease died a median of 10 months after recurrence. Those without associated distant disease remain well without evidence of disease at a median follow-up of 17 months (3-25) after recurrence. Six of the 11 with local recurrence underwent mastectomy and the remainder further local excision. In an attempt to determine factors which might predict those women likely to develop local recurrence after conservation surgery retrospective studies have analysed local recurrence patterns3. One such study derived an index based on clinical and pathological factors and advocates more radical local surgery in some cases3. Analysis of our data would indicate that such an approach (which is not 100% selective) might result in a mastectomy in women who subsequently rapidly succumbed to associated distant disease. Further, since there is a finite risk of locoregional recurrence after mastectomy in the order of
5%1, a more radical approach would not guarantee freedom of local recurrence. Such indices therefore must take into account the pattern of distant recurrence as well as local and regional recurrence before they can be applied clinically to select patients for breast conservation. Local recurrence while not desirable will never be
completely
eliminated and
viewed against the overwhelming impact of distant
455
456
Journal of the Royal Society of Medicine Volume 85 August 1992
Table 3. Outcome after recurrence Distant
Loco-regional
Time to death (n= 14) 10 months (0-30)
Time surviving (n=10) 16.3 months (2-49)
Distant/loco-regional Death (n=1) 8 months
recurrence in this study it can perhaps-, be seen in perspective. More than 80% of all first recurrences were at distant sites and only 52% are predicted to survive 6 years. Local treatment failure as opposed to local recurrence is of course to be prevented if possible and in this series there were three such cases. In one case synchronous recurrence of disease in the ipsilateral and contralateral breast proceeded rapidly to carcinoma en curasse. In the other two cases bilateral supraclavicular fossa disease was unresponsive to radiotherapy and chemotherapy. Clearly more radical initial surgery would not have prevented either of these recurrences. These low treatment failure rates are similar to other studies where wide local excision and axillary clearance together with radiotherapy to the breast have been employed as the breast conservation management of choice 4. Of interest when treatment failure rather than local recurrence has been compared in prospective studies local surgery without radiotherapy has fared no worse than after simple mastectomy with failure rates of 4 and 4.6% respectivelyl. Perhaps therefore the time has come to accept that local recurrence is a possibility regardless-of treatment and that locoregional treatment failure, is a rare event with adequate initial loco-regional surgery. Our current obsession with local recurrence might in part derive from our inability to prevent it. Based on our results the simple answer is not more radical initial surgery since in more than half of our cases with local recurrence these women rapidly succumbed to distant disease and few would advocate initial aggressive local surgery for women with limited life span. Detailed analysis of pathological variables by others suggests that there are none that absolutely contra indicate conservation surgery'. Certainly our data does not support a movement away from breast conserving surgery in early breast cancer using simple clinical and mammographic criteria for selection. Regarding regional control however our data
Surviving (n=4) 17.2 months (3-26)
Time to death (n=8) 14 months (3-45)
Time surviving (n=2) 18.5 months (11.26)
supports the findings of others" 4 that surgical axillary clearance virtually eliminates the problem. References 1 Fisher B, Bauer M, Margolese R, et aL Five-year results of a randomized clinical trial comparing total mastectomy and segmental mastectomy with or without radiation in the treatment of breast cancer. N Engl J Med 1985;312:665-73 2 Fentiman IS, Mansel E. The axilla: not a no-go zone. Lancet 1991;337:221-3 3 Veronesi U, Banfi A, del Vecchio M, et al Comparison of Halsted mastectomy with quadrantectomy axillary
4
5 6 7 8
9 10 11
