Aggressive local treatment for screen-Èdetected DCIS results in very low rates of recurrence

EJSO 2001; 27: 454–458 doi:10.1053/ejso.2001.1163, available online at http://www.idealibrary.com on

Aggressive local treatment for screendetected DCIS results in very low rates of recurrence M. K. Jha∗, V. S. Avlonitis∗, C. D. M. Griffith∗, T. W. J. Lennard∗, R. G. Wilson∗, L. M. McLean†, P. D. Dawes‡ and J. Shrimankar§ Departments of ∗Surgical Oncology, †Radiology, ‡Clinical Oncology and §Pathology, Newcastle NHS Hospitals Trust, Newcastle-upon-Tyne, UK

Aims: To review our institution’s practice of treatment of a mammographically detected population of ductal carcinoma in situ (DCIS) patients and to determine the outcome. Methods: Between April 1989 and March 1994, 304 women with median age 59 years (range 51–65) with DCIS detected on screening mammogram, were treated in the Newcastle General and Royal Victoria Infirmary Hospitals, Newcastle-upon-Tyne, UK. More than half of the women (n=176, 57.8%) decided to have mastectomy. Other treatment options were wide local excision (WLE) with radiotherapy (n=97, 32%) and WLE alone (n=31, 10.2%). All except five received adjuvant hormone treatment. Results: Predominant DCIS was comedo in 122 (42%), followed by cribriform in 87 (30%) and micropapillary in 44 (15%) cases. Grade I was found to be commonest grade (54%) followed by grade II (27%) and grade III (11%). With a median follow-up of 88 months, there were six (2%) recurrences, all of which were in women who were given breast conservation treatment, WLE with radiotherapy (n=1, 1%) and without radiotherapy (n=5, 16.6%). Mastectomy in this series was not associated with any recurrence at all. In three cases the recurrence was invasive, one of who also had distant metastasis. Conclusions: The findings of this study suggest that in women with DCIS suitable for breast conservation, WLE when combined with radiotherapy is associated with a very low recurrence rate.  2001 Harcourt Publishers Ltd Key words: ductal carcinoma in situ; breast conservation therapy; mastectomy.

INTRODUCTION Ductal carcinoma in situ (DCIS) was initially described by Borders in 1932 who defined it as neoplastic epithelial cells of ductal origin within the breast that show no evidence of invasion.1 The incidence rate of DCIS of the breast has increased considerably (2% to 30%), as quoted in literature.2,3 In the UK, with the introduction of NHS Breast Screening Programme (NHSBSP), the detection rate of DCIS has reached up to 19%.4 This rise in the incidence of DCIS, and the success of breast conserving treatment for appropriate invasive breast cancers has led to renewed interest in conservative surgery with or without radiotherapy in such patients. The proportion of patients with DCIS treated by mastectomy has actually

Correspondence to: Mr. C. D. M. Griffith, Consultant Surgeon, Leazes Wing, Royal Victoria Infirmary, Newcastle-upon-Tyne, UK. 0748–7983/01/050454+05 $35.00/0

declined from 71% to 44% with a consequent increase in the breast-conserving treatment from 26% to 53%.3 Where invasive carcinoma is concerned, the randomized controlled trials of mastectomy vs breast conserving treatment has not shown any difference in the long-term survival.5–9 No similar trials have been conducted for the DCIS, and its optimal treatment still remains controversial. It is the risk of local recurrence with the possibility of its invasive variant rather than the metastatic disease which remains the main concern related to the conservative treatment of women with DCIS,10,11 rate in the treated breast.12,13 Age is also a significant factor for local recurrence of invasive breast cancer. This, however, does not seem to be a significant risk for patients with DCIS.14–20 The purpose of this study was to evaluate the frequency of local recurrence of in situ or invasive breast cancer in a group of women treated for DCIS by mastectomy and breast conserving surgery over a 5year period between 1989–94 in a defined geographical cohort.  2001 Harcourt Publishers Ltd

AGGRESSIVE LOCAL TREATMENT FOR SCREEN-DETECTED DCIS

455

Table 1 Details of various treatment offered Year 1989–90 1990–91 1991–92 1992–93 1993–94 Total

Number 53 51 65 66 69 304

Patey’s mastectomy 19 17 12 14 10 72

(36%) (33%) (18%) (22%) (15%) (24%)

PATIENTS AND METHODS A total of 304 patients who were detected to have DCIS by the National Breast Cancer Screening Programmes between 1989–94, were enrolled in this study. Their median age at diagnosis was 59 years (range 51–65). The notes of these patients were obtained from the medical records department and surgical details and pathological reports were reviewed by one of the authors. The screening mammograms in these women were performed at Newcastle General Hospital or with mobile screening units to cover the rural catchment area. Women with mammographic evidence of malignant microcalcification were further assessed at the hospital, and pathological diagnosis established by either X-rayguided fine needle aspiration cytology or biopsy, under the supervision of a consultant radiologist. After confirmation of the diagnosis of DCIS, the treatment options were discussed by the consultant surgeon and the patients were offered either mastectomy or breast conserving treatment on the basis of unifocal or multifocal nature of disease, the area of the DCIS as well as patients’ informed choice. Local excision was performed after the placement of a marker wire and radiological confirmation of complete excision of the mammographic area of DCIS was obtained. In a group of women treated with WLE, a margin of 5 mm clear of DCIS was ensured prior to breast irradiation with a total dose of 50 Gy over 5 weeks. All of them were prescribed adjuvant tamoxifen treatment, but this was interrupted in five women who experienced difficulties in tolerating it due to the side-effects. The recurrence-free survival was calculated by using the Kaplan–Meier method. The analysis for statistical difference between the curves was performed with Logrank test. A P value of less than 0.05 was considered statistically significant. Computation was performed using Stata Statistical Software.21 The follow-up period began at the date of first excision and subsequently on every anniversary with clinical examination and mammography according to an agreed protocol.

RESULTS The details of various treatment offered is summarized in Table 1. Majority of the women had mastectomy (n=

Simple mastectomy 24 26 23 18 13 104

(45%) (51%) (35%) (28%) (19%) (34%)

WLE and radiotherapy 05 02 24 29 37 97

(09%) (8%) (37%) (45%) (55%) (32%)

WLE alone 06 07 08 07 03 31

(12%) (14%) (13%) (11%) (4.4%) (10%)

176; 57.8%). Wide local excision was performed on 128 (42.1%), of which 97 (75.7%) received radiotherapy. One hundred and six women (60.2%) out of 176 had a simple mastectomy and the remaining 70 (39.7%) had Patey mastectomy with level II axillary clearance. Of the 304 patients, six were lost to follow-up, four had invasive component in addition to DCIS and two women had bilateral disease. These women (n=12) were excluded from further analysis. Among the women (n=292), the microcalcification was the most common mammographic findings (n= 219, 75%), mass lesion was noted in 55 (19%) and the remaining 18 (6%) women showed non-specific appearances including radial scars. Of the histology typings, the majority of cases showed comedo DCIS (n=122, 42%) followed by cribriform (n=87, 30%), micropapillary DCIS (n=44, 15%) and solid DCIS (n= 20, 7%). In 19 cases, no specific pathological type was described. One hundred and thirty-one patients had mixed histology (54%) with more than one type of DCIS present. The predominant nuclear grading was grade I in 157 (54%) cases followed by grade II in 80 (27%) cases and grade III in 30 (11%) cases. In the remaining 25 (8%) no grade of DCIS was reported. Of the 124 patients who had breast-conserving surgery, 42 (34%) required a further wide local excision on the basis of histological report in order to clear the excision margin of DCIS. In 15 of these patients, residual DCIS was found in the further excision of breast tissue. With a median follow-up of 88 months (range 62–126), only six patients out of the 292 (2%) in this study developed local recurrence in the treated breast. All of the patients who developed local recurrence had been treated with breast conservation and tamoxifen. Five of these patients had wide local excision alone and one had breast radiotherapy in addition. Three of the local recurrences were detected by routine follow-up mammography and other three presented with palpable lump in the breast. In four of these six women, recurrence was in the same quadrant of the treated breast as the primary tumour, in two others recurrence occurred in a separate quadrant of the breast. Three recurrences were DCIS (all comedo type) and three were invasive, of which one patient was found to have axillary node involvement as well as liver metastases.