dissection and radiotherapy in early breast cancer: long-term results. Eur J Cancer Clin Oncol 1986;22: 1085-9 Locker AP, Ellis I0, Morgan DAL, Elston CW, Mitchell A, Blamey RW. Factors influencing local recurrence after excision and radiotherapy for primary breast cancer. Br J Surg 1989;76:890-4 Hoe AL, Iven D, Royle GT, Taylor I. Incidence of arm swelling following axillary clearance for breast cancer. Br J Surg 1992;79:261-2 Kissin MW, Querci della Rovere G, Easton D, Westbury G. Risk of lymphoedema following the treatment of breast cancer. Br J Surg 1986;73:580- 4 Kissin MW, Thompson EM, Price AB, Slavin G, Kark AE. The inadequacy of axillary sampling in breast cancer. Lancet 1982i:1210-11 Matthiem W, Bougeois P, Delcorde A, et aL Axillary dissection in breast cancer revisited. Eur J Surg Oncol 1989;15:490-5 Veronesi U, Luini A, Galimberti V, et aL Extent of metastatic axillary involvement of 1446 cases of breast cancer. Eur J Surg Oncol 1990;16:127-33 McLean RG, Ege GN. Prognostic value of axillary lymphoscintigraphy in breast carcinoma patients. J Nuci Med,1986;27:116-24 Bruneton JN, Caramella E, Hery M, et aL Axillary lymph node metastases in breast cancer: preoperative detection with US. Radiology 1986;158:325-6
(Accepted 23 March 1992)
Journal of the Royal Society of Medicine Volume 85 August 1992
Loco-regional recurrence and survival, after wide local excision, radiotherapy and axillary clearance for early breast cancer
C Hamilton FRCR R Carpenter MS FRCS G T Royle MS FRCS M Cross R Buchanan FRCR FRCP I Taylor MD FRCS Untversity Surgical Unit and Department of Radiotherapy, Royal South Hants Hospital; Graham Road; Southampton Keywords: breast cancer; conservation surgery; local recurrence; axillary clearance
Summary After breast conservation for early breast cancer which comprised wide local excision, axillary clearance and radiotherapy to the breast, 145 women have been followed prospectively for a median of 42 months. Local recurrence occurred in 11 (7%) and axillary recurrence in three (2%). Distant recurrence has occurred in 32 and accounted for 80% of all first recurrences. Local treatment failure has occurred in three women and would not have been prevented by mastectomy. Loco-regional recurrence in the absence of preceding or synchronous distant disease was unusual and did not pose a significant clinical problem. Introduction Breast conservation does not prejudice survival of women with early breast cancer'. However, controversy persists regarding 'what constitutes adequate loco-regional disease control and most recently this has centred on the surgical treatment of the axilla2. Loco-regional recurrence rates after conservation surgery vary from 8% in prospective studies"3 to 21% in a recent retrospective review4. These studies differ in that in the former the axilla was surgically cleared, in the latter, node sampling was undertaken. Since 1983 the policy in Southampton has been to offer women with early breast cancer conservation surgery which consists of wide local excision and axillary clearance together with radiother,apy to the breast. Selection is based on simple clinical and mammographic criteria and we report the results of a prospective follow-up -of patients over the years 1983-1990. Patients and methods Indications for conservation surgery were a tumour less than 5 cm in maximum clinical dimension which was freely mobile in the breast and unifocal on mammography. Single mobile axillary nodes were not a contraindication to conservation surgery; however, central lesions or those which involved the nipple were considered unsuitable. All patients were assessed clinically by mammography and by aspiration cytology and a diagnosis made by a combination of all three modalities. After diagnosis, women were
offered a choice of treatment by conservation surgery or mastectomy. One hundred and forty-five women have been followed-up between 1983 and 1990. Conservation treatment consisted of macroscopic clearance aiming to provide at least a centimetre of non involved breast tissue around the tumour. The excision was routinely taken to include the pectoral fascia although it did not constitute a segmental excision. Either by the same or more commonly a separate incision the axillary contents -were cleared below the level of the axillary vein 'and included the apical lymph node. Pectoralis minor was not routinely divided. Subsequently the women underwent radiotherapy to the breast to a total dose of 5000 rads delivered over a 5-week period. Women older than 50 were commenced on adjuvant tamoxifen 20 mg daily, women younger than 50 with positive nodes were offered adjuvant chemotherapy. All women were reviewed at 3 monthly intervals for the first 2 years, 6 monthly intervals for the -next 2 years and subsequently -annually. Data was recorded prospectively. At first recurrence screening inve*tigations of bone scan, liver scan and chest Xrays were undertaken.