456

M. K. JHA ET AL. Table 2 Local recurrence in WLE with or without radiotherapy Treatment

Median age

No recurrence

Local recurrence

WLE+XRT (n=94) WLE alone (n=30)

57 years range (51–64) 58 years range (51–64)

93

1 (1%)

25

5 (16.6%)

DISCUSSION

0.0008

WLE and RT

1.00 Recurrence-free survival

This study describes the observed rate of local recurrence in a group of women with screen detected DCIS and treated with various modalities. Although retrospective, this is a large series with approximately 97% follow-up and represents a population from a defined geographical cohort. The optimal management of women with DCIS remains a major challenge since up to 20% of all newly diagnosed breast cancers are DCIS.22 Until the past decade, most patients with DCIS underwent radical or modified radical mastectomy with a cure rate of almost 100%.23 Over the years it has been reported that axillary node clearance is unnecessary for patients with pure DCIS.11,24–26 and excellent results can be obtained with simple mastectomy.27 For localized DCIS there is now a trend towards breast-conserving surgery, with or without breast radiotherapy. In the National Surgical Adjuvant Breast and Bowel Project (NSABP) B17 trial with 90 months of follow-up, 26.8% of patients developed local recurrence when treated with wide local excision alone, compared with 11.9% when WLE was combined with radiotherapy.13 Other retrospective series report local recurrence rates of 5–65% for local excision alone27–33 and 6–21% for local excision plus breast radiotherapy.15,23,24,33–38 The rate of local recurrence in this study shows that wide local excision alone of the area of DCIS, results in the highest recurrence (n=5 out of 30, 16.6%) and that this effect can be reduced with the addition of breast radiotherapy (n=1 out of 94, 1%). Mastectomy in this series was associated with no local recurrence at all. The women in the group treated with WLE and radiotherapy showed significantly better recurrence-free survival (P= 0.0008) in comparison with those treated with WLE alone (Table 2, Fig. 1). The results of local excision and radiotherapy for mammographically detected DCIS are presented in Table 3. The local recurrence as observed in this study is lower as compared with other published series. The current study supports the idea that breast radiotherapy when combined with wide local excision results in a low rate of local recurrence. As observed in other studies, mastectomy in our series was also not associated with any recurrence.23 Despite acceptance of wide local excision as an effective treatment, many of our patients when told about the diagnosis of breast

P-value (Log-rank test)

WLE 0.75

0.50

0.25

0

50

100

150

Months

Figure 1 Recurrence-free survival in women treated with wide local excision (WLE) and radiotherapy vs WLE alone.

cancer and given the treatment options, decided to have mastectomy, which accounts for the relatively high rate of mastectomy in this series. There appears to be a preference towards mastectomy among the women in this region as shown in a previous study.45 A considerable increase in the number of women being treated with breast conservation was noted from 1991 onwards (Table 1). There appears to be no definite explanation for this trend except that there had been a surge of published articles during that period comparing the results of mastectomy and breast conservation for both invasive as well as non-invasive disease.7,28,32,34,35 The unequal distribution of patients in different treatment group in our series was most probably due to lack of randomization (WLE in 124; 42.4% and mastectomy in 168; 57.6%), nonetheless, each group had sufficient number to provide a useful follow-up data. Until recently, there has been no published trial except B-17 of NSABP which randomized women with DCIS to different treatments.13 An analysis of a subset of patients from the same series treated with a combination of wide excision and radiotherapy showed a local recurrence of 10% over a median follow-up of 43.2 months.12 The present series represents the median follow-up of more than twice this period (88 months) and shows much less recurrence. A recent study suggests that with a resection margin of 10 mm or more clear of DCIS may be advantageous as in such cases the addition of breast radiotherapy did

AGGRESSIVE LOCAL TREATMENT FOR SCREEN-DETECTED DCIS

457

Table 3 Results of wide excision and radiation for mammographically detected DCIS

NSABP B-1712,39 Kuske et al.40 White et al.41 Hiramatsu et al.42 Silverstein et al.43 Fowble et al.44 Current series

No. of patients

Actuarial 5-year recurrence %

399∗ 44 46 54 133† 110 94

10% 7% 5% 2% 7% 1% 1%

Median follow-up 43.2 48.0 68.4 74.4 93.6 63.6 88.0

months months months months months months months

∗81% mammo detected, †89% mammo detected.

not seem to offer any extra advantage of reducing local recurrence.46 The current ongoing DCIS trials in the UK are designed to compare wide local excision alone with wide excision plus tamoxifen or wide excision olus tamoxifen with breast radiotherapy. The result of the study should provide insight into the merits and demerits of various treatment. Based on our findings it would appear that wide local excision combined with breast radiotherapy may be the choice of treatment as this was associated with low rates of local recurrence in this study. Mastectomy, whether done for specific indications or by patients’ choice was also associated with equally low recurrence, but this has the obvious disadvantage of impairment of body image.47,48 The findings in this study indicate that WLE alone is inadequate treatment for DCIS.

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