Results One hundred and forty-five women underwent conservation surgery between 1983 and 1989. The median follow-up for the group is 42 months (12-72). The median age was 54 years (19-77) and the median tumour size was 2 cm (0.5-5) Thirty-six per cent of the group were premenopausal; 34% were node positive.9-; Overall survival by life table analysis at6years was 47% 52% and disease free survivalfor the sami6-rod -(Figures 1 and 2). Of all fils recurrenc2 (80%) were at distant sites. Loco-regional recurrence occurred in 16 (11%). Isolated loco-regional recurrence 100 I-
III
n
N- 145
I
40
d 20
0141-0768/92
080454-03/$02.00/0 Correspondence to: Mr R Carpenter, 1st Floor Surgical, St Bartholomew's Hospital, West Smithfield, London EClA 7BE
2
4
TIME (YEARS)
Figure 1. Survival
a
a
1
1992
i) Royal EThe
Society of Medicine
Journal of the Royal Society of Medicine Volume 85 August 1992 Table 2. Pattern of recurrence, local and distant disease (n=10)
JooI
Ls
Z
1st distant
1st local/regional
Synchronous
2
2
6
m m
a v
Bo
J.-
a
2
N- 14S
o 40
" 40
w I.-
n x :3
u
20
2
10
4
J°e
TIM E ( YEARS )
Figure 2. Recurrence free survival
occurred in six (4%), five withir i the breast, and one in the ipselateral axilla (Table 1L). In 10 further cases of loco-regional recurrence tblere was associated distant disease. In those with b oth loco-regional and distant recurrence, local recurr ence occurred first in only two; in the remainder dist;ant disease occurred first or was synchronous wilth local recurrence (Table 2). Loco-regional treatment fail ure or uncontrolled disease occurred in three cases. In two this involved both supra clavicular fossae aind in one there was synchronous recurrence of diseEase in the ipsilateral and contralateral breast. In allI three cases distant disease occurred rapidly and miedian survival after loco-regional recurrence in this group was 9 months. Of those with loco-regional recgurrence, six women underwent mastectomy and t;he remainder were treated by local excision irncluding the three recurrences within the ipsilate ral axilla. Outcome after recurrence is se(en in Table 3. Median time to death after distant recur rence was 10 months (0-30) and 14 months (3-45) in the group with both local and distant recurrence. Seventeen premenopausal node positive women received adjuvant chemotherapy and 96 postnnenopausal women received tamoxifen. The median hospital stay for tthe group was 5 days (4-8) 24 seromas required aspirattion as an outpatient procedure. There have been nLo cases of clinically disabling lymphoedema. Discussion The most recent controversy surrounding breast conservation surgery has cent red on the need for axillary clearance2. Opinions vw ary but impressed by low regional recurrence rates of 3% following axillary clearance in prospective studies in both America and Italy'4 this form of regional co: ntrol was adopted in Southampton in 1983. Findings of low regional reci arrence rates in this series support this choice. Ther e have been no cases of treatment failure in the axilla and all three axillary recurrences were amenable to E simple local surgery. Comparison between series is toebe used with caution however, loco-regional recurre nce rates of 22% in Table 1. Recurrence after breast Distant
Local
24 (16.6%) 5 (3.4%)
co
Regional 1!oco-regional & distant 1 (0.7%)
1L0 (6.9%)
specialist centres where node sampling only has been employed would seem to indicate that prevention of ,recurrence is both possible and desirable3. While hospital stay is longer for conservation surgery involving axillary clearance than lumpectomy and node samnpling the vast majority of our patients were managed on a 5-day surgical ward. The argument that axillary clearance has significant morbidity was not borne out by the study and objective assessment of arm swelling has shown no significant lymphoedema5. This compares favourably with other studies where objective assessments of lymphoedema have been undertaken6. As a result of our policy to clear the axilla surgically, radiotherapy planning has been simplified since only the breast is irradiated. We have also gained accurate data on nodal status and in 17 premenopausal women with positive nodes we have been able to offer adjuvant chemotherapy. None of those with histologically-proven lymph node metastases had clinically involved lymph nodes. Since axillary node sampling has been shown to be unreliable7-9 and current techniques to image nodal metastatic disease are insufficiently sensitive01ll, these women might not have been offered adjuvant chemotherapy if they had not undergone axillary clearance. We would therefore support recent advocates of axillary clearance on the basis that currently only axillary clearance gives sufficient information to allow selection of adjuvant chemo-
therapy
2
.
Local recurrence in the breast occurred in 11 (7.6%) cases. In five of these cases, however, there was preceding or synchronous distant disease and those with such combination of disease died a median of 10 months after recurrence. Those without associated distant disease remain well without evidence of disease at a median follow-up of 17 months (3-25) after recurrence. Six of the 11 with local recurrence underwent mastectomy and the remainder further local excision. In an attempt to determine factors which might predict those women likely to develop local recurrence after conservation surgery retrospective studies have analysed local recurrence patterns3. One such study derived an index based on clinical and pathological factors and advocates more radical local surgery in some cases3. Analysis of our data would indicate that such an approach (which is not 100% selective) might result in a mastectomy in women who subsequently rapidly succumbed to associated distant disease. Further, since there is a finite risk of locoregional recurrence after mastectomy in the order of
5%1, a more radical approach would not guarantee freedom of local recurrence. Such indices therefore must take into account the pattern of distant recurrence as well as local and regional recurrence before they can be applied clinically to select patients for breast conservation. Local recurrence while not desirable will never be
completely
eliminated and
viewed against the overwhelming impact of distant
455
456
Journal of the Royal Society of Medicine Volume 85 August 1992
Table 3. Outcome after recurrence Distant
Loco-regional
Time to death (n= 14) 10 months (0-30)
Time surviving (n=10) 16.3 months (2-49)
Distant/loco-regional Death (n=1) 8 months
recurrence in this study it can perhaps-, be seen in perspective. More than 80% of all first recurrences were at distant sites and only 52% are predicted to survive 6 years. Local treatment failure as opposed to local recurrence is of course to be prevented if possible and in this series there were three such cases. In one case synchronous recurrence of disease in the ipsilateral and contralateral breast proceeded rapidly to carcinoma en curasse. In the other two cases bilateral supraclavicular fossa disease was unresponsive to radiotherapy and chemotherapy. Clearly more radical initial surgery would not have prevented either of these recurrences. These low treatment failure rates are similar to other studies where wide local excision and axillary clearance together with radiotherapy to the breast have been employed as the breast conservation management of choice 4. Of interest when treatment failure rather than local recurrence has been compared in prospective studies local surgery without radiotherapy has fared no worse than after simple mastectomy with failure rates of 4 and 4.6% respectivelyl. Perhaps therefore the time has come to accept that local recurrence is a possibility regardless-of treatment and that locoregional treatment failure, is a rare event with adequate initial loco-regional surgery. Our current obsession with local recurrence might in part derive from our inability to prevent it. Based on our results the simple answer is not more radical initial surgery since in more than half of our cases with local recurrence these women rapidly succumbed to distant disease and few would advocate initial aggressive local surgery for women with limited life span. Detailed analysis of pathological variables by others suggests that there are none that absolutely contra indicate conservation surgery'. Certainly our data does not support a movement away from breast conserving surgery in early breast cancer using simple clinical and mammographic criteria for selection. Regarding regional control however our data
Surviving (n=4) 17.2 months (3-26)
Time to death (n=8) 14 months (3-45)
Time surviving (n=2) 18.5 months (11.26)
supports the findings of others" 4 that surgical axillary clearance virtually eliminates the problem. References 1 Fisher B, Bauer M, Margolese R, et aL Five-year results of a randomized clinical trial comparing total mastectomy and segmental mastectomy with or without radiation in the treatment of breast cancer. N Engl J Med 1985;312:665-73 2 Fentiman IS, Mansel E. The axilla: not a no-go zone. Lancet 1991;337:221-3 3 Veronesi U, Banfi A, del Vecchio M, et al Comparison of Halsted mastectomy with quadrantectomy axillary
4
5 6 7 8
9 10 11
dissection and radiotherapy in early breast cancer: long-term results. Eur J Cancer Clin Oncol 1986;22: 1085-9 Locker AP, Ellis I0, Morgan DAL, Elston CW, Mitchell A, Blamey RW. Factors influencing local recurrence after excision and radiotherapy for primary breast cancer. Br J Surg 1989;76:890-4 Hoe AL, Iven D, Royle GT, Taylor I. Incidence of arm swelling following axillary clearance for breast cancer. Br J Surg 1992;79:261-2 Kissin MW, Querci della Rovere G, Easton D, Westbury G. Risk of lymphoedema following the treatment of breast cancer. Br J Surg 1986;73:580- 4 Kissin MW, Thompson EM, Price AB, Slavin G, Kark AE. The inadequacy of axillary sampling in breast cancer. Lancet 1982i:1210-11 Matthiem W, Bougeois P, Delcorde A, et aL Axillary dissection in breast cancer revisited. Eur J Surg Oncol 1989;15:490-5 Veronesi U, Luini A, Galimberti V, et aL Extent of metastatic axillary involvement of 1446 cases of breast cancer. Eur J Surg Oncol 1990;16:127-33 McLean RG, Ege GN. Prognostic value of axillary lymphoscintigraphy in breast carcinoma patients. J Nuci Med,1986;27:116-24 Bruneton JN, Caramella E, Hery M, et aL Axillary lymph node metastases in breast cancer: preoperative detection with US. Radiology 1986;158:325-6
(Accepted 23 March 1992)